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Secord, Angeles Alvarez

Overview:

My primary research interest has focused on angiogenesis, molecular signatures, clinical trial development, and ovarian cancer. My fundamental goal is to develop a strong translational research program at Duke University in the Gynecologic Oncology Division where knowledge we glean from our basic science research can be incorporated into our clinical trial program. Specifically on anti-angiogenic therapy and molecular tumor signatures to direct therapy in patients with ovarian cancer to determine if a strategy that incorporates both clinical and genomic information can improve clinical outcome, minimize unnecessary toxicity, and impact positively on quality of life.
In addition I am interested in robotic-assisted laparoscopic surgery for women with endometrial, ovarian, and cervical cancers as well as for benign gynecologic conditions.

Positions:

Professor of Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1994

M.D. — University of Washington

Resident, Obstetrics & Gynecology

Duke University

Grants:

Lynparza Open Acess Olaparib

Administered By
Duke Cancer Institute
AwardedBy
AstraZeneca AB
Role
Principal Investigator
Start Date
July 12, 2017
End Date
February 17, 2022

Phase 2 Trial of Dose Dense (Weekly) Paclitaxel with Pembrolizumab (MK-3475) in Platinum Resistant Recurrent Ovarian Cancer

Administered By
Duke Cancer Institute
AwardedBy
H. Lee Moffitt Cancer Center & Research Institute
Role
Principal Investigator
Start Date
August 12, 2016
End Date
July 10, 2021

GOG3005-ABB VIE Protocol M13-694

Administered By
Duke Cancer Institute
AwardedBy
Gynecologic Oncology Group
Role
Principal Investigator
Start Date
November 01, 2015
End Date
October 31, 2020

Quadra Study

Administered By
Duke Cancer Institute
AwardedBy
TESARO
Role
Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2020

NCI National Clinical Trials Network U10 (Year 4)

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 14, 2014
End Date
February 28, 2019

Predictive value of the IL6 pathway to direct anti-angiogenic therapy in advanced ovarian cancer

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
American Association of Obstetricians and Gynecologists Foundation
Role
Principal Investigator
Start Date
July 27, 2017
End Date
June 30, 2018

Women with BRCA-mutated Advanced Stage Ovarian Cancer

Administered By
Duke Clinical Research Institute
AwardedBy
AstraZeneca LP
Role
Co Investigator
Start Date
May 25, 2017
End Date
February 28, 2018

Assessing the relevance of weighted values in the ASCO value framework in ovarian cancer patients

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
Gynecologic Oncology Group
Role
Investigator
Start Date
January 01, 2016
End Date
December 31, 2017

A Phase 2 Randomized Double-Blind Trial of Maintenance with Niraparib vs Placebo

Administered By
Duke Cancer Institute
AwardedBy
TESARO
Role
Principal Investigator
Start Date
November 01, 2013
End Date
October 31, 2017

Blood-based Angiome Profiling to Direct Bevacizumab Therapy in Ovarian Cancer

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 2014
End Date
April 30, 2017

Tesaro Ovarian Cancer Practicum

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
TESARO
Role
Principal Investigator
Start Date
October 25, 2016
End Date
December 01, 2016

A Phase III Randomized, Double-Blind, Placebo Controlled Multicrentre Study of Olaparib Maintenance Monotherapy

Administered By
Duke Cancer Institute
AwardedBy
AstraZeneca Pharmaceuticals, LP
Role
Principal Investigator
Start Date
May 01, 2014
End Date
November 03, 2015
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Publications:

An evaluation of progression free survival and overall survival of ovarian cancer patients with clear cell carcinoma versus serous carcinoma treated with platinum therapy: An NRG Oncology/Gynecologic Oncology Group experience.

