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Willett, Christopher G.

Positions:

Chair, Department of Radiation Oncology

Radiation Oncology
School of Medicine

Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1977

B.S. — Tufts University

M.D. 1981

M.D. — Tufts University

Grants:

Motion Management Using 4D-MRI for Liver Cancer in Radiation Therapy

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Collaborating Investigator
Start Date
January 11, 2013
End Date
December 31, 2016

Robotic SPECT for Biological Imaging Onboard Radiation Therapy Machines

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
September 22, 2011
End Date
November 30, 2013

Digital tomosynthesis: a new paradigm for radiation treatment verification

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 11, 2007
End Date
July 31, 2009

Angiogenic Profile of Rectal Cancer

Administered By
Radiation Oncology
AwardedBy
National Cancer Institute
Role
Principal Investigator
Start Date
August 15, 2003
End Date
July 31, 2008

Cancer Care Quality Measures: Diagnosis and Treatment of Colorectal Cancer

Administered By
Institutes and Centers
AwardedBy
Agency for Healthcare Research and Quality
Role
Investigator
Start Date
December 01, 2004
End Date
December 31, 2005
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Publications:

The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer.

The optimal approach to patients with locally recurrent, non-metastatic rectal cancer is unclear. This study evaluates the outcomes and toxicity associated with pelvic re-irradiation.Patients undergoing re-irradiation for locally recurrent, non-metastatic, rectal cancer between 2000 and 2014 were identified. Acute and late toxicities were assessed using common terminology criteria for adverse events version 4.0. Disease-related endpoints included palliation of local symptoms, surgical outcomes, and local progression-free survival (PFS), distant PFS and overall survival (OS) using the Kaplan-Meier method.Thirty-three patients met the criteria for inclusion in this study. Two (6 %) experienced early grade 3+ toxicity and seven (21 %) experienced late grade 3+ toxicity. Twenty-three patients presented with symptomatic local recurrence and 18 (78 %) reported symptomatic relief. Median local PFS was 8.7 (95 % CI 3.8-15.2) months, with a 2-year rate of 15.7 % (4.1-34.2), and median time to distant progression was 4.4 (2.2-33.3) months, with a 2-year distant PFS rate of 38.9 % (20.1-57.3). Median OS time for patients was 23.1 (11.1-33.0) months. Of the 14 patients who underwent surgery, median survival was 32.3 (13.8-48.0) months compared with 13.3 (2.2-33.0) months in patients not undergoing surgery (p = 0.10). A margin-negative (R0) resection was achieved in 10 (71 %) of the surgeries. Radiation treatment modality (intensity-modulated radiation therapy, three-dimensional conformal radiotherapy, intraoperative radiation therapy) did not influence local or distant PFS or OS.Re-irradiation is a beneficial treatment modality for the management of locally recurrent, non-metastatic rectal cancer. It is associated with symptom improvement, low rates of toxicity, and similar benefits among radiation modalities.

Authors
Susko, M; Lee, J; Salama, J; Thomas, S; Uronis, H; Hsu, D; Migaly, J; Willett, C; Czito, B; Palta, M
MLA Citation
Susko, M, Lee, J, Salama, J, Thomas, S, Uronis, H, Hsu, D, Migaly, J, Willett, C, Czito, B, and Palta, M. "The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer." Annals of surgical oncology 23.11 (October 2016): 3609-3615.
PMID
27169769
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
11
Publish Date
2016
Start Page
3609
End Page
3615
DOI
10.1245/s10434-016-5250-z

Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology

Authors
Ajani, JA; D'Amico, TA; Almhanna, K; Bentrem, DJ; Chao, J; Das, P; Denlinger, CS; Fanta, P; Farjah, F; Fuchs, CS; Gerdes, H; Gibson, M; Glasgow, RE; Hayman, JA; Hochwald, S; Hofstetter, WL; Ilson, DH; Jaroszewski, D; Johung, KL; Keswani, RN; Kleinberg, LR; Korn, WM; Leong, S; Linn, C; Lockhart, AC; Ly, QP; Mulcahy, MF; Orringer, MB; Perry, KA; Poultsides, GA; Scott, WJ; Strong, VE; Washington, MK; Weksler, B; Willett, CG; Wright, CD; Zelman, D; McMillian, N; Sundar, H
MLA Citation
Ajani, JA, D'Amico, TA, Almhanna, K, Bentrem, DJ, Chao, J, Das, P, Denlinger, CS, Fanta, P, Farjah, F, Fuchs, CS, Gerdes, H, Gibson, M, Glasgow, RE, Hayman, JA, Hochwald, S, Hofstetter, WL, Ilson, DH, Jaroszewski, D, Johung, KL, Keswani, RN, Kleinberg, LR, Korn, WM, Leong, S, Linn, C, Lockhart, AC, Ly, QP, Mulcahy, MF, Orringer, MB, Perry, KA, Poultsides, GA, Scott, WJ, Strong, VE, Washington, MK, Weksler, B, Willett, CG, Wright, CD, Zelman, D, McMillian, N, and Sundar, H. "Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology." Journal of the National Comprehensive Cancer Network 14.10 (October 2016): 1286-1312.
Source
crossref
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
14
Issue
10
Publish Date
2016
Start Page
1286
End Page
1312
DOI
10.6004/jnccn.2016.0137

Role of Adjuvant Radiotherapy in Locally Advanced Colonic Carcinoma in the Modern Chemotherapy Era.

The role of adjuvant radiation therapy (RT) in the treatment of resected, locally advanced colon cancer is unclear. One randomized controlled trial (Intergroup-0130) addressed this question but failed to meet its accrual goals. Since this trial, few attempts have been made to reassess the role of RT in this clinical setting.Sixty-two patients with non-metastatic, American Joint Committee on Cancer 7th edition stage T4 colonic adenocarcinoma were treated at our institution between 2000 and 2013. All underwent curative-intent surgery. Sixteen patients underwent resection only, 33 patients received adjuvant chemotherapy (ChT), and 13 patients received adjuvant chemoradiation therapy (CRT).Patients receiving adjuvant CRT were more likely to have T4b (vs. T4a) disease and were more likely to undergo R1 or R2 resection compared with those receiving adjuvant ChT alone. Despite this, multivariate analysis demonstrated that treatment with adjuvant CRT (vs. adjuvant ChT) enhanced locoregional control and disease-free survival (hazard ratio 0.044 and 0.145, respectively; p < 0.05).Adjuvant RT for T4 colon cancers may be appropriate in select patients, specifically those with T4b lesions and/or residual disease following resection.

Authors
Ludmir, EB; Arya, R; Wu, Y; Palta, M; Willett, CG; Czito, BG
MLA Citation
Ludmir, EB, Arya, R, Wu, Y, Palta, M, Willett, CG, and Czito, BG. "Role of Adjuvant Radiotherapy in Locally Advanced Colonic Carcinoma in the Modern Chemotherapy Era." Annals of surgical oncology 23.3 (March 2016): 856-862.
PMID
26480849
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
3
Publish Date
2016
Start Page
856
End Page
862
DOI
10.1245/s10434-015-4907-3

Nonoperative management of rectal cancer.

Surgery has long been the primary curative modality for localized rectal cancer. Neoadjuvant chemoradiation has significantly improved local control rates and, in a significant minority, eradicated all disease. Patients who achieve a pathologic complete response to neoadjuvant therapy have an excellent prognosis, although the combination treatment is associated with long-term morbidity. Because of this, a nonoperative management (NOM) strategy has been pursued to preserve sphincter function in select patients. Clinical and radiographic findings are used to identify patients achieving a clinical complete response to chemoradiation, and they are then followed with intensive surveillance. Incomplete, nonresponding and those demonstrating local progression are referred for salvage with standard surgery. Habr-Gama and colleagues have published extensively on this treatment strategy and have laid the groundwork for this approach. This watch-and-wait strategy has evolved over time, and several groups have now reported their results, including recent prospective experiences. Although initial results appear promising, several significant challenges remain for NOM of rectal cancer. Further study is warranted before routine implementation in the clinic.

Authors
Torok, JA; Palta, M; Willett, CG; Czito, BG
MLA Citation
Torok, JA, Palta, M, Willett, CG, and Czito, BG. "Nonoperative management of rectal cancer." Cancer 122.1 (January 2016): 34-41. (Review)
PMID
26599064
Source
epmc
Published In
Cancer
Volume
122
Issue
1
Publish Date
2016
Start Page
34
End Page
41
DOI
10.1002/cncr.29735

A current perspective on stereotactic body radiation therapy for pancreatic cancer.

Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies.

Authors
Hong, JC; Czito, BG; Willett, CG; Palta, M
MLA Citation
Hong, JC, Czito, BG, Willett, CG, and Palta, M. "A current perspective on stereotactic body radiation therapy for pancreatic cancer." OncoTargets and therapy 9 (January 2016): 6733-6739. (Review)
Website
http://hdl.handle.net/10161/13277
PMID
27826200
Source
epmc
Published In
OncoTargets and Therapy
Volume
9
Publish Date
2016
Start Page
6733
End Page
6739

Reflections from a chair: Leadership of a clinical department at an academic medical center.

The leadership position of an academic departmental chair can be a positive and rewarding opportunity. These rewards principally stem from the success of the faculty, residents, other trainees, nurses, and everyone supporting the department. With health care reform and the constraints of the federal budget, increasing attention and time has become directed toward administrative management. There are multiple and often competing constituencies and agendas requiring thoughtful strategies to achieve departmental goals. The objectives of a chair are advancing patient care, education, and research. True excellence of a department is achieved by the innovation of its faculty.

Authors
Willett, CG
MLA Citation
Willett, CG. "Reflections from a chair: Leadership of a clinical department at an academic medical center." Cancer 121.21 (November 2015): 3795-3798.
PMID
26218104
Source
epmc
Published In
Cancer
Volume
121
Issue
21
Publish Date
2015
Start Page
3795
End Page
3798
DOI
10.1002/cncr.29588

Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases.

To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported.Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes (n = 9-12). We further test our results in patient samples (n = 20 colon cancer patients; n = 20 head and neck cancer patients). Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW. All statistical tests were two-sided.Using the CLNW, we reveal the surprising lack of sprouting angiogenesis during metastatic growth, despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases (day 10: untreated mean = 1.2%, 95% confidence interval [CI] = 0.7% to 1.7%; control mean = 0.7%, 95% CI = 0.1% to 1.3%; DC101 mean = 0.4%, 95% CI = 0.0% to 3.3%; sunitinib mean = 0.5%, 95% CI = 0.0% to 1.0%, analysis of variance P = .34). We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab (no bevacizumab group mean = 257 vessels/mm(2), 95% CI = 149 to 365 vessels/mm(2); bevacizumab group mean = 327 vessels/mm(2), 95% CI = 140 to 514 vessels/mm(2), P = .78).We provide preclinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, and thus reveals a new mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The targets of clinically approved angiogenesis inhibitors are not active during early cancer progression in the lymph node, suggesting that inhibitors of sprouting angiogenesis as a class will not be effective in treating lymph node metastases.

Authors
Jeong, H-S; Jones, D; Liao, S; Wattson, DA; Cui, CH; Duda, DG; Willett, CG; Jain, RK; Padera, TP
MLA Citation
Jeong, H-S, Jones, D, Liao, S, Wattson, DA, Cui, CH, Duda, DG, Willett, CG, Jain, RK, and Padera, TP. "Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases." Journal of the National Cancer Institute 107.9 (September 2015).
PMID
26063793
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
107
Issue
9
Publish Date
2015
DOI
10.1093/jnci/djv155

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

Authors
Boyle, J; Czito, B; Willett, C; Palta, M
MLA Citation
Boyle, J, Czito, B, Willett, C, and Palta, M. "Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new." Journal of gastrointestinal oncology 6.4 (August 2015): 436-444. (Review)
PMID
26261730
Source
epmc
Published In
Journal of Gastrointestinal Oncology
Volume
6
Issue
4
Publish Date
2015
Start Page
436
End Page
444
DOI
10.3978/j.issn.2078-6891.2015.014

Human papillomavirus tumor infection in esophageal squamous cell carcinoma.

The association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) has been recognized for over three decades. Recently, multiple meta-analyses have drawn upon existing literature to assess the strength of the HPV-ESCC linkage. Here, we review these analyses and attempt to provide a clinically-relevant overview of HPV infection in ESCC. HPV-ESCC detection rates are highly variable across studies. Geographic location likely accounts for a majority of the variation in HPV prevalence, with high-incidence regions including Asia reporting significantly higher HPV-ESCC infection rates compared with low-incidence regions such as Europe, North America, and Oceania. Based on our examination of existing data, the current literature does not support the notion that HPV is a prominent carcinogen in ESCC. We conclude that there is no basis to change the current clinical approach to ESCC patients with respect to tumor HPV status.

Authors
Ludmir, EB; Stephens, SJ; Palta, M; Willett, CG; Czito, BG
MLA Citation
Ludmir, EB, Stephens, SJ, Palta, M, Willett, CG, and Czito, BG. "Human papillomavirus tumor infection in esophageal squamous cell carcinoma." Journal of gastrointestinal oncology 6.3 (June 2015): 287-295. (Review)
PMID
26029456
Source
epmc
Published In
Journal of Gastrointestinal Oncology
Volume
6
Issue
3
Publish Date
2015
Start Page
287
End Page
295
DOI
10.3978/j.issn.2078-6891.2015.001

Rectal Cancer, Version 2.2015.

The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease.

Authors
Benson, AB; Venook, AP; Bekaii-Saab, T; Chan, E; Chen, Y-J; Cooper, HS; Engstrom, PF; Enzinger, PC; Fenton, MJ; Fuchs, CS; Grem, JL; Grothey, A; Hochster, HS; Hunt, S; Kamel, A; Kirilcuk, N; Leong, LA; Lin, E; Messersmith, WA; Mulcahy, MF; Murphy, JD; Nurkin, S; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Sofocleous, CT; Stoffel, EM; Stotsky-Himelfarb, E; Willett, CG; Gregory, KM; Freedman-Cass, D
MLA Citation
Benson, AB, Venook, AP, Bekaii-Saab, T, Chan, E, Chen, Y-J, Cooper, HS, Engstrom, PF, Enzinger, PC, Fenton, MJ, Fuchs, CS, Grem, JL, Grothey, A, Hochster, HS, Hunt, S, Kamel, A, Kirilcuk, N, Leong, LA, Lin, E, Messersmith, WA, Mulcahy, MF, Murphy, JD, Nurkin, S, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Sofocleous, CT, Stoffel, EM, Stotsky-Himelfarb, E, Willett, CG, Gregory, KM, and Freedman-Cass, D. "Rectal Cancer, Version 2.2015." Journal of the National Comprehensive Cancer Network : JNCCN 13.6 (June 2015): 719-728.
PMID
26085388
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
13
Issue
6
Publish Date
2015
Start Page
719
End Page
728
DOI
10.6004/jnccn.2015.0087

Esophageal and esophagogastric junction cancers, version 1.2015.

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.

Authors
Ajani, JA; D'Amico, TA; Almhanna, K; Bentrem, DJ; Besh, S; Chao, J; Das, P; Denlinger, C; Fanta, P; Fuchs, CS; Gerdes, H; Glasgow, RE; Hayman, JA; Hochwald, S; Hofstetter, WL; Ilson, DH; Jaroszewski, D; Jasperson, K; Keswani, RN; Kleinberg, LR; Korn, WM; Leong, S; Lockhart, AC; Mulcahy, MF; Orringer, MB; Posey, JA; Poultsides, GA; Sasson, AR; Scott, WJ; Strong, VE; Varghese, TK; Washington, MK; Willett, CG; Wright, CD; Zelman, D; McMillian, N; Sundar, H; National comprehensive cancer network,
MLA Citation
Ajani, JA, D'Amico, TA, Almhanna, K, Bentrem, DJ, Besh, S, Chao, J, Das, P, Denlinger, C, Fanta, P, Fuchs, CS, Gerdes, H, Glasgow, RE, Hayman, JA, Hochwald, S, Hofstetter, WL, Ilson, DH, Jaroszewski, D, Jasperson, K, Keswani, RN, Kleinberg, LR, Korn, WM, Leong, S, Lockhart, AC, Mulcahy, MF, Orringer, MB, Posey, JA, Poultsides, GA, Sasson, AR, Scott, WJ, Strong, VE, Varghese, TK, Washington, MK, Willett, CG, Wright, CD, Zelman, D, McMillian, N, Sundar, H, and National comprehensive cancer network, . "Esophageal and esophagogastric junction cancers, version 1.2015." Journal of the National Comprehensive Cancer Network : JNCCN 13.2 (February 2015): 194-227.
PMID
25691612
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
13
Issue
2
Publish Date
2015
Start Page
194
End Page
227
DOI
10.6004/jnccn.2015.0028

Cancer of the colon

Authors
Libutti, SK; Saltz, LB; Willett, CG; Levine, RA
MLA Citation
Libutti, SK, Saltz, LB, Willett, CG, and Levine, RA. "Cancer of the colon." DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology: Tenth Edition. January 7, 2015.
Source
scopus
Publish Date
2015

Cancer of the rectum

Authors
Libutti, SK; Willett, CG; Saltz, LB; Levine, RA
MLA Citation
Libutti, SK, Willett, CG, Saltz, LB, and Levine, RA. "Cancer of the rectum." DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology: Tenth Edition. January 7, 2015.
Source
scopus
Publish Date
2015

Cancer of the stomach

Authors
Avital, I; Stojadinovic, A; Pisters, PWT; Kelsen, DP; Willett, CG
MLA Citation
Avital, I, Stojadinovic, A, Pisters, PWT, Kelsen, DP, and Willett, CG. "Cancer of the stomach." DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology: Tenth Edition. January 7, 2015.
Source
scopus
Publish Date
2015

Rectal cancer, version 2.2015: Featured updates to the NCCN guidelines

© National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease.

Authors
Benson, AB; Venook, AP; Bekaii-Saab, T; Chan, E; Chen, YJ; Cooper, HS; Engstrom, PF; Enzinger, PC; Fenton, MJ; Fuchs, CS; Grem, JL; Grothey, A; Hochster, HS; Hunt, S; Kamel, A; Kirilcuk, N; Leong, LA; Lin, E; Messersmith, WA; Mulcahy, MF; Murphy, JD; Nurkin, S; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Sofocleous, CT; Stoffel, EM; Stotsky-Himelfarb, E; Willett, CG; Gregory, KM; Freedman-Cass, D
MLA Citation
Benson, AB, Venook, AP, Bekaii-Saab, T, Chan, E, Chen, YJ, Cooper, HS, Engstrom, PF, Enzinger, PC, Fenton, MJ, Fuchs, CS, Grem, JL, Grothey, A, Hochster, HS, Hunt, S, Kamel, A, Kirilcuk, N, Leong, LA, Lin, E, Messersmith, WA, Mulcahy, MF, Murphy, JD, Nurkin, S, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Sofocleous, CT, Stoffel, EM, Stotsky-Himelfarb, E, Willett, CG, Gregory, KM, and Freedman-Cass, D. "Rectal cancer, version 2.2015: Featured updates to the NCCN guidelines." JNCCN Journal of the National Comprehensive Cancer Network 13.6 (January 1, 2015): 719-728.
Source
scopus
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
13
Issue
6
Publish Date
2015
Start Page
719
End Page
728

Anal canal cancer

© Springer Japan 2015. Radiation therapy with concurrent chemotherapy is the standard treatment for patients with nonmetastatic squamous cell carcinoma of the anal canal. In the studies that established this approach, high rates of locoregional control have been reported, but the incidence of acute and late toxicity has been significant. Moreover, treatment-related acute toxicity may cause treatment interruptions that are potentially detrimental to locoregional control and colostomy-free survival. Intensity-modulated radiation therapy (IMRT) has recently been instituted as an alternative to conventional two-dimensional (2D) or three-dimensional (3D) conformal radiotherapy. Multiple institutional experiences, as well as a single phase II multi-institution prospective study, have demonstrated improved acute toxicity rates with IMRT, potentially minimizing treatment interruptions and improving treatment outcomes. Pilot studies evaluating IMRT show no reduction in overall or colostomy-free survival versus historical studies. Due to its high precision, the use of IMRT in anal cancer requires thorough understanding of the patterns of spread of anal cancer with thoughtful delineation of target volumes and organs at risk. In this chapter, we highlight the available data on the use of IMRT for anal cancer and summarize established approaches for IMRT planning in this disease.

Authors
Perez, BA; Willett, CG; Czito, BG; Palta, M
MLA Citation
Perez, BA, Willett, CG, Czito, BG, and Palta, M. "Anal canal cancer." Intensity-Modulated Radiation Therapy: Clinical Evidence and Techniques. January 1, 2015. 337-354.
Source
scopus
Publish Date
2015
Start Page
337
End Page
354
DOI
10.1007/978-4-431-55486-8_18

Efficacy endpoints of radiation therapy group protocol 0247: a randomized, phase 2 study of neoadjuvant radiation therapy plus concurrent capecitabine and irinotecan or capecitabine and oxaliplatin for patients with locally advanced rectal cancer.

To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%).A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m(2)/d Monday-Friday) plus irinotecan (50 mg/m(2)/wk × 4); and (2) capecitabine (1650 mg/m(2)/d Monday-Friday) plus oxaliplatin (50 mg/m(2)/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m(2); leucovorin 400 mg/m(2); 5-fluorouracil 400 mg/m(2); 5-fluorouracil 2400 mg/m(2)) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local-regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually.A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively.Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.

Authors
Wong, SJ; Moughan, J; Meropol, NJ; Anne, PR; Kachnic, LA; Rashid, A; Watson, JC; Mitchell, EP; Pollock, J; Lee, RJ; Haddock, M; Erickson, BA; Willett, CG
MLA Citation
Wong, SJ, Moughan, J, Meropol, NJ, Anne, PR, Kachnic, LA, Rashid, A, Watson, JC, Mitchell, EP, Pollock, J, Lee, RJ, Haddock, M, Erickson, BA, and Willett, CG. "Efficacy endpoints of radiation therapy group protocol 0247: a randomized, phase 2 study of neoadjuvant radiation therapy plus concurrent capecitabine and irinotecan or capecitabine and oxaliplatin for patients with locally advanced rectal cancer." International journal of radiation oncology, biology, physics 91.1 (January 2015): 116-123.
PMID
25446610
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
91
Issue
1
Publish Date
2015
Start Page
116
End Page
123
DOI
10.1016/j.ijrobp.2014.09.031

Intraoperative radiotherapy in the treatment of gastrointestinal malignancies

Intraoperative radiotherapy (IORT) is a technique that allows delivery of a single high dose of radiation to a target volume during surgery. Where conventional external beam radiation therapy (EBRT) is limited by the normal tissue tolerance of abdominal and pelvic organs, IORT has an advantage that surrounding organs can be shielded or moved. This approach permits delivery of a biologically potent dose of radiation with minimal toxicity. Many gastrointestinal malignancies are characterized by high rates of local failure, thus IORT has been investigated as a means to improve local control either alone or as part of a combined modality approach. In pancreatic, gastric and rectal cancers, available data suggest that the addition of IORT consistently improves local control. The effect on survival has been variable in these cancers with a significant competing risk of distant failure. As EBRT techniques improve, the utility of IORT will need to be further validated in prospective trials.

Authors
Torok, JA; Palta, M; Czito, BG; Willett, CG
MLA Citation
Torok, JA, Palta, M, Czito, BG, and Willett, CG. "Intraoperative radiotherapy in the treatment of gastrointestinal malignancies." Translational Cancer Research 3.6 (December 1, 2014): 537-540.
Source
scopus
Published In
Translational cancer research
Volume
3
Issue
6
Publish Date
2014
Start Page
537
End Page
540
DOI
10.3978/j.issn.2218-676X.2014.04.05

Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience.

Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. Given high survival rates in stage I patients reported in small series with surgery alone, adjuvant chemoradiotherapy (CRT) has traditionally been recommended only for patients with high risk disease. Recent population-based data have demonstrated inferior outcomes to previous series. We examined disease-related outcomes for stage I tumors treated with pancreaticoduodenectomy, with and without CRT.All patients with stage I ampullary adenocarcinoma treated from 1976 to 2011 at Duke University were reviewed. Disease-related endpoints including local control (LC), metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.Forty-four patients were included in this study. Thirty-one patients underwent surgery alone, while 13 also received adjuvant CRT. Five-year LC, MFS, DFS and OS for patients treated with surgery only and surgery with CRT were 56% and 83% (P=0.13), 67% and 83% (P=0.31), 56% and 83% (P=0.13), and 53% and 68% (P=0.09), respectively.The prognosis for patients diagnosed with stage I ampullary adenocarcinoma may not be as favorable as previously described. Our data suggests a possible benefit of adjuvant CRT delivery.

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; McSherry, F; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, McSherry, F, Tyler, DS, Uronis, HE, and Czito, BG. "Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience." Journal of gastrointestinal oncology 5.6 (December 2014): 421-427.
PMID
25436120
Source
epmc
Published In
Journal of Gastrointestinal Oncology
Volume
5
Issue
6
Publish Date
2014
Start Page
421
End Page
427
DOI
10.3978/j.issn.2078-6891.2014.084

Is proton beam therapy better than standard radiation therapy? A paucity of practicality puts photons ahead of protons.

Authors
Salama, JK; Willett, CG
MLA Citation
Salama, JK, and Willett, CG. "Is proton beam therapy better than standard radiation therapy? A paucity of practicality puts photons ahead of protons." Clinical advances in hematology & oncology : H&O 12.12 (December 2014): 861-869.
PMID
25674847
Source
epmc
Published In
Clinical advances in hematology & oncology : H&O
Volume
12
Issue
12
Publish Date
2014
Start Page
861
End Page
869

Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?

OPINION STATEMENT: There is significant debate regarding the optimal neoadjuvant regimen for resectable rectal cancer patients. Short-course radiotherapy, a standard approach throughout most of northern Europe, is generally defined as 25 Gy in 5 fractions over the course of 1 week without the concurrent administration of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy in 25-28 fractions with the administration of concurrent 5-fluoropyrimidine-based chemotherapy and is the standard approach in other parts of Europe and the United States. At present, two randomized trials have compared outcomes for short course radiotherapy with long-course chemoradiation showing no difference in respective study endpoints. Late toxicity data are lacking given limited follow-up. Although the ideal neoadjuvant regimen is controversial, our current bias is long-course chemoradiation to treat patients with locally advanced, resectable rectal cancer.

Authors
Palta, M; Willett, CG; Czito, BG
MLA Citation
Palta, M, Willett, CG, and Czito, BG. "Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?." Current treatment options in oncology 15.3 (September 1, 2014): 421-428. (Review)
Source
scopus
Published In
Current Treatment Options in Oncology
Volume
15
Issue
3
Publish Date
2014
Start Page
421
End Page
428
DOI
10.1007/s11864-014-0296-2

Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?

OPINION STATEMENT: There is significant debate regarding the optimal neoadjuvant regimen for resectable rectal cancer patients. Short-course radiotherapy, a standard approach throughout most of northern Europe, is generally defined as 25 Gy in 5 fractions over the course of 1 week without the concurrent administration of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy in 25-28 fractions with the administration of concurrent 5-fluoropyrimidine-based chemotherapy and is the standard approach in other parts of Europe and the United States. At present, two randomized trials have compared outcomes for short course radiotherapy with long-course chemoradiation showing no difference in respective study endpoints. Late toxicity data are lacking given limited follow-up. Although the ideal neoadjuvant regimen is controversial, our current bias is long-course chemoradiation to treat patients with locally advanced, resectable rectal cancer.

Authors
Palta, M; Willett, CG; Czito, BG
MLA Citation
Palta, M, Willett, CG, and Czito, BG. "Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?." Current treatment options in oncology 15.3 (September 2014): 421-428. (Review)
PMID
24915746
Source
epmc
Published In
Current Treatment Options in Oncology
Volume
15
Issue
3
Publish Date
2014
Start Page
421
End Page
428
DOI
10.1007/s11864-014-0296-2

Results of the FFCD 9901 trial in early-stage esophageal carcinoma: is it really about neoadjuvant therapy?

Authors
Czito, BG; Palta, M; Willett, CG
MLA Citation
Czito, BG, Palta, M, and Willett, CG. "Results of the FFCD 9901 trial in early-stage esophageal carcinoma: is it really about neoadjuvant therapy?." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32.23 (August 2014): 2398-2400.
PMID
24982460
Source
epmc
Published In
Journal of Clinical Oncology
Volume
32
Issue
23
Publish Date
2014
Start Page
2398
End Page
2400
DOI
10.1200/jco.2014.55.7231

Patterns of recurrence after trimodality therapy for esophageal cancer.

Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined.All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery.Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%).Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes.

Authors
Dorth, JA; Pura, JA; Palta, M; Willett, CG; Uronis, HE; D'Amico, TA; Czito, BG
MLA Citation
Dorth, JA, Pura, JA, Palta, M, Willett, CG, Uronis, HE, D'Amico, TA, and Czito, BG. "Patterns of recurrence after trimodality therapy for esophageal cancer." Cancer 120.14 (July 2014): 2099-2105.
PMID
24711267
Source
epmc
Published In
Cancer
Volume
120
Issue
14
Publish Date
2014
Start Page
2099
End Page
2105
DOI
10.1002/cncr.28703

Colon cancer, version 3.2014.

The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference.

Authors
Benson, AB; Venook, AP; Bekaii-Saab, T; Chan, E; Chen, Y-J; Cooper, HS; Engstrom, PF; Enzinger, PC; Fenton, MJ; Fuchs, CS; Grem, JL; Hunt, S; Kamel, A; Leong, LA; Lin, E; Messersmith, W; Mulcahy, MF; Murphy, JD; Nurkin, S; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Sofocleous, CT; Stoffel, EM; Stotsky-Himelfarb, E; Willett, CG; Gregory, KM; Freedman-Cass, DA; National Comprehensive Cancer Network,
MLA Citation
Benson, AB, Venook, AP, Bekaii-Saab, T, Chan, E, Chen, Y-J, Cooper, HS, Engstrom, PF, Enzinger, PC, Fenton, MJ, Fuchs, CS, Grem, JL, Hunt, S, Kamel, A, Leong, LA, Lin, E, Messersmith, W, Mulcahy, MF, Murphy, JD, Nurkin, S, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Sofocleous, CT, Stoffel, EM, Stotsky-Himelfarb, E, Willett, CG, Gregory, KM, Freedman-Cass, DA, and National Comprehensive Cancer Network, . "Colon cancer, version 3.2014." Journal of the National Comprehensive Cancer Network : JNCCN 12.7 (July 2014): 1028-1059.
PMID
24994923
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
12
Issue
7
Publish Date
2014
Start Page
1028
End Page
1059
DOI
10.6004/jnccn.2014.0099

Radiotherapy for Gastrointestinal Malignancies

© 2014 John Wiley and Sons, Inc.. This chapter talks about four case studies of radiotherapy for gastrointestinal malignancies. One of the case study, a 65-year-old female presents with painless jaundice and diarrhea for 1 month. Labs show an elevation in liver function tests and total bilirubin of 13.4. Computed tomography (CT) scan reveals a 2 cm lesion in the pancreatic head. CT scan confirms no involvement of major vessels and no evidence of distant metastases. The patient undergoes pancreaticoduodenectomy, revealing pT1N0 poorly differentiated adenocarcinoma with negative margins. The chapter talks about multiple questions and answers for the gastrointestinal malignancies.

Authors
Palta, M; Willett, C; Czito, B
MLA Citation
Palta, M, Willett, C, and Czito, B. "Radiotherapy for Gastrointestinal Malignancies." Cancer Consult: Expertise for Clinical Practice. June 20, 2014. 785-788.
Source
scopus
Publish Date
2014
Start Page
785
End Page
788
DOI
10.1002/9781118589199.ch121

Colorectal cancer: adjuvant chemotherapy for rectal cancer-an unresolved issue.

Authors
Palta, M; Czito, BG; Willett, CG
MLA Citation
Palta, M, Czito, BG, and Willett, CG. "Colorectal cancer: adjuvant chemotherapy for rectal cancer-an unresolved issue." Nature reviews. Clinical oncology 11.4 (April 2014): 182-184.
PMID
24642673
Source
epmc
Published In
Nature Reviews Clinical Oncology
Volume
11
Issue
4
Publish Date
2014
Start Page
182
End Page
184
DOI
10.1038/nrclinonc.2014.43

The role of intraoperative radiation therapy in patients with pancreatic cancer.

Intraoperative radiation therapy (IORT) techniques allow for the delivery of high doses of radiation therapy while excluding part or all of the nearby dose-limiting sensitive structures. Therefore, the effective radiation dose is increased and local tumor control potentially improved. This is pertinent in the case of pancreatic cancer because local failure rates are as high as 50%-80% in patients with resected and locally advanced disease. Available data in patients receiving IORT after pancreaticoduodenectomy reveal an improvement in local control, though overall survival benefit is unclear. Series of patients with locally advanced pancreatic cancer also suggest pain relief, and in select studies, improved survival associated with the inclusion of IORT. At present, no phase III data clearly supports the use of IORT in the management of pancreatic cancer.

Authors
Palta, M; Willett, C; Czito, B
MLA Citation
Palta, M, Willett, C, and Czito, B. "The role of intraoperative radiation therapy in patients with pancreatic cancer." Seminars in radiation oncology 24.2 (April 2014): 126-131. (Review)
PMID
24635869
Source
epmc
Published In
Seminars in Radiation Oncology
Volume
24
Issue
2
Publish Date
2014
Start Page
126
End Page
131
DOI
10.1016/j.semradonc.2013.11.004

Patterns of recurrence after trimodality therapy for esophageal cancer

BACKGROUND Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined. METHODS All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery. RESULTS Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%). CONCLUSIONS Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes. © 2014 American Cancer Society.

Authors
Dorth, JA; Pura, JA; Palta, M; Willett, CG; Uronis, HE; D'Amico, TA; Czito, BG
MLA Citation
Dorth, JA, Pura, JA, Palta, M, Willett, CG, Uronis, HE, D'Amico, TA, and Czito, BG. "Patterns of recurrence after trimodality therapy for esophageal cancer." Cancer 120.14 (January 1, 2014): 2099-2105.
Source
scopus
Published In
Cancer
Volume
120
Issue
14
Publish Date
2014
Start Page
2099
End Page
2105
DOI
10.1002/cncr.28703

Colorectal cancer: adjuvant chemotherapy for rectal cancer-an unresolved issue.

Authors
Palta, M; Czito, BG; Willett, CG
MLA Citation
Palta, M, Czito, BG, and Willett, CG. "Colorectal cancer: adjuvant chemotherapy for rectal cancer-an unresolved issue." Nature reviews. Clinical oncology 11.4 (January 1, 2014): 182-184.
Source
scopus
Published In
Nature Reviews Clinical Oncology
Volume
11
Issue
4
Publish Date
2014
Start Page
182
End Page
184
DOI
10.1038/nrclinonc.2014.43

A paucity of practicality puts photons ahead of protons

Authors
Salama, JK; G willett, C
MLA Citation
Salama, JK, and G willett, C. "A paucity of practicality puts photons ahead of protons." Clinical Advances in Hematology and Oncology 12.12 (January 1, 2014): 861-869.
Source
scopus
Published In
Clinical advances in hematology & oncology : H&O
Volume
12
Issue
12
Publish Date
2014
Start Page
861
End Page
869

A prospective feasibility study of respiratory-gated proton beam therapy for liver tumors

© 2014 American Society for Radiation Oncology. Purpose: To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors. Methods and materials: Fifteen patients were enrolled in a prospective institutional review board-approved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectable biopsy- proven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤. 6 cm. Patients received 15 fractions to a total dose of 45-75 GyE [gray equivalent] using respiratory-gated proton beam therapy. Gating was performed with an external respiratory position monitoring based system. Results: Of the 15 patients enrolled in this clinical trial, 11 had HCC, 3 had ICC, and 1 had metastasis from another primary. Ten patients had a single lesion, 3 patients had 2 lesions, and 2 patients had 3 lesions. Toxicities were grade 3 bilirubinemia-2, grade 3 gastrointestinal bleed-1, and grade 5 stomach perforation-1. One patient had a marginal recurrence, 3 had hepatic recurrences elsewhere in the liver, and 2 had extrahepatic recurrence. With a median follow-up for survivors of 69 months, 1-, 2-, and 3-year overall survivals are 53%, 40%, and 33%, respectively. Progression-free survivals are 40%, 33%, and 27% at 1, 2, and 3 years, respectively. Conclusions: Respiratory-gated proton beam therapy for liver tumors is feasible. Phase 2 studies for primary liver tumors and metastatic tumors are underway.

Authors
Hong, TS; DeLaney, TF; Mamon, HJ; Willett, CG; Yeap, BY; Niemierko, A; Wolfgang, JA; Lu, HM; Adams, J; Weyman, EA; Arellano, RS; Blaszkowsky, LS; Allen, JN; Tanabe, KK; Ryan, DP; Zhu, AX
MLA Citation
Hong, TS, DeLaney, TF, Mamon, HJ, Willett, CG, Yeap, BY, Niemierko, A, Wolfgang, JA, Lu, HM, Adams, J, Weyman, EA, Arellano, RS, Blaszkowsky, LS, Allen, JN, Tanabe, KK, Ryan, DP, and Zhu, AX. "A prospective feasibility study of respiratory-gated proton beam therapy for liver tumors." Practical Radiation Oncology 4.5 (January 1, 2014): 316-322.
Source
scopus
Published In
Practical Radiation Oncology
Volume
4
Issue
5
Publish Date
2014
Start Page
316
End Page
322
DOI
10.1016/j.prro.2013.10.002

Incidence and prognostic impact of high-risk HPV tumor infection in cervical esophageal carcinoma

© Pioneer Bioscience Publishing Company. All rights reserved. Background: Cervical esophageal carcinoma (CEC) is an uncommon malignancy. Limited data supports the use of definitive chemoradiotherapy (CRT) as primary treatment. Furthermore, the role of human papillomavirus (HPV) tumor infection in CEC remains unknown. This study retrospectively analyzes both outcomes of CEC patients treated with CRT and the incidence and potential role of HPV tumor infection in CEC lesions. Methods: A total of 37 CEC patients were treated with definitive CRT at our institution between 1987 and 2013. Of these, 19 had tumor samples available for high-risk HPV (types 16 and 18) pathological analysis. Results: For all patients (n=37), 5-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 34.1%, 40.2%, and 65.6%, respectively. On pathological analysis, 1/19 (5.3%) patients had an HPV-positive lesion. Conclusions: Definitive CRT provides disease-related outcomes comparable to surgery. Moreover, HPV tumor infection in CEC is uncommon and its prognostic role is unclear. Our data contribute to the construction of an anatomical map of HPV tumor infection in squamous cell carcinomas (SCC) of the upper aerodigestive tract, and suggest a steep drop in viral infection rates at sites distal to the oropharynx, including the cervical esophagus.

Authors
Ludmir, EB; Palta, M; Zhang, X; Wu, Y; Willett, CG; Czito, BG
MLA Citation
Ludmir, EB, Palta, M, Zhang, X, Wu, Y, Willett, CG, and Czito, BG. "Incidence and prognostic impact of high-risk HPV tumor infection in cervical esophageal carcinoma." Journal of Gastrointestinal Oncology 5.6 (January 1, 2014): 401-407.
Source
scopus
Published In
Journal of Gastrointestinal Oncology
Volume
5
Issue
6
Publish Date
2014
Start Page
401
End Page
407
DOI
10.3978/j.issn.2078-6891.2014.05

Incidence and Prognostic Impact of High-Risk HPV Tumor Infection in Cervical Esophageal Carcinoma

Authors
Ludmir, E; Palta, M; Zhang, X; Wu, Y; Willett, C; Czito, B
MLA Citation
Ludmir, E, Palta, M, Zhang, X, Wu, Y, Willett, C, and Czito, B. "Incidence and Prognostic Impact of High-Risk HPV Tumor Infection in Cervical Esophageal Carcinoma." Journal of Gastrointestinal Oncology 5.6 (2014): 401-407.
PMID
25436117
Source
manual
Published In
Journal of Gastrointestinal Oncology
Volume
5
Issue
6
Publish Date
2014
Start Page
401
End Page
407
DOI
10.3978/j.issn.2078-6891.2014.053

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

Authors
Gunderson, LL; Moughan, J; Ajani, JA; Pedersen, JE; Winter, KA; III, BAB; Jr, TCR; Mayer, RJ; Haddock, MG; Rich, TA; Willett, CG
MLA Citation
Gunderson, LL, Moughan, J, Ajani, JA, Pedersen, JE, Winter, KA, III, BAB, Jr, TCR, Mayer, RJ, Haddock, MG, Rich, TA, and Willett, CG. "Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial." INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 87.4 (November 15, 2013): 638-645.
PMID
24035327
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
4
Publish Date
2013
Start Page
638
End Page
645
DOI
10.1016/j.ijrobp.2013.07.035

Inhibiting the inhibitor: targeting vascular endothelial protein tyrosine phosphatase to promote tumor vascular maturation.

Authors
Kontos, CD; Willett, CG
MLA Citation
Kontos, CD, and Willett, CG. "Inhibiting the inhibitor: targeting vascular endothelial protein tyrosine phosphatase to promote tumor vascular maturation." J Natl Cancer Inst 105.16 (August 21, 2013): 1163-1165.
PMID
23899554
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
105
Issue
16
Publish Date
2013
Start Page
1163
End Page
1165
DOI
10.1093/jnci/djt199

Oncology scan-treatment, consequences, and genomics in gastrointestinal cancer.

Authors
Willett, CG; Chang, DT; Czito, BG; Meyer, J; Wo, J
MLA Citation
Willett, CG, Chang, DT, Czito, BG, Meyer, J, and Wo, J. "Oncology scan-treatment, consequences, and genomics in gastrointestinal cancer." Int J Radiat Oncol Biol Phys 86.1 (May 1, 2013): 1-3.
PMID
23582240
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
86
Issue
1
Publish Date
2013
Start Page
1
End Page
3
DOI
10.1016/j.ijrobp.2012.12.006

Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+.

Authors
Ajani, JA; Bentrem, DJ; Besh, S; D'Amico, TA; Das, P; Denlinger, C; Fakih, MG; Fuchs, CS; Gerdes, H; Glasgow, RE; Hayman, JA; Hofstetter, WL; Ilson, DH; Keswani, RN; Kleinberg, LR; Korn, WM; Lockhart, AC; Meredith, K; Mulcahy, MF; Orringer, MB; Posey, JA; Sasson, AR; Scott, WJ; Strong, VE; Varghese, TK; Warren, G; Washington, MK; Willett, C; Wright, CD; McMillian, NR; Sundar, H; National Comprehensive Cancer Network,
MLA Citation
Ajani, JA, Bentrem, DJ, Besh, S, D'Amico, TA, Das, P, Denlinger, C, Fakih, MG, Fuchs, CS, Gerdes, H, Glasgow, RE, Hayman, JA, Hofstetter, WL, Ilson, DH, Keswani, RN, Kleinberg, LR, Korn, WM, Lockhart, AC, Meredith, K, Mulcahy, MF, Orringer, MB, Posey, JA, Sasson, AR, Scott, WJ, Strong, VE, Varghese, TK, Warren, G, Washington, MK, Willett, C, Wright, CD, McMillian, NR, Sundar, H, and National Comprehensive Cancer Network, . "Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines." J Natl Compr Canc Netw 11.5 (May 1, 2013): 531-546.
PMID
23667204
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
5
Publish Date
2013
Start Page
531
End Page
546

Multidisciplinary management of locally advanced rectal cancer: neoadjuvant approaches.

Although tumor biology and genomics of colon and rectal cancer are no different, patients with locally advanced rectal cancer (LARC) require neoadjuvant fluoropyrimidine-based chemoradiation and total mesorectal excision. In addition to known clinical risk factors, improved algorithms integrating molecular tools are needed to stratify patients with LARC to improve treatment outcomes and reduce acute and long-term toxicities. Simply combining newer systemic or targeted agents with standard treatment in all patients yielded little success but added toxicities. This article reviews the historical data, current standards of care, and ongoing research efforts regarding biomarkers, molecular imaging, and personalized genomic information.

Authors
Murugappan, S; Harris, WP; Willett, CG; Lin, E
MLA Citation
Murugappan, S, Harris, WP, Willett, CG, and Lin, E. "Multidisciplinary management of locally advanced rectal cancer: neoadjuvant approaches." J Natl Compr Canc Netw 11.5 (May 1, 2013): 548-557. (Review)
PMID
23667205
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
5
Publish Date
2013
Start Page
548
End Page
557

ACT II: treatment of anal cancer comes full circle.

Authors
Willett, CG; Czito, BG; Palta, M
MLA Citation
Willett, CG, Czito, BG, and Palta, M. "ACT II: treatment of anal cancer comes full circle." Lancet Oncol 14.6 (May 2013): 443-445.
PMID
23578723
Source
pubmed
Published In
The Lancet Oncology
Volume
14
Issue
6
Publish Date
2013
Start Page
443
End Page
445
DOI
10.1016/S1470-2045(13)70121-9

The role of local excision in invasive adenocarcinoma of the ampulla of Vater.

BACKGROUND: Ampulla of Vater carcinomas are rare malignancies that have been traditionally treated with radical surgical resection. Given the mortality associated with pancreaticoduodenectomy, some patients may benefit from local resection. A single-institution outcomes analysis was performed to define the role of local resection. METHODS: Patients undergoing local resection (ampullectomy) for ampullary carcinomas at Duke University between 1976 and 2010 were analyzed retrospectively. Time-to-event analysis was conducted analyzing all patients undergoing surgery, with and without adjuvant chemoradiation therapy (CRT). Overall survival (OS), local control (LC), metastases-free survival (MFS), and disease-free survival (DFS) were studied using Kaplan-Meier analysis. RESULTS: A total of 17 patients with invasive carcinoma underwent ampullectomy. The 3-and 5-year LC, MFS, DFS and OS rates were 36% and 24%, 68% and 54%, 31% and 21%, and 35% and 21%, respectively. Patients receiving adjuvant CRT did not appear to have improved outcomes compared with surgery alone, although this group tended to have poorer histological grade, more advanced tumor staging and involved surgical margins. CONCLUSIONS: Ampullectomy for invasive ampullary adenocarcinomas is a safe procedure but does not offer satisfactory long-term results, mostly due to high local failure rates. Adjuvant CRT therapy does not appear to offer increased local control or survival benefit following ampullectomy, although these results may suffer from selection bias and small sample size. Local resection should be limited to benign ampullary lesions or patients with very small, early tumors with favorable histologic features where radical resection is not feasible.

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; Bulusu, A; Tyler, DS; White, RR; Uronis, HE; Pappas, TN; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, Bulusu, A, Tyler, DS, White, RR, Uronis, HE, Pappas, TN, and Czito, BG. "The role of local excision in invasive adenocarcinoma of the ampulla of Vater." J Gastrointest Oncol 4.1 (March 2013): 8-13.
PMID
23450004
Source
pubmed
Published In
Journal of Gastrointestinal Oncology
Volume
4
Issue
1
Publish Date
2013
Start Page
8
End Page
13
DOI
10.3978/j.issn.2078-6891.2012.055

Preoperative chemoradiotherapy for locally advanced gastric cancer.

BACKGROUND: To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. METHODS: Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. RESULTS: Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. CONCLUSIONS: Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

Authors
Pepek, JM; Chino, JP; Willett, CG; Palta, M; Blazer Iii, DG; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Pepek, JM, Chino, JP, Willett, CG, Palta, M, Blazer Iii, DG, Tyler, DS, Uronis, HE, and Czito, BG. "Preoperative chemoradiotherapy for locally advanced gastric cancer. (Published online)" Radiat Oncol 8 (January 4, 2013): 6-.
PMID
23286735
Source
pubmed
Published In
Radiation Oncology
Volume
8
Publish Date
2013
Start Page
6
DOI
10.1186/1748-717X-8-6

Technical considerations in radiation therapy for gastroesophageal junction cancer.

Contemporary randomized trials have demonstrated that radiation therapy combined with chemotherapy and surgery improves survival in both the neoadjuvant and adjuvant treatment of gastroesophageal cancers. Consequently, radiation treatment planning and administration have taken on an added importance to ensure optimal outcomes as well as minimize treatment-related morbidity. This article highlights recent technical advances and considerations for radiation therapy planning for gastroesophageal junction tumors.

Authors
Pepek, JM; Willett, CG; Czito, BG
MLA Citation
Pepek, JM, Willett, CG, and Czito, BG. "Technical considerations in radiation therapy for gastroesophageal junction cancer." Semin Radiat Oncol 23.1 (January 2013): 51-59. (Review)
PMID
23207047
Source
pubmed
Published In
Seminars in Radiation Oncology
Volume
23
Issue
1
Publish Date
2013
Start Page
51
End Page
59
DOI
10.1016/j.semradonc.2012.09.005

A prospective feasibility study of respiratory-gated proton beam therapy for liver tumors

Purpose: To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors. Methods and materials: Fifteen patients were enrolled in a prospective institutional review board-approved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectable biopsy- proven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤ 6 cm. Patients received 15 fractions to a total dose of 45-75 GyE [gray equivalent] using respiratory-gated proton beam therapy. Gating was performed with an external respiratory position monitoring based system. Results: Of the 15 patients enrolled in this clinical trial, 11 had HCC, 3 had ICC, and 1 had metastasis from another primary. Ten patients had a single lesion, 3 patients had 2 lesions, and 2 patients had 3 lesions. Toxicities were grade 3 bilirubinemia-2, grade 3 gastrointestinal bleed-1, and grade 5 stomach perforation-1. One patient had a marginal recurrence, 3 had hepatic recurrences elsewhere in the liver, and 2 had extrahepatic recurrence. With a median follow-up for survivors of 69 months, 1-, 2-, and 3-year overall survivals are 53%, 40%, and 33%, respectively. Progression-free survivals are 40%, 33%, and 27% at 1, 2, and 3 years, respectively. Conclusions: Respiratory-gated proton beam therapy for liver tumors is feasible. Phase 2 studies for primary liver tumors and metastatic tumors are underway. © 2013 American Society for Radiation Oncology.

Authors
Hong, TS; DeLaney, TF; Mamon, HJ; Willett, CG; Yeap, BY; Niemierko, A; Wolfgang, JA; Lu, H-M; Adams, J; Weyman, EA; Arellano, RS; Blaszkowsky, LS; Allen, JN; Tanabe, KK; Ryan, DP; Zhu, AX
MLA Citation
Hong, TS, DeLaney, TF, Mamon, HJ, Willett, CG, Yeap, BY, Niemierko, A, Wolfgang, JA, Lu, H-M, Adams, J, Weyman, EA, Arellano, RS, Blaszkowsky, LS, Allen, JN, Tanabe, KK, Ryan, DP, and Zhu, AX. "A prospective feasibility study of respiratory-gated proton beam therapy for liver tumors (Accepted)." Practical Radiation Oncology (2013).
PMID
25194100
Source
scopus
Published In
Practical Radiation Oncology
Publish Date
2013
DOI
10.1016/j.prro.2013.10.002

James et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): A randomised, phase 3, open-label, 232 factorial trial. Lancet Oncol 2013. (6)

Authors
Willett, CG; Chang, D; Czito, B; Meyer, J; Wo, J
MLA Citation
Willett, CG, Chang, D, Czito, B, Meyer, J, and Wo, J. "James et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): A randomised, phase 3, open-label, 232 factorial trial. Lancet Oncol 2013. (6)." International Journal of Radiation Oncology Biology Physics 87.5 (2013): 862-863.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
5
Publish Date
2013
Start Page
862
End Page
863
DOI
10.1016/j.ijrobp.2013.09.006

Ngan et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol 2012. (1)

Authors
Willett, CG; Chang, D; Czito, B; Meyer, J; Wo, J
MLA Citation
Willett, CG, Chang, D, Czito, B, Meyer, J, and Wo, J. "Ngan et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol 2012. (1)." International Journal of Radiation Oncology Biology Physics 87.5 (2013): 861--.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
5
Publish Date
2013
Start Page
861-
DOI
10.1016/j.ijrobp.2013.09.006

Gordon et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol 2013. (4)

Authors
Willett, CG; Chang, D; Czito, B; Meyer, J; Wo, J
MLA Citation
Willett, CG, Chang, D, Czito, B, Meyer, J, and Wo, J. "Gordon et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol 2013. (4)." International Journal of Radiation Oncology Biology Physics 87.5 (2013): 861-862.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
5
Publish Date
2013
Start Page
861
End Page
862
DOI
10.1016/j.ijrobp.2013.09.006

Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010

BACKGROUND In the current study, the authors evaluated long-term outcomes, intraoperative radiotherapy (IORT)-related toxicity, and prognostic factors for overall survival (OS) among patients with unresectable locally advanced pancreatic cancer (LAPC) who received IORT as part of their treatment at the Massachusetts General Hospital (MGH). METHODS Medical records were reviewed for 194 consecutive patients with unresectable LAPC who were treated with IORT at MGH between 1978 and 2010. OS was calculated using the Kaplan-Meier method. Prognostic factors were evaluated at the univariate level by the log-rank test and at the multivariate level by the Cox proportional hazards model. Rates of disease progression and treatment toxicity were calculated. RESULTS The 1-year, 2-year, and 3-year survival rates were 49%, 16%, and 6%, respectively. Six patients (3%) survived for > 5 years. The median OS was 12.0 months. Among 183 patients with known post-IORT disease status, the 2-year local progression-free survival and distant metastasis-free survival rates were 41% and 28%, respectively. On multivariate analysis, an IORT applicator diameter ≤ 8 cm (hazards ratio [HR], 0.51; 95% confidence interval [95% CI], 0.30-0.84 [P =.009]), a Charlson age-comorbidity index ≤ 3 (HR, 0.47; 95% CI, 0.31-0.73 [P =.001]), and receipt of chemotherapy (HR, 0.46; 95% CI, 0.33-0.66 [P <.001]) predicted improved OS. The median OS for patients with all 3 positive prognostic factors was 21.2 months. CONCLUSIONS Well-selected patients with LAPC with small tumors and low Charlson age-comorbidity indices can achieve good long-term survival outcomes with a treatment regimen that incorporates chemotherapy and IORT. © 2013 American Cancer Society.

Authors
Cai, S; Hong, TS; Goldberg, SI; Castillo, CF-D; Thayer, SP; Ferrone, CR; Ryan, DP; Blaszkowsky, LS; Kwak, EL; Willett, CG; al, E
MLA Citation
Cai, S, Hong, TS, Goldberg, SI, Castillo, CF-D, Thayer, SP, Ferrone, CR, Ryan, DP, Blaszkowsky, LS, Kwak, EL, Willett, CG, and al, E. "Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010." Cancer 119.23 (2013): 4196-4204.
Source
scival
Published In
Cancer
Volume
119
Issue
23
Publish Date
2013
Start Page
4196
End Page
4204
DOI
10.1002/cncr.28329

Implementing and integrating a clinically driven electronic medical record for radiation oncology in a large medical enterprise.

PURPOSE/OBJECTIVE: While our department is heavily invested in computer-based treatment planning, we historically relied on paper-based charts for management of Radiation Oncology patients. In early 2009, we initiated the process of conversion to an electronic medical record (EMR) eliminating the need for paper charts. Key goals included the ability to readily access information wherever and whenever needed, without compromising safety, treatment quality, confidentiality, or productivity. METHODOLOGY: In February, 2009, we formed a multi-disciplinary team of Radiation Oncology physicians, nurses, therapists, administrators, physicists/dosimetrists, and information technology (IT) specialists, along with staff from the Duke Health System IT department. The team identified all existing processes and associated information/reports, established the framework for the EMR system and generated, tested and implemented specific EMR processes. RESULTS: Two broad classes of information were identified: information which must be readily accessed by anyone in the health system versus that used solely within the Radiation Oncology department. Examples of the former are consultation reports, weekly treatment check notes, and treatment summaries; the latter includes treatment plans, daily therapy records, and quality assurance reports. To manage the former, we utilized the enterprise-wide system, which required an intensive effort to design and implement procedures to export information from Radiation Oncology into that system. To manage "Radiation Oncology" data, we used our existing system (ARIA, Varian Medical Systems.) The ability to access both systems simultaneously from a single workstation (WS) was essential, requiring new WS and modified software. As of January, 2010, all new treatments were managed solely with an EMR. We find that an EMR makes information more widely accessible and does not compromise patient safety, treatment quality, or confidentiality. However, compared to paper charts, time required by clinicians to access/enter patient information has substantially increased. While productivity is improving with experience, substantial growth will require better integration of the system components, decreased access times, and improved user interfaces. $127K was spent on new hardware and software; elimination of paper yields projected savings of $21K/year. One year after conversion to an EMR, more than 90% of department staff favored the EMR over the previous paper charts. CONCLUSION: Successful implementation of a Radiation Oncology EMR required not only the effort and commitment of all functions of the department, but support from senior health system management, corporate IT, and vendors. Realization of the full benefits of an EMR will require experience, faster/better integrated software, and continual improvement in underlying clinical processes.

Authors
Kirkpatrick, JP; Light, KL; Walker, RM; Georgas, DL; Antoine, PA; Clough, RW; Cozart, HB; Yin, F-F; Yoo, S; Willett, CG
MLA Citation
Kirkpatrick, JP, Light, KL, Walker, RM, Georgas, DL, Antoine, PA, Clough, RW, Cozart, HB, Yin, F-F, Yoo, S, and Willett, CG. "Implementing and integrating a clinically driven electronic medical record for radiation oncology in a large medical enterprise. (Published online)" Front Oncol 3 (2013): 69-.
PMID
23616946
Source
pubmed
Published In
Frontiers in Oncology
Volume
3
Publish Date
2013
Start Page
69
DOI
10.3389/fonc.2013.00069

Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m2 per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m2 per day, Monday to Friday, plus irinotecan, 50 mg/m2 once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival. © 2013 Elsevier Inc. All rights reserved.

Authors
Mohiuddin, M; Paulus, R; Mitchell, E; Hanna, N; Yuen, A; Nichols, R; Yalavarthi, S; Hayostek, C; Willett, C
MLA Citation
Mohiuddin, M, Paulus, R, Mitchell, E, Hanna, N, Yuen, A, Nichols, R, Yalavarthi, S, Hayostek, C, and Willett, C. "Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer." International Journal of Radiation Oncology, Biology, Physics (2013).
PMID
23545284
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Publish Date
2013
DOI
10.1016/j.ijrobp.2013.02.020

Practical Radiation Oncology for Surgeons

Authors
Willett, CG
MLA Citation
Willett, CG. "Practical Radiation Oncology for Surgeons." Surgical Oncology Clinics of North America (2013).
PMID
23622084
Source
scival
Published In
Surgical Oncology Clinics of North America
Publish Date
2013
DOI
10.1016/j.soc.2013.02.013

Oncology scan - Treatment, consequences, and genomics in gastrointestinal cancer

Authors
Willett, CG; Chang, DT; Czito, BG; Meyer, J; Wo, J
MLA Citation
Willett, CG, Chang, DT, Czito, BG, Meyer, J, and Wo, J. "Oncology scan - Treatment, consequences, and genomics in gastrointestinal cancer." International Journal of Radiation Oncology Biology Physics 86.1 (2013): 1-2.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
86
Issue
1
Publish Date
2013
Start Page
1
End Page
2
DOI
10.1016/j.ijrobp.2012.12.006

De Vathaire et al. Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors:

Authors
Willett, CG; Chang, DT; Czito, BG; Meyer, J; Wo, J
MLA Citation
Willett, CG, Chang, DT, Czito, BG, Meyer, J, and Wo, J. "De Vathaire et al. Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors:." International Journal of Radiation Oncology Biology Physics 86.1 (2013): 2-3.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
86
Issue
1
Publish Date
2013
Start Page
2
End Page
3
DOI
10.1016/j.ijrobp.2012.12.006

RTOG 0529: A phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal

Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials. © 2013 Elsevier Inc. All rights reserved.

