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Czito, Brian Gary

Overview:

Listed in Best Doctors in America. Listed in Top Doctors in North Carolina. His research interests include gastrointestinal malignancies, including treatment and integration of novel systemic agents with radiation therapy in the treatment of esophageal, gastric, hepatobiliary, pancreatic, colorectal and anal malignancies; phase I/II clinical trials evaluating novel systemic/targeted agents in conjunction with radiation therapy; investigation and optimization of the treatment of gastrointestinal malignancies, with focus on the above tumor sites.

Positions:

Gary Hock and Lyn Proctor Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1996

M.D. — Medical College of Georgia School of Medicine

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

Biomarker Studies for Novel Anti-Cancer Agents

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
May 28, 2003
End Date
February 29, 2008

Publications:

Total neoadjuvant therapy for rectal cancer: An emerging option.

The treatment of locally advanced rectal cancer (LARC) has benefited from improved surgical techniques and from the implementation of neoadjuvant chemoradiotherapy (CRT), which have markedly decreased the rates of local recurrence. However, distant metastatic disease remains the most significant cause of death for these patients. Although adjuvant chemotherapy (ChT) after neoadjuvant CRT and definitive surgery is commonly recommended, the value of adjuvant systemic therapy remains less clear. Trials evaluating adjuvant ChT for rectal cancer have been handicapped by poor compliance rates and inconsistent survival results. Shifting systemic therapy delivery to the neoadjuvant setting has the promise to improve compliance rates, reduce toxicity, and decrease distant relapse rates. Recently, multiple prospective trials have reported on the use of total neoadjuvant therapy (TNT) for patients with LARC, incorporating both ChT and CRT in the neoadjuvant setting. Here, the authors review the promising results from those trials. Because the studies have largely focused on pathologic outcomes (primarily pathologic complete response rates), ongoing phase 2 and 3 trials are now underway assessing the long-term disease-related outcomes with TNT. In addition to improving survival, TNT has the potential to increase the pool of patients with LARC who are eligible for organ preservation, which is also being evaluated. Cancer 2017. © 2017 American Cancer Society.

Authors
Ludmir, EB; Palta, M; Willett, CG; Czito, BG
MLA Citation
Ludmir, EB, Palta, M, Willett, CG, and Czito, BG. "Total neoadjuvant therapy for rectal cancer: An emerging option." Cancer (March 10, 2017).
PMID
28295220
Source
epmc
Published In
Cancer
Publish Date
2017
DOI
10.1002/cncr.30600

Association Between Incomplete Neoadjuvant Radiotherapy and Survival for Patients With Locally Advanced Rectal Cancer.

Failing to complete chemotherapy adversely affects survival in patients with colorectal cancer. However, the effect of incomplete delivery of neoadjuvant radiotherapy is unclear.To determine whether incomplete radiotherapy delivery is associated with worse clinical outcomes and survival.Data on 17 600 patients with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy followed by surgical resection were included. Multivariable regression methods were used to compare resection margin positivity, permanent colostomy rate, 30-day readmission, 90-day mortality, and overall survival between patients who received complete (45.0-50.4 Gy) and incomplete (<45.0 Gy) doses of radiation as preoperative therapy.The primary outcome measure was overall survival; short-term perioperative and oncologic outcomes encompassing margin positivity, permanent ostomy rate, postoperative readmission, and postoperative mortality were also assessed.Among 17 600 patients included, 10 862 were men, with an overall median age of 59 years (range, 51-68 years). Of these, 874 patients (5.0%) received incomplete doses of neoadjuvant radiation. The median radiation dose received among those who did not achieve complete dosing was 34.2 Gy (interquartile range, 19.8-40.0 Gy). Female sex (adjusted odds ratio [OR] 0.69; 95% CI, 0.59-0.81; P < .001) and receiving radiotherapy at a different hospital than the one where surgery was performed (OR, 0.72; 95% CI, 0.62-0.85; P < .001) were independent predictors of failing to achieve complete dosing; private insurance status was predictive of completing radiotherapy (OR, 1.60; 95% CI, 1.16-2.21; P = .004). At 5-year follow-up, overall survival was improved among patients who received a complete course of radiotherapy (3086 [estimated survival probability, 73.2%] vs 133 [63.0%]; P < .001). After adjustment for demographic, clinical, and tumor characteristics, patients receiving a complete vs incomplete radiation dose had a similar resection margin positivity (OR, 0.99; 95% CI, 0.72-1.35; P = .92), permanent colostomy rate (OR, 0.96; 95% CI, 0.70-1.32; P = .81), 30-day readmission rate (OR, 0.92; 95% CI, 0.67-1.27; P = .62), and 90-day mortality (OR, 0.72; 95% CI, 0.33-1.54; P = .41). However, a complete radiation dose had a significantly lower risk of long-term mortality (adjusted hazard ratio, 0.70; 95% CI, 0.59-0.84; P < .001).Achieving a target radiation dose of 45.0 to 50.4 Gy is associated with a survival benefit in patients with locally advanced rectal cancer. Aligning all aspects of multimodal oncology care may increase the probability of completing neoadjuvant therapy.

Authors
Freischlag, K; Sun, Z; Adam, MA; Kim, J; Palta, M; Czito, BG; Migaly, J; Mantyh, CR
MLA Citation
Freischlag, K, Sun, Z, Adam, MA, Kim, J, Palta, M, Czito, BG, Migaly, J, and Mantyh, CR. "Association Between Incomplete Neoadjuvant Radiotherapy and Survival for Patients With Locally Advanced Rectal Cancer." JAMA surgery (March 8, 2017).
PMID
28273303
Source
epmc
Published In
JAMA Surgery
Publish Date
2017
DOI
10.1001/jamasurg.2017.0010

Four-dimensional diffusion-weighted MR imaging (4D-DWI): a feasibility study.

Diffusion-weighted Magnetic Resonance Imaging (DWI) has been shown to be a powerful tool for cancer detection with high tumor-to-tissue contrast. This study aims to investigate the feasibility of developing a four-dimensional DWI technique (4D-DWI) for imaging respiratory motion for radiation therapy applications.Image acquisition was performed by repeatedly imaging a volume of interest (VOI) using an interleaved multislice single-shot echo-planar imaging (EPI) 2D-DWI sequence in the axial plane. Each 2D-DWI image was acquired with an intermediately low b-value (b = 500 s/mm2 ) and with diffusion-encoding gradients in x, y, and z diffusion directions. Respiratory motion was simultaneously recorded using a respiratory bellow, and the synchronized respiratory signal was used to retrospectively sort the 2D images to generate 4D-DWI. Cine MRI using steady-state free precession was also acquired as a motion reference. As a preliminary feasibility study, this technique was implemented on a 4D digital human phantom (XCAT) with a simulated pancreas tumor. The respiratory motion of the phantom was controlled by regular sinusoidal motion profile. 4D-DWI tumor motion trajectories were extracted and compared with the input breathing curve. The mean absolute amplitude differences (D) were calculated in superior-inferior (SI) direction and anterior-posterior (AP) direction. The technique was then evaluated on two healthy volunteers. Finally, the effects of 4D-DWI on apparent diffusion coefficient (ADC) measurements were investigated for hypothetical heterogeneous tumors via simulations.Tumor trajectories extracted from XCAT 4D-DWI were consistent with the input signal: the average D value was 1.9 mm (SI) and 0.4 mm (AP). The average D value was 2.6 mm (SI) and 1.7 mm (AP) for the two healthy volunteers.A 4D-DWI technique has been developed and evaluated on digital phantom and human subjects. 4D-DWI can lead to more accurate respiratory motion measurement. This has a great potential to improve the visualization and delineation of cancer tumors for radiotherapy.

Authors
Liu, Y; Zhong, X; Czito, BG; Palta, M; Bashir, MR; Dale, BM; Yin, F-F; Cai, J
MLA Citation
Liu, Y, Zhong, X, Czito, BG, Palta, M, Bashir, MR, Dale, BM, Yin, F-F, and Cai, J. "Four-dimensional diffusion-weighted MR imaging (4D-DWI): a feasibility study." Medical physics 44.2 (February 2017): 397-406.
PMID
28121369
Source
epmc
Published In
Medical physics
Volume
44
Issue
2
Publish Date
2017
Start Page
397
End Page
406
DOI
10.1002/mp.12037

Intensity-Modulated Radiation Therapy Is Not Associated with Perioperative or Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer.

The use of intensity-modulated radiation therapy (IMRT) in rectal cancer has steadily increased over traditional 3D conformal radiotherapy (3D-CRT) due to perceived benefit of delivering higher treatment doses while minimizing exposure to surrounding tissues. However, IMRT is technically challenging and costly, and its effects on rectal cancer outcomes remain unclear.Adults with clinical stage II and III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy with 45-54 Gy of radiation and surgery were included from the 2006-2013 National Cancer Data Base. Patients were grouped based the modality of radiation received: IMRT or 3D-CRT. Multivariable regression modeling adjusting for demographic, clinical, and treatment characteristics was used to examine the impact of IMRT vs. 3D-CRT on pathologic downstaging, resection margin positivity, sphincter loss surgery, 30-day unplanned readmission and mortality after surgery, and overall survival.Among 7386 patients included, 3330 (45 %) received IMRT and 4056 (55 %) received 3D-CRT. While the mean radiation dose delivered was higher with IMRT (4735 vs. 4608 cGy, p < 0.001), it was associated with higher risks of positive margins (adjusted odds ratio (OR) 1.57; p < 0.001) and sphincter loss surgery (OR 1.32; p < 0.001). There were no differences between IMRT and 3D-CRT in the likelihood of pathologic downstaging (OR 0.89, p = 0.051), unplanned readmission (OR 0.79; p = 0.07), or 30-day mortality (OR 0.61; p = 0.31) after surgery. Additionally, there were no differences in overall survival at 8 years (IMRT vs. 3D-CRT: 64 vs. 64 %; adjusted hazard ratio 1.06, p = 0.47).IMRT is associated with worse local tumor control without any long-term survival benefit for patients with locally advanced rectal cancer. Given the lack of significant advantage and the higher cost of IMRT, caution should be exercised when using IMRT instead of traditional 3D-CRT for rectal cancer.

Authors
Sun, Z; Adam, MA; Kim, J; Czito, B; Mantyh, C; Migaly, J
MLA Citation
Sun, Z, Adam, MA, Kim, J, Czito, B, Mantyh, C, and Migaly, J. "Intensity-Modulated Radiation Therapy Is Not Associated with Perioperative or Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 21.1 (January 2017): 106-111.
PMID
27510332
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
21
Issue
1
Publish Date
2017
Start Page
106
End Page
111
DOI
10.1007/s11605-016-3242-8

Evolution and Management of Treatment-Related Toxicity in Anal Cancer.

Over the past several decades, clinical trials have demonstrated improved disease-related outcomes in the definitive treatment of anal cancer. Although treatment with radiation and concurrent chemotherapy results in high rates of cure, significant acute and late toxicities are seen. This review focuses on the evolution of treatment-related toxicity for anal cancer. Management of these adverse effects is reviewed, as are future directions in anal cancer treatment and their impact on toxicity.

Authors
Ludmir, EB; Kachnic, LA; Czito, BG
MLA Citation
Ludmir, EB, Kachnic, LA, and Czito, BG. "Evolution and Management of Treatment-Related Toxicity in Anal Cancer." Surgical oncology clinics of North America 26.1 (January 2017): 91-113.
PMID
27889040
Source
epmc
Published In
Surgical Oncology Clinics of North America
Volume
26
Issue
1
Publish Date
2017
Start Page
91
End Page
113
DOI
10.1016/j.soc.2016.07.004

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer.The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice.Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT.US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased patient convenience, and lower acute toxicity will increase the adoption of SC-RT by radiation oncologists in the United States. Cancer 2016. © 2016 American Cancer Society.

Authors
Mowery, YM; Salama, JK; Zafar, SY; Moore, HG; Willett, CG; Czito, BG; Hopkins, MB; Palta, M
MLA Citation
Mowery, YM, Salama, JK, Zafar, SY, Moore, HG, Willett, CG, Czito, BG, Hopkins, MB, and Palta, M. "Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States." Cancer (December 16, 2016).
PMID
27984651
Source
epmc
Published In
Cancer
Publish Date
2016
DOI
10.1002/cncr.30461

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

Radiation Therapy for Soft Tissue Sarcoma: Indications and Controversies for Neoadjuvant Therapy, Adjuvant Therapy, Intraoperative Radiation Therapy, and Brachytherapy.