We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC).We reviewed data from FIGO stage I-IV epithelial ovarian cancer patients who participated in 12 prospective randomized GOG protocols. Proportional hazards models were used to compare progression-free survival (PFS) and overall survival (OS) by cell type (clear cell versus serous).There were 10,803 patients enrolled, 9531 were eligible, evaluable and treated with platinum, of whom 544 (6%) had OCCC, 7054 (74%) had SOC, and 1933 (20%) had other histologies and are not included further. In early stage (I-II) patients, PFS was significantly better in OCCC than in SOC patients. For late stage (III, IV) patients, OCCC had worse PFS and OS compared to SOC, OS HR=1.66 (1.43, 1.91; p<0.001). After adjusting for age and stratifying by protocol and treatment arm, stage, performance status, and race, OCCC had a significantly decreased OS, HR=1.53 (1.33, 1.76; p<0.001). In early stage cases, there was a significantly decreased treatment effect on PFS for consolidative therapy with weekly Paclitaxel versus observation in OCCC compared to SOC (p=0.048).This is one of the largest analyses to date of OCCC treated on multiple cooperative group trials. OCCC histology is more common than SOC in early stage disease. When adjusted for prognostic factors, in early stage patients, PFS was better for OCCC than for SOC; however, in late-stage patients, OCCC was significantly associated with decreased OS. Finally, treatment effect was influenced by histology.

Authors
Oliver, KE; Brady, WE; Birrer, M; Gershenson, DM; Fleming, G; Copeland, LJ; Tewari, K; Argenta, PA; Mannel, RS; Secord, AA; Stephan, J-M; Mutch, DG; Stehman, FB; Muggia, FM; Rose, PG; Armstrong, DK; Bookman, MA; Burger, RA; Farley, JH
MLA Citation
Oliver, KE, Brady, WE, Birrer, M, Gershenson, DM, Fleming, G, Copeland, LJ, Tewari, K, Argenta, PA, Mannel, RS, Secord, AA, Stephan, J-M, Mutch, DG, Stehman, FB, Muggia, FM, Rose, PG, Armstrong, DK, Bookman, MA, Burger, RA, and Farley, JH. "An evaluation of progression free survival and overall survival of ovarian cancer patients with clear cell carcinoma versus serous carcinoma treated with platinum therapy: An NRG Oncology/Gynecologic Oncology Group experience." Gynecologic oncology 147.2 (November 2017): 243-249.
PMID
28807367
Source
epmc
Published In
Gynecologic Oncology
Volume
147
Issue
2
Publish Date
2017
Start Page
243
End Page
249
DOI
10.1016/j.ygyno.2017.08.004

Use of a novel sentinel lymph node mapping algorithm reduces the need for pelvic lymphadenectomy in low-grade endometrial cancer.

To evaluate the capability of a novel sentinel lymph node (SLN) mapping algorithm to reduce the need for pelvic lymphadenectomy (PLND) in patients with low-grade (G1-2) endometrial cancer (LGEC).Patients with LGEC underwent evaluation according to a novel lymphatic assessment algorithm during hysterectomy with SLN biopsy at two academic gynecologic oncology programs. Side-specific PLND was only performed if ipsilateral SLN mapping failed and high-risk uterine features were identified on frozen section (FS). Side-specific and PLND rates were compared to theoretical PLND rates based on the NCCN EC SLN mapping algorithm.Since 11/2015, 113 LGEC patients have been managed according to the algorithm. SLN mapping was bilateral (81%), unilateral (12%), or neither (6%). Nine patients (8.0%) had LN metastases identified. Of the 21 patients requiring intraoperative FS due to failed SLN mapping, high-risk uterine features were identified in eight (38%). These patients underwent either bilateral (2) or unilateral (6) PLND. Side-specific and overall PLND rates were 5.3% and 7.1%, respectively. If all patients with failed mapping had undergone PLND according to the NCCN algorithm, side-specific and overall PLND rates would have been higher, 12.4% and 18.6%, respectively (P=0.01). All patients who failed to map and did not undergo side-specific PLND had low-risk uterine features on final pathology.Lymphatic assessment using SLN mapping followed by selective FS to determine need for PLND is feasible. When compared to the NCCN algorithm, this novel "Reflex Frozen Section" strategy eliminates PLND in patients at lowest risk for metastasis without compromising identification of metastatic nodal disease.