Authors
Kachnic, LA; Winter, K; Myerson, RJ; Goodyear, MD; Willins, J; Esthappan, J; Haddock, MG; Rotman, M; Parikh, PJ; Safran, H; Willett, CG
MLA Citation
Kachnic, LA, Winter, K, Myerson, RJ, Goodyear, MD, Willins, J, Esthappan, J, Haddock, MG, Rotman, M, Parikh, PJ, Safran, H, and Willett, CG. "RTOG 0529: A phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal." International Journal of Radiation Oncology Biology Physics 86.1 (2013): 27-33.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
86
Issue
1
Publish Date
2013
Start Page
27
End Page
33
DOI
10.1016/j.ijrobp.2012.09.023

ACT II: Treatment of anal cancer comes full circle

Authors
Willett, CG; Czito, BG; Palta, M
MLA Citation
Willett, CG, Czito, BG, and Palta, M. "ACT II: Treatment of anal cancer comes full circle." The Lancet Oncology 14.6 (2013): 443-445.
Source
scival
Published In
The Lancet Oncology
Volume
14
Issue
6
Publish Date
2013
Start Page
443
End Page
445
DOI
10.1016/S1470-2045(13)70121-9

Practical Radiation Oncology for Surgeons

Authors
Willett, CG
MLA Citation
Willett, CG. "Practical Radiation Oncology for Surgeons." Surgical Oncology Clinics of North America 22.3 (2013): xv-xvi.
Source
scival
Published In
Surgical Oncology Clinics of North America
Volume
22
Issue
3
Publish Date
2013
Start Page
xv
End Page
xvi
DOI
10.1016/j.soc.2013.02.013

Metastatic colon cancer, version 3.2013: Featured updates to the NCCN guidelines

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, peri-operative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy. Copyright © 2013 JNCCN-Journal of the National Comprehensive Cancer Network.

Authors
III, ABB; Bekaii-Saab, T; Chan, E; Chen, Y-J; Choti, MA; Cooper, HS; Engstrom, PF; Enzinger, PC; Fakih, MG; Fenton, MJ; Fuchs, CS; Grem, JL; Hunt, S; Kamel, A; Leong, LA; Lin, E; May, KS; Mulcahy, MF; Murphy, K; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Jr, WS; Sofocleous, CT; Venook, AP; Willett, CG; Gregory, KM; Freedman-Cass, DA
MLA Citation
III, ABB, Bekaii-Saab, T, Chan, E, Chen, Y-J, Choti, MA, Cooper, HS, Engstrom, PF, Enzinger, PC, Fakih, MG, Fenton, MJ, Fuchs, CS, Grem, JL, Hunt, S, Kamel, A, Leong, LA, Lin, E, May, KS, Mulcahy, MF, Murphy, K, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Jr, WS, Sofocleous, CT, Venook, AP, Willett, CG, Gregory, KM, and Freedman-Cass, DA. "Metastatic colon cancer, version 3.2013: Featured updates to the NCCN guidelines." JNCCN Journal of the National Comprehensive Cancer Network 11.2 (2013): 141-152.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
2
Publish Date
2013
Start Page
141
End Page
152

Neoadjuvant chemoradiation for distal rectal cancer: 5-year updated results of a randomized phase 2 study of neoadjuvant combined modality chemoradiation for distal rectal cancer

One hundred six rectal cancer patients were randomized to receive neoadjuvant 5-FU and hyperfractionated radiation (55-60 Gy) or irinotecan/5-FU and once daily radiation (50-55 Gy). Surgery was performed 4 to 10 weeks later. Diseasespecific survival (DSS) rates were 78% and 85%, and 5-year overall survival rates were 61% and 75% for Arm1 and Arm 2, respectively. High DSS rates were observed in both arms, but Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m2 per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m2 per day, Monday to Friday, plus irinotecan, 50 mg/m2 once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Diseasespecific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. © 2013 Elsevier Inc.

Authors
Mohiuddin, M; Paulus, R; Mitchell, E; Hanna, N; Yuen, A; Nichols, R; Yalavarthi, S; Hayostek, C; Willett, C
MLA Citation
Mohiuddin, M, Paulus, R, Mitchell, E, Hanna, N, Yuen, A, Nichols, R, Yalavarthi, S, Hayostek, C, and Willett, C. "Neoadjuvant chemoradiation for distal rectal cancer: 5-year updated results of a randomized phase 2 study of neoadjuvant combined modality chemoradiation for distal rectal cancer." International Journal of Radiation Oncology Biology Physics 86.3 (2013): 523-528.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
86
Issue
3
Publish Date
2013
Start Page
523
End Page
528
DOI
10.1016/j.ijrobp.2013.02.020

Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010

BACKGROUND: In the current study, the authors evaluated long-term outcomes, intraoperative radiotherapy (IORT)-related toxicity, and prognostic factors for overall survival (OS) among patients with unresectable locally advanced pancreatic cancer (LAPC) who received IORT as part of their treatment at the Massachusetts General Hospital (MGH). METHODS: Medical records were reviewed for 194 consecutive patients with unresectable LAPC who were treated with IORT at MGH between 1978 and 2010. OS was calculated using the Kaplan-Meier method. Prognostic factors were evaluated at the univariate level by the log-rank test and at the multivariate level by the Cox proportional hazards model. Rates of disease progression and treatment toxicity were calculated. RESULTS: The 1-year, 2-year, and 3-year survival rates were 49%, 16%, and 6%, respectively. Six patients (3%) survived for >5 years. The median OS was 12.0 months. Among 183 patients with known post-IORT disease status, the 2-year local progression-free survival and distant metastasis-free survival rates were 41% and 28%, respectively. On multivariate analysis, an IORT applicator diameter ≤8 cm (hazards ratio [HR], 0.51; 95% confidence interval [95% CI], 0.30-0.84 [P=.009]), a Charlson age-comorbidity index ≤3 (HR, 0.47; 95% CI, 0.31-0.73 [P=.001]), and receipt of chemotherapy (HR, 0.46; 95% CI, 0.33-0.66 [P<.001]) predicted improved OS. The median OS for patients with all 3 positive prognostic factors was 21.2 months. CONCLUSIONS: Well-selected patients with LAPC with small tumors and low Charlson age-comorbidity indices can achieve good long-term survival outcomes with a treatment regimen that incorporates chemotherapy and IORT. © 2013 American Cancer Society.

Authors
Cai, S; Hong, TS; Goldberg, SI; Castillo, CF-D; Thayer, SP; Ferrone, CR; Ryan, DP; Blaszkowsky, LS; Kwak, EL; Willett, CG; al, E
MLA Citation
Cai, S, Hong, TS, Goldberg, SI, Castillo, CF-D, Thayer, SP, Ferrone, CR, Ryan, DP, Blaszkowsky, LS, Kwak, EL, Willett, CG, and al, E. "Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010." Cancer (2013).
PMID
24006012
Source
scival
Published In
Cancer
Publish Date
2013
DOI
10.1002/cncr.28329

Localized Colon Cancer, version 3.2013

The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions regarding the treatment of localized disease for the 2013 update of the guidelines. Copyright © 2013 by the National Comprehensive Cancer Network. All rights reserved.

Authors
III, ABB; Bekaii-Saab, T; Chan, E; Chen, Y-J; Choti, MA; Cooper, HS; Engstrom, PF; Enzinger, PC; Fakih, MG; Fenton, MJ; Fuchs, CS; Grem, JL; Hunt, S; Kamel, A; Leong, LA; Lin, E; May, KS; Mulcahy, MF; Murphy, K; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Jr, WS; Sofocleous, CT; Venook, AP; Willett, CG; Gregory, KM; Freedman-Cass, DA
MLA Citation
III, ABB, Bekaii-Saab, T, Chan, E, Chen, Y-J, Choti, MA, Cooper, HS, Engstrom, PF, Enzinger, PC, Fakih, MG, Fenton, MJ, Fuchs, CS, Grem, JL, Hunt, S, Kamel, A, Leong, LA, Lin, E, May, KS, Mulcahy, MF, Murphy, K, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Jr, WS, Sofocleous, CT, Venook, AP, Willett, CG, Gregory, KM, and Freedman-Cass, DA. "Localized Colon Cancer, version 3.2013." JNCCN Journal of the National Comprehensive Cancer Network 11.5 (2013): 519-528.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
5
Publish Date
2013
Start Page
519
End Page
528

Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Survival, Relapse, and Colostomy Failure With Concurrent Chemoradiation Involving Fluorouracil/Mitomycin Versus Fluorouracil/Cisplatin

Authors
Gunderson, LL; Winter, KA; Ajani, JA; Pedersen, JE; Moughan, J; III, BAB; Jr, TCR; Mayer, RJ; Haddock, MG; Rich, TA; Willett, CG
MLA Citation
Gunderson, LL, Winter, KA, Ajani, JA, Pedersen, JE, Moughan, J, III, BAB, Jr, TCR, Mayer, RJ, Haddock, MG, Rich, TA, and Willett, CG. "Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Survival, Relapse, and Colostomy Failure With Concurrent Chemoradiation Involving Fluorouracil/Mitomycin Versus Fluorouracil/Cisplatin." JOURNAL OF CLINICAL ONCOLOGY 30.35 (December 10, 2012): 4344-4351.
PMID
23150707
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
35
Publish Date
2012
Start Page
4344
End Page
4351
DOI
10.1200/JCO.2012.43.8085

Anal Cancer

This chapter provides an overview of the epidemiology, diagnosis, and treatment of the various tumors that arise in the anal canal and surrounding perianal skin. In particular, we focus on the evolution of treatment for squamous cell anal canal cancers, and discuss recent advances in combined modality therapy for this disease. We also highlight potential future developments aimed at improving tumor control rates while minimizing treatment-associated toxicities. This edition first published 2013 © 2013 John Wiley & Sons Ltd.

Authors
Meyer, JJ; Willett, CG; Czito, BG
MLA Citation
Meyer, JJ, Willett, CG, and Czito, BG. "Anal Cancer." (November 15, 2012): 137-160. (Chapter)
Source
scopus
Publish Date
2012
Start Page
137
End Page
160
DOI
10.1002/9781118423318.ch6

Compliance with therapeutic guidelines in Radiation Therapy Oncology Group prospective gastrointestinal clinical trials.

BACKGROUND: This report analyzes the adherence to radiation therapy protocol guidelines in contemporary Radiation Therapy Oncology Group (RTOG) gastrointestinal trials. We aim to provide insight into current standards and compliance of radiation therapy field design and administration. METHODS: From 1994 to 2006, the Gastrointestinal Cancer Committee of the RTOG initiated and completed 15 phase I-III clinical trials utilizing radiation therapy in the multimodality treatment of gastrointestinal cancers. In each protocol, details for planning and executing radiation therapy were outlined and each protocol contained scoring criteria for these components of radiation therapy, characterized according to per-protocol, variation acceptable and deviation unacceptable. Review of treatment planning and implementation was performed in all studies following therapy completion. RESULTS: Radiation therapy planning and implementation was reviewed in 2309 of 2312 (99.9%) patients. The mean rate of compliance over all for the 15 protocols was 65% (total of the 2309 analyzed patients). The mean variation acceptable rate was 21% whereas the mean deviation unacceptable rate was 5%. The mean "other" rate (no RT given or incomplete RT due to death, progression or refusal) was 8%. Two of the 15 trials (13%) had deviation unacceptable rates >10%. In four studies incorporating pre-treatment review of radiation therapy planning and treatment, compliance with protocol therapy was enhanced. CONCLUSIONS: The fidelity of radiation planning and execution detailed in protocol to actual therapy is heterogeneous, with a mean per-protocol rate of 65%. As clinical trials evolve, available technology should permit efficient pre-treatment review processes, thus facilitating compliance to protocol therapy. These analyses should also permit prospective analysis of outcome measures by compliance to therapy.

Authors
Willett, CG; Moughan, J; O'Meara, E; Galvin, JM; Crane, CH; Winter, K; Manfredi, D; Rich, TA; Rabinovitch, R; Lustig, R; Machtay, M; Curran, WJ
MLA Citation
Willett, CG, Moughan, J, O'Meara, E, Galvin, JM, Crane, CH, Winter, K, Manfredi, D, Rich, TA, Rabinovitch, R, Lustig, R, Machtay, M, and Curran, WJ. "Compliance with therapeutic guidelines in Radiation Therapy Oncology Group prospective gastrointestinal clinical trials." Radiother Oncol 105.1 (October 2012): 9-13.
PMID
23084596
Source
pubmed
Published In
Radiotherapy and Oncology
Volume
105
Issue
1
Publish Date
2012
Start Page
9
End Page
13
DOI
10.1016/j.radonc.2012.09.011

Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy.

PURPOSE: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic disease. Little is known regarding the use of radiotherapy in the prevention of local recurrence after resection. To better define the role of radiotherapy, we performed an analysis of resected patients at our institution. METHODS: Between 1994 and 2009, 33 patients with NET of the pancreatic head and neck underwent treatment with curative intent at Duke University Medical Center. Sixteen patients were treated with surgical resection alone while an additional 17 underwent resection with adjuvant or neoadjuvant radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. RESULTS: Thirteen patients (39%) experienced treatment failure. Eleven of the initial failures were distant, one was local only and one was local and distant. Two-year overall survival was 77% for all patients. Two-year local control for all patients was 87%: 85% for the CMT group and 90% for the surgery alone group (p = 0.38). Two-year distant metastasis-free survival was 56% for all patients: 46% and 69% for the CMT and surgery patients, respectively (p = 0.10). CONCLUSIONS: The primary mode of failure is distant which often results in mortality, with local failure occurring much less commonly. The role of radiotherapy in the adjuvant management of NET remains unclear.

Authors
Zagar, TM; White, RR; Willett, CG; Tyler, DS; Papavassiliou, P; Papalezova, KT; Guy, CD; Broadwater, G; Clough, RW; Czito, BG
MLA Citation
Zagar, TM, White, RR, Willett, CG, Tyler, DS, Papavassiliou, P, Papalezova, KT, Guy, CD, Broadwater, G, Clough, RW, and Czito, BG. "Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy." Int J Radiat Oncol Biol Phys 83.4 (July 15, 2012): 1126-1131.
PMID
22270161
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
83
Issue
4
Publish Date
2012
Start Page
1126
End Page
1131
DOI
10.1016/j.ijrobp.2011.09.041

Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?

The objective of this study was to compare survival between all patients with radiographically resectable adenocarcinoma of the proximal pancreas who underwent preoperative chemoradiation therapy (PRE-OP CRT) or surgical exploration first (SURGERY) with "intention to resect." Pancreatic cancer patients who undergo resection after PREOP CRT live longer than patients who undergo resection without PREOP CRT, a difference that may be attributable to patient selection. We retrospectively identified 236 patients with pancreatic head adenocarcinoma seen between 1999 and 2007 with sufficient data to be confirmed medically and radiographically resectable. The outcomes of 144 patients who underwent PREOP CRT were compared to those of 92 patients who proceeded straight to SURGERY. The groups were similar in age and gender. Tumors were slightly larger in the PREOP CRT group (mean 2.5 cm vs. 2.1 cm, P < 0.01), and there were trends toward more venous abutment (54% vs. 39%, P = 0.06) and a higher Charlson comorbidity index (P = 0.1). In the PREOP CRT group, 76 patients (53%) underwent resection, 28 (19%) had metastatic and 17 (12%) locally unresectable disease after PREOP CRT, and 23 (16%) were not explored due to performance status or loss to follow-up. In the SURGERY group, 68 patients (74%) underwent resection. Sixteen patients (17%) had metastatic and eight patients (9%) locally unresectable disease at exploration. In patients who underwent resection, the PREOP CRT group had smaller pathologic tumor size and lower incidence of positive lymph nodes than the SURGERY group but no difference in positive margins or need for vascular resection. Median overall survival (OS) in patients undergoing resection was 27 months in the PREOP CRT group and 17 months in the SURGERY group (P = 0.04). Median OS in all patients treated with PREOP CRT or surgically explored with intention to resect was 15 and 13 months, respectively, with superimposable survival curves. Despite a lower resection rate, the PREOP CRT group as a whole had a similar OS to the SURGERY group as a whole. For patients who underwent resection, those in the PREOP CRT had longer survival than those in the SURGERY group, suggesting that PREOP CRT allows better patient selection for resection. PREOP CRT should be considered an acceptable alternative for most patients with resectable pancreatic cancer.

Authors
Papalezova, KT; Tyler, DS; Blazer, DG; Clary, BM; Czito, BG; Hurwitz, HI; Uronis, HE; Pappas, TN; Willett, CG; White, RR
MLA Citation
Papalezova, KT, Tyler, DS, Blazer, DG, Clary, BM, Czito, BG, Hurwitz, HI, Uronis, HE, Pappas, TN, Willett, CG, and White, RR. "Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?." J Surg Oncol 106.1 (July 1, 2012): 111-118.
PMID
22311829
Source
pubmed
Published In
Journal of Surgical Oncology
Volume
106
Issue
1
Publish Date
2012
Start Page
111
End Page
118
DOI
10.1002/jso.23044

Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas.

PURPOSE: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. METHODS AND MATERIALS: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. RESULTS: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. CONCLUSIONS: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

Authors
Gay, HA; Barthold, HJ; O'Meara, E; Bosch, WR; El Naqa, I; Al-Lozi, R; Rosenthal, SA; Lawton, C; Lee, WR; Sandler, H; Zietman, A; Myerson, R; Dawson, LA; Willett, C; Kachnic, LA; Jhingran, A; Portelance, L; Ryu, J; Small, W; Gaffney, D; Viswanathan, AN; Michalski, JM
MLA Citation
Gay, HA, Barthold, HJ, O'Meara, E, Bosch, WR, El Naqa, I, Al-Lozi, R, Rosenthal, SA, Lawton, C, Lee, WR, Sandler, H, Zietman, A, Myerson, R, Dawson, LA, Willett, C, Kachnic, LA, Jhingran, A, Portelance, L, Ryu, J, Small, W, Gaffney, D, Viswanathan, AN, and Michalski, JM. "Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas." Int J Radiat Oncol Biol Phys 83.3 (July 1, 2012): e353-e362.
PMID
22483697
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
83
Issue
3
Publish Date
2012
Start Page
e353
End Page
e362
DOI
10.1016/j.ijrobp.2012.01.023

Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy.

BACKGROUND: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. METHODS: A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. RESULTS: A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. CONCLUSIONS: Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.

Authors
Palta, M; Patel, P; Broadwater, G; Willett, C; Pepek, J; Tyler, D; Zafar, SY; Uronis, H; Hurwitz, H; White, R; Czito, B
MLA Citation
Palta, M, Patel, P, Broadwater, G, Willett, C, Pepek, J, Tyler, D, Zafar, SY, Uronis, H, Hurwitz, H, White, R, and Czito, B. "Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy." Ann Surg Oncol 19.5 (May 2012): 1535-1540.
PMID
22045467
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
19
Issue
5
Publish Date
2012
Start Page
1535
End Page
1540
DOI
10.1245/s10434-011-2117-1

The Ninth Annual ISGIO Meeting.

Authors
Willett, CG
MLA Citation
Willett, CG. "The Ninth Annual ISGIO Meeting." Gastrointest Cancer Res 5.3 (May 2012): 75-.
PMID
22888386
Source
pubmed
Published In
Gastrointestinal Cancer Research
Volume
5
Issue
3
Publish Date
2012
Start Page
75

Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas.

PURPOSE: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. METHODS AND MATERIALS: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. RESULTS: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. CONCLUSIONS: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach.

Authors
Cuneo, KC; Vredenburgh, JJ; Sampson, JH; Reardon, DA; Desjardins, A; Peters, KB; Friedman, HS; Willett, CG; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Vredenburgh, JJ, Sampson, JH, Reardon, DA, Desjardins, A, Peters, KB, Friedman, HS, Willett, CG, and Kirkpatrick, JP. "Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas." Int J Radiat Oncol Biol Phys 82.5 (April 1, 2012): 2018-2024.
PMID
21489708
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
82
Issue
5
Publish Date
2012
Start Page
2018
End Page
2024
DOI
10.1016/j.ijrobp.2010.12.074

IMRT treatment of anal cancer with a scrotal shield.

The risk of sterility in males undergoing radiotherapy in the pelvic region indicates the use of a shielding device, which offers protection to the testes for patients wishing to maintain fertility. The use of such devices in the realm of intensity-modulated radiotherapy (IMRT) in the pelvic region can pose many obstacles during simulation, treatment planning, and delivery of radiotherapy. This work focuses on the development and execution of an IMRT plan for the treatment of anal cancer using a scrotal shielding device on a clinical patient. An IMRT plan was developed using Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA), using a wide array of gantry angles as well as fixed jaw and fluence editing techniques. When possible, the entire target volume was encompassed by the treatment field. When the beam was incident on the scrotal shield, the jaw was fixed to avoid the device and the collimator rotation optimized to irradiate as much of the target as possible. This technique maximizes genital sparing and allows minimal irradiation of the gonads. When this fixed-jaw technique was found to compromise adequate coverage of the target, manual fluence editing techniques were used to avoid the shielding device. Special procedures for simulation, imaging, and treatment verification were also developed. In vivo dosimetry was used to verify and ensure acceptable dose to the gonads. The combination of these techniques resulted in a highly conformal plan that spares organs and risk and avoids the genitals as well as entrance of primary radiation onto the shielding device.

Authors
Hood, RC; Wu, QJ; McMahon, R; Czito, B; Willett, C
MLA Citation
Hood, RC, Wu, QJ, McMahon, R, Czito, B, and Willett, C. "IMRT treatment of anal cancer with a scrotal shield." Med Dosim 37.4 (2012): 432-435.
PMID
22538113
Source
pubmed
Published In
Medical Dosimetry
Volume
37
Issue
4
Publish Date
2012
Start Page
432
End Page
435
DOI
10.1016/j.meddos.2012.03.007

The CROSS trial: End of the debate on neoadjuvant therapy for esophageal cancer?

Authors
Pepek, JM; Willett, CG; Czito, BG
MLA Citation
Pepek, JM, Willett, CG, and Czito, BG. "The CROSS trial: End of the debate on neoadjuvant therapy for esophageal cancer?." Clinical Practice 9.6 (2012): 607-609.
Source
scival
Published In
Clinical Practice
Volume
9
Issue
6
Publish Date
2012
Start Page
607
End Page
609
DOI
10.2217/cpr.12.68

Potential novel drugs to combine with radiation in rectal cancer

The management of rectal cancer has seen significant advances in surgery, radiation therapy, and chemotherapy in recent years. These advances have translated into improved rates of local and distant disease control, survival, and quality of life for these patients. The recent implementation of novel chemotherapeutic and targeted agents in patients with advanced colorectal cancer has led to further improvements in disease-free and overall survival. These radiosensitizing agents are now being studied in combination with radiation therapy in the neoadjuvant therapy of rectal cancer. © The Author(s) 2012.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Potential novel drugs to combine with radiation in rectal cancer." Current Colorectal Cancer Reports 8.2 (2012): 105-117.
Source
scival
Published In
Current Colorectal Cancer Reports
Volume
8
Issue
2
Publish Date
2012
Start Page
105
End Page
117
DOI
10.1007/s11888-012-0120-y

Development of a 4D dosimetry simulation system in radiotherapy

4D CT image sets are used to encode patient-organ motion and to calculate the dose delivered during each respiratory phase. The dose-per-phase is summarised to the total dose via deformable registration. The system incorporates the actual beam parameters and synchronises the beam motion (e.g., gantry/MLC motion of the DARC and MLC motion of the IMRT) to the patient's respiratory motion. Furthermore, this system incorporates different treatment techniques such as 3D conformal (3DCRT), dynamic arc (DARC), and Intensity-Modulated Radiation Therapy (IMRT), thus allows better understanding of organ motion effect on dose delivery, treatment techniques and corresponding optimal margins. Copyright © 2012 Inderscience Enterprises Ltd.

Authors
Wu, QJ; Thongphiew, D; Wang, Z; Willett, C; Marks, L; Yin, F-F
MLA Citation
Wu, QJ, Thongphiew, D, Wang, Z, Willett, C, Marks, L, and Yin, F-F. "Development of a 4D dosimetry simulation system in radiotherapy." International Journal of Biomedical Engineering and Technology 8.2-3 (2012): 230-244.
Source
scival
Published In
International Journal of Biomedical Engineering and Technology
Volume
8
Issue
2-3
Publish Date
2012
Start Page
230
End Page
244
DOI
10.1504/IJBET.2012.046088

Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 ≤90 U/mL and comparison to the CONKO-001 trial

Purpose: Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of ≤90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. Methods and Materials: CA 19-9 expression was analyzed as a dichotomized variable (≤90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. Results: Both univariate (hazard ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of ≥90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 ≥90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. Conclusions: This analysis demonstrates that patients with postresection CA 19-9 values ≥90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848). © 2012 Elsevier Inc.

Authors
Berger, AC; Winter, K; Hoffman, JP; Regine, WF; Abrams, RA; Safran, H; Freedman, GM; III, ABB; MacDonald, J; Willett, CG
MLA Citation
Berger, AC, Winter, K, Hoffman, JP, Regine, WF, Abrams, RA, Safran, H, Freedman, GM, III, ABB, MacDonald, J, and Willett, CG. "Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 ≤90 U/mL and comparison to the CONKO-001 trial." International Journal of Radiation Oncology Biology Physics 84.3 (2012): e291-e297.
PMID
22682806
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
84
Issue
3
Publish Date
2012
Start Page
e291
End Page
e297
DOI
10.1016/j.ijrobp.2012.04.035

Going beyond systemic fluoropyrimidines with radiation therapy for rectal cancer: what should be the priority?

Authors
Duda, DG; Willett, CG
MLA Citation
Duda, DG, and Willett, CG. "Going beyond systemic fluoropyrimidines with radiation therapy for rectal cancer: what should be the priority?." Oncology (Williston Park, N.Y.) 26.8 (2012): 741-743.
PMID
22957407
Source
scival
Published In
Oncology
Volume
26
Issue
8
Publish Date
2012
Start Page
741
End Page
743

Pancreatic neuroendocrine tumors with involved surgical margins: Prognostic factors and the role of adjuvant radiotherapy

Purpose: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized. Methods and Materials: We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS). Results: Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with decreased OS. Conclusions: Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further evaluation. © 2012 Elsevier Inc. All rights reserved.

Authors
Arvold, ND; Willett, CG; Castillo, CF-D; Ryan, DP; Ferrone, CR; Clark, JW; Blaszkowsky, LS; Deshpande, V; Niemierko, A; Allen, JN; Kwak, EL; Wadlow, RC; Zhu, AX; Warshaw, AL; Hong, TS
MLA Citation
Arvold, ND, Willett, CG, Castillo, CF-D, Ryan, DP, Ferrone, CR, Clark, JW, Blaszkowsky, LS, Deshpande, V, Niemierko, A, Allen, JN, Kwak, EL, Wadlow, RC, Zhu, AX, Warshaw, AL, and Hong, TS. "Pancreatic neuroendocrine tumors with involved surgical margins: Prognostic factors and the role of adjuvant radiotherapy." International Journal of Radiation Oncology Biology Physics 83.3 (2012): e337-e343.
PMID
22414286
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
83
Issue
3
Publish Date
2012
Start Page
e337
End Page
e343
DOI
10.1016/j.ijrobp.2011.12.068

Anal carcinoma, version 2.2012: Featured updates to the NCCN guidelines

The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings. © JNCCN-Journal of the National Comprehensive Cancer Network.

Authors
III, ABB; Arnoletti, JP; Bekaii-Saab, T; Chan, E; Chen, Y-J; Choti, MA; Cooper, HS; Dilawari, RA; Engstrom, PF; Enzinger, PC; Fakih, MG; Jr, JWF; Fuchs, CS; Grem, JL; Leong, LA; Lin, E; May, KS; Mulcahy, MF; Murphy, K; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Jr, WS; Sofocleous, CT; Venook, AP; Willett, C; Freedman-Cass, DA
MLA Citation
III, ABB, Arnoletti, JP, Bekaii-Saab, T, Chan, E, Chen, Y-J, Choti, MA, Cooper, HS, Dilawari, RA, Engstrom, PF, Enzinger, PC, Fakih, MG, Jr, JWF, Fuchs, CS, Grem, JL, Leong, LA, Lin, E, May, KS, Mulcahy, MF, Murphy, K, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Jr, WS, Sofocleous, CT, Venook, AP, Willett, C, and Freedman-Cass, DA. "Anal carcinoma, version 2.2012: Featured updates to the NCCN guidelines." JNCCN Journal of the National Comprehensive Cancer Network 10.4 (2012): 449-454.
PMID
22491045
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
4
Publish Date
2012
Start Page
449
End Page
454

A phase II study of a paclitaxel-based chemoradiation regimen with selective surgical salvage for resectable locoregionally advanced esophageal cancer: Initial reporting of RTOG 0246

Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% (α = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg 2/day), cisplatin (15 mg/mg 2/day), and paclitaxel (200 mg/mg 2/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg 2/day) with cisplatin (15 mg/mg 2/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was ≥T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%). © 2012 Elsevier Inc.

Authors
Swisher, SG; Winter, KA; Komaki, RU; Ajani, JA; Wu, TT; Hofstetter, WL; Konski, AA; Willett, CG
MLA Citation
Swisher, SG, Winter, KA, Komaki, RU, Ajani, JA, Wu, TT, Hofstetter, WL, Konski, AA, and Willett, CG. "A phase II study of a paclitaxel-based chemoradiation regimen with selective surgical salvage for resectable locoregionally advanced esophageal cancer: Initial reporting of RTOG 0246." International Journal of Radiation Oncology Biology Physics 82.5 (2012): 1967-1972.
PMID
21507583
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
5
Publish Date
2012
Start Page
1967
End Page
1972
DOI
10.1016/j.ijrobp.2011.01.043

Radiation therapy oncology group 0247: A randomized phase II study of neoadjuvant capecitabine and irinotecan or capecitabine and oxaliplatin with concurrent radiotherapy for patients with locally advanced rectal cancer

Purpose: To evaluate the rate of pathologic complete response (pCR) and the toxicity of two neoadjuvant chemoradiotherapy (chemoRT) regimens for Stage T3-T4 rectal cancer in a randomized Phase II study. Methods and Materials: Patients with Stage T3 or T4 rectal cancer of <12 cm from the anal verge were randomized to preoperative RT (50.4 Gy in 1.8-Gy fractions) with concurrent capecitabine (1,200 mg/m 2/d Mondays through Friday) and irinotecan (50 mg/m 2 weekly in four doses) (Arm 1) or concurrent capecitabine (1,650 mg/m 2/d Monday through Friday) and oxaliplatin (50 mg/m 2 weekly in five doses) (Arm 2). Surgery was performed 4-8 weeks after chemoRT, and adjuvant chemotherapy 4-6 weeks after surgery. The primary endpoint was the pCR rate, requiring 48 evaluable patients per arm. Results: A total of 146 patients were enrolled. The protocol chemotherapy was modified because of excessive gastrointestinal toxicity after treatment of 35 patients; 96 were assessed for the primary endpoint - the final regimen described above. The patient characteristics were similar for both arms. After chemoRT, the rate of tumor downstaging was 52% and 60% and the rate of nodal downstaging (excluding N0 patients) was 46% and 40%, for Arms 1 and 2, respectively. The pCR rate for Arm 1 was 10% and for Arm 2 was 21%. For Arm 1 and 2, the preoperative chemoRT rate of Grade 3-4 hematologic toxicity was 9% and 4% and the rate of Grade 3-4 nonhematologic toxicity was 26% and 27%, respectively. Conclusions: Preoperative chemoRT with capecitabine plus oxaliplatin for distal rectal cancer has significant clinical activity (10 of 48 pCRs) and acceptable toxicity. This regimen is currently being evaluated in a Phase III randomized trial (National Surgical Adjuvant Breast and Bowel Project R04). Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.

Authors
Wong, SJ; Winter, K; Meropol, NJ; Anne, PR; Kachnic, L; Rashid, A; Watson, JC; Mitchell, E; Pollock, J; Lee, RJ; Haddock, M; Erickson, BA; Willett, CG
MLA Citation
Wong, SJ, Winter, K, Meropol, NJ, Anne, PR, Kachnic, L, Rashid, A, Watson, JC, Mitchell, E, Pollock, J, Lee, RJ, Haddock, M, Erickson, BA, and Willett, CG. "Radiation therapy oncology group 0247: A randomized phase II study of neoadjuvant capecitabine and irinotecan or capecitabine and oxaliplatin with concurrent radiotherapy for patients with locally advanced rectal cancer." International Journal of Radiation Oncology Biology Physics 82.4 (2012): 1367-1375.
PMID
21775070
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
4
Publish Date
2012
Start Page
1367
End Page
1375
DOI
10.1016/j.ijrobp.2011.05.027

Hvid-Jensen F, Pedersen L, Drewes A, et al. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Eng J Med 2011:365:1375-83, 2011. Kahrilas P, the problems with surveillance of Barrett's esophagus. N Engl J Med 2011; 365:1437-1438

Authors
Willett, CG
MLA Citation
Willett, CG. "Hvid-Jensen F, Pedersen L, Drewes A, et al. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Eng J Med 2011:365:1375-83, 2011. Kahrilas P, the problems with surveillance of Barrett's esophagus. N Engl J Med 2011; 365:1437-1438." International Journal of Radiation Oncology Biology Physics 82.4 (2012): 1301-1302.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
4
Publish Date
2012
Start Page
1301
End Page
1302
DOI
10.1016/S0360-3016(12)00163-0

Patel U, Taylor F, Blomqvist L, et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol 29:3753-3760, 2011

Authors
Willett, CG
MLA Citation
Willett, CG. "Patel U, Taylor F, Blomqvist L, et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol 29:3753-3760, 2011." International Journal of Radiation Oncology Biology Physics 82.4 (2012): 1302--.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
4
Publish Date
2012
Start Page
1302-
DOI
10.1016/S0360-3016(12)00163-0

Palefsky J, Giuliano A, Gladstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. New Eng J Med 2011; 365:1576-85

Authors
Willett, CG
MLA Citation
Willett, CG. "Palefsky J, Giuliano A, Gladstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. New Eng J Med 2011; 365:1576-85." International Journal of Radiation Oncology Biology Physics 82.4 (2012): 1301--.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
4
Publish Date
2012
Start Page
1301-
DOI
10.1016/S0360-3016(12)00163-0

Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704 - A phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas

Purpose: In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials: RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (<PP). Scoring occurred after therapy but before trial analysis and without knowledge of individual patient treatment outcomes. Scoring was done for all tumor locations and for the subset of pancreatic head location. Results: RT was scored for 416 patients: 216 PP and 200 <PP. For all pancreatic sites (head, body/tail) median survival (MS) for PP vs. <PP was 1.74 vs. 1.46 years (log-rank p = 0.0077). In multivariate analysis, PP vs. <PP score correlated more strongly with MS than assigned treatment arm (p = 0.014, p = NS, respectively); for patients with pancreatic head tumors, both PP score and gemcitabine treatment correlated with improved MS (p = 0.016, p = 0.043, respectively). For all tumor locations, PP score was associated with decreased risk of failure (p = 0.016) and, for gemcitabine patients, a trend toward reduced Grade 4/5 nonhematologic toxicity (p = 0.065). Conclusions: This is the first Phase III, multicenter, adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity. © 2012 Elsevier Inc.

Authors
Abrams, RA; Winter, KA; Regine, WF; Safran, H; Hoffman, JP; Lustig, R; Konski, AA; Benson, AB; MacDonald, JS; Rich, TA; Willett, CG
MLA Citation
Abrams, RA, Winter, KA, Regine, WF, Safran, H, Hoffman, JP, Lustig, R, Konski, AA, Benson, AB, MacDonald, JS, Rich, TA, and Willett, CG. "Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704 - A phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas." International Journal of Radiation Oncology Biology Physics 82.2 (2012): 809-816.
PMID
21277694
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
2
Publish Date
2012
Start Page
809
End Page
816
DOI
10.1016/j.ijrobp.2010.11.039

Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364:1817-25.

Authors
Willett, CG
MLA Citation
Willett, CG. "Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364:1817-25." International Journal of Radiation Oncology Biology Physics 82.4 (2012): 1301--.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
4
Publish Date
2012
Start Page
1301-
DOI
10.1016/S0360-3016(12)00163-0

RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials. © 2012 Elsevier Inc. All rights reserved.

Authors
Kachnic, LA; Winter, K; Myerson, RJ; Goodyear, MD; Willins, J; Esthappan, J; Haddock, MG; Rotman, M; Parikh, PJ; Safran, H; al, E
MLA Citation
Kachnic, LA, Winter, K, Myerson, RJ, Goodyear, MD, Willins, J, Esthappan, J, Haddock, MG, Rotman, M, Parikh, PJ, Safran, H, and al, E. "RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal." International Journal of Radiation Oncology, Biology, Physics (2012).
PMID
23154075
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Publish Date
2012
DOI
10.1016/j.ijrobp.2012.09.023

Rectal cancer

These NCCN Clinical Practice Guidelines in Oncology provide recommendations for the management of rectal cancer, beginning with the clinical presentation of the patient to the primary care physician or gastroenterologist through diagnosis, pathologic staging, neoadjuvant treatment, surgical management, adjuvant treatment, surveillance, management of recurrent and metastatic disease, and survivorship. This discussion focuses on localized disease. The NCCN Rectal Cancer Panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with rectal cancer. © JNCCN-Journal of the National Comprehensive Cancer Network.

Authors
III, ABB; Bekaii-Saab, T; Chan, E; Chen, Y-J; Choti, MA; Cooper, HS; Engstrom, PF; Enzinger, PC; Fakih, MG; Fuchs, CS; Grem, JL; Hunt, S; Leong, LA; Lin, E; Martin, MG; May, KS; Mulcahy, MF; Murphy, K; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Jr, WS; Sofocleous, CT; Venook, AP; Willett, CG; Freedman-Cass, DA; Gregory, KM
MLA Citation
III, ABB, Bekaii-Saab, T, Chan, E, Chen, Y-J, Choti, MA, Cooper, HS, Engstrom, PF, Enzinger, PC, Fakih, MG, Fuchs, CS, Grem, JL, Hunt, S, Leong, LA, Lin, E, Martin, MG, May, KS, Mulcahy, MF, Murphy, K, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Jr, WS, Sofocleous, CT, Venook, AP, Willett, CG, Freedman-Cass, DA, and Gregory, KM. "Rectal cancer." JNCCN Journal of the National Comprehensive Cancer Network 10.12 (2012): 1528-1564.
PMID
23221790
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
12
Publish Date
2012
Start Page
1528
End Page
1564

Going beyond systemic fluoropyrimidines with radiation therapy for rectal cancer: What should be the priority?

Authors
Duda, DG; Willett, CG
MLA Citation
Duda, DG, and Willett, CG. "Going beyond systemic fluoropyrimidines with radiation therapy for rectal cancer: What should be the priority?." ONCOLOGY (United States) 26.8 (2012).
Source
scival
Published In
Oncology
Volume
26
Issue
8
Publish Date
2012

Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer

Purpose: The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low-dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation. Patients and methods: Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m2/week, and paclitaxel, 40 mg/m2/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until disease progression or unacceptable toxicity. Results: One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were also reported. The median survival time was 11.5 months and 8.9 months for the CXRT and CXRT+R115777 arms, respectively. Conclusions: The CXRT arm achieved a median survival of almost 1-year, supporting chemoradiation as an important therapeutic modality for locally advanced pancreatic cancer. Maintenance R115777 is not effective and is associated with a broad range of toxicities. These findings provide clinical evidence that inhibition of farnesylation affects many metabolic pathways, underscoring the challenge of developing an effective K-ras inhibitor. © 2012 Rich et al, publisher and licensee Dove Medical Press Ltd.

Authors
Rich, TA; Winter, K; Safran, H; Hoffman, JP; Erickson, B; Anne, PR; Myerson, RJ; Cline-Burkhardt, VJ; Perez, K; Willett, C
MLA Citation
Rich, TA, Winter, K, Safran, H, Hoffman, JP, Erickson, B, Anne, PR, Myerson, RJ, Cline-Burkhardt, VJ, Perez, K, and Willett, C. "Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer." OncoTargets and Therapy 5 (2012): 161-170.
Source
scival
Published In
OncoTargets and Therapy
Volume
5
Publish Date
2012
Start Page
161
End Page
170
DOI
10.2147/OTT.S33560

Accomplishments in 2011 in Gastrointestinal Oncology

Authors
Willett, CG
MLA Citation
Willett, CG. "Accomplishments in 2011 in Gastrointestinal Oncology." Gastrointestinal Cancer Research 5.4 SUPPL.2 (2012): S1-.
Source
scival
Published In
Gastrointestinal Cancer Research
Volume
5
Issue
4 SUPPL.2
Publish Date
2012
Start Page
S1

The international society of gastrointestinal oncology: Selected proceedings from the eighth annual conference

Authors
Willett, CG
MLA Citation
Willett, CG. "The international society of gastrointestinal oncology: Selected proceedings from the eighth annual conference." Gastrointestinal Cancer Research 5.3 SUPPL.1 (2012).
Source
scival
Published In
Gastrointestinal Cancer Research
Volume
5
Issue
3 SUPPL.1
Publish Date
2012

Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma.

PURPOSE: Extrahepatic cholangiocarcinoma is an uncommon but lethal malignancy. We analyzed the role of definitive chemoradiotherapy for patients with nonmetastatic, locally advanced extrahepatic cholangiocarcinoma treated at a single institution. METHODS AND MATERIALS: This retrospective analysis included 37 patients who underwent external beam radiation therapy (EBRT) with concurrent chemotherapy and/or brachytherapy (BT) for locally advanced extrahepatic cholangiocarcinoma. Local control (LC) and overall survival (OS) were assessed, and univariate regression analysis was used to evaluate the effects of patient- and treatment-related factors on clinical outcomes. RESULTS: Twenty-three patients received EBRT alone, 8 patients received EBRT plus BT, and 6 patients received BT alone (median follow-up of 14 months). Two patients were alive without evidence of recurrence at the time of analysis. Actuarial OS and LC rates at 1 year were 59% and 90%, respectively, and 22% and 71%, respectively, at 2 years. Two patients lived beyond 5 years without evidence of recurrence. On univariate analysis, EBRT with or without BT improved LC compared to BT alone (97% vs. 56% at 1 year; 75% vs. 56% at 2 years; p = 0.096). Patients who received EBRT alone vs. BT alone also had improved LC (96% vs. 56% at 1 year; 80% vs. 56% at 2 years; p = 0.113). Age, gender, tumor location (proximal vs. distal), histologic differentiation, EBRT dose (≤ or >50 Gy), EBRT planning method (two-dimensional vs. three-dimensional), and chemotherapy were not associated with patient outcomes. CONCLUSIONS: Patients with locally advanced extrahepatic cholangiocarcinoma have poor survival. Long-term survival is rare. The majority of patients treated with EBRT had local control at the time of death, suggesting that symptoms due to the local tumor effect might be effectively controlled with radiation therapy, and EBRT is an important element of treatment. Novel treatment approaches are indicated in the therapy for this disease.

Authors
Ghafoori, AP; Nelson, JW; Willett, CG; Chino, J; Tyler, DS; Hurwitz, HI; Uronis, HE; Morse, MA; Clough, RW; Czito, BG
MLA Citation
Ghafoori, AP, Nelson, JW, Willett, CG, Chino, J, Tyler, DS, Hurwitz, HI, Uronis, HE, Morse, MA, Clough, RW, and Czito, BG. "Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma." Int J Radiat Oncol Biol Phys 81.3 (November 1, 2011): 654-659.
PMID
20864265
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
81
Issue
3
Publish Date
2011
Start Page
654
End Page
659
DOI
10.1016/j.ijrobp.2010.06.018

Colon Cancer

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Colon Cancer." Clinical Radiation Oncology: Third Edition. October 27, 2011. 975-967.
Source
scopus
Publish Date
2011
Start Page
975
End Page
967
DOI
10.1016/B978-1-4377-1637-5.00048-1

Intraoperative Irradiation

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Intraoperative Irradiation." Clinical Radiation Oncology: Third Edition. October 27, 2011. 317-330.
Source
scopus
Publish Date
2011
Start Page
317
End Page
330
DOI
10.1016/B978-1-4377-1637-5.00016-X

Esophageal and esophagogastric junction cancers.

Authors
Ajani, JA; Barthel, JS; Bentrem, DJ; D'Amico, TA; Das, P; Denlinger, CS; Fuchs, CS; Gerdes, H; Glasgow, RE; Hayman, JA; Hofstetter, WL; Ilson, DH; Keswani, RN; Kleinberg, LR; Korn, WM; Lockhart, AC; Mulcahy, MF; Orringer, MB; Osarogiagbon, RU; Posey, JA; Sasson, AR; Scott, WJ; Shibata, S; Strong, VEM; Varghese, TK; Warren, G; Washington, MK; Willett, C; Wright, CD; National Comprehensive Cancer Network,
MLA Citation
Ajani, JA, Barthel, JS, Bentrem, DJ, D'Amico, TA, Das, P, Denlinger, CS, Fuchs, CS, Gerdes, H, Glasgow, RE, Hayman, JA, Hofstetter, WL, Ilson, DH, Keswani, RN, Kleinberg, LR, Korn, WM, Lockhart, AC, Mulcahy, MF, Orringer, MB, Osarogiagbon, RU, Posey, JA, Sasson, AR, Scott, WJ, Shibata, S, Strong, VEM, Varghese, TK, Warren, G, Washington, MK, Willett, C, Wright, CD, and National Comprehensive Cancer Network, . "Esophageal and esophagogastric junction cancers." J Natl Compr Canc Netw 9.8 (August 1, 2011): 830-887.
PMID
21900218
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
8
Publish Date
2011
Start Page
830
End Page
887

Beyond 5-fluorouracil: the emerging role of newer chemotherapeutics and targeted agents with radiation therapy.

The management of rectal cancer has undergone significant evolution with advances in surgery, radiation therapy, and chemotherapy. These advances have translated into improved rates of local control, survival, and quality of life. More recently, the integration of newer chemotherapeutic and targeted agents in patients with advanced colorectal cancer have led to further improvements in disease-free and overall survival. These agents are now being studied with radiation therapy in the neoadjuvant therapy of rectal cancer.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Beyond 5-fluorouracil: the emerging role of newer chemotherapeutics and targeted agents with radiation therapy." Semin Radiat Oncol 21.3 (July 2011): 203-211. (Review)
PMID
21645865
Source
pubmed
Published In
Seminars in Radiation Oncology
Volume
21
Issue
3
Publish Date
2011
Start Page
203
End Page
211
DOI
10.1016/j.semradonc.2011.02.006

Introduction: current controversies in rectal cancer.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Introduction: current controversies in rectal cancer." Semin Radiat Oncol 21.3 (July 2011): 167-168.
PMID
21645860
Source
pubmed
Published In
Seminars in Radiation Oncology
Volume
21
Issue
3
Publish Date
2011
Start Page
167
End Page
168
DOI
10.1016/j.semradonc.2011.02.001

Role of radiation therapy in patients with resectable pancreatic cancer.

The 5-year overall survival of patients with pancreatic cancer is approximately 5%, with potentially resectable disease representing the curable minority. Although surgical resection remains the cornerstone of treatment, local and distant failure rates are high after complete resection, and debate continues as to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant chemotherapy alone, given that high rates of systemic metastases are the primary cause of patient mortality. Others, however, view locoregional failure as a significant contributor to morbidity and mortality, thereby justifying the use of adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant chemoradiotherapy offers potential advantages in resectable patients, and clinical investigation of this approach has shown promising results; however, phase III data are lacking. Further therapeutic advances and prospective trials are needed to better define the optimal role of adjuvant and neoadjuvant treatment in patients with resectable pancreatic cancer.

Authors
Palta, M; Willett, C; Czito, B
MLA Citation
Palta, M, Willett, C, and Czito, B. "Role of radiation therapy in patients with resectable pancreatic cancer." Oncology (Williston Park) 25.8 (July 2011): 715-727. (Review)
PMID
21874833
Source
pubmed
Published In
Oncology
Volume
25
Issue
8
Publish Date
2011
Start Page
715
End Page
727

SU-E-T-419: Clinical Protocol for the Use of Scrotal Shields in IMRT Treatment of Anal Cancer

Authors
Wu, Q; McMahon, R; Hood, R; Willett, C; Czito, B
MLA Citation
Wu, Q, McMahon, R, Hood, R, Willett, C, and Czito, B. "SU-E-T-419: Clinical Protocol for the Use of Scrotal Shields in IMRT Treatment of Anal Cancer." June 2011.
Source
crossref
Published In
Medical physics
Volume
38
Issue
6Part17
Publish Date
2011
Start Page
3584
End Page
3584
DOI
10.1118/1.3612373

Update on treatment advances in combined-modality therapy for anal and rectal carcinomas.

Concurrent radiation therapy and chemotherapy is the primary treatment for patients with squamous cell tumors of the anal canal, and is also employed in the neoadjuvant setting for patients with stage II and III adenocarcinoma of the rectum. There is constant clinical study involving modifications of chemoradiotherapy regimens in an effort to maximize tumor responses while reducing normal tissue toxicity. This review will discuss established regimens as well as newer and novel treatment approaches to treatment of anal and rectal cancer.

Authors
Meyer, J; Balch, G; Willett, C; Czito, B
MLA Citation
Meyer, J, Balch, G, Willett, C, and Czito, B. "Update on treatment advances in combined-modality therapy for anal and rectal carcinomas." Curr Oncol Rep 13.3 (June 2011): 177-185. (Review)
PMID
21465120
Source
pubmed
Published In
Current Oncology Reports
Volume
13
Issue
3
Publish Date
2011
Start Page
177
End Page
185
DOI
10.1007/s11912-011-0166-z

Potentially resectable pancreatic cancer in elderly patients: Is surgery a reasonable choice?

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Potentially resectable pancreatic cancer in elderly patients: Is surgery a reasonable choice?." Aging Health 7.3 (2011): 463-467.
Source
scival
Published In
Aging health
Volume
7
Issue
3
Publish Date
2011
Start Page
463
End Page
467
DOI
10.2217/ahe.11.30

Role of radiation therapy in patients with resectable pancreatic cancer

The 5-year overall survival of patients with pancreatic cancer is approximately 5%, with potentially resectable disease representing the curable minority. Although surgical resection remains the cornerstone of treatment, local and distant failure rates are high after complete resection, and debate continues as to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant chemotherapy alone, given that high rates of systemic metastases are the primary cause of patient mortality. Others, however, view locoregional failure as a significant contributor to morbidity and mortality, thereby justifying the use of adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant chemoradiotherapy offers potential advantages in resectable patients, and clinical investigation of this approach has shown promising results; however, phase III data are lacking. Further therapeutic advances and prospective trials are needed to better define the optimal role of adjuvant and neoadjuvant treatment in patients with resectable pancreatic cancer.

Authors
Palta, M; Willett, C; Czito, B
MLA Citation
Palta, M, Willett, C, and Czito, B. "Role of radiation therapy in patients with resectable pancreatic cancer." Oncology 25.8 (2011): 1-11.
Source
scival
Published In
Oncology
Volume
25
Issue
8
Publish Date
2011
Start Page
1
End Page
11

Tolerability of combined modality therapy for rectal cancer in elderly patients aged 75 years and older

Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham & Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability. Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed ≥4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0). Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of combined modality therapy for rectal cancer should be performed with caution in elderly patients, who require aggressive supportive care to complete treatment. © 2011 Elsevier Inc.

Authors
Margalit, DN; Mamon, HJ; Ancukiewicz, M; Kobayashi, W; Ryan, DP; Blaszkowsky, LS; Clark, J; Willett, CG; Hong, TS
MLA Citation
Margalit, DN, Mamon, HJ, Ancukiewicz, M, Kobayashi, W, Ryan, DP, Blaszkowsky, LS, Clark, J, Willett, CG, and Hong, TS. "Tolerability of combined modality therapy for rectal cancer in elderly patients aged 75 years and older." International Journal of Radiation Oncology Biology Physics 81.5 (2011): e735-e741.
PMID
21377289
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
5
Publish Date
2011
Start Page
e735
End Page
e741
DOI
10.1016/j.ijrobp.2010.12.056

The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant chemoradiation for pancreatic cancer: A secondary analysis of RTOG 9704

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors - number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE) - on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques. © 2011 Elsevier Inc.

Authors
Showalter, TN; Winter, KA; Berger, AC; Regine, WF; Abrams, RA; Safran, H; Hoffman, JP; Benson, AB; MacDonald, JS; Willett, CG
MLA Citation
Showalter, TN, Winter, KA, Berger, AC, Regine, WF, Abrams, RA, Safran, H, Hoffman, JP, Benson, AB, MacDonald, JS, and Willett, CG. "The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant chemoradiation for pancreatic cancer: A secondary analysis of RTOG 9704." International Journal of Radiation Oncology Biology Physics 81.5 (2011): 1328-1335.
PMID
20934270
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
5
Publish Date
2011
Start Page
1328
End Page
1335
DOI
10.1016/j.ijrobp.2010.07.1993

Clinical practice guidelines in oncology

The panel believes that a multidisciplinary approach is necessary for managing colorectal cancer. The panel endorses the concept that treating patients in a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for resectable colon cancer is an en bloc resection and adequate lymphadenectomy. Adequate pathologic assessment of the resected lymph nodes is important, with a goal of evaluating at least 12 nodes. Adjuvant therapy with FOLFOX (category 1, preferred), FLOX (category 1), CapeOx (category 1), 5-FU/LV (category 2A), or capecitabine (category 2A) is recommended by the panel for patients with stage III disease. Adjuvant therapy for patients with high-risk stage II disease is also an option; the panel recommends 5-FU/LV with or without oxaliplatin (FOLFOX or FLOX) or capecitabine with or without oxaliplatin (category 2A for all treatment options). Patients with metastatic disease in the liver or lung should be considered for surgical resection if they are candidates for surgery and if all original sites of disease are amenable to resection (R0) and/or ablation. Preoperative chemotherapy can be considered as initial therapy in patients with synchronous or metachronous resectable metastatic disease. When a response to chemotherapy would likely convert a patient from an unresectable to a resectable state (i.e., conversion therapy), this therapy should be initiated. Adjuvant chemotherapy should be considered after resection of liver or lung metastases. The recommended posttreatment surveillance program includes serial CEA determinations and periodic chest, abdominal, and pelvic CT scans, colonoscopic evaluations, and a survivorship plan to manage long-term side effects of treatment, facilitate disease prevention, and promote a healthy lifestyle. Recommendations for patients with disseminated metastatic disease represent a continuum of care in which lines of treatment are blurred rather than discrete. Principles to consider at initiation of therapy include preplanned strategies for altering therapy for patients in both the presence and absence of disease progression, including plans for adjusting therapy for patients who experience certain toxicities. Recommended initial therapy options for advanced or metastatic disease depend on whether the patient is appropriate for intensive therapy. The more-intensive initial therapy options include FOLFOX, FOLFIRI, CapeOx, and FOLFOXIRI (category 2B). Addition of a biologic agent (e.g., bevacizumab, cetuximab, panitumumab) is either recommended or listed as an option in combination with some of these regimens, depending on available data. Chemotherapy options for patients with progressive disease depend on the choice of initial therapy. © JNCCN-Journal of the National Comprehensive Cancer Network.

Authors
III, ABB; Arnoletti, JP; Bekaii-Saab, T; Chan, E; Chen, Y-J; Choti, MA; Cooper, HS; Dilawari, RA; Engstrom, PF; Enzinger, PC; Jr, JWF; Fuchs, CS; Grem, JL; Knol, JA; Leong, LA; Lin, E; May, KS; Mulcahy, MF; Murphy, K; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Jr, WS; Sofocleous, CT; Venook, AP; Willett, C
MLA Citation
III, ABB, Arnoletti, JP, Bekaii-Saab, T, Chan, E, Chen, Y-J, Choti, MA, Cooper, HS, Dilawari, RA, Engstrom, PF, Enzinger, PC, Jr, JWF, Fuchs, CS, Grem, JL, Knol, JA, Leong, LA, Lin, E, May, KS, Mulcahy, MF, Murphy, K, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Jr, WS, Sofocleous, CT, Venook, AP, and Willett, C. "Clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 9.11 (2011): 1238-1289.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
11
Publish Date
2011
Start Page
1238
End Page
1289

Intraductal papillary mucinous adenocarcinoma of the pancreas: Clinical outcomes, prognostic factors, and the role of adjuvant therapy

Background: Pancreatic ductal adenocarcinoma (PDAC) arising in intraductal papillary mucinous neoplasms (IPMN) may represent a different biologic entity than classic PDAC, and there is little evidence to inform adjuvant treatment decisions. The purpose of this study was to identify prognostic factors for PDAC arising in IPMN and determine the benefit of postoperative adjuvant therapy. Methods: Forty-four patients without previous therapy who underwent surgery for invasive PDAC arising in association with IPMN at our institution were identified. Medical records were reviewed for clinical and pathologic features, adjuvant therapy, and outcomes. Results: On univariate analysis, positive nodes (hazard rate [HR] 14, 95% confidence interval [CI] 4.2-44), CA 19-9 > 80 (HR 6.2, 95% CI 2.2-17), lymphovascular invasion (HR 4.7, 95% CI 1.5-15), perineural invasion (HR 3.9, 95% CI 1.5-10), and positive margins (HR 3.1, 95% CI 1.2-8.0) were associated with inferior cancer-specific survival. Patients with positive nodes who received adjuvant therapy had higher median cancer-specific survival (20 months) than those who received no adjuvant therapy (3.3 months). Conclusions: Patients with PDAC arising in IPMN presented at an earlier stage than is reported for classical PDAC. Adjuvant chemoradiotherapy was associated with improved overall and cancer-specific survival for patients with advanced disease. These hypothesis-generating results require validation in a larger prospective trial. © 2011 by International Society of Gastrointestinal Oncology.

Authors
Alexander, BM; Castillo, CF-D; Ryan, DP; Kachnic, LA; Hezel, AF; Niemierko, A; Willett, CG; Kozak, KR; Blaszkowsky, LS; Clark, JW; Warshaw, AL; Hong, TS
MLA Citation
Alexander, BM, Castillo, CF-D, Ryan, DP, Kachnic, LA, Hezel, AF, Niemierko, A, Willett, CG, Kozak, KR, Blaszkowsky, LS, Clark, JW, Warshaw, AL, and Hong, TS. "Intraductal papillary mucinous adenocarcinoma of the pancreas: Clinical outcomes, prognostic factors, and the role of adjuvant therapy." Gastrointestinal Cancer Research 4.4 (2011): 116-121.
Source
scival
Published In
Gastrointestinal Cancer Research
Volume
4
Issue
4
Publish Date
2011
Start Page
116
End Page
121

Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. intergroup/RTOG 9704 phase III trial

Background: The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods: After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m2/day, and gemcitabine was provided at 1000 mg/m2 weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head. Results: Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%. Conclusions: The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine. © 2011 Society of Surgical Oncology.

Authors
Regine, WF; Winter, KA; Abrams, R; Safran, H; Hoffman, JP; Konski, A; Benson, AB; MacDonald, JS; Rich, TA; Willett, CG
MLA Citation
Regine, WF, Winter, KA, Abrams, R, Safran, H, Hoffman, JP, Konski, A, Benson, AB, MacDonald, JS, Rich, TA, and Willett, CG. "Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. intergroup/RTOG 9704 phase III trial." Annals of Surgical Oncology 18.5 (2011): 1319-1326.
PMID
21499862
Source
scival
Published In
Annals of Surgical Oncology
Volume
18
Issue
5
Publish Date
2011
Start Page
1319
End Page
1326
DOI
10.1245/s10434-011-1630-6

Longitudinal quality-of-life analysis of RTOG 94-05 (Int 0123): A phase III trial of definitive chemoradiotherapy for esophageal cancer

Background: Longitudinal quality of life (QoL) was compared for patients with esophageal cancer receiving definitive chemoradiotherapy (CRT) with conventional-dose (CD) vs. high-dose (HD) radiotherapy as used in the RTOG phase III 94-05 trial (Intergroup 0123). Methods: Between June 12, 1995, and July 1, 1999, 236 patients with cT1-4NxM0 esophageal cancer were randomized to CD CRT (50.4 Gy and concurrent 5-fluorouracil and cisplatin) vs. HD CRT (64.8 Gy and the same chemotherapy). QoL was assessed using the Functional Assessment of Cancer Therapy, Head & Neck (version 2) at baseline, after CRT, at 8 months from the start of CRT, and at 1 year. Results: Of 218 eligible patients, 166 participated in pretreatment QoL assessments (82 HD, 84 CD). Patients with ≥10% weight loss and Karnofsky Performance Status 60-80 were less likely to participate (P=.02 and P=.002, respectively). Pretreatment characteristics for participating patients were similar in both arms. At CRT completion, 96 patients completed QoL (46 HD, 50 CD) assessment. Total mean QoL was significantly lower in the HD arm (P=.02) and remained lower at 8 and 12 months after the start of CRT, but these values did not reach statistical significance. Change in mean QoL from baseline to each of the three subsequent assessment time points did not differ significantly between the two treatment arms. Conclusions: For patients treated with definitive CRT for esophageal cancer, radiation dose escalation to 64.8 Gy does not significantly improve QoL. These results provide additional evidence that radiotherapy to 50.4 Gy should remain the standard of care. © 2011 by International Society of Gastrointestinal Oncology.