Soft tissue sarcomas are rare mesenchymal cancers that pose a treatment challenge. Although small superficial soft tissue sarcomas can be managed by surgery alone, adjuvant radiotherapy in addition to limb-sparing surgery substantially increases local control of extremity sarcomas. Compared with postoperative radiotherapy, preoperative radiotherapy doubles the risk of a wound complication, but decreases the risk for late effects, which are generally irreversible. For retroperitoneal sarcomas, intraoperative radiotherapy can be used to safely escalate the radiation dose to the tumor bed. Patients with newly diagnosed sarcoma should be evaluated before surgery by a multidisciplinary team that includes a radiation oncologist.

Authors
Larrier, NA; Czito, BG; Kirsch, DG
MLA Citation
Larrier, NA, Czito, BG, and Kirsch, DG. "Radiation Therapy for Soft Tissue Sarcoma: Indications and Controversies for Neoadjuvant Therapy, Adjuvant Therapy, Intraoperative Radiation Therapy, and Brachytherapy." Surgical oncology clinics of North America 25.4 (October 2016): 841-860.
PMID
27591502
Source
epmc
Published In
Surgical Oncology Clinics of North America
Volume
25
Issue
4
Publish Date
2016
Start Page
841
End Page
860
DOI
10.1016/j.soc.2016.05.012

Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection.The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate.In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate.This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings. Ongoing trials may clarify areas of continuing uncertainty and allow further customization.

Authors
Goodman, KA; Patton, CE; Fisher, GA; Hoffe, SE; Haddock, MG; Parikh, PJ; Kim, J; Baxter, NN; Czito, BG; Hong, TS; Herman, JM; Crane, CH; Hoffman, KE
MLA Citation
Goodman, KA, Patton, CE, Fisher, GA, Hoffe, SE, Haddock, MG, Parikh, PJ, Kim, J, Baxter, NN, Czito, BG, Hong, TS, Herman, JM, Crane, CH, and Hoffman, KE. "Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method." Practical radiation oncology 6.3 (May 2016): 166-175.
PMID
26922700
Source
epmc
Published In
Practical Radiation Oncology
Volume
6
Issue
3
Publish Date
2016
Start Page
166
End Page
175
DOI
10.1016/j.prro.2015.11.014

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

Effect of combined neoadjuvant chemoradiation on overall survival for patients with locally advanced rectal cancer.

Authors
Sun, Z; Adam, MA; Kim, J; Hsu, S-WD; Palta, M; Czito, BG; Migaly, J; Mantyh, C
MLA Citation
Sun, Z, Adam, MA, Kim, J, Hsu, S-WD, Palta, M, Czito, BG, Migaly, J, and Mantyh, C. "Effect of combined neoadjuvant chemoradiation on overall survival for patients with locally advanced rectal cancer." February 1, 2016.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
34
Issue
4
Publish Date
2016

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.
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

Evaluation of Adjuvant Radiation Therapy for Resected Gallbladder Carcinoma: A Multi-institutional Experience.

The role of adjuvant radiation for gallbladder carcinoma (GBC) is uncertain. We combine the experience of six National Cancer Institute-designated cancer centers to explore the impact of adjuvant radiation following oncologic resection of GBC.Patients who underwent extended surgery for GBC at Johns Hopkins, Mayo Clinic, Duke University, Oregon Health & Science University, University of Michigan, and University of Texas MD Anderson between 1985 and 2008 were reviewed. Patients with metastatic disease at surgery, gross residual disease, or missing pathologic information were excluded.Of the 112 patients identified, 61 % received adjuvant radiation, 93 % of whom received concurrent chemotherapy. Median follow-up of surviving patients was 47.3 (range 2.2-167.7) months. Patients who received adjuvant radiation had a higher rate of advanced T-stage (57 vs. 16 %, p < 0.01), lymph node involvement (63 vs. 18 %, p < 0.01), and positive microscopic margins (37 vs. 9 %, p < 0.01) compared with patients managed with surgery alone, but overall survival (OS) was comparable between the two cohorts (5-year OS: 49.7 vs. 52.5 %, p = 0.20). Lymph node involvement had the strongest association with poor OS (p < 0.01). Adjuvant radiation was associated with decreased isolated local failure (hazard ratio 0.17, 95 % confidence interval 0.05-0.63, p = 0.01). However, 71 % of recurrences included distant failure.Following oncologic resection for GBC, adjuvant radiation may offer improved local control compared with observation. The benefit of adjuvant radiation beyond chemotherapy alone should therefore be explored. Certainly, the high rate of distant failure highlights the need for more effective systemic therapy.

Authors
Wang, J; Narang, AK; Sugar, EA; Luber, B; Rosati, LM; Hsu, CC; Fuller, CD; Pawlik, TM; Miller, RC; Czito, BG; Tuli, R; Crane, CH; Ben-Josef, E; Thomas, CR; Herman, JM
MLA Citation
Wang, J, Narang, AK, Sugar, EA, Luber, B, Rosati, LM, Hsu, CC, Fuller, CD, Pawlik, TM, Miller, RC, Czito, BG, Tuli, R, Crane, CH, Ben-Josef, E, Thomas, CR, and Herman, JM. "Evaluation of Adjuvant Radiation Therapy for Resected Gallbladder Carcinoma: A Multi-institutional Experience." Annals of surgical oncology 22 Suppl 3 (December 2015): S1100-S1106.
PMID
26224402
Source
epmc
Published In
Annals of Surgical Oncology
Volume
22 Suppl 3
Publish Date
2015
Start Page
S1100
End Page
S1106
DOI
10.1245/s10434-015-4685-y

Analysis of perioperative radiation therapy in the surgical treatment of primary and recurrent retroperitoneal sarcoma.

Radiation therapy (RT) is increasingly utilized in conjunction with surgery for the treatment of retroperitoneal soft tissue sarcomas (RPS). Despite multiple theoretical advantages of RT, its role in the surgical management of this disease remains ill defined.Patients undergoing surgery for RPS from 1990 to 2011 were identified. Patients were classified as having primary or recurrent disease, and then further stratified by the use of perioperative RT. Primary outcomes, including overall survival (OS) and recurrence-free survival (RFS), were estimated using the Kaplan-Meier method with comparisons based on the log rank test. Cox-proportional hazards modeling was used to estimate the independent effect of RT on survival.Ninety-four patients met final inclusion criteria. After adjusting for confounding variables, perioperative RT remained independently associated with a reduced risk of recurrence (HR 0.34, P < 0.01) and death (HR 0.30, P = 0.02).In this retrospective series, perioperative RT is an independent predictor of improved OS and RFS. These results provide additional support for the use of RT in the multimodality treatment of retroperitoneal sarcoma.

Authors
Lane, WO; Cramer, CK; Nussbaum, DP; Speicher, PJ; Gulack, BC; Czito, BG; Kirsch, DG; Tyler, DS; Blazer, DG
MLA Citation
Lane, WO, Cramer, CK, Nussbaum, DP, Speicher, PJ, Gulack, BC, Czito, BG, Kirsch, DG, Tyler, DS, and Blazer, DG. "Analysis of perioperative radiation therapy in the surgical treatment of primary and recurrent retroperitoneal sarcoma." Journal of surgical oncology 112.4 (September 2015): 352-358.
PMID
26238282
Source
epmc
Published In
Journal of Surgical Oncology
Volume
112
Issue
4
Publish Date
2015
Start Page
352
End Page
358
DOI
10.1002/jso.23996

T2-weighted four dimensional magnetic resonance imaging with result-driven phase sorting.

T2-weighted MRI provides excellent tumor-to-tissue contrast for target volume delineation in radiation therapy treatment planning. This study aims at developing a novel T2-weighted retrospective four dimensional magnetic resonance imaging (4D-MRI) phase sorting technique for imaging organ/tumor respiratory motion.A 2D fast T2-weighted half-Fourier acquisition single-shot turbo spin-echo MR sequence was used for image acquisition of 4D-MRI, with a frame rate of 2-3 frames/s. Respiratory motion was measured using an external breathing monitoring device. A phase sorting method was developed to sort the images by their corresponding respiratory phases. Besides, a result-driven strategy was applied to effectively utilize redundant images in the case when multiple images were allocated to a bin. This strategy, selecting the image with minimal amplitude error, will generate the most representative 4D-MRI. Since we are using a different image acquisition mode for 4D imaging (the sequential image acquisition scheme) with the conventionally used cine or helical image acquisition scheme, the 4D dataset sufficient condition was not obviously and directly predictable. An important challenge of the proposed technique was to determine the number of repeated scans (NR) required to obtain sufficient phase information at each slice position. To tackle this challenge, the authors first conducted computer simulations using real-time position management respiratory signals of the 29 cancer patients under an IRB-approved retrospective study to derive the relationships between NR and the following factors: number of slices (NS), number of 4D-MRI respiratory bins (NB), and starting phase at image acquisition (P0). To validate the authors' technique, 4D-MRI acquisition and reconstruction were simulated on a 4D digital extended cardiac-torso (XCAT) human phantom using simulation derived parameters. Twelve healthy volunteers were involved in an IRB-approved study to investigate the feasibility of this technique.4D data acquisition completeness (Cp) increases as NR increases in an inverse-exponential fashion (Cp = 100 - 99 × exp(-0.18 × NR), when NB = 6, fitted using 29 patients' data). The NR required for 4D-MRI reconstruction (defined as achieving 95% completeness, Cp = 95%, NR = NR,95) is proportional to NB (NR,95 ∼ 2.86 × NB, r = 1.0), but independent of NS and P0. Simulated XCAT 4D-MRI showed a clear pattern of respiratory motion. Tumor motion trajectories measured on 4D-MRI were comparable to the average input signal, with a mean relative amplitude error of 2.7% ± 2.9%. Reconstructed 4D-MRI for healthy volunteers illustrated clear respiratory motion on three orthogonal planes, with minimal image artifacts. The artifacts were presumably caused by breathing irregularity and incompleteness of data acquisition (95% acquired only). The mean relative amplitude error between critical structure trajectory and average breathing curve for 12 healthy volunteers is 2.5 ± 0.3 mm in superior-inferior direction.A novel T2-weighted retrospective phase sorting 4D-MRI technique has been developed and successfully applied on digital phantom and healthy volunteers.

Authors
Liu, Y; Yin, F-F; Czito, BG; Bashir, MR; Cai, J
MLA Citation
Liu, Y, Yin, F-F, Czito, BG, Bashir, MR, and Cai, J. "T2-weighted four dimensional magnetic resonance imaging with result-driven phase sorting." Medical physics 42.8 (August 2015): 4460-4471.
PMID
26233176
Source
epmc
Published In
Medical physics
Volume
42
Issue
8
Publish Date
2015
Start Page
4460
End Page
4471
DOI
10.1118/1.4923168

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

Neoadjuvant radiation therapy does not increase perioperative morbidity among patients undergoing gastrectomy for gastric cancer.

BACKGROUND: Neoadjuvant radiation therapy (RT) as a component of the multimodality treatment of gastric cancer has demonstrated promising results. Data regarding its effect on perioperative safety are limited. METHODS: Adults undergoing gastrectomy for gastric cancer in the 2005-2011 National Surgical Quality Improvement Program were included. Groups were defined by neoadjuvant RT use, and then propensity-matched based on preoperative variables. Multivariable logistic regression was performed to assess neoadjuvant RT as an independent predictor of outcomes. RESULTS: Among 2,764 patients identified, 55 (2.0%) were treated with neoadjuvant RT. Patients who received neoadjuvant RT were more likely to have received preoperative chemotherapy and steroids, and experienced weight loss (all P < 0.01). After matching, however, there were no preoperative differences. At time of surgery, total (vs. partial) gastrectomy was more common among patients who underwent neoadjuvant RT (70.9 vs. 46.7%, P < 0.01), and operative time was longer (290 vs. 236 min, P < 0.01). There were no differences in overall complications (23.6 vs. 29.7%, P = 0.49) or 30-day mortality (3.6 vs. 3.6%, P = 0.99). CONCLUSIONS: Neoadjuvant RT was not associated with increased morbidity or mortality following resection for gastric cancer. These findings support the ongoing investigation of neoadjuvant RT as part of the multidisciplinary management of resectable gastric cancer.

Authors
Sun, Z; Nussbaum, DP; Speicher, PJ; Czito, BG; Tyler, DS; Blazer, DG
MLA Citation
Sun, Z, Nussbaum, DP, Speicher, PJ, Czito, BG, Tyler, DS, and Blazer, DG. "Neoadjuvant radiation therapy does not increase perioperative morbidity among patients undergoing gastrectomy for gastric cancer." Journal of surgical oncology 112.1 (July 14, 2015): 46-50.
PMID
26179329
Source
epmc
Published In
Journal of Surgical Oncology
Volume
112
Issue
1
Publish Date
2015
Start Page
46
End Page
50
DOI
10.1002/jso.23957

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

Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer (LARC): Final results of a phase Ib study.