Authors
Tanner, E; Puechl, A; Levinson, K; Havrilesky, LJ; Sinno, A; Secord, AA; Fader, AN; Lee, PS
MLA Citation
Tanner, E, Puechl, A, Levinson, K, Havrilesky, LJ, Sinno, A, Secord, AA, Fader, AN, and Lee, PS. "Use of a novel sentinel lymph node mapping algorithm reduces the need for pelvic lymphadenectomy in low-grade endometrial cancer." Gynecologic oncology (October 19, 2017).
PMID
29056441
Source
epmc
Published In
Gynecologic Oncology
Publish Date
2017
DOI
10.1016/j.ygyno.2017.10.020

Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.

Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC).Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis.Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001).Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC.

Authors
Phippen, NT; Secord, AA; Wolf, S; Samsa, G; Davidson, B; Abernethy, AP; Cella, D; Havrilesky, LJ; Burger, RA; Monk, BJ; Leath, CA
MLA Citation
Phippen, NT, Secord, AA, Wolf, S, Samsa, G, Davidson, B, Abernethy, AP, Cella, D, Havrilesky, LJ, Burger, RA, Monk, BJ, and Leath, CA. "Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study." Gynecologic oncology 147.1 (October 2017): 98-103.
PMID
28743369
Source
epmc
Published In
Gynecologic Oncology
Volume
147
Issue
1
Publish Date
2017
Start Page
98
End Page
103
DOI
10.1016/j.ygyno.2017.07.121

Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer.

To determine whether the processing of additional adipose tissue collected during lymph node (LN) dissection results in the identification of additional LNs during endometrial cancer (EC) staging and to determine if the division of LNs into nodal basin-specific specimens has an effect on the number of LNs identified during EC staging. A prospective randomized controlled trial was performed on women with high-grade EC undergoing surgical staging. Subjects were randomized to collection of LNs into nodal basin-specific containers on the randomized side versus simple labeling on the nonrandomized side. The total number of LNs and total number of LNs with metastases on the randomized versus the nonrandomized side were compared. The remaining adipose tissue from each LN specimen was submitted for histologic examination. We analyzed the number of LNs with and without metastases identified from additional adipose tissue. Of 120 consented subjects, 56 had sufficient data for analysis. The additional adipose tissue contained 7.5 additional LNs per patient on average (range: 0-26). In 2/54 total cases (3.7%) and 2/5 cases with nodal metastases (40%), the additional adipose contained LNs with metastases. In both cases, metastases were also detected in grossly identified LN candidates. The mean number of LNs identified was not significantly different based on method of collection (P=0.22). The mean number of LNs containing metastases per side was not significantly different (P=0.58). Processing of adipose tissue does increase the total number of LNs identified, however, it does not influence EC stage. No difference in LN counts was noted with basin-specific collection.

Authors
Davidson, BA; Ehrisman, J; Abbott, S; Harmon, Z; Secord, AA; Berchuck, A; Lee, PS; Valea, FA; Li, X; Havrilesky, LJ; Hall, AHS
MLA Citation
Davidson, BA, Ehrisman, J, Abbott, S, Harmon, Z, Secord, AA, Berchuck, A, Lee, PS, Valea, FA, Li, X, Havrilesky, LJ, and Hall, AHS. "Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer." International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists (July 11, 2017).
PMID
28700428
Source
epmc
Published In
International Journal of Gynecological Pathology
Publish Date
2017
DOI
10.1097/pgp.0000000000000418

Synuclein-γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study.

Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023).High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression-free survival were assessed using log-rank tests and Cox proportional-hazards models, which also were adjusted for age, race, and stage.The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log-rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91-1.9 in adjusted Cox model). The progression-free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log-rank P = .0081; HR, 1.36; 95% CI, 0.96-1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54-11.45]; p16: HR, 1.95 [95% CI, 1.01-3.75]) and progression-free survival (p53: HR, 2.16 [95% CI, 1.09-4.27]; p16: HR, 1.53 [95% CI, 0.87-2.69]) compared with low levels.This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144-1155. © 2016 American Cancer Society.