Authors
Kachnic, LA; Winter, K; Wasserman, T; Kelsen, D; Ginsberg, R; Pisansky, TM; Martenson, J; Komaki, R; Okawara, G; Rosenthal, SA; Willett, CG; Minsky, BD
MLA Citation
Kachnic, LA, Winter, K, Wasserman, T, Kelsen, D, Ginsberg, R, Pisansky, TM, Martenson, J, Komaki, R, Okawara, G, Rosenthal, SA, Willett, CG, and Minsky, BD. "Longitudinal quality-of-life analysis of RTOG 94-05 (Int 0123): A phase III trial of definitive chemoradiotherapy for esophageal cancer." Gastrointestinal Cancer Research 4.2 (2011): 45-52.
Source
scival
Published In
Gastrointestinal Cancer Research
Volume
4
Issue
2
Publish Date
2011
Start Page
45
End Page
52

Colon cancer.

Authors
3rd, ABB; Arnoletti, JP; Bekaii-Saab, T; Chan, E; Chen, Y-J; Choti, MA; Cooper, HS; Dilawari, RA; Engstrom, PF; Enzinger, PC; Jr, JWF; Fuchs, CS; Grem, JL; Knol, JA; Leong, LA; Lin, E; May, KS; Mulcahy, MF; Murphy, K; Rohren, E; Ryan, DP; Saltz, L; Sharma, S; Shibata, D; Skibber, JM; Jr, WS; Sofocleous, CT; Venook, AP; Willett, C; Network, NCC
MLA Citation
3rd, ABB, Arnoletti, JP, Bekaii-Saab, T, Chan, E, Chen, Y-J, Choti, MA, Cooper, HS, Dilawari, RA, Engstrom, PF, Enzinger, PC, Jr, JWF, Fuchs, CS, Grem, JL, Knol, JA, Leong, LA, Lin, E, May, KS, Mulcahy, MF, Murphy, K, Rohren, E, Ryan, DP, Saltz, L, Sharma, S, Shibata, D, Skibber, JM, Jr, WS, Sofocleous, CT, Venook, AP, Willett, C, and Network, NCC. "Colon cancer." Journal of the National Comprehensive Cancer Network : JNCCN 9.11 (2011): 1238-1290.
PMID
22056656
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
11
Publish Date
2011
Start Page
1238
End Page
1290

Intensity-modulated radiation therapy for anal malignancies: a preliminary toxicity and disease outcomes analysis.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has the potential to reduce toxicities associated with chemoradiotherapy in the treatment of anal cancer. This study reports the results of using IMRT in the treatment of anal cancer. METHODS AND MATERIALS: Records of patients with anal malignancies treated with IMRT at Duke University were reviewed. Acute toxicity was graded using the NCI CTCAEv3.0 scale. Overall survival (OS), metastasis-free survival (MFS), local-regional control (LRC) and colostomy-free survival (CFS) were calculated using the Kaplan-Meier method. RESULTS: Forty-seven patients with anal malignancy (89% canal, 11% perianal skin) were treated with IMRT between August 2006 and September 2008. Median follow-up was 14 months (19 months for SCC patients). Median radiation dose was 54 Gy. Eight patients (18%) required treatment breaks lasting a median of 5 days (range, 2-7 days). Toxicity rates were as follows: Grade 4: leukopenia (7%), thrombocytopenia (2%); Grade 3: leukopenia (18%), diarrhea (9%), and anemia (4%); Grade 2: skin (93%), diarrhea (24%), and leukopenia (24%). The 2-year actuarial overall OS, MFS, LRC, and CFS rates were 85%, 78%, 90% and 82%, respectively. For SCC patients, the 2-year OS, MFS, LRC, and CFS rates were 100%, 100%, 95%, and 91%, respectively. CONCLUSIONS: IMRT-based chemoradiotherapy for anal cancer results in significant reductions in normal tissue dose and acute toxicities versus historic controls treated without IMRT, leading to reduced rates of toxicity-related treatment interruption. Early disease-related outcomes seem encouraging. IMRT is emerging as a standard therapy for anal cancer.

Authors
Pepek, JM; Willett, CG; Wu, QJ; Yoo, S; Clough, RW; Czito, BG
MLA Citation
Pepek, JM, Willett, CG, Wu, QJ, Yoo, S, Clough, RW, and Czito, BG. "Intensity-modulated radiation therapy for anal malignancies: a preliminary toxicity and disease outcomes analysis." Int J Radiat Oncol Biol Phys 78.5 (December 1, 2010): 1413-1419.
PMID
20231064
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
78
Issue
5
Publish Date
2010
Start Page
1413
End Page
1419
DOI
10.1016/j.ijrobp.2009.09.046

Adjuvant radiation therapy for distal pancreatic cancer: is there a role?

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Adjuvant radiation therapy for distal pancreatic cancer: is there a role?." Ann Surg Oncol 17.12 (December 2010): 3082-3084.
PMID
20878486
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
17
Issue
12
Publish Date
2010
Start Page
3082
End Page
3084
DOI
10.1245/s10434-010-1356-x

Intensity-modulated radiation therapy for anal cancer: toxicity versus outcomes.

The treatment of cancer of the anal canal has changed significantly over the past several decades. Although the abdominoperineal resection (APR) was the historical standard of care, a therapeutic paradigm shift occurred with the seminal work of Nigro, who reported that anal canal cancer could be treated with definitive chemoradiation, with APR reserved for salvage therapy only. This remains an attractive approach for patients and physicians alike and the standard of care in this disease. Now, nearly four decades later, a similar approach continues to be utilized, albeit with higher radiation doses; however, this strategy remains fraught with considerable treatment-related morbidities. With the advent of intensity-modulated radiation therapy (IMRT), many oncologists are beginning to utilize this technology in the treatment of anal cancer in order to decrease these toxicities while maintaining similar treatment efficacy. This article reviews the relevant literature leading up to the modern treatment of anal canal cancer, and discusses IMRT-related toxicity and disease-related outcomes in the context of outcomes of conventionally treated anal cancer.

Authors
Zagar, TM; Willett, CG; Czito, BG
MLA Citation
Zagar, TM, Willett, CG, and Czito, BG. "Intensity-modulated radiation therapy for anal cancer: toxicity versus outcomes." Oncology (Williston Park) 24.9 (August 2010): 815-828. (Review)
PMID
20923035
Source
pubmed
Published In
Oncology
Volume
24
Issue
9
Publish Date
2010
Start Page
815
End Page
828

Epigenetic markers in rectal cancer.

DNA methylation changes in rectal cancer may serve as a new screening marker and a tool for monitoring recurrence. Importantly, these changes may also function as a predictive marker to allow appropriate exclusion of (neo)adjuvant therapies in patients at low risk for disease recurrence, sparing them from potential treatment-related morbidities.

Authors
Xu, L; Czito, BG; Willett, CG
MLA Citation
Xu, L, Czito, BG, and Willett, CG. "Epigenetic markers in rectal cancer." Clin Cancer Res 16.10 (May 15, 2010): 2699-2701. (Review)
PMID
20460492
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
16
Issue
10
Publish Date
2010
Start Page
2699
End Page
2701
DOI
10.1158/1078-0432.CCR-10-0559

Current and emerging treatment strategies for anal cancer.

Concurrent radiotherapy and chemotherapy (5-fluorouracil and mitomycin-C) is established as a sphincter-preserving treatment for squamous cell carcinoma of the anal canal. However, there is room for improvement in rates of tumor control as well as a need to reduce treatment-induced toxicity. Efforts are underway to test the value of newer radiosensitizing chemotherapeutic and molecular targeted agents, as well as to establish the value of advances in radiation therapy planning and delivery. This review discusses the evolution of therapy for anal cancer, from early clinical trials establishing the current standard to more recent studies evaluating cisplatin, capecitabine, oxaliplatin, and cetuximab. Early clinical results from studies incorporating intensity-modulated radiation therapy are also discussed.

Authors
Meyer, J; Willett, C; Czito, B
MLA Citation
Meyer, J, Willett, C, and Czito, B. "Current and emerging treatment strategies for anal cancer." Curr Oncol Rep 12.3 (May 2010): 168-174. (Review)
PMID
20425076
Source
pubmed
Published In
Current Oncology Reports
Volume
12
Issue
3
Publish Date
2010
Start Page
168
End Page
174
DOI
10.1007/s11912-010-0100-9

Nonoperative management of rectal cancer: current perspectives.

While surgery plays a central role in the management of all stages of operable rectal cancer, nonoperative approaches for both early-stage and locally advanced disease are being explored. This comprehensive review summarizes the current literature regarding the nonoperative management of rectal cancer and discusses caveats and controversies to such an approach.

Authors
Higgins, KA; Willett, CG; Czito, BG
MLA Citation
Higgins, KA, Willett, CG, and Czito, BG. "Nonoperative management of rectal cancer: current perspectives." Clin Colorectal Cancer 9.2 (April 2010): 83-88. (Review)
PMID
20378501
Source
pubmed
Published In
Clinical colorectal cancer
Volume
9
Issue
2
Publish Date
2010
Start Page
83
End Page
88
DOI
10.3816/CCC.2010.n.011

Radiation therapy advances for treatment of anal cancer.

Radiation therapy (RT) is established as the primary treatment of squamous cell carcinoma of the anus. Multiple randomized trials have shown that combined modality therapy with RT, 5-fluorouracil, and mitomycin-C results in high rates of local control, disease-free survival, and sphincter preservation. However, treatment-related toxicity using conventional radiation approaches remains high and may compromise therapeutic efficacy because of prolonged treatment breaks and inability to deliver adequate radiation dose. Recent developments, including the use of PET for staging, radiation planning, and response assessment, and advanced RT planning using intensity-modulated radiation therapy (IMRT), may decrease acute and late treatment-related toxicity, provide high-dose target conformality, and permit safe radiation dose escalation. This article reviews the basic principles of IMRT and highlights current literature on these recent advances and the application of new RT techniques.

Authors
Pepek, JM; Willett, CG; Czito, BG
MLA Citation
Pepek, JM, Willett, CG, and Czito, BG. "Radiation therapy advances for treatment of anal cancer." J Natl Compr Canc Netw 8.1 (January 2010): 123-129. (Review)
PMID
20064294
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
8
Issue
1
Publish Date
2010
Start Page
123
End Page
129

A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer.

INTRODUCTION: Bevacizumab is increasingly being tested with neoadjuvant regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. As a benchmark, we used data from an analysis of 42 patients with locally advanced rectal cancer treated with a contemporary approach of preoperative fluoropyrimidine-based radiation therapy. MATERIALS AND METHODS: Outcome analyses were performed on 32 patients treated prospectively with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery as well as 42 patients treated with standard fluoropyrimidine-based chemoradiation. RESULTS: Overall survival, disease-free survival, and local control showed favorable trends in patients treated with bevacizumab with chemoradiation followed by surgery. Acute and postoperative toxicity appeared acceptable. CONCLUSIONS: Neoadjuvant bevacizumab with standard chemoradiation and surgery shows promising long-term efficacy and safety profiles in locally advanced rectal cancer patients.

Authors
Willett, CG; Duda, DG; Ancukiewicz, M; Shah, M; Czito, BG; Bentley, R; Poleski, M; Fujita, H; Lauwers, GY; Carroll, M; Tyler, D; Mantyh, C; Shellito, P; Chung, DC; Clark, JW; Jain, RK
MLA Citation
Willett, CG, Duda, DG, Ancukiewicz, M, Shah, M, Czito, BG, Bentley, R, Poleski, M, Fujita, H, Lauwers, GY, Carroll, M, Tyler, D, Mantyh, C, Shellito, P, Chung, DC, Clark, JW, and Jain, RK. "A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer." Oncologist 15.8 (2010): 845-851.
PMID
20667969
Source
pubmed
Published In
The oncologist
Volume
15
Issue
8
Publish Date
2010
Start Page
845
End Page
851
DOI
10.1634/theoncologist.2010-0030

Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer.

We explored plasma and urinary concentrations of two members of the vascular endothelial growth factor (VEGF) family and their receptors as potential response and toxicity biomarkers of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The concentrations of VEGF, placental growth factor (PlGF), soluble VEGF receptor 1 (sVEGFR-1), and sVEGFR-2 were measured in plasma and urine at baseline and during treatment. Pretreatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment as well as for acute toxicity in patients with locally advanced rectal cancer treated prospectively in 2002-2008 with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery in a phase I/II trial. Of all biomarkers, pretreatment plasma sVEGFR-1-an endogenous blocker of VEGF and PlGF, and a factor linked with "vascular normalization"-was associated with both primary tumor regression and the development of adverse events after neoadjuvant bevacizumab and chemoradiation. Based on the findings in this exploratory study, we propose that plasma sVEGFR-1 should be further studied as a potential biomarker to stratify patients in future studies of bevacizumab and/or cytotoxics in the neoadjuvant setting.

Authors
Duda, DG; Willett, CG; Ancukiewicz, M; di Tomaso, E; Shah, M; Czito, BG; Bentley, R; Poleski, M; Lauwers, GY; Carroll, M; Tyler, D; Mantyh, C; Shellito, P; Clark, JW; Jain, RK
MLA Citation
Duda, DG, Willett, CG, Ancukiewicz, M, di Tomaso, E, Shah, M, Czito, BG, Bentley, R, Poleski, M, Lauwers, GY, Carroll, M, Tyler, D, Mantyh, C, Shellito, P, Clark, JW, and Jain, RK. "Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer." Oncologist 15.6 (2010): 577-583.
PMID
20484123
Source
pubmed
Published In
The oncologist
Volume
15
Issue
6
Publish Date
2010
Start Page
577
End Page
583
DOI
10.1634/theoncologist.2010-0029

Intensity-modulated radiation therapy for anal cancer: Toxicity versus Outcomes

The treatment of cancer of the anal canal has changed significantly over the past several decades. Although the abdominoperineal resection (APR) was the historical standard of care, a therapeutic paradigm shift occurred with the seminal work of Nigro, who reported that anal canal cancer could be treated with definitive chemoradiation, with APR reserved for salvage therapy only. This remains an attractive approach for patients and physicians alike and the standard of care in this disease. Now, nearly four decades later, a similar approach continues to be utilized, albeit with higher radiation doses; however, this strategy remains fraught with considerable treatment-related morbidities. With the advent of intensity-modulated radiation therapy (IMRT), many oncologists are beginning to utilize this technology in the treatment of anal cancer in order to decrease these toxicities while maintaining similar treatment efficacy. This article reviews the relevant literature leading up to the modern treatment of anal canal cancer, and discusses IMRT-related toxicity and disease-related outcomes in the context of outcomes of conventionally treated anal cancer.

Authors
Zagar, TM; Willett, CG; Czito, BG
MLA Citation
Zagar, TM, Willett, CG, and Czito, BG. "Intensity-modulated radiation therapy for anal cancer: Toxicity versus Outcomes." ONCOLOGY 24.9 (2010).
Source
scival
Published In
Oncology
Volume
24
Issue
9
Publish Date
2010

Gastric cancer: Clinical practice guidelines in oncology™

Gastric cancer is rampant in several countries. Its incidence in the Western Hemisphere has been declining for more than 40 years. In the past 15 years, the incidence of proximal gastric cancer has increased in Western countries compared with non-proximal gastric cancer, which is more prevalent in Japan and other parts of the world. Diffuse histology is also more common now than intestinal type of histology. H. pylori infection, smoking, and high salt intake are risk factors for gastric cancer. Few gastric cancers are associated with inherited gastric cancer predisposition syndromes. Several advances have been made in therapeutic approaches, imaging techniques, and staging procedures. Multidisciplinary team management is essential for treating patients with gastric cancer. Patients with locoregional disease should be referred to high-volume treatment centers. Surgery is the primary treatment option for medically fit patients with resectable gastric cancer. However, in the West, surgery alone is an insufficient therapy for most patients. Subtotal gastrectomy is preferred for distal gastric cancers, whereas proximal or total gastrectomy is recommended for proximal tumors. Based on the results of recent clinical trials, perioperative chemotherapy with ECF or its modifications is recommended for medically fit patients with resectable locoregional distal esophageal, gastroesophageal junction, and gastric adenocarcinoma (category 1). Preoperative chemoradiation may also be considered for these patients (category 2B). Post-operative treatment is based on surgical margins and nodal status. All patients with unresectable disease may be treated with 5-FU-based chemoradiation. Targeted therapies in combination with chemotherapy have produced encouraging results in the treatment of patients with advanced gastric, esophageal, and gastroesophageal junction cancers. Based on the results of the ToGA trial, the NCCN panel included trastuzumab plus chemotherapy in the guidelines as a new treatment option for patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma. The efficacy of VEGFR and EGFR inhibitors in combination with chemotherapy for patients with advanced gastric and gastroesophageal junction cancers are being evaluated in ongoing randomized phase III trials. Best supportive care is an integral part of treatment, especially in patients with metastatic and advanced gastric cancer. Patients with good performance status can be treated with chemotherapy or best supportive care, whereas best supportive care alone is the appropriate treatment for patients with poor performance status. Assessment of disease severity and related symptoms is essential to initiate appropriate palliative interventions that will prevent and relieve suffering and improve quality of life for patients and their caregivers. Treatment options used for palliation of symptoms in patients with advanced gastric cancer include endoscopic placement of self-expanding metal stents, laser surgery, or RT. The NCCN Gastric Cancer Guidelines provide an evidence-based systematic approach to the management of gastric cancer in the United States. Many new chemotherapeutic agents, targeted therapies, vaccines, gene therapy, and antiangiogenic agents are being studied in clinical trials. The panel encourages patients to participate in well-designed clinical trials to enable further advances. © Journal of the National Comprehensive Cancer Network.

Authors
Ajani, JA; Barthel, JS; Bekaii-Saab, T; Bentrem, DJ; D'Amico, TA; Das, P; Denlinger, C; Fuchs, CS; Gerdes, H; Hayman, JA; Hazard, L; Hofstetter, WL; Ilson, DH; Keswani, RN; Kleinberg, LR; Korn, M; Meredith, K; Mulcahy, MF; Orringer, MB; Osarogiagbon, RU; Posey, JA; Sasson, AR; Scott, WJ; Shibata, S; Strong, VEM; Washington, MK; Willett, C; Wood, DE; Wright, CD; Yang, G
MLA Citation
Ajani, JA, Barthel, JS, Bekaii-Saab, T, Bentrem, DJ, D'Amico, TA, Das, P, Denlinger, C, Fuchs, CS, Gerdes, H, Hayman, JA, Hazard, L, Hofstetter, WL, Ilson, DH, Keswani, RN, Kleinberg, LR, Korn, M, Meredith, K, Mulcahy, MF, Orringer, MB, Osarogiagbon, RU, Posey, JA, Sasson, AR, Scott, WJ, Shibata, S, Strong, VEM, Washington, MK, Willett, C, Wood, DE, Wright, CD, and Yang, G. "Gastric cancer: Clinical practice guidelines in oncology™." JNCCN Journal of the National Comprehensive Cancer Network 8.4 (2010): 378-409.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
8
Issue
4
Publish Date
2010
Start Page
378
End Page
409

Pancreatic adenocarcinoma: Clinical practice guidelines in oncology

Overall, in view of the relatively high likelihood of a poor outcome for patients with all stages of pancreatic cancer, the panel recommends that investigational options be considered in all phases of disease management. Specific palliative measures are recommended for patients with advanced pancreatic adenocarcinoma characterized by biliary or gastric obstruction, severe abdominal pain, or other tumor-associated manifestations of the disease. © JNCCN - Journal of the National Comprehensive Cancer Network.

Authors
Tempero, MA; Arnoletti, JP; Behrman, S; Ben-Josef, E; III, ABB; Berlin, JD; Cameron, JL; Casper, ES; Cohen, SJ; Duff, M; Ellenhorn, JDI; Hawkins, WG; Hoffman, JP; II, BWK; Malafa, MP; II, PM; Nakakura, EK; Sasson, AR; Thayer, SP; Tyler, DS; Warren, RS; Whiting, S; Willett, C; Wolff, RA
MLA Citation
Tempero, MA, Arnoletti, JP, Behrman, S, Ben-Josef, E, III, ABB, Berlin, JD, Cameron, JL, Casper, ES, Cohen, SJ, Duff, M, Ellenhorn, JDI, Hawkins, WG, Hoffman, JP, II, BWK, Malafa, MP, II, PM, Nakakura, EK, Sasson, AR, Thayer, SP, Tyler, DS, Warren, RS, Whiting, S, Willett, C, and Wolff, RA. "Pancreatic adenocarcinoma: Clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 8.9 (2010): 972-973+991-1016-.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
8
Issue
9
Publish Date
2010
Start Page
972-973+991-1016

Impact of overall treatment time on survival and local control in patients with anal cancer: A pooled data analysis of radiation therapy oncology group trials 87-04 and 98-11

Purpose: To determine whether increased duration of radiation therapy (RT) and overall treatment (RX) time has a detrimental effect in anal cancer. Patients and Methods: Data from Radiation Therapy Oncology Group (RTOG) 87-04 and RTOG 98-11 trials were combined to form three treatment groups: RT/fluorouracil (FU)/mitomycin (n = 472), RT/FU/cisplatin (n = 320), and RT/FU (n = 145). Cox proportional hazards models were used with the following variables: RT duration, RT intensity, RX duration, treatment group, age, sex, Karnofsky performance score (KPS), T stage, N stage, and RT dose. Results: In the univariate analysis, there was a significant association between RX duration and colostomy failure (CF; hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.14; P = .02), local failure (HR = 1.52; 95% CI, 1.14 to 2.03; P = .005), locoregional failure (HR = 1.51; 95% CI, 1.15 to 1.98; P = .003), and time to failure (HR = 1.40; 95% CI, 1.10 to 1.79; P = .007). The significance of RX duration was maintained after adjusting for treatment group. In multivariate modeling there was a trend toward an association between RX duration and CF (HR = 1.57; 95% CI, 0.98 to 2.50; P = .06) and a statistically significant association with local failure (HR = 1.96; 95% CI, 1.34 to 2.87; P = .0006). Age, sex, KPS, T stage, N stage, and RT dose, but not RT duration, RT intensity, or RX duration, were found to be statistically significant predictors of OS and colostomyfree survival. Conclusion: Total treatment time, but not duration of radiation therapy, seems to have a detrimental effect on local failure and colostomy rate in anal cancer. Induction chemotherapy may contribute to local failure by increasing total treatment time. © 2010 by American Society of Clinical Oncology.

Authors
Ben-Josef, E; Moughan, J; Ajani, JA; Flam, M; Gunderson, L; Pollock, J; Myerson, R; Anne, R; Rosenthal, SA; Willett, C
MLA Citation
Ben-Josef, E, Moughan, J, Ajani, JA, Flam, M, Gunderson, L, Pollock, J, Myerson, R, Anne, R, Rosenthal, SA, and Willett, C. "Impact of overall treatment time on survival and local control in patients with anal cancer: A pooled data analysis of radiation therapy oncology group trials 87-04 and 98-11." Journal of Clinical Oncology 28.34 (2010): 5061-5066.
PMID
20956625
Source
scival
Published In
Journal of Clinical Oncology
Volume
28
Issue
34
Publish Date
2010
Start Page
5061
End Page
5066
DOI
10.1200/JCO.2010.29.1351

Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: The intergroup trial (RTOG 98-11)

BACKGROUND: Only 4 prospective randomized phase 3 trials have been reported for anal cancer. A prognostic factor analysis for anal cancer from a prospective database has been published from only 1 study (N = 110). To confirm and uncover new prognostic factors,we analyzed the prospective database of intergroup RTOG 98-11. METHODS: Univariate and multivariate analyses of the baseline characteristics for 5-year overall survival (OS) and disease-free survival (DFS) were carried out. Various combinations of tumor diameter and clinically positive nodes (N+) were analyzed to identify subgroups. RESULTS: A total of 644 were assessable and analyzed. Tumor diameter >5 cm was associated with poorer 5-year DFS (P = .0003) and poorer 5-year OS (P = .0031), and N+ was associated with poorer 5-year DFS (P ≤ .0001) and poorer 5-year OS (P = ≤ .0001) in the multivariate analysis. In stratified analyses, N+ had more adverse influence on DFS and OS than did tumor diameter. Patients with >5-cm tumor and N+ had the worst DFS (only 30% at 3 years compared with 74% for the best group; <5 cm primary and N0) and OS (only 48% at 4 years compared with 81% for the best group; <5 cm primary and N0). Men had worse DFS (P = .02) and OS (P = .016). These factors maintained their influence in each treatment arm. CONCLUSIONS: This prospective prognostic factor analysis establishes tumor diameter as an independent prognosticator of poorer 5-year DFS and OS and confirms N + and male sex as poor prognostic factors. This analysis also uncovers novel subgroups (derived from combining prognostic factors) with incremental worsening of DFS and OS. © 2010 American Cancer Society.

Authors
Ajani, JA; Winter, KA; Gunderson, LL; Pedersen, J; III, ABB; Jr, CRT; Mayer, RJ; Haddock, MG; Rich, TA; Willett, CG
MLA Citation
Ajani, JA, Winter, KA, Gunderson, LL, Pedersen, J, III, ABB, Jr, CRT, Mayer, RJ, Haddock, MG, Rich, TA, and Willett, CG. "Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: The intergroup trial (RTOG 98-11)." Cancer 116.17 (2010): 4007-4013.
PMID
20564111
Source
scival
Published In
Cancer
Volume
116
Issue
17
Publish Date
2010
Start Page
4007
End Page
4013
DOI
10.1002/cncr.25188

Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older

Purpose: To review the outcomes and tolerability of full-dose chemoradiation in elderly patients aged 75 years or older with localized pancreatic cancer. Methods and Materials: We retrospectively reviewed patients aged 75 years or older with nonmetastatic pancreatic cancer treated with chemoradiation therapy at two institutions from 2002 to 2007. Patients were analyzed for treatment toxicity, local recurrences, distant metastases, and survival. Results: A total of 42 patients with a median age of 78 years (range, 75-90 years) who received chemoradiation therapy for pancreatic cancer were identified. Of the patients, 24 had locally advanced disease treated with definitive chemoradiation, and 18 had disease treated with surgery and chemoradiation. Before chemoradiotherapy, the mean Eastern Cooperative Oncology Group performance status was 1.0 ± 0.8, and the mean 6-month weight loss was 5.3 ± 3.8 kg. The mean radiation dose delivered was 48.1 ± 9.2 Gy. All patients received fluoropyrimidine-based chemotherapy concurrently with radiotherapy. In all, 8 patients (19%) were hospitalized, 7 (17%) had an emergency room visit, 15 (36%) required a radiation treatment break, 3 (7%) required a chemotherapy break, 9 (21%) did not complete therapy, and 22 (49%) had at least one of these adverse events. The most common toxicities were nausea, pain, and failure to thrive. Median overall survival was 8.6 months (95% confidence interval, 7.2-13.1) in patients who received definitive chemoradiation therapy and 20.6 months (95% confidence interval, 9.5-∞) in patients who underwent resection and chemoradiation therapy. Conclusions: In this dataset of very elderly patients with pancreatic cancer and good Eastern Cooperative Oncology Group performance status, outcomes after chemoradiotherapy were similar to those among historic controls for patients with locally advanced and resected pancreatic cancer, although many patients experienced substantial treatment-related toxicity. © 2010 Elsevier Inc. All rights reserved.

Authors
Miyamoto, DT; Mamon, HJ; Ryan, DP; Willett, CG; Ancukiewicz, M; Kobayashi, WK; Blaszkowsky, L; Castillo, CF-D; Hong, TS
MLA Citation
Miyamoto, DT, Mamon, HJ, Ryan, DP, Willett, CG, Ancukiewicz, M, Kobayashi, WK, Blaszkowsky, L, Castillo, CF-D, and Hong, TS. "Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older." International Journal of Radiation Oncology Biology Physics 77.4 (2010): 1171-1177.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
77
Issue
4
Publish Date
2010
Start Page
1171
End Page
1177
DOI
10.1016/j.ijrobp.2009.06.020

Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older

Randomized trials of chemoradiation for esophageal cancer have included very few patients age ≥ 75. In this retrospective study, we describe the outcomes and toxicity of full-dose chemoradiation in elderly patients with esophageal cancer. Patients, age ≥ 75, treated with full-dose chemoradiation for esophageal carcinoma from 2002 to 2008 were retrospectively reviewed. Thirty-four patients were identified with a median age of 79.5 (range 75-89). The median Eastern Cooperative Oncology Group performance status was 1 (range 0-3) and the median Adult Comorbidity Evaluation-27 score was 1 (range 0-3). Twenty-eight patients received definitive and six received neoadjuvant chemoradiation. The median radiation dose delivered was 50.4 Gray (range 3.6-68.4 Gray). Platinum-based chemotherapy was used in 79.4% of patients. Fifty percent of the patients completed all planned radiation therapy (RT) and chemotherapy; 85.3% completed RT. Acute toxicity ≥ grade 4 occurred in 38.2% of patients, and 70.6% of the patients required hospitalization, emergency department visit, and/or RT break. Median follow-up was 14.5 months among 7 survivors, and median survival was 12.0 months (95% confidence interval [CI]: 9.7 to 24.1 months). The actuarial overall survival at 2 years was 29.7% (95% CI: 16.6 to 52.6%). There were four treatment-related deaths. The median time to any recurrence was 10.4 months. Nineteen patients had a local and/or distant recurrence. In conclusion, elderly patients experienced substantial morbidity from chemoradiation, and long-term survival was low. Future efforts to improve treatment tolerability in the elderly are needed. © 2009 Copyright the Authors Journal compilation © 2010, Wiley Periodicals, Inc.

Authors
Mak, RH; Mamon, HJ; Ryan, DP; Miyamoto, DT; Ancukiewicz, M; Kobayashi, WK; Willett, CG; Choi, NC; Blaszkowsky, LS; Hong, TS
MLA Citation
Mak, RH, Mamon, HJ, Ryan, DP, Miyamoto, DT, Ancukiewicz, M, Kobayashi, WK, Willett, CG, Choi, NC, Blaszkowsky, LS, and Hong, TS. "Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older." Diseases of the Esophagus 23.4 (2010): 316-323.
PMID
19788436
Source
scival
Published In
Diseases of the Esophagus
Volume
23
Issue
4
Publish Date
2010
Start Page
316
End Page
323
DOI
10.1111/j.1442-2050.2009.01014.x

Anal carcinoma: Clinical practice guidelines in oncology™

The panel believes that a multidisciplinary approach, including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with anal carcinoma. Recommendations for the primary treatment of anal margin and anal canal cancer are very similar and include 5-FU/mitomycin-based RT, although small, well-differentiated anal margin lesions can be treated with margin-negative local excision alone. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because salvage is possible. Patients with biopsy-proven evidence of locoregional progressive disease after primary treatment should undergo an APR. After complete remission of disease, patients with a local recurrence should be treated with an APR with groin dissection if they have evidence of inguinal nodal metastasis, and patients with a regional recurrence in the inguinal nodes can be treated with an inguinal node dissection, with consideration of RT with or without chemotherapy, if limited prior RT to the groin was given. Patients with evidence of extrapelvic metastatic disease should be treated with cisplatin-based chemotherapy or enrolled in a clinical trial. The panel endorses the concept that treating patients in a clinical trial has priority over standard or accepted therapy. © Journal of the National Comprehensive Cancer Network 2010.

Authors
Engstrom, PF; Arnoletti, JP; III, ABB; Berlin, JD; Berry, JM; Chen, Y-J; Choti, MA; Cooper, HS; Dilawari, RA; Early, DS; Enzinger, PC; Fakih, MG; Jr, JF; Fuchs, C; Grem, JL; Knol, JA; Leong, LA; Lin, E; Mulcahy, MF; Rohren, E; Ryan, DP; Saltz, L; Shibata, D; Skibber, JM; Jr, WS; Sofocleous, C; Thomas, J; Venook, AP; Willett, C
MLA Citation
Engstrom, PF, Arnoletti, JP, III, ABB, Berlin, JD, Berry, JM, Chen, Y-J, Choti, MA, Cooper, HS, Dilawari, RA, Early, DS, Enzinger, PC, Fakih, MG, Jr, JF, Fuchs, C, Grem, JL, Knol, JA, Leong, LA, Lin, E, Mulcahy, MF, Rohren, E, Ryan, DP, Saltz, L, Shibata, D, Skibber, JM, Jr, WS, Sofocleous, C, Thomas, J, Venook, AP, and Willett, C. "Anal carcinoma: Clinical practice guidelines in oncology™." JNCCN Journal of the National Comprehensive Cancer Network 8.1 (2010): 106-120.
PMID
20064293
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
8
Issue
1
Publish Date
2010
Start Page
106
End Page
120

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US GI Intergroup RTOG 98-11 Phase III Trial

Authors
Gunderson, LL; Moughan, J; Ajani, JA; Pedersen, JE; Benson, AB; Thomas, CR; Mayer, RJ; Haddock, MG; Rich, TA; Willett, CG
MLA Citation
Gunderson, LL, Moughan, J, Ajani, JA, Pedersen, JE, Benson, AB, Thomas, CR, Mayer, RJ, Haddock, MG, Rich, TA, and Willett, CG. "Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US GI Intergroup RTOG 98-11 Phase III Trial." 2010.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S55
End Page
S56

Intensity-modulated radiation therapy for anal cancer.

The contemporary treatment of anal cancer is combined-modality therapy with radiation therapy, fluorouracil, and mitomycin. This therapy results in long-term disease-free survival and sphincter preservation in the majority of patients. Tempering these positive results is the high rate of treatment-related morbidity associated with chemoradiation therapy for anal cancer. The use of intensity-modulated radiation therapy (IMRT) has the potential to reduce acute and chronic treatment-related toxicity, minimize treatment breaks, and potentially improve disease-related outcomes by permitting radiation dose escalation in selected cases.

Authors
Czito, BG; Pepek, JM; Meyer, JJ; Yoo, S; Willett, CG
MLA Citation
Czito, BG, Pepek, JM, Meyer, JJ, Yoo, S, and Willett, CG. "Intensity-modulated radiation therapy for anal cancer." Oncology (Williston Park) 23.12 (November 15, 2009): 1082-1089. (Review)
PMID
20017291
Source
pubmed
Published In
Oncology
Volume
23
Issue
12
Publish Date
2009
Start Page
1082
End Page
1089

Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality, despite significant improvements in diagnostic imaging and operative mortality rates. The 5-year survival rate remains less than 5% because of microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials Planning Meeting in pancreatic cancer was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to discuss the integration of basic and clinical knowledge in the design of clinical trials in PDAC. Major emphasis was placed on the enhancement of research to identify and validate the relevant targets and molecular pathways in PDAC, cancer stem cells, and the microenvironment. Emphasis was also placed on developing rational combinations of targeted agents and the development of predictive biomarkers to assist selection of patient subsets. The development of preclinical tumor models that are better predictive of human PDAC must be supported with wider availability to the research community. Phase III clinical trials should be implemented only if there is a meaningful clinical signal of efficacy and safety in the phase II setting. The emphasis must therefore be on performing well-designed phase II studies with uniform sets of basic entry and evaluation criteria with survival as a primary endpoint. Patients with either metastatic or locally advanced PDAC must be studied separately.

Authors
Philip, PA; Mooney, M; Jaffe, D; Eckhardt, G; Moore, M; Meropol, N; Emens, L; O'Reilly, E; Korc, M; Ellis, L; Benedetti, J; Rothenberg, M; Willett, C; Tempero, M; Lowy, A; Abbruzzese, J; Simeone, D; Hingorani, S; Berlin, J; Tepper, J
MLA Citation
Philip, PA, Mooney, M, Jaffe, D, Eckhardt, G, Moore, M, Meropol, N, Emens, L, O'Reilly, E, Korc, M, Ellis, L, Benedetti, J, Rothenberg, M, Willett, C, Tempero, M, Lowy, A, Abbruzzese, J, Simeone, D, Hingorani, S, Berlin, J, and Tepper, J. "Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.33 (November 2009): 5660-5669. (Review)
PMID
19858397
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
33
Publish Date
2009
Start Page
5660
End Page
5669
DOI
10.1200/jco.2009.21.9022

Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer.

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy.

Authors
Xu, L; Duda, DG; di Tomaso, E; Ancukiewicz, M; Chung, DC; Lauwers, GY; Samuel, R; Shellito, P; Czito, BG; Lin, P-C; Poleski, M; Bentley, R; Clark, JW; Willett, CG; Jain, RK
MLA Citation
Xu, L, Duda, DG, di Tomaso, E, Ancukiewicz, M, Chung, DC, Lauwers, GY, Samuel, R, Shellito, P, Czito, BG, Lin, P-C, Poleski, M, Bentley, R, Clark, JW, Willett, CG, and Jain, RK. "Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer." Cancer Res 69.20 (October 15, 2009): 7905-7910.
PMID
19826039
Source
pubmed
Published In
Cancer Research
Volume
69
Issue
20
Publish Date
2009
Start Page
7905
End Page
7910
DOI
10.1158/0008-5472.CAN-09-2099

Chemoradiotherapy in gastrointestinal malignancies.

Over the past 30 years, significant advances have been made in the integration of radiation therapy and chemotherapy in the treatment of patients with localised gastrointestinal malignancies. The therapeutic goal of chemoradiotherapy is to enhance local control resulting in improved survival and outcome of these patients. To define the optimal sequence, agents and efficacy of these modalities, an array of randomised studies have been conducted in malignancies of the oesophagus, stomach, pancreas, colon, rectum and anus. In oesophageal cancer, recent studies from Germany and France indicate that patients treated with 'definitive' chemoradiotherapy have similar survival to patients undergoing neoadjuvant chemoradiotherapy followed by surgery. For patients with locally advanced rectal cancer undergoing surgery, a phase III trial from Germany showed higher rates of local control with less acute and late morbidity for patients receiving neoadjuvant chemoradiotherapy vs adjuvant chemoradiotherapy. In contrast, the role of chemoradiotherapy in pancreatic cancer patients remains unclear and contentious. This overview highlights current results, controversies and potential future directions in the chemoradiotherapeutic treatment of selected gastrointestinal malignancies.

Authors
Willett, CG; Czito, BG
MLA Citation
Willett, CG, and Czito, BG. "Chemoradiotherapy in gastrointestinal malignancies." Clin Oncol (R Coll Radiol) 21.7 (September 2009): 543-556. (Review)
PMID
19577442
Source
pubmed
Published In
Comparative Haematology International
Volume
21
Issue
7
Publish Date
2009
Start Page
543
End Page
556
DOI
10.1016/j.clon.2009.05.004

Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study.

PURPOSE: To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response. PATIENTS AND METHODS: In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m(2)/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy. RESULTS: Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuarial 5-year local control and overall survival of 100%. Actuarial 5-year disease-free survival was 75% and five patients developed metastases postsurgery. Bevacizumab with chemoradiotherapy showed acceptable toxicity. Bevacizumab decreased tumor interstitial fluid pressure and blood flow. Baseline plasma soluble vascular endothelial growth factor receptor 1 (sVEGFR1), plasma vascular endothelial growth factor (VEGF), placental-derived growth factor (PlGF), and interleukin 6 (IL-6) during treatment, and circulating endothelial cells (CECs) after treatment showed significant correlations with outcome. CONCLUSION: Bevacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer. Plasma VEGF, PlGF, sVEGFR1, and IL-6 and CECs should be further evaluated as candidate biomarkers of response for this regimen.

Authors
Willett, CG; Duda, DG; di Tomaso, E; Boucher, Y; Ancukiewicz, M; Sahani, DV; Lahdenranta, J; Chung, DC; Fischman, AJ; Lauwers, GY; Shellito, P; Czito, BG; Wong, TZ; Paulson, E; Poleski, M; Vujaskovic, Z; Bentley, R; Chen, HX; Clark, JW; Jain, RK
MLA Citation
Willett, CG, Duda, DG, di Tomaso, E, Boucher, Y, Ancukiewicz, M, Sahani, DV, Lahdenranta, J, Chung, DC, Fischman, AJ, Lauwers, GY, Shellito, P, Czito, BG, Wong, TZ, Paulson, E, Poleski, M, Vujaskovic, Z, Bentley, R, Chen, HX, Clark, JW, and Jain, RK. "Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study." J Clin Oncol 27.18 (June 20, 2009): 3020-3026.
PMID
19470921
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
18
Publish Date
2009
Start Page
3020
End Page
3026
DOI
10.1200/JCO.2008.21.1771

SU-FF-T-545: Feasibility Study for Treatment of Intracranial Multi-Focal Stereotactic Radiosurgery with Multiple Intensity Modulated Arc Technique

Authors
Wang, Z; Kirkpatrick, J; Chang, Z; O'Daniel, J; Willett, C; Yin, F
MLA Citation
Wang, Z, Kirkpatrick, J, Chang, Z, O'Daniel, J, Willett, C, and Yin, F. "SU-FF-T-545: Feasibility Study for Treatment of Intracranial Multi-Focal Stereotactic Radiosurgery with Multiple Intensity Modulated Arc Technique." June 2009.
Source
crossref
Published In
Medical physics
Volume
36
Issue
6Part17
Publish Date
2009
Start Page
2649
End Page
2649
DOI
10.1118/1.3182043

SU-FF-T-548: Comparison of Cone-Beam CT and Frame-Based Localizations for Stereotactic Radiosurgery with Fixed Head Rings and Removable Frames

Authors
Wang, Z; Kirkpatrick, J; Wu, Q; Chang, Z; Willett, C; Yin, F
MLA Citation
Wang, Z, Kirkpatrick, J, Wu, Q, Chang, Z, Willett, C, and Yin, F. "SU-FF-T-548: Comparison of Cone-Beam CT and Frame-Based Localizations for Stereotactic Radiosurgery with Fixed Head Rings and Removable Frames." June 2009.
Source
crossref
Published In
Medical physics
Volume
36
Issue
6Part17
Publish Date
2009
Start Page
2650
End Page
2650
DOI
10.1118/1.3182046

Reply to C.D. Atkins

Authors
Berger, AC; Hoffman, JP; Winter, K; Regine, W; Safran, H; Abrams, R; Willet, C
MLA Citation
Berger, AC, Hoffman, JP, Winter, K, Regine, W, Safran, H, Abrams, R, and Willet, C. "Reply to C.D. Atkins." Journal of Clinical Oncology 27.15 (May 20, 2009): 2573-2573.
Source
crossref
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009
Start Page
2573
End Page
2573
DOI
10.1200/JCO.2009.21.9600

Current management of anal canal cancer.

Squamous cell carcinoma of the anal canal historically has been treated with abdominoperineal resection, resulting in high rates of morbidity and local recurrence. Pioneering work led to the finding that radiation therapy (RT) combined with 5-fluorouracil (5-FU) and mitomycin results in high rates of local control and disease-free and colostomy-free survival without surgery. Prospective randomized trials from Europe and the United States have shown the superiority of RT, 5-FU, and mitomycin over 1) RT alone, 2) RT with 5-FU, and 3) neoadjuvant cisplatin/5-FU with concurrent radiation, cisplatin, and 5-FU. At present, RT with 5-FU and mitomycin is the standard of care for anal cancer patients. Recent advances include the integration of positron emission tomography into staging, radiation treatment planning and monitoring, and the use of intensity modulated RT. European randomized trials are further evaluating the role of cisplatin in the neoadjuvant, concurrent, and adjuvant settings, as well as radiation dose escalation. Other studies are evaluating the use of capecitabine, oxaliplatin, and the anti-epidermal growth factor receptor agent cetuximab with RT in this malignancy.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Current management of anal canal cancer." Curr Oncol Rep 11.3 (May 2009): 186-192. (Review)
PMID
19336010
Source
pubmed
Published In
Current Oncology Reports
Volume
11
Issue
3
Publish Date
2009
Start Page
186
End Page
192

In pursuit of progress: multimodality strategies will form the cornerstone of cure for esophageal cancer.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "In pursuit of progress: multimodality strategies will form the cornerstone of cure for esophageal cancer." Gastrointest Cancer Res 3.2 (March 2009): 74-76.
PMID
19461910
Source
pubmed
Published In
Gastrointestinal Cancer Research
Volume
3
Issue
2
Publish Date
2009
Start Page
74
End Page
76

Metastatic Liver Cancer: Treatment: Radiation therapy

The liver is the most common site for blood-borne metastasis from colorectal cancers. Until the early 1980s, it was generally accepted that hepatic metastases from colorectal cancer represented just one site in a wide systemic dissemination of tumor, and hepatectomy was rarely used as treatment. Since then, numerous studies have shown that resection can prolong survival and potentially provide cure. Surgical excision for hepatic metastases from colorectal cancer is now considered standard therapy for patients with metastases isolated to the liver. In the next section, we will summarize the data supporting such therapies, as well as clinical parameters that infl uence outcome. Since acceptance of surgery as a local therapy for this disease, a number of other local therapies have emerged as effective treatment options for hepatic metastases. The data supporting use of radiotherapy will be presented, as well as recent data documenting outcome of treatment with ablative therapies such as radiofrequency ablation and cryoablation. These tissuesparing local treatments for hepatic colorectal metastases have further extended treatment possibilities. Recent advancements in chemotherapies and biologic therapies have also contributed to effective treatment for hepatic colorectal metastases and extended the possibility for cure. As many as 5% of patients previously beyond curative therapies are being converted by systemic therapies to resectable. Those not resectable for cure are effectively treated by systemic and regional therapies to achieve extension of life. In the following sections we will present the current approach of palliative and adjuvant chemotherapy. The use of systemic and regional chemotherapy as neoadjuvant therapy prior to hepatectomy will also be discussed. The combined advances in surgery, systemic therapies, and regional ablative therapies have transformed this disease from uniformly and immediately fatal to increasingly curable. © 2008 by Blackwell Publishing.

Authors
Willet, C; Czito, BG; Fong, Y
MLA Citation
Willet, C, Czito, BG, and Fong, Y. "Metastatic Liver Cancer: Treatment: Radiation therapy." (January 14, 2009): 494-497. (Chapter)
Source
scopus
Publish Date
2009
Start Page
494
End Page
497
DOI
10.1002/9781444300147.ch20

Concurrent chemoradiotherapy in resected extrahepatic cholangiocarcinoma.

PURPOSE: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. METHODS AND MATERIALS: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. RESULTS: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age

Authors
Nelson, JW; Ghafoori, AP; Willett, CG; Tyler, DS; Pappas, TN; Clary, BM; Hurwitz, HI; Bendell, JC; Morse, MA; Clough, RW; Czito, BG
MLA Citation
Nelson, JW, Ghafoori, AP, Willett, CG, Tyler, DS, Pappas, TN, Clary, BM, Hurwitz, HI, Bendell, JC, Morse, MA, Clough, RW, and Czito, BG. "Concurrent chemoradiotherapy in resected extrahepatic cholangiocarcinoma." Int J Radiat Oncol Biol Phys 73.1 (January 1, 2009): 148-153.
PMID
18805651
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
73
Issue
1
Publish Date
2009
Start Page
148
End Page
153
DOI
10.1016/j.ijrobp.2008.07.008

Intensity-modulated radiation therapy for anal cancer

The contemporary treatment of anal cancer is combined-modality therapy with radiation therapy, fluorouracil, and mitomycin. This therapy results in long-term disease-free survival and sphincter preservation in the majority of patients. Tempering these positive results is the high rate of treatment-related morbidity associated with chemoradiation therapy for anal cancer. The use of intensity-modulated radiation therapy (IMRT) has the potential to reduce acute and chronic treatment-related toxicity, minimize treatment breaks, and potentially improve disease-related outcomes by permitting radiation dose escalation in selected cases.

Authors
Czito, BG; Pepek, JM; Meyer, JJ; Yoo, S; Willett, CG
MLA Citation
Czito, BG, Pepek, JM, Meyer, JJ, Yoo, S, and Willett, CG. "Intensity-modulated radiation therapy for anal cancer." ONCOLOGY 23.12 (2009).
Source
scival
Published In
Oncology
Volume
23
Issue
12
Publish Date
2009

Rectal cancer

The NCCN Rectal Cancer Guidelines panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary for treating patients with rectal cancer. Adequate pathologic assessment of the resected lymph nodes is important with a goal of evaluating at least 12 nodes when possible. Patients with very early stage tumors lesions that are node-negative by endorectal ultrasound or endorectal or pelvic MRI and who meet carefully defined criteria can be managed with a transanal excision. A transabdominal resection is appropriate for all other rectal lesions. Preoperative chemoRT is preferred for the majority of patients with suspected or proven T3/T4 disease and/or regional node involvement and adjuvant chemotherapy is recommended. Patients with recurrent localized disease should be considered for resection with or without radiotherapy. A patient with metastatic disease in the liver or lung should be considered for surgical resection if he or she is a candidate for surgery and if complete resection (RO) or ablation can be achieved. Preoperative chemotherapy can be considered as initial therapy in patients with synchronous or metachronous resectable metastatic disease (i.e., neoadjuvant therapy) or when a response to chemotherapy may convert a patient from an unresectable to resectable state (i.e., conversion therapy). Other options for patients with resectable synchronous metastases are initial treatment with chemoRT or chemotherapy with or without a bevacizumab or cetuximab (KRAS wild type tumor only) followed by consolidating chemoRT. Resection should be followed by adjuvant therapy based on prior therapy received. The recommended post-treatment surveillance program for rectal cancer patients includes serial CEA determinations, as well as periodic chest, abdominal and pelvic CT scans, and periodic evaluations by colonoscopy and proctoscopy. Recommendations for patients with previously untreated disseminated metastatic disease represent a continuum of care in which lines of treatment are blurred rather than discrete. Principles to consider at the start of therapy include pre-planned strategies for altering therapy for patients in both the presence and absence of disease progression, including plans for adjusting therapy for patients who experience certain toxicities. Recommended initial therapy options for advanced or metastatic disease depend on whether or not the patient is appropriate for intensive therapy. The more intensive initial therapy options include FOLFOX, FOLFIRI, CapeOX, and FOLFOXIRI (category 2B). Addition of a biologic agent (e.g., bevacizumab or cetuximab) is either recommended, or listed as an option, in combination with some of these regimens, depending on available data. Chemotherapy options for patients with progressive disease are dependent on the choice of initial therapy. The panel endorses the concept that treating patients in a clinical trial has priority over standard or accepted therapy. © Journal of the National Comprehensive Cancer Network 2009.

Authors
Engstrom, PF; Arnoletti, JP; III, ABB; Chen, Y-J; Choti, MA; Cooper, HS; Covey, A; Dilawari, RA; Early, DS; Enzinger, PC; Fakih, MG; Jr, JF; Fuchs, C; Grem, JL; Kiel, K; Knol, JA; Leong, LA; Lin, E; Mulcahy, MF; Rao, S; Ryan, DP; Saltz, L; Shibata, D; Skibber, JM; Sofocleous, C; Thomas, J; Venook, AP; Willett, C
MLA Citation
Engstrom, PF, Arnoletti, JP, III, ABB, Chen, Y-J, Choti, MA, Cooper, HS, Covey, A, Dilawari, RA, Early, DS, Enzinger, PC, Fakih, MG, Jr, JF, Fuchs, C, Grem, JL, Kiel, K, Knol, JA, Leong, LA, Lin, E, Mulcahy, MF, Rao, S, Ryan, DP, Saltz, L, Shibata, D, Skibber, JM, Sofocleous, C, Thomas, J, Venook, AP, and Willett, C. "Rectal cancer." JNCCN Journal of the National Comprehensive Cancer Network 7.8 (2009): 838-881.
PMID
19755047
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
7
Issue
8
Publish Date
2009
Start Page
838
End Page
881

Colon cancer

The NCCN Colon/Rectal/Anal Cancer Guidelines panel believes that a multidisciplinary approach is necessary for managing colorectal cancer. The panel endorses the concept that treating patients in a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for resectable colon cancer is an en bloc resection and adequate lymphadenectomy. Adequate pathologic assessment of the resected lymph nodes is important with a goal of evaluating at least 12 nodes. Adjuvant therapy with FOLFOX (category 1), 5-FU/LV (category 2A), or capecitabine (category 2A) is recommended by the panel for patients with stage III disease, and as an option for patients with high-risk stage II disease (category 2A for all 3 treatment options). Patients with metastatic disease in the liver or lung should be considered for surgical resection if they are candidates for surgery and if all original sites of disease are amenable to resection (R0) and/or ablation. Preoperative chemotherapy can be considered as initial therapy in patients with synchronous or metachronous resectable metastatic disease or when a response to chemotherapy may convert a patient from an unresectable to a resectable state (i.e., conversion therapy). Adjuvant chemotherapy should be considered following resection of liver or lung metastases. The recommended post-treatment surveillance program for colon cancer patients includes serial CEA determinations; periodic chest, abdominal, and pelvic CT scans; colonoscopic evaluations; and a survivorship plan to manage long-term side effects of treatment, facilitate disease prevention, and promote a healthy lifestyle. Recommendations for patients with previously untreated disseminated metastatic disease represent a continuum of care in which lines of treatment are blurred rather than discrete. Principles to consider at the start of therapy include pre-planned strategies for altering therapy for patients in both the presence and absence of disease progression, including plans for adjusting therapy for patients who experience certain toxicities. Recommended initial therapy options for advanced or metastatic disease depend on whether or not the patient is appropriate for intensive therapy. The more intensive initial therapy options include FOLFOX, FOLFIRI, CapeOX, and FOLFOXIRI (category 2B). Addition of a biologic agent (e.g., bevacizumab or cetuximab) is either recommended, or listed as an option, in combination with some of these regimens, depending on available data. Chemotherapy options for patients with progressive disease are dependent on the choice of initial therapy. © Journal of the National Comprehensive Cancer Network 2009.

Authors
Engstrom, PF; Arnoletti, JP; III, ABB; Chen, Y-J; Choti, MA; Cooper, HS; Covey, A; Dilawari, RA; Early, DS; Enzinger, PC; Fakih, MG; Jr, JF; Fuchs, C; Grem, JL; Kiel, K; Knol, JA; Leong, LA; Lin, E; Mulcahy, MF; Rao, S; Ryan, DP; Saltz, L; Shibata, D; Skibber, JM; Sofocleous, C; Thomas, J; Venook, AP; Willett, C
MLA Citation
Engstrom, PF, Arnoletti, JP, III, ABB, Chen, Y-J, Choti, MA, Cooper, HS, Covey, A, Dilawari, RA, Early, DS, Enzinger, PC, Fakih, MG, Jr, JF, Fuchs, C, Grem, JL, Kiel, K, Knol, JA, Leong, LA, Lin, E, Mulcahy, MF, Rao, S, Ryan, DP, Saltz, L, Shibata, D, Skibber, JM, Sofocleous, C, Thomas, J, Venook, AP, and Willett, C. "Colon cancer." JNCCN Journal of the National Comprehensive Cancer Network 7.8 (2009): 778-831.
PMID
19755046
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
7
Issue
8
Publish Date
2009
Start Page
778
End Page
831

Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation Therapy Oncology Group RTOG 0411

Purpose: The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR). Patients and Methods: Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m2 orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m2 weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA). Results: Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05). Conclusion: The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials. © 2009 by the American Society of Clinical Oncology.

Authors
Crane, CH; Winter, K; Regine, WF; Safran, H; Rich, TA; Curran, W; Wolff, RA; Willett, CG
MLA Citation
Crane, CH, Winter, K, Regine, WF, Safran, H, Rich, TA, Curran, W, Wolff, RA, and Willett, CG. "Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation Therapy Oncology Group RTOG 0411." Journal of Clinical Oncology 27.25 (2009): 4096-4102.
PMID
19636002
Source
scival
Published In
Journal of Clinical Oncology
Volume
27
Issue
25
Publish Date
2009
Start Page
4096
End Page
4102
DOI
10.1200/JCO.2009.21.8529

Elective Clinical Target Volumes for Conformal Therapy in Anorectal Cancer: A Radiation Therapy Oncology Group Consensus Panel Contouring Atlas

Purpose: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. Methods and Materials: The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning and for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas. Results: The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed. Conclusion: This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials. © 2009 Elsevier Inc. All rights reserved.

Authors
Myerson, RJ; Garofalo, MC; Naqa, IE; Abrams, RA; Apte, A; Bosch, WR; Das, P; Gunderson, LL; Hong, TS; Kim, JJJ; Willett, CG; Kachnic, LA
MLA Citation
Myerson, RJ, Garofalo, MC, Naqa, IE, Abrams, RA, Apte, A, Bosch, WR, Das, P, Gunderson, LL, Hong, TS, Kim, JJJ, Willett, CG, and Kachnic, LA. "Elective Clinical Target Volumes for Conformal Therapy in Anorectal Cancer: A Radiation Therapy Oncology Group Consensus Panel Contouring Atlas." International Journal of Radiation Oncology Biology Physics 74.3 (2009): 824-830.
PMID
19117696
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
74
Issue
3
Publish Date
2009
Start Page
824
End Page
830
DOI
10.1016/j.ijrobp.2008.08.070

Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114)

Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. © 2009 by American Society of Clinical Oncology.

Authors
Schwartz, GK; Winter, K; Minsky, BD; Crane, C; Thomson, PJ; Anne, P; Gross, H; Willett, C; Kelsen, D
MLA Citation
Schwartz, GK, Winter, K, Minsky, BD, Crane, C, Thomson, PJ, Anne, P, Gross, H, Willett, C, and Kelsen, D. "Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114)." Journal of Clinical Oncology 27.12 (2009): 1956-1962.
PMID
19273696
Source
scival
Published In
Journal of Clinical Oncology
Volume
27
Issue
12
Publish Date
2009
Start Page
1956
End Page
1962
DOI
10.1200/JCO.2008.20.3745

Stereotactic radiotherapy for pancreatic cancer?

Authors
Crane, CH; Willett, CG
MLA Citation
Crane, CH, and Willett, CG. "Stereotactic radiotherapy for pancreatic cancer?." Cancer 115.3 (2009): 468-472.
PMID
19117338
Source
scival
Published In
Cancer
Volume
115
Issue
3
Publish Date
2009
Start Page
468
End Page
472
DOI
10.1002/cncr.24069

US intergroup anal carcinoma trial: Tumor diameter predicts for colostomy

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤.0001), large (> 5 cm) tumor diameter (P =.01), and male sex (P =.016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P =.03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P =.008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P =.0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. © 2009 by American Society of Clinical Oncology.

Authors
Ajani, JA; Winter, KA; Gunderson, LL; Pedersen, J; Iii, ABB; Jr, CRT; Mayer, RJ; Haddock, MG; Rich, TA; Willett, CG
MLA Citation
Ajani, JA, Winter, KA, Gunderson, LL, Pedersen, J, Iii, ABB, Jr, CRT, Mayer, RJ, Haddock, MG, Rich, TA, and Willett, CG. "US intergroup anal carcinoma trial: Tumor diameter predicts for colostomy." Journal of Clinical Oncology 27.7 (2009): 1116-1121.
PMID
19139424
Source
scival
Published In
Journal of Clinical Oncology
Volume
27
Issue
7
Publish Date
2009
Start Page
1116
End Page
1121
DOI
10.1200/JCO.2008.19.6857

Biomarkers of response and resistance to antiangiogenic therapy

No validated biological markers (or biomarkers) currently exist for appropriately selecting patients with cancer for antiangiogenic therapy. Nor are there biomarkers identifying escape pathways that should be targeted after tumors develop resistance to a given antiangiogenic agent. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged from recently completed phase I-III studies. Some of these are measured at baseline (for example VEGF polymorphisms), others are measured during treatment (such as hypertension, MRI-measured Ktrans, circulating angiogenic molecules or collagen IV), and all are mechanistically based. Some of these biomarkers might be pharmacodynamic (for example, increase in circulating VEGF, placental growth factor) while others have potential for predicting clinical benefit or identifying the escape pathways (for example, stromal-cell-derived factor 1α, interleukin-6). Most biomarkers are disease and/or agent specific and all of them need to be validated prospectively. We discuss the current challenges in establishing biomarkers of antiangiogenic therapy, define systemic, circulating, tissue and imaging biomarkers and their advantages and disadvantages, and comment on the future opportunities for validating biomarkers of antiangiogenic therapy.