Authors
Michael, M; Mulcahy, MF; Deming, DA; Vaghefi, H; Jameson, GS; DeLuca, A; Xiong, H; Munasinghe, W; Dudley, MW; Komarnitsky, P; Holen, KD; Czito, BG
MLA Citation
Michael, M, Mulcahy, MF, Deming, DA, Vaghefi, H, Jameson, GS, DeLuca, A, Xiong, H, Munasinghe, W, Dudley, MW, Komarnitsky, P, Holen, KD, and Czito, BG. "Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer (LARC): Final results of a phase Ib study." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study.

Authors
Czito, BG; Mulcahy, MF; Deming, DA; Vaghefi, H; Jameson, GS; Deluca, A; Xiong, H; Munasinghe, W; Dudley, MW; Komarnitsky, P; Holen, KD; Michael, M
MLA Citation
Czito, BG, Mulcahy, MF, Deming, DA, Vaghefi, H, Jameson, GS, Deluca, A, Xiong, H, Munasinghe, W, Dudley, MW, Komarnitsky, P, Holen, KD, and Michael, M. "The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study." January 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
3
Publish Date
2015

Cancer of the anal region

Authors
Czito, BG; Ahmed, S; Kalady, M; Eng, C
MLA Citation
Czito, BG, Ahmed, S, Kalady, M, and Eng, C. "Cancer of the anal region." DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology: Tenth Edition. January 7, 2015.
Source
scopus
Publish Date
2015

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

Intraoperative radiotherapy for gastrointestinal malignancies: contemporary outcomes with multimodality therapy.

The integration of intraoperative radiotherapy (IORT) into the multimodal treatment of gastrointestinal cancer is feasible and leads to high rates of local control. In-field tumoral control using IORT-containing strategies can be achieved in over 90 % of most cases, regardless of the site or status of the tumor (primary or recurrent). Electron beam IORT, or intraoperative electron radiation therapy, is the dominant technology used in institutions reporting data in publications the 21st century. Neither surgery nor systemic therapy is compromised by the integration of IORT-containing radiotherapy.

Authors
Calvo, FA; Sole, CV; Marsiglia, H; Alvarado, E; Ferrer, C; Czito, B
MLA Citation
Calvo, FA, Sole, CV, Marsiglia, H, Alvarado, E, Ferrer, C, and Czito, B. "Intraoperative radiotherapy for gastrointestinal malignancies: contemporary outcomes with multimodality therapy." Current oncology reports 17.1 (January 2015): 419-.
PMID
25416313
Source
epmc
Published In
Current Oncology Reports
Volume
17
Issue
1
Publish Date
2015
Start Page
419
DOI
10.1007/s11912-014-0419-8

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

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

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 (December 2014): 401-407.
PMID
25436117
Source
epmc
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

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 diaphragm motion a good surrogate for liver tumor motion?

To evaluate the relationship between liver tumor motion and diaphragm motion.Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine-magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation-based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis (Diff). The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions.Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small.This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.

Authors
Yang, J; Cai, J; Wang, H; Chang, Z; Czito, BG; Bashir, MR; Palta, M; Yin, F-F
MLA Citation
Yang, J, Cai, J, Wang, H, Chang, Z, Czito, BG, Bashir, MR, Palta, M, and Yin, F-F. "Is diaphragm motion a good surrogate for liver tumor motion?." International journal of radiation oncology, biology, physics 90.4 (November 2014): 952-958.
PMID
25223297
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Issue
4
Publish Date
2014
Start Page
952
End Page
958
DOI
10.1016/j.ijrobp.2014.07.028

Investigation of sagittal image acquisition for 4D-MRI with body area as respiratory surrogate.

The authors have recently developed a novel 4D-MRI technique for imaging organ respiratory motion employing cine acquisition in the axial plane and using body area (BA) as a respiratory surrogate. A potential disadvantage associated with axial image acquisition is the space-dependent phase shift in the superior-inferior (SI) direction, i.e., different axial slice positions reach the respiratory peak at different respiratory phases. Since respiratory motion occurs mostly in the SI and anterior-posterior (AP) directions, sagittal image acquisition, which embeds motion information in these two directions, is expected to be more robust and less affected by phase-shift than axial image acquisition. This study aims to develop and evaluate a 4D-MRI technique using sagittal image acquisition.The authors evaluated axial BA and sagittal BA using both 4D-CT images (11 cancer patients) and cine MR images (6 healthy volunteers and 1 cancer patient) by comparing their corresponding space-dependent phase-shift in the SI direction (δSPS (SI)) and in the lateral direction (δSPS (LAT)), respectively. To evaluate sagittal BA 4D-MRI method, a motion phantom study and a digital phantom study were performed. Additionally, six patients who had cancer(s) in the liver were prospectively enrolled in this study. For each patient, multislice sagittal MR images were acquired for 4D-MRI reconstruction. 4D retrospective sorting was performed based on respiratory phases. Single-slice cine MRI was also acquired in the axial, coronal, and sagittal planes across the tumor center from which tumor motion trajectories in the SI, AP, and medial-lateral (ML) directions were extracted and used as references from comparison. All MR images were acquired in a 1.5 T scanner using a steady-state precession sequence (frame rate ∼ 3 frames/s).4D-CT scans showed that δSPS (SI) was significantly greater than δSPS (LAT) (p-value: 0.012); the median phase-shift was 16.9% and 7.7%, respectively. Body surface motion measurement from axial and sagittal MR cines also showed δSPS (SI) was significantly greater than δSPS (LAT). The median δSPS (SI) and δSPS (LAT) was 11.0% and 9.2% (p-value = 0.008), respectively. Tumor motion trajectories from 4D-MRI matched with those from single-slice cine MRI: the mean (±SD) absolute differences in tumor motion amplitude between the two were 1.5 ± 1.6 mm, 2.1 ± 1.9 mm, and 1.1 ± 1.0 mm in the SI, ML, and AP directions from this patient study.Space-dependent phase shift is less problematic for sagittal acquisition than for axial acquisition. 4D-MRI using sagittal acquisition was successfully carried out in patients with hepatic tumors.

Authors
Liu, Y; Yin, F-F; Chang, Z; Czito, BG; Palta, M; Bashir, MR; Qin, Y; Cai, J
MLA Citation
Liu, Y, Yin, F-F, Chang, Z, Czito, BG, Palta, M, Bashir, MR, Qin, Y, and Cai, J. "Investigation of sagittal image acquisition for 4D-MRI with body area as respiratory surrogate." Medical physics 41.10 (October 2014): 101902-.
PMID
25281954
Source
epmc
Published In
Medical physics
Volume
41
Issue
10
Publish Date
2014
Start Page
101902
DOI
10.1118/1.4894726

Definitive Chemoradiation Therapy for Cervical Esophageal Carcinoma: A Single-Institution Experience

Authors
Ludmir, EB; Palta, M; Wu, Y; Willett, CG; Czito, BG
MLA Citation
Ludmir, EB, Palta, M, Wu, Y, Willett, CG, and Czito, BG. "Definitive Chemoradiation Therapy for Cervical Esophageal Carcinoma: A Single-Institution Experience." September 1, 2014.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Publish Date
2014
Start Page
S348
End Page
S348

Intensity Modulated Radiation Therapy Utilization in the Treatment of Gastrointestinal Malignancies Between 2000 and 2009 in the SEER-Medicare population

Authors
Palta, M; Czito, BG; Willett, CG; Dirian, MA
MLA Citation
Palta, M, Czito, BG, Willett, CG, and Dirian, MA. "Intensity Modulated Radiation Therapy Utilization in the Treatment of Gastrointestinal Malignancies Between 2000 and 2009 in the SEER-Medicare population." September 1, 2014.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Publish Date
2014
Start Page
S401
End Page
S402

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.
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

Pancreatic Adenocarcinoma, Version 2.2014

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings. © National Comprehensive Cancer Network, Inc. 2014, All rights reserved.

Authors
Tempero, MA; Malafa, MP; Behrman, SW; Benson, AB; Casper, ES; Chiorean, EG; Chung, V; Cohen, SJ; Czito, B; Engebretson, A; Feng, M; Hawkins, WG; Herman, J; Hoffman, JP; Ko, A; Komanduri, S; Koong, A; Lowy, AM; Ma, WW; Merchant, NB; Mulvihill, SJ; Muscarella, P; Nakakura, EK; Obando, J; Pitman, MB; Reddy, S; Sasson, AR; Thayer, SP; Weekes, CD; Wolff, RA; Wolpin, BM; Burns, JL; Freedman-Cass, DA
MLA Citation
Tempero, MA, Malafa, MP, Behrman, SW, Benson, AB, Casper, ES, Chiorean, EG, Chung, V, Cohen, SJ, Czito, B, Engebretson, A, Feng, M, Hawkins, WG, Herman, J, Hoffman, JP, Ko, A, Komanduri, S, Koong, A, Lowy, AM, Ma, WW, Merchant, NB, Mulvihill, SJ, Muscarella, P, Nakakura, EK, Obando, J, Pitman, MB, Reddy, S, Sasson, AR, Thayer, SP, Weekes, CD, Wolff, RA, Wolpin, BM, Burns, JL, and Freedman-Cass, DA. "Pancreatic Adenocarcinoma, Version 2.2014." JNCCN Journal of the National Comprehensive Cancer Network 12.8 (August 1, 2014): 1083-1093. (Review)
Source
scopus
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
12
Issue
8
Publish Date
2014
Start Page
1083
End Page
1093

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

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

The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study.

Authors
Czito, BG; Mulcahy, MF; Schelman, WR; Vaghefi, H; Jameson, GS; Deluca, A; Xiong, H; Munasinghe, W; Dudley, MW; Holen, KD; Michael, M
MLA Citation
Czito, BG, Mulcahy, MF, Schelman, WR, Vaghefi, H, Jameson, GS, Deluca, A, Xiong, H, Munasinghe, W, Dudley, MW, Holen, KD, and Michael, M. "The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

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.
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

Four-dimensional magnetic resonance imaging using axial body area as respiratory surrogate: Initial patient results

Purpose To evaluate the feasibility of a retrospective binning technique for 4-dimensional magnetic resonance imaging (4D-MRI) using body area (BA) as a respiratory surrogate. Methods and Materials Seven patients with hepatocellular carcinoma (4 of 7) or liver metastases (3 of 7) were enrolled in an institutional review board-approved prospective study. All patients were simulated with both computed tomography (CT) and MRI to acquire 3-dimensinal and 4D images for treatment planning. Multiple-slice multiple-phase cine-MR images were acquired in the axial plane for 4D-MRI reconstruction. Image acquisition time per slice was set to 10-15 seconds. Single-slice 2-dimensinal cine-MR images were also acquired across the center of the tumor in orthogonal planes. Tumor motion trajectories from 4D-MRI, cine-MRI, and 4D-CT were analyzed in the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions, respectively. Their correlation coefficients (CC) and differences in tumor motion amplitude were determined. Tumor-to-liver contrast-to-noise ratio (CNR) was measured and compared between 4D-CT, 4D-MRI, and conventional T2-weighted fast spin echo MRI. Results The means (±standard deviations) of CC comparing 4D-MRI with cine-MRI were 0.97 ± 0.03, 0.97 ± 0.02, and 0.99 ± 0.04 in SI, AP, and ML directions, respectively. The mean differences were 0.61 ± 0.17 mm, 0.32 ± 0.17 mm, and 0.14 ± 0.06 mm in SI, AP, and ML directions, respectively. The means of CC comparing 4D-MRI and 4D-CT were 0.95 ± 0.02, 0.94 ± 0.02, and 0.96 ± 0.02 in SI, AP, and ML directions, respectively. The mean differences were 0.74 ± 0.02 mm, 0.33 ± 0.13 mm, and 0.18 ± 0.07 mm in SI, AP, and ML directions, respectively. The mean tumor-to-tissue CNRs were 2.94 ± 1.51, 19.44 ± 14.63, and 39.47 ± 20.81 in 4D-CT, 4D-MRI, and T2-weighted MRI, respectively. Conclusions The preliminary evaluation of our 4D-MRI technique results in oncologic patients demonstrates its potential usefulness to accurately measure tumor respiratory motion with improved tumor CNR compared with 4D-CT. © 2014 Elsevier Inc. All rights reserved.