Authors
Winder, AD; Maniar, KP; Wei, J-J; Liu, D; Scholtens, DM; Lurain, JR; Schink, JC; Buttin, BM; Filiaci, VL; Lankes, HA; Ramirez, NC; Park, K; Singh, M; Lieberman, RW; Mannel, RS; Powell, MA; Backes, FJ; Mathews, CA; Pearl, ML; Secord, AA; Peace, DJ; Mutch, DG; Creasman, WT; Kim, JJ
MLA Citation
Winder, AD, Maniar, KP, Wei, J-J, Liu, D, Scholtens, DM, Lurain, JR, Schink, JC, Buttin, BM, Filiaci, VL, Lankes, HA, Ramirez, NC, Park, K, Singh, M, Lieberman, RW, Mannel, RS, Powell, MA, Backes, FJ, Mathews, CA, Pearl, ML, Secord, AA, Peace, DJ, Mutch, DG, Creasman, WT, and Kim, JJ. "Synuclein-γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study." Cancer 123.7 (April 2017): 1144-1155.
PMID
27926776
Source
epmc
Published In
Cancer
Volume
123
Issue
7
Publish Date
2017
Start Page
1144
End Page
1155
DOI
10.1002/cncr.30477

Prior breast cancer and tamoxifen exposure does not influence outcomes in women with uterine papillary serous carcinoma.

To evaluate progression-free survival (PFS) and overall survival (OS) outcomes in women diagnosed with uterine papillary serous carcinoma (UPSC) who have had (UPSCBR+) or have not had (UPSCBR-) an antecedent history of breast cancer and to correlate their outcomes to prior tamoxifen exposure.Data were collected for women diagnosed with UPSC at two academic institutions between January 1997 and July 2012. Patient demographics, tumor histology, stage, and treatments were recorded. Patients were divided into two groups: those with and without a personal history of breast cancer. Within the UPSCBR+ cohort, we identified those with a history of tamoxifen use. Cox regression modeling was used to explore associations between selected covariates of interest and the time-to-event outcomes of PFS and OS.Of 323 patients with UPSC, 46 (14%) were UPSCBR+. Of these, 15 (33%) had a history of tamoxifen use. UPSCBR+ patients were older than UPSCBR- (median years, 72 vs. 68, p=0.004). UPSCBR+ women showed no significant difference in PFS or OS compared to UPSCBR- (p=0.64 and p=0.73 respectively), even after controlling for age (p=0.15 and p=0.48 respectively). Within the UPSCBR+ cohort, there was no difference in PFS or OS with or without tamoxifen exposure (p=0.98 and p=0.94 respectively).There was no difference in PFS or OS between the UPSCBR+ and UPSCBR- cohorts. We did not demonstrate significant OS or PFS differences in women who took tamoxifen prior to their endometrial cancer diagnosis. These findings have implications for counseling, and should be encouraging to women who are facing their second cancer diagnosis.

Authors
Pierce, SR; Stine, JE; Gehrig, PA; Havrilesky, LJ; Secord, AA; Nakayama, J; Snavely, AC; Moore, DT; Kim, KH
MLA Citation
Pierce, SR, Stine, JE, Gehrig, PA, Havrilesky, LJ, Secord, AA, Nakayama, J, Snavely, AC, Moore, DT, and Kim, KH. "Prior breast cancer and tamoxifen exposure does not influence outcomes in women with uterine papillary serous carcinoma." Gynecologic oncology 144.3 (March 2017): 531-535.
PMID
28062116
Source
epmc
Published In
Gynecologic Oncology
Volume
144
Issue
3
Publish Date
2017
Start Page
531
End Page
535
DOI
10.1016/j.ygyno.2016.12.024

Chemotherapy completion in elderly women with ovarian, primary peritoneal or fallopian tube cancer - An NRG oncology/Gynecologic Oncology Group study.