Authors
Jain, RK; Duda, DG; Willett, CG; Sahani, DV; Zhu, AX; Loeffler, JS; Batchelor, TT; Sorensen, AG
MLA Citation
Jain, RK, Duda, DG, Willett, CG, Sahani, DV, Zhu, AX, Loeffler, JS, Batchelor, TT, and Sorensen, AG. "Biomarkers of response and resistance to antiangiogenic therapy." Nature Reviews Clinical Oncology 6.6 (2009): 327-338.
PMID
19483739
Source
scival
Published In
Nature Reviews Clinical Oncology
Volume
6
Issue
6
Publish Date
2009
Start Page
327
End Page
338
DOI
10.1038/nrclinonc.2009.63

Normalization of tumor vasculature and microenvironment

Solid tumors require blood vessels for growth, and many new cancer therapies are targeted against the tumor vasculature. The widely held view is that these antiangiogenic therapies destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Indeed, that is the ultimate goal of antiangiogenic therapies. However, emerging preclinical and clinical evidence support an alternative hypothesis, that judicious application of agents that block angiogenesis directly (e.g., bevacizumab, AZD2171) and indirectly (e.g., trastuzumab) can also transiently normalize the abnormal structure and function of tumor vasculature. In addition to being more efficient for oxygen and drug delivery, the normalized vessels are fortified with pericytes, which can hinder intravasation of cancer cells, a necessary step in hematogenous metastasis. Drugs that induce vascular normalization can also normalize the tumor microenvironment-reduce hypoxia and interstitial fluid pressure-and thus increase the efficacy of many conventional therapies if both are carefully scheduled. Reduced interstitial fluid pressure can decrease tumor-associated edema as well as the probability of lymphatic dissemination. Independent of these effects, alleviation of hypoxia can decrease the selection pressure for a more malignant phenotype. Finally, the increase in proliferation of cancer cells during the vascular normalization window can potentially sensitize tumors to cytotoxic agents. Our recent Phase II clinical trial in glioblastoma patients shows that the normalization window-identified using advanced magnetic resonance imaging (MRI) techniques-can last one to four months, and the resulting changes in tumor vasculature correlate with circulating molecular and cellular biomarkers in these patients. © 2008 Springer US.

Authors
Jain, RK; Duda, DG; Batchelor, TT; Sorensen, AG; Willett, CG
MLA Citation
Jain, RK, Duda, DG, Batchelor, TT, Sorensen, AG, and Willett, CG. "Normalization of tumor vasculature and microenvironment." (December 1, 2008): 273-281. (Chapter)
Source
scopus
Publish Date
2008
Start Page
273
End Page
281
DOI
10.1007/978-0-387-71518-6_24

Thirty years of rectal cancer research: a brief history.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Thirty years of rectal cancer research: a brief history." Oncology (Williston Park) 22.12 (November 15, 2008): 1441-1444.
PMID
19322951
Source
pubmed
Published In
Oncology
Volume
22
Issue
12
Publish Date
2008
Start Page
1441
End Page
1444

Esophageal cancer.

Authors
Ajani, JA; Barthel, JS; Bekaii-Saab, T; Bentrem, DJ; D'Amico, TA; Fuchs, CS; Gerdes, H; Hayman, JA; Hazard, L; Ilson, DH; Kleinberg, LR; McAleer, MF; Meropol, NJ; Mulcahy, MF; Orringer, MB; Osarogiagbon, RU; Posey, JA; Sasson, AR; Scott, WJ; Shibata, S; Strong, VEM; Swisher, SG; Washington, MK; Willett, C; Wood, DE; Wright, CD; Yang, G; NCCN Esophageal Cancer Panel,
MLA Citation
Ajani, JA, Barthel, JS, Bekaii-Saab, T, Bentrem, DJ, D'Amico, TA, Fuchs, CS, Gerdes, H, Hayman, JA, Hazard, L, Ilson, DH, Kleinberg, LR, McAleer, MF, Meropol, NJ, Mulcahy, MF, Orringer, MB, Osarogiagbon, RU, Posey, JA, Sasson, AR, Scott, WJ, Shibata, S, Strong, VEM, Swisher, SG, Washington, MK, Willett, C, Wood, DE, Wright, CD, Yang, G, and NCCN Esophageal Cancer Panel, . "Esophageal cancer." J Natl Compr Canc Netw 6.9 (October 2008): 818-849.
PMID
18926093
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
9
Publish Date
2008
Start Page
818
End Page
849

Impact of time duration after neoadjuvant therapy to surgery on response and outcome in rectal cancer patients.

Authors
Willett, CG; Czito, BG
MLA Citation
Willett, CG, and Czito, BG. "Impact of time duration after neoadjuvant therapy to surgery on response and outcome in rectal cancer patients." Ann Surg Oncol 15.10 (October 2008): 2636-2638.
PMID
18663534
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
15
Issue
10
Publish Date
2008
Start Page
2636
End Page
2638
DOI
10.1245/s10434-008-0058-0

Does adjuvant chemoradiation benefit patients who have undergone resection of pancreatic or periampullary cancer?

Authors
Willett, CG; Czito, BG
MLA Citation
Willett, CG, and Czito, BG. "Does adjuvant chemoradiation benefit patients who have undergone resection of pancreatic or periampullary cancer?." Nat Clin Pract Gastroenterol Hepatol 5.7 (July 2008): 364-365.
PMID
18506163
Source
pubmed
Published In
Nature Clinical Practice Gastroenterology & Hepatology
Volume
5
Issue
7
Publish Date
2008
Start Page
364
End Page
365
DOI
10.1038/ncpgasthep1152

Intensity-modulated radiation therapy for gastrointestinal tumors.

Radiation plays an important role in the multimodal management of tumors of the gastrointestinal (GI) system. Intensity-modulated radiation therapy (IMRT) is a technological development that was introduced to limit the acute and late toxicities commonly associated with conventional radiation therapy. Numerous preclinical dosimetric comparisons of conventional and intensity-modulated radiation plans for treating various GI tumors have been reported. In general, these studies have shown that IMRT can spare organs at risk in the high-dose region while maintaining adequate target coverage. Clinical reports on the efficacy and tolerability of IMRT are emerging. This review provides a description of the differences between conventional irradiation and IMRT and discusses the preclinical and early clinical investigations of the role of IMRT in the treatment of GI tumors. The ultimate role of IMRT in GI tumor management will be determined through further clinical study.

Authors
Meyer, JJ; Czito, BG; Willett, CG
MLA Citation
Meyer, JJ, Czito, BG, and Willett, CG. "Intensity-modulated radiation therapy for gastrointestinal tumors." Curr Oncol Rep 10.3 (May 2008): 206-211. (Review)
PMID
18765150
Source
pubmed
Published In
Current Oncology Reports
Volume
10
Issue
3
Publish Date
2008
Start Page
206
End Page
211

Emerging role of intensity-modulated radiation therapy in anorectal cancer.

Although radiation therapy has an established role to play in the management of rectal and anal tumors, there are often treatment-related morbidities that negatively impact on patients. There is a long-standing interest in radiation oncology on maximizing treatment efficacy while minimizing treatment-related toxicities, which can be pronounced in the treatment of pelvic malignancies. Intensity-modulated radiation therapy is a recently introduced technology that has the potential to increase the efficacy:toxicity ratio. It has been implemented in the treatment of prostate and head and neck tumors with success. This article reviews the rationale for its use in treating anorectal tumors and discusses early clinical data supporting its continued investigation.

Authors
Meyer, JJ; Willett, CG; Czito, BG
MLA Citation
Meyer, JJ, Willett, CG, and Czito, BG. "Emerging role of intensity-modulated radiation therapy in anorectal cancer." Expert Rev Anticancer Ther 8.4 (April 2008): 585-593. (Review)
PMID
18402525
Source
pubmed
Published In
Expert Review of Anticancer Therapy
Volume
8
Issue
4
Publish Date
2008
Start Page
585
End Page
593
DOI
10.1586/14737140.8.4.585

Is there a role for advanced radiation therapy technologies in the treatment of pancreatic adenocarcinoma?

Pancreatic cancer remains a highly challenging problem in oncology. Oncologists continue to search for therapies that are more effective than those currently available to improve on the existing poor treatment results. Persistence of both systemic and local disease causes high rates of morbidity and mortality for patients. Radiation continues to play a role in the treatment of pancreatic cancer, in both the adjuvant and locally advanced settings. Efforts to improve on the results of radiotherapy have led to the use of new and improved technologies. This review discusses a variety of these technological improvements and their current and potential future roles in the clinic.

Authors
Meyer, JJ; Willett, CG; Czito, BG
MLA Citation
Meyer, JJ, Willett, CG, and Czito, BG. "Is there a role for advanced radiation therapy technologies in the treatment of pancreatic adenocarcinoma?." Future Oncol 4.2 (April 2008): 241-255. (Review)
PMID
18407737
Source
pubmed
Published In
Future oncology (London, England)
Volume
4
Issue
2
Publish Date
2008
Start Page
241
End Page
255
DOI
10.2217/14796694.4.2.241

Integration of cone-beam CT in stereotactic body radiation therapy.

This report describes the technique and initial experience using cone beam CT (CBCT) for localization of treatment targets in patients undergoing stereotactic body radiation therapy (SBRT). Patients selected for SBRT underwent 3-D or 4-D CT scans in a customized immobilization cradle. GTV, CTV, ITV, and PTV were defined. Intensity-modulated radiation beams, multiple 3-D conformal beams, or dynamic conformal arcs were delivered using a Varian 21EX with 120-leaf MLC. CBCT images were obtained prior to each fraction, and registered to the planning CT by using soft tissue and bony structures to assure accurate isocenter localization. Patients were repositioned for treatment based on the CBCT images. Radiographic images (kV, MV, or CBCT) were taken before and after beam delivery to further assess set-up accuracy. Ten patients with lung, liver, and spine lesions received 29 fractions of treatment using this technique. The prescription doses ranged 1250 approximately 6000 cGy in 1 approximately 5 fractions. Compared to traditional 2-D matching using bony structures, CBCT corrects target deviation from 1 mm to 15 mm, with an average of 5 mm. Comparison of pre-treatment to post-treatment radiographic images demonstrated an average 2 mm deviation (ranging from 0-4 mm). Improved immobilization may enhance positioning accuracy. Typical total "in-room" times for the patients are approximately 1 hour. CBCT-guided SBRT is feasible and enhances setup accuracy using 3-D anatomical information.

Authors
Yin, F-F; Wang, Z; Yoo, S; Wu, QJ; Kirkpatrick, J; Larrier, N; Meyer, J; Willett, CG; Marks, LB
MLA Citation
Yin, F-F, Wang, Z, Yoo, S, Wu, QJ, Kirkpatrick, J, Larrier, N, Meyer, J, Willett, CG, and Marks, LB. "Integration of cone-beam CT in stereotactic body radiation therapy." Technol Cancer Res Treat 7.2 (April 2008): 133-139.
PMID
18345702
Source
pubmed
Published In
Technology in cancer research & treatment
Volume
7
Issue
2
Publish Date
2008
Start Page
133
End Page
139
DOI
10.1177/153303460800700206

A phase I study of UFT/leucovorin, carboplatin, and paclitaxel in combination with external beam radiation therapy for advanced esophageal carcinoma.

PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is not well established. We evaluated the safety and preliminary efficacy of a combination of UFT/leucovorin, carboplatin, and paclitaxel with RT in a Phase I study of patients with advanced esophageal cancer. METHODS AND MATERIALS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received UFT/leucovorin, carboplatin, and paclitaxel with RT (1.8 Gy daily to 45 Gy). After completion, the disease was restaged and patients were evaluated for surgery. Primary end points included determination of dose-limiting toxicities (DLTs) and a recommended Phase II dose. Secondary objectives included determination of non-DLTs, as well as preliminary radiographic and pathologic response rates. RESULTS: Twelve patients were enrolled (11 men, 1 woman). All were assessable for toxicity and efficacy. One of 6 patients at Dose Level 1 (UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, area under the curve [AUC] 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4) had a DLT (febrile neutropenia). Of these 6 patients, 4 underwent esophagectomy and none achieved a pathologic complete response. Six patients were then enrolled at Dose Level 2 (UFT/leucovorin, 300/30 mg in the morning and 200/30 mg in the evening on RT days; carboplatin, AUC 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4). Two of 6 patients at Dose Level 2 developed DLTs (febrile neutropenia in both). Esophagectomy was performed in 3 patients, with 2 achieving a pathologic complete response. CONCLUSIONS: Maximum tolerated doses in this study were UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, AUC 5, Weeks 1 and 4; and paclitaxel, 175 mg/m2 Weeks 1 and 4 when delivered with external RT. In this small study, this regimen appears active, but toxic.

Authors
Czito, BG; Cohen, DP; Kelsey, CR; Lockhart, AC; Bendell, JC; Willett, CG; Petros, WP; D'Amico, TA; Truax, R; Hurwitz, HI
MLA Citation
Czito, BG, Cohen, DP, Kelsey, CR, Lockhart, AC, Bendell, JC, Willett, CG, Petros, WP, D'Amico, TA, Truax, R, and Hurwitz, HI. "A phase I study of UFT/leucovorin, carboplatin, and paclitaxel in combination with external beam radiation therapy for advanced esophageal carcinoma." Int J Radiat Oncol Biol Phys 70.4 (March 15, 2008): 1066-1072.
PMID
17881149
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
70
Issue
4
Publish Date
2008
Start Page
1066
End Page
1072
DOI
10.1016/j.ijrobp.2007.07.2347

IntroductionIntroduction

© Cambridge University Press 2008. The goal of this book is to provide practical guidance for anyone who is interested in initiating a teledermatology program or expanding their current system. This book was written for a wide audience to include anyone in a private practice, academic center, large multispecialty clinic, state or federal sector. To build a successful program several features require consideration and each is addressed in turn throughout this book. Specifically, relevant questions include the following: What are your motivating factors? Do you want to increase access for the underserved? Increase your revenue stream? Maximize flexibility in your lifestyle? Or a combination of these factors? What type of technology should you implement – store-and-forward, real-time interactive, or a hybrid model? What are the equipment needs? What communication systems are available for data transmission? Who should be targeted as users (e.g., referring clinicians, patient population, and/or participating teledermatologists)? Is teledermatology a sustainable enterprise and what are the business models that can be followed? Is teledermatology reimbursable and, if so, how? Is image quality good, and what are the training requirements? Is teledermatology a diagnostically viable way of delivering dermatologic healthcare? What legal, regulatory, and confidentiality issues arise? What are the ethical considerations of using the technology? Can teledermatology be integrated into dermatology training programs? Although this may seem like a daunting list, it should not discourage you from pursuing a teledermatology implementation plan. With proper fore-thought and planning, the development of a teledermatology program can be tremendously successful.

Authors
Whited, JD; Edison, KE; Willett, CG; Tepper, JF
MLA Citation
Whited, JD, Edison, KE, Willett, CG, and Tepper, JF. "IntroductionIntroduction (PublishedPublished)." Teledermatology: A User's Guide. January 1, 2008. 1-4.
Source
scopus
Publish Date
2008
Start Page
1
End Page
4
DOI
10.1017/CBO9780511547386.001

Neoadjuvant Chemoradiation for Rectal Cancer

Significant advances have been made in the treatment of rectal cancer patients. Phase III studies have demonstrated the efficacy of neoadjuvant and adjuvant radiation therapy and chemotherapy in improving the outcome of patients with locally advanced disease. Data from the randomized German CAO/ARO/AIO-94 trial of preoperative versus postoperative chemoradiation has established the foundation for the use of preoperative chemoradiation in the treatment of patients with clinical stage II and III rectal cancer. Phase III studies are now examining innovative strategies of chemotherapy and targeted agents with radiation therapy. © 2008 Elsevier Inc. All rights reserved.

Authors
Willett, CG; Czito, BG
MLA Citation
Willett, CG, and Czito, BG. "Neoadjuvant Chemoradiation for Rectal Cancer." Seminars in Colon and Rectal Surgery 19.4 (2008): 197-202.
Source
scival
Published In
Seminars in Colon and Rectal Surgery
Volume
19
Issue
4
Publish Date
2008
Start Page
197
End Page
202
DOI
10.1053/j.scrs.2008.09.003

Erratum (Retracted article): Is there a role for advanced radiation therapy technologies in the treatment of pancreatic adenocarcinoma? (Future Oncology (2008) vol. 4(2)(241-255))

Authors
Meyer, JJ; Willett, CG; Czito, BG
MLA Citation
Meyer, JJ, Willett, CG, and Czito, BG. "Erratum (Retracted article): Is there a role for advanced radiation therapy technologies in the treatment of pancreatic adenocarcinoma? (Future Oncology (2008) vol. 4(2)(241-255))." Future Oncology 4.3 (2008): 448--.
Source
scival
Published In
Future oncology (London, England)
Volume
4
Issue
3
Publish Date
2008
Start Page
448-
DOI
10.2217/14796694.4.3.448

An odd but synergistic couple: Immunotherapy combined with radiotherapy

In summary, there is considerable promise for combinations of immunotherapy with radiotherapy, but clinical experience is still limited. Preclinical models with greater relevance to human tumors should be used to continue identifying the best combinations and timing of radiation therapy and immunotherapy, but of course, only clinical trials will establish the true value of these combinations. Because we are entering an era with numerous therapies for cancer, all of which might act synergistically, the importance of patient selection is paramount. Predictive factors that indicate which patients are most likely to benefit from immunotherapy or radiation therapy are critically needed.

Authors
Morse, MA; Willett, CG
MLA Citation
Morse, MA, and Willett, CG. "An odd but synergistic couple: Immunotherapy combined with radiotherapy." ONCOLOGY 22.9 (2008): 1075-1080.
Source
scival
Published In
Oncology
Volume
22
Issue
9
Publish Date
2008
Start Page
1075
End Page
1080

Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781

Purpose: The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have curative potential, there has been great interest in the use of trimodality therapy. To this end, we compared survival, response, and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer. Patients and Methods: Four hundred seventy-five eligible patients were planned for enrollment. Patients were randomly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m 2 and fluorouracil 1,000 mg/m2/d for 4 days on weeks 1 and 5 concurrent with radiation therapy (50.4 Gy total: 1.8 Gy/fraction over 5.6 weeks) followed by esophagectomy with node dissection. Results: Fifty-six patients were enrolled between October 1997 and March 2000, when the trial was closed due to poor accrual. Thirty patients were randomly assigned to trimodality therapy and 26 were assigned to surgery alone. Patient and tumor characteristics were similar between groups. Treatment was generally well tolerated. Median follow-up was 6 years. An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy (exact stratified log-rank, P = .002). Five-year survival was 39% (95% CI, 21% to 57%) v 16% (95% CI, 5% to 33%) in favor of trimodality therapy. Conclusion: The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer, and support trimodality therapy as a standard of care for patients with this disease. © 2008 by American Society of Clinical Oncology.

Authors
Tepper, J; Krasna, MJ; Niedzwiecki, D; Hollis, D; Reed, CE; Goldberg, R; Kiel, K; Willett, C; Sugarbaker, D; Mayer, R
MLA Citation
Tepper, J, Krasna, MJ, Niedzwiecki, D, Hollis, D, Reed, CE, Goldberg, R, Kiel, K, Willett, C, Sugarbaker, D, and Mayer, R. "Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781." Journal of Clinical Oncology 26.7 (2008): 1086-1092.
PMID
18309943
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
7
Publish Date
2008
Start Page
1086
End Page
1092
DOI
10.1200/JCO.2007.12.9593

Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: A prospective validation by RTOG 9704

Purpose: CA 19-9 is an important tumor marker in patients with pancreatic adenocarcinoma. A secondary end point of Radiation Therapy Oncology Group trial 9704 was prospective evaluation of the ability of postresectional CA 19-9 to predict survival. Methods: CA 19-9 expression was analyzed as a dichotomized variable (< 180 v ≥ 180) or (≤ 90 v > 90). Cox proportional hazards models were utilized to identify the impact of CA 19-9 expression on overall survival (OS). Actuarial estimates for OS were calculated using Kaplan-Meier methods. Results: Three hundred eighty-five patients patients had assessable CA 19-9 levels. The majority had a CA 19-9 level lower than 180 or ≤ 90 (n = 220 and 200, respectively), while 34% were Lewis Antigen negative and 33 (9%) and 53 (14%) patients had levels higher than 180 and higher than 90. When CA 19-9 was analyzed as a dichotomized variable, there was a significant survival difference favoring patients with CA 19-9 lower than 180 (hazard ratio [HR], 3.53; P < .0001). This corresponds to a 72% reduction in the risk of death for patients with a CA 19-9 lower than 180. This was also true for patients with CA 19-9 ≤ 90 (HR, 3.4; P < .0001). Multivariate analyses confirmed that CA 19-9, when analyzed as both a continuous and a dichotomized variable, is a highly significant predictor of OS in patients with resected pancreatic cancer. Conclusion: To our knowledge, this is the first phase III trial to perform prospective analysis of CA 19-9 levels in patients treated with adjuvant chemoradiotherapy. It definitively confirms the prognostic importance of postresectional CA 19-9 levels after surgery with curative intent in patients with pancreatic cancer. © 2008 by American Society of Clinical Oncology.

Authors
Berger, AC; Jr, MG; Hoffman, JP; Regine, WF; Abrams, RA; Safran, H; Konski, A; III, ABB; MacDonald, J; Willett, CG
MLA Citation
Berger, AC, Jr, MG, Hoffman, JP, Regine, WF, Abrams, RA, Safran, H, Konski, A, III, ABB, MacDonald, J, and Willett, CG. "Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: A prospective validation by RTOG 9704." Journal of Clinical Oncology 26.36 (2008): 5918-5922.
PMID
19029412
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
36
Publish Date
2008
Start Page
5918
End Page
5922
DOI
10.1200/JCO.2008.18.6288

Principles and techniques of radiation therapy for esophageal and gastroesophageal junction cancers

Radiation therapy serves an integral role in the primary and adjuvant treatment of esophagus cancer. Radiation techniques continue to improve, providing more accurate localization of the tumor while limiting dose to normal structures. This article reviews current practices and recommendations for radiation therapy technique for esophageal and gastroesophageal malignancies. © Journal of the National Comprehensive Cancer Network.

Authors
Hazard, L; Yang, G; McAleer, MF; Hayman, J; Willett, C
MLA Citation
Hazard, L, Yang, G, McAleer, MF, Hayman, J, and Willett, C. "Principles and techniques of radiation therapy for esophageal and gastroesophageal junction cancers." JNCCN Journal of the National Comprehensive Cancer Network 6.9 (2008): 870-878.
PMID
18926096
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
9
Publish Date
2008
Start Page
870
End Page
878

Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113

Purpose: Two nonoperative approaches (one without fluorouracil) using induction chemotherapy and then definitive chemoradiotherapy developed at two centers were compared in patients with localized esophageal cancer (LEC). The primary end point was to assess whether any approach would achieve a ≥ 77.5% 1-year survival rate, surpassing the historical 66% rate from the Radiation Therapy Oncology Group (RTOG) protocol 9405. Patients and Methods: In a multi-institutional cooperative group setting, patients with LEC who had unresectable cancer, were unwilling to undergo surgery, or were medically unfit for surgery were randomly assigned to receive either induction with fluorouracil, cisplatin, and paclitaxel and then fluorouracil plus paclitaxel with 50.4 Gy of radiation (arm A) or induction with paclitaxel plus cisplatin and then the same chemotherapy with 50.4 Gy of radiation (arm B). Safety and survival rates were assessed. Results: A total of 84 patients were randomly assigned (arm A, n = 41; arm B, n = 43), and 72 were assessable (arm A, n = 37; arm B, n = 35). The median survival time was 28.7 months for patients in arm A and 14.9 months for patients in arm B (18.8 months for patients in RTOG 9405). The 1-year survival rate of 75.7% in arm A was close to, but did not meet or surpass, the 77.5% goal. The 2-year survival rate was 56% for arm A and 37% for arm B. Grade 3 (arm A = 54%, arm B = 43%) and grade 4 toxicities (arm A = 27%, arm B = 40%) were frequent. Treatment-related death occurred in 3% of patients in arm A and 6% of patients in arm B. Conclusion: Both arms of RTOG 0113 were associated with high morbidity, and the study did not meet its 1-year survival end point. © 2008 by American Society of Clinical Oncology.

Authors
Ajani, JA; Winter, K; Komaki, R; Kelsen, DP; Minsky, BD; Liao, Z; Bradley, J; Fromm, M; Hornback, D; Willett, CG
MLA Citation
Ajani, JA, Winter, K, Komaki, R, Kelsen, DP, Minsky, BD, Liao, Z, Bradley, J, Fromm, M, Hornback, D, and Willett, CG. "Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113." Journal of Clinical Oncology 26.28 (2008): 4551-4556.
PMID
18574157
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
28
Publish Date
2008
Start Page
4551
End Page
4556
DOI
10.1200/JCO.2008.16.6918

Evaluation of Planned Treatment Breaks During Radiation Therapy for Anal Cancer: Update of RTOG 92-08

Purpose: Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study. Methods and Materials: Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure were estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test. Results: Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity. Conclusions: No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts. © 2008 Elsevier Inc. All rights reserved.

Authors
Konski, A; Jr, MG; John, M; Krieg, R; Pinover, W; Myerson, R; Willett, C
MLA Citation
Konski, A, Jr, MG, John, M, Krieg, R, Pinover, W, Myerson, R, and Willett, C. "Evaluation of Planned Treatment Breaks During Radiation Therapy for Anal Cancer: Update of RTOG 92-08." International Journal of Radiation Oncology Biology Physics 72.1 (2008): 114-118.
PMID
18472363
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
114
End Page
118
DOI
10.1016/j.ijrobp.2007.12.027

Intersociety Radiation Oncology Summit-SCOPE II

Authors
Tripuraneni, P; Watson, RL; Ang, KK; Harrison, L; Eifel, P; Zietman, A; Haffty, B; Thevenot, LI; Willett, CG; Schomberg, PJ; Pickles, T; Halberg, FE; Devlin, PM
MLA Citation
Tripuraneni, P, Watson, RL, Ang, KK, Harrison, L, Eifel, P, Zietman, A, Haffty, B, Thevenot, LI, Willett, CG, Schomberg, PJ, Pickles, T, Halberg, FE, and Devlin, PM. "Intersociety Radiation Oncology Summit-SCOPE II." International Journal of Radiation Oncology Biology Physics 72.2 (2008): 323-326.
PMID
18793951
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
2
Publish Date
2008
Start Page
323
End Page
326
DOI
10.1016/j.ijrobp.2008.06.1904

Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: A randomized controlled trial

Context: Chemoradiation as definitive therapy is the preferred primary therapy for patients with anal canal carcinoma; however, the 5-year disease-free survival rate from concurrent fluorouracil/mitomycin and radiation is only approximately 65%. Objective: To compare the efficacy of cisplatin-based (experimental) therapy vs mitomycin-based (standard) therapy in treatment of anal canal carcinoma. Design, Setting, and Participants: US Gastrointestinal Intergroup trial RTOG 98-11, a multicenter, phase 3, randomized controlled trial comparing treatment with fluorouracil plus mitomycin and radiotherapy vs treatment with fluorouracil plus cisplatin and radiotherapy in 682 patients with anal canal carcinoma enrolled between October 31, 1998, and June 27, 2005. Stratifications included sex, clinical nodal status, and tumor diameter. Intervention: Participants were randomly assigned to 1 of 2 intervention groups: (1) the mitomycin-based group (n=341), who received fluorouracil (1000 mg/m2 on days 1-4 and 29-32) plus mitomycin (10 mg/m2 on days 1 and 29) and radiotherapy (45-59 Gy) or (2) the cisplatin-based group (n=341), who received fluorouracil (1000 mg/m2 on days 1-4, 29-32, 57-60, and 85-88) plus cisplatin (75 mg/m2 on days 1, 29, 57, and 85) and radiotherapy (45-59 Gy; start day=day 57). Main Outcome Measures: The primary end point was 5-year disease-free survival; secondary end points were overall survival and time to relapse. Results A total of 644 patients were assessable. The median follow-up for all patients was 2.51 years. Median age was 55 years, 69% were women, 27% had a tumor diameter greater than 5 cm, and 26% had clinically positive nodes. The 5-year disease-free survival rate was 60% (95% confidence interval [CI], 53%-67%) in the mitomycin-based group and 54% (95% CI, 46%-60%) in the cisplatin-based group (P=.17). The 5-year overall survival rate was75%(95% CI, 67%-81%) in the mitomycin-based group and 70% (95% CI, 63%-76%) in the cisplatin-based group (P=.10). The 5-year local-regional recurrence and distant metastasis rates were 25% (95% CI, 20%-30%) and 15% (95% CI, 10%-20%), respectively, for mitomycin-based treatment and33%(95% CI, 27%-40%) and19%(95% CI, 14%-24%), respectively, for cisplatinbased treatment. The cumulative rate of colostomy was significantly better for mitomycinbased than cisplatin-based treatment (10% vs 19%; P=.02). Severe hematologic toxicity was worse with mitomycin-based treatment (P<.001). Conclusions: In this population of patients with anal canal carcinoma, cisplatinbased therapy failed to improve disease-free-survival compared with mitomycinbased therapy, but cisplatin-based therapy resulted in a significantly worse colostomy rate. These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma. Trial Registration: clinicaltrials.gov Identifier: NCT00003596. ©2008 American Medical Association. All rights reserved.

Authors
Ajani, JA; Winter, KA; Gunderson, LL; Pedersen, J; III, ABB; Jr, CRT; Mayer, RJ; Haddock, MG; Rich, TA; Willett, C
MLA Citation
Ajani, JA, Winter, KA, Gunderson, LL, Pedersen, J, III, ABB, Jr, CRT, Mayer, RJ, Haddock, MG, Rich, TA, and Willett, C. "Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: A randomized controlled trial." JAMA - Journal of the American Medical Association 299.16 (2008): 1914-1921.
PMID
18430910
Source
scival
Published In
JAMA : the journal of the American Medical Association
Volume
299
Issue
16
Publish Date
2008
Start Page
1914
End Page
1921
DOI
10.1001/jama.299.16.1914

Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: A randomized controlled trial

Context: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention: Chemotherapy with either fluorouracil (continuous infusion of 250mg/m2 per day; n=230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n=221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n=388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P=.09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P=.05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P<.001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%). Conclusions: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration: clinicaltrials.gov Identifier: NCT00003216. ©2008 American Medical Association. All rights reserved.

Authors
Regine, WF; Winter, KA; Abrams, RA; Safran, H; Hoffman, JP; Konski, A; Benson, AB; Macdonald, JS; Kudrimoti, MR; Fromm, ML; Haddock, MG; Schaefer, P; Willett, CG; Rich, TA
MLA Citation
Regine, WF, Winter, KA, Abrams, RA, Safran, H, Hoffman, JP, Konski, A, Benson, AB, Macdonald, JS, Kudrimoti, MR, Fromm, ML, Haddock, MG, Schaefer, P, Willett, CG, and Rich, TA. "Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: A randomized controlled trial." JAMA - Journal of the American Medical Association 299.9 (2008): 1019-1026.
PMID
18319412
Source
scival
Published In
JAMA : the journal of the American Medical Association
Volume
299
Issue
9
Publish Date
2008
Start Page
1019
End Page
1026
DOI
10.1001/jama.299.9.1019

Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy.

PURPOSE: To report patterns of disease recurrence after resection of adenocarcinoma of the duodenum and compare outcomes between patients undergoing surgery only vs. surgery with concurrent chemotherapy and radiation therapy (CT-RT). METHODS AND MATERIALS: This was a retrospective analysis of all patients undergoing potentially curative therapy for adenocarcinoma of the duodenum at Duke University Medical Center and affiliated hospitals between 1975 and 2005. Overall survival (OS), disease-free survival (DFS), and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis evaluated the effect of CT-RT on clinical endpoints. RESULTS: Thirty-two patients were identified (23 M, 9 F). Median age was 60 years (range, 32-77 years). Surgery alone was performed in 16 patients. An additional 16 patients received either preoperative (n = 11) or postoperative (n = 5) CT-RT. Median RT dose was 50.4 Gy (range, 12.6-54 Gy). All patients treated with RT also received concurrent 5-fluorouracil-based CT. Two patients treated preoperatively had a pathologic complete response (18%), and none had involved lymph nodes at resection. Five-year OS, DFS, and LC for the entire group were 48%, 47%, and 55%, respectively. Five-year survival did not differ between patients receiving CT-RT vs. surgery alone (57% vs. 44%, p = 0.42). However, in patients undergoing R0 resection, CT-RT appeared to improve OS (5-year 83% vs. 53%, p = 0.07). CONCLUSIONS: Local failure after surgery alone is high. Given the patterns of relapse with surgery alone and favorable outcomes in patients undergoing complete resection with CT-RT, the use of CT-RT in selected patients should be considered.

Authors
Kelsey, CR; Nelson, JW; Willett, CG; Chino, JP; Clough, RW; Bendell, JC; Tyler, DS; Hurwitz, HI; Morse, MA; Clary, BM; Pappas, TN; Czito, BG
MLA Citation
Kelsey, CR, Nelson, JW, Willett, CG, Chino, JP, Clough, RW, Bendell, JC, Tyler, DS, Hurwitz, HI, Morse, MA, Clary, BM, Pappas, TN, and Czito, BG. "Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy." Int J Radiat Oncol Biol Phys 69.5 (December 1, 2007): 1436-1441.
PMID
17689032
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
5
Publish Date
2007
Start Page
1436
End Page
1441
DOI
10.1016/j.ijrobp.2007.05.006

The impact of advanced technologies on treatment deviations in radiation treatment delivery.

PURPOSE: To assess the impact of new technologies on deviation rates in radiation therapy (RT). METHODS AND MATERIALS: Treatment delivery deviations in RT were prospectively monitored during a time of technology upgrade. In January 2003, our department had three accelerators, none with "modern" technologies (e.g., without multileaf collimators [MLC]). In 2003 to 2004, we upgraded to five new accelerators, four with MLC, and associated advanced capabilities. The deviation rates among patients treated on "high-technology" versus "low-technology" machines (defined as those with vs. without MLC) were compared over time using the two-tailed Fisher's exact test. RESULTS: In 2003, there was no significant difference between the deviation rate in the "high-technology" versus "low-technology" groups (0.16% vs. 0.11%, p = 0.45). In 2005 to 2006, the deviation rate for the "high-technology" groups was lower than the "low-technology" (0.083% vs. 0.21%, p = 0.009). This difference was caused by a decline in deviations on the "high-technology" machines over time (p = 0.053), as well as an unexpected trend toward an increase in deviations over time on the "low-technology" machines (p = 0.15). CONCLUSIONS: Advances in RT delivery systems appear to reduce the rate of treatment deviations. Deviation rates on "high-technology" machines with MLC decline over time, suggesting a learning curve after the introduction of new technologies. Associated with the adoption of "high-technology" was an unexpected increase in the deviation rate with "low-technology" approaches, which may reflect an over-reliance on tools inherent to "high-technology" machines. With the introduction of new technologies, continued diligence is needed to ensure that staff remain proficient with "low-technology" approaches.

Authors
Marks, LB; Light, KL; Hubbs, JL; Georgas, DL; Jones, EL; Wright, MC; Willett, CG; Yin, FF
MLA Citation
Marks, LB, Light, KL, Hubbs, JL, Georgas, DL, Jones, EL, Wright, MC, Willett, CG, and Yin, FF. "The impact of advanced technologies on treatment deviations in radiation treatment delivery." Int J Radiat Oncol Biol Phys 69.5 (December 1, 2007): 1579-1586.
PMID
18035214
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
5
Publish Date
2007
Start Page
1579
End Page
1586
DOI
10.1016/j.ijrobp.2007.08.017

Radiation therapy in stage II and III rectal cancer.

Over the past 25 years, significant advances have been made in the management of patients with rectal cancer. Phase III studies have shown the efficacy of postoperative radiation therapy and chemotherapy in improving local control and survival of patients with resected stage II and III disease. Data from the randomized German CAO/ARO/AIO-94 trial of preoperative versus postoperative chemoradiation have provided a strong rationale and support for the use of preoperative chemoradiation in the treatment of patients with clinical stage II and III rectal cancer. Current phase III studies are evaluating novel combinations of chemotherapy and targeted agents with radiation therapy.

Authors
Willett, CG; Czito, BG; Bendell, JC
MLA Citation
Willett, CG, Czito, BG, and Bendell, JC. "Radiation therapy in stage II and III rectal cancer." Clin Cancer Res 13.22 Pt 2 (November 15, 2007): 6903s-6908s. (Review)
PMID
18006798
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
22 Pt 2
Publish Date
2007
Start Page
6903s
End Page
6908s
DOI
10.1158/1078-0432.CCR-07-1158

Paclitaxel-based chemoradiotherapy in the treatment of patients with operable esophageal cancer.

PURPOSE: To compare a neoadjuvant regimen of cisplatin/5-fluorouracil (5-FU) and concurrent radiation therapy (RT) with paclitaxel-based regimens and RT in the management of operable esophageal (EC)/gastroesophageal junction (GEJ) cancer. METHODS AND MATERIALS: All patients receiving neoadjuvant chemotherapy (CT) and RT for EC/GEJ cancer at Duke University between January 1995 and December 2004 were included. Clinical end points were compared for patients receiving paclitaxel-based regimens (TAX) vs. alternative regimens (non-TAX). Local control (LC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Chi-square analysis was performed to test the effect of TAX on pathologic complete response (pCR) rates and toxicity. RESULTS: A total of 109 patients received CT-RT followed by esophagectomy (95 M; 14 F). Median RT dose was 45 Gy (range, 36-66 Gy). The TAX and non-TAX groups comprised 47% and 53% of patients, respectively. Most (83%) TAX patients received three drug regimens including platinum and a fluoropyrimidine. In the non-TAX group, 89% of the patients received cisplatin and 5-FU. The remainder received 5-FU or capecitabine alone. Grade 3-4 toxicity occurred in 41% of patients receiving TAX vs. 24% of those receiving non-TAX (p = 0.19). Overall pCR rate was 39% (39% with TAX vs. 40% with non-TAX, p = 0.9). Overall LC, DFS, and OS at 3 years were 80%, 34%, and 37%, respectively. At 3 years, there were no differences in LC (75% vs. 85%, p = 0.33) or OS (37% vs. 37%, p = 0.32) between TAX and non-TAX groups. CONCLUSIONS: In this large experience, paclitaxel-containing regimens did not improve pCR rates or clinical end points compared to non-paclitaxel-containing regimens.

Authors
Kelsey, CR; Chino, JP; Willett, CG; Clough, RW; Hurwitz, HI; Morse, MA; Bendell, JC; D'Amico, TA; Czito, BG
MLA Citation
Kelsey, CR, Chino, JP, Willett, CG, Clough, RW, Hurwitz, HI, Morse, MA, Bendell, JC, D'Amico, TA, and Czito, BG. "Paclitaxel-based chemoradiotherapy in the treatment of patients with operable esophageal cancer." Int J Radiat Oncol Biol Phys 69.3 (November 1, 2007): 770-776.
PMID
17889266
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
770
End Page
776
DOI
10.1016/j.ijrobp.2007.03.035

Commentary: rectal cancer an evolution of treatment.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Commentary: rectal cancer an evolution of treatment." Oncologist 12.11 (November 2007): 1319-1320.
PMID
18055851
Source
pubmed
Published In
The oncologist
Volume
12
Issue
11
Publish Date
2007
Start Page
1319
End Page
1320
DOI
10.1634/theoncologist.12-11-1319

Combined-modality therapy for rectal cancer: future prospects.

The management of rectal cancer has undergone significant evolution with advances in surgery, radiation therapy, and chemotherapy. These advances have translated into improved rates of local control, survival, and quality of life. More recently, the integration of newer chemotherapeutic and targeted agents in patients with advanced colorectal cancer have led to further improvements in disease-free survival and overall survival. These agents are now being studied with radiation therapy in the neoadjuvant therapy of rectal cancer.

Authors
Czito, BG; Willett, CG; Bendell, JC
MLA Citation
Czito, BG, Willett, CG, and Bendell, JC. "Combined-modality therapy for rectal cancer: future prospects." Clin Colorectal Cancer 6.9 (September 2007): 625-633. (Review)
PMID
17945034
Source
pubmed
Published In
Clinical colorectal cancer
Volume
6
Issue
9
Publish Date
2007
Start Page
625
End Page
633
DOI
10.3816/CCC.2007.n.030

Targeted therapy in rectal cancer.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.

Authors
Willett, CG; Duda, DG; Czito, BG; Bendell, JC; Clark, JW; Jain, RK
MLA Citation
Willett, CG, Duda, DG, Czito, BG, Bendell, JC, Clark, JW, and Jain, RK. "Targeted therapy in rectal cancer." Oncology (Williston Park) 21.9 (August 2007): 1055-1065. (Review)
PMID
17910311
Source
pubmed
Published In
Oncology
Volume
21
Issue
9
Publish Date
2007
Start Page
1055
End Page
1065

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results.

PURPOSE: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. METHODS AND MATERIALS: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. RESULTS: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m2 weekly, and capecitabine 625 mg/m2 bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. CONCLUSIONS: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further investigation with this regimen is being pursued in a Phase II setting.

Authors
Czito, BG; Bendell, JC; Willett, CG; Morse, MA; Blobe, GC; Tyler, DS; Thomas, J; Ludwig, KA; Mantyh, CR; Ashton, J; Yu, D; Hurwitz, HI
MLA Citation
Czito, BG, Bendell, JC, Willett, CG, Morse, MA, Blobe, GC, Tyler, DS, Thomas, J, Ludwig, KA, Mantyh, CR, Ashton, J, Yu, D, and Hurwitz, HI. "Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results." Int J Radiat Oncol Biol Phys 68.2 (June 1, 2007): 472-478.
PMID
17498568
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
68
Issue
2
Publish Date
2007
Start Page
472
End Page
478
DOI
10.1016/j.ijrobp.2007.02.001

SU-FF-T-252: Improvement of Localization Accuracy by Using 3D Cone Beam CT for Stereotactic Body Radiation Therapy of Liver, Lung and Spine Lesions

Authors
Wang, Z; Nelson, J; Yoo, S; Wu, QJ; Kirkpatrick, J; Larrier, N; Meyer, J; Willett, C; Yin, F
MLA Citation
Wang, Z, Nelson, J, Yoo, S, Wu, QJ, Kirkpatrick, J, Larrier, N, Meyer, J, Willett, C, and Yin, F. "SU-FF-T-252: Improvement of Localization Accuracy by Using 3D Cone Beam CT for Stereotactic Body Radiation Therapy of Liver, Lung and Spine Lesions." June 2007.
Source
crossref
Published In
Medical physics
Volume
34
Issue
6Part11
Publish Date
2007
Start Page
2459
End Page
2459
DOI
10.1118/1.2760913

Reduction of organ motion by combined cardiac gating and respiratory gating.

PURPOSE: To investigate whether the effect of organ motion can be further reduced with the application of a cardiac gating technique, together with respiratory gating. METHODS AND MATERIALS: Axial and coronal images through the heart and liver were continuously scanned with fast cine magnetic resonance imaging scans at three different gating settings: (1) without respiratory and cardiac gating; (2) with respiratory gating, but without cardiac gating; and (3) with both respiratory and cardiac gating. The effect of motion for either the heart or liver was analyzed with probability maps. RESULTS: With the application of respiratory gating only, the marginal region on the probability map was reduced by 10.0% in the axial slice and 19.8% in the coronal slice for the heart. It was reduced by 5.2% in the axial slice and 20.8% in the coronal slice for the liver. With the application of cardiac gating together with respiratory gating, the marginal region on the probability map was reduced further. The reduction was 8.0% in the axial slice and 13.6% in the coronal slice for the heart and 5.9% in the axial slice and 7.0% in the coronal slice for the liver. CONCLUSION: The effect of organ motion can be further reduced with the application of cardiac gating together with respiratory gating. The potential application to treatment planning merits further investigation.

Authors
Wang, Z; Willett, CG; Yin, F-F
MLA Citation
Wang, Z, Willett, CG, and Yin, F-F. "Reduction of organ motion by combined cardiac gating and respiratory gating." Int J Radiat Oncol Biol Phys 68.1 (May 1, 2007): 259-266.
PMID
17321071
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
68
Issue
1
Publish Date
2007
Start Page
259
End Page
266
DOI
10.1016/j.ijrobp.2006.11.057

Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer.

BACKGROUND: Localized rectal cancer responds well to 5-fluorouracil and radiation-based regimens. A phase I-II trial is currently testing the efficacy of adding bevacizumab, a VEGF-specific antibody, to standard chemoradiotherapy. The case presented here is a complete pathological response seen in a patient with extensive and locally invasive carcinoma after receiving this combined treatment. INVESTIGATIONS: Physical examination, rectal ultrasound, PET-CT scan, laboratory tests, proctoscopic examination, chest radiograph, rectal forcep biopsies with immunohistochemistry, and protein and flow cytometric analyses. DIAGNOSIS: Large, invasive, ultrasound stage T4 carcinoma of the rectum, which was positive for survivin. MANAGEMENT: One 2-week cycle of bevacizumab alone, followed by 3 cycles of bevacizumab with continuous 5-fluorouracil infusion, and external-beam radiation therapy given 5 days per week to the pelvis, abdominoperineal resection with posterior vaginectomy, hysterectomy and bilateral salpingo-oophorectomy.

Authors
Willett, CG; Duda, DG; di Tomaso, E; Boucher, Y; Czito, BG; Vujaskovic, Z; Vlahovic, G; Bendell, J; Cohen, KS; Hurwitz, HI; Bentley, R; Lauwers, GY; Poleski, M; Wong, TZ; Paulson, E; Ludwig, KA; Jain, RK
MLA Citation
Willett, CG, Duda, DG, di Tomaso, E, Boucher, Y, Czito, BG, Vujaskovic, Z, Vlahovic, G, Bendell, J, Cohen, KS, Hurwitz, HI, Bentley, R, Lauwers, GY, Poleski, M, Wong, TZ, Paulson, E, Ludwig, KA, and Jain, RK. "Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer." Nat Clin Pract Oncol 4.5 (May 2007): 316-321.
PMID
17464339
Source
pubmed
Published In
Nature Clinical Practice Oncology
Volume
4
Issue
5
Publish Date
2007
Start Page
316
End Page
321
DOI
10.1038/ncponc0813

Adjuvant therapy of pancreatic cancer.

Of the 33,370 patients diagnosed with pancreatic carcinoma in the United States this year, approximately 20% will present with resectable disease. At present, surgery offers the only means of cure. Radiation therapy and chemotherapy approaches have been used to enhance local and systemic control and survival. Phase III trials evaluating these modalities have led to conflicting results, leading to controversy in the use and selection of therapy. Phase II studies are now being conducted to evaluate target agent therapy with chemoradiation.

Authors
Willett, CG; Czito, BG; Bendell, JC
MLA Citation
Willett, CG, Czito, BG, and Bendell, JC. "Adjuvant therapy of pancreatic cancer." Cancer J 13.3 (May 2007): 185-191. (Review)
PMID
17620768
Source
pubmed
Published In
Cancer Journal
Volume
13
Issue
3
Publish Date
2007
Start Page
185
End Page
191
DOI
10.1097/PPO.0b013e318074e071

Evaluation of an artificial intelligence guided inverse planning system: clinical case study.

PURPOSE: An artificial intelligence (AI) guided method for parameter adjustment of inverse planning was implemented on a commercial inverse treatment planning system. For evaluation purpose, four typical clinical cases were tested and the results from both plans achieved by automated and manual methods were compared. METHODS AND MATERIALS: The procedure of parameter adjustment mainly consists of three major loops. Each loop is in charge of modifying parameters of one category, which is carried out by a specially customized fuzzy inference system. A physician prescribed multiple constraints for a selected volume were adopted to account for the tradeoff between prescription dose to the PTV and dose-volume constraints for critical organs. The searching process for an optimal parameter combination began with the first constraint, and proceeds to the next until a plan with acceptable dose was achieved. The initial setup of the plan parameters was the same for each case and was adjusted independently by both manual and automated methods. After the parameters of one category were updated, the intensity maps of all fields were re-optimized and the plan dose was subsequently re-calculated. When final plan arrived, the dose statistics were calculated from both plans and compared. RESULTS: For planned target volume (PTV), the dose for 95% volume is up to 10% higher in plans using the automated method than those using the manual method. For critical organs, an average decrease of the plan dose was achieved. However, the automated method cannot improve the plan dose for some critical organs due to limitations of the inference rules currently employed. For normal tissue, there was no significant difference between plan doses achieved by either automated or manual method. CONCLUSION: With the application of AI-guided method, the basic parameter adjustment task can be accomplished automatically and a comparable plan dose was achieved in comparison with that achieved by the manual method. Future improvements to incorporate case-specific inference rules are essential to fully automate the inverse planning process.

Authors
Yan, H; Yin, F-F; Willett, C
MLA Citation
Yan, H, Yin, F-F, and Willett, C. "Evaluation of an artificial intelligence guided inverse planning system: clinical case study." Radiother Oncol 83.1 (April 2007): 76-85.
PMID
17368843
Source
pubmed
Published In
Radiotherapy & Oncology
Volume
83
Issue
1
Publish Date
2007
Start Page
76
End Page
85
DOI
10.1016/j.radonc.2007.02.013

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma.

PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study. METHODS AND MATERIALS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy daily to 50.4 Gy). After completion, patients were restaged and evaluated for surgery. Primary endpoints included determination of dose-limiting toxicities (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and pathologic response rates. RESULTS: Thirteen patients were enrolled (10 men, 3 women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose level 1 (capecitabine 825 mg/m(2) twice daily on RT days, carboplatin area under the curve (AUC) 2 weekly, paclitaxel 60 mg/m(2) weekly) had DLT (both Grade 4 esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m(2)). Overall, 3 of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3 hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had pathologic downstaging and 2 of 6 had pCR. CONCLUSIONS: The maximally tolerated/recommended phase II doses were capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m(2) weekly with RT to 50.4 Gy. In our small study, this regimen appears active but is accompanied by significant toxicities, primarily esophagitis.

Authors
Czito, BG; Kelsey, CR; Hurwitz, HI; Willett, CG; Morse, MA; Blobe, GC; Fernando, NH; D'Amico, TA; Harpole, DH; Honeycutt, W; Yu, D; Bendell, JC
MLA Citation
Czito, BG, Kelsey, CR, Hurwitz, HI, Willett, CG, Morse, MA, Blobe, GC, Fernando, NH, D'Amico, TA, Harpole, DH, Honeycutt, W, Yu, D, and Bendell, JC. "A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma." Int J Radiat Oncol Biol Phys 67.4 (March 15, 2007): 1002-1007.
PMID
17197129
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
67
Issue
4
Publish Date
2007
Start Page
1002
End Page
1007
DOI
10.1016/j.ijrobp.2006.10.027

Intraoperative radiation therapy.

Intraoperative radiation therapy (IORT) is the delivery of irradiation at the time of an operation. This is performed by different techniques including intraoperative electron beam techniques and high-dose rate brachytherapy. IORT is usually given in combination with external-beam radiation therapy with or without chemotherapy and surgical resection. IORT excludes part or all dose-limiting sensitive structures, thereby increasing the effective dose to the tumor bed (and therefore local control) without significantly increasing normal tissue morbidity. Despite best contemporary therapy, high rates of local failure occur in patients with locally advanced or recurrent rectal cancer, retroperitoneal sarcoma, select gynecologic cancers, and other malignancies. The addition of IORT to conventional treatment methods has improved local control as well as survival in many disease sites in both the primary and locally recurrent disease settings. More recently, there has been interest in the use of IORT as a technique of partial breast irradiation for women with early breast cancer. Given newer and lower cost treatment devices, the use of IORT in clinical practice will likely grow, with increasing integration into the treatment of nonconventional malignancies. Optimally, phase III randomized trials will be carried out to prove its efficacy in these disease sites.

Authors
Willett, CG; Czito, BG; Tyler, DS
MLA Citation
Willett, CG, Czito, BG, and Tyler, DS. "Intraoperative radiation therapy." J Clin Oncol 25.8 (March 10, 2007): 971-977. (Review)
PMID
17350946
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
8
Publish Date
2007
Start Page
971
End Page
977
DOI
10.1200/JCO.2006.10.0255

Multiple etiologies of tumor hypoxia require multifaceted solutions.

Authors
Dewhirst, MW; Navia, IC; Brizel, DM; Willett, C; Secomb, TW
MLA Citation
Dewhirst, MW, Navia, IC, Brizel, DM, Willett, C, and Secomb, TW. "Multiple etiologies of tumor hypoxia require multifaceted solutions." Clin Cancer Res 13.2 Pt 1 (January 15, 2007): 375-377.
PMID
17255256
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
2 Pt 1
Publish Date
2007
Start Page
375
End Page
377
DOI
10.1158/1078-0432.CCR-06-2629

Advanced radiation therapy technologies in the treatment of rectal and anal cancer: intensity-modulated photon therapy and proton therapy.

Intensity-modulated photon radiation therapy (RT; IMRT) and proton therapy are advanced radiation technologies that permit improved conformation of radiation dose to target structures while limiting irradiation of surrounding normal tissues. Application of these technologies in the treatment of rectal and anal cancer is attractive, based on the potential reduction in radiation treatment toxicities that are frequently incurred in the pelvis and perineum. Furthermore, conformal RT might also allow for dose escalation to target areas, leading to improved tumor control. This review discusses the underlying principles of IMRT. In addition, the rationale and clinical data regarding the efficacy of radiation dose escalation for rectal and anal cancer will be highlighted, as well as tolerance of pelvic organs to RT and chemotherapy. Finally, preliminary results of IMRT in the treatment of lower gastrointestinal tract cancers will be reviewed. The potential and rationale for proton therapy in treatment of these malignancies are also discussed.

Authors
Meyer, J; Czito, B; Yin, F-F; Willett, C
MLA Citation
Meyer, J, Czito, B, Yin, F-F, and Willett, C. "Advanced radiation therapy technologies in the treatment of rectal and anal cancer: intensity-modulated photon therapy and proton therapy." Clin Colorectal Cancer 6.5 (January 2007): 348-356. (Review)
PMID
17311699
Source
pubmed
Published In
Clinical colorectal cancer
Volume
6
Issue
5
Publish Date
2007
Start Page
348
End Page
356
DOI
10.3816/CCC.2007.n.003

Is radiation therapy required for patients with intermediate-risk rectal cancer?

Randomized trials have demonstrated that radiation therapy improves local control in patients with rectal cancer. Because pelvic irradiation may result in acute and/or late morbidity, identification of patients with the highest probability of benefiting from this therapy would be optimal. Though radiation is usually recommended for patients with tumors invading through the muscularis propria into the mesorectum with or without lymph-node involvement, several studies suggest that patients with only one of these risk factors may comprise a more favorable risk group who may not require radiation as part of their overall management. Current data permit identification of these patients, but no randomized studies have yet demonstrated that selected patients with locally advanced rectal cancer can safely be spared adjuvant or neoadjuvant radiation.

Authors
Mamon, H; Willett, CG
MLA Citation
Mamon, H, and Willett, CG. "Is radiation therapy required for patients with intermediate-risk rectal cancer?." Clinical Advances in Hematology and Oncology 5.8 (2007): 638-644+585.
PMID
17982404
Source
scival
Published In
Clinical advances in hematology & oncology : H&O
Volume
5
Issue
8
Publish Date
2007
Start Page
638
End Page
644+585

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

Despite setbacks, the clinical development of antiangiogenic agents has accelerated remarkably over the past 3-4 years. Consequently, there are currently three direct inhibitors of the VEGF pathway approved for use in cancer therapy. Other agents that block the VEGF pathway are in advanced stages of clinical development and have shown promising results. With these exciting developments come crucial questions regarding the use of these new molecular-targeted agents, alone or in combination with standard cytotoxic or targeted agents. Importantly, the mechanisms of action of anti-VEGF therapy remain unknown. Here, we discuss several potential mechanisms of action such as tumor vascular normalization, bone marrow-derived cell recruitment blockade and cytostatic effects of anti-VEGF therapy. We review the current progress, the major stumbling blocks and the future directions for anti-cancer therapy using anti-VEGF agents, emphasizing clarification of the underlying molecular mechanisms of action and biomarker identification and validation.

Authors
Duda, DG; Batchelor, TT; Willett, CG; Jain, RK
MLA Citation
Duda, DG, Batchelor, TT, Willett, CG, and Jain, RK. "VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects." Trends in Molecular Medicine 13.6 (2007): 223-230.
PMID
17462954
Source
scival
Published In
Trends in Molecular Medicine
Volume
13
Issue
6
Publish Date
2007
Start Page
223
End Page
230
DOI
10.1016/j.molmed.2007.04.001

Microsatellite Instability is Frequently Observed in Rectal Cancer and Influenced by Neoadjuvant Chemoradiation

Authors
Choi, MY; Lauwers, GY; Hur, C; Willett, CG; Chung, DC
MLA Citation
Choi, MY, Lauwers, GY, Hur, C, Willett, CG, and Chung, DC. "Microsatellite Instability is Frequently Observed in Rectal Cancer and Influenced by Neoadjuvant Chemoradiation." International Journal of Radiation Oncology Biology Physics 68.5 (2007): 1584--.
PMID
17674996
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
68
Issue
5
Publish Date
2007
Start Page
1584-
DOI
10.1016/j.ijrobp.2007.04.045

Monitoring changes in the microenvironment during targeted therapies

Both antiangiogenic and vascular-targeted therapies hold great promise. The approval of some antiangiogenic agents in combination with other therapies bode well for the future clinical use of these agents. Similarly, the increased interest in vascular-targeting approaches shows potential, particularly when combined with radiotherapy and/or chemotherapy. In both of these approaches, however, it is imperative that suitable biomarkers be employed to monitor treatment effects and ensure optimal use. To achieve the highest efficacy of these treatment modalities, it may be mandatory to determine the response of antiangiogenic and antivascular compounds to ascertain an appropriate treatment schedule on an individualized basis (see Figure 1).

Authors
Wergin, M; Willett, CG; Dewhirst, MW
MLA Citation
Wergin, M, Willett, CG, and Dewhirst, MW. "Monitoring changes in the microenvironment during targeted therapies." ONCOLOGY 21.11 (2007): 1354-1370.
Source
scival
Published In
Oncology
Volume
21
Issue
11
Publish Date
2007
Start Page
1354
End Page
1370

Pancreatic adenocarcinoma

Overall, in view of the poor outcome of patients with all stages of pancreatic cancer, the panel recommends that investigational options be considered in all phases of disease management. Specific palliative measures are recommended for patients with advanced pancreatic adenocarcinoma characterized by biliary or gastric obstruction, severe abdominal pain, or other tumor-associated manifestations of the disease. © Journal of the National Comprehensive Cancer Network.

Authors
Tempero, M; Alasadi, R; Arnoletti, JP; Behrman, S; Ben-Josef, E; III, ABB; Bhargava, P; Cameron, JL; Casper, ES; Hoffman, JP; Kim, P; Koh, W-J; Kuvshinoff, B; Malafa, MP; II, PM; Nakakura, EK; Sasson, AR; Shibata, S; Shrieve, DC; Talamonti, M; Tyler, DS; Wang, H; Warren, RS; Willett, C; Wolff, RA
MLA Citation
Tempero, M, Alasadi, R, Arnoletti, JP, Behrman, S, Ben-Josef, E, III, ABB, Bhargava, P, Cameron, JL, Casper, ES, Hoffman, JP, Kim, P, Koh, W-J, Kuvshinoff, B, Malafa, MP, II, PM, Nakakura, EK, Sasson, AR, Shibata, S, Shrieve, DC, Talamonti, M, Tyler, DS, Wang, H, Warren, RS, Willett, C, and Wolff, RA. "Pancreatic adenocarcinoma." JNCCN Journal of the National Comprehensive Cancer Network 5.10 (2007): 998-1033.
PMID
18053426
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
5
Issue
10
Publish Date
2007
Start Page
998
End Page
1033

Discussion: Surgical issues in colon and rectal cancers

Authors
Bilchik, A; Stamos, M; Nelson, H; Rosen, L; Willett, C; Lynch, PM; Jr, RWB; Compton, CC
MLA Citation
Bilchik, A, Stamos, M, Nelson, H, Rosen, L, Willett, C, Lynch, PM, Jr, RWB, and Compton, CC. "Discussion: Surgical issues in colon and rectal cancers." Clinical Cancer Research 13.22 (2007): 6901S-6902S.
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
22
Publish Date
2007
Start Page
6901S
End Page
6902S

Discussion: Issues in adjuvant therapy for early-stage disease

Authors
Grothey, A; Haller, D; Willett, C; Rosen, L; Beart, R; Stamos, M; Bilchik, A; Benson, A
MLA Citation
Grothey, A, Haller, D, Willett, C, Rosen, L, Beart, R, Stamos, M, Bilchik, A, and Benson, A. "Discussion: Issues in adjuvant therapy for early-stage disease." Clinical Cancer Research 13.22 (2007): 6919S-6920S.
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
22
Publish Date
2007
Start Page
6919S
End Page
6920S

New approaches to assessing and treating early-stage colon and rectal cancer: Summary statement from 2007 Santa Monica Conference

The 2007 Santa Monica Conference on Assessing and Treating Early-Stage Colon and Rectal Cancer, a multidisciplinary meeting of leaders in surgery, medical and radiation oncology, and pathology, was convened on January 12 to 13, 2007. The purpose of the meeting was to assess current data and issues in the field and to develop recommendations for advancing patient care and clinical research. Topics included pathologic assessment and staging, transanal versus laparoscopic versus open resection, adjuvant therapy, genetic testing and counseling, cooperative group strategies, and the use of biological therapies and novel agents. A review of the key issues discussed, as well as conclusions and recommendations considered significant to the field, is summarized below and presented at greater length in the individual manuscripts and accompanying discussion that comprise the full conference proceedings. Although the management of early-stage colon and rectal cancers remains a challenge for all of us, the development and use of new technologies and methods of assessment and treatment over the past several decades is yielding encouraging results. A variety of opportunities to further improve outcomes were addressed in this forum, including recommendations that specific protocols be adopted regarding surgical and pathologic dissection and reporting, particularly for stage II disease; the corollary need to increase active multidisciplinary collaboration; and the development of comprehensive consensus guidelines and recommendations to standardize care in early-stage colorectal cancer. ©2007 American Association for Cancer Research.