Authors
Yang, J; Cai, J; Wang, H; Chang, Z; Czito, BG; Bashir, MR; Yin, FF
MLA Citation
Yang, J, Cai, J, Wang, H, Chang, Z, Czito, BG, Bashir, MR, and Yin, FF. "Four-dimensional magnetic resonance imaging using axial body area as respiratory surrogate: Initial patient results." International Journal of Radiation Oncology Biology Physics 88.4 (March 15, 2014): 907-912.
Source
scopus
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
88
Issue
4
Publish Date
2014
Start Page
907
End Page
912
DOI
10.1016/j.ijrobp.2013.11.245

Four-dimensional magnetic resonance imaging using axial body area as respiratory surrogate: initial patient results.

To evaluate the feasibility of a retrospective binning technique for 4-dimensional magnetic resonance imaging (4D-MRI) using body area (BA) as a respiratory surrogate.Seven patients with hepatocellular carcinoma (4 of 7) or liver metastases (3 of 7) were enrolled in an institutional review board-approved prospective study. All patients were simulated with both computed tomography (CT) and MRI to acquire 3-dimensional and 4D images for treatment planning. Multiple-slice multiple-phase cine-MR images were acquired in the axial plane for 4D-MRI reconstruction. Image acquisition time per slice was set to 10-15 seconds. Single-slice 2-dimensional cine-MR images were also acquired across the center of the tumor in orthogonal planes. Tumor motion trajectories from 4D-MRI, cine-MRI, and 4D-CT were analyzed in the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions, respectively. Their correlation coefficients (CC) and differences in tumor motion amplitude were determined. Tumor-to-liver contrast-to-noise ratio (CNR) was measured and compared between 4D-CT, 4D-MRI, and conventional T2-weighted fast spin echo MRI.The means (± standard deviations) of CC comparing 4D-MRI with cine-MRI were 0.97 ± 0.03, 0.97 ± 0.02, and 0.99 ± 0.04 in SI, AP, and ML directions, respectively. The mean differences were 0.61 ± 0.17 mm, 0.32 ± 0.17 mm, and 0.14 ± 0.06 mm in SI, AP, and ML directions, respectively. The means of CC comparing 4D-MRI and 4D-CT were 0.95 ± 0.02, 0.94 ± 0.02, and 0.96 ± 0.02 in SI, AP, and ML directions, respectively. The mean differences were 0.74 ± 0.02 mm, 0.33 ± 0.13 mm, and 0.18 ± 0.07 mm in SI, AP, and ML directions, respectively. The mean tumor-to-tissue CNRs were 2.94 ± 1.51, 19.44 ± 14.63, and 39.47 ± 20.81 in 4D-CT, 4D-MRI, and T2-weighted MRI, respectively.The preliminary evaluation of our 4D-MRI technique results in oncologic patients demonstrates its potential usefulness to accurately measure tumor respiratory motion with improved tumor CNR compared with 4D-CT.

Authors
Yang, J; Cai, J; Wang, H; Chang, Z; Czito, BG; Bashir, MR; Yin, F-F
MLA Citation
Yang, J, Cai, J, Wang, H, Chang, Z, Czito, BG, Bashir, MR, and Yin, F-F. "Four-dimensional magnetic resonance imaging using axial body area as respiratory surrogate: initial patient results." International journal of radiation oncology, biology, physics 88.4 (March 2014): 907-912.
PMID
24444759
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
88
Issue
4
Publish Date
2014
Start Page
907
End Page
912
DOI
10.1016/j.ijrobp.2013.11.245

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

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

Radiosensitive orbital metastasis as presentation of occult colonic adenocarcinoma.

An 82-year-old man presented with progressive right frontal headaches. The patient's history was significant for benign polyps on surveillance colonoscopy 2 years prior, without high-grade dysplasia or carcinoma. MRI revealed an enhancing lesion arising within the superomedial aspect of the right orbit. Lesion biopsy demonstrated histological appearance and immunophenotype suggestive of colonic adenocarcinoma. Staging positron emission tomography/CT showed visceral metastases and diffuse activity in the posterior rectosigmoid, consistent with metastatic colon cancer. Treatment of the orbital lesion with external beam radiotherapy to 30 Gy resulted in significant palliation of the patient's headaches. The patient expired 2 months following treatment completion due to disease progression. Orbital metastasis as the initial presentation of an occult colorectal primary lesion is exceedingly rare, and occurred in this patient despite surveillance colonoscopy. Radiotherapy remains an efficacious modality for treatment of orbital metastases.

Authors
Ludmir, EB; McCall, SJ; Czito, BG; Palta, M
MLA Citation
Ludmir, EB, McCall, SJ, Czito, BG, and Palta, M. "Radiosensitive orbital metastasis as presentation of occult colonic adenocarcinoma." BMJ case reports 2014 (January 2014).
PMID
25240005
Source
epmc
Published In
BMJ Case Reports
Volume
2014
Publish Date
2014
DOI
10.1136/bcr-2014-206407

Intraoperative Radiotherapy for Gastrointestinal Malignancies: Contemporary Outcomes With Multimodality Therapy

© 2014, Springer Science+Business Media New York.The integration of intraoperative radiotherapy (IORT) into the multimodal treatment of gastrointestinal cancer is feasible and leads to high rates of local control. In-field tumoral control using IORT-containing strategies can be achieved in over 90 % of most cases, regardless of the site or status of the tumor (primary or recurrent). Electron beam IORT, or intraoperative electron radiation therapy, is the dominant technology used in institutions reporting data in publications the 21st century. Neither surgery nor systemic therapy is compromised by the integration of IORT-containing radiotherapy.

Authors
Calvo, FA; Sole, CV; Marsiglia, H; Alvarado, E; Ferrer, C; Czito, B
MLA Citation
Calvo, FA, Sole, CV, Marsiglia, H, Alvarado, E, Ferrer, C, and Czito, B. "Intraoperative Radiotherapy for Gastrointestinal Malignancies: Contemporary Outcomes With Multimodality Therapy." Current Oncology Reports 17.1 (2014).
Source
scival
Published In
Current Oncology Reports
Volume
17
Issue
1
Publish Date
2014
DOI
10.1007/s11912-014-0419-8

Cancer of the Anal Canal

Authors
Goodman, KA; Kachnic, LA; Czito, BG
MLA Citation
Goodman, KA, Kachnic, LA, and Czito, BG. "Cancer of the Anal Canal." Abeloff's Clinical Oncology: Fifth Edition. October 22, 2013. 1360-1372.e2.
Source
scopus
Publish Date
2013
Start Page
1360
End Page
1372.e2
DOI
10.1016/B978-1-4557-2865-7.00079-5

Patterns of Failure for Stage I Ampulla of Vater Adenocarcinoma: A Single Institutional Experience

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; McSherry, F; Uronis, HE; Tyler, DS; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, McSherry, F, Uronis, HE, Tyler, DS, and Czito, BG. "Patterns of Failure for Stage I Ampulla of Vater Adenocarcinoma: A Single Institutional Experience." October 1, 2013.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S317
End Page
S317

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

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

Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy and morbidity of intraoperative radiation therapy (IORT) for advanced colorectal cancer. METHODS: All patients undergoing IORT for locally advanced rectal cancer from 2001-2009 were reviewed for cancer recurrence, survival, and procedure-related morbidity. Cumulative event rates were estimated using the method of Kaplan and Meier. RESULTS: Twenty-nine patients with locally advanced (n = 8) or recurrent (n = 21) rectal cancers were treated with IORT and resection. Surgical interventions included low anterior resection, abdominoperineal resection, pelvic exenteration, and a variety of non-anatomic resections of pelvic recurrences. R(0) resections were achieved in 16 patients, while R(1) resections were achieved in 10, and margins were grossly positive in 3 patients. IORT was delivered to all patients over a median area of 48 (42-72) cm(2) at a median dose of 12 (12-15) Gy. Local and overall recurrence rates were 24 % (locally advanced group) and 45 % (recurrent group). Median disease-free and overall survival were 25 and 40 months respectively at a median follow-up of 26 (18-42) months. The short-term (≤30 days) complication rate was 45 %. Eight patients developed local wound complications, 5 of which required operative intervention. Four patients developed intra-abdominal abscesses requiring drainage. Long-term (>30 days) complications were identified in 11 patients (38 %) and included long-term wound complications (n = 3), ureteral obstruction requiring stenting (n = 1), neurogenic bladder (n = 3), enteric fistulae (n = 2), small bowel obstruction (n = 1), and neuropathic pain (n = 1). CONCLUSIONS: Intraoperative brachytherapy is a viable IORT option during pelvic surgery for locally advanced or recurrent colorectal cancer but is associated with high postoperative morbidity. Whether intraoperative brachytherapy can improve local recurrence rates for locally advanced or recurrent colorectal cancer will require further prospective investigation.

Authors
Turley, RS; Czito, BG; Haney, JC; Tyler, DS; Mantyh, CR; Migaly, J
MLA Citation
Turley, RS, Czito, BG, Haney, JC, Tyler, DS, Mantyh, CR, and Migaly, J. "Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer." Tech Coloproctol 17.1 (February 2013): 95-100.
PMID
22986843
Source
pubmed
Published In
Techniques in Coloproctology
Volume
17
Issue
1
Publish Date
2013
Start Page
95
End Page
100
DOI
10.1007/s10151-012-0892-8

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

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

Radiation Therapy in Anal and Rectal Cancer

Historically, squamous cell carcinoma of the anal canal was treated with abdominoperineal resection. Nigro discovered that radiation therapy combined with 5-fluorouracil and mitomycin resulted in high rates of local control and complication-free and overall survival without surgical intervention. Advances include the integration of PET into staging, radiation treatment planning, disease monitoring, and intensity-modulated radiation therapy. Ongoing studies are evaluating the use of other agents with radiation therapy. Trials established the role for neoadjuvant therapy for T3-4 and/or node-positive tumor presentations. Chemotherapy and targeted agents are under study to improve on the standard combination of 5-fluorouracil and radiation. © 2013 Elsevier Inc. All rights reserved.

Authors
Czito, BG; Meyer, J
MLA Citation
Czito, BG, and Meyer, J. "Radiation Therapy in Anal and Rectal Cancer." Surgical Oncology Clinics of North America (2013).
PMID
23622078
Source
scival
Published In
Surgical Oncology Clinics of North America
Publish Date
2013
DOI
10.1016/j.soc.2013.02.010

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

Radiation Therapy in Anal and Rectal Cancer

Historically, squamous cell carcinoma of the anal canal was treated with abdominoperineal resection. Nigro discovered that radiation therapy combined with 5-fluorouracil and mitomycin resulted in high rates of local control and colostomy-free and overall survival without surgical intervention. Recent advances include the integration of PET into staging, radiation treatment planning, disease monitoring, and the use of intensity-modulated radiation therapy. For rectal cancer, clinical trials have established the role for neoadjuvant therapy for T3-4 and/or node-positive tumor presentations. Chemotherapy and targeted agents are under study in both anal and rectal cancers to improve on the standard combinations of chemotherapy and radiation. © 2013 Elsevier Inc.

Authors
Czito, BG; Meyer, J
MLA Citation
Czito, BG, and Meyer, J. "Radiation Therapy in Anal and Rectal Cancer." Surgical Oncology Clinics of North America 22.3 (2013): 525-543.
Source
scival
Published In
Surgical Oncology Clinics of North America
Volume
22
Issue
3
Publish Date
2013
Start Page
525
End Page
543
DOI
10.1016/j.soc.2013.02.010

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

Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer

Background: The aim of this study was to evaluate the efficacy and morbidity of intraoperative radiation therapy (IORT) for advanced colorectal cancer. Methods: All patients undergoing IORT for locally advanced rectal cancer from 2001-2009 were reviewed for cancer recurrence, survival, and procedure-related morbidity. Cumulative event rates were estimated using the method of Kaplan and Meier. Results: Twenty-nine patients with locally advanced (n = 8) or recurrent (n = 21) rectal cancers were treated with IORT and resection. Surgical interventions included low anterior resection, abdominoperineal resection, pelvic exenteration, and a variety of non-anatomic resections of pelvic recurrences. R0resections were achieved in 16 patients, while R1 resections were achieved in 10, and margins were grossly positive in 3 patients. IORT was delivered to all patients over a median area of 48 (42-72) cm2 at a median dose of 12 (12-15) Gy. Local and overall recurrence rates were 24 % (locally advanced group) and 45 % (recurrent group). Median disease-free and overall survival were 25 and 40 months respectively at a median follow-up of 26 (18-42) months. The short-term (≤30 days) complication rate was 45 %. Eight patients developed local wound complications, 5 of which required operative intervention. Four patients developed intraabdominal abscesses requiring drainage. Long-term (>30 days) complications were identified in 11 patients (38 %) and included long-term wound complications (n = 3), ureteral obstruction requiring stenting (n = 1), neurogenic bladder (n = 3), enteric fistulae (n = 2), small bowel obstruction (n = 1), and neuropathic pain (n = 1). Conclusions: Intraoperative brachytherapy is a viable IORT option during pelvic surgery for locally advanced or recurrent colorectal cancer but is associated with high postoperative morbidity. Whether intraoperative brachytherapy can improve local recurrence rates for locally advanced or recurrent colorectal cancer will require further prospective investigation. © Springer-Verlag 2012.