A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living (IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or >7days delay in elderly ovarian cancer patients.Patients' age ≥70 along with their physicians chose between two regimens: CP (Carboplatin AUC 5, Paclitaxel 135mg/m2) or C (Carboplatin AUC 5), both given every 3weeks either after primary surgery or as neoadjuvant chemotherapy (NACT) with IADL and quality of life assessments performed at baseline, pre-cycle 3, and post-cycle 4.Two-hundred-twelve women were enrolled, 152 selecting CP and 60 selecting C. Those who selected CP had higher baseline IADL scores (p<0.001). After adjusting for age and PS, baseline IADL was independently associated with the choice of regimen (p=0.035). The baseline IADL score was not found to be associated with completion of 4 cycles of chemotherapy without dose reduction or delays (p=0.21), but was associated with completion of 4 cycles of chemotherapy regardless of dose reduction and delay (p=0.008) and toxicity, with the odds ratio (OR) of grade 3+ toxicity decreasing 17% (OR: 0.83; 95%CI: 0.72-0.96; p=0.013) for each additional activity in which the patient was independent. After adjustment for chemotherapy regimen, IADL was also associated with overall survival (p=0.019) for patients receiving CP.Patients with a higher baseline IADL score (more independent) were more likely to complete 4 cycles of chemotherapy and less likely to experience grade 3 or higher toxicity.

Authors
von Gruenigen, VE; Huang, HQ; Beumer, JH; Lankes, HA; Tew, W; Herzog, T; Hurria, A; Mannel, RS; Rizack, T; Landrum, LM; Rose, PG; Salani, R; Bradley, WH; Rutherford, TJ; Higgins, RV; Secord, AA; Fleming, G
MLA Citation
von Gruenigen, VE, Huang, HQ, Beumer, JH, Lankes, HA, Tew, W, Herzog, T, Hurria, A, Mannel, RS, Rizack, T, Landrum, LM, Rose, PG, Salani, R, Bradley, WH, Rutherford, TJ, Higgins, RV, Secord, AA, and Fleming, G. "Chemotherapy completion in elderly women with ovarian, primary peritoneal or fallopian tube cancer - An NRG oncology/Gynecologic Oncology Group study." Gynecologic oncology 144.3 (March 2017): 459-467.
PMID
28089376
Source
epmc
Published In
Gynecologic Oncology
Volume
144
Issue
3
Publish Date
2017
Start Page
459
End Page
467
DOI
10.1016/j.ygyno.2016.11.033

Angiogenesis

© 2017 Elsevier Inc. All rights reserved. Angiogenesis is a complex multifaceted process essential for cancer growth and progression. The underlying biology regulating angiogenesis is incredibly complicated, involving interaction between cancer cells and the tumor microenvironment. Angiogenic growth factor and receptor targets have been exploited to develop antiangiogenic therapies that have been successfully translated into clinical trials. Adoption of these agents into the clinical arena has improved survival in women with selected gynecologic cancers. The incorporation of bevacizumab, the most studied antiangiogenic, has received regulatory approval for the treatment of ovarian and cervical cancers. Further research has elucidated novel biomarkers and targets currently in preclinical and early clinical trial development. Translational research from pivotal trials has identified predictive biomarkers that can be explored in integral biomarker-directed trials. If successful, biomarkers to direct antiangiogenic therapy will identify women most likely to benefit from treatment and avoid unnecessary toxicity and cost.

Authors
Secord, AA; Siamakpour-Reihani, S
MLA Citation
Secord, AA, and Siamakpour-Reihani, S. "Angiogenesis." Translational Advances in Gynecologic Cancers. February 22, 2017. 79-109.
Source
scopus
Publish Date
2017
Start Page
79
End Page
109
DOI
10.1016/B978-0-12-803741-6.00005-7

Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer.

The advent of multigene panels has increased genetic testing options for women with epithelial ovarian cancer (EOC). We designed a decision model to compare costs and probabilities of identifying a deleterious mutation or variant of uncertain significance (VUS) using different genetic testing strategies.A decision model was developed to compare costs and outcomes of two testing strategies for women with EOC: multigene testing (MGT) versus single-gene testing for BRCA1/2. Outcomes were mean cost and number of deleterious mutations and VUSs identified. Model inputs were obtained from published genetic testing data in EOC. One-way sensitivity analyses and Monte Carlo probabilistic sensitivity analyses were performed.No family history model: MGT cost $1,160 more on average than BRCA1/2 testing and identified an additional 3.8 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $30,812 and identified 5.4 additional VUSs. Family history model: MGT cost $654 more on average and identified an additional 