Authors
Rosen, LS; Bilchik, AJ; Jr, RWB; III, ABB; Chang, KJ; Compton, CC; Grothey, A; Haller, DG; Ko, CY; Lynch, PM; Nelson, H; Stamos, MJ; Turner, RR; Willett, CG
MLA Citation
Rosen, LS, Bilchik, AJ, Jr, RWB, III, ABB, Chang, KJ, Compton, CC, Grothey, A, Haller, DG, Ko, CY, Lynch, PM, Nelson, H, Stamos, MJ, Turner, RR, and Willett, CG. "New approaches to assessing and treating early-stage colon and rectal cancer: Summary statement from 2007 Santa Monica Conference." Clinical Cancer Research 13.22 (2007): 6853S-6856S.
PMID
18006789
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
22
Publish Date
2007
Start Page
6853S
End Page
6856S
DOI
10.1158/1078-0432.CCR-07-1629

Antiangiogenics: The potential role of integrating this novel treatment modality with chemoradiation for solid cancers

Although still in very early stages of clinical development, the combination of antiangiogenics with contemporary chemoradiotherapy regimens has emerged as a feasible and promising approach to many cancers. We review the rationale and the current understanding of antiangiogenics and their therapeutic potential in combination with chemoradiotherapy. Finally, we offer a perspective on future research directions aimed at making this complex therapeutic approach successful in the clinic. © 2007 by American Society of Clinical Oncology.

Authors
Duda, DG; Jain, RK; Willett, CG
MLA Citation
Duda, DG, Jain, RK, and Willett, CG. "Antiangiogenics: The potential role of integrating this novel treatment modality with chemoradiation for solid cancers." Journal of Clinical Oncology 25.26 (2007): 4033-4042.
PMID
17827451
Source
scival
Published In
Journal of Clinical Oncology
Volume
25
Issue
26
Publish Date
2007
Start Page
4033
End Page
4042
DOI
10.1200/JCO.2007.11.3985

Long-term results of RTOG trial 8911 (USA intergroup 113): A random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer

Purpose: We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed. Patients and Methods: The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated. Results: Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival. Conclusion: For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients. © 2007 by American Society of Clinical Oncology.

Authors
Kelsen, DP; Winter, KA; Gunderson, LL; Mortimer, J; Estes, NC; Haller, DG; Ajani, JA; Kocha, W; Minsky, BD; Roth, JA; Willett, CG
MLA Citation
Kelsen, DP, Winter, KA, Gunderson, LL, Mortimer, J, Estes, NC, Haller, DG, Ajani, JA, Kocha, W, Minsky, BD, Roth, JA, and Willett, CG. "Long-term results of RTOG trial 8911 (USA intergroup 113): A random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer." Journal of Clinical Oncology 25.24 (2007): 3719-3725.
PMID
17704421
Source
scival
Published In
Journal of Clinical Oncology
Volume
25
Issue
24
Publish Date
2007
Start Page
3719
End Page
3725
DOI
10.1200/JCO.2006.10.4760

In reply [10]

Authors
Duda, DG; Cohen, KS; Au, P; Scadden, DT; Willett, CG; Jain, RK
MLA Citation
Duda, DG, Cohen, KS, Au, P, Scadden, DT, Willett, CG, and Jain, RK. "In reply [10]." Journal of Clinical Oncology 25.5 (2007): e3-e5.
Source
scival
Published In
Journal of Clinical Oncology
Volume
25
Issue
5
Publish Date
2007
Start Page
e3
End Page
e5
DOI
10.1200/JCO.2006.08.5100

Surrogate biomarkers for anti-angiogenic therapy for advanced colorectal cancer

Vascular endothelial growth factor (VEGF)-overexpressed in colorectal cancer-is associated with disease progression and inferior survival. Based on successful, randomized, phase III trials, anti-VEGF therapeutics have entered clinical practice. Bevacizumab, a VEGF-specific antibody, was the first anti-angiogenic agent to be approved by the Food and Drug Administration to be used in combination with standard chemotherapy in the first and second line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also normalize tumor vasculature thereby leading to greater tumor oxygenation (a known radiosensitizer) and drug penetration. A dose-escalation phase I trial has demonstrated that the combination of bevacizumab at the 5-mg/kg dose with radiochemotherapy was well tolerated by patients with rectal cancers. In addition, results from an array of correlative studies have demonstrated that bevacizumab has antivascular effects and supported the normalization hypothesis. The ongoing phase II study will further elucidate the mechanisms of action and efficacy of bevacizumab in locally advanced rectal cancer. Copyright © 2007 by Current Medicine Group LLC.

Authors
Willett, CG; Duda, DG; Jain, RK
MLA Citation
Willett, CG, Duda, DG, and Jain, RK. "Surrogate biomarkers for anti-angiogenic therapy for advanced colorectal cancer." Current Colorectal Cancer Reports 3.2 (2007): 94-98.
Source
scival
Published In
Current Colorectal Cancer Reports
Volume
3
Issue
2
Publish Date
2007
Start Page
94
End Page
98
DOI
10.1007/s11888-007-0007-5

IMRT for malignancies of the upper abdomen and retroperitoneum

Authors
Landry, JC; Willett, CG; Esiashvili, N; Koshy, M
MLA Citation
Landry, JC, Willett, CG, Esiashvili, N, and Koshy, M. "IMRT for malignancies of the upper abdomen and retroperitoneum." (December 1, 2006): 383-390. (Chapter)
Source
scopus
Publish Date
2006
Start Page
383
End Page
390
DOI
10.1007/3-540-30356-1_30

Combined vascular endothelial growth factor-targeted therapy and radiotherapy for rectal cancer: theory and clinical practice.

Despite the routine use of adjuvant and neoadjuvant chemoradiotherapy, patients with advanced rectal tumors experience significant rates of treatment failure and disease recurrence. Resistance to radiation is a particular problem. Adding a vascular endothelial growth factor (VEGF)-targeted therapy may improve outcomes in these patients. Epidemiologic studies have shown that tumor expression of VEGF predicts disease recurrence and lower overall survival in patients treated with radiation. In tumor xenograft models in mice, VEGF-targeted agents increase the response to radiation, with a greater probability of tumor control and a greater delay in tumor growth. In addition to killing cancer cells indirectly by damaging tumor blood vessels (antivascular effect), VEGF-targeted therapy may sensitize tumors to radiation through two mechanisms: by normalizing the tumor vasculature, leading to greater tumor oxygenation, and thereby increasing the cytotoxicity of radiation to cancer cells, and by increasing the radiosensitivity of tumor-associated endothelial cells. In addition, anti-VEGF agents may inhibit the regrowth of tumors after radiation by decreasing the number of circulating endothelial cells and endothelial progenitor cells. A phase I dose-escalation study has shown the safety of bevacizumab at a dose of 5 mg/kg in combination with 5-fluorouracil and radiation in patients with rectal carcinoma, and has provided evidence of both vascular normalization and antivascular mechanisms. Phase II evaluation of bevacizumab in this setting is under way.

Authors
Willett, CG; Kozin, SV; Duda, DG; di Tomaso, E; Kozak, KR; Boucher, Y; Jain, RK
MLA Citation
Willett, CG, Kozin, SV, Duda, DG, di Tomaso, E, Kozak, KR, Boucher, Y, and Jain, RK. "Combined vascular endothelial growth factor-targeted therapy and radiotherapy for rectal cancer: theory and clinical practice." Semin Oncol 33.5 Suppl 10 (October 2006): S35-S40. (Review)
PMID
17145523
Source
pubmed
Published In
Seminars in Oncology
Volume
33
Issue
5 Suppl 10
Publish Date
2006
Start Page
S35
End Page
S40
DOI
10.1053/j.seminoncol.2006.08.007

Radiation therapy in the treatment of cholangiocarcinoma.

The prognosis of patients with biliary cancers is poor. Although surgery is potentially curative in selected patients, local recurrence is a common pattern of failure. Adjuvant or neoadjuvant radiation therapy improves local control and possibly survival. In locally advanced patients, radiation therapy provides palliation and may prolong survival. Concurrently administered chemotherapy may further enhance these results. Newer radiation therapy techniques, including intraluminal transcatheter brachytherapy, intraoperative radiation therapy, intensity-modulated radiation therapy, and three- and four-dimensional treatment planning, permit radiation dose escalation without significant increases in normal tissue toxicity, thereby increasing the effective radiation dose. Preliminary results of studies employing hepatic transplantation with radiation therapy are encouraging. Although these new approaches hold promise, the prognosis in patients with biliary cancers remains poor, and the integration of novel therapeutic strategies is indicated.

Authors
Czito, BG; Anscher, MS; Willett, CG
MLA Citation
Czito, BG, Anscher, MS, and Willett, CG. "Radiation therapy in the treatment of cholangiocarcinoma." Oncology (Williston Park) 20.8 (July 2006): 873-884. (Review)
PMID
16922259
Source
pubmed
Published In
Oncology
Volume
20
Issue
8
Publish Date
2006
Start Page
873
End Page
884

SU-FF-T-66: A Technique for Cone-Beam CT-Guided Stereotactic Body Radiation Therapy

Authors
Yin, F; Marks, L; Wang, Z; Kirkpatrick, J; Wu, J; Yoo, S; Larrier, N; Meyer, J; Willett, C
MLA Citation
Yin, F, Marks, L, Wang, Z, Kirkpatrick, J, Wu, J, Yoo, S, Larrier, N, Meyer, J, and Willett, C. "SU-FF-T-66: A Technique for Cone-Beam CT-Guided Stereotactic Body Radiation Therapy." June 2006.
Source
crossref
Published In
Medical physics
Volume
33
Issue
6Part7
Publish Date
2006
Start Page
2063
End Page
2063
DOI
10.1118/1.2240992

Verifying internal target volume using cone-beam CT for stereotactic body radiotherapy treatment

Authors
Wang, Z; Yin, F; Yoo, S; Wu, Q; Willett, C; Marks, L
MLA Citation
Wang, Z, Yin, F, Yoo, S, Wu, Q, Willett, C, and Marks, L. "Verifying internal target volume using cone-beam CT for stereotactic body radiotherapy treatment." June 2006.
Source
wos-lite
Published In
Medical physics
Volume
33
Issue
6
Publish Date
2006
Start Page
1991
End Page
1991
DOI
10.1118/1.2240160

A tool for off-line review of 3D target verification and localization with cone-beam computed tomography

Authors
Wu, Q; Yan, H; Yin, F; Yoo, S; Das, S; Willett, C
MLA Citation
Wu, Q, Yan, H, Yin, F, Yoo, S, Das, S, and Willett, C. "A tool for off-line review of 3D target verification and localization with cone-beam computed tomography." June 2006.
Source
wos-lite
Published In
Medical physics
Volume
33
Issue
6
Publish Date
2006
Start Page
2023
End Page
2023
DOI
10.1118/1.2240795

Digital tomosynthesis with an on-board kilovoltage imaging device.

PURPOSE: To generate on-board digital tomosynthesis (DTS) and reference DTS images for three-dimensional image-guided radiation therapy (IGRT) as an alternative to conventional portal imaging or on-board cone-beam computed tomography (CBCT). METHODS AND MATERIALS: Three clinical cases (prostate, head-and-neck, and liver) were selected to illustrate the capabilities of on-board DTS for IGRT. Corresponding reference DTS images were reconstructed from digitally reconstructed radiographs computed from planning CT image sets. The effect of scan angle on DTS slice thickness was examined by computing the mutual information between coincident CBCT and DTS images, as the DTS scan angle was varied from 0 degrees to 165 degrees . A breath-hold DTS acquisition strategy was implemented to remove respiratory motion artifacts. RESULTS: Digital tomosynthesis slices appeared similar to coincident CBCT planes and yielded substantially more anatomic information than either kilovoltage or megavoltage radiographs. Breath-hold DTS acquisition improved soft-tissue visibility by suppressing respiratory motion. CONCLUSIONS: Improved bony and soft-tissue visibility in DTS images is likely to improve target localization compared with radiographic verification techniques and might allow for daily localization of a soft-tissue target. Breath-hold DTS is a potential alternative to on-board CBCT for sites prone to respiratory motion.

Authors
Godfrey, DJ; Yin, F-F; Oldham, M; Yoo, S; Willett, C
MLA Citation
Godfrey, DJ, Yin, F-F, Oldham, M, Yoo, S, and Willett, C. "Digital tomosynthesis with an on-board kilovoltage imaging device." Int J Radiat Oncol Biol Phys 65.1 (May 1, 2006): 8-15.
PMID
16618573
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
65
Issue
1
Publish Date
2006
Start Page
8
End Page
15
DOI
10.1016/j.ijrobp.2006.01.025

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. PATIENTS AND METHODS: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. RESULTS: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. CONCLUSION: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

Authors
Czito, BG; Willett, CG; Bendell, JC; Morse, MA; Tyler, DS; Fernando, NH; Mantyh, CR; Blobe, GC; Honeycutt, W; Yu, D; Clary, BM; Pappas, TN; Ludwig, KA; Hurwitz, HI
MLA Citation
Czito, BG, Willett, CG, Bendell, JC, Morse, MA, Tyler, DS, Fernando, NH, Mantyh, CR, Blobe, GC, Honeycutt, W, Yu, D, Clary, BM, Pappas, TN, Ludwig, KA, and Hurwitz, HI. "Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results." J Clin Oncol 24.4 (February 1, 2006): 656-662.
PMID
16446337
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
4
Publish Date
2006
Start Page
656
End Page
662
DOI
10.1200/JCO.2005.04.1749

Radiation therapy for resectable colon cancer. Is there a role in the modern chemotherapy era?

Colon cancer is a major public health problem. The primary treatment is resection. For patients with early-stage disease, surgery results in excellent survival rates. In contrast, patients with locally advanced tumors arising in "anatomically immobile" segments of large bowel have a less satisfactory outcome, in part secondary to compromised surgical clearance. Patterns-of-failure analyses suggest that for tumors that invade adjacent organs, exhibit perforation or fistula, or are subtotally resected, local failure rates exceed 30%. Multiple single-institution retrospective studies have shown improved local control and possibly survival with the addition of external irradiation and/or intraoperative radiation. In contrast, a recent Intergroup trial failed to show any benefit by the addition of adjuvant radiation therapy combined with chemotherapy. Interpretation of this trial's results is handicapped by low patient accrual. With the advent of novel and more effective systemic therapies for metastatic colon cancer, current and future clinical research will address the efficacy of these agents in the adjuvant setting. Adjuvant radiation therapy should be considered in patients with colon cancer at high risk for local failure.

Authors
Czito, BG; Bendell, J; Willett, CG
MLA Citation
Czito, BG, Bendell, J, and Willett, CG. "Radiation therapy for resectable colon cancer. Is there a role in the modern chemotherapy era?." Oncology (Williston Park) 20.2 (February 2006): 179-187.
PMID
16562650
Source
pubmed
Published In
Oncology
Volume
20
Issue
2
Publish Date
2006
Start Page
179
End Page
187

Outcomes in a series of 103 retroperitoneal sarcomas

Aims: To report the effect on outcome of selection in patients receiving intra-operative electron beam radiation (IOERT) and external beam radiation therapy (EBRT). Methods: One hundred and three patients treated for primary RS were studied. Median follow-up was 27 months. Clinical presentation, tumor characteristics, and treatment methods were analyzed to determine impact on survival and recurrence and if selection was occurring. Results: Mean age was 55 ± 17 years. Mean tumor size was 15 ± 6 cm and 88 were high-grade. Complete gross tumor resection (CR) occurred in 62 patients and improved survival vs. both debulking (p = 0.0005) and biopsy (p < 0.0001). The 5- and 10-year survival rates were 62% and 52% for those with CR vs. 29% and 20% after incomplete resection. Among the 62 CR patients, there was selection to receive additional EBRT ± IOERT in patients with high-grade tumors (p = 0.005) and/or microscopically positive margins (p = 0.011). In these high-risk patients there was a trend for IOERT to further augment survival vs. EBRT alone and to increase the time to both local and distant recurrences (p = 0.036). Conclusions: Complete gross resection is the primary form of curative treatment for retroperitoneal sarcomas. Selection led to patients with high-risk tumors receiving additional radiation therapy. There appears to be a beneficial effect of IOERT plus EBRT in these high-risk patients after complete tumor resection. © 2006.

Authors
Pierie, J-PEN; Betensky, RA; Choudry, U; Willett, CG; Souba, WW; Ott, MJ
MLA Citation
Pierie, J-PEN, Betensky, RA, Choudry, U, Willett, CG, Souba, WW, and Ott, MJ. "Outcomes in a series of 103 retroperitoneal sarcomas." European Journal of Surgical Oncology 32.10 (2006): 1235-1241.
PMID
16919908
Source
scival
Published In
EJSO - European Journal of Surgical Oncology
Volume
32
Issue
10
Publish Date
2006
Start Page
1235
End Page
1241
DOI
10.1016/j.ejso.2006.07.002

Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): Quality of combined modality therapy and pathologic response

Purpose: Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. Patients and Methods: Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. Results: Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. Conclusion: For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer. © 2006 by American Society of Clinical Oncology.

Authors
Ajani, JA; Winter, K; Okawara, GS; Donohue, JH; Pisters, PWT; Crane, CH; Greskovich, JF; Anne, PR; Bradley, JD; Willett, C; Rich, TA
MLA Citation
Ajani, JA, Winter, K, Okawara, GS, Donohue, JH, Pisters, PWT, Crane, CH, Greskovich, JF, Anne, PR, Bradley, JD, Willett, C, and Rich, TA. "Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): Quality of combined modality therapy and pathologic response." Journal of Clinical Oncology 24.24 (2006): 3953-3958.
PMID
16921048
Source
scival
Published In
Journal of Clinical Oncology
Volume
24
Issue
24
Publish Date
2006
Start Page
3953
End Page
3958
DOI
10.1200/JCO.2006.06.4840

Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation therapy oncology group trial 0012

Authors
Mohiuddin, M; Winter, K; Mitchell, E; Hanna, N; Yuen, A; Nichols, C; Shane, R; Hayostek, C; Willett, C; Cutsem, EV
MLA Citation
Mohiuddin, M, Winter, K, Mitchell, E, Hanna, N, Yuen, A, Nichols, C, Shane, R, Hayostek, C, Willett, C, and Cutsem, EV. "Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation therapy oncology group trial 0012." Advances in Gastrointestinal Cancers 4.2 (2006): 27--.
Source
scival
Published In
Advances in Gastrointestinal Cancers
Volume
4
Issue
2
Publish Date
2006
Start Page
27-

Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

Purpose: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted. © 2006 Elsevier Inc. All rights reserved.

Authors
Roof, KS; Coen, J; Lynch, TJ; Wright, C; Fidias, P; Willett, CG; Choi, NC
MLA Citation
Roof, KS, Coen, J, Lynch, TJ, Wright, C, Fidias, P, Willett, CG, and Choi, NC. "Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer." International Journal of Radiation Oncology Biology Physics 65.4 (2006): 1120-1128.
PMID
16730135
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
65
Issue
4
Publish Date
2006
Start Page
1120
End Page
1128
DOI
10.1016/j.ijrobp.2006.02.013

Pancreatoblastoma in a teenage patient

Authors
Bendell, JC; Lauwers, GY; Willett, C; Clark, JW; Warshaw, AL; Wain, JC; Ryan, DP
MLA Citation
Bendell, JC, Lauwers, GY, Willett, C, Clark, JW, Warshaw, AL, Wain, JC, and Ryan, DP. "Pancreatoblastoma in a teenage patient." Clinical Advances in Hematology and Oncology 4.2 (2006): 150-153.
PMID
16728924
Source
scival
Published In
Clinical advances in hematology & oncology : H&O
Volume
4
Issue
2
Publish Date
2006
Start Page
150
End Page
153

Differential CD146 expression on circulating versus tissue endothelial cells in rectal cancer patients: Implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy

Purpose: Circulating endothelial cells (CECs) and progenitor cells are currently evaluated as potential biomarkers of antiangiogenic therapy. CD146 is considered a panendothelial-specific marker, but its utility as a CEC marker in cancer patients remains unclear. Patients and Methods: We analyzed the expression of CD146 on mononuclear blood cells, primary tissue endothelial cells, and malignant and normal tissues by flow cytometric and immunohistochemical analyses. Furthermore, we measured the circulation kinetics of CD146+ cells before, and then 3 and 12 days after vascular endothelial growth factor (VEGF) antibody blockade by bevacizumab infusion in rectal cancer patients enrolled in a phase I trial. Results: In the peripheral blood of these cancer patients, over 90% of the CD146+ cells were CD45+ hematopoietic cells. CD146 expression was primarily detected on a subset of CD3+CD4+ lymphocytes, and was undetectable on CD34+CD133+CD45dim progenitor cells or CD31brightCD45- viable CECs. In contradistinction, CD146 was detectable in tissues on both cellular components of tumor vessel wall: CD31brightCD45- endothelial cells and α-SMA + pericytes. Unlike viable CECs and progenitor cells, CD146 + cell concentration in the peripheral blood of cancer patients did not decrease during VEGF blockade. Conclusion: CD146 is fairly homogeneously expressed on vascular endothelium but not on viable CECs or progenitor cells. The vast majority of CD146+ blood cells are lymphocytes, and VEGF blockade by bevacizumab did not significantly change their number in rectal cancer patients. These results underscore the need for further characterization and identification of new markers for CEC subpopulations for their development as biomarkers of antiangiogenic therapy. © 2006 by American Society of Clinical Oncology.

Authors
Duda, DG; Cohen, KS; Tomaso, ED; Au, P; Klein, RJ; Scadden, DT; Willett, CG; Jain, RK
MLA Citation
Duda, DG, Cohen, KS, Tomaso, ED, Au, P, Klein, RJ, Scadden, DT, Willett, CG, and Jain, RK. "Differential CD146 expression on circulating versus tissue endothelial cells in rectal cancer patients: Implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy." Journal of Clinical Oncology 24.9 (2006): 1449-1453.
PMID
16549839
Source
scival
Published In
Journal of Clinical Oncology
Volume
24
Issue
9
Publish Date
2006
Start Page
1449
End Page
1453
DOI
10.1200/JCO.2005.04.2861

Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation therapy oncology group trial 0012

Purpose: To evaluate the rate of pathologic complete response and toxicity of neoadjuvant chemoradiation for advanced T3/T4 distal rectal cancers in a randomized phase II study Patients and Methods: Patients with clinical T3/T4 distal rectal cancers were randomly assigned in a phase II study to receive combined neoadjuvant chemoradiotherapy followed by surgical resection. Patients were randomly assigned to receive continuous venous infusion (CVI) fluorouracil (FU) 225 mg/m2 per day, 7 days per week, plus pelvic hyperfractionated radiation 55.2 to 60 Gy at 1.2 Gy bid (arm 1) or CVI FU 225 mg/m2 per day Monday to Friday, 120 hours per week plus irinotecan 50 mg/m2 once weekly for 4 weeks plus pelvic radiation therapy 50.4 to 54 Gy at 1.8 Gy per day (arm 2). Surgery was performed 4 to 10 weeks after completion of neoadjuvant therapy. The primary end point of this study was pathologic complete response (pCR). Secondary end points included acute and late normal tissue morbidity. Results: A total of 106 patients were entered onto the study, with 103 assessable for response. The overall resectability rate was 93%. The median time to surgery was 7 weeks. Tumor downstaging was observed in 78% of patients in both arms. The pCR rate for all assessable patients was 26% in each arm. For patients who had surgery, the pCR rate was also the same (28%) in both arms. Acute and late toxicity was also similar. Grade 3 and 4 acute hematologic and nonhematologic toxicity occurred in 13% and 38% in arm 1 and 12% and 45% in arm 2, respectively. Conclusion: Although the overall complete response rate and toxicity seems similar in both arms, this is the first multi-institutional study to establish a relatively high (28%) pCR rate after neoadjuvant therapy. © 2006 by American Society of Clinical Oncology.

Authors
Mohiuddin, M; Winter, K; Mitchell, E; Hanna, N; Yuen, A; Nichols, C; Shane, R; Hayostek, C; Willett, C
MLA Citation
Mohiuddin, M, Winter, K, Mitchell, E, Hanna, N, Yuen, A, Nichols, C, Shane, R, Hayostek, C, and Willett, C. "Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation therapy oncology group trial 0012." Journal of Clinical Oncology 24.4 (2006): 650-655.
PMID
16446336
Source
scival
Published In
Journal of Clinical Oncology
Volume
24
Issue
4
Publish Date
2006
Start Page
650
End Page
655
DOI
10.1200/JCO.2005.03.6095

Detection of stool DNA mutations before and after treatment of colorectal neoplasia

BACKGROUND. Whether stool DNA abnormalities arise solely from colorectal neoplastic lesions or are due to more pervasive field effects is not known. In the current study, the authors conducted a prospective multicenter study to evaluate the performance of stool-based DNA testing in a large cohort and to examine whether the findings before treatment persist after surgical resection and/or adjuvant therapy. METHODS. Patients with newly diagnosed colorectal carcinoma or advanced adenomas (AA) provided stool samples before therapy, 1-3 months after surgical resection, and 6-9 months postresection. Stool samples were analyzed using the multitarget DNA assay panel (MTAP) consisting of 23 markers: 21 mutations in the p53, K-ras, and APC genes, a microsatellite instability marker (BAT-26), and the DNA integrity assay (DIA), a marker of loss of apoptosis. RESULTS. Overall, 49 of 91 individuals (54%) tested positive with the MTAP test. The sensitivity of the MTAP test was 63% for invasive tumors compared with 26% for AA. Individuals whose lesions had a more advanced TNM stage or were located distal to the splenic flexure were significantly more likely to have a positive MTAP test. Of the 79 samples collected at 1-3 months after surgical resection of the neoplasm, 14 (18%) had a positive MTAP result, 12 of which were positive for DIA only. Of those collected at 6-9 months of follow-up, 5 of 72 (7%) tested positive on the MTAP panel. CONCLUSIONS. Although many samples collected 1-3 months after surgical resection of the colorectal neoplasm tested positive on the MTAP, most were negative by 6-9 months, indicating that stool DNA abnormalities disappear after treatment of the neoplastic lesions. Surgery and chemoradiation appear to induce transient DIA abnormalities that maybe independent of the presence of neoplasia. © 2005 American Cancer Society.

Authors
Syngal, S; Stoffel, E; Chung, D; Willett, C; Schoetz, D; Schroy, P; Jagadeesh, D; Morel, K; Ross, M
MLA Citation
Syngal, S, Stoffel, E, Chung, D, Willett, C, Schoetz, D, Schroy, P, Jagadeesh, D, Morel, K, and Ross, M. "Detection of stool DNA mutations before and after treatment of colorectal neoplasia." Cancer 106.2 (2006): 277-283.
PMID
16342248
Source
scival
Published In
Cancer
Volume
106
Issue
2
Publish Date
2006
Start Page
277
End Page
283
DOI
10.1002/cncr.21558

Upper gastrointestinal tract.

Authors
Bendell, JC; Willett, C
MLA Citation
Bendell, JC, and Willett, C. "Upper gastrointestinal tract." Cancer treatment and research 128 (2006): 111-124.
PMID
16335015
Source
scival
Published In
Cancer Treatment and Research
Volume
128
Publish Date
2006
Start Page
111
End Page
124

Pancreatic adenocarcinoma: Clinical Practice Guidelines in Oncology.

Authors
Tempero, MA; Behrman, S; Ben-Josef, E; Benson, AB; Cameron, JL; Casper, ES; Hoffman, JP; Karl, RC; Kim, P; Koh, W-J; Kuvshinoff, BW; Melvin, WS; Muscarella, P; Sasson, AR; Shibata, S; Shrieve, DC; Talamonti, MS; Tyler, DS; Vickers, SM; Warren, RS; Willett, C; Wolff, RA; National Comprehensive Cancer Network,
MLA Citation
Tempero, MA, Behrman, S, Ben-Josef, E, Benson, AB, Cameron, JL, Casper, ES, Hoffman, JP, Karl, RC, Kim, P, Koh, W-J, Kuvshinoff, BW, Melvin, WS, Muscarella, P, Sasson, AR, Shibata, S, Shrieve, DC, Talamonti, MS, Tyler, DS, Vickers, SM, Warren, RS, Willett, C, Wolff, RA, and National Comprehensive Cancer Network, . "Pancreatic adenocarcinoma: Clinical Practice Guidelines in Oncology." J Natl Compr Canc Netw 3.5 (September 2005): 598-626.
PMID
16194453
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
3
Issue
5
Publish Date
2005
Start Page
598
End Page
626

Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience.

PURPOSE: Primary adenocarcinoma of the gallbladder is a rare malignancy. To better define the role of adjuvant radiation therapy and chemotherapy, a retrospective analysis of the outcome of patients undergoing surgery and adjuvant therapy was undertaken. METHODS AND MATERIALS: Twenty-two patients with primary and nonmetastatic gallbladder cancer were treated with radiation therapy after surgical resection. Median radiation dose was 45 Gy. Eighteen patients received concurrent 5-fluorouracil (5-FU) chemotherapy. Median follow-up was 1.7 years in all patients and 3.9 years in survivors. RESULTS: The 5-year actuarial overall survival, disease-free survival, metastases-free survival, and local-regional control of all 22 patients were 37%, 33%, 36%, and 59%, respectively. Median survival for all patients was 1.9 years. CONCLUSION: Our series suggests that an approach of radical resection followed by external-beam radiation therapy with radiosensitizing 5-FU in patients with locally advanced, nonmetastatic carcinoma of the gallbladder may improve survival. This regimen should be considered in patients with resectable gallbladder carcinoma.

Authors
Czito, BG; Hurwitz, HI; Clough, RW; Tyler, DS; Morse, MA; Clary, BM; Pappas, TN; Fernando, NH; Willett, CG
MLA Citation
Czito, BG, Hurwitz, HI, Clough, RW, Tyler, DS, Morse, MA, Clary, BM, Pappas, TN, Fernando, NH, and Willett, CG. "Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience." Int J Radiat Oncol Biol Phys 62.4 (July 15, 2005): 1030-1034.
PMID
15990005
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
62
Issue
4
Publish Date
2005
Start Page
1030
End Page
1034
DOI
10.1016/j.ijrobp.2004.12.059

Locally advanced pancreatic cancer.

Of the 32,180 patients diagnosed with pancreatic carcinoma in the United States this year, approximately 40% will present with locally advanced disease. Radiotherapeutic approaches are often employed because these patients have unresectable tumors by virtue of local invasion into the retroperitoneal vessels in the absence of clinically detectable metastases. These treatments include external-beam irradiation with and without fluorouracil-based chemotherapy, intraoperative irradiation, and, more recently, external-beam irradiation with new systemic targeted agents.

Authors
Willett, CG; Czito, BG; Bendell, JC; Ryan, DP
MLA Citation
Willett, CG, Czito, BG, Bendell, JC, and Ryan, DP. "Locally advanced pancreatic cancer." J Clin Oncol 23.20 (July 10, 2005): 4538-4544. (Review)
PMID
16002845
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
20
Publish Date
2005
Start Page
4538
End Page
4544
DOI
10.1200/JCO.2005.23.911

Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus.

PURPOSE: A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States. METHODS: A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model. RESULTS: Adenocarcinoma was diagnosed in 51% of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01; P = .001), whereas those treated with chemoradiotherapy followed by surgery (HR, 0.32; P < .0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P = .03) compared with patients treated at larger facilities. CONCLUSION: Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies.

Authors
Suntharalingam, M; Moughan, J; Coia, LR; Krasna, MJ; Kachnic, L; Haller, DG; Willet, CG; John, MJ; Minsky, BD; Owen, JB
MLA Citation
Suntharalingam, M, Moughan, J, Coia, LR, Krasna, MJ, Kachnic, L, Haller, DG, Willet, CG, John, MJ, Minsky, BD, and Owen, JB. "Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 23.10 (April 2005): 2325-2331.
PMID
15800323
Source
epmc
Published In
Journal of Clinical Oncology
Volume
23
Issue
10
Publish Date
2005
Start Page
2325
End Page
2331
DOI
10.1200/jco.2005.00.448

Four-dimensional image-based treatment planning: Target volume segmentation and dose calculation in the presence of respiratory motion.

PURPOSE: To describe approaches to four-dimensional (4D) treatment planning, including acquisition of 4D-CT scans, target delineation of spatio-temporal image data sets, 4D dose calculations, and their analysis. METHODS AND MATERIALS: The study included patients with thoracic and hepatocellular tumors. Specialized tools were developed to facilitate visualization, segmentation, and analysis of 4D-CT data: maximum intensity volume to define the extent of lung tumor motion, a 4D browser to examine and dynamically assess the 4D data sets, dose calculations, including respiratory motion, and deformable registration to combine the dose distributions at different points. RESULTS: Four-dimensional CT was used to visualize and quantitatively assess respiratory target motion. The gross target volume contours derived from light breathing scans showed significant differences compared with those extracted from 4D-CT. Evaluation of deformable registration using difference images of original and deformed anatomic maps suggested the algorithm is functionally useful. Thus, calculation of effective dose distributions, including respiratory motion, was implemented. CONCLUSION: Tools and methods to use 4D-CT data for treatment planning in the presence of respiratory motion have been developed and applied to several case studies. The process of 4D-CT-based treatment planning has been implemented, and technical barriers for its routine use have been identified.

Authors
Rietzel, E; Chen, GTY; Choi, NC; Willet, CG
MLA Citation
Rietzel, E, Chen, GTY, Choi, NC, and Willet, CG. "Four-dimensional image-based treatment planning: Target volume segmentation and dose calculation in the presence of respiratory motion." International journal of radiation oncology, biology, physics 61.5 (April 2005): 1535-1550.
PMID
15817360
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
61
Issue
5
Publish Date
2005
Start Page
1535
End Page
1550
DOI
10.1016/j.ijrobp.2004.11.037

Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer.

SUMMARY BACKGROUND DATA: To analyze the effects of a treatment program of intraoperative electron beam radiation therapy (IOERT) and external beam radiation therapy and chemotherapy on the outcome of patients with unresectable or locally advanced pancreatic cancer. METHODS: From 1978 to 2001, 150 patients with unresectable and nonmetastatic pancreatic cancer received IOERT combined with external beam radiation therapy and 5-fluorouracil-based chemotherapy for definitive treatment. RESULTS: The 1-, 2-, and 3-year actuarial survival rates of all 150 patients were 54%, 15%, and 7%, respectively. Median and mean survival rates were 13 and 17 months, respectively. Long-term survival has been observed in 8 patients. Five patients have survived beyond 5 years and 3 more between 3 and 4 years. There was a statistically significant correlation of survival to the diameter of treatment applicator (a surrogate for tumor size) used during IOERT. For 26 patients treated with a small-diameter applicator (5 cm or 6 cm), the 2- and 3-year actuarial survival rates were 27% and 17%, respectively. In contrast, none of the 11 patients treated with a 9-cm-diameter applicator survived beyond 18 months. Intermediate survival rates were seen for patients treated with a 7- or 8-cm-diameter applicator. Operative mortality was 0.6%, and postoperative and late complications were 20% and 15%, respectively. CONCLUSIONS: A treatment strategy employing IOERT has resulted in long-term survival in 8 of 150 patients with unresectable pancreatic cancer. Survival benefit was limited to patients with small tumors. Enrollment of selected patients with small tumors into innovative protocols employing this treatment approach is appropriate.

Authors
Willett, CG; Del Castillo, CF; Shih, HA; Goldberg, S; Biggs, P; Clark, JW; Lauwers, G; Ryan, DP; Zhu, AX; Warshaw, AL
MLA Citation
Willett, CG, Del Castillo, CF, Shih, HA, Goldberg, S, Biggs, P, Clark, JW, Lauwers, G, Ryan, DP, Zhu, AX, and Warshaw, AL. "Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer." Ann Surg 241.2 (February 2005): 295-299.
PMID
15650640
Source
pubmed
Published In
Annals of Surgery
Volume
241
Issue
2
Publish Date
2005
Start Page
295
End Page
299

The Chadha/Kuvshinoff/Javle article reviewed

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "The Chadha/Kuvshinoff/Javle article reviewed." ONCOLOGY 19.9 (2005): 1231-1232.
Source
scival
Published In
Oncology
Volume
19
Issue
9
Publish Date
2005
Start Page
1231
End Page
1232

The Pisters/Wolff/Crane et al article reviewed

Authors
Czito, B; Tyler, D; Willett, C
MLA Citation
Czito, B, Tyler, D, and Willett, C. "The Pisters/Wolff/Crane et al article reviewed." ONCOLOGY 19.3 (2005): 412+415-412+416.
Source
scival
Published In
Oncology
Volume
19
Issue
3
Publish Date
2005
Start Page
412+415
End Page
412+416

Erratum: The correlation between internal and external markers for abdominal tumors: Implications for respiratory gating (International Journal of Radiation Oncology Biology Physics (2005) 61 (1551-1558)

Authors
Gierga, DP; Brewer, J; Sharp, GC; Betke, M; Willett, CG; Chen, GTY
MLA Citation
Gierga, DP, Brewer, J, Sharp, GC, Betke, M, Willett, CG, and Chen, GTY. "Erratum: The correlation between internal and external markers for abdominal tumors: Implications for respiratory gating (International Journal of Radiation Oncology Biology Physics (2005) 61 (1551-1558)." International Journal of Radiation Oncology Biology Physics 62.4 (2005): 1257--.
Source
scival
Published In
International Journal of Radiation Oncology Biology Physics
Volume
62
Issue
4
Publish Date
2005
Start Page
1257-
DOI
10.1016/j.ijrobp.2005.06.001

Case 20-2005: A 58-year-old man with locally advanced pancreatic cancer

Authors
Ryan, DP; Castillo, CF-D; Willett, CG; Brugge, WR; Sahani, D; Brachtel, EF
MLA Citation
Ryan, DP, Castillo, CF-D, Willett, CG, Brugge, WR, Sahani, D, and Brachtel, EF. "Case 20-2005: A 58-year-old man with locally advanced pancreatic cancer." New England Journal of Medicine 352.26 (2005): 2734-2741.
PMID
15987923
Source
scival
Published In
New England Journal of Medicine
Volume
352
Issue
26
Publish Date
2005
Start Page
2734
End Page
2741
DOI
10.1056/NEJMcpc059014

A challenge to the therapeutic nihilism of ESPAC-1

Authors
Koshy, MC; Landry, JC; Cavanaugh, SX; Fuller, CD; Willett, CG; Abrams, RA; Hoffman, JP; Jr, CRT
MLA Citation
Koshy, MC, Landry, JC, Cavanaugh, SX, Fuller, CD, Willett, CG, Abrams, RA, Hoffman, JP, and Jr, CRT. "A challenge to the therapeutic nihilism of ESPAC-1." International Journal of Radiation Oncology Biology Physics 61.4 (2005): 965-966.
PMID
15752874
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
61
Issue
4
Publish Date
2005
Start Page
965
End Page
966
DOI
10.1016/j.ijrobp.2004.11.018

The correlation between internal and external markers for abdominal tumors: Implications for respiratory gating

Purpose: The correlation of the respiratory motion of external patient markers and abdominal tumors was examined. Data of this type are important for image-guided therapy techniques, such as respiratory gating, that monitor the movement of external fiducials. Methods and Materials: Fluoroscopy sessions for 4 patients with internal, radiopaque tumor fiducial clips were analyzed by computer vision techniques. The motion of the internal clips and the external markers placed on the patient's abdominal skin surface were quantified and correlated. Results: In general, the motion of the tumor and external markers were well correlated. The maximum amount of peak-to-peak craniocaudal tumor motion was 2.5 cm. The ratio of tumor motion to external-marker motion ranged from 0.85 to 7.1. The variation in tumor position for a given external-marker position ranged from 2 to 9 mm. The period of the breathing cycle ranged from 2.7 to 4.5 seconds, and the frequency patterns for both the tumor and the external markers were similar. Conclusions: Although tumor motion generally correlated well with external fiducial marker motion, relatively large underlying tumor motion can occur compared with external-marker motion and variations in the tumor position for a given marker position. Treatment margins should be determined on the basis of a detailed understanding of tumor motion, as opposed to relying only on external-marker information. © 2005 Elsevier Inc.

Authors
Gierga, DP; Brewer, J; Sharp, GC; Betke, M; Willett, CG; Chen, GTY
MLA Citation
Gierga, DP, Brewer, J, Sharp, GC, Betke, M, Willett, CG, and Chen, GTY. "The correlation between internal and external markers for abdominal tumors: Implications for respiratory gating." International Journal of Radiation Oncology Biology Physics 61.5 (2005): 1551-1558.
PMID
15817361
Source
scival
Published In
International Journal of Radiation Oncology Biology Physics
Volume
61
Issue
5
Publish Date
2005
Start Page
1551
End Page
1558
DOI
10.1016/j.ijrobp.2004.12.013

Combined modality treatment for rectal cancer

Significant gains have been achieved in the integration of radiation therapy (RT) and chemotherapy with surgery in the management of patients with localized rectal cancer. Treatment combinations of RT and chemotherapy with surgery have evolved to neoadjuvant approaches of these modalities to enhance sphincter preservation, tumor control, and reduction of acute and late treatment-related morbidity. Although 5-fluorouracil (5-FU)-based chemotherapy in combination with RT remains the standard adjuvant therapy for rectal cancer, the integration of novel chemotherapeutic agents and biologic modulators is being actively investigated. © 2005 Elsevier Inc. All rights reserved.

Authors
Zhu, AX; Willett, CG
MLA Citation
Zhu, AX, and Willett, CG. "Combined modality treatment for rectal cancer." Seminars in Oncology 32.1 SPEC. ISS. (2005): 103-112.
PMID
15726512
Source
scival
Published In
Seminars in Oncology
Volume
32
Issue
1 SPEC. ISS.
Publish Date
2005
Start Page
103
End Page
112
DOI
10.1053/j.seminoncol.2004.09.032

Assessing tumor perfusion and treatment response in rectal cancer with multisection CT: Initial observations

PURPOSE: To use first-pass perfusion computed tomography (CT) to prospectively investigate tumor vascularity in rectal cancer and to determine whether any of the perfusion parameters would predict tumor response to chemotherapy and radiation therapy. MATERIALS AND METHODS: The institutional review board approved this study, and informed prior consent was obtained from participants. Perfusion CT of rectal cancer was performed with four-section multi-detector row CT in 15 patients (13 men, two women; mean age, 62.1 years; age range, 46-84 years). Five patients with prostate cancer served as controls. All patients with rectal cancer underwent 6-8 weeks of chemotherapy and radiation therapy followed by surgery. In nine patients, perfusion CT was repeated after completion of chemotherapy and radiation therapy. Contrast medium-enhanced dynamic CT was performed with a static table position for 45 seconds, and the data were analyzed by using commercial software to calculate tissue blood flow (BF), blood volume, mean transit time (MTT), and vascular permeability-surface area product. Perfusion parameters of normal rectum and tumor were compared. Perfusion parameters before and after chemotherapy and radiation therapy were compared. A tumor was considered to have responded if its stage at pathologic analysis indicated regression compared with the preoperative stage. Baseline perfusion values were compared between responders and nonresponders. Statistical analysis was performed with the Student t test. RESULTS: Rectal cancer showed higher BF and shorter MTT compared with those of normal rectum (P ≤ .05). After chemotherapy and radiation therapy, tumors showed significant reduction in BF and increase in MTT (P ≤ .05). There was a significant difference in baseline BF and MTT values between responders and nonresponders (P ≤ .05). Tumors in three patients with high initial BF and short MTT showed poor response. CONCLUSION: Perfusion CT of rectal cancer can enable assessment of tumor vascularity and perfusion changes that result from chemotherapy and radiation therapy. In this small patient sample, tumors with initial high BF and short MTT values tended to respond poorly to chemotherapy and radiation therapy. © RSNA, 2005.

Authors
Sahani, DV; Kalva, SP; Hamberg, LM; Hahn, PF; Willett, CG; Saini, S; Mueller, PR; Lee, T-Y
MLA Citation
Sahani, DV, Kalva, SP, Hamberg, LM, Hahn, PF, Willett, CG, Saini, S, Mueller, PR, and Lee, T-Y. "Assessing tumor perfusion and treatment response in rectal cancer with multisection CT: Initial observations." Radiology 234.3 (2005): 785-792.
PMID
15734934
Source
scival
Published In
Radiology
Volume
234
Issue
3
Publish Date
2005
Start Page
785
End Page
792
DOI
10.1148/radiol.2343040286

Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: Continued experience of a phase I trial in rectal cancer patients [18]

Authors
Willett, CG; Boucher, Y; Duda, DG; Tomaso, ED; Munn, LL; Tong, RT; Kozin, SV; Petit, L; Jain, RK; Chung, DC; Sahani, DV; Kalva, SP; Cohen, KS; Scadden, DT; Fischman, AJ; Clark, JW; Ryan, DP; Zhu, AX; Blaszkowsky, LS; Shellito, PC; Mino-Kenudson, M; Lauwers, GY
MLA Citation
Willett, CG, Boucher, Y, Duda, DG, Tomaso, ED, Munn, LL, Tong, RT, Kozin, SV, Petit, L, Jain, RK, Chung, DC, Sahani, DV, Kalva, SP, Cohen, KS, Scadden, DT, Fischman, AJ, Clark, JW, Ryan, DP, Zhu, AX, Blaszkowsky, LS, Shellito, PC, Mino-Kenudson, M, and Lauwers, GY. "Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: Continued experience of a phase I trial in rectal cancer patients [18]." Journal of Clinical Oncology 23.31 (2005): 8136-8139.
PMID
16258121
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
31
Publish Date
2005
Start Page
8136
End Page
8139
DOI
10.1200/JCO.2005.02.5635

Patients undergoing treatment for pancreatic adenocarcinoma can mount an effective immune response to vaccinations

Background: Immunotherapy has been proposed as a novel treatment for pancreatic cancer. However, patients with pancreatic cancer have been observed to have depressed immune responses, suggesting that immunotherapy might have limited utility in this group of patients. We sought to determine whether patients undergoing postresection or primary medical treatment for pancreatic adenocarcinoma were immunocompetent. Methods: We enrolled patients with pancreatic adenocarcinoma scheduled for postresection or primary chemotherapy and/or radiation therapy. At the initiation of therapy, the patients had an anergy panel placed and baseline blood work performed. During the first week of treatment, patients received tetanus toxoid (TT), Haemophilus influenzae and Pneumococcus vaccines. Twelve weeks after vaccine administration, IgG titers against the 3 administered vaccines were done, and lymphocyte proliferation assays in response to TT were performed. Results: Eighteen patients were originally enrolled, and 14 patients completed all elements of the trial. Anergy panel responses were obtained for 15 patients who comprised the final study group; both pre-and postvaccination data were available for 14 patients. Nine of 15 patients demonstrated at least a 10-mm induration in response to mumps or Candida antigen (60% response rate, 95% confidence interval (CI) 32-84%). Thirteen of 14 patients demonstrated a ≥3-fold increase in IgG against one or more vaccines (93% response rate, 95% CI 66-100%). Nine of 14 patients (64% response rate, 95% CI 35-87%) demonstrated at least a 3-fold rise of lymphocyte proliferation against TT. Conclusions: Patients with pancreatic cancer were capable of mounting effective cellular and humoral responses to standard vaccines. These data suggest that immunotherapy for pancreatic cancer may be feasible and merits further investigation. Copyright © 2005 S. Karger AG, Basel and IAP.

Authors
Tseng, JF; Willett, CG; Castillo, CF-D; Ryan, DP; Clark, JW; Zhu, AX; Rattner, DW; Winkelmann, JL; Warshaw, AL
MLA Citation
Tseng, JF, Willett, CG, Castillo, CF-D, Ryan, DP, Clark, JW, Zhu, AX, Rattner, DW, Winkelmann, JL, and Warshaw, AL. "Patients undergoing treatment for pancreatic adenocarcinoma can mount an effective immune response to vaccinations." Pancreatology 5.1 (2005): 67-74.
PMID
15775701
Source
scival
Published In
Pancreatology
Volume
5
Issue
1
Publish Date
2005
Start Page
67
End Page
74
DOI
10.1159/000084492

Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114.

PURPOSE: To study the relationship between body mass index (BMI) and rates of sphincter-preserving operations, overall survival, cancer recurrence, and treatment-related toxicities in patients with rectal cancer. PATIENTS AND METHODS: We evaluated a nested cohort of 1,688 patients with stage II and III rectal cancer participating in a randomized trial of postoperative fluorouracil-based chemotherapy and radiation therapy. RESULTS: Obese patients were more likely to undergo an abdominoperineal resection (APR) than normal-weight patients (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing adiposity in men was a strong predictor of having an APR (P <.0001). Obese men with rectal cancer were also more likely than normal-weight men to have a local recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity was not predictive of cancer recurrence in women, nor was BMI predictive of overall mortality in either men or women. Underweight patients had an increased risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight patients but no increase in cancer recurrences. Among all study participants, obese patients had a significantly lower rate of grade 3 to 4 leukopenia, neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity when compared with normal-weight individuals. CONCLUSION: Increasing BMI in male patients with rectal cancer is associated with a decreased likelihood of sphincter preservation and a higher chance of local recurrence. For both men and women, overweight and obese patients experience less toxicity associated with adjuvant chemoradiotherapy, suggesting that actual body weight dosing of fluorouracil for obese patients is justified.

Authors
Meyerhardt, JA; Tepper, JE; Niedzwiecki, D; Hollis, DR; McCollum, AD; Brady, D; O'Connell, MJ; Mayer, RJ; Cummings, B; Willett, C; Macdonald, JS; Benson, AB; Fuchs, CS
MLA Citation
Meyerhardt, JA, Tepper, JE, Niedzwiecki, D, Hollis, DR, McCollum, AD, Brady, D, O'Connell, MJ, Mayer, RJ, Cummings, B, Willett, C, Macdonald, JS, Benson, AB, and Fuchs, CS. "Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114." J Clin Oncol 22.4 (February 15, 2004): 648-657.
PMID
14966087
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
4
Publish Date
2004
Start Page
648
End Page
657
DOI
10.1200/JCO.2004.07.121

Impact of hospital procedure volume on surgical operation and long-term outcomes in high-risk curatively resected rectal cancer: findings from the Intergroup 0114 Study.

PURPOSE: Prior studies have demonstrated superior outcomes after a curative surgical resection of rectal cancer at hospitals where the volume of such surgeries is high. However, because these studies often lack detailed information on tumor and treatment characteristics as well as cancer recurrence, the true nature of this relation remains uncertain. PATIENTS AND METHODS: We studied a nested cohort of 1,330 patients with stage II and stage III rectal cancer participating in a multicenter, adjuvant chemoradiotherapy trial. We analyzed differences in rates of sphincter-preserving operations, overall survival, and cancer recurrence by hospital surgical volume. RESULTS: We observed a significant difference in the rates of abdominoperineal resections across tertiles of hospital procedure volume (46.3% for patients resected at low-volume, 41.3% at medium-volume, and 31.8% at high-volume hospitals; P <.0001), even after adjustment for tumor distance from the anal verge. However, this higher rate of sphincter-sparing operations at high-volume centers was not accompanied by any increase in recurrence rates. Hospital surgical volume did not predict overall, disease-free, recurrence-free, or local recurrence-free survival. However, among patients who did not complete the planned adjuvant chemoradiotherapy (270 patients), those who underwent surgery at low-volume hospitals had a significant increase in cancer recurrence (adjusted hazard ratio, 1.94; 95% CI, 1.01 to 3.72; P =.04 for the trend) and a nonsignificant trend toward increased overall mortality (P =.08) and local recurrence (P =.10). In contrast, no significant volume-outcome relation was noted among patients who did complete postoperative therapy. CONCLUSION: Using prospectively recorded data, we found that hospital surgical volume had no significant effect on rectal cancer recurrence or survival when patients completed standard adjuvant therapy. Sphincter-preserving surgery was more commonly performed at high-volume centers.

Authors
Meyerhardt, JA; Tepper, JE; Niedzwiecki, D; Hollis, DR; Schrag, D; Ayanian, JZ; O'Connell, MJ; Weeks, JC; Mayer, RJ; Willett, CG; MacDonald, JS; Benson, AB; Fuchs, CS
MLA Citation
Meyerhardt, JA, Tepper, JE, Niedzwiecki, D, Hollis, DR, Schrag, D, Ayanian, JZ, O'Connell, MJ, Weeks, JC, Mayer, RJ, Willett, CG, MacDonald, JS, Benson, AB, and Fuchs, CS. "Impact of hospital procedure volume on surgical operation and long-term outcomes in high-risk curatively resected rectal cancer: findings from the Intergroup 0114 Study." J Clin Oncol 22.1 (January 1, 2004): 166-174.
PMID
14701779
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
1
Publish Date
2004
Start Page
166
End Page
174
DOI
10.1200/JCO.2004.04.172

Moving targets: Detection and tracking of internal organ motion for treatment planning and patient set-up

Background and Purpose: Clinical target volumes of the thorax and abdomen are typically expanded to account for inter- and intrafractional organ motion. Usually, such expansions are based on clinical experience and planar observations of target motion during simulation. More precise, 4- dimensional motion margins for a specific patient may improve dose coverage of mobile targets and yet limit unnecessarily large field expansions. We are studying approaches to targeting moving tumors throughout the entire treatment process, from treatment planning to beam delivery. Material and Methods: Radio-opaque markers were implanted under CT guidance in the liver at the gross tumor periphery. Organ motion during light respiration was volumetrically imaged by 4D Computed Tomography. Marker motion was also acquired by fluoroscopy and compared with 4DCT data. During treatment, daily diagnostic x-ray images were captured at end-exhale and -inhale for patient set-up and target localization. Results: Based on the time-resolved CT data, target volumes can be designed to account for respiratory motion during treatment. Motion of the tumor as derived from 4DCT was consistent with fluoroscopic motion analysis. Radiographs acquired in the treatment room enabled millimeter-level patient set-up and assessment of target position relative to bony anatomy. Daily positional variations between bony anatomy and implanted markers were observed. Conclusions: Image guided therapy, based on 4DCT imaging, fluoroscopic imaging studies, and daily gated diagonstic energy set-up radiographs is being developed to improve beam delivery precision. Monitoring internal target motion throughout the entire treatment process will ensure adequate dose coverage of the target while sparing the maximum healthy tissue.

Authors
Rietzel, E; Rosenthal, SJ; Gierga, DP; Willett, CG; Chen, GTY
MLA Citation
Rietzel, E, Rosenthal, SJ, Gierga, DP, Willett, CG, and Chen, GTY. "Moving targets: Detection and tracking of internal organ motion for treatment planning and patient set-up." Radiotherapy and Oncology 73.SUPPL. 2 (2004): S68-S72.
PMID
15971313
Source
scival
Published In
Radiotherapy and Oncology
Volume
73
Issue
SUPPL. 2
Publish Date
2004
Start Page
S68
End Page
S72

Adjuvant therapy for pancreatic cancer: An evolving paradigm

Pancreatic cancer is the fourth leading cause of death in men and fifth in women in the United States. The median survival is 8 to 12 months for patients with locally advanced and unresectable disease and only 3 to 6 months for those with metastatic disease at presentation. Surgical resection offers the only potentially curative treatment. However, only 15% to 20% of patients present with tumors amenable to resection at initial diagnosis. Even for those who undergo resection, the prognosis remains poor. The 5-year survival following pancreaticoduodenectomy is only about 25% to 30% for node-negative tumors and 10% for node-positive tumors. Because of the dismal outcome for patients with resectable pancreatic cancer, adjuvant therapy has been administered in an attempt to improve the local control and overall survival. This review highlights historic and current perspectives of adjuvant therapy in resected pancreatic cancer.

Authors
Zhu, AX; Clark, JW; Willett, CG
MLA Citation
Zhu, AX, Clark, JW, and Willett, CG. "Adjuvant therapy for pancreatic cancer: An evolving paradigm." Surgical Oncology Clinics of North America 13.4 (2004): 605-620.
PMID
15350937
Source
scival
Published In
Surgical Oncology Clinics of North America
Volume
13
Issue
4
Publish Date
2004
Start Page
605
End Page
620
DOI
10.1016/j.soc.2004.06.003

Case 18-2004: A 61-year-old man with rectal bleeding and a 2-cm mass in the rectum

Authors
Shellito, PC; Clark, JW; Willett, CG; Caplan, AP
MLA Citation
Shellito, PC, Clark, JW, Willett, CG, and Caplan, AP. "Case 18-2004: A 61-year-old man with rectal bleeding and a 2-cm mass in the rectum." New England Journal of Medicine 350.24 (2004): 2500-2509.
PMID
15190143
Source
scival
Published In
New England Journal of Medicine
Volume
350
Issue
24
Publish Date
2004
Start Page
2500
End Page
2509
DOI
10.1056/NEJMcpc049007

PET concerns in bevacizumab treatment (multiple letters)

Authors
Goessl, C; Grozdanovic, Z; Willett, CG; Duda, D; Fischman, A; Jain, RK
MLA Citation
Goessl, C, Grozdanovic, Z, Willett, CG, Duda, D, Fischman, A, and Jain, RK. "PET concerns in bevacizumab treatment (multiple letters)." Nature Medicine 10.6 (2004): 561--.
PMID
15170192
Source
scival
Published In
Nature Medicine
Volume
10
Issue
6
Publish Date
2004
Start Page
561-

Erratum: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer (Nature Medicine (2004) 10 (145-147))

Authors
Willett, CG; Boucher, Y; Tomaso, ED; Duda, DG; Munn, LL; Tong, RT; Chung, DC; Sahani, DV; Kalva, SP; Kozin, SV; Mino, M; Cohen, KS; Scadden, DT; Hartford, AC; Fischman, AJ; Clark, JW; Ryan, DP; Zhu, AX; Blaszkowsky, LS; Chen, HX; Shellito, PC; Lauwers, GY; Jain, RK
MLA Citation
Willett, CG, Boucher, Y, Tomaso, ED, Duda, DG, Munn, LL, Tong, RT, Chung, DC, Sahani, DV, Kalva, SP, Kozin, SV, Mino, M, Cohen, KS, Scadden, DT, Hartford, AC, Fischman, AJ, Clark, JW, Ryan, DP, Zhu, AX, Blaszkowsky, LS, Chen, HX, Shellito, PC, Lauwers, GY, and Jain, RK. "Erratum: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer (Nature Medicine (2004) 10 (145-147))." Nature Medicine 10.6 (2004): 649--.
Source
scival
Published In
Nature Medicine
Volume
10
Issue
6
Publish Date
2004
Start Page
649-

Quantification of respiration-induced abdominal tumor motion and its impact on IMRT dose distributions

Purpose The treatment of moving targets with intensity-modulated radiotherapy may introduce errors in dose delivery. The motion of tumors in the abdomen was studied using quantitative fluoroscopic analysis, and the effect on dose delivery to the target was studied. Methods and materials Fluoroscopy sessions for 7 patients with pancreas or liver tumors and fiducial clips were recorded, converted to digital format, and analyzed to quantify the characteristics of tumor motion. Intensity-modulated radiotherapy plans were generated for 3 patients (a total of five plans), and the dose-volume histograms for the target volume were compared between plans with and without tumor motion. Results The average magnitude of the peak-to-peak motion for the 7 patients in the craniocaudal and AP directions was 7.4 mm and 3.8 mm, respectively. The clip motion varied widely, because the maximal clip excursions were about 47% greater than the average clip excursions for each patient. The inclusion of tumor motion did not lead to a significant degradation in the target dose-volume histogram for four of five treatment plans studied. Conclusion The amount of tumor motion for most patients in this study was not large but could, in some instances, significantly degrade the planned target dose-volume histogram. For some patients, therefore, motion mitigation or intervention during treatment may be necessary. © 2004 Elsevier Inc.