Authors
Turley, RS; Czito, BG; Haney, JC; Tyler, DS; Mantyh, CR; Migaly, J
MLA Citation
Turley, RS, Czito, BG, Haney, JC, Tyler, DS, Mantyh, CR, and Migaly, J. "Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer." Techniques in Coloproctology 17.1 (2013): 95-100.
Source
scival
Published In
Techniques in Coloproctology
Volume
17
Issue
1
Publish Date
2013
Start Page
95
End Page
100
DOI
10.1007/s10151-012-0892-8

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

Oncology scan - gastrointestinal cancer.

Authors
Willett, C; Chang, D; Czito, B; Meyer, J; Wo, J
MLA Citation
Willett, C, Chang, D, Czito, B, Meyer, J, and Wo, J. "Oncology scan - gastrointestinal cancer." International journal of radiation oncology, biology, physics 84.2 (October 2012): 297-300. (Academic Article)
Source
manual
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
84
Issue
2
Publish Date
2012
Start Page
297
End Page
300
DOI
10.1016/S0360-3016(12)03363-9

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

Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

Authors
Tempero, MA; Arnoletti, JP; Behrman, SW; Ben-Josef, E; Benson, AB; Casper, ES; Cohen, SJ; Czito, B; Ellenhorn, JDI; Hawkins, WG; Herman, J; Hoffman, JP; Ko, A; Komanduri, S; Koong, A; Ma, WW; Malafa, MP; Merchant, NB; Mulvihill, SJ; Muscarella, P; Nakakura, EK; Obando, J; Pitman, MB; Sasson, AR; Tally, A; Thayer, SP; Whiting, S; Wolff, RA; Wolpin, BM; Freedman-Cass, DA; Shead, DA; National Comprehensive Cancer Networks,
MLA Citation
Tempero, MA, Arnoletti, JP, Behrman, SW, Ben-Josef, E, Benson, AB, Casper, ES, Cohen, SJ, Czito, B, Ellenhorn, JDI, Hawkins, WG, Herman, J, Hoffman, JP, Ko, A, Komanduri, S, Koong, A, Ma, WW, Malafa, MP, Merchant, NB, Mulvihill, SJ, Muscarella, P, Nakakura, EK, Obando, J, Pitman, MB, Sasson, AR, Tally, A, Thayer, SP, Whiting, S, Wolff, RA, Wolpin, BM, Freedman-Cass, DA, Shead, DA, and National Comprehensive Cancer Networks, . "Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines." J Natl Compr Canc Netw 10.6 (June 1, 2012): 703-713.
PMID
22679115
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
6
Publish Date
2012
Start Page
703
End Page
713

Neoadjuvant chemoradiation for potentially resectable gastric cancer.

Authors
Barfield, ME; Untch, BR; Arcury, JT; Czito, BG; Willett, C; Pappas, TN; White, RR; Tyler, DS; Blazer, DG
MLA Citation
Barfield, ME, Untch, BR, Arcury, JT, Czito, BG, Willett, C, Pappas, TN, White, RR, Tyler, DS, and Blazer, DG. "Neoadjuvant chemoradiation for potentially resectable gastric cancer." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

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

A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC).

Authors
Czito, BG; Willett, C; Palta, M; McCall, S; Gee, N; Hurwitz, H; Coleman, RE; Zafar, Y
MLA Citation
Czito, BG, Willett, C, Palta, M, McCall, S, Gee, N, Hurwitz, H, Coleman, RE, and Zafar, Y. "A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC)." February 1, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
4
Publish Date
2012
DOI
10.1200/jco.2012.30.4_suppl.68

Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC).

Authors
Dorth, JA; Willett, C; Czito, BG
MLA Citation
Dorth, JA, Willett, C, and Czito, BG. "Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC)." February 1, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
4
Publish Date
2012
DOI
10.1200/jco.2012.30.4_suppl.88

A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC).

68 Background: EC is commonly managed with concurrent chemoradiotherapy, with or without surgical resection. The optimal combination and dose of agents is the subject of continued investigation. This study examines chemotherapeutic agents with known efficacy in EC in combination with the EGFR inhibitor panitumumab.Eligible pts received RT (1.8 Gy qd to 50.4 Gy) combined with concurrent chemotherapy. Dose-level (DL) 1 was cape (625 mg/m2/bid RT days), ox (40 mg/m2 weekly X 6 weeks), and pmab (3.6 mg/kg, weeks 1, 3 and 5). Chemotherapy doses were escalated barring dose limiting toxicity (DLT). The primary endpoint was defining the maximally tolerated dose with this combination. Secondary endpoints included toxicity and radiographic/pathologic response rates.Twenty-nine pts were enrolled. Twenty-five had adenocarcinoma, 24 (83%) were cN+ and 9 (31%) had M1a/b disease. DLT was not encountered in DL 1. Two of 6 patients at DL 2 (cape 825 mg/m2/bid RT days, ox 50 mg/m2 weekly, pmab 4.8 mg/kg, weeks 1, 3 and 5) developed DLT (one hospitalization due to dehydration; one with drug reaction requiring hospitalization). Twenty additional pts were enrolled at DL1. Primary toxicities were EGFR-rash, esophagitis, nausea/vomiting and fatigue. On repeat endoscopy, 16 (55%) had CR, 10 (35%) PR and 2 (7%) SD. Using PERCIST criteria, 12 (41%), 11 (38%), 2 (7%) and 3 (10%) had CR, PR, SD and PD response on restaging PET, respectively. Twenty pts underwent esophagectomy, revealing Gr 0 response (no residual disease) in 9 (45%), Gr 1 (single/microscopic cells) in 3 (15%), Gr 2 (fibrosis > gross disease) in 4 (20%) and Gr 3 (gross residual > fibrosis or no evident response) in 4 (20%). Seven pts (35%) experienced anastomotic leak (2 requiring reoperation and 3 stent placement).Concurrent chemoradiotherapy utilizing capecitabine, oxaliplatin, panitumumab is reasonably well-tolerated and associated with high rates of radiographic, endoscopic and pathologic response. Postoperative anastomotic leak rates were higher than expected. Further study of this regimen in the operative and nonoperative settings is warranted.

Authors
Czito, BG; Willett, C; Palta, M; McCall, S; Gee, N; Hurwitz, H; Coleman, RE; Zafar, Y; Kennedy-Newton, P; Uronis, H
MLA Citation
Czito, BG, Willett, C, Palta, M, McCall, S, Gee, N, Hurwitz, H, Coleman, RE, Zafar, Y, Kennedy-Newton, P, and Uronis, H. "A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30.4_suppl (February 2012): 68-.
PMID
27982872
Source
epmc
Published In
Journal of Clinical Oncology
Volume
30
Issue
4_suppl
Publish Date
2012
Start Page
68

Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC).

88 Background: Patterns of local-regional failure (LRF) after neoadjuvant chemoradiotherapy (CRT) and surgery for locally-advanced EC are poorly defined.This study reviewed pts treated with CRT followed by surgery for M0 esophageal cancer from 1995-2009. Staging and regional nodes (supraclavicular (SCV) through celiac) were defined based on AJCC 7(th) edition. Patterns of first failure were analyzed. LRF included: 1) initially involved nodal failure (INF), 2) initially uninvolved (subclinical) nodal failure (SNF), and/or 3) anastomotic. Abdominal para-aortic failure (PAF) at or below the superior mesenteric artery was scored separately. Isolated SNF or PAF was defined as no other local or distant failure. Actuarial local-regional control (LRC), event-free survival (EFS), and overall survival (OS) were estimated by the Kaplan-Meier method.156 patients were identified with a median age of 60 years. Primary location was upper in 1%, middle 17%, lower 32% and gastroesophageal junction (GEJ) 50% (Adeno: 79%; SCC: 21%). Staging included EUS (73%), CT (46%), and/or PET/CT (54%). 40% had stage II and 60% stage III disease. Concurrent CRT was primarily cisplatin/taxane and/or 5-FU-based. Primary RT fields (median dose: 45Gy) encompassed the tumor with an approximate 5 cm proximal and distal margin and included standard regional nodes. Boost fields (median total dose: 50.4Gy) encompassed gross disease with a 2 cm margin. Surgical technique was transhiatial (28%), Ivor-Lewis (47%), or tri-incisional (25%) with a median of 8 nodes dissected. Median f/u was 1.3 years. 2-yr LRC, EFS, and OS were 83%, 36%, and 49%. 2-yr SNF was 15% (n=14); anastomotic failure was 7% (n=7). SNFs were SCV (n=5), mediastinal (n=12), and/or celiac (n=3). 95% of SNFs were outside or near the margin of the primary RT fields. 2-yr isolated SNF was 3% (n=3), PAF was 11% (n=9), and isolated PAF 6% (n=5).SNF is the most common type of LRF after tri-modality therapy for locally-advanced EC. A limited subset of patients experience isolated SNF or PAF as first disease recurrence. The potential benefit of targeting additional SN or PA regions with RT is small and likely eclipsed by high rates of distant failure.

Authors
Dorth, JA; Willett, C; Czito, BG
MLA Citation
Dorth, JA, Willett, C, and Czito, BG. "Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30.4_suppl (February 2012): 88-.
PMID
27982811
Source
epmc
Published In
Journal of Clinical Oncology
Volume
30
Issue
4_suppl
Publish Date
2012
Start Page
88

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

Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer

Authors
Turley, RS; Czito, BG; Haney, JC; Tyler, DS; Mantyh, CR; Migaly, J
MLA Citation
Turley, RS, Czito, BG, Haney, JC, Tyler, DS, Mantyh, CR, and Migaly, J. "Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer." Techniques in Coloproctology (2012): 1-6.
Source
scopus
Published In
Techniques in Coloproctology
Publish Date
2012
Start Page
1
End Page
6

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

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

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

Carcinoma of the ampulla of Vater: Patterns of failure after resection and benefit of adjuvant radiotherapy.

Authors
Palta, M; Willett, CG; Patel, P; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Palta, M, Willett, CG, Patel, P, Tyler, DS, Uronis, HE, and Czito, BG. "Carcinoma of the ampulla of Vater: Patterns of failure after resection and benefit of adjuvant radiotherapy." JOURNAL OF CLINICAL ONCOLOGY 29.4 (February 1, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
4
Publish Date
2011

Single-institution experience of preoperative chemoradiotherapy for locally advanced gastric cancer

Authors
Pepek, JM; Chino, JP; Willett, CG; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Pepek, JM, Chino, JP, Willett, CG, Tyler, DS, Uronis, HE, and Czito, BG. "Single-institution experience of preoperative chemoradiotherapy for locally advanced gastric cancer." JOURNAL OF CLINICAL ONCOLOGY 29.4 (February 1, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
4
Publish Date
2011

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

Authors
Zagar, TM; White, RR; Willett, CG; Papavassiliou, P; Tyler, DS; Papalezova, K; Guy, C; Clough, R; Czito, BG
MLA Citation
Zagar, TM, White, RR, Willett, CG, Papavassiliou, P, Tyler, DS, Papalezova, K, Guy, C, Clough, R, and Czito, BG. "Resected pancreatic neuroendocrine tumors: Patterns of failure and disease-related outcomes with or without radiotherapy." February 1, 2011.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
4
Publish Date
2011

Multicenter evaluation of adjuvant therapy for gallbladder cancer

Authors
Wang, J; Hsu, CC; Fuller, CD; Pawlik, TM; Miller, RC; Czito, BG; Tuli, R; Ben-Josef, E; Herman, JM
MLA Citation
Wang, J, Hsu, CC, Fuller, CD, Pawlik, TM, Miller, RC, Czito, BG, Tuli, R, Ben-Josef, E, and Herman, JM. "Multicenter evaluation of adjuvant therapy for gallbladder cancer." JOURNAL OF CLINICAL ONCOLOGY 29.4 (February 1, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
4
Publish Date
2011

A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC)

Authors
Czito, BG; Willett, C; Kennedy-Newton, P; Tyler, DS; Hurwitz, H; Uronis, HE
MLA Citation
Czito, BG, Willett, C, Kennedy-Newton, P, Tyler, DS, Hurwitz, H, and Uronis, HE. "A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC)." JOURNAL OF CLINICAL ONCOLOGY 29.4 (February 1, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
4
Publish Date
2011

A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC).

281 Background: Localized PC is commonly managed with chemoradiotherapy, with or without surgical resection. The optimal combination of agents and doses is the subject of continued investigation. This phase I study examines the combination of two targeted radiosensitizing agents in combination with radiation therapy.Eligible patients had resectable, borderline resectable or locally advanced adenocarcinoma. Patients received RT (1.8 Gy qd to 50.4 Gy) concurrent with bevacizumab and erlotinib. Dose-level 1 was bevacizumab 10 mg/kg weeks 1, 3 and 5 and erlotinib 100 mg daily, RT days only. Drug doses were escalated depending on encountered toxicity. The primary endpoint was determination of the maximally tolerated dose of this combination. Secondary endpoints included toxicity and activity assessment.Nine patients were enrolled in the phase I study. Maximal EUS/CT stage was T2N0 (n=1), T3N0 (n=1), T3N1 (n=2) or T4N0 (n=5). Of 3 patients in dose-level 1, two had radiographic stable disease (SD) and one partial response (PR). One pt underwent exploratory laparotomy and found to be unresectable, experiencing prolonged postoperative incisional healing. Three patients were then enrolled at dose-level 2 (bevacizumab 10 mg/kg, erlotinib 125 mg). Two had SD and one progressive disease (PD). One pt underwent exploratory laparotomy, aborted due to previously undetected hepatic metastases. Three patients were then enrolled at dose-level 3 (bevacizumab 10 mg/kg, erlotinib 150 mg). One pt had SD and two PR. One pt underwent distal pancreatectomy, experiencing postoperative pancreatic leak and abscess formation. All patients with elevated CA 19-9 at baseline had a decrease, with amedian decrease of 69% (R:13-93%). Dose-limiting toxicity (DLT) was not encountered at any dose-level. Primary non-dose limiting toxicities in all cohorts included NCI CTCAE v3.0 grade 1-2 nausea/vomiting, rash, diarrhea, fatigue, and anorexia.Concurrent chemoradiotherapy utilizing erlotinib and bevacizumab is reasonably well-tolerated. The recommended phase II dose is bevacizumab 10 mg/kg weeks 1, 3, and 5 and erlotinib 150 mg RT days only. Phase II accrual is underway. [Table: see text].

Authors
Czito, BG; Willett, C; Kennedy-Newton, P; Tyler, DS; Hurwitz, H; Uronis, HE
MLA Citation
Czito, BG, Willett, C, Kennedy-Newton, P, Tyler, DS, Hurwitz, H, and Uronis, HE. "A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.4_suppl (February 2011): 281-.
PMID
27985636
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
4_suppl
Publish Date
2011
Start Page
281

Carcinoma of the ampulla of Vater: Patterns of failure after resection and benefit of adjuvant radiotherapy.

254 Background: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. To define the role of radiation therapy and chemotherapy with surgery, we performed a single institution analysis of treatment- related outcomes.A retrospective analysis was performed of all patients undergoing potentially curative therapy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1975 and 2009. Local control (LC), overall survival (OS), disease-free survival (DFS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier Method.One hundred thirty-seven patients with ampullary carcinoma underwent potentially curative pancreaticoduodenectomy. Sixty-one patients undergoing resection received adjuvant (n= 43) or neoadjuvant (n=18) radiation therapy with concurrent chemotherapy (CRT). Patients receiving radiotherapy were more likely to have poorly differentiated tumors. Median radiation dose was 50 Gy. Median follow up was 8.8 years. Of patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response. Three-year local control was significantly improved in patients receiving CRT (88% vs. 55% p= 0.001) with trend toward a 3-year OS benefit in patients receiving CRT (62% vs. 46% p=0.074). Despite this, there was no significant difference in 3-year DFS (66% CRT vs 48% surgery alone p=0.09) or MFS (69% CRT vs 63% surgery alone p=0.337).Long term survival rates are low. Local failure rates are high following radical resection alone and improved with CRT. Despite more adverse pathologic features in patients receiving CRT, survival outcomes were at least equivalent with a trend toward statistical significance. Given the patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered. No significant financial relationships to disclose.

Authors
Palta, M; Willett, CG; Patel, P; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Palta, M, Willett, CG, Patel, P, Tyler, DS, Uronis, HE, and Czito, BG. "Carcinoma of the ampulla of Vater: Patterns of failure after resection and benefit of adjuvant radiotherapy." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.4_suppl (February 2011): 254-.
PMID
27985514
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
4_suppl
Publish Date
2011
Start Page
254

Single-institution experience of preoperative chemoradiotherapy for locally advanced gastric cancer.

99 Background: To examine acute toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer.Patients with gastroesophageal (GE) junction (Siewert type II and III) or stomach adenocarcinoma who underwent curative intent CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Tumors were staged according to AJCC 6th edition. Local recurrence was defined as radiographic or biopsy- proven disease within the radiation treatment field. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to CTCAE v4.0.Forty-eight patients (60% stage III, 8% stage IV) were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Thirty-five percent had signet ring histology, 52% had poorly differentiated tumors and 10% had linitis plastica. Median age was 60 years and median RT dose was 45 Gy. All patients received concurrent chemotherapy (CT) with 40 (83%) receiving 5-FU-based CT. Rates of acute > grade 2 hematologic and non-hematologic toxicity were 38% and 10%, respectively. Six patients (13%) required treatment break and two (4%) were unable to complete the prescribed treatment course. Thirty-six patients (75%) underwent surgery. Patients did not undergo surgery due to distant metastases at laparotomy or restaging (n=9), patient refusal (n=2) or poor performance status (n=1). 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 for all patients was 40%. For those undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively.Preoperative CRT for gastric cancer is reasonably well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with advanced disease, LC, DFS and OS rates in resected patients are comparable to similarly staged, adjuvantly treated historic controls. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated. No significant financial relationships to disclose.

Authors
Pepek, JM; Chino, JP; Willett, CG; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Pepek, JM, Chino, JP, Willett, CG, Tyler, DS, Uronis, HE, and Czito, BG. "Single-institution experience of preoperative chemoradiotherapy for locally advanced gastric cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.4_suppl (February 2011): 99-.
PMID
27985467
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
4_suppl
Publish Date
2011
Start Page
99

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

325 Background: Pancreatic neuroendocrine tumors (NET) are rare with improved prognosis compared to adenocarcinomas. Surgical resection remains the standard of care although many patients present with unresectable/metastatic disease. While many resected patients will fail distantly, little is known regarding the use of adjuvant radiotherapy. To define this and establish specific patterns of failure, an analysis of resected patients from a single institution was performed.From 1994 to 2009, 33 patients with NET of the pancreatic head underwent resection with curative intent at Duke University. Sixteen patients were treated with surgical resection alone, and an additional 17 underwent resection with adjuvant (n=10) or neoadjuvant (n=7) radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months.Patients receiving radiation therapy were more likely to have involved nodes (47% vs 19%, p=0.09), more mitoses per high power field (p=0.10) and involved margins (47% vs 31%, p=0.20) compared to surgery alone patients. Median survival for the whole cohort was 52 months. Two-year survival was 68% for the CMT group and 93% for the surgery alone group (p=0.03). Two-year local control was 85% for the CMT and 90% for the surgery group (p=0.49). Two-year metastasis-free survival was 45% and 69% for the CMT and surgery patients, respectively (p=0.02).Patients receiving CMT were more likely to have adverse pathologic features compared to surgery-alone patients. Survival outcomes were high in both groups, although less so in the CMT group. Distant metastasis development dominated patterns of failure. Local failure following resection of NETs is uncommon, and the role of adjuvant radiotherapy in this setting remains unclear. No significant financial relationships to disclose.

Authors
Zagar, TM; White, RR; Willett, CG; Papavassiliou, P; Tyler, DS; Papalezova, K; Guy, C; Clough, R; Czito, BG
MLA Citation
Zagar, TM, White, RR, Willett, CG, Papavassiliou, P, Tyler, DS, Papalezova, K, Guy, C, Clough, R, and Czito, BG. "Resected pancreatic neuroendocrine tumors: Patterns of failure and disease-related outcomes with or without radiotherapy." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.4_suppl (February 2011): 325-.
PMID
27985899
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
4_suppl
Publish Date
2011
Start Page
325

Multicenter evaluation of adjuvant therapy for gallbladder cancer.

251 Background: To assess the effect of adjuvant therapy in gallbladder adenocarcinoma (GBC).Retrospective review was conducted at five institutions to identify pts who had surgery for confirmed dx of GBC from 1985-2008 (N = 189). Pts were excluded if they had chemo alone (N = 8), path other than adenoca (N= 7), carcinoma in situ (N=1), < 30 days of follow-up (N = 2), or missing data (N=14). Of the remaining 156 pts, 58 received surgery only and 98 received adj RT ± chemo. Kaplan-Meier was used for overall survival (OS) and Cox proportional hazards to compare risk factors.Median age of dx was 64.4, 68.0% were female, 37.9% had ≥ stage 2b, 37.2% had + nodes, and 32.1% had + margins. Overall, 35.9% of the patients had simple cholecystectomy (SC) only and 64.1% had radical resection (ER). mOS for pts treated with surgery alone was 49.7 months (95% CI: 24.8 to Inf). On univariate analysis, + margins (HR 2.72, p<0.001) was associated with worse OS, whereas ER compared to SC improved survival in both univariate (HR 0.46, p<0.001) and multivariate (HR 0.53, p=0.033) analyses after adjusting for node/margins, T-stage, adj RT, age, gender, and institution. mOS for the entire cohort vs. adj RT (median 50.4 Gy) ± chemo was 30.7 months (95% CI: 19.2 to 46.9) vs. 26.9 months (95% CI: 15.5 to 39.1). But, compared to surgery alone, the adj group was more likely to have had node +, margin +, or T-stage 3+ (all p<0.001). The adj RT group was also less likely than surgery alone pts to have undergone ER (p = 0.007). On multivariate analysis, decreased OS was also found for node + (HR 2.09, p=0.004), margin + (HR 1.84, p=0.043), and T3/T4 disease (HR 2.37, p=0.002). After adjusting for surgical extent, node, margin, T stage, age, gender, and institution, there was improved OS with adj therapy (HR: 0.43, p = 0.020). When stratified by surgical extent, the risk estimate for adj RT improved OS among those with SC (n=56; HR 0.20, p=0.135) and ER (n=100; HR 0.46, p=0.067), but was not statistically significant.ER was associated with improved OS, whereas node/margin+ and T-stage 3+ were associated with worse survival. In multivariate analysis, adj RT improved OS after surgery. Given the poor prognosis of GBC patients with advanced disease, consideration of adj therapy is appropriate. No significant financial relationships to disclose.

Authors
Wang, J; Hsu, CC; Fuller, CD; Pawlik, TM; Miller, RC; Czito, BG; Tuli, R; Ben-Josef, E; Herman, JM
MLA Citation
Wang, J, Hsu, CC, Fuller, CD, Pawlik, TM, Miller, RC, Czito, BG, Tuli, R, Ben-Josef, E, and Herman, JM. "Multicenter evaluation of adjuvant therapy for gallbladder cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.4_suppl (February 2011): 251-.
PMID
27985532
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
4_suppl
Publish Date
2011
Start Page
251

Rectal cancer: A moving target?