Authors
Gierga, DP; Chen, GTY; Kung, JH; Betke, M; Lombardi, J; Willett, CG
MLA Citation
Gierga, DP, Chen, GTY, Kung, JH, Betke, M, Lombardi, J, and Willett, CG. "Quantification of respiration-induced abdominal tumor motion and its impact on IMRT dose distributions." International Journal of Radiation Oncology Biology Physics 58.5 (2004): 1584-1595.
PMID
15050340
Source
scival
Published In
International Journal of Radiation Oncology Biology Physics
Volume
58
Issue
5
Publish Date
2004
Start Page
1584
End Page
1595
DOI
10.1016/j.ijrobp.2003.09.077

Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer

The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors.

Authors
Willett, CG; Boucher, Y; Tomaso, ED; Duda, DG; Munn, LL; Tong, RT; Chung, DC; Sahani, DV; Kalva, SP; Kozin, SV; Mino, M; Cohen, KS; Scadden, DT; Hartford, AC; Fischman, AJ; Clark, JW; Ryan, DP; Zhu, AX; Blaszkowsky, LS; Chen, HX; Shellito, PC; Lauwers, GY; Jain, RK
MLA Citation
Willett, CG, Boucher, Y, Tomaso, ED, Duda, DG, Munn, LL, Tong, RT, Chung, DC, Sahani, DV, Kalva, SP, Kozin, SV, Mino, M, Cohen, KS, Scadden, DT, Hartford, AC, Fischman, AJ, Clark, JW, Ryan, DP, Zhu, AX, Blaszkowsky, LS, Chen, HX, Shellito, PC, Lauwers, GY, and Jain, RK. "Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer." Nature Medicine 10.2 (2004): 145-147.
PMID
14745444
Source
scival
Published In
Nature Medicine
Volume
10
Issue
2
Publish Date
2004
Start Page
145
End Page
147
DOI
10.1038/nm988

Palliative treatment of rectal cancer: Is radiotherapy alone a good option?

Authors
Willett, CG; Gunderson, LL
MLA Citation
Willett, CG, and Gunderson, LL. "Palliative treatment of rectal cancer: Is radiotherapy alone a good option?." Journal of Gastrointestinal Surgery 8.3 (2004): 277-279.
PMID
15019923
Source
scival
Published In
Journal of Gastrointestinal Surgery
Volume
8
Issue
3
Publish Date
2004
Start Page
277
End Page
279
DOI
10.1016/j.gassur.2003.11.015

Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: A pooled analysis

Purpose: To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies. Patients and Methods: Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) ± semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU ± leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%. Results: Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P < .001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT. Conclusion: Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement. © 2004 by American Society of Clinical Oncology.

Authors
Gunderson, LL; Sargent, DJ; Tepper, JE; Wolmark, N; O'Connell, MJ; Begovic, M; Allmer, C; Colangelo, L; Smalley, SR; Haller, DG; Martenson, JA; Mayer, RJ; Rich, TA; Ajani, JA; MacDonald, JS; Willett, CG; Goldberg, RM
MLA Citation
Gunderson, LL, Sargent, DJ, Tepper, JE, Wolmark, N, O'Connell, MJ, Begovic, M, Allmer, C, Colangelo, L, Smalley, SR, Haller, DG, Martenson, JA, Mayer, RJ, Rich, TA, Ajani, JA, MacDonald, JS, Willett, CG, and Goldberg, RM. "Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: A pooled analysis." Journal of Clinical Oncology 22.10 (2004): 1785-1796.
PMID
15067027
Source
scival
Published In
Journal of Clinical Oncology
Volume
22
Issue
10
Publish Date
2004
Start Page
1785
End Page
1796
DOI
10.1200/JCO.2004.08.173

Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: Results of intergroup protocol 0130

Purpose: Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients. Patients and Methods: Patients with resected colon cancer with tumor adherence or invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending or descending colon were randomly assigned to receive fluorouracil and levamisole therapy with or without radiation therapy. Patients who received chemotherapy and radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions beginning 28 days after starting chemotherapy. Patient enrollment was terminated because of slow accrual after 222 patients enrolled (original goal was 700 patients); 187 patients were assessable. Results: Overall 5-year survival was 62% for chemotherapy patients and 58% for chemoRT patients (P > .50); 5-year disease-free survival was 51 % for both groups (P > .50). Toxicity (≥ grade 3) occurred in 42% of chemotherapy patients and 54% of chemoRT patients (P = .04). Leukopenia (≥ grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT patients (P = .02). No significant difference in nonhematologic toxicity (≥ grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P= .26). Conclusion: Patients who received chemotherapy or chemoRT had similar overall survival and disease-free survival. Toxicity was higher among chemoRT patients. These results must be interpreted with caution because of the high number of ineligible patients and the limited power of the study to detect potentially meaningful differences. © 2004 by American Society of Clinical Oncology.

Authors
Jr, JAM; Willett, CG; Sargent, DJ; Mailliard, JA; Donohue, JH; Gunderson, LL; Jr, CRT; Fisher, B; III, ABB; Myerson, R; Goldberg, RM
MLA Citation
Jr, JAM, Willett, CG, Sargent, DJ, Mailliard, JA, Donohue, JH, Gunderson, LL, Jr, CRT, Fisher, B, III, ABB, Myerson, R, and Goldberg, RM. "Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: Results of intergroup protocol 0130." Journal of Clinical Oncology 22.16 (2004): 3277-3283.
PMID
15249584
Source
scival
Published In
Journal of Clinical Oncology
Volume
22
Issue
16
Publish Date
2004
Start Page
3277
End Page
3283
DOI
10.1200/JCO.2004.01.029

Intraoperative radiation therapy in the management of gynecologic and genitourinary malignancies.

Women with locally advanced primary or recurrent gynecologic malignancies have a poor prognosis. The doses of external radiation necessary to treat gross or microscopic recurrent disease in patients previously irradiated exceed the doses tolerated by normal tissue [1,3-5]. IORT has been added to the treatment armamentarium in this group of patients to maximize local control and minimize the radiation exposure to dose-limiting surrounding structures. In addition, IORT may improve the long-term local control and the overall survival rates in women with pelvic sidewall or para-aortic nodal recurrence [1,4,5]. The most encouraging results are seen in cases of microscopic residual disease following surgical debulking [4,6]. In gynecologic malignancies, IORT has served to reiterate the importance of optimal surgical resection. Higher 5-year disease-free and overall survival rates have been documented in women who have microscopic residual disease, compared with those who have gross residual disease [1,3-6]. IORT in the management of GU malignancies has not been used extensively. In RCC, where surgery alone often results in suboptimal treatment results, IORT seems to be well tolerated and controls local disease [2,27,29,30]. Because of the chemoresistant nature of RCC, IORT may play an important role in the future in the management of locally advanced and recurrent RCC. In bladder cancer, IORT had been used in combination with chemotherapy and EBRT, as part of bladder-sparing protocols. The data suggest that IORT in this patient population is also well tolerated, and may become more widely used as less radical surgical procedures gain clinical importance. IORT in the treatment of prostate and testicular cancers has not been used frequently, given the highly efficacious treatment modalities currently available to treat these malignancies. A review of institutional experiences with IORT may allow the establishment of guidelines for patient selection. These criteria, in turn, may be useful in the design of clinical trials. The construction, execution, and evaluation of clinical trials are mandatory to adequately assess the role of IORT in the treatment of patients with gynecologic and GU malignancies.

Authors
del Carmen, MG; Eisner, B; Willet, CG; Fuller, AF
MLA Citation
del Carmen, MG, Eisner, B, Willet, CG, and Fuller, AF. "Intraoperative radiation therapy in the management of gynecologic and genitourinary malignancies." Surgical oncology clinics of North America 12.4 (October 2003): 1031-1042. (Review)
PMID
14989131
Source
epmc
Published In
Surgical Oncology Clinics of North America
Volume
12
Issue
4
Publish Date
2003
Start Page
1031
End Page
1042
DOI
10.1016/s1055-3207(03)00086-3

Clinical physics, applicator choice, technique, and equipment for electron intraoperative radiation therapy

IORT has been a widely used modality since the 1980s. The initial euphoria experienced at the beginning, however, has subsided, with the result that most centers still practicing IORT are academic institutions. The reason for the reduction in IORT performed at community hospitals is partly related to the method of treatment-namely, transporting the patient from the OR to the radiation therapy department. The advent of mobile linear accelerators, which require little or no shielding and can therefore be used in most OR rooms, is likely to reignite interest in this modality. There are currently six new centers in the United States that practice IORT with a mobile linear accelerator and more than that in Europe.

Authors
Biggs, PJ; Noyes, RD; Willett, CG
MLA Citation
Biggs, PJ, Noyes, RD, and Willett, CG. "Clinical physics, applicator choice, technique, and equipment for electron intraoperative radiation therapy." Surgical Oncology Clinics of North America 12.4 (2003): 899-924.
PMID
14989123
Source
scival
Published In
Surgical Oncology Clinics of North America
Volume
12
Issue
4
Publish Date
2003
Start Page
899
End Page
924
DOI
10.1016/S1055-3207(03)00101-7

Update on combined-modality treatment options for pancreatic cancer.

Cancer of the pancreas remains a formidable challenge in oncology. This malignancy ranks as the fourth leading cause of cancer death in the United States in 2003, with an estimated 30,700 new cases to be diagnosed and 30,000 deaths. Although gains have been achieved in the clinical management of these patients, this malignancy is rarely curable. Long-term survival is limited to patients undergoing resection. For patients with localized but unresectable malignancy, radiation therapy combined with fluorouracil, gemcitabine (Gemzar), or paclitaxel has shown modest improvements in survival and symptom palliation. However, there has been significant progress in the diagnostic evaluation of pancreatic cancer patients, which has aided clinicians in caring for these patients and in selecting therapies. The use of computed tomography, endoscopic ultrasonography, and laparoscopy techniques will be discussed. Newer techniques of radiation therapy, such as intraoperative electron-beam radiation therapy and three-dimensional conformal radiation therapy, with the integration of new biologically targeted agents may provide new avenues of research and progress in this disease.

Authors
Willett, CG; Clark, JW
MLA Citation
Willett, CG, and Clark, JW. "Update on combined-modality treatment options for pancreatic cancer." Oncology (Williston Park, N.Y.) 17.12 Suppl 13 (2003): 29-36.
PMID
14723004
Source
scival
Published In
Oncology (Williston Park, N.Y.)
Volume
17
Issue
12 Suppl 13
Publish Date
2003
Start Page
29
End Page
36

Chemotherapeutic and Biologic Agents as Radiosensitizers in Rectal Cancer

Over the past 25 years, important advances have been made in the management of patients with resectable rectal cancer. Clinical studies have shown the efficacy of combined chemoradiation therapy in enhancing resectability and sphincter preservation rates, decreasing local recurrence, and improving survival of patients with rectal cancer. Although 5-fluorouracil (5-FU) remains the standard chemotherapeutic agent used concurrently with radiation therapy, newer chemotherapeutic agents including capecitabine, irinotecan, and oxaliplatin have also been studied as radiosensitizers in this setting. Novel targeted biologic agents including celecoxib and bevacizumab are being explored in combination with standard chemotherapy and radiation therapy. In this review, we will discuss the mechanism of action and the key clinical studies of each agent as a radiosensitizer. © 2003 Elsevier Inc. All rights reserved.

Authors
Zhu, AX; Willett, CG
MLA Citation
Zhu, AX, and Willett, CG. "Chemotherapeutic and Biologic Agents as Radiosensitizers in Rectal Cancer." Seminars in Radiation Oncology 13.4 (2003): 454-468.
PMID
14586834
Source
scival
Published In
Seminars in Radiation Oncology
Volume
13
Issue
4
Publish Date
2003
Start Page
454
End Page
468
DOI
10.1016/S1053-4296(03)00048-1

Adjuvant Therapy of Rectal Cancer: Introduction

Authors
Willett, CG
MLA Citation
Willett, CG. "Adjuvant Therapy of Rectal Cancer: Introduction." Seminars in Radiation Oncology 13.4 (2003): 381--.
Source
scival
Published In
Seminars in Radiation Oncology
Volume
13
Issue
4
Publish Date
2003
Start Page
381-
DOI
10.1016/S1053-4296(03)00046-8

Advances in combined radiation therapy for the management of rectal cancer

Significant advances have been made in the use of adjuvant radiation for patients with localized rectal cancer. Recent progress in adjuvant postoperative radiation regimens relates to the integration of systemic therapy into radiation, as well as redefining the techniques and sequences for both modalities. The adjuvant radiation management approach in both North America and Europe has been shifting towards preoperative adjuvant therapy to promote sphincter-preserving surgery and to decrease acute and late toxicity. Although 5-fluorouracil-based chemotherapy in combination with radiation remains the standard adjuvant therapy for rectal cancer, the integration of novel chemotherapeutic agents and biologic modulators remains an active area of investigation.

Authors
Kachnic, LA; Shih, HA; Willett, CG
MLA Citation
Kachnic, LA, Shih, HA, and Willett, CG. "Advances in combined radiation therapy for the management of rectal cancer." Expert Review of Anticancer Therapy 3.4 (2003): 471-483.
PMID
12934659
Source
scival
Published In
Expert Review of Anticancer Therapy
Volume
3
Issue
4
Publish Date
2003
Start Page
471
End Page
483

Combined modality therapy for rectal and colon cancer

Combined modality therapy (CMT) with radiation therapy and chemotherapy plays an important role in the management of rectal cancer. Postoperatively, pelvic irradiation and 5-fluorouracil-based chemotherapy have been used to improve local control and survival for high-risk patients after local excision, as well as for patients undergoing abdominoperineal or low anterior resection. For patients treated preoperatively, CMT can also be used to facilitate sphincter-sparing surgery for distal rectal tumors. Preoperative CMT in conjunction with surgery and intraoperative radiation therapy has been useful for patients with locally advanced and recurrent rectal cancer as well. While chemotherapy has benefit for patients with stage III colon cancer above the peritoneal reflection, the role of CMT is less well defined. Retrospective reviews suggest improved local control and survival in subgroups of patients treated with postoperative radiation therapy and chemotherapy. Active areas of investigation in CMT for colorectal cancer include the integration of biologic predictors, radiation modulators, and novel systemic agents. © 2003 Elsevier Inc. All rights reserved.

Authors
Chawla, AK; Kachnic, LA; Clark, JW; Willett, CG
MLA Citation
Chawla, AK, Kachnic, LA, Clark, JW, and Willett, CG. "Combined modality therapy for rectal and colon cancer." Seminars in Oncology 30.4 SUPPL. 9 (2003): 101-112.
PMID
12908141
Source
scival
Published In
Seminars in Oncology
Volume
30
Issue
4 SUPPL. 9
Publish Date
2003
Start Page
101
End Page
112

Clinical research in pancreatic cancer: The Radiation Therapy Oncology Group trials

Purpose: To summarize the clinical research activities of the Radiation Therapy Oncology Group program in the treatment of patients with locally advanced, as well as resected, pancreatic cancer. Methods and Materials: Phase II and III clinical trials are underway, examining novel cytotoxic and targeted agents with irradiation (RT) for patients with locally advanced and resected pancreatic cancer. Results: A Phase II study incorporating concurrent paclitaxel with external beam radiotherapy in the locally advanced setting has been completed and recently analyzed. This experience has served as the foundation of a Phase II study using concurrent paclitaxel and gemcitabine with RT followed by R115777, a farnesyltransferase inhibitor, as maintenance therapy. In the adjuvant treatment of pancreatic cancer, an Intergroup Phase III trial has compared "conventional" postoperative chemoirradiation (5-fluorouracil before, after, and during RT) and gemcitabine before and after RT (with 5-fluorouracil during RT). This study has recently closed, meeting its accrual goal. The successor study will evaluate the use of gemcitabine given concurrently with RT, as well as in a maintenance schedule. Conclusion: This report summarizes current and future Radiation Therapy Oncology Group clinical trials in the treatment of patients with localized pancreatic cancer. © 2003 Elsevier Inc.

Authors
Willett, CG; Safran, H; Abrams, RA; Regine, WF; Rich, TA
MLA Citation
Willett, CG, Safran, H, Abrams, RA, Regine, WF, and Rich, TA. "Clinical research in pancreatic cancer: The Radiation Therapy Oncology Group trials." International Journal of Radiation Oncology Biology Physics 56.4 SUPPL. (2003): 31-37.
PMID
12826249
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
56
Issue
4 SUPPL.
Publish Date
2003
Start Page
31
End Page
37
DOI
10.1016/S0360-3016(03)00446-2

The national practice for patients receiving radiation therapy for carcinoma of the esophagus: Results of the 1996-1999 Patterns of Care Study

Purpose: A Patterns of Care Study (PCS) was conducted to evaluate the standards of practice for patients receiving radiation therapy for esophageal cancer from 1996 to 1999. This study examined the evaluation and treatment schemes used during this time and compared these results to the PCS data obtained between 1992 and 1994 to identify any fundamental changes in national practice. Methods: A national survey was conducted using a two-stage cluster sampling technique. Specific information was collected on 414 patients with esophageal cancer who received radiotherapy (RT) as part of definitive or adjuvant management at 59 institutions. Patients were staged according to the 1983 AJCC. Eligibility criteria for case review included RT between 1996 and 1999, no evidence of distant metastasis (including CT evidence of either supraclavicular or celiac nodes >1 cm), squamous cell or adenocarcinoma histology, Karnofsky performance status >60, tumors in the thoracic esophagus with <2 cm extension into the stomach, and no prior malignancies within the last 5 years. Statistical analysis was performed on the database using SUDAAN software to accurately reflect the type of sampling technique used by PCS. For the purpose of this analysis, institutions were stratified as either large or small based on the number of new cases seen each year. For the purposes of comparison, the 1992-1994 PCS esophageal survey results were subjected to the same statistical procedures and tests. Results: The median age of patients was 64 years. Seventy-seven percent were male, and 23% were female. Karnofsky performance status was ≥80% in 85% of patients. The racial profile mirrors the previous survey with 75% Caucasian, 21% African-American, 3% Asian, and <1% Hispanic. A review of the histology revealed a nearly 50:50 split between squamous cell and adenocarcinoma. Sixteen percent were clinical Stage I, 39% clinical Stage II, and 33% clinical Stage III according to the 1983 AJCC system. Workup included endoscopy (96%), CT of the chest (87%), CT of the abdomen (75%), and esophagram (64%). Endoscopic ultrasound (EUS) was used in 18% of cases as compared to <2% in the original survey (p < 0.0001). Patients treated at large centers were more likely to undergo EUS than those treated at small centers (23% vs. 12%, p = 0.047). Fifty-six percent of patients received concurrent chemoradiation as definitive treatment. There was a significant increase in the use of concurrent chemoradiation before planned surgical resection as compared to the original survey (27% vs. 10%, p = 0.007). Other schemes included RT alone (10%), postoperative RT (1%), and postoperative chemoradiation (5%). Forty-six percent of patients with adenocarcinoma underwent trimodality therapy as compared to 19% with squamous cell carcinomas (p = 0.0002). Patients undergoing preoperative chemoradiation were more likely to have had an EUS. The median total dose of external RT was 50.4 Gy, and the median dose per fraction was 1.8 Gy. Brachytherapy was used in 6% of cases. The chemotherapy agents most commonly used included 5-fluorouracil (82%), cisplatin (67%), and paclitaxel (22%). Paclitaxel was more commonly employed as part of a preoperative chemoradiation regimen than in the setting of definitive chemoradiation (46% vs. 12%, p = 0.03). Compared to the original survey, paclitaxel use significantly increased between 1996 and 1999 (0.2% vs. 22%, p = 0.001). Conclusions: The Patterns of Care Survey confirms the use of concurrent chemoradiation as part of the national standards of practice for the management of esophageal cancer patients. A comparison with the previous study documents the significant rise in the use of EUS, preoperative chemoradiation followed by surgery, and the increasing use of paclitaxel as part of a combined modality regimen. © 2003 Elsevier Inc.

Authors
Suntharalingam, M; Moughan, J; Coia, LR; Krasna, MJ; Kachnic, L; Haller, DG; Willett, CG; John, MJ; Minsky, BD; Owen, JB
MLA Citation
Suntharalingam, M, Moughan, J, Coia, LR, Krasna, MJ, Kachnic, L, Haller, DG, Willett, CG, John, MJ, Minsky, BD, and Owen, JB. "The national practice for patients receiving radiation therapy for carcinoma of the esophagus: Results of the 1996-1999 Patterns of Care Study." International Journal of Radiation Oncology Biology Physics 56.4 (2003): 981-987.
PMID
12829133
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
56
Issue
4
Publish Date
2003
Start Page
981
End Page
987
DOI
10.1016/S0360-3016(03)00256-6

Radiation dose escalation in combined-modality therapy for esophageal cancer

Authors
Willett, CG
MLA Citation
Willett, CG. "Radiation dose escalation in combined-modality therapy for esophageal cancer." Journal of Clinical Oncology 20.5 (2002): 1151-1153.
PMID
11870151
Source
scival
Published In
Journal of Clinical Oncology
Volume
20
Issue
5
Publish Date
2002
Start Page
1151
End Page
1153

Management of locally advanced adenocarcinoma of the pancreas

Pancreatic cancer is one of the deadliest malignancies and is fatal in more than 95% of affected individuals. For locally advanced disease, the combination of 5-FU and radiation appears to offer the best chance for delaying disease progression. The introduction of gemcitabine into chemoradiotherapy regimens may provide additional improvements in the management of patients. Preoperative therapy has proved feasible but has not shown improvement in overall survival.

Authors
Ryan, DP; Willett, CG
MLA Citation
Ryan, DP, and Willett, CG. "Management of locally advanced adenocarcinoma of the pancreas." Hematology/Oncology Clinics of North America 16.1 (2002): 95-103.
PMID
12063831
Source
scival
Published In
Hematology/Oncology Clinics of North America
Volume
16
Issue
1
Publish Date
2002
Start Page
95
End Page
103
DOI
10.1016/S0889-8588(01)00009-0

Gastric surgical adjuvant radiotherapy consensus report: Rationale and treatment implementation

Purpose: Radiation therapy has recently emerged as a pivotal modality in the management of completely resected, high-risk gastric cancer. The recently published results of the Intergroup 0116 Gastric Surgical Adjuvant Trial randomized high-risk (T3,4 and/or node positive), completely resected gastric or gastroesophageal adenocarcinomas to receive either observation alone or radiochemotherapy after complete resection. Radiochemotherapy produced significant improvements in relapse-free (p < 0.0001) and overall survival (p = 0.01). Radiation oncologists must now clearly comprehend the principles governing the rationale supporting this therapy to apply it to those afflicted with this disease. This paper represents a consensus report reviewing data supporting radiotherapy, important clinical and anatomic issues related to radiotherapy, and details of the practical application of radiation therapy to commonly occurring clinical presentations. Supportive therapy during and after radiochemotherapy is also discussed. Copyright © 2002 Elsevier Science Inc.

Authors
Smalley, SR; Gunderson, L; Tepper, J; Jr, JAM; Minsky, B; Willett, C; Rich, T
MLA Citation
Smalley, SR, Gunderson, L, Tepper, J, Jr, JAM, Minsky, B, Willett, C, and Rich, T. "Gastric surgical adjuvant radiotherapy consensus report: Rationale and treatment implementation." International Journal of Radiation Oncology Biology Physics 52.2 (2002): 283-293.
PMID
11872272
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
52
Issue
2
Publish Date
2002
Start Page
283
End Page
293
DOI
10.1016/S0360-3016(01)02646-3

Results of radiation therapy in gastric cancer

Radiation therapy has been used in the treatment of patients with gastric cancer in two clinical settings: definitive therapy for locally advanced, unresectable tumors and adjuvant therapy following surgery for high-risk disease. For patients with locally advanced, unresectable or subtotally resected gastric carcinoma, radiotherapeutic approaches with and without chemotherapy have been employed, because these tumors appear localized, without clinically detectable metastases. Combined treatment with radiation therapy and chemotherapy appears to prolong survival but rarely results in long-term cure. Although only a modest effect was seen on survival, importantly, these studies established the foundation of contemporary combined-modality therapy and have served to stimulate further clinical investigation in gastric cancer as well as other gastrointestinal disease sites. For patients undergoing resection and lymphadenectomy with curative intent, the development of local or regional failure is common, occurring in 40% to 65% of patients. Sites of local and regional failure following resection include the gastric/tumor bed in 20% to 55%, the anastomosis in 25% to 50%, and the regional nodes in 40% to 50% of patients. Intergroup Trial 0116 (INT 0116), a phase III trial, has recently demonstrated that adjuvant radiation therapy with concurrent and maintenance 5-fluorouracil (5-FU) and leucovorin (LV) reduces local failure and improves survival. Adjuvant therapy is now routinely administered to patients undergoing resection of gastric cancer for high-risk disease. Ongoing trials are now investigating new systemic agents with radiation therapy to establish efficacy compared to 5-FU and LV, as well as evaluating neoadjuvant approaches prior to resection. Copyright 2002, Elsevier Science (USA). All rights reserved.

Authors
Willett, CG
MLA Citation
Willett, CG. "Results of radiation therapy in gastric cancer." Seminars in Radiation Oncology 12.2 (2002): 170-175.
PMID
11979418
Source
scival
Published In
Seminars in Radiation Oncology
Volume
12
Issue
2
Publish Date
2002
Start Page
170
End Page
175

Radiation Therapy Oncology Group. Research Plan 2002-2006. Gastrointestinal Cancer Committee.

Authors
Willett, C; Ajani, J; Kelsen, D; Sigurdson, E; Abrams, R; Berkey, B; Benetz, M; Crane, C; Gaspar, L; Goodyear, MD; Gunderson, L; Haddock, M; Hoffmann, J; Janjan, N; John, M; Kachnic, L; Krieg, R; Landry, J; Meropol, N; Minsky, B; Mitchell, E; Mohiuddin, M; Moulder, J; Myerson, R; Noyes, D; Pajak, TF; Raben, D; Regine, W; Rich, T; Robertson, JM; Russell, A; Skibber, J; Kim, P; Radiation Therapy Oncology Group,
MLA Citation
Willett, C, Ajani, J, Kelsen, D, Sigurdson, E, Abrams, R, Berkey, B, Benetz, M, Crane, C, Gaspar, L, Goodyear, MD, Gunderson, L, Haddock, M, Hoffmann, J, Janjan, N, John, M, Kachnic, L, Krieg, R, Landry, J, Meropol, N, Minsky, B, Mitchell, E, Mohiuddin, M, Moulder, J, Myerson, R, Noyes, D, Pajak, TF, Raben, D, Regine, W, Rich, T, Robertson, JM, Russell, A, Skibber, J, Kim, P, and Radiation Therapy Oncology Group, . "Radiation Therapy Oncology Group. Research Plan 2002-2006. Gastrointestinal Cancer Committee." International journal of radiation oncology, biology, physics 51.3 Suppl 2 (January 2001): 19-27.
PMID
11641011
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
51
Issue
3 Suppl 2
Publish Date
2001
Start Page
19
End Page
27

Radiation Therapy Oncology Group. Research Plan 2002-2006. Tumor Utilization Committee.

Authors
Hammond, ME; Ang, K; Byhardt, R; Campbell, B; Chapman, JD; Eisenberg, B; Greven, K; Harris, J; Hoffman, J; Lange, C; McCormick, B; Mehta, M; Sandler, H; Trotti, A; Willet, C; Wolfson, A; Furness, A; Jensen, T; Grignon, D; Okunieff, P; Radiation Therapy Oncology Group,
MLA Citation
Hammond, ME, Ang, K, Byhardt, R, Campbell, B, Chapman, JD, Eisenberg, B, Greven, K, Harris, J, Hoffman, J, Lange, C, McCormick, B, Mehta, M, Sandler, H, Trotti, A, Willet, C, Wolfson, A, Furness, A, Jensen, T, Grignon, D, Okunieff, P, and Radiation Therapy Oncology Group, . "Radiation Therapy Oncology Group. Research Plan 2002-2006. Tumor Utilization Committee." International journal of radiation oncology, biology, physics 51.3 Suppl 2 (January 2001): 103-109.
PMID
11641024
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
51
Issue
3 Suppl 2
Publish Date
2001
Start Page
103
End Page
109

Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2 receptor expression in endothelial cells: The role of VEGF165

Purpose: Late thrombosis of irradiated vascular segments may be the consequence of endothelial cell (EC) dysfunction after radiation therapy. We investigated the effects of β ionizing radiation on human EC viability, thymidine uptake, and differentiation. Methods and Materials: Endothelial cells were exposed to 32P-labeled DNA oligonucleotides in incremental doses of 2, 6, and 10 Gy. The modulation of the VEGFR2 receptor expression after irradiation and the overall potential radioprotective effect of VEGF165 on these functions were assayed. Results: A dose-dependent inhibitory effect of β irradiation on ECs' thymidine uptake and differentiation was observed. EC viability, however, was not affected at levels of radiation up to 10 Gy. VEGF165 proved to have a radioprotective effect as ECs' thymidine uptake, after radiation doses of 2, 6, and 10 Gy, was increased by 1.5-, 2-, and 4-fold, respectively, in the presence of 10 ng/ml of VEGF165 (p < 0.05 vs. LacZ). This concentration of VEGF165 also proved beneficial in maintaining cell differentiation at 16 h postirradiation when compared to controls. These biologic effects were in direct correlation with the upregulation of VEGFR2 receptor expression in irradiated ECs. Conclusions: β irradiation interacts directly with EC functions by significantly reducing their ability to differentiate and proliferate, associated with upregulation of VEGFR2. These effects can be prevented in part by pretreating cells with VEGF165, an effect potentially favored by the upregulation of VEGFR2 receptor expression after irradiation. Copyright © 2001 Elsevier Science Inc.

Authors
Gieschen, HL; Spiro, IJ; Suit, HD; Ott, MJ; Rattner, DW; Ancukiewicz, M; Willett, CG
MLA Citation
Gieschen, HL, Spiro, IJ, Suit, HD, Ott, MJ, Rattner, DW, Ancukiewicz, M, and Willett, CG. "Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2 receptor expression in endothelial cells: The role of VEGF165." International Journal of Radiation Oncology Biology Physics 50.1 (2001): 213-220.
PMID
11316566
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
50
Issue
1
Publish Date
2001
Start Page
213
End Page
220
DOI
10.1016/S0360-3016(01)01445-6

Local excision of rectal cancer

The treatment of distal rectal cancer is in evolution. Although abdominoperineal resection has been long regarded as the definitive treatment of distal rectal cancer, it is associated with significant morbidity loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction. To overcome these limitations, innovative efforts are underway that are studying the feasibility and efficacy of a variety of sphincter-preserving surgeries, usually in combination with radiation therapy and chemotherapy. Local excision procedures with adjuvant therapy represent 1 such treatment strategy that attempts to optimize local control and survivial with preservation of sphincter integrity. This article summarizes the current role of local excision and postoperative irradiation and chemotherapy for patients with carcinoma of the rectum. Copyright © 2001 by W.B. Saunders Company.

Authors
El-Ghamry, M; Willett, CG
MLA Citation
El-Ghamry, M, and Willett, CG. "Local excision of rectal cancer." Seminars in Colon and Rectal Surgery 12.4 (2001): 209-213.
Source
scival
Published In
Seminars in Colon and Rectal Surgery
Volume
12
Issue
4
Publish Date
2001
Start Page
209
End Page
213

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer

Background and purpose: To update and summarize the experience at the Massachusetts General Hospital of a treatment program of high-dose preoperative irradiation, surgical re-resection, and intraoperative radiation therapy (IORT) as a salvage treatment for patients with recurrent rectal or rectosigmoid carcinoma. Patients and methods: From June 1978 to February 1997, the records of 69 patients with locally recurrent rectal carcinomas or rectosigmoid carcinomas without metastases referred for consideration of IORT were reviewed. Forty-nine patients received IORT and local control and disease-free survival curves were calculated using the actuarial method of Kaplan-Meier. Results: The 5-year overall survival, local control and disease-free survival rates of 49 patients receiving IORT were 27, 35, and 20%, respectively. Thirty-four patients who underwent a macroscopic complete resection had a significantly better 5-year overall survival than the remaining 15 patients with gross residual disease (33 vs. 13%, P=0.05, log rank). For those patients, local control and disease-free survival rates were 46 and 27%, respectively. Patients with a microscopic complete resection had a superior 5-year overall survival than partially resected patients (40 vs. 14%, P = 0.0001, log rank). Chemotherapy had no significant influence on overall or disease-free survival. Conclusion: The current analysis shows the importance of a microscopic complete resection in a multi-modality approach with IORT for survival and local control. Salvage is rare for patients undergoing subtotal resection. © 2001 Elsevier Science Ireland Ltd.

Authors
Lindel, K; Willett, CG; Shellito, PC; Ott, MJ; Clark, J; Grossbard, M; Ryan, D; Ancukiewicz, M
MLA Citation
Lindel, K, Willett, CG, Shellito, PC, Ott, MJ, Clark, J, Grossbard, M, Ryan, D, and Ancukiewicz, M. "Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer." Radiotherapy and Oncology 58.1 (2001): 83-87.
PMID
11165686
Source
scival
Published In
Radiotherapy & Oncology
Volume
58
Issue
1
Publish Date
2001
Start Page
83
End Page
87
DOI
10.1016/S0167-8140(00)00309-1

Adjuvant radiation therapy for colon carcinoma

Although the benefit of adjuvant chemotherapy in high-risk carcinoma of the colon after surgical resection has been shown through randomized trials, the role of external beam radiotherapy is uncertain. Historic studies on patterns and predictors of failure in colon cancer have identified subsets of patients with tumors that, based on specific anatomic, clinical, and pathologic features, have a propensity toward increased risk of local-regional failure. Single institution analyses of the role of external beam radiotherapy in such patients have been performed and have suggested benefits to local aggressive treatment in terms of both local control and, possibly, survival. The following review presents the rationale and results with adjuvant radiotherapy for this disease. In addition, appropriate radiotherapy techniques and novel treatment strategies in which external beam radiotherapy is used will be considered briefly. Copyright © 2001 by W.B. Saunders Company.

Authors
Chawla, AK; Willett, CG
MLA Citation
Chawla, AK, and Willett, CG. "Adjuvant radiation therapy for colon carcinoma." Seminars in Colon and Rectal Surgery 12.4 (2001): 186-193.
Source
scival
Published In
Seminars in Colon and Rectal Surgery
Volume
12
Issue
4
Publish Date
2001
Start Page
186
End Page
193

Intraoperative radiation therapy

The modern use of intraoperative radiation therapy (IORT) was initiated by the studies of Abe and colleagues at the University of Kyoto. This work stimulated significant laboratory and clinical investigation into the use of IORT throughout Japan, Europe, and the United States. Because of this experience, single high doses of irradiation can be safely delivered to a tumor volume in appropriate clinical situations. Most importantly, this high dose of additional radiation treatment yields improved local control of selected tumors. Treatment programs of external beam radiation therapy, surgical resection, and IORT for patients with locally advanced primary and recurrent rectal carcinoma and retroperitoneal sarcoma have yielded excellent local control and higher survival rates. The future of IORT will be in the successful integration of this therapy into multimodality treatment programs of chemotherapy, external beam irradiation, and surgery for locally advanced malignancies.

Authors
Willett, CG
MLA Citation
Willett, CG. "Intraoperative radiation therapy." International Journal of Clinical Oncology 6.5 (2001): 209-214.
PMID
11723741
Source
scival
Published In
International Journal of Clinical Oncology
Volume
6
Issue
5
Publish Date
2001
Start Page
209
End Page
214

Squamous cell carcinoma of the anal canal and anal margin

Invasive carcinomas of the anal canal and margin, although relatively uncommon, remain important and curable malignancies for which clinical suspicion and awareness must remain high. Significant progress has occurred in epidemiology, in the identification of high-risk populations, and in the clinical management of this disease. Understanding of the disease pathogenesis has increased dramatically, and a profound improvement in the quality of life of many patients has resulted. Nevertheless, overall disease management must be improved. Future considerations in detection and treatment include the possible initiation of screening programs for high-risk individuals, further study into the optimal administration of current modalities, and expanded molecular biology research to uncover novel treatment techniques. With these and other advances, the survival and quality of life of patients who have anal cancer should continue to improve.

Authors
Chawla, AK; Willett, CG
MLA Citation
Chawla, AK, and Willett, CG. "Squamous cell carcinoma of the anal canal and anal margin." Hematology/Oncology Clinics of North America 15.2 (2001): 321-344.
PMID
11370496
Source
scival
Published In
Hematology/Oncology Clinics of North America
Volume
15
Issue
2
Publish Date
2001
Start Page
321
End Page
344
DOI
10.1016/S0889-8588(05)70215-X

Radiation therapy in the management of rectal cancer

Substantial advances have been made in the adjuvant management of patients with resectable rectal cancer. Increasing interest in patient quality of life has promoted the use of radiation therapy to enhance sphincter-preserving surgical approaches as an alternative to the standard abdominoperineal resection. Because of the suggestion of enhanced sphincter preservation with preoperative therapy and the potential advantage of decreased acute morbidity, randomized trials comparing preoperative and postoperative adjuvant combined modality therapy are ongoing. Recent progress in adjuvant postoperative treatment regimens relates to the integration of systemic therapy to radiation, and redefining the techniques for both modalities. The incorporation of improved radiation planning may reduce treatment-related bowel toxicity. The integration of novel chemotherapeutic agents in the adjuvant therapy of rectal cancer remains an active area of investigation. © 2001 Lippincott Williams & Wilkins, Inc.

Authors
Kachnic, LA; Willett, CG
MLA Citation
Kachnic, LA, and Willett, CG. "Radiation therapy in the management of rectal cancer." Current Opinion in Oncology 13.4 (2001): 300-306.
PMID
11429489
Source
scival
Published In
Current Opinion in Oncology
Volume
13
Issue
4
Publish Date
2001
Start Page
300
End Page
306
DOI
10.1097/00001622-200107000-00014

Gastrointestinal cancer committee

Authors
Willett, C; Ajani, J; Kelsen, D; Sigurdson, E; Abrams, R; Berkey, B; Benetz, M; Crane, C; Gaspar, L; Goodyear, MD; Gunderson, L; Haddock, M; Hoffman, J; Janjan, N; John, M; Kacknic, L; Krieg, R; Landry, J; Meropol, N; Minsky, B; Mitchell, E; Mohiuddin, M; Moulder, J; Myerson, R; Noyes, D; Pajak, TF; Raben, D; Regine, W; Rich, T; Robertson, JM; Russell, A; Skibber, J; Kim, P
MLA Citation
Willett, C, Ajani, J, Kelsen, D, Sigurdson, E, Abrams, R, Berkey, B, Benetz, M, Crane, C, Gaspar, L, Goodyear, MD, Gunderson, L, Haddock, M, Hoffman, J, Janjan, N, John, M, Kacknic, L, Krieg, R, Landry, J, Meropol, N, Minsky, B, Mitchell, E, Mohiuddin, M, Moulder, J, Myerson, R, Noyes, D, Pajak, TF, Raben, D, Regine, W, Rich, T, Robertson, JM, Russell, A, Skibber, J, and Kim, P. "Gastrointestinal cancer committee." International Journal of Radiation Oncology Biology Physics 51.3 SUPPL. 2 (2001): 19-27.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
51
Issue
3 SUPPL. 2
Publish Date
2001
Start Page
19
End Page
27

Current perspectives on locally advanced pancreatic cancer.

This year, approximately 40% of the 28,300 patients diagnosed with pancreatic carcinoma in the United States will present with locally advanced disease. Radiotherapeutic approaches are often employed, as these patients have unresectable tumors by virtue of local invasion into the retroperitoneal vessels in the absence of clinically detectable metastases. These treatments include external-beam irradiation with and without fluorouracil (5-FU)-based chemotherapy, intraoperative irradiation, and more recently, external-beam irradiation with new systemic agents, such as gemcitabine (Gemzar).

Authors
Czito, BG; Willett, CG; Clark, JW; Fernandez Del Castillo, C
MLA Citation
Czito, BG, Willett, CG, Clark, JW, and Fernandez Del Castillo, C. "Current perspectives on locally advanced pancreatic cancer." Oncology (Williston Park) 14.11 (November 2000): 1535-1545. (Review)
PMID
11125940
Source
pubmed
Published In
Oncology
Volume
14
Issue
11
Publish Date
2000
Start Page
1535
End Page
1545

Sphincter preservation in rectal cancer.

Distal rectal cancer poses two challenges to the oncologist: local tumor control and sphincter preservation. The abdominoperineal resection (APR), long considered the standard treatment of tumors with a distal edge located up to 6 cm from the anal verge, provides local control in many patients but results in sphincter loss with a permanent colostomy. This is a critical limitation. Consequently, there has been significant interest in sphincter-conserving approaches, frequently combining chemoradiation with surgery. These approaches have evolved along two fronts. For patients with small rectal cancers confined to the rectal wall, local excision techniques with and without chemoradiation may offer comparable local control and survival rates as an APR and preserve sphincter function. For patients with larger and more invasive tumors of the distal rectum where local excision is inappropriate, preoperative chemoradiation promotes tumor regression and may facilitate a resection sparing the sphincter with a coloanal anastomosis. Preliminary results from single institution studies appear promising. In both these settings (favorable and more invasive rectal cancer), chemoradiation is employed to compensate for the limitations of the sphincter-preserving surgical technique. In local excision procedures, the excision margins are invariably small, and the mesorectum (lymphatics, soft tissue) surrounding the tumor is not excised. For patients undergoing resection with coloanal anastomosis, there are narrow radial and distal surgical margins. With these approaches of chemoradiation and sphincter-sparing surgery, satisfactory local control and survival with avoidance of colostomy are possible for many patients with distal rectal cancer.

Authors
Willett, CG
MLA Citation
Willett, CG. "Sphincter preservation in rectal cancer." Current treatment options in oncology 1.5 (2000): 399-405.
PMID
12057147
Source
scival
Published In
Current treatment options in oncology
Volume
1
Issue
5
Publish Date
2000
Start Page
399
End Page
405

Impact of laparoscopic staging in the treatment of pancreatic cancer

Hypothesis: Staging laparoscopy in patients with pancreatic cancer identifies unsuspected metastases, allows treatment selection, and helps predict survival. Design: Inception cohort. Setting: Tertiary referral center. Patients: A total of 125 consecutive patients with radiographic stage II to III pancreatic ductal adenocarcinoma who underwent staging laparoscopy with peritoneal cytologic examination between July 1994 and November 1998. Seventy-eight proximal tumors and 47 distal tumors were localized. Interventions: Based on the findings of spiral computed tomography (CT) and laparoscopy, patients were stratified into 3 groups. Group 1 patients had unsuspected metastases found at laparoscopy and were palliated without further operation. Group 2 patients had no demonstrable metastases, but CT indicated unresectability due to vessel invasion. This group underwent external beam radiation with fluorouracil chemotherapy followed in selected cases by intraoperative radiation. Patients in group 3 had no metastases or definitive vessel invasion and were resection candidates. Main Outcome Measure: Survival. Results: Staging laparoscopy revealed unsuspected metastases in 39 patients (31.2%), with 9 having positive cytologic test results as the only evidence of metastatic disease (group 1). Fifty-five patients (44.0%) had localized but unresectable carcinoma (group 2), of whom 2 (3.6%) did not tolerate treatment, 20 (36.4%) developed metastatic disease during treatment, and 21 (38.2%) received intraoperative radiation. Of 31 patients with potentially resectable tumors (group 3), resection for cure was performed in 23 (resectability rate, 74.2%). Median survival was 7.5 months for patients with metastatic disease, 10.5 months for those receiving chemoradiation, and 14.5 months for those who underwent tumor resection (P = .01 for group 2 vs group 1; P<.001 for group 3 vs group 1). Conclusions: Staging laparoscopy, combined with spiral CT, allowed stratification of patients into 3 treatment groups that correlated with treatment opportunity and subsequent survival. Among the 125 patients, laparoscopy obviated 39 unnecessary operations and irradiation in patients with metastatic disease not detectable by CT. Laparoscopic staging can help focus aggressive treatment on patients with pancreatic cancer who might benefit.

Authors
Jimenez, RE; Warshaw, AL; Rattner, DW; Willett, CG; McGrath, D; Castillo, CF-D
MLA Citation
Jimenez, RE, Warshaw, AL, Rattner, DW, Willett, CG, McGrath, D, and Castillo, CF-D. "Impact of laparoscopic staging in the treatment of pancreatic cancer." Archives of Surgery 135.4 (2000): 409-415.
PMID
10768705
Source
scival
Published In
Archives of Surgery
Volume
135
Issue
4
Publish Date
2000
Start Page
409
End Page
415

Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms

Purpose: Little data exists in the medical literature describing the response of patients with inflammatory bowel disease (IBD) to abdominal and pelvic irradiation. To clarify the use of this modality in this setting, this study assesses the short- and long-term tolerance of 28 patients with IBD to abdominal and pelvic irradiation. Methods and Materials: From 1970 to 1999, 28 patients with IBD (10 patients-Crohn's disease, 18 patients-ulcerative colitis) were identified and underwent external beam abdominal or pelvic irradiation. Mean follow-up time after radiation therapy was 32 months. Patients were treated either by specialized techniques (16 patients) to minimize small and large bowel irradiation or by more conventional approaches (12 patients). Acute and late toxicity was scored. Results: The overall incidence of severe toxicity was 46% (13/28 patients). Six of 28 patients (21%) experienced severe acute toxicity necessitating cessation of radiation therapy. Late toxicity requiring hospitalization or surgical intervention was observed in 8 of 28 patients (29%). One patient experienced both an acute as well as late toxicity. For patients undergoing radiation therapy by conventional approaches, the 5-year actuarial rate of late toxicity was 73%. This figure was 23% for patients treated by specialized techniques (p = 0.02). Conclusions: Because of the potentially severe toxicity experienced by patients with IBD undergoing abdominal and pelvic irradiation, judicious use of this modality must be employed. Definition of IBD location and activity as well as careful attention to irradiation technique may allow treatment of these patients with acceptable rates of morbidity. Copyright (C) 2000 Elsevier Science Inc.

Authors
Willett, CG; Ooi, C-J; Zietman, AL; Menon, V; Goldberg, S; Sands, BE; Podolsky, DK
MLA Citation
Willett, CG, Ooi, C-J, Zietman, AL, Menon, V, Goldberg, S, Sands, BE, and Podolsky, DK. "Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms." International Journal of Radiation Oncology Biology Physics 46.4 (2000): 995-998.
PMID
10705022
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
46
Issue
4
Publish Date
2000
Start Page
995
End Page
998
DOI
10.1016/S0360-3016(99)00374-0

Prognostic factors in colorectal cancer: College of American Pathologists consensus statement 1999

Background. - Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. Materials and Methods. - The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. Results and Conclusions. - Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). Factors in category IIB included the following: histologic type, histologic features associated with microsatellite instability (MSI) (ie, host lymphoid response to tumor and medullary or mucinous histologic type), high degree of MSI (MSI-H), loss of heterozygosity at 18q (DCC gene allelic loss), and tumor border configuration (infiltrating vs pushing border). Factors grouped in category III included the following: DNA content, all other molecular markers except loss of heterozygosity 18q/DCC and MSI-H, perineural invasion, microvessel density, tumor cell-associated proteins or carbohydrates, peritumoral fibrosis, peritumoral inflammatory response, focal neuroendocrine differentiation, nuclear organizing regions, and proliferation indices. Category IV factors included tumor size and gross tumor configuration. This report records findings and recommendations of the consensus conference group, organized according to structural guidelines defined herein.

Authors
Compton, CC; Fielding, LP; Burgart, LJ; Conley, B; Cooper, HS; Hamilton, SR; Hammond, MEH; Henson, DE; Hutter, RVP; Nagle, RB; Nielsen, ML; Sargent, DJ; Taylor, CR; Welton, M; Willett, C
MLA Citation
Compton, CC, Fielding, LP, Burgart, LJ, Conley, B, Cooper, HS, Hamilton, SR, Hammond, MEH, Henson, DE, Hutter, RVP, Nagle, RB, Nielsen, ML, Sargent, DJ, Taylor, CR, Welton, M, and Willett, C. "Prognostic factors in colorectal cancer: College of American Pathologists consensus statement 1999." Archives of Pathology and Laboratory Medicine 124.7 (2000): 979-994.
PMID
10888773
Source
scival
Published In
Archives of Pathology and Laboratory Medicine
Volume
124
Issue
7
Publish Date
2000
Start Page
979
End Page
994

Outcome of patients receiving radiation for cancer of the esophagus: Results of the 1992-1994 patterns of care study

Purpose: A Patterns of Care Study examined the records of patients with esophageal cancer (EC) treated with radiation in 1992 through 1994 to determine the national practice processes of care and outcomes and to compare the results with those of clinical trials. Patients and Methods: A national survey of 63 institutions was conducted using two-stage cluster sampling, and specific information was collected on 400 patients with squamous cell (62%) or adenocarcinoma (37%) of the thoracic esophagus who received radiation therapy (RT) as part of primary or adjuvant treatment. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Fifteen percent of patients had clinical stage (CS) I disease, 40% had CS II disease, and 30% had CS III disease. Twenty-six percent of patients underwent esophagectomy. Seventy-five percent of patients received chemotherapy; 84% of these received concurrent chemotherapy and radiation (CRT). Results: Significant variables for overall survival in multivariate analysis include the use of esophagectomy (risk ratio [RR] = 0.62), the use of chemotherapy (RR = 0.63), Karnofsky performance status (KPS) greater than 80 (RR = 0.61), CS I or II disease (RR = 0.66), and facility type (RR = 0.72). Age, sex, and histology were not significant. Preoperative CRT resulted in a nonsignificantly higher 2-year survival rate compared with definitive CRT alone (63% v 39%; P = .11), whereas 2-year survival by planned treatment rather than treatment given was 47.7% for preoperative CRT and 35.4% for definitive CRT (P = .23). Definitive CRT compared with definitive RT alone resulted in significantly higher 2-year survival (39% v 20.6%; P = .027) and lower 2-year local regional failure (30% v 57.9%; P = .0031). Conclusion: This study confirms the value of CRT in EC treatment. It indicates that the results obtained in practice settings nationwide are similar to those obtained in clinical trials and that KPS and the 1983 clinical staging system are useful prognostic indicators. The suggested value of esophagectomy and superiority of preoperative CRT over CRT alone in this study should be tested in a randomized trial. (C) 2000 by American Society of Clinical Oncology.

Authors
Coia, LR; Minsky, BD; Berkey, BA; John, MJ; Haller, D; Landry, J; Pisansky, TM; Willett, CG; Hoffman, JP; Owen, JB; Hanks, GE
MLA Citation
Coia, LR, Minsky, BD, Berkey, BA, John, MJ, Haller, D, Landry, J, Pisansky, TM, Willett, CG, Hoffman, JP, Owen, JB, and Hanks, GE. "Outcome of patients receiving radiation for cancer of the esophagus: Results of the 1992-1994 patterns of care study." Journal of Clinical Oncology 18.3 (2000): 455-462.
PMID
10653860
Source
scival
Published In
Journal of Clinical Oncology
Volume
18
Issue
3
Publish Date
2000
Start Page
455
End Page
462

Intraoperative radiation therapy in resected bile duct cancer

Authors
Willett, CG
MLA Citation
Willett, CG. "Intraoperative radiation therapy in resected bile duct cancer." International Journal of Radiation Oncology Biology Physics 46.3 (2000): 523-524.
PMID
10701729
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
46
Issue
3
Publish Date
2000
Start Page
523
End Page
524
DOI
10.1016/S0360-3016(99)00471-X

CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia.

In previous studies, we demonstrated that pulmonary neuroendocrine cell (PNEC) hyperplasia in hamsters treated with diethylnitrosamine (DEN) plus 65% hyperoxia (DEN/O2) reflects predominantly neuroendocrine cell differentiation. Several peptides implicated in non-neoplastic PNEC hyperplasia are hydrolyzed by CD10/neutral endopeptidase 24.11 (CD10/NEP), an enzyme known to downregulate neurogenic inflammation of the lung by modulating locally effective concentrations of multiple bioactive peptides. In fetal mice, we observed that CD10/NEP inhibition by SCH32615 potentiates cell proliferation and type II cell differentiation in the lung in utero. Further, CD10/NEP messenger RNA levels parallelled relative PNEC numbers in DEN/O2-treated hamster lung, suggesting that the enzyme might mediate spontaneous regression of PNEC hyperplasia. The goals of the present study were: (1) to determine whether CD10/NEP inhibition would alter the extent of PNEC hyperplasia occurring in these hamsters, and (2) to analyze cellular mechanisms potentially involved in altering numbers of PNECs in this model. We administered SCH32615 chronically to a subset of DEN/O2-treated hamsters. Immunostaining of lungs from the CD10/ NEP-inhibited subset demonstrated significant acceleration of the development of PNEC hyperplasia, increased PNEC proliferation, and diminished PNEC apoptosis as compared with animals receiving no SCH32615. These observations indicate that PNEC hyperplasia can occur as a result of multiple cellular processes, including increased neuroendocrine cell differentiation, proliferation, and survival. CD10/NEP modulates PNEC numbers primarily by promoting cell differentiation and proliferation during lung injury, probably via increasing the half-life of bioactive peptides in the lung.

Authors
Willett, CG; Shahsafei, A; Graham, SA; Sunday, ME
MLA Citation
Willett, CG, Shahsafei, A, Graham, SA, and Sunday, ME. "CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia." Am J Respir Cell Mol Biol 21.1 (July 1999): 13-20.
PMID
10385588
Source
pubmed
Published In
American journal of respiratory cell and molecular biology
Volume
21
Issue
1
Publish Date
1999
Start Page
13
End Page
20
DOI
10.1165/ajrcmb.21.1.3389

Irradiation for Unresectable Pancreatic Cancer

Authors
Willett, CG
MLA Citation
Willett, CG. "Irradiation for Unresectable Pancreatic Cancer." Journal of Gastrointestinal Surgery 3.4 (1999): 351-353.
Source
scival
Published In
Journal of Gastrointestinal Surgery
Volume
3
Issue
4
Publish Date
1999
Start Page
351
End Page
353

Long-term follow-up of patients with rectal cancer managed by local excision with and without adjuvant irradiation

Objective: The long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation after local excision of T1 and T2 rectal cancers. Methods: Ninety-nine patients with T1 or T2 rectal cancers underwent local excision with or without adjuvant irradiation at Massachusetts General Hospital and Emory University Hospital between January 1966 and January 1997. Of these, 52 patients were treated by local excision alone and 47 patients by local excision plus adjuvant irradiation. Twenty-six of these 47 patients were treated by irradiation in combination with 5-fluorouracil chemotherapy. The outcomes of these groups were compared. Results: The 5-year actuarial local control and recurrence-free survival rates were 72% and 66%, respectively, for the local excision alone group and 90% and 74%, respectively, for the adjuvant irradiation group. This improvement in outcome was evident despite the presence of a higher-risk patient population in the adjuvant irradiation group. Adverse pathologic features such as poorly differentiated histology and lymphatic or blood vessel invasion decreased local control and recurrence-free survival rates in the local excision only group. Adjuvant irradiation significantly improved 5-year outcomes in patients with high-risk pathologic features. Four cases of late local recurrence were seen at 64, 72, 86, and 91 months in the adjuvant irradiation group. Conclusions: The authors recommend adjuvant chemoradiation for all patients undergoing local excision for T2 tumors, and for T1 tumors with high-risk pathologic features. The four cases of late local failures beyond 5 years in the adjuvant irradiation group underscores the need for careful long-term follow-up in these patients.

Authors
Chakravarti, A; Compton, CC; Shellito, PC; Wood, WC; Landry, J; Machuta, SR; Kaufman, D; Ancukiewicz, M; Willett, CG
MLA Citation
Chakravarti, A, Compton, CC, Shellito, PC, Wood, WC, Landry, J, Machuta, SR, Kaufman, D, Ancukiewicz, M, and Willett, CG. "Long-term follow-up of patients with rectal cancer managed by local excision with and without adjuvant irradiation." Annals of Surgery 230.1 (1999): 49-54.
PMID
10400036
Source
scival
Published In
Annals of Surgery
Volume
230
Issue
1
Publish Date
1999
Start Page
49
End Page
54
DOI
10.1097/00000658-199907000-00008

Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer?

PURPOSE: This study analyzes the long-term outcome of patients with stage T4 colon cancer who receive postoperative irradiation. The purpose of the study is to define the potential role of this modality with current systemic therapies. PATIENTS AND METHODS: A retrospective analysis was performed of 152 patients undergoing resection of T4 colon cancer followed by moderate- to high-dose postoperative tumor bed irradiation with and without 5-fluorouracil-based chemotherapy. Of the 152 patients, 110 patients (T4N0 or T4N+) were treated adjuvantly, whereas 42 patients received irradiation for the control of gross or microscopic residual local tumor. RESULTS: For 79 adjuvantly treated patients with stage T4N0 or T4N+ cancer with one lymph node metastasis, the 10-year actuarial rates of local control and recurrence- free survival were 88% and 58%, respectively. Results were less satisfactory for patients with more extensive nodal involvement. The 10-year actuarial rates of local control and recurrence-free survival of 39 patients with T4 tumors complicated by perforation or fistulas were 81% and 53%, respectively. For 42 patients with incompletely resected tumors, the 10-year actuarial recurrence-free survival was 19%. CONCLUSIONS: In comparison with historical controls, postoperative tumor bed irradiation improves local control for some subsets of patients. In addition to standard 5-fluorouracil-based chemotherapy, adjuvant tumor bed irradiation should be considered when colon cancers invade adjoining structures, when they are complicated by perforation or fistulas, or when they are incompletely excised at the primary site.

Authors
Willett, CG; Goldberg, S; Shellito, PC; Grossbard, M; Clark, J; Fung, C; Proulx, G; Daly, M; Kaufman, DS
MLA Citation
Willett, CG, Goldberg, S, Shellito, PC, Grossbard, M, Clark, J, Fung, C, Proulx, G, Daly, M, and Kaufman, DS. "Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer?." Cancer Journal from Scientific American 5.4 (1999): 242-247.
PMID
10439171
Source
scival
Published In
The cancer journal from Scientific American
Volume
5
Issue
4
Publish Date
1999
Start Page
242
End Page
247

The evaluation and treatment of patients receiving radiation therapy for carcinoma of the esophagus: Results of the 1992-1994 Patterns of Care Study

BACKGROUND. For the first time, a Patterns of Care Study (PCS) was conducted in 1992-1994 to determine the national practice standards in evaluating and treating patients with esophageal carcinoma and to determine the degree to which clinical trials have been incorporated into national practice. METHODS. A national survey of 61 institutions using 2-stage cluster sampling was conducted, and specific information was collected on 400 patients with squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who received radiation therapy (RT) as part of definitive or adjuvant management of their disease. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Chi-square tests for significant differences between academic and nonacademic institutions for a particular variable were performed. RESULTS. The median age of patients was 66.7 years (range, 26-89 years); 76.5% were male and 23.5% were female Karnofsky performance status was ≥80 for 88.3% of patients. Squamous cell carcinoma was diagnosed in 61.5% and adenocarcinoma in 36.8%. Fifteen percent were Clinical Stage (CS) I. 39.5% CS II, and 29.5% CS III. Evaluative procedures included endoscopy (>93%), computed tomography (CT) of the chest (86%), CT of the abdomen (75%), esophagography (68.5%), and endoscopic ultrasound (3.5%). Endoscopic ultrasound and CT of the chest were performed significantly more frequently at academic than nonacademic facilities (6.1% vs. 1.0% and 91.9% vs 81.3%, respectively). Three-quarters of all patients received chemotherapy and RT and 62.5% received concurrent chemotherapy and RT as part of their treatment. Treatments included chemotherapy plus RT (54.0%), RT alone (20.3%), preoperative chemotherapy + RT (13.3%), postoperative chemotherapy + RT (7.7%), postoperative RT (3.5%), and preoperative RT (1.2%). The chemotherapeutic agents most frequently used were 5-fluorouracil (84%), cisplatin (64%), and mitomycin (9%); academic institutions used cisplatin significantly more often and mitomycin significantly less often than nonacademic institutions. Brachytherapy was used in 8.5% of cases. The median total dose of external beam radiation was 50.4 gray and the median dose per fraction was 1.8 gray. CONCLUSIONS. This study establishes the national benchmarks for the evaluation and treatment of patients with esophageal carcinoma at radiation facilities in the U.S. It also indicates that the majority of patients given RT as a component of treatment for esophageal carcinoma receive chemoradiation rather than RT alone, as supported by clinical trials. Although some differences in the evaluation of esophageal carcinoma were noted between academic and nonacademic facilities, there was no difference in the frequency of use of chemoradiation versus RT by facility type.