Authors
Czito, B
MLA Citation
Czito, B. "Rectal cancer: A moving target?." Practical Radiation Oncology 1.2 (2011): 95-96.
Source
scival
Published In
Practical Radiation Oncology
Volume
1
Issue
2
Publish Date
2011
Start Page
95
End Page
96
DOI
10.1016/j.prro.2011.02.006

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

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

Abstract LB-213: Plasma soluble VEGFR1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer

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. "Abstract LB-213: Plasma soluble VEGFR1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer." Cancer Research 70.8 Supplement (April 15, 2010): LB-213-LB-213.
Source
crossref
Published In
Cancer Research
Volume
70
Issue
8 Supplement
Publish Date
2010
Start Page
LB-213
End Page
LB-213
DOI
10.1158/1538-7445.AM10-LB-213

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

Neoadjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma: A Single Institution Experience

Authors
Pepek, JM; Chino, JP; Willett, CG; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Pepek, JM, Chino, JP, Willett, CG, Tyler, DS, Uronis, HE, and Czito, BG. "Neoadjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma: A Single Institution Experience." 2010.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S73
End Page
S73

Resected Pancreatic Neuroendocrine Tumors: Patterns of Failure and Disease-related Outcomes with or without Radiotherapy

Authors
Zagar, TM; White, RR; Willett, CG; Papavassiliou, P; Tyler, DS; Papalezova, KT; Guy, CD; Clough, R; Czito, BG
MLA Citation
Zagar, TM, White, RR, Willett, CG, Papavassiliou, P, Tyler, DS, Papalezova, KT, Guy, CD, Clough, R, and Czito, BG. "Resected Pancreatic Neuroendocrine Tumors: Patterns of Failure and Disease-related Outcomes with or without Radiotherapy." 2010.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S309
End Page
S310

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

Multimodality therapy for locoregional extrahepatic cholangiocarcinoma: a population-based analysis.

BACKGROUND: Although surgical resection is the mainstay of treatment for extrahepatic cholangiocarcinoma, the majority of patients present with advanced disease. Due in part to numeric rarity, the optimum role of radiotherapy (RT) for extrahepatic cholangiocarcinoma, as well as its relative benefit, is an area of debate. The specific aim of this series was to estimate survival for extrahepatic cholangiocarcinoma patients receiving surgery and adjuvant RT using a robust population-based data set. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) limited-use data set for selected extrahepatic cholangiocarcinoma cases. Lognormal multivariate survival analysis was implemented to estimate survival for patients for treatment cohorts based on extent of surgical intervention and RT. RESULTS: Parametric estimated median survival for patients receiving total/radical resection + RT was 26 months; it was 25 months for total/radical resection alone, 25 months for subtotal/debulking resection + RT, 21 months for subtotal/debulking resection, 12 months for RT alone, and 9 months for those not receiving surgery or RT. Parametric multivariate analysis revealed age, American Joint Committee on Cancer Stage, grade, and surgical/radiation regimen as statistically significant covariates with survival. Surgery alone and adjuvant RT cohorts demonstrated evidence of improved survival compared with no treatment; comparatively, RT alone was associated with survival decrement. Early improvement in survival in adjuvant cohorts was not observed at later time points. CONCLUSIONS: Survival estimates using SEER data suggest an early survival advantage for adjuvant RT for patients with locoregional extrahepatic cholangiocarcinoma. Although future prospective series are needed to confirm these observations, SEER data represent the largest domestic population-based extrahepatic cholangiocarcinoma cohort, and may provide useful baseline survival estimates for future studies.

Authors
Fuller, CD; Wang, SJ; Choi, M; Czito, BG; Cornell, J; Welzel, TM; McGlynn, KA; Luh, JY; Thomas, CR
MLA Citation
Fuller, CD, Wang, SJ, Choi, M, Czito, BG, Cornell, J, Welzel, TM, McGlynn, KA, Luh, JY, and Thomas, CR. "Multimodality therapy for locoregional extrahepatic cholangiocarcinoma: a population-based analysis." Cancer 115.22 (November 15, 2009): 5175-5183.
PMID
19637356
Source
pubmed
Published In
Cancer
Volume
115
Issue
22
Publish Date
2009
Start Page
5175
End Page
5183
DOI
10.1002/cncr.24572

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

Accomplishments in 2008 in the adjuvant treatment of rectal cancer.

Overview of the Disease IncidencePrognostic FactorsCurrent General Therapy Standards Surgery(Neo) Adjuvant Radiotherapy and ChemotherapyAccomplishments During the Year Time Duration Between Radiotherapy and SurgeryHistopathology Post-Neoadjuvant TherapyMetabolic Imaging During Neoadjuvant TherapyNew Drugs in Combination with RadiotherapyNew StrategiesFuture Strategies ControversiesComments on ResearchObstacles to Progress.

Authors
Czito, B; Lordick, F
MLA Citation
Czito, B, and Lordick, F. "Accomplishments in 2008 in the adjuvant treatment of rectal cancer." Gastrointest Cancer Res 3.5 Supplement 2 (September 2009): S8-S14.
PMID
20011572
Source
pubmed
Published In
Gastrointestinal Cancer Research
Volume
3
Issue
5 Supplement 2
Publish Date
2009
Start Page
S8
End Page
S14

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

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

Potential Benefit of Radiation Therapy in Resectable Anorectal Melanoma

Authors
Reese, AS; Willett, CG; Tyler, DS; Seigler, HF; Clough, RW; Czito, BG
MLA Citation
Reese, AS, Willett, CG, Tyler, DS, Seigler, HF, Clough, RW, and Czito, BG. "Potential Benefit of Radiation Therapy in Resectable Anorectal Melanoma." 2009.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S274
End Page
S275

Intensity Modulated Radiation Therapy (IMRT) for Anal Cancer: The Duke University Experience

Authors
Pepek, JM; Willett, CG; Clough, RW; Wu, QJ; Yoo, S; Czito, BG
MLA Citation
Pepek, JM, Willett, CG, Clough, RW, Wu, QJ, Yoo, S, and Czito, BG. "Intensity Modulated Radiation Therapy (IMRT) for Anal Cancer: The Duke University Experience." 2009.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S267
End Page
S267

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

Multidisciplinary Management of Resectable Rectal Cancer New Developments and Controversies The Minsky/Guillem Article Reviewed

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Multidisciplinary Management of Resectable Rectal Cancer New Developments and Controversies The Minsky/Guillem Article Reviewed." ONCOLOGY-NEW YORK 22.12 (November 15, 2008): 1441-+.
Source
wos-lite
Published In
Oncology
Volume
22
Issue
12
Publish Date
2008
Start Page
1441
End Page
+

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

Is there a role for advanced radiation therapy technologies in the treatment of pancreatic adenocarcinoma? (vol 4, pg 241, 2008)

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? (vol 4, pg 241, 2008)." FUTURE ONCOLOGY 4.3 (June 2008): 448-448.
Source
wos-lite
Published In
Future oncology (London, England)
Volume
4
Issue
3
Publish Date
2008
Start Page
448
End Page
448

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

Is neoadjuvant chemoradiation for locally advanced gastric cancer feasible?

Authors
Untch, BR; Barfield, ME; Bendell, JC; Czito, BG; Willett, CG; Pappas, TN; White, R; Tyler, DS
MLA Citation
Untch, BR, Barfield, ME, Bendell, JC, Czito, BG, Willett, CG, Pappas, TN, White, R, and Tyler, DS. "Is neoadjuvant chemoradiation for locally advanced gastric cancer feasible?." GASTROENTEROLOGY 134.4 (April 2008): A873-A873.
Source
wos-lite
Published In
Gastroenterology
Volume
134
Issue
4
Publish Date
2008
Start Page
A873
End Page
A873

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

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

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

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

Radiation Therapy for Disease of the Biliary Tree and Gallbladder

Authors
Czito, BG; Anscher, MS
MLA Citation
Czito, BG, and Anscher, MS. "Radiation Therapy for Disease of the Biliary Tree and Gallbladder." (October 25, 2007): 147-162. (Chapter)
Source
scopus
Publish Date
2007
Start Page
147
End Page
162
DOI
10.1002/9780470986981.ch7

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

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

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

Contemporary management of rectal cancer: new standards, mounting questions, emerging challenges.

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Contemporary management of rectal cancer: new standards, mounting questions, emerging challenges." Gastrointest Cancer Res 1.2 (March 2007): 66-67.
PMID
19262722
Source
pubmed
Published In
Gastrointestinal Cancer Research
Volume
1
Issue
2
Publish Date
2007
Start Page
66
End Page
67

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

Particle radiation therapy for gastrointestinal malignancies.

Treatment-related toxicity is common in the radiotherapeutic management of cancers of the gastrointestinal tract. These toxicities can diminish treatment efficacy by necessitating treatment breaks, limiting the radiation dose that can be delivered, and hindering concomitant use of chemotherapy and targeted drug agents. Many efforts have focused on widening the gap between the likelihood of tumor control and the likelihood of toxicities associated with radiation. Use of particles that exhibit a Bragg peak phenomenon in their interactions with tissue, such as protons, heavier ions like carbon ions, and pions, is one means of concentrating radiation dose in tumors and away from normal tissues. Neutron beams have also been used in the treatment of gastrointestinal cancers in an effort to take advantage of their potent biologic effects. This report reviews basic particle radiation physics and biology, as well as the clinical experience with protons, heavier ions, pions, and neutrons in the treatment of various gastrointestinal malignancies. Potential future directions in clinical research with particle therapy are discussed.

Authors
Meyer, JJ; Czito, BG; Willett, CG
MLA Citation
Meyer, JJ, Czito, BG, and Willett, CG. "Particle radiation therapy for gastrointestinal malignancies." Gastrointest Cancer Res 1.4 Suppl 2 (2007): S50-S59.
PMID
19360149
Source
pubmed
Published In
Gastrointestinal Cancer Research
Volume
1
Issue
4 Suppl 2
Publish Date
2007
Start Page
S50
End Page
S59

Concurrent chemoradiation for resectable extrahepatic cholangiocarcinoma

Authors
Nelson, JW; Willett, CG; Clough, R; Clary, BM; Pappas, TN; Tyler, DS; Bendell, JC; Hurwitz, HI; Morse, MA; Czito, BG
MLA Citation
Nelson, JW, Willett, CG, Clough, R, Clary, BM, Pappas, TN, Tyler, DS, Bendell, JC, Hurwitz, HI, Morse, MA, and Czito, BG. "Concurrent chemoradiation for resectable extrahepatic cholangiocarcinoma." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S303
End Page
S303
DOI
10.1016/j.ijrobp.2007.07.1354

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

A phase I study of capecitabine (CAP), carboplatin (CARB), paclitaxel (TAX) and external beam radiation therapy (EBRT) for patients with esophageal carcinoma (EC).

14044 Background: Chemoradiotherapy is used to treat esophageal cancer with curative intent or local symptom control. A phase I study of 5-FU + CARB + TAX + EBRT showed 100% RR and 50% pCR rate. CAP allows for fluoropyrimidine treatment without the inconvenience of an infusion pump. CARB allows for platinum treatment with less toxicity than cisplatin. We evaluated this combination of agents in a phase I study.Patients with squamous cell carcinoma or adenocarcinoma of the esophagus requiring local therapy received CAP (825 mg/m2 bid on radiation days) + CARB (AUC 2 qweek) + TAX (60 mg/m2 qweek) + EBRT (1.8 Gy qd to 50.4 Gy). DLT was defined as any grade 4 heme toxicity, grade 3 heme toxicity lasting ≥ 7 days, ≥ grade 3 N/V, diarrhea, or esophagitis lasting ≥ 4 days despite optimal medical management, grade 3 other toxicity, inability to deliver 75% of scheduled CAP dose, or treatment delay > 3 days.13 pts were enrolled (10M, 3F). Median age was 62 (R- 48-78). EUS stage was uT3N0 (n=1), uT2N1 (n=1), or T3N1 (n=11). 2/3 pts had DLT at dose level 1 (both grade 4 esophagitis). Esophagectomy was performed in 2/3 patients, both pCR. Three pts were then enrolled at dose level -1 (CAP 600 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2). One patient developed DLT (grade 3 esophagitis) so 7 more pts were added at this dose level. Overall, 3/10 patients at dose level -1 developed DLT (two grade 3 esophagitis, one grade 3 hypotension). Esophagectomy was performed in 6/10 pts - 2/6 had pCR; 6/6 had pathologic downstaging.MTD for this regimen was CAP 625 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2 with EBRT to 50.4 Gy. However, at the MTD, this regimen is relatively toxic with no significant improvement in rate of pCR. [Table: see text].

Authors
Kelsey, CR; Czito, BG; Bendell, JC; Willett, CG; Morse, MA; D'Amico, TA; Honeycutt, W; Franklin, A; Yu, D; Hurwitz, HI
MLA Citation
Kelsey, CR, Czito, BG, Bendell, JC, Willett, CG, Morse, MA, D'Amico, TA, Honeycutt, W, Franklin, A, Yu, D, and Hurwitz, HI. "A phase I study of capecitabine (CAP), carboplatin (CARB), paclitaxel (TAX) and external beam radiation therapy (EBRT) for patients with esophageal carcinoma (EC)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 24.18_suppl (June 2006): 14044-.
PMID
27952282
Source
epmc
Published In
Journal of Clinical Oncology
Volume
24
Issue
18_suppl
Publish Date
2006
Start Page
14044

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

A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract.

PURPOSE: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. METHODS AND MATERIALS: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m(2) q12h)/5-FU (starting at 0.6 mg/m(2) q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. RESULTS: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m(2) q12h/1 mg/m(2) q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. CONCLUSION: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.

Authors
Czito, BG; Hong, TJ; Cohen, DP; Petros, WP; Tyler, DS; Pappas, TN; Yu, D; Lee, CG; Lockhart, AC; Morse, MA; Fernando, N; Hurwitz, HI
MLA Citation
Czito, BG, Hong, TJ, Cohen, DP, Petros, WP, Tyler, DS, Pappas, TN, Yu, D, Lee, CG, Lockhart, AC, Morse, MA, Fernando, N, and Hurwitz, HI. "A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract." Cancer Invest 24.1 (February 2006): 9-17.
PMID
16466986
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
24
Issue
1
Publish Date
2006
Start Page
9
End Page
17
DOI
10.1080/07357900500449454

Neoadjuvant chemoradiotherapy for operable esophageal cancer: Is paclitaxel necessary?

Authors
Chino, JP; Kelsey, CR; Willett, CG; Clough, R; Bendell, JC; Hurwitz, HI; D'Amico, T; Czito, BG
MLA Citation
Chino, JP, Kelsey, CR, Willett, CG, Clough, R, Bendell, JC, Hurwitz, HI, D'Amico, T, and Czito, BG. "Neoadjuvant chemoradiotherapy for operable esophageal cancer: Is paclitaxel necessary?." 2006.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S292
End Page
S293
DOI
10.1016/j.ijrobp.2006.07.552

Adenocarcinoma of the duodenum: A 30-year experience

Authors
Nelson, JW; Kelsey, CR; Willett, CG; Tyler, DS; Pappas, TN; Hurwitz, HI; Bendell, JC; Morse, MA; Clough, R; Czito, BG
MLA Citation
Nelson, JW, Kelsey, CR, Willett, CG, Tyler, DS, Pappas, TN, Hurwitz, HI, Bendell, JC, Morse, MA, Clough, R, and Czito, BG. "Adenocarcinoma of the duodenum: A 30-year experience." 2006.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S286
End Page
S286
DOI
10.1016/j.ijrobp.2006.07.540

Neoadjuvant therapy for gastric cancer - The Chadha/Kuvshinoff/Javle article reviewed

Authors
Czito, BG; Willett, CG
MLA Citation
Czito, BG, and Willett, CG. "Neoadjuvant therapy for gastric cancer - The Chadha/Kuvshinoff/Javle article reviewed." ONCOLOGY-NEW YORK 19.9 (August 2005): 1231-1232.
Source
wos-lite
Published In
Oncology
Volume
19
Issue
9
Publish Date
2005
Start Page
1231
End Page
1232

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

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.

BACKGROUND: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. METHODS: Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods. RESULTS: The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation. CONCLUSIONS: Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Authors
White, RR; Xie, HB; Gottfried, MR; Czito, BG; Hurwitz, HI; Morse, MA; Blobe, GC; Paulson, EK; Baillie, J; Branch, MS; Jowell, PS; Clary, BM; Pappas, TN; Tyler, DS
MLA Citation
White, RR, Xie, HB, Gottfried, MR, Czito, BG, Hurwitz, HI, Morse, MA, Blobe, GC, Paulson, EK, Baillie, J, Branch, MS, Jowell, PS, Clary, BM, Pappas, TN, and Tyler, DS. "Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer." Ann Surg Oncol 12.3 (March 2005): 214-221.
PMID
15827813
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
12
Issue
3
Publish Date
2005
Start Page
214
End Page
221
DOI
10.1245/ASO.2005.03.105

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

Carcinoma of the ampulla of vater: Patterns of failure after resection and possible benefit of adjuvant radiotherapy

Authors
Czito, BG; Clough, R; Pappas, T; Tyler, D; White, R; Hurwitz, H; Morse, M; Fernando, N; Clary, B; Willett, C
MLA Citation
Czito, BG, Clough, R, Pappas, T, Tyler, D, White, R, Hurwitz, H, Morse, M, Fernando, N, Clary, B, and Willett, C. "Carcinoma of the ampulla of vater: Patterns of failure after resection and possible benefit of adjuvant radiotherapy." 2005.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
63
Issue
2
Publish Date
2005
Start Page
S166
End Page
S167
DOI
10.1016/j.ijrobp.2005.07.287

Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter.

PURPOSE: Transitional cell carcinoma of the upper urinary tract is a relatively uncommon malignancy. The role of adjuvant radiation therapy and chemotherapy is not well defined. We retrospectively reviewed the records of 31 patients who underwent surgery followed by adjuvant radiotherapy with or without concurrent chemotherapy to determine overall outcome as well as impact of concurrent chemotherapy administration. MATERIALS AND METHODS: Between 1970 and 1997, 31 patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (renal pelvis in 13, ureter in 15, and renal pelvis and ureter in 3) were treated with radiotherapy following attempted curative resection. Most patients (28 of 31) had T3/4 and/or N+ disease. The median radiation dose was 46.9 Gy. Nine patients received methotrexate, cisplatin and vinblastine chemotherapy for 2 to 4 cycles, followed by concurrent cisplatin with radiation. RESULTS: Median followup was 2.6 years in all patients and 8.5 years in survivors. Median survival in all patients was 2.4 years. Of the patients 16 (52%) experienced disease relapse, including 9 (29%) with distant metastases alone. Seven patients (23%) experienced locoregional failure with distant metastases developing in all except 1 within 8 months of locoregional failure diagnosis. Five-year actuarial overall survival, disease specific survival, locoregional control and metastasis-free survival rates were 39%, 52%, 67% and 48%, respectively. On univariate analysis patients had improved 5-year actuarial overall and disease specific survival with the administration of concurrent chemotherapy (27% vs 67%, p = 0.01 and 41% vs 76%, p = 0.06, respectively). CONCLUSIONS: Our series suggests that the addition of concurrent cisplatin to adjuvant radiotherapy improves the ultimate outcome in patients with resected, locally advanced upper tract urothelial malignancies. This regimen should be considered in patients with T3/4 and/or node positive upper tract transitional cell carcinoma.

Authors
Czito, B; Zietman, A; Kaufman, D; Skowronski, U; Shipley, W
MLA Citation
Czito, B, Zietman, A, Kaufman, D, Skowronski, U, and Shipley, W. "Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter." J Urol 172.4 Pt 1 (October 2004): 1271-1275.
PMID
15371822
Source
pubmed
Published In
The Journal of Urology
Volume
172
Issue
4 Pt 1
Publish Date
2004
Start Page
1271
End Page
1275

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Authors
Gerke, H; White, R; Byrne, MF; Stiffier, H; Mitchell, RM; Hurwitz, HI; Morse, MA; Branch, MS; Jowell, PS; Czito, B; Clary, B; Pappas, TN; Tyler, DS; Baillie, J
MLA Citation
Gerke, H, White, R, Byrne, MF, Stiffier, H, Mitchell, RM, Hurwitz, HI, Morse, MA, Branch, MS, Jowell, PS, Czito, B, Clary, B, Pappas, TN, Tyler, DS, and Baillie, J. "Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage." Dig Liver Dis 36.6 (June 2004): 412-418.
PMID
15248382
Source
pubmed
Published In
Digestive and Liver Disease
Volume
36
Issue
6
Publish Date
2004
Start Page
412
End Page
418

A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon.

PURPOSE: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase, allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU combined with preoperative radiotherapy and determined the recommended Phase II dose and dose-limiting toxicity in patients with locally advanced rectal and colon cancer. METHODS AND MATERIALS: Patients with TNM Stage II or III rectal cancer and residual or recurrent colon cancer received eniluracil (starting at 6.0 mg/m(2) every 12 h) and 5-FU (starting at 0.6 mg/m(2) every 12 h). Eniluracil and 5-FU were given with a 5-week course of preoperative radiotherapy of 4500 cGy, with a possible 540-cGy boost. Surgery was performed approximately 4 weeks after completion of chemoradiotherapy. RESULTS: Twenty-two patients were enrolled; 1 patient was withdrawn owing to noncompliance. Chemotherapy was completed in all patients; radiotherapy was completed in 20 patients. The recommended Phase II dose of eniluracil and 5-FU was 8 mg/m(2) every 12 h and 0.8 mg/m(2) every 12 h, respectively. Diarrhea was the dose-limiting toxicity. Eleven of the 17 patients with primary rectal cancer underwent a sphincter-sparing procedure. One patient had a pathologic complete response. CONCLUSION: Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well tolerated. Additional investigation is warranted.

Authors
Czito, BG; Hong, TJ; Cohen, DP; Tyler, DS; Lee, CG; Anscher, MS; Ludwig, KA; Seigler, HF; Mantyh, C; Morse, MA; Lockhart, AC; Petros, WP; Honeycutt, W; Spector, NL; Ertel, PJ; Mangum, SG; Hurwitz, HI
MLA Citation
Czito, BG, Hong, TJ, Cohen, DP, Tyler, DS, Lee, CG, Anscher, MS, Ludwig, KA, Seigler, HF, Mantyh, C, Morse, MA, Lockhart, AC, Petros, WP, Honeycutt, W, Spector, NL, Ertel, PJ, Mangum, SG, and Hurwitz, HI. "A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon." Int J Radiat Oncol Biol Phys 58.3 (March 1, 2004): 779-785.
PMID
14967434
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
58
Issue
3
Publish Date
2004
Start Page
779
End Page
785
DOI
10.1016/S0360-3016(03)01567-0

Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter

Purpose: Transitional cell carcinoma of the upper urinary tract is a relatively uncommon malignancy. The role of adjuvant radiation therapy and chemotherapy is not well defined. We retrospectively reviewed the records of 31 patients who underwent surgery followed by adjuvant radiotherapy with or without concurrent chemotherapy to determine overall outcome as well as impact of concurrent chemotherapy administration. Materials and Methods: Between 1970 and 1997, 31 patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (renal pelvis in 13, ureter in 15, and renal pelvis and ureter in 3) were treated with radiotherapy following attempted curative resection. Most patients (28 of 31) had T3/4 and/or N+ disease. The median radiation dose was 46.9 Gy. Nine patients received methotrexate, cisplatin and vinblastine chemotherapy for 2 to 4 cycles, followed by concurrent cisplatin with radiation. Results: Median followup was 2.6 years in all patients and 8.5 years in survivors. Median survival in all patients was 2.4 years. Of the patients 16 (52%) experienced disease relapse, including 9 (29%) with distant metastases alone. Seven patients (23%) experienced locoregional failure with distant metastases developing in all except 1 within 8 months of locoregional failure diagnosis. Five-year actuarial overall survival, disease specific survival, locoregional control and metastasis-free survival rates were 39%, 52%, 67% and 48%, respectively. On univariate analysis patients had improved 5-year actuarial overall and disease specific survival with the administration of concurrent chemotherapy (27% vs 67%, p = 0.01 and 41% vs 76%, p = 0.06, respectively). Conclusions: Our series suggests that the addition of concurrent cisplatin to adjuvant radiotherapy improves the ultimate outcome in patients with resected, locally advanced upper tract urothelial malignancies. This regimen should be considered in patients with T3/4 and/or node positive upper tract transitional cell carcinoma.

Authors
Czito, B; Zietman, A; Kaufman, D; Skowronski, U; Shipley, W
MLA Citation
Czito, B, Zietman, A, Kaufman, D, Skowronski, U, and Shipley, W. "Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter." Journal of Urology 172.4 I (2004): 1271-1275.
Source
scival
Published In
Journal of Urology
Volume
172
Issue
4 I
Publish Date
2004
Start Page
1271
End Page
1275
DOI
10.1097/01.ju.0000137910.38441.8a

Prognostic significance of histologic response to preoperative chemoradiation for periampullary tumors

Authors
White, R; Xie, HB; Gottfried, MR; Czito, BG; Hurwitz, HI; Morse, MA; Paulson, EK; Jowell, PS; Baillie, J; Branch, MS; Clary, BM; Pappas, TN; Tyler, DS
MLA Citation
White, R, Xie, HB, Gottfried, MR, Czito, BG, Hurwitz, HI, Morse, MA, Paulson, EK, Jowell, PS, Baillie, J, Branch, MS, Clary, BM, Pappas, TN, and Tyler, DS. "Prognostic significance of histologic response to preoperative chemoradiation for periampullary tumors." January 2003.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
10
Issue
1
Publish Date
2003
Start Page
S62
End Page
S62

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
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