Authors
Coia, LR; Minsky, BD; John, MJ; Haller, DG; Landry, J; Pisansky, TM; Willett, CG; Hoffman, JP; Berkey, BA; Owen, JB; Hanks, GE
MLA Citation
Coia, LR, Minsky, BD, John, MJ, Haller, DG, Landry, J, Pisansky, TM, Willett, CG, Hoffman, JP, Berkey, BA, Owen, JB, and Hanks, GE. "The evaluation and treatment of patients receiving radiation therapy for carcinoma of the esophagus: Results of the 1992-1994 Patterns of Care Study." Cancer 85.12 (1999): 2499-2505.
PMID
10375094
Source
scival
Published In
Cancer
Volume
85
Issue
12
Publish Date
1999
Start Page
2499
End Page
2505
DOI
10.1002/(SICI)1097-0142(19990615)85:12<2499::AID-CNCR2>3.0.CO;2-T

Prognostic factors in stage T3N0 rectal cancer: Do all patients require postoperative pelvic irradiation and chemotherapy?

PURPOSE: To further define the indications for postoperative pelvic irradiation and chemotherapy, an analysis of the influence of extent of tumor invasion into perirectal fat, lymphatic or venous vessel invasion, and tumor grade on the clinical course of patients with Stage T3N0 rectal cancer undergoing surgery was undertaken. METHODS: From 1968 to 1985, 117 patients with Stage T3N0 rectal cancer underwent resection with curative intent. No patient received neoadjuvant or adjuvant irradiation or chemotherapy. Surgical specimens were assessed for maximum depth of tumor invasion into perirectal fat, lymphatic or venous involvement, and tumor grade. After surgery the clinical course of these patients was assessed for local control, distant metastases, and survival rate. RESULTS: For 25 patients with tumors exhibiting favorable histologic features (well-differentiated or moderately well-differentiated carcinomas invading less than 2 mm into perirectal fat, without lymphatic or venous vessel involvement), the ten-year actuarial rates of local control and recurrence-free survival were 95 and 87 percent, respectively. In contrast, the ten-year actuarial rates of local control and recurrence-free survival were inferior (71 and 55 percent, respectively) for 88 patients with tumors exhibiting moderate to deep perirectal fat invasion, vessel involvement, or poor differentiation. CONCLUSIONS: In the design of future trials of rectal cancer, selection of patients with rectal cancer for postoperative adjuvant therapy should be based not only on stage, but also on depth of invasion into the perirectal fat, vessel involvement, tumor grade, and integrity of the radial resection margin. For subsets of patients with Stage T3N0 rectal cancer, there may be little benefit to adjuvant therapy after surgery.

Authors
Willett, CG; Badizadegan, K; Ancukiewicz, M; Shellito, PC
MLA Citation
Willett, CG, Badizadegan, K, Ancukiewicz, M, and Shellito, PC. "Prognostic factors in stage T3N0 rectal cancer: Do all patients require postoperative pelvic irradiation and chemotherapy?." Diseases of the Colon and Rectum 42.2 (1999): 167-173.
PMID
10211491
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
42
Issue
2
Publish Date
1999
Start Page
167
End Page
173
DOI
10.1007/BF02237122

Technical advances in the treatment of patients with rectal cancer

Authors
Willett, CG
MLA Citation
Willett, CG. "Technical advances in the treatment of patients with rectal cancer." International Journal of Radiation Oncology Biology Physics 45.5 (1999): 1107-1108.
PMID
10613301
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
45
Issue
5
Publish Date
1999
Start Page
1107
End Page
1108
DOI
10.1016/S0360-3016(99)00329-6

Patterns of care study decision tree and management guidelines for esophageal cancer. American College of Radiology.

PURPOSE: The Patterns of Care Study (PCS) of the American College of Radiology periodically develops a decision tree and current management guidelines for major malignancies where radiation has an important role. The decision tree is a framework which depicts the division of patients into treatment groups. The treatment guidelines are useful in management and also serve as a starting point for quality assessment. For the first time, PCS decided to develop consensus management guidelines for esophageal cancer. MATERIALS AND METHODS: A consensus panel was convened to define the key issues and develop guidelines for esophageal cancer management. A modified Delphi process was used to achieve consensus. RESULTS: The consensus panel developed guidelines for the management of patients with adenocarcinoma or squamous cell carcinoma of the esophagus with a Karnofsky performance status of over 50. Patients with clinical stage I or II esophageal cancer can be treated with curative intent using either a primary surgical or primary chemoradiation approach. For patients with clinical stage III malignancy, where the most common approaches are palliative, surgical resection is generally not recommended and chemoradiation is the preferred treatment. CONCLUSION: The PCS has developed treatment guidelines for esophageal cancer based on consensus committee deliberations. These guidelines can be useful for those who manage esophageal cancer.

Authors
Coia, LR; Minsky, BD; John, MJ; Haller, D; Landry, J; Pisansky, TM; Willet, CG; Mahon, I; Owen, J; Hanks, GE
MLA Citation
Coia, LR, Minsky, BD, John, MJ, Haller, D, Landry, J, Pisansky, TM, Willet, CG, Mahon, I, Owen, J, and Hanks, GE. "Patterns of care study decision tree and management guidelines for esophageal cancer. American College of Radiology." Radiation medicine 16.4 (July 1998): 321-327. (Review)
PMID
9814432
Source
epmc
Published In
Radiation medicine
Volume
16
Issue
4
Publish Date
1998
Start Page
321
End Page
327

Macrophage-stimulating protein and its receptor in non-small-cell lung tumors: induction of receptor tyrosine phosphorylation and cell migration.

Previously, we identified macrophage-stimulating protein (MSP) as being expressed during hamster lung injury induced by nitrosamine carcinogens. Transient, generalized epithelial-cell hyperplasia during the preneoplastic period, and eventually nonneuroendocrine (non-NE) lung tumors, are known to develop in these nitrosamine-treated hamsters. We wished to test the hypothesis that MSP and its tyrosine kinase receptor, RON, might represent an autocrine/paracrine system involved in the pathogenesis of human nonneuroendocrine lung tumors, the non-small-cell carcinomas (NSCLCs). We found that this occurred in a paracrine fashion in three of eight primary human NSCLCs that expressed messenger RNA (mRNA) for MSP at high levels in histologically normal lung adjacent to the tumor, but not in the primary tumor, together with mRNA for RON in both normal and tumor tissue. MSP and RON could also constitute an autocrine/paracrine system in human NSCLC cell lines: five of 16 cell lines (squamous and adenosquamous) expressed both MSP and RON; and an additional five of 16 cell lines expressed RON without detectable MSP. Although three cases of primary squamous-cell carcinomas expressed MSP (two of three in the tumor and one of three in nonneoplastic lung), mRNA for RON was not detectable in these cases. RON was functional in all tested RON mRNA-positive cell lines, with exogenous MSP inducing RON-mediated tyrosine phosphorylation. Treatment of a RON-positive adenosquamous carcinoma cell line with MSP additionally resulted in increased motility in a cell-migration assay, suggesting that MSP might promote cell migration of some NSCLCs. In conclusion, MSP and RON might represent an autocrine/paracrine system involved in the pathogenesis of lung cancer, although the nature of the biologic responses in different cell types might vary considerably.

Authors
Willett, CG; Wang, MH; Emanuel, RL; Graham, SA; Smith, DI; Shridhar, V; Sugarbaker, DJ; Sunday, ME
MLA Citation
Willett, CG, Wang, MH, Emanuel, RL, Graham, SA, Smith, DI, Shridhar, V, Sugarbaker, DJ, and Sunday, ME. "Macrophage-stimulating protein and its receptor in non-small-cell lung tumors: induction of receptor tyrosine phosphorylation and cell migration." Am J Respir Cell Mol Biol 18.4 (April 1998): 489-496.
PMID
9533936
Source
pubmed
Published In
American journal of respiratory cell and molecular biology
Volume
18
Issue
4
Publish Date
1998
Start Page
489
End Page
496
DOI
10.1165/ajrcmb.18.4.2978

Intraoperatic electron beam irradiation in pancreatic cancer.

Intraoperative electron beam radiation therapy (IOERT) is a technique in which a single high fraction radiation treatment is administered at the time of surgery. Using IOERT, the total radiation dose delivered to a tumor can be increased since sensitive normal tissues are removed from the radiation field during the surgical procedure. Furthermore, while the biologic effectiveness of this single fraction is incompletely understood, it is believed to be equivalent to that of a dose at least two times greater given by means of conventional fractionation. IOERT may improve local tumor control in patients with resectable or locally advanced pancreatic cancer. At the Massachusetts General Hospital (MGH), IOERT is being investigated in the management of pancreatic cancer as a boost treatment in combination with external beam radiation, surgery and chemotherapy.

Authors
Willett, CG; Warshaw, AL
MLA Citation
Willett, CG, and Warshaw, AL. "Intraoperatic electron beam irradiation in pancreatic cancer." Frontiers in bioscience : a journal and virtual library 3 (1998): E207-E213.
PMID
9820742
Source
scival
Published In
Frontiers in bioscience : a journal and virtual library
Volume
3
Publish Date
1998
Start Page
E207
End Page
E213

Radiation therapy for rectosigmoid and rectal cancer: Results of the 1992-1994 patterns of care process survey

Purpose: To determine the US national practice standards far patients with adenocarcinoma of the rectum treated in radiation oncology facilities. Materials and Methods: A national survey of 57 institutions identified 507 eligible patients who received radiation therapy as a component of their treatment for rectal cancer. A stratified two-stage cluster sampling with simple random sampling at each stage for each stratum was used and on-site surveys were performed. Results: Of the 507 patients, 378 (75%) received postoperative therapy, 110 (22%) received preoperative therapy, 17 (2%) received both preoperative and postoperative therapy, and less than 0.5% received intraoperative radiation alone. To more accurately assess the utilization of modem radiation techniques as well as recommendations of the National Cancer Institute (NCI)-sponsored, randomized, postoperative, adjuvant combined modality therapy rectal cancer trials into current practice, the analysis was limited to the 243 (48%) patients with tumor, node, and metastasis staging system classification T3 and/or N1-2M0 disease who underwent conventional surgery with negative margins. Although only 7% were treated on a clinical trial, 90% received chemotherapy for a median of 21 weeks. Most were treated with modern radiation treatment techniques. In contrast, techniques to identify and help exclude the small bowel from the radiation field were not routinely used. Conclusion: Despite the fact that only 7% of patients with T3 and/or N1-2M0 disease were treated on a clinical trial, such trials appear to have resulted in a positive influence on the standard of practice within the oncology community. Although there are still some deficiencies, the majority of these patients received combined modality therapy and were treated with modern radiation therapy techniques.

Authors
Minsky, BD; Coia, L; Haller, DG; Hoffman, J; John, M; Landry, J; Pisansky, TM; Willett, C; Mahon, I; Owen, J; Berkey, B; Katz, A; Hanks, G
MLA Citation
Minsky, BD, Coia, L, Haller, DG, Hoffman, J, John, M, Landry, J, Pisansky, TM, Willett, C, Mahon, I, Owen, J, Berkey, B, Katz, A, and Hanks, G. "Radiation therapy for rectosigmoid and rectal cancer: Results of the 1992-1994 patterns of care process survey." Journal of Clinical Oncology 16.7 (1998): 2542-2547.
PMID
9667276
Source
scival
Published In
Journal of Clinical Oncology
Volume
16
Issue
7
Publish Date
1998
Start Page
2542
End Page
2547

The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer

Objective: To analyze the effects of 5-fluorouracil (5-FU) chemotherapy combined with preoperative irradiation and the role of intraoperative electron beam irradiation (IOERT) on the outcome of patients with primary locally advanced rectal or rectosigmoid cancer. Methods: From 1978 to 1996, 145 patients with locally advanced rectal cancer underwent moderate- to high- dose preoperative irradiation followed by surgical resection. Ninety-three patients received 5-FU as a bolus for 3 days during the first and last weeks of radiation therapy (84 patients) or as a continuous infusion throughout irradiation (9 patients). At surgery, IOERT was administered to the surgical bed of 73 patients with persistent tumor adherence or residual disease in the pelvis. Results: No differences in sphincter preservation, pathologic down- staging, or resectability rates were observed by 5-FU use. However, there were statistically significant improvements in 5-year actuarial local control and disease-specific survival in patients receiving 5-FU during irradiation compared with patients undergoing irradiation without 5-FU. For the 73 patients selected to receive IOERT, local control and disease-specific survival correlated with resection extent. For the 45 patients undergoing complete resection and IOERT, the 5-year actuarial local control and disease- specific survival were 89% and 63%, respectively. These figures were 65% and 32%, respectively, for the 28 patients undergoing IOERT for residual disease. The overall 5-year actuarial complication rate was 11%. Conclusions: Treatment strategies using 5-FU during irradiation and IOERT for patients with locally advanced rectal cancer are beneficial and well tolerated.

Authors
Nakfoor, BM; Willett, CG; Shellito, PC; Kaufman, DS; Daly, WJ
MLA Citation
Nakfoor, BM, Willett, CG, Shellito, PC, Kaufman, DS, and Daly, WJ. "The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer." Annals of Surgery 228.2 (1998): 194-200.
PMID
9712564
Source
scival
Published In
Annals of Surgery
Volume
228
Issue
2
Publish Date
1998
Start Page
194
End Page
200
DOI
10.1097/00000658-199808000-00008

Implications of peritoneal cytology for pancreatic cancer management

Objective: To assess the implications of positive cytology for malignant cells (positive results) from peritoneal washings in the management of patients with pancreatic cancer. Design: Retrospective cohort study. Setting: Referral practice in a university hospital. Patients: A total of 32 consecutive pancreatic cancer patients with positive results from peritoneal washings during a 4-year period, 17 with visible biopsy-proven intraabdominal metastases at the time of laparoscopy or laparotomy and 15 without visible metastases. A treatment-matched control group of 30 patients was randomly selected from a group of 105 patients with negative cytology for malignant cells (negative results) from peritoneal fluid cytology. Interventions: Eight of 17 patients with visible metastases underwent treatment with chemotherapy, radiation, or both 13 of the 15 patients with no visible metastases underwent further treatment, including pancreatic resection in 2 patients and external beam radiation in 13 patients (3 with intraoperative radiation therapy). Main Outcome Measures: Time to metastases and mortality. Results: Median survival among patients with and without visible metastasis was 7.8 months and 8.6 months, respectively (P=.95), despite the fact that patients without visible metastases received more treatment. Patients without visible metastases at, presentation were found to have metastatic disease as documented by computed tomographic scan or subsequent laparotomy at a median time of 2.9 months. The survival of treatment-matched patients with negative cytology was significantly longer (median, 13.5 months; P=.04). Conclusions: Pancreatic cancer patients with peritoneal micrometastases have a dismal outcome even without macroscopic metastases. Since these patients do not benefit from local therapy, the finding of a positive result from peritoneal-fluid cytologic testing contraindicates further irradiation or surgery, except for specific complications.

Authors
Makary, MA; Warshaw, AL; Centeno, BA; Willett, CG; Rattner, DW; Castillo, CF-D
MLA Citation
Makary, MA, Warshaw, AL, Centeno, BA, Willett, CG, Rattner, DW, and Castillo, CF-D. "Implications of peritoneal cytology for pancreatic cancer management." Archives of Surgery 133.4 (1998): 361-365.
PMID
9565114
Source
scival
Published In
Archives of Surgery
Volume
133
Issue
4
Publish Date
1998
Start Page
361
End Page
365
DOI
10.1001/archsurg.133.4.361

Treatment systems guidelines for primary rectal cancer from the 1996 patterns of care study

Purpose: The Patterns of Care Rectal Cancer Committee was formed to develop consensus recommendations for patients with adenocarcinoma of the rectum limited to the pelvis. Methods and Materials: The Committee was composed of a multidisciplinary group of oncologists, and clinical scenarios were chosen to address most of the major treatment controversies in the combined modality treatment of rectal cancer. A literature search was then conducted and the major articles were identified. A modified Delphi technique was used to arrive at consensus. Serial surveys were conducted by distributing questionnaires to the Committee members to consolidate expert opinion. Voting was conducted using a scoring system and opinions were unified to the highest degree possible. Results: Consensus voting was performed for 4 clinical scenarios. Acceptability ratings for treatment were grouped into 3 broad categories: not acceptable, acceptable, and most acceptable. Based on the treatment options, a decision tree was developed that reflects the consensus of the committee. Conclusion: These options may help guide treatment decisions in rectal cancer.

Authors
Minsky, BD; Coia, L; Haller, D; Hoffman, J; John, M; Landry, J; Pisansky, TM; Willett, C; Mahon, I; Owen, J; Hanks, G
MLA Citation
Minsky, BD, Coia, L, Haller, D, Hoffman, J, John, M, Landry, J, Pisansky, TM, Willett, C, Mahon, I, Owen, J, and Hanks, G. "Treatment systems guidelines for primary rectal cancer from the 1996 patterns of care study." International Journal of Radiation Oncology Biology Physics 41.1 (1998): 21-27.
PMID
9588913
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
41
Issue
1
Publish Date
1998
Start Page
21
End Page
27
DOI
10.1016/S0360-3016(98)00027-3

Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation

PURPOSE: This study examines the effect of 5-fluorouracil administration during preoperative irradiation on rectal cancer tumor proliferation. PATIENTS AND METHODS: One hundred and fifty-three patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation with (103 patients) and without (50 patients) concurrent 5-fluorouracil, followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating cell nuclear antigen immunostaining and the number of mitoses per ten high-powered fields. Postirradiation specimens were also assessed for downstaging. RESULTS: Although 5-fluorouracil did not improve downstaging rates, marked decreases in the activity of all three markers of proliferation (mitotic counts, Ki-67, and proliferating cell nuclear antigen immunostaining) were seen in rectal cancers of patients receiving the drug. No significant decreases were noted in patients undergoing irradiation only. CONCLUSION: The addition of 5-fluorouracil to preoperative irradiation resulted in a more complete inactivation of the proliferating population. Frequency of downstaging, however, was unaffected. Thus, the quiescent cell population appears to represent a substantial barrier to further down- staging. New treatment strategies should be aimed at controlled recruitment of quiescent tumor cells at the time of irradiation.

Authors
Willett, CG; Hagan, M; Daley, W; Warland, G; Shellito, PC; Compton, CC
MLA Citation
Willett, CG, Hagan, M, Daley, W, Warland, G, Shellito, PC, and Compton, CC. "Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation." Diseases of the Colon and Rectum 41.1 (1998): 62-67.
PMID
9510312
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
41
Issue
1
Publish Date
1998
Start Page
62
End Page
67
DOI
10.1007/BF02236897

Local excision followed by postoperative radiation therapy

The management of distal rectal cancer is in evolution. Although abdominoperineal resection has been long regarded as the definitive treatment of distal rectal cancer, it is associated with significant morbidity - loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction. To overcome these limitations, innovative efforts are underway studying the feasibility and efficacy of a variety of sphincter-preserving operations, usually in combination with radiation therapy and chemotherapy. Local excision procedures with adjuvant therapy represent one such treatment strategy that attempts to optimize local control and survival with preservation of sphincter integrity. This article summarizes the current role of local excision and postoperative irradiation and chemotherapy for patients with carcinoma of the rectum.

Authors
Willett, CG
MLA Citation
Willett, CG. "Local excision followed by postoperative radiation therapy." Seminars in Radiation Oncology 8.1 (1998): 24-29.
PMID
9516580
Source
scival
Published In
Seminars in Radiation Oncology
Volume
8
Issue
1
Publish Date
1998
Start Page
24
End Page
29
DOI
10.1016/S1053-4296(98)80033-7

NCCN Practice Guidelines for Pancreatic Cancer

Authors
Tempero, M; Abbruzzese, J; Benson, AB; Cameron, JL; Casper, ES; Hoffman, J; Lawrence, T; Martin, T; McGinn, C; Willet, C
MLA Citation
Tempero, M, Abbruzzese, J, Benson, AB, Cameron, JL, Casper, ES, Hoffman, J, Lawrence, T, Martin, T, McGinn, C, and Willet, C. "NCCN Practice Guidelines for Pancreatic Cancer." ONCOLOGY 11.11 SUPPL. 11A (December 1, 1997): 41-55.
Source
scopus
Published In
Oncology
Volume
11
Issue
11 SUPPL. 11A
Publish Date
1997
Start Page
41
End Page
55

Adjuvant therapy for colorectal cancer background and results of surgical resection

Authors
Cohen, AM; Kelsen, D; Saltz, L; Minsky, BD; Nelson, H; Farouk, R; Gunderson, LL; Michelassi, F; Arenas, RB; Schilsky, RL; Willet, CG
MLA Citation
Cohen, AM, Kelsen, D, Saltz, L, Minsky, BD, Nelson, H, Farouk, R, Gunderson, LL, Michelassi, F, Arenas, RB, Schilsky, RL, and Willet, CG. "Adjuvant therapy for colorectal cancer background and results of surgical resection." Current Problems in Surgery 34.8 (December 1, 1997): 611-676.
Source
scopus
Published In
Current Problems in Surgery
Volume
34
Issue
8
Publish Date
1997
Start Page
611
End Page
676

Adjuvant therapy for colorectal cancer.

Authors
Cohen, AM; Kelsen, D; Saltz, L; Minsky, BD; Nelson, H; Farouk, R; Gunderson, LL; Michelassi, F; Arenas, RB; Schilsky, RL; Willet, CG
MLA Citation
Cohen, AM, Kelsen, D, Saltz, L, Minsky, BD, Nelson, H, Farouk, R, Gunderson, LL, Michelassi, F, Arenas, RB, Schilsky, RL, and Willet, CG. "Adjuvant therapy for colorectal cancer." Current problems in surgery 34.8 (August 1997): 601-676. (Review)
PMID
9251585
Source
epmc
Published In
Current Problems in Surgery
Volume
34
Issue
8
Publish Date
1997
Start Page
601
End Page
676
DOI
10.1016/s0011-3840(97)80013-5

Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival.

Transient pulmonary neuroendocrine cell hyperplasia and non-neuroendocrine lung tumors develop in nitrosaminetreated hamsters, which we hypothesized might modulate epithelial cell phenotype by expressing gene(s) homologous to human chromosome 3p gene(s) deleted in small cell carcinoma of the lung (SCLC). We differentially screened a chromosome 3 library using nitrosamine-treated versus normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) in injured lung. HGFL/MSP mRNA is low to undetectable in human SCLC and carcinoid tumors, but the HGFL/MSP tyrosine kinase receptor, RON, is present and functional on many of these neuroendocrine tumors. In H835, a pulmonary carcinoid cell line, and H187, a SCLC cell line, HGFL/ MSP induced adhesion/flattening and apoptosis. Using viable cell counts to assess proliferation after 14 d of treatment with HGFL/MSP, there is growth inhibition of H835 but not H187. Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/ MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia. These observations suggest that HGFL/MSP might regulate neuroendocrine cell survival during preneoplastic lung injury, which could influence the ultimate tumor cell phenotype.

Authors
Willett, CG; Smith, DI; Shridhar, V; Wang, MH; Emanuel, RL; Patidar, K; Graham, SA; Zhang, F; Hatch, V; Sugarbaker, DJ; Sunday, ME
MLA Citation
Willett, CG, Smith, DI, Shridhar, V, Wang, MH, Emanuel, RL, Patidar, K, Graham, SA, Zhang, F, Hatch, V, Sugarbaker, DJ, and Sunday, ME. "Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival." J Clin Invest 99.12 (June 15, 1997): 2979-2991.
PMID
9185522
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
99
Issue
12
Publish Date
1997
Start Page
2979
End Page
2991
DOI
10.1172/JCI119493

Intraoperative irradiation: Current and future status

Intraoperative radiation therapy (IORT) in its broadest sense refers to the delivery of irradiation at the time of an operation. This article will discusses the rationale for and results of both intraoperative electron radiation therapy and intraoperative high dose rate brachytherapy when used in conjunction with surgical exploration and resection and external beam radiation therapy and chemotherapy. Both IORT methods evolved with similar philosophies as an attempt to achieve higher effective doses of irradiation while dose limiting structures are surgically displaced.

Authors
Gunderson, LL; Willett, CG; Harrisor, LB; Petersen, IA; Haddock, MG
MLA Citation
Gunderson, LL, Willett, CG, Harrisor, LB, Petersen, IA, and Haddock, MG. "Intraoperative irradiation: Current and future status." Seminars in Oncology 24.6 (1997): 715-731.
PMID
9422267
Source
scival
Published In
Seminars in Oncology
Volume
24
Issue
6
Publish Date
1997
Start Page
715
End Page
731

The role of radiation therapy and 5-fluorouracil in colon and rectal cancer

Since the original report of improved survival of patients with locally unresectable gastric cancer treated with irradiation and 5-fluorouracil (5- FU) in 1968, there has been extensive investigation of this treatment combination in a variety of gastrointestinal tumors, including colon and rectal cancer. There are now extensive data supporting the use of 5-FU-based chemotherapy with irradiation in the adjuvant treatment of rectal cancer and increasing experience defining its role in neoadjuvant therapy. The value of adjuvant 5-FU-based chemotherapy and irradiation in colonic cancer is controversial, but there may be subsets of patients who benefit from this treatment. Ongoing studies in rectal and colon cancer are evaluating the role of irradiation with various modes of 5-FU administration {bolus v short or continuous infusion) as well as its modulation with other agents.

Authors
Willett, CG
MLA Citation
Willett, CG. "The role of radiation therapy and 5-fluorouracil in colon and rectal cancer." Seminars in Radiation Oncology 7.4 (1997): 300-305.
Source
scival
Published In
Seminars in Radiation Oncology
Volume
7
Issue
4
Publish Date
1997
Start Page
300
End Page
305
DOI
10.1016/S1053-4296(97)80029-X

Pathological downstaging does not guide the need for IORT in primary locally advanced rectal cancer.

Authors
Willett, CG; Nakfoor, BK; Daley, W; Shellito, PC
MLA Citation
Willett, CG, Nakfoor, BK, Daley, W, and Shellito, PC. "Pathological downstaging does not guide the need for IORT in primary locally advanced rectal cancer." Frontiers of radiation therapy and oncology 31 (1997): 245-246.
PMID
9263832
Source
scival
Published In
Frontiers of Radiation Therapy and Oncology
Volume
31
Publish Date
1997
Start Page
245
End Page
246

Appendiceal carcinoma: Patterns of failure following surgery and implications for adjuvant therapy

Background and Objectives: Primary adenocarcinoma of the appendix is rare, which makes an understanding of its natural history difficult. To date, it is treated predominantly with surgery alone. This review aims to elucidate the patterns of failure and treatment outcomes when adjuvant treatment is given after primary surgical resection. Methods: Twenty-three patients were treated with either surgery alone, or with surgery and adjuvant radiation +/- chemotherapy. A review of the clinical course of these patients was undertaken with an analysis of the local control, distant failure, disease- free survival, and overall survival. Results: Most patients presented with local invasion or metastatic disease often involving the peritoneum. Overall survival was 32%, similar to the results of other studies. Analysis of patients with locally advanced disease showed improvement in overall survival and local control with postoperative radiation therapy compared to surgery alone. Conclusions: Adenocarcinoma of the appendix is a rare disease that presents most often in an advanced stage. It has been shown by others that a right hemicolectomy provides the best outcome with respect to surgical procedure. Postoperative irradiation appears to provide a benefit for both local control and overall survival.

Authors
Proulx, GM; Willett, CG; Daley, W; Shellito, PC
MLA Citation
Proulx, GM, Willett, CG, Daley, W, and Shellito, PC. "Appendiceal carcinoma: Patterns of failure following surgery and implications for adjuvant therapy." Journal of Surgical Oncology 66.1 (1997): 51-53.
PMID
9290693
Source
scival
Published In
Journal of Surgical Oncology
Volume
66
Issue
1
Publish Date
1997
Start Page
51
End Page
53
DOI
10.1002/(SICI)1096-9098(199709)66:1<51::AID-JSO10>3.0.CO;2-R

Time-dose considerations in the treatment of anal cancer

Purpose: To analyze the impact of patient and treatment parameters in concurrent chemoradiation treatment for anal carcinoma. Methods and Materials: Retrospective review of 50 MO anal cancer patients treated from 1984-1994. Most patients received concurrent 5-FU, mitomycin, and radiation. Local control and disease-free/overall survival were determined and analyzed according to patient and treatment parameters. Results: With 43 month median follow-up; projected overall survival is 66% at 5 and 8 years. Disease-free survival is 67% at 5 years and 59% at 8 years. Local control is 70% at 5 and 8 years. Doses of ≤54 Gy are associated with improved 5-year survival (84 vs. 47%, p = 0.02), disease-free survival (74 v. 56%, p = 0.09), and local control (77 vs 61%, p = 0.04). Although local control, disease-free survival, and overall survival were improved in patients whose overall treatment time was <40 days, this was not statistically significant. Outcome in the four patients with pretreatment hemoglobin (Hgb) <10 appeared worse with 3-year overall survival 50 vs. 68% (p = 0.07), disease-free survival 0 vs. 67% (p = 0.11), and local control 0 vs. 74% (p = 0.05). Projected 5-year overall survival, relapse-free survival, and local control in 4 HIV(+) patients is 0, 75, and 75%. Multivariate analysis reveals that dose (p = 0.02) and Hgb (p = 0.05) independently affect local control, dose (p = 0.02) affects disease- free survival, and dose (p = 0.01), Hgb (p = 0.03), T-stage (p = 0.03), and HIV-status (0.07) independently influence overall survival. Conclusion: Radiation doses of ≤54 Gy are associated with significantly improved survival and local control in anal cancer patients treated with chemoradiation. Overall treatment times of less than 40 days age associated with a trend towards improved outcome, but this is not significant. Pretreatment hemoglobin <10 is associated with worse treatment outcome. Survival of HIV (+) patient is poor, but the majority of such patients in this series died of intercurrent disease with their anal carcinomas controlled by chemoradiation.

Authors
Constantinou, EC; Daly, W; Fung, CY; Willett, CG; Kaufman, DS; DeLaney, TF
MLA Citation
Constantinou, EC, Daly, W, Fung, CY, Willett, CG, Kaufman, DS, and DeLaney, TF. "Time-dose considerations in the treatment of anal cancer." International Journal of Radiation Oncology Biology Physics 39.3 (1997): 651-657.
PMID
9336145
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
39
Issue
3
Publish Date
1997
Start Page
651
End Page
657
DOI
10.1016/S0360-3016(97)00329-5

High risk of breast carcinoma after irradiation of young women with Hodgkin's disease

BACKGROUND. Treatment-associated second neoplasms have emerged as a major threat to the continued survival of patients cured of Hodgkin's disease. In this study, the authors investigated the risk of breast carcinoma in an irradiated Hodgkin's disease population. METHODS. One hundred and eleven women younger than 60 years presenting between 1964 and 1984 with Stage I and II Hodgkin's disease who received mantle irradiation were retrospectively analyzed and compared with an age specific population. Median follow-up was 18 years (range, 10-30 years), and the median age at initiation of therapy was 24 years. Kaplan-Meier actual risks, relative risks (RRs) (the ratio of the observed to the expected cases) with 95% confidence intervals (CIs), and the log rank test for trends were calculated. RESULTS. Fourteen women developed breast carcinoma: 8 of 33 patients younger than 20 years at the time of irradiation, 5 of 48 patients age 20 to 29 years, and 1 of 30 patients age 30 years or older. Actuarial calculation predicted a 34.0% (CI, 14.2-53.8) risk of breast carcinoma at 25 years after therapy for the youngest group, 22.3% (CI, 4.1-40.5) for the group of intermediate age, and 3.5% (CI, 0-10.1) for the oldest group. The RR of breast carcinoma was 56 (CI, 23.3-107) for those 19 years or younger at the time of treatment, 7.0 (CI, 2.3-16.4) for those age 20-29 years, and 0.9 (CI, 0-5.3) for those 30 years and older. Excluding 1 patient who was age 38 years at the time of irradiation, the remaining 13 breast carcinomas were tightly clustered in women irradiated between the ages of 14 through 25, and were detected in years 11 through 25 after treatment, with 7 occurring in years 15 through 18. CONCLUSIONS. Women younger than 30 years, particularly those younger than 20 years, who have received mantle irradiation for Hodgkin's disease require meticulous follow-up for breast carcinoma. The high incidence of breast carcinoma in this patient population should be considered when making treatment decisions in young women with early stage Hodgkin's disease.

Authors
Aisenberg, AC; Finkelstein, DM; Doppke, KP; Koerner, FC; Boivin, J-F; Willett, CG
MLA Citation
Aisenberg, AC, Finkelstein, DM, Doppke, KP, Koerner, FC, Boivin, J-F, and Willett, CG. "High risk of breast carcinoma after irradiation of young women with Hodgkin's disease." Cancer 79.6 (1997): 1203-1210.
PMID
9070499
Source
scival
Published In
Cancer
Volume
79
Issue
6
Publish Date
1997
Start Page
1203
End Page
1210
DOI
10.1002/(SICI)1097-0142(19970315)79:6<1203::AID-CNCR20>3.0.CO;2-2

Organ preservation in anal and rectal cancers

For the past 10 to 15 years, radiation therapy and chemotherapy have played an increasingly important role in the treatment of various gastrointestinal malignancies, most prominently in anal and rectal cancer. Critical issues in the care of patients with anal and rectal cancer include not only local control and survival but organ preservation as well. For patients with carcinoma of the anal canal, external-beam irradiation with 5- fluorouracil and chemotherapy with mitomycin C have replaced surgery as primary therapy. Current studies are optimizing this therapy. In contrast, the management of distal rectal cancer is in evolution. Although the abdominoperineal resection has been long regarded as the definitive treatment of distal rectal cancer, it is associated with substantial morbidity (loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction). As an alternative, treatment programs utilizing sphincter-preserving procedures with radiation therapy and chemotherapy are under active investigation. In selected patients, these strategies appear promising, and there have been reports of satisfactory local control and survival, as well as preservation of sphincter integrity.

Authors
Willett, CG
MLA Citation
Willett, CG. "Organ preservation in anal and rectal cancers." Current Opinion in Oncology 8.4 (1996): 329-333.
PMID
8869809
Source
scival
Published In
Current Opinion in Oncology
Volume
8
Issue
4
Publish Date
1996
Start Page
329
End Page
333

CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer

PURPOSE: This study examines the changes of serum levels of CA 19-9 in patients with pancreatic cancer following neoadjuvant irradiation and chemotherapy to define the potential role of this tumor marker in preoperative management of these patients. MATERIALS AND METHODS: Serum CA 19-9 levels were measured in 42 patients before receiving external beam irradiation with concurrent 5-fluorouracil in preparation for laparotomy and Whipple procedure or intraoperative irradiation (IORT). The CA 19-9 levels were determined again after irradiation, and changes were correlated with findings of restaging computed tomography (CT) scan and laparotomy. RESULTS: Following preoperative irradiation, 10 patients (24%) experienced an increase in CA 199 levels whereas 29 patients (69%) showed a decrease in CA 19-9. There was no change in the CA 19-9 levels of 3 patients (7%) after treatment. Of the 10 patients with increased CA 19-9 levels after irradiation, 9 (90%) had developed distant metastases or local tumor progression as determined by restaging CT scan or at laparotomy. In contrast, only 6 of 29 patients (21%) with declining CA 19-9 levels after irradiation demonstrated metastases or local tumor progression on restaging CT scan or at laparotomy. The correlation of CA 19-9 increase or decrease with disease progression or control, respectively, was statistically significant (P = 0.009). CONCLUSIONS: Serum CA 19-9 levels may rise or fall during neoadjuvant therapy. A rising CA 19-9 reliably indicates cancer progression while a falling CA 19-9 connotes disease control in the majority of patients. In developing strategies for application of neoadjuvant therapy for pancreatic cancer, monitoring of CA 19-9 appears most useful for the identification of patients who manifest progressive tumor growth and metastasis in spite of this treatment.

Authors
Willett, CG; Daly, WJ; Warshaw, AL
MLA Citation
Willett, CG, Daly, WJ, and Warshaw, AL. "CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer." American Journal of Surgery 172.4 (1996): 350-352.
PMID
8873528
Source
scival
Published In
The American Journal of Surgery
Volume
172
Issue
4
Publish Date
1996
Start Page
350
End Page
352
DOI
10.1016/S0002-9610(97)89547-5

Histochemical characterization of non-neuroendocrine tumors and neuroendocrine cell hyperplasia induced in hamster lung by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone with or without hyperoxia.

Lung tumors induced by 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) with or without hyperoxia have frequent K-ras mutations but only rare p53 mutations, suggesting that this may be a model for non-small cell lung cancers. The goals of the present study were (1) to characterize the histopathology of lung tumors induced in hamsters by NNK with or without O2 and (2) as a corollary, to quantitate the pulmonary neuroendocrine cell hyperplasia in the different treatment groups early and late in the treatment period. Lung tumors induced by NNK with or without O2 were 71% adenomas, 22% adenocarcinomas, approximately 4% bronchoalveolar carcinomas, and approximately 4% squamous/adenosquamous carcinomas. One-half of all tumors were positive for the Clara cell antigen CC10 and 21% of NNK-induced tumors were mucin positive, compared with 2% of NNK/O2-induced tumors (P = 0.003). Immunostaining for PGP9.5 was positive in 5% of tumors induced by NNK alone, but in none of NNK/O2-induced tumors (P = 0.024). Abundant proliferating cell nuclear antigen occurred in 55% of NNK-induced tumors, compared with 19% of NNK/O2-induced tumors (P = 0.009). These data indicate that NNK with or without O2 induces non-neuroendocrine lung tumors. Hyperoxia appears to inhibit cell proliferation and suppress mucinous and partial neuroendocrine differentiation in some of these tumors.

Authors
Sunday, ME; Willett, CG; Graham, SA; Oreffo, VI; Linnoila, RI; Witschi, H
MLA Citation
Sunday, ME, Willett, CG, Graham, SA, Oreffo, VI, Linnoila, RI, and Witschi, H. "Histochemical characterization of non-neuroendocrine tumors and neuroendocrine cell hyperplasia induced in hamster lung by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone with or without hyperoxia." Am J Pathol 147.3 (September 1995): 740-752.
PMID
7677185
Source
pubmed
Published In
The American journal of pathology
Volume
147
Issue
3
Publish Date
1995
Start Page
740
End Page
752

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer

Recurrent rectal or rectosigmoid cancer is a difficult therapeutic problem. A treatment program of external beam irradiation, surgery, and intraoperative irradiation has been used for 41 patients. The 5-year actuarial local control and disease-free survival of all 41 patients was 30% and 16%, respectively. Subset analysis demonstrated differences in outcome by extent of surgical resection. The 5 year actuarial local control and disease- free survival of 27 patients undergoing complete resection was 47% and 21%, respectively. By contrast, the outcome of 14 patients undergoing partial resection was poor, with a 5-year actuarial local control and survival of 21% and 7%, respectively. Late complications included soft tissue or peripheral nerve injury, with many of these resolving within 4-18 months. Local control and disease-free survival rates are favorable in comparison with the results achieved by aggressive surgery. Patients who achieve a gross total resection at intraoperative irradiation have a markedly better prognosis than that of patients with residual gross disease.

Authors
III, HJW; Willett, CG; Shellito, PC; Coen, JJ; Jr, HCH
MLA Citation
III, HJW, Willett, CG, Shellito, PC, Coen, JJ, and Jr, HCH. "Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer." Journal of Surgical Oncology 60.2 (1995): 122-127.
PMID
7564378
Source
scival
Published In
Journal of Surgical Oncology
Volume
60
Issue
2
Publish Date
1995
Start Page
122
End Page
127
DOI
10.1002/jso.2930600211

Rectal cancer: The influence of tumor proliferation on response to preoperative irradiation

Purpose: Regression of rectal carcinoma after preoperative irradiation is variable, likely reflecting differences in the physical and biologic properties of these tumors. This study examines the assocation between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by the activity of the proliferative dependent antigens (Ki-67, PCNA) and mitotic counts. Methods and Materials: One hundred and twenty-two patients with locally advanced rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for the extent of Ki-67 and PCNa immunostaining and the number of mitoses per 10 high-powered fields. Postirradiation surgical specimens were examined for extent of residual disease. Results: The tumors of 38 of 122 patients (31%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to teh rectal wall) after preoperative irradiation. Two features were associated with the likelihood of marked pathologic regression after preoperative irradiation: tumor proliferative activity and lesion size. When stratified by lesion size, marked tumor regression occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate Ki-67, PCNA, and mitotic activity. Conclusion: Tumor Ki-67, PCNA, and mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer. © 1995.

Authors
Willett, CG; Warland, G; Coen, J; Shellito, PC; Compton, CC
MLA Citation
Willett, CG, Warland, G, Coen, J, Shellito, PC, and Compton, CC. "Rectal cancer: The influence of tumor proliferation on response to preoperative irradiation." International Journal of Radiation Oncology, Biology, Physics 32.1 (1995): 57-61.
PMID
7721640
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
32
Issue
1
Publish Date
1995
Start Page
57
End Page
61
DOI
10.1016/0360-3016(94)00457-V

Tumor proliferation in rectal cancer following preoperative irradiation

Purpose: This study examines the effect of preoperative irrradiation on tumor proliferation in rectal cancer. Patients and Methods: One hundred twenty-two patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating-cell nuclear antigen (PCNA) immunostaining and the number of mitoses per 10 high-power fields (hpf). Preirradiation and postirradiation proliferative activity was determined and correlated to clinical outcome. Results: There was an overall reduction in the tumor proliferative activity of rectal cancer after irradiation compared with its preirradiation state. Decreases in the activity of all three markers of tumor proliferation (Ki-67 and PCNA immunostaining, and mitotic counts) were observed in irradiated tumors compared with pretreatment biopsies. Postirradiation tumor proliferative activity was associated with pathologic turner stage. A high level of proliferative activity was observed in tumors downstaged to the rectal wall (T1-2) compared with tumors that retained transmural penetration (T3-4). Multivariate analysis indicated that postirradiation proliferative activity and stage were independently associated with survival following surgery. Patients with tumors that exhibited elevated proliferative activity postirradiation had improved survival compared with patients with tumors that showed less proliferative activity. Conclusion: Moderate- to high-dose preoperative irradiation decreases bath the tumor size and proliferative activity of rectal cancers. Elevated postirradiation tumor proliferative activity correlates strongly with improved survival. This may aid in identifying high-risk patients following preoperative irradiation and surgery.

Authors
Willett, CG; Warland, G; Hagan, MP; Daly, WJ; Coen, J; Shellito, PC; Compton, CC
MLA Citation
Willett, CG, Warland, G, Hagan, MP, Daly, WJ, Coen, J, Shellito, PC, and Compton, CC. "Tumor proliferation in rectal cancer following preoperative irradiation." Journal of Clinical Oncology 13.6 (1995): 1417-1424.
PMID
7751887
Source
scival
Published In
Journal of Clinical Oncology
Volume
13
Issue
6
Publish Date
1995
Start Page
1417
End Page
1424

Modulation of oncogene and tumor suppressor gene expression in a hamster model of chronic lung injury with varying degrees of pulmonary neuroendocrine cell hyperplasia.

BACKGROUND: Intense pulmonary neuroendocrine cell (PNEC) hyperplasia occurs during preneoplastic lung injury in hamsters treated with diethylnitrosamine (DEN) plus hyperoxia. Alterations in oncogene and tumor suppressor gene expression during this process have not been explored. EXPERIMENTAL DESIGN: Our goals were: (a) to analyze expression of genes potentially involved in growth and differentiation of PNECs and/or nonneuroendocrine pulmonary epithelial cells (non-PNECs) in hamsters treated for up to 20 weeks with hyperoxia and DEN or the major tobacco-derived nitrosamine, 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK); and (b) as a corollary, to determine which cells were most mitotically active by immunostaining for c-myc and proliferating cell nuclear antigen. RESULTS: Immunohistochemical analyses demonstrated intense PNEC hyperplasia after treatment with either DEN/O2 or NNK/O2. Whereas DEN/O2-induced PNEC hyperplasia spontaneously regressed, NNK/O2-induced PNEC hyperplasia continued to increase up to 20 weeks. Rb transcripts were decreased similarly in lungs from all treatment groups (NNK/O2 = DEN/O2 = DEN alone) in spite of large differences in PNEC hyperplasia between these groups. c-myc was overexpressed in lungs from animals treated with NNK/O2, DEN/O2 and DEN alone, in which c-myc protein immunostaining occurred predominantly in non-PNECs. Proliferating cell nuclear antigen immunostaining confirmed that non-PNECs were most mitotically active. CONCLUSIONS: These data indicate that PNEC hyperplasia is primarily due to PNEC differentiation, suggesting that this model is ideal for studying mechanisms of neuroendocrine differentiation. Paracrine effects of PNEC-derived growth factors may then contribute to dysregulation of non-PNEC growth preceding the ultimate development of non-neuroendocrine lung tumors in nitrosamine-treated hamsters.

Authors
Sunday, ME; Willett, CG; Patidar, K; Graham, SA
MLA Citation
Sunday, ME, Willett, CG, Patidar, K, and Graham, SA. "Modulation of oncogene and tumor suppressor gene expression in a hamster model of chronic lung injury with varying degrees of pulmonary neuroendocrine cell hyperplasia." Lab Invest 70.6 (June 1994): 875-888.
PMID
8015292
Source
pubmed
Published In
Laboratory Investigation
Volume
70
Issue
6
Publish Date
1994
Start Page
875
End Page
888

Chemoradiotherapy for anal carcinoma:What is the optimal radiation dose?

Authors
Fung, CY; Willett, CG; Efird, JT; Shellito, PC; Kaufman, DS
MLA Citation
Fung, CY, Willett, CG, Efird, JT, Shellito, PC, and Kaufman, DS. "Chemoradiotherapy for anal carcinoma:What is the optimal radiation dose?." Radiation Oncology Investigations 2.3 (1994): 152-156.
Source
crossref
Published In
Radiation Oncology Investigations
Volume
2
Issue
3
Publish Date
1994
Start Page
152
End Page
156
DOI
10.1002/roi.2970020307

Proliferating cell nuclear antigen and mitotic activity in rectal cancer: Predictor of response to preoperative irradiation

Purpose: This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by proliferating cell nuclear antigen (PCNA) and mitotic activity. Patients and Methods: Ninety patients with clinical stage T3 and T4 rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for PCNA activity (number of tumor cells staining immunohistochemically with an anti-PCNA monoclonal antibody) and the number of mitoses per 10 high-powered fields (hpf). Postirradiation surgical specimens were examined for extent of residual disease. Results: The tumors of 33 of 90 patients (37%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were independently associated with the likelihood of marked pathologic regression after preoperative irradiation: lesion size and PCNA/mitotic activity. When stratified by tumor size, marked tumor regression occurred most frequently in smaller tumors with high PCNA/mitotic activity compared with larger tumors with lower PCNA/mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate PCNA/mitotic activity. Conclusion: Tumor PCNA/mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.

Authors
Willett, CG; Warland, G; Cheek, R; Coen, J; Efird, J; Shellito, PC; Compton, CC
MLA Citation
Willett, CG, Warland, G, Cheek, R, Coen, J, Efird, J, Shellito, PC, and Compton, CC. "Proliferating cell nuclear antigen and mitotic activity in rectal cancer: Predictor of response to preoperative irradiation." Journal of Clinical Oncology 12.4 (1994): 679-682.
PMID
7908689
Source
scival
Published In
Journal of Clinical Oncology
Volume
12
Issue
4
Publish Date
1994
Start Page
679
End Page
682

The effect of pelvic radiation therapy on serum levels of prostate specific antigen

To determine the effect of prostatic irradiation on the production of prostate specific antigen (PSA), serum PSA levels were measured in 36 men who received pelvic irradiation (45 to 65 Gy.) for nonprostatic malignancies, and compared with those of a control group of 79 men of comparable age without prostate cancer or prior pelvic irradiation identified from the records of the Massachusetts General Hospital internal physicians. The median PSA level was lower in the irradiated group than in the control group (0.65 versus 1.1 ng./ml.). Of the irradiated patients 47% had undetectable PSA levels versus 20% of the controls (p = 0.004, Fisher's exact test). A group of 27 prostate cancer patients who received up to 68 Gy. 8 to 16 years (median 10 years) previously and who remained clinically disease-free were also studied. The median PSA level was less than 0.5 ng./ml. The proportion of patients with undetectable PSA levels was significantly higher than that of the controls (p <0.001) but it was not significantly different from those irradiated for other pelvic cancers. Of those patients 67% had an undetectable PSA level and 78% had a level of less than 1 ng./ml. Our study suggests that radiation therapy results in a permanent decrease in PSA production by the prostate gland and that patients whose PSA values do not reach less than 1 ng./ml. following radical radiation therapy for prostate cancer are unlikely to be long-term clinical disease-free survivors.

Authors
Willett, CG; Zietman, AL; Shipley, WU; Coen, JJ
MLA Citation
Willett, CG, Zietman, AL, Shipley, WU, and Coen, JJ. "The effect of pelvic radiation therapy on serum levels of prostate specific antigen." Journal of Urology 151.6 (1994): 1579-1581.
PMID
7514692
Source
scival
Published In
Journal of Urology
Volume
151
Issue
6
Publish Date
1994
Start Page
1579
End Page
1581

Selection factors for local excision or abdominoperineal resection of early stage rectal cancer

Background. This study reviews the experience of patients with early stage rectal cancer managed by local excision or abdominoperineal resection to clarify the relative indications and results of these two approaches. Methods. From 1962 to 1991, 125 patients with T1 and T2 rectal cancer underwent local excision (56 patients) or abdominoperineal resection (69 patients). Outcome was analyzed by stage, treatment, and pathologic features of tumor grade and vessel involvement. Results. The 5-year actuarial recurrence-free survival and local control was 87% and 96%, respectively, for 28 patients undergoing local excision with favorable histologic features (well or moderately well differentiated histologic findings without venous/lymph vessel involvement). These results were 57% and 68% for 28 patients with unfavorable histologic features (poorly differentiated histology and/or venous/lymph vessel involvement). For patients undergoing abdominoperineal resection, the 5-year actuarial recurrence-free survival and local control of 49 patients with favorable histologic features was 91% and 91%, respectively. These results were 79% and 89%, respectively, for patients with poorly differentiated histology or venous/lymph vessel involvement. Conclusions. For patients with T1 and T2 tumors having favorable histologic features, a satisfactory survival and local control was achieved for patients undergoing local excision or abdominoperineal resection. In contrast, patients with T1 and T2 tumors having poorly differentiated histologic features and/or venous/lymph vessel involvement undergoing local excision or abdominoperineal resection appeared to have decreased rates of survival and of local control. For these patients, radical resection combined with pelvic irradiation and 5-fluorouracil-based chemotherapy should be investigated.

Authors
Willett, CG; Compton, CC; Shellito, PC; Efird, JT
MLA Citation
Willett, CG, Compton, CC, Shellito, PC, and Efird, JT. "Selection factors for local excision or abdominoperineal resection of early stage rectal cancer." Cancer 73.11 (1994): 2716-2720.
PMID
8194011
Source
scival
Published In
Cancer
Volume
73
Issue
11
Publish Date
1994
Start Page
2716
End Page
2720
DOI
10.1002/1097-0142(19940601)73:11<2716::AID-CNCR2820731111>3.0.CO;2-9

Radical radiation therapy in the management of prostatic adenocarcinoma: The initial prostate specific antigen value as a predictor of treatment outcome

We studied 161 prostate cancer patients treated by radical irradiation alone without endocrine therapy in whom pretreatment and posttreatment prostate specific antigen (PSA) values were measured, and who had a minimum followup of 2 years. Outcome was analyzed in an actuarial fashion using clinical disease-free survival and biochemical disease-free survival (freedom from an increasing PSA level or a PSA level of greater than 1.0 ng./ml. 2 years following irradiation) as end points. Of the patients 54% achieved a post-irradiation nadir value in the range 0 to 1.0 ng./ml. and 29% had a nadir value that was undetectably low (less than 0.5 ng./ml.). The likelihood of achieving these values was greater among patients with early stage than locally advanced tumors. For all T stages the likelihood of being disease- free at 4 years was substantially and significantly lower when PSA was used as an end point than when clinical evaluation alone was used: stages T1 and T2 (85 patients) 41% versus 71%, and stages T3 and T4 (76 patients) 15% versus 61%. For the whole group at 4 years clinical control was 67% but biochemical control was only 26% (p <0.05). The likelihood of being free of biochemical evidence of persistent disease at 4 years was a function of the initial PSA value (PSA less than 4.0 in 81% of the cases, 4.1 to 10.0 in 43%, 10.1 to 20.0 in 31%, 20.1 to 50.0 in 6% and greater than 50.0 in 0%). For stages T1 and T2 cancer patients with an initial PSA level of less than 15 ng./ml. (67% of all early stage cases) this value was 65% and it was even higher (73%) when poorly differentiated tumors were excluded. When the initial PSA level for stages T1 and T2 tumors was greater than 15 ng./ml. the projected 4-year rate of freedom from biochemical failure was only 7%. For stages T3 and T4 cancer patients the corresponding figures were 39% for those with an initial PSA level of less than 15 ng./ml. and 0% for those with an initial PSA level of greater than 15 ng./ml. The prognostic power of the initial PSA level was independent of stage, grade, patient age and prior transurethral resection of the prostate in a multivariate analysis. An initial serum PSA level of more than 15 ng./ml. is, therefore, a powerful predictor of probable failure with conventional radiation therapy. Serum PSA monitoring is a sensitive detector of early relapse. Knowledge of both will, in the future, allow the selection of patients for more intensive initial therapy or for early salvage.

Authors
Zietman, AL; Coen, JJ; Shipley, WU; Willett, CG; Efird, JT
MLA Citation
Zietman, AL, Coen, JJ, Shipley, WU, Willett, CG, and Efird, JT. "Radical radiation therapy in the management of prostatic adenocarcinoma: The initial prostate specific antigen value as a predictor of treatment outcome." Journal of Urology 151.3 (1994): 640-645.
PMID
7508522
Source
scival
Published In
Journal of Urology
Volume
151
Issue
3
Publish Date
1994
Start Page
640
End Page
645

Resection margins in carcinoma of the head of the pancreas: Implications for radiation therapy

A retrospective review of the pathology and clinical course of 72 patients undergoing resection of carcinoma of the head of the pancreas was undertaken to identify the frequency of tumor involvement at standard surgical transection margins (stomach, duodenum, pancreas, and bile duct) as well as the peripancreatic soft tissue margin and the potential clinical significance of these findings. Of 72 patients undergoing resection, 37 patients (51%) were found to have tumor extension to the surgical margins. The most commonly involved margin was peripancreatic soft tissue (27 patients) followed by pancreatic transection line (14 patients) and bile duct transection line (4 patients). For 37 patients with tumor present at a resection margin, there were no survivors beyond 41 months. No difference in survival or local control was seen between 14 patients receiving postoperative radiation therapy and 5-fluorouracil (5-FU) compared with 23 patients not receiving additional treatment. In contrast, the 5-year actuarial survival and local control of 35 patients undergoing resection without tumor invasion to a resection margin was 22% and 43%, respectively. The 5-year survival and local control of 16 patients receiving adjuvant radiation therapy and 5-FU was 29% and 42%, respectively, whereas these figures were 18% and 31% for 19 patients not receiving adjuvant therapy (p > 0.10). Because residual local tumor after resection is common, preoperative radiation therapy may be beneficial in this disease. It should minimize the risk of dissemination during operative manipulation and facilitate a curative resection by promoting tumor regression. Because local failure rates approach 60% after resection and adjuvant therapy even in cases having clear resection margins, intraoperative radiation therapy to the tumor bed at the time of resection also might be considered. Protocols evaluating the feasibility and efficacy of preoperative radiation therapy and resection with intraoperative radiation therapy for patients with pancreatic cancer are underway.

Authors
Willett, CG; Lewandrowski, K; Warshaw, AL; Efird, J; Compton, CC
MLA Citation
Willett, CG, Lewandrowski, K, Warshaw, AL, Efird, J, and Compton, CC. "Resection margins in carcinoma of the head of the pancreas: Implications for radiation therapy." Annals of Surgery 217.2 (1993): 144-148.
PMID
8094952
Source
scival
Published In
Annals of Surgery
Volume
217
Issue
2
Publish Date
1993
Start Page
144
End Page
148

Residual disease after radical surgery or radiation therapy for prostate cancer: Clinical significance and therapeutic implications

Radical treatment for prostate cancer aims at complete eradication of tumor. This review of published data makes clear that the goal is less frequently achieved than commonly presumed. Following radical prostatectomy extracapsular disease, carrying a significant risk of local recurrence, is found from 12-68% of the time depending on the clinical tumor stage. Local regrowth is associated with a poorer prognosis. A substantial proportion of patients whose prostate glands are rebiopsied more than 18 months after radiation therapy also have residual tumor. This again predicts for clinical relapse. The likelihood of a positive rebiopsy is dependent on original tumor size and current prostate specific antigen (PSA) levels. Strategies for managing residual disease are critically discussed.

Authors
Zietman, AL; Shipley, WU; Willett, CG
MLA Citation
Zietman, AL, Shipley, WU, and Willett, CG. "Residual disease after radical surgery or radiation therapy for prostate cancer: Clinical significance and therapeutic implications." Cancer 71.3 SUPPL. (1993): 959-969.
PMID
7679046
Source
scival
Published In
Cancer
Volume
71
Issue
3 SUPPL.
Publish Date
1993
Start Page
959
End Page
969

Late rectal bleeding following combined x-ray and proton high dose irradiation for patients with stages T3-T4 prostate carcinoma

Purpose: Dose escalation for prostate cancer by external beam irradiation is feasible by a 160 MeV perineal proton beam that reduces the volume of rectum irradiated. We correlated the total doses received to portions of the anterior rectum to study the possible relationship of the volume irradiated to the incidence of late rectal toxicity. Methods: We have randomized 191 patients with stages T3 and T4 prostatic carcinoma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy-equivalent (CGE), 50.4 Gy delivered by 107-25 MV photons followed by 25.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE delivered by 10-25 MV photons (Arm 2). Results: With a median follow-up of 3.7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none requiring surgery or hospitalization) from telangietatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients (p = 0.013). Dose-volume histograms (DVHs) for the anterior rectal wall, the posterior rectal wall and the total rectum in 41 patients treated on Arm 1 were calculated from the three dimensional dose distributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH-analyzed subset of Arm-1 patients. Both the fractional volume of the anterior rectum and the total dose received by fractional volumes of the anterior rectum significantly correlate with the actuarial probability of bleeding. Conclusions: Clinicians planning dose escalation to men with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CGE without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will otherwise have rectal bleeding. © 1993.

Authors
Benk, VA; Adams, JA; Shipley, WU; Urie, MM; McManus, PL; Efird, JT; Willett, CG; Goitein, M
MLA Citation
Benk, VA, Adams, JA, Shipley, WU, Urie, MM, McManus, PL, Efird, JT, Willett, CG, and Goitein, M. "Late rectal bleeding following combined x-ray and proton high dose irradiation for patients with stages T3-T4 prostate carcinoma." International Journal of Radiation Oncology, Biology, Physics 26.3 (1993): 551-557.
PMID
8514551
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
26
Issue
3
Publish Date
1993
Start Page
551
End Page
557

Postoperative radiation therapy for high-risk colon carcinoma

Purpose: This study examines the experience of patients treated with postoperative radiation therapy after resection of high-risk colon carcinoma in an effort to assess the potential role of this modality in combination with current systemic therapies. Patients and Methods: From 1976 to 1989, 203 patients received postoperative radiation therapy with and without concurrent fluorouracil (5-FU) chemotherapy following resection of modified Astler-Coller B2, B3, C2, and C3 colon tumors. Of the 203 patients, 30 (15%) were identified as having residual local tumor after subtotal resection, whereas 173 (85%) had no known residual disease. The 173 patients treated with adjuvant radiation therapy were compared with a historical control group of 395 patients undergoing surgery only. Results: Three groups of patients who appeared to benefit from postoperative radiation were identified. Improved local control and recurrence-free survival rates were seen for patients with stage B3 and C3 colon carcinoma treated with postoperative radiation therapy compared with a similarly staged group of patients undergoing surgery only. Irradiated patients whose tumors had an associated abscess or fistula formation had improved local control and recurrence-free survival rates compared with a similar group of patients undergoing surgery only. There appears to be a subset of patients with residual local disease after subtotal resection that may be salvaged by high-dose postoperative radiation therapy. Conclusion: Selected groups of patients with colon carcinoma may benefit from postoperative radiation in addition to current systemic therapies. Integration of 5-FU and levamisole with postoperative radiation therapy should be considered for patients with (1) stage B3 and C3 lesions, (2) tumors associated with abscess or fistula formation, and (3) residual local disease after subtotal resection.

Authors
Willett, CG; Fung, CY; Kaufman, DS; Efird, J; Shellito, PC
MLA Citation
Willett, CG, Fung, CY, Kaufman, DS, Efird, J, and Shellito, PC. "Postoperative radiation therapy for high-risk colon carcinoma." Journal of Clinical Oncology 11.6 (1993): 1112-1117.
PMID
8501497
Source
scival
Published In
Journal of Clinical Oncology
Volume
11
Issue
6
Publish Date
1993
Start Page
1112
End Page
1117

A phase I/II study of intraoperative radiotherapy in advanced unresectable or recurrent carcinoma of the rectum: A Radiation Therapy Oncology Group (RTOG) study

The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2-year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.0001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recurrent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow- up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress.

Authors
Lanciano, RM; Calkins, AR; Wolkov, HB; Buzydlowski, J; Noyes, RD; Sause, W; Nelson, D; Willett, C; Owens, JC; Hanks, GM
MLA Citation
Lanciano, RM, Calkins, AR, Wolkov, HB, Buzydlowski, J, Noyes, RD, Sause, W, Nelson, D, Willett, C, Owens, JC, and Hanks, GM. "A phase I/II study of intraoperative radiotherapy in advanced unresectable or recurrent carcinoma of the rectum: A Radiation Therapy Oncology Group (RTOG) study." Journal of Surgical Oncology 53.1 (1993): 20-29.
PMID
8479193
Source
scival
Published In
Journal of Surgical Oncology
Volume
53
Issue
1
Publish Date
1993
Start Page
20
End Page
29

Adjuvant postoperative radiation therapy for colonic carcinoma

Authors
Willett, CG; Tepper, JE; Kaufman, DS; Shellito, PC
MLA Citation
Willett, CG, Tepper, JE, Kaufman, DS, and Shellito, PC. "Adjuvant postoperative radiation therapy for colonic carcinoma." Seminars in Radiation Oncology 3.1 (1993): 64-67.
Source
scival
Published In
Seminars in Radiation Oncology
Volume
3
Issue
1
Publish Date
1993
Start Page
64
End Page
67

Introduction

Authors
Willett, CG; Tepper, JF
MLA Citation
Willett, CG, and Tepper, JF. "Introduction." Seminars in Radiation Oncology 3.1 (1993): 1--.
Source
scival
Published In
Seminars in Radiation Oncology
Volume
3
Issue
1
Publish Date
1993
Start Page
1-

Patterns of failure after pancreaticoduodenectomy for ampullary carcinoma

The clinical courses of 41 patients with ampullary carcinoma were retrospectively reviewed to determine patterns of failure after resection. The five year actuarial local control and overall survival rates of 29 patients undergoing only pancreaticoduodenectomy were 69 and 55 percent, respectively. For 12 patients with 'low risk' pathologic features (tumors limited to the ampulla or duodenum, well or moderately well-differentiated histologic factors, uninvolved lymph nodes or resection margins), the five year actuarial local control and survival rate was 100 and 80 percent, respectively. Adjuvant treatment may be unnecessary for this favorable subset of patients. On the other hand, the five year actuarial local control and survival after pancreaticoduodenectomy of 17 patients with 'high-risk' pathologic features (tumors invasive of the pancreas, poorly differentiated histologic findings, involved lymph nodes or resection margins) was only 50 and 38 percent, respectively (p<0.05). In 12 patients at 'high risk' who also received postoperative radiation therapy after pancreaticoduodenectomy, there was a trend toward better local control (83 percent), but there was no improvement in survival. Distant metastases (liver, peritoneum and pleura) were the dominant factor in determining outcome in this group. Therefore, we propose a trial of preoperative irradiation in hopes of enhancing these outcomes by reducing the risk of dissemination of cancer cells during surgical resection, especially among the 70 percent of patients with high risk pathologic features.

Authors
Willett, CG; Warshaw, AL; Convery, K; Compton, CC
MLA Citation
Willett, CG, Warshaw, AL, Convery, K, and Compton, CC. "Patterns of failure after pancreaticoduodenectomy for ampullary carcinoma." Surgery Gynecology and Obstetrics 176.1 (1993): 33-38.
PMID
8093983
Source
scival
Published In
Surgery Gynecology and Obstetrics
Volume
176
Issue
1
Publish Date
1993
Start Page
33
End Page
38

Adjuvant postoperative radiation therapy for rectal adenocarcinoma

From October 1975 to August 1988, 261 patients at high risk for local recurrence after curative resection of rectal carcinoma underwent high-dose postoperative irradiation. Patients received 45 Gy by a 4-field box usually followed by a boost to 50.4 Gy or higher when small bowel could be excluded from the reduced field. Since January 1986, patients also received 5- fluorouracil (5-FU) for 3 consecutive days during the first and last week of radiotherapy. Five-year actuarial local control and disease-free survival decreased with increasing stage of disease; patients with Stage B2 and B3 disease had local control rates of 83% and 87% and disease-free survivals of 55% and 74%, respectively. In patients with Stage C1 through C3 tumors, local control rates ranged from 76% to 23%, and disease-free survivals ranged from 62% to 10%, respectively. For patients with Stage C disease, disease-free survival decreased progressively with increasing lymph node involvement, but local control was independent of the extent of lymph node involvement. For each stage of disease, local control and disease-free survival did not correlate with the dose of pelvic irradiation. Preliminary data from this study suggest a trend toward improved local control for patients with Stage B2, C1, and C2 tumors who receive 5-FU for 3 consecutive days during the first and last weeks of irradiation compared with patients who do not receive 5-FU. Current prospective randomized studies are addressing questions regarding the optimum administration of chemotherapy with pelvic irradiation for patients following resection of rectal carcinoma.

Authors
Willett, CG; Tepper, JE; Kaufman, DS; Shellito, PC; Eliseo, R; Convery, K; Wood, WC
MLA Citation
Willett, CG, Tepper, JE, Kaufman, DS, Shellito, PC, Eliseo, R, Convery, K, and Wood, WC. "Adjuvant postoperative radiation therapy for rectal adenocarcinoma." American Journal of Clinical Oncology: Cancer Clinical Trials 15.5 (1992): 371-375.
PMID
1524036
Source
scival
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
15
Issue
5
Publish Date
1992
Start Page
371
End Page
375

Prophylaxis for heterotopic bone formation after total hip arthroplasty using low-dose radiation in high-risk patients

Fifteen consecutive total hip arthroplasties (THAs) in 14 patients considered at risk for developing significant heterotopic ossification (HO) were treated postoperatively with 7.5 Gy of external beam radiation in three fractions. Eight hips in eight of the patients (Group I) had developed previous Brooker Class III or IV HO after THA and were radiated after having excision of HO in conjunction with a revision THA. Three additional hips in three patients (Group II) were radiated after primary THA, because they developed significant HO on the contralateral hip after a previous THA. The remaining four hips in three patients (Group III) were radiated after primary THA because they had bilateral hypertrophic arthritis. Precision shielding was employed to minimize the volume of tissue in the radiation field and to protect the bone-implant interface around porous-coated components and the trochanteric osteotomy sites. Of the eight hips in which Class III or IV bone was excised during revision THA (Group I), no new bone formed in five hips and in the other three hips, only Class I bone formed. No heterotopic bone formed in the remaining seven hips of Groups II and III. All six trochanteric osteotomies healed. There were no wound healing problems. There were no significant radiolucencies around any of the components and there was no radiographic evidence of implant instability. This regimen using 7.5 Gy over three fractions minimizes the radiobiologic impact, whereas the use of precision shielding minimizes the total volume of tissue treated. This regimen is an effective means of preventing significant HO after THA in high- risk patients while minimizing radiation exposure.

Authors
Maloney, WJ; Jasty, M; Willett, C; Jr, RDM; Harris, WH
MLA Citation
Maloney, WJ, Jasty, M, Willett, C, Jr, RDM, and Harris, WH. "Prophylaxis for heterotopic bone formation after total hip arthroplasty using low-dose radiation in high-risk patients." Clinical Orthopaedics and Related Research 280 (1992): 230-234.
PMID
1611750
Source
scival
Published In
Clinical Orthopaedics and Related Research
Issue
280
Publish Date
1992
Start Page
230
End Page
234

3-D comparative study of proton vs. x-ray radiation therapy for rectal cancer

To assess the usefulness of proton beams for treatment of patients with rectal cancer, we have performed comparative 3D treatment planning for proton beam and x-ray beam therapy. Three common x-ray techniques (AP-PA, 3-field, and 4-field box), a proton beam only plan, and a proton boost plan were compared. The plan which would have been treated without the aid of the 3D planning system was also simulated. Dose distributions were analyzed and dose-volume histograms computed for the target volumes and critical normal tissues. Analyses of these plans demonstrate that the proton beam techniques reduce the volume of small bowel irradiated. This may allow higher doses to be delivered to the tumor, with a probable increase in local control, or a reduction in normal tissue complications probability. All the plans developed with the 3D planning system treated significantly less bowel than the one planned without it. © 1991.

Authors
Tatsuzaki, H; Urie, MM; Willett, CG
MLA Citation
Tatsuzaki, H, Urie, MM, and Willett, CG. "3-D comparative study of proton vs. x-ray radiation therapy for rectal cancer." International Journal of Radiation Oncology, Biology, Physics 22.2 (1992): 369-374.
PMID
1310972
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
22
Issue
2
Publish Date
1992
Start Page
369
End Page
374

Are there patients with Stage I rectal carcinoma at risk for failure after abdominoperineal resection?

The clinical courses of 64 patients undergoing abdominoperineal resection for Stage I lower rectal carcinoma (tumors confined to the muscularis propria without lymph node involvement) were reviewed to identify subsets at risk for failure. Twelve of 12 patients with tumors limited to the submucosa remained disease free without evidence of recurrence. Of the 52 patients with muscularis propria involvement, there have been eight failures with three patients having local failure only, three patients with local failure and distant metastases, and two patients with distant metastases only. The 6-year actuarial disease-free survival, local control, and freedom from distant metastases rates for patients with tumors invasive of the muscularis propria were 80%, 84%, and 88%, respectively. Patients with tumors exhibiting vascular/lymph vessel involvement were at even higher risk for failure. Although adjuvant treatment is infrequently advised for these patients, the use of radiation therapy and chemotherapy should be reconsidered for patients with Stage I lower rectal carcinoma, specifically for patients with tumors invasive of the muscularis propria with vascular/lymph vessel involvement.

Authors
Willett, CG; Lewandrowski, K; Donnelly, S; Shellito, PC; Convery, K; Eliseo, R; Compton, CC
MLA Citation
Willett, CG, Lewandrowski, K, Donnelly, S, Shellito, PC, Convery, K, Eliseo, R, and Compton, CC. "Are there patients with Stage I rectal carcinoma at risk for failure after abdominoperineal resection?." Cancer 69.7 (1992): 1651-1655.
PMID
1551050
Source
scival
Published In
Cancer
Volume
69
Issue
7
Publish Date
1992
Start Page
1651
End Page
1655

Induction and spontaneous regression of intense pulmonary neuroendocrine cell differentiation in a model of preneoplastic lung injury

Pulmonary neuroendocrine cell (PNEC) hyperplasia is associated with chronic lung diseases in humans, where it is thought to play a role in reparative responses to lung injury. To investigate the kinetics of strongly induced PNEC hyperplasia in an animal model, we exposed hamsters to a combination of hyperoxia (60% O2) and diethylnitrosamine (DEN) for up to 20 weeks. We thus demonstrate not only the induction but also spontaneous regression of intense PNEC differentiation and growth, which are much more intense than those observed with DEN alone. Lung tissues were immunostained for serotonin, calcitonin gene-related peptide (CGRP), calcitonin (CT), and gastrin-releasing peptide (GRP) (mammalian bombesin). Between 9 and 12 weeks of treatment, the number of CGRP- and serotonin-positive neuroepithelial bodies per cm airway epithelium increased over 10-fold, and CT became detectable. The number of neuroepithelial bodies immunostained for CGRP, serotonin, and CT peaked at 12-14 weeks of treatment, thereafter regressing to near-control levels by 20 weeks, in spite of continued DEN/O2 treatment. Simultaneously, by 6-7 weeks of treatment, there was a significant increase in the mean number of CGRP-positive cells per neuroepithelial body, which continued to rise up to double control levels, with a plateau it 13-20 weeks. GRP and pro-GRP immunostaining were not detectable at any time point. Polymerase chain reaction analyses of neuroendocrine-specific mRNAs demonstrated that CGRP, CT, and GRP mRNAs (normalized for β-actin) peaked in lung tissues from most animals at 9-14 weeks after the beginning of DEN/O2 treatment, with decreased expression at 16-20 weeks. These data suggest that regulation of levels of these neuropeptides may be primarily transcriptional. This model may be a valuable system for analyzing mechanisms of induction and regression of normal PNEC differentiation and growth.

Authors
Sunday, ME; Willett, CG
MLA Citation
Sunday, ME, and Willett, CG. "Induction and spontaneous regression of intense pulmonary neuroendocrine cell differentiation in a model of preneoplastic lung injury." Cancer Research 52.9 SUPPL. (1992): 2677s-2686s.
Source
scival
Published In
Cancer Research
Volume
52
Issue
9 SUPPL.
Publish Date
1992
Start Page
2677s
End Page
2686s

Induction and spontaneous regression of pulmonary neuroendocrine cell hyperplasia in a hamster model

Authors
Sunday, ME; Willett, CG
MLA Citation
Sunday, ME, and Willett, CG. "Induction and spontaneous regression of pulmonary neuroendocrine cell hyperplasia in a hamster model." Chest 101.3 SUPPL. (1992): 21S-.
Source
scival
Published In
Chest
Volume
101
Issue
3 SUPPL.
Publish Date
1992
Start Page
21S

The accelerated repopulation of a murine fibrosarcoma, FSA-II, during the fractionated irradiation and the linear-quadratic model.

Radiation response of a spontaneous mouse fibrosarcoma, FSa-II, to various fractionated doses was studied in vivo together with single dose cell survival curves. Early generation isotransplants were used. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Lung colony and TD50 assays were used to determine cell survival. Surviving fractions were determined following fractionated irradiations of 1.0 to 5.0 Gy each per fraction with interfractional time intervals of 4 hr. The alpha/beta ratio based on fractionated irradiations was 8.8 Gy for aerobic FSa-II tumor cells and flexure dose was less than 1.3 Gy. Multiple fractions of 5.0 Gy each given with 4, 12, and 24 hr intervals showed an increase in survival with increasing interfractional time interval, suggesting a rapid repopulation of tumor cells between fractions; namely, cell doubling time was shortened between fractions after the first 5.0 Gy doses. These results indicated that tumor cell repopulation is a critical factor in the fractionated radiotherapy. Linear-quadratic model was fitted to single dose survival data. Single dose survival curve of aerobic FSa-II tumor cells following lung colony assays which allowed determination of minimal survival of approximately 3.0 x 10(-3) showed that alpha, beta, and alpha/beta ratios were 0.25 Gy-1, 0.048 Gy-2, and 8.47 Gy, respectively. Single dose survival curve of the same aerobic cells determined by both lung colony and TD50 assays to a survival level of approximately 3.0 x 10(-6) demonstrated that alpha, beta, and alpha/beta ratios were 0.375, 0.0127, and 29.5, respectively. Similar determination for hypoxic FSa-II tumor cells showed that alpha, beta values were smaller whereas the alpha/beta ratio was much larger than for aerobic cells. The oxygen enhancement ratio calculated by the alpha/beta ratios was greater than 3.0.

Authors
Abe, Y; Urano, M; Kenton, LA; Kahn, J; Willet, CG
MLA Citation
Abe, Y, Urano, M, Kenton, LA, Kahn, J, and Willet, CG. "The accelerated repopulation of a murine fibrosarcoma, FSA-II, during the fractionated irradiation and the linear-quadratic model." International journal of radiation oncology, biology, physics 21.6 (November 1991): 1529-1534.
PMID
1938563
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
21
Issue
6
Publish Date
1991
Start Page
1529
End Page
1534

Preoperative irradiation for tethered rectal carcinoma

Twenty-eight patients with resectable but tethered rectal carcinomas were treated with preoperative irradiation (EBRT) and surgical resection. The 5-year actuarial disease-free survival and local control rates of these 28 patients were 66 and 76%, respectively. Two patients have developed local failure only, 2 patients concurrent local failures and distant metastases, and 4 patients distant metastases only. All local failures occurred in areas of tumor adherence to unresectable structures (sacrum, pelvic side wall). Patients with tethered rectal tumors are at risk for local failure despite preoperative irradiation and surgical resection. To improve local control in this subset of patients, an intraoperative radiation therapy (IORT) boost is given to areas of tumor adherence at resection following EBRT. © 1991.

Authors
Willett, CG; Shellito, PC; Rodkey, GV; Wood, WC
MLA Citation
Willett, CG, Shellito, PC, Rodkey, GV, and Wood, WC. "Preoperative irradiation for tethered rectal carcinoma." Radiotherapy and Oncology 21.2 (1991): 141-142.
PMID
1866465
Source
scival
Published In
Radiotherapy & Oncology
Volume
21
Issue
2
Publish Date
1991
Start Page
141
End Page
142

Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma

From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance.

Authors
Willett, CG; Suit, HD; Tepper, JE; Mankin, HJ; Convery, K; Rosenberg, AL; Wood, WC
MLA Citation
Willett, CG, Suit, HD, Tepper, JE, Mankin, HJ, Convery, K, Rosenberg, AL, and Wood, WC. "Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma." Cancer 68.2 (1991): 278-283.
PMID
1906369
Source
scival
Published In
Cancer
Volume
68
Issue
2
Publish Date
1991
Start Page
278
End Page
283
DOI
10.1002/1097-0142(19910715)68:2<278::AID-CNCR2820680211>3.0.CO;2-C

Radiation therapy of sarcomas of the soft tissues.

Authors
Suit, HD; Willett, CG
MLA Citation
Suit, HD, and Willett, CG. "Radiation therapy of sarcomas of the soft tissues." Cancer treatment and research 56 (1991): 61-74.
PMID
1681880
Source
scival
Published In
Cancer treatment and research
Volume
56
Publish Date
1991
Start Page
61
End Page
74

Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma

A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinate local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.

Authors
Willett, CG; Shellito, PC; Tepper, JE; Eliseo, R; Convery, K; Wood, WC
MLA Citation
Willett, CG, Shellito, PC, Tepper, JE, Eliseo, R, Convery, K, and Wood, WC. "Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma." Cancer 67.6 (1991): 1504-1508.
PMID
2001537
Source
scival
Published In
Cancer
Volume
67
Issue
6
Publish Date
1991
Start Page
1504
End Page
1508

Intraoperative electron beam radiation therapy for primary locally advanced rectal and rectosigmoid carcinoma

To improve local control and survival in patients with primary locally advanced rectal and rectosigmoid carcinoma, intraoperative electron beam radiation therapy (IORT) has been used with a combination of moderate- to high-dose preoperative radiation therapy and surgical resection. Sixty-five patients underwent resection with the intention of using IORT if areas at high risk for local recurrence were apparent at surgery. For 20 patients undergoing complete resection with IORT, the 5-year actuarial local control and disease-free survival (DFS) was 88% and 53%, respectively. The results for 22 patients with pathologically documented residual carcinoma were less satisfactory with a 5-year actuarial local control and DFS of 60% and 32%, respectively. In this latter group, local control and DFS correlated with the extent of residual disease patients with only microscopic disease had a 5-year actuarial local control and DFS of 69% and 47%, respectively, whereas for patients with macroscopic disease, these figures were 50% and 17%, respectively. For 18 patients undergoing complete resection without IORT or additional postoperative radiation therapy, the 5-year actuarial local control and DFS was 67% and 53%, respectively. Because local failure will occur in at least 30% of patients undergoing partial resection with or without IORT as well as patients undergoing complete resection of advanced tumors without IORT, additional postoperative radiation therapy should be considered. © 1991 by American Society of Clinical Oncology.

Authors
Willett, CG; Shellito, PC; Tepper, JE; Eliseo, R; Convery, K; Wood, WC
MLA Citation
Willett, CG, Shellito, PC, Tepper, JE, Eliseo, R, Convery, K, and Wood, WC. "Intraoperative electron beam radiation therapy for primary locally advanced rectal and rectosigmoid carcinoma." Journal of Clinical Oncology 9.5 (1991): 843-849.
PMID
2016628
Source
scival
Published In
Journal of Clinical Oncology
Volume
9
Issue
5
Publish Date
1991
Start Page
843
End Page
849

Considerations in fractionated proton radiation therapy: clinical potential and results

Protons have a finite range in tissue and can provide a better concentration of radiation dose in the tumor than conventional X-rays in certain situations. The development of optimized treatment plans for X-rays and protons followed by a comparative evaluation is one method of selecting tumor sites best suited for proton treatment. The preliminary results of comparative treatment planning for base of skull tumors and carcinoma of the prostate are discussed. These comparisons suggest a clinical gain for proton treatment of tumors in these locations. The clinical experience with fractionated proton treatment of several tumor sites is also discussed. The results of high dose proton treatment of chordomas and low grade chondrosarcomas of the base of skull is particularly promising: an actuarial 5-year local control of 78% has been obtained in 50 patients followed for a minimum of 22 months. © 1990.

Authors
Austin-Seymour, M; Urie, M; Munzenrider, J; Willett, C; Goitein, M; Verhey, L; Gentry, R; McNulty, P; Koehler, A; Suit, H
MLA Citation
Austin-Seymour, M, Urie, M, Munzenrider, J, Willett, C, Goitein, M, Verhey, L, Gentry, R, McNulty, P, Koehler, A, and Suit, H. "Considerations in fractionated proton radiation therapy: clinical potential and results." Radiotherapy and Oncology 17.1 (1990): 29-35.
PMID
2157240
Source
scival
Published In
Radiotherapy & Oncology
Volume
17
Issue
1
Publish Date
1990
Start Page
29
End Page
35

Editorial: Internally administered isotopes in the treatment of solid malignancy

Authors
Willett, CG
MLA Citation
Willett, CG. "Editorial: Internally administered isotopes in the treatment of solid malignancy." Journal of Nuclear Medicine 31.5 (1990): 601-602.
PMID
2341895
Source
scival
Published In
Journal of Nuclear Medicine
Volume
31
Issue
5
Publish Date
1990
Start Page
601
End Page
602

Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties

Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

Authors
Jasty, M; Schutzer, S; Tepper, J; Willett, C; Stracher, MA; Harris, WH
MLA Citation
Jasty, M, Schutzer, S, Tepper, J, Willett, C, Stracher, MA, and Harris, WH. "Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties." Clinical Orthopaedics and Related Research 257 (1990): 138-145.
PMID
2116254
Source
scival
Published In
Clinical Orthopaedics and Related Research
Issue
257
Publish Date
1990
Start Page
138
End Page
145

Altered growth of a human neuroendocrine carcinoma line after transfection of a major histocompatibility complex class I gene.

The major histocompatibility complex (MHC) class I molecules are known to serve as recognition elements for cytotoxic T cells in mediating the rejection of transplanted tumors. We demonstrate that MHC molecules may have nonimmune functions in modulating tumor cell growth in addition to their classical role in antitumor immunity. A human neuroendocrine carcinoma cell line, COLO 320, with low levels of endogenous class I expression was transfected with the murine H-2Ld gene. Eleven independent stable clones were established, four containing only pRSV-neo and seven also containing varying copy numbers of the transfected Ld gene. The ability of the different clones to grow as colonies in soft agar correlated strongly with the relative amounts of Ld antigen expression (r = 0.89; P less than 0.001). There was a weaker correlation between increased clonogenic ability and higher levels of Ld mRNA (r = 0.67; P less than 0.05). There was no correlation between clonogenic ability and relative expression of amplified c-myc gene or of integrated pRSV-neo. Furthermore, in nude mice, Ld antigen expression was associated with increased formation of metastatic lung colonies 6 weeks after intravenous injection of 10(5) cells. These observations are consistent with the concept that MHC class I antigens may have a role in modulating the growth potential of certain tumor cells independent of their involvement in immune responses.

Authors
Sunday, ME; Isselbacher, KJ; Gattoni-Celli, S; Willett, CG
MLA Citation
Sunday, ME, Isselbacher, KJ, Gattoni-Celli, S, and Willett, CG. "Altered growth of a human neuroendocrine carcinoma line after transfection of a major histocompatibility complex class I gene." Proc Natl Acad Sci U S A 86.12 (June 1989): 4700-4704.
PMID
2660144
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
86
Issue
12
Publish Date
1989
Start Page
4700
End Page
4704

Indications for adjuvant radiotherapy in extrapelvic colonic carcinoma.

Although the value of postoperative radiotherapy has been demonstrated for subsets of patients with rectal carcinoma, the efficacy of postoperative radiation therapy for colonic carcinoma (above the peritoneal reflection) is much less clear. Recent studies examining the failure patterns of colonic carcinoma following resection indicate that local failure increases as a function of bowel mobility, disease extension through bowel wall, and lymph node involvement. Retrospective series reporting the results of postoperative irradiation suggest that postoperative radiation therapy to the tumor bed may be beneficial for patients with Stage B3, C2 and C3 disease with limited nodal involvement. Randomized prospective trials are required to further evaluate the efficacy of such adjuvant radiotherapy.

Authors
Willett, CG; Tepper, JE; Shellito, PC; Wood, WC
MLA Citation
Willett, CG, Tepper, JE, Shellito, PC, and Wood, WC. "Indications for adjuvant radiotherapy in extrapelvic colonic carcinoma." Oncology (Williston Park, N.Y.) 3.7 (1989): 25-32.
PMID
2641912
Source
scival
Published In
Oncology (Williston Park, N.Y.)
Volume
3
Issue
7
Publish Date
1989
Start Page
25
End Page
32

Patterns of failure following local excision and local excision and postoperative radiation therapy for invasive rectal adenocarcinoma

The clinical course of 40 patients undergoing conservative surgical excision and 26 patients undergoing local excision and postoperative radiation therapy of rectal carcinoma was reviewed. Surgical procedures were transanal excision (55 patients), Kraske procedure (ten patients), and fulguration (one patient). The five-year actuarial survival, disease-free survival, and local control of all 66 patients were 70%, 77%, and 63%, respectively. For patients undergoing local excision alone, the prognostic features of lesion size greater than 3 cm, poorly differentiated histology, invasion into muscularis propria or deeper, moderate to marked stromal fibrosis, vascular or lymph vessel invasion, fragmented resection, and positive resection margins were associated with a local failure rate of 20% or greater. Of the 26 patients receiving postoperative radiation therapy, four patients have developed local failure. For subgroups of patients with small rectal carcinomas confined to the mucosa, local excision may be a reasonable alternative to abdominoperineal resection. For tumors with deeper invasion but limited to the bowel wall, local excision plus pelvic irradiation can be offered to preserve anorectal function.

Authors
Willett, CG; Tepper, JE; Donnelly, S; Wood, WC; Shellito, PC; Rodkey, GV; Stracher, MA; Compton, CC
MLA Citation
Willett, CG, Tepper, JE, Donnelly, S, Wood, WC, Shellito, PC, Rodkey, GV, Stracher, MA, and Compton, CC. "Patterns of failure following local excision and local excision and postoperative radiation therapy for invasive rectal adenocarcinoma." Journal of Clinical Oncology 7.8 (1989): 1003-1008.
PMID
2754446
Source
scival
Published In
Journal of Clinical Oncology
Volume
7
Issue
8
Publish Date
1989
Start Page
1003
End Page
1008

Modulation of the transformed and neoplastic phenotype of rat fibroblasts by MHC-I gene expression

Transfection of the activated ras oncogene (Ha-ras) into second passage rat embryo fibroblasts can induce the metastatic phenotype, while cotransfection of Ha-ras with the adenovirus type 2 E1a gene (Ad2-E1a) yields cells which are tumorigenic but nonmetastatic in nude mice. Because of the presence in nude mice of natural killer cells and B-lymphocytes, which might account for the different metastatic behavior of single versus double transfectants, we used triple deficient mutants as recipient animals in tumorigenicity assays. These mice carry two additional mutations resulting in the deficiency of natural killer cells and activated B-lymphocytes. We observed that the rat embryo fibroblast transfectants exhibit the same metastatic behavior in nude as well as in triple deficient mice, indicating that natural killer and B-cells are not responsible for the observed difference in metastatic phenotype between Ha-ras and Ha-ras plus Ad2-E1a transfectants. Double transfectants were found to express higher levels of major histocompatibility complex class I genes and the degree of expression appeared to correlate inversely with in vitro and in vivo parameters such as the ability to grow in agar-containing semisolid media and rate of tumor formation in triple deficient mice. Our observations are consistent with the concept that expression of major histocompatibility class I genes may be involved in regulating and modifying cell behavior by mechanisms independent of their role in immune recognition.

Authors
Gattoni-Celli, S; Strauss, RM; Willett, CG; Pozzatti, R; Isselbacher, KJ
MLA Citation
Gattoni-Celli, S, Strauss, RM, Willett, CG, Pozzatti, R, and Isselbacher, KJ. "Modulation of the transformed and neoplastic phenotype of rat fibroblasts by MHC-I gene expression." Cancer Research 49.12 (1989): 3392-3395.
PMID
2655894
Source
scival
Published In
Cancer Research
Volume
49
Issue
12
Publish Date
1989
Start Page
3392
End Page
3395

Stage IA to IIB mediastinal Hodgkin's disease: Three-dimensional volumetric assessment of response to treatment

From 1979 to 1986, the response to treatment of 53 patients with stage IA to IIB mediastinal Hodgkin's disease was evaluated by three-dimensional volumetric analysis using thoracic computed tomographic (CT) scans. The mean initial volume of mediastinal disease in 34 patients treated with mantle and para-aortic irradiation was 166 mL, whereas for 19 patients treated with two to six cycles of multiagent chemotherapy and mantle and para-aortic irradiation the mean initial volume was 446 mL. Preliminary data suggested that patients with mediastinal volumes of < 200 mL had a lower mediastinal relapse rate (13%) than patients with volumes > 200 mL (32%). For 12 patients receiving six cycles of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), those with a > 85% reduction in volume 1 to 2 months after chemotherapy had a lower incidence of mediastinal relapse (zero of six, 0%) compared with patients having 85% or less reduction in volume (four of six, 67%). The primary value of this technique is that it provides a sensitive assessment of response to treatment and may aid in monitoring the effectiveness of a given treatment.

Authors
Willett, CG; Linggood, RM; Leong, JC; Miketic, LM; Stracher, MA; Skates, SJ; Kushner, DC
MLA Citation
Willett, CG, Linggood, RM, Leong, JC, Miketic, LM, Stracher, MA, Skates, SJ, and Kushner, DC. "Stage IA to IIB mediastinal Hodgkin's disease: Three-dimensional volumetric assessment of response to treatment." Journal of Clinical Oncology 6.5 (1988): 819-824.
PMID
3367187
Source
scival
Published In
Journal of Clinical Oncology
Volume
6
Issue
5
Publish Date
1988
Start Page
819
End Page
824

Three-dimensional volumetric assessment of response to treatment: Stage I and II diffuse large cell lymphoma of the mediastinum

From 1981 to 1986, 12 patients with Stage I and II diffuse large cell lymphoma of the mediastinum were treated with 4 or more cycles of multiagent chemotherapy and for nine patients this was followed by mediastinal irradiation. The response to treatment was assessed by three-dimensional volumetric analysis utilizing thoracic CT scans. The initial mean tumor volume of the five patients relapsing was 540 ml in contrast to an initial mean tumor volume of 360 ml for the seven patients remaining in remission. Of the eight patients in whom mediastinal lymphoma volumes could be assessed 1-2 months after chemotherapy prior to mediastinal irradiation, the three patients who have relapsed had volumes of 292, 92, and 50 ml (mean volume 145 ml) in contrast to five patients who have remained in remission with residual volume abnormalities of 4-87 ml (mean volume 32 ml). Four patients in prolonged remission with CT scans taken one year after treatment have been noted to have mediastinal tumor volumes of 0-28 ml with a mean value of 10 ml. This volumetric technique to assess the extent of mediastinal large cell lymphoma from thoracic CT scans appears to be a useful method to quantitate the amount of disease at presentation as well as objectively monitor response to treament. © 1988.

Authors
Willett, CG; Stracher, MA; Linggood, RM; Miketic, LM; Leong, JC; Skates, SJ; Kushner, DC; Jacobson, JO
MLA Citation
Willett, CG, Stracher, MA, Linggood, RM, Miketic, LM, Leong, JC, Skates, SJ, Kushner, DC, and Jacobson, JO. "Three-dimensional volumetric assessment of response to treatment: Stage I and II diffuse large cell lymphoma of the mediastinum." Radiotherapy and Oncology 12.3 (1988): 193-198.
PMID
3175046
Source
scival
Published In
Radiotherapy & Oncology
Volume
12
Issue
3
Publish Date
1988
Start Page
193
End Page
198

Effects of pentobarbital anesthesia on the energy metabolism of murine tumors studied by in vivo 31P nuclear magnetic resonance spectroscopy

The effects of pentobarbital anesthesia on the energy metabolism of FSaII and MCaIV foot tumors in mice were studied by 31P MRS. Using an 8.5 T spectrometer, in vivo spectra were obtained in 15 animals before and after pentobarbital anesthesia (0.05 mg/g ip). The average phosphocreatine/inorganic phosphate ratios (PCr/P(i)) with and without pentobarbital were similar for both tumor histologies. Effects on individual tumors, however, were greater than 20% in 9/15 animals and greater than 50% in 6/15 animals. Pentobarbital anesthesia increased the variability of tumor intracellular pH, and the phosphomonoester/nucleotide triphosphate (PME/NTP) and nucleotide triphosphate/inorganic phosphate ratios (NTP/P(i)). When examining the average in a cohort, pentobarbital anesthesia had no significant effect on the PCr/P(i), PME/NTP, NTP/P(i) ratios or the pH. However, ≃ 50% of individual tumors do have significant changes in these parameters. The anesthesia-induced variability of tumor energy metabolism may explain the decrease in TCD50 observed in previous studies using multifraction radiation.

Authors
Okunieff, P; Rummeny, E; Vaupel, P; Skates, S; Willett, C; Neuringer, LJ; Suit, HD
MLA Citation
Okunieff, P, Rummeny, E, Vaupel, P, Skates, S, Willett, C, Neuringer, LJ, and Suit, HD. "Effects of pentobarbital anesthesia on the energy metabolism of murine tumors studied by in vivo 31P nuclear magnetic resonance spectroscopy." Radiation Research 115.2 (1988): 361-372.
PMID
3406373
Source
scival
Published In
Radiation Research
Volume
115
Issue
2
Publish Date
1988
Start Page
361
End Page
372

Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy

Thirty adults with large cell lymphoma predominantly localized to the mediastinum diagnosed at the Massachusetts General Hospital between 1976 and 1985 were identified. The median age of the 20 females and 10 males was 34 years. All but one presented with symptoms due to an enlarging mediastinal mass, which was localized in 22 patients (73%) and exceeded 10 cm in maximal diameter in 65%. Superior vena cava syndrome and large pleural and pericardial effusions were common. Employing CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) and consolidation radiation therapy in most cases, 80% achieved a complete remission and 59% survive failure-free at 5 years by actuarial calculation. The size of the mediastinal mass adversely affected failure-free survival (89% vs. 40%, P < 0.05). No other pretreatment risk factor predicted outcome, but more intense chemotherapy was associated with improved survival (P = 0.035). Large cell mediastinal lymphoma is a locally invasive, often bulky malignancy with a predilection for young women; disease of low or moderate bulk is curable with full dose CHOP chemotherapy and consolidation radiation, but bulky disease requires more aggressive treatment.

Authors
Jacobson, JO; Aisenberg, AC; Lamarre, L; Willett, CG; Linggood, RM; Miketic, LM; Harris, NL
MLA Citation
Jacobson, JO, Aisenberg, AC, Lamarre, L, Willett, CG, Linggood, RM, Miketic, LM, and Harris, NL. "Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy." Cancer 62.9 (1988): 1893-1898.
PMID
3167803
Source
scival
Published In
Cancer
Volume
62
Issue
9
Publish Date
1988
Start Page
1893
End Page
1898

Partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the H-2 class I gene H-2L(d) into a huamn colon cancer cell line (HCT)

Many human tumors, particularly those of epithelial origin, appear to express greatly reduced levels of major histocompatibility complex class I antigens on their surface. It has been previously reported that the class I gene H-2L(d), introduced into adenovirus type 12-transformed mouse cells, induces reversal of oncogenesis in immunocompetent BALB/c mice. We have tested the hypothesis that the H-2L(d) gene, when transfected into HCT colon cancer cells, may alter their transformed phenotype. Two H-2L(d) transfectants, HCT-Ii and HCT-If, were found to exhibit a markedly reduced-to-virtually suppressed ability to form colonies in soft agar in comparison to a transfectant (HCTh) carrying only the neomycin-resistant gene. We also compared the tumorigenicity of HCTh vs. HCT-If cells in two different strains of immunodeficient mice: nude (T-) and triple-deficient mutants (T-, NK-, B-). At 28 days postinjection of 107 and 106 cells, the size and growth rate of HCT-If tumors were greatly reduced compared to HCTh cells. Therefore, as assayed in immunodeficient animals, expression of the class I H-2L(d) gene in HCT cells appears to correlate with partial suppression of the tumorigenic phenotype, suggesting that the expression of a transfected class I gene may by itself alter the phenotype of the recipient cell and that such phenotypic changes may be independent of the immune system.

Authors
Gattoni-Celli, S; Willett, CG; Rhoads, DB; Simon, B; Strauss, RM; Kirsch, K; Isselbacher, KJ
MLA Citation
Gattoni-Celli, S, Willett, CG, Rhoads, DB, Simon, B, Strauss, RM, Kirsch, K, and Isselbacher, KJ. "Partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the H-2 class I gene H-2L(d) into a huamn colon cancer cell line (HCT)." Proceedings of the National Academy of Sciences of the United States of America 85.22 (1988): 8543-8547.
PMID
3186742
Source
scival
Published In
Proceedings of the National Academy of Sciences of the United States of America
Volume
85
Issue
22
Publish Date
1988
Start Page
8543
End Page
8547

Resident award essay: Effect of temperature on blood flow and hypoxic fraction in a murine fibrosarcoma

The effect of hypo to hyperthermic temperatures on tumor blood flow and hypoxic cell fractions was studied in a murine fibrosarcoma transplanted in the hind leg of anesthetized mice. The blood flow to the tumor was assessed by the determination of the uptake of Thallium-201; the hypoxic cell fraction was estimated from cell survival curves derived from data based on lung colony assay. Over a temperature range of 18° to 46°C, the maximal blood flow occurred at 35°C which was approximately two times greater than that at room temperature (24°C) or at 39°C. The hypoxic cell fraction at 35°C was 11%, and was significantly less than that at 24°C or at 39°C. The hypoxic cell fractions at 24°C and at 39°C were 45% and 32°10, respectively. These results suggest that the optimal radiation sensitivity of peripherally located tumors can be obtained by warming the tumors to temperatures where maximal blood flow and minimal hypoxic cell fraction occur. © 1987.

Authors
Willett, CG; Urano, M; Suit, HD; Strauss, HW; Kahn, J; Okunieff, PG
MLA Citation
Willett, CG, Urano, M, Suit, HD, Strauss, HW, Kahn, J, and Okunieff, PG. "Resident award essay: Effect of temperature on blood flow and hypoxic fraction in a murine fibrosarcoma." International Journal of Radiation Oncology, Biology, Physics 13.9 (1987): 1309-1312.
PMID
3624040
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
13
Issue
9
Publish Date
1987
Start Page
1309
End Page
1312

The effect of the respiratory cycle on mediastinal and lung dimensions in Hodgkin's disease. Implications for radiotherapy gated to respiration

Changes in mediastinal and lung dimensions during respiration were studied to assess the potential of radiotherapy gated to respiration to minimize normal tissue irradiation. Twelve patients with mediastinal Hodgkin's disease were assessed using chest radiographs and thoracic computed tomography (CT) scans both during quiet breathing and at maximum inspiration in the standing, supine, and prone positions. A simple measure of the bulk of mediastinal disease, the ratio of the width of mediastinal mass to thoracic diameter, was determined from posteroanterior (PA) chest radiographs. The volumes of mediastinum, irradiated and protected lung if anteroposterior (AP) and PA mantle fields were used were determined from sequential thoracic CT scans and three-dimensional treatment planning and compared at quiet breathing and deep inspiration. The mediastinal width to thoracic diameter ratio decreased from quiet breathing to deep inspiration an average of 3%, 9%, and 11% for the standing, supine, and prone positions, respectively. Lung volumes as measured from the thoracic CT scans showed that on average, 8% more lung was protected at deep inspiration than at quiet breathing, independent of treatment position. The maximum increase in the percentage of protected lung from quiet breathing to deep inspiration was seen in patients with extensive mediastinal adenopathy suggesting that radiotherapy gated to respiration may be most advantageous in the subset of patients.

Authors
Willett, CG; Linggood, RM; Stracher, MA; Goitein, M; Doppke, K; Kushner, DC; Morris, T; Pardy, J; Carroll, R
MLA Citation
Willett, CG, Linggood, RM, Stracher, MA, Goitein, M, Doppke, K, Kushner, DC, Morris, T, Pardy, J, and Carroll, R. "The effect of the respiratory cycle on mediastinal and lung dimensions in Hodgkin's disease. Implications for radiotherapy gated to respiration." Cancer 60.6 (1987): 1232-1237.
PMID
3621109
Source
scival
Published In
Cancer
Volume
60
Issue
6
Publish Date
1987
Start Page
1232
End Page
1237

Adjuvant postoperative radiation therapy for colonic carcinoma

One hundred thirty-three patients with Stage B2, B3, and C colonic carcinoma had resection for curative intent followed by adjuvant postoperative radiotherapy to the tumor bed. The 5-year actuarial local control and disease-free survival rates for these 133 patients were 82% and 61%, respectively. Stage for stage, the development of local regional failure was reduced for patients receiving postoperative radiotherapy compared with a historic control series. Local recurrence occurred in 8%, 21%, and 31% of patients with Stage B3, C2, and C3 tumors who had radiation therapy, respectively, whereas the local failure rates were 31%, 36%, and 53% in patients treated with surgery alone. There was a 13% and 12% improvement in the 5-year disease-free survival rate in the patients with Stage B3 and C3 lisions who had radiotherapy compared with the historic controls. For patients with Stage C disease, local control and disease-free survival rates dicreases progressively with increasing nodal involvement; however, local control and disease-free survival rates were higher in the patents who had radiotherapy in those who had surgery alone. Failure patterns in the patients who had radiotherapy did not show any notable changes compared with those for patients who had surgery alone. Postoperative radiation therapy for Stage B3, C2, and C3 colonic carcinoma is a prominsing treatment approach that deserves further investigation.

Authors
Willett, CG; Tepper, JE; Skates, SJ; Wood, WC; Orlow, EC; Duttenhaver, JR
MLA Citation
Willett, CG, Tepper, JE, Skates, SJ, Wood, WC, Orlow, EC, and Duttenhaver, JR. "Adjuvant postoperative radiation therapy for colonic carcinoma." Annals of Surgery 206.6 (1987): 694-698.
PMID
3689006
Source
scival
Published In
Annals of Surgery
Volume
206
Issue
6
Publish Date
1987
Start Page
694
End Page
698

Effects of oxygen on the metabolism of murine tumors using in vivo phosphorus-31 NMR

Authors
Okunieff, P; McFarland, E; Rummeny, E; Willett, C; Hitzig, B; Neuringer, L; Suit, H
MLA Citation
Okunieff, P, McFarland, E, Rummeny, E, Willett, C, Hitzig, B, Neuringer, L, and Suit, H. "Effects of oxygen on the metabolism of murine tumors using in vivo phosphorus-31 NMR." American Journal of Clinical Oncology: Cancer Clinical Trials 10.6 (1987): 475-482.
PMID
3687832
Source
scival
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
10
Issue
6
Publish Date
1987
Start Page
475
End Page
482

The histologic response of soft tissue sarcoma to radiation therapy

Twenty-seven patients with soft tissue sarcoma had preoperative radiotherapy, limb-sparing marginal surgical resection and whole-mount tumor histologic analysis. Incisional biopsy specimens before radiotherapy and reviewed for tumor type, grade, and extent of necrosis. Preoperative radiotherapy was given in either of two regimens: 13 patients received a mean total dose of 5250 cGy in one daily 180 to 200 cGy fractions and 14 patients a mean total dose of 4770 cGy in two daily fractions of 180 to 200 cGy separated by 4 hours. Twenty-one specimens had at least 80% necrosis or severely altered cells, a 3+ to 4+ response. Grade and size of the tumor appeared to be indicators of response to treatment rather than histologic type. Three of five patients (60%) with Grade 1, eight of 11 patients (73%) with Grade 2 lesions, and ten of 11 patients (91%) with Grade 3 tumors had 80% or greater necrosis or severely altered cells. For tumors 10 cm or less in greatest diameter, the 3+ to 4+ histologic response was seen in 12 of 14 patients (86%) whereas for lesions greater than 10 cm, this response was observed in nine of 13 patients (69%). For patients with Grade 2 or 3 soft tissue sarcoma, 13 of 14 patients (93%) treated with two fractions per day and two of four patients (50%) receiving one fraction per day exhibited significant response. All six patients treated daily for lesions greater than 10 cm had 3+ to 4+ histologic response compared to three of seven (43%) patients treated once per day. Therefore, grade and size of soft tissue sarcoma are important predictors of response to radiotherapy and preoperative twice daily radiotherapy may more likely permit the conservative surgical excision of sarcomas of borderline resectability.

Authors
Willett, CG; Schiller, AL; Suit, HD; Mankin, HJ; Rosenberg, A
MLA Citation
Willett, CG, Schiller, AL, Suit, HD, Mankin, HJ, and Rosenberg, A. "The histologic response of soft tissue sarcoma to radiation therapy." Cancer 60.7 (1987): 1500-1504.
PMID
3040219
Source
scival
Published In
Cancer
Volume
60
Issue
7
Publish Date
1987
Start Page
1500
End Page
1504

Results of treatment of Stage 3A Hodgkin's disease

From 1975 to 1981, 38 patients with Stage 3A Hodgkin's disease (35 patients pathologically staged) underwent mantle and para-aortic irradiation, and in 36 patients this was preceded or followed by at least six cycles of multiagent chemotherapy. Both the 5-year actuarial survival and disease-free survival for all 38 patients were 83%. There have been six treatment failures: two patients have relapsed within irradiated nodal groups, one patient in apical pericardial lymph nodes as a marginal recurrence, one patient concurrently infield and in unirradiated nodal groups, and two patients systemically (concurrently in unirradiated nodal groups). Of these six relapses, three patients have died of Hodgkin's disease, one patient has been salvaged, and two patients currently are under treatment for salvage. One patient has developed acute nonlymphocytic leukemia and died of this disease. Extensive disease, as estimated by the number of sites of involvement at presentation, degree of splenic involvement, extent of intra-abdominal disease or mediastinal involvement, did not reveal statistically significant prognostic subgroups for relapse. It is currently recommended that patients with Stage 3A Hodgkin's disease receive six cycles of multiagent chemotherapy and mantle and para-aortic irradiation.

Authors
Willett, CG; Linggood, RM; Meyer, J; Orlow, E; Lindfors, K; Doppke, K; Aisenberg, AC
MLA Citation
Willett, CG, Linggood, RM, Meyer, J, Orlow, E, Lindfors, K, Doppke, K, and Aisenberg, AC. "Results of treatment of Stage 3A Hodgkin's disease." Cancer 59.1 (1987): 27-30.
PMID
3791147
Source
scival
Published In
Cancer
Volume
59
Issue
1
Publish Date
1987
Start Page
27
End Page
30

Results of treatment of stage IA and IIA Hodgkin's disease

This study analyzed the 5 year actuarial survival and disease-free survival of 122 patients with Stage IA and IIA Hodgkin's disease, (108 patients laparotomy staged) treated with mantle and paraaortic irradiation from 1975 to 1981. Prognostic subgroups and patterns of treatment failure were investigated. The 5 year actuarial survival and disease-free survival was 91% and 75% respectively for the entire group. For Stage IA patients, the 5 year survival and disease-free survival was 92% and 86% respectively, whereas for those in Stage IIA the respective figures were 86% and 65%. Individuals with greater than four sites of involvement at initial presentation; extensive mediastinal adenopathy; hilar or extramediastinal extension to lung, pleura or pericardium, had a poorer 5 year actuarial disease-free survival (43%-60%) than those without these factors (70-85%). Of the 122 patients, there were 26 relapses: nine infield failures; two concurrent infield and systemic failures; nine marginal recurrences, and three relapses occurring systemically and three in nodal groups not irradiated. Following relapse, 17 patients were salvaged with chemotherapy. Two patients are alive with disease and seven patients died of Hodgkin's disease. Patients with less extensive mediastinal adenopathy and supradiaphragmatic nonmediastinal presentations can be satisfactorily treated with mantle and paraaortic irradiation, whereas patients with extensive mediastinal adenopathy receive six cycles of multiagent chemotherapy before irradiation.

Authors
Willett, CG; Linggood, RM; Meyer, J; Orlow, E; Lindfors, K; Doppke, K; Aisenberg, AC
MLA Citation
Willett, CG, Linggood, RM, Meyer, J, Orlow, E, Lindfors, K, Doppke, K, and Aisenberg, AC. "Results of treatment of stage IA and IIA Hodgkin's disease." Cancer 59.6 (1987): 1107-1111.
PMID
3815284
Source
scival
Published In
Cancer
Volume
59
Issue
6
Publish Date
1987
Start Page
1107
End Page
1111
DOI
10.1002/1097-0142(19870315)59:6<1107::AID-CNCR2820590611>3.0.CO;2-W

Renal complications secondary to radiation treatment of upper abdominal malignancies

A retrospective review of all patients undergoing radiotherapy for carcinoma of the colon, pancreas, stomach, small bowel and bile ducts, lymphomas of the stomach, and other GI sites and retroperitoneal sarcomas was completed to assess the effects of secondary irradiation on the kidney. Eighty-six adult patients were identified who were treated with curative intent, received greater than 50% unilateral kidney irradiation to doses of at least 2600 cGy and survived for 1 year or more. Following treatment, the clinical course, blood pressure, addition of anti-hypertensive medications, serum creatinine and creatinine clearance were determined. Creatinine clearance was calculated by the formula: creatiinine clearance equals [(140 - age) × (weight in kilograms)] ÷ (72 × serum creatinine) which has a close correlation to creatinine clearances measured by 24 hr. urine measurements. The percent change in creatinine clearance from pre-treatment values was analyzed. Of the thirteen patients with pre-radiotherapy hypertension, four required an increase in the number of medications for control and nine required no change in medication. Two patients developed hypertension in follow-up, one controlled with medication and the other malignant hypertension. Acute or chronic renal failure was not observed in any patient. The serum creatinine for all 86 patients prior to radiation therapy was below 2 mg/100 ml; in follow-up it rose to between 2.2-2.9 mg/100 ml. in five patients. The mean creatinine clearance for all 86 patients prior to radiotherapy was 77 ml/minute and for 16 patients with at least 5 years of follow-up it was 62 ml/minute. The mean percent decrease in creatinine clearance appeared to correspond to the percentage of kidney irradiated: for 38 patients with only 50% of the kidney irradiated the mean percent decrease was 10%, whereas for 31 patients having 90 to 100% of the kidney treated the decrease was 24%. Although physiologic changes were seen in patients receiving 50% or more unilateral kidney irradiation, the development of significant clinical sequelae was limited to one patient. © 1986.

Authors
Willett, CG; Tepper, JE; Orlow, EL; Shipley, WU
MLA Citation
Willett, CG, Tepper, JE, Orlow, EL, and Shipley, WU. "Renal complications secondary to radiation treatment of upper abdominal malignancies." International Journal of Radiation Oncology, Biology, Physics 12.9 (1986): 1601-1604.
PMID
3759586
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
12
Issue
9
Publish Date
1986
Start Page
1601
End Page
1604

Obstructive and perforative colonic carcinoma: Patterns of failure

Carcinoma of the colon complicated by obstruction or perforation has been recognized as having a poorer prognosis than tumors without obstruction or perforation. To clarify the natural history, failure patterns, and implications for adjuvant treatment after resection with curative intent, a review of the recent Massachusetts General Hospital (MGH) experience was undertaken. From 1970 to 1977, 77 patients with obstructive colonic carcinoma and 34 patients with localized perforation at the tumor site were identified and compared with a control group of 400 patients without obstruction or perforation undergoing curative resection. All patients were observed for a minimum of five years or until the patient's death. The actuarial five-year survival and disease-free survival rates in patients with obstruction was 31% and 44%, respectively, in contrast to 59% and 75% in control patients. For patients with localized perforation, the five-year actuarial survival and disease-free survival rates were 44% and 35%, respectively. Of the 77 patients with obstructing tumors, 32 patients (42%) developed local failure - nine with local failure only and 23 patients with local failure and distant metastases. Thirty-four patients (44%) developed distant metastases. Fifteen (44%) patients of 34 with perforative colonic carcinoma had local failure. Distant metastases occurred in 15 patients (44%). The incidence of local failure and distant metastases in the control group was 14% and 21%, respectively. The rate of local failure and distant metastases increased with stage and was generally higher stage for stage than in the control group. Patients with stage B2 disease with obstruction of perforation experienced a 20% incidence of local failure in contrast to only 6% in patients with either of these findings. The incidence of local failure in patients with stages B3, C2, and C3 disease with obstruction or perforation was 52% v 27% in the control group. Intra-abdominal metastatic failure (liver or peritoneal surfaces) for obstructive or perforative patients was 32% and 42%, respectively, v 19% in the control group.

Authors
Willett, C; Tepper, JE; Cohen, A; Orlow, E; Welch, C
MLA Citation
Willett, C, Tepper, JE, Cohen, A, Orlow, E, and Welch, C. "Obstructive and perforative colonic carcinoma: Patterns of failure." Journal of Clinical Oncology 3.3 (1985): 379-384.
PMID
3973649
Source
scival
Published In
Journal of Clinical Oncology
Volume
3
Issue
3
Publish Date
1985
Start Page
379
End Page
384

Local failure following curative resection of colonic adenocarcinoma

A retrospective review of the medical records of 533 patients undergoing resection with curative intent of large bowel above the peritoneal reflection was undertaken to identify subsets of patients at high risk for local failure. The overall local failure rate was 102 533 (19%) with 32 102 patients having local failure only and 70 102 patients having concurrent local failure and distant metastases. Pathological confirmation of local failure was obtained in 79% of the cases and by surgical exploration in 75%. Overall local failure rates increased with advancing stage of disease. Tumors staged B3, C2 and C3 all had local failure rates in excess of 30%, whereas for Stage A, B1, B2 and C1 lesions, the incidence of local failure was less than 4%. Stage B2 tumors arising in high and low sigmoid and splenic and hepatic flexure had a moderate incidence of local failure (21%) compared to low incidence (5%) at all other sites. The majority of local and regional failures 84 102 (82%) occurred in tumor bed and adjacent soft tissues whereas only 18 102 (18%) local failures occurred in regional nodal groups. The overall local failure rate increased from 27% with one lymph node involved to 50% with greater than 5 lymph nodes involved. Patients with Stage B3, C2 and C3 colon tumors at all sites and selected B2 tumors have a high rate of local failure after surgical resection. The value of postoperative radiotherapy should be formally studied in these patients. © 1984.

Authors
Willett, C; Tepper, JE; Cohen, A; Orlow, E; Welch, C; Donaldson, G
MLA Citation
Willett, C, Tepper, JE, Cohen, A, Orlow, E, Welch, C, and Donaldson, G. "Local failure following curative resection of colonic adenocarcinoma." International Journal of Radiation Oncology, Biology, Physics 10.5 (1984): 645-651.
PMID
6735753
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
10
Issue
5
Publish Date
1984
Start Page
645
End Page
651

Failure patterns following curative resection of colonic carcinoma

To identify patterns of failure following curative resection of colonic (nonrectal) carcinoma, the medical records of 533 patients undergoing resection with curative intent were reviewed. The overall local failure rate was 19% (102/533 patients) with 32 patients having local failure alone and 70 patients having concurrent local failure and distant metastases. The incidence of local failure rose with advancing stage of disease. Tumors staged B3, C2, and C3 had local failure rates in excess of 30%. Local failures occurred predominantly in tumor bed and adjoining structures (82%) and not by regional nodal failure (18%). One hundred thirty-one patients (25%) developed distant metastases. One hundred ten patients (84%) failed in the abdomen-liver, peritoneal seeding, para-aortic, or portahepatic lymph nodes. Patients with Stage B3, C2, and C3 tumors were found to have abdominal failure rates (excluding local failure) of greater than 20%. The highest failure rates in the liver were in Stage C2 and C3 patients in which the subsequent development of liver metastases was 29% and 31%, respectively. In Stage C3, peritoneal seeding and abdominal lymph node failure occurred in 18% and 14% of the patients, respectively.

Authors
Willett, CG; Tepper, JE; Cohen, AM; Orlow, E; Welch, CE
MLA Citation
Willett, CG, Tepper, JE, Cohen, AM, Orlow, E, and Welch, CE. "Failure patterns following curative resection of colonic carcinoma." Annals of Surgery 200.6 (1984): 685-690.
PMID
6508395
Source
scival
Published In
Annals of Surgery
Volume
200
Issue
6
Publish Date
1984
Start Page
685
End Page
690

The impact of coronary artery disease on carotid endarterectomy.

In a series of 531 CENDX, preoperative cardiac risk was categorized by clinical criteria. Patients with CAD (history of previous MI, angina, congestive heart failure, and/or electrocardiographic evidence of CAD were selected for more invasive studies based on clinical criteria. The overall incidence of postoperative myocardial infarction was 2.5% and increased slightly to 4% in patients with symptomatic cardiac disease. More importantly, the overall mortality was 0.9% and only 3 of 13 (23%) postoperative myocardial infarctions were fatal. Neurologic complications averaged 1.4% and approximately 70% were related to preceding cardiac events. Twenty-two patients or 4% of the entire series underwent carotid endarterectomy combined with coronary artery bypass graft and this approach was associated with one death and one stroke. Therefore, we conclude that a selective approach to coronary arteriography and subsequent CABG based on clinical criteria is associated with an acceptably low mortality and cardiac morbidity.

Authors
O'Donnell, TF; Callow, AD; Willet, C; Payne, D; Cleveland, RJ
MLA Citation
O'Donnell, TF, Callow, AD, Willet, C, Payne, D, and Cleveland, RJ. "The impact of coronary artery disease on carotid endarterectomy." Annals of surgery 198.6 (December 1983): 705-712.
PMID
6605729
Source
epmc
Published In
Annals of Surgery
Volume
198
Issue
6
Publish Date
1983
Start Page
705
End Page
712
DOI
10.1097/00000658-198312000-00007

Effect of preoperative irradiation on resectability of colorectal carcinomas

From 1968 to January 1, 1977, 44 patients with initially unresectable colorectal carcinoma were treated with preoperative radiotherapy and surgery. On presentation, unresectability was determined either clinically (26 patients) or by preradiotherapy laparotomy (18 patients). Preoperative irradiation consisted of 4500-5000 rad. After radiotherapy, 33 of 44 lesions were considered resectable. Seven of 33 patients underwent incomplete resection with mean survival of 17 months. Resection was complete in 26 of the 33 patients. Of the latter group (26), 18 patients are alive with no evidence of disease with minimum follow-up of 36 months. Detailed results are discussed. © 1982.

Authors
Emami, B; Pilepich, M; Willett, C; Munzenrider, JE; Miller, HH
MLA Citation
Emami, B, Pilepich, M, Willett, C, Munzenrider, JE, and Miller, HH. "Effect of preoperative irradiation on resectability of colorectal carcinomas." International Journal of Radiation Oncology, Biology, Physics 8.8 (1982): 1295-1299.
PMID
7141908
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
8
Issue
8
Publish Date
1982
Start Page
1295
End Page
1299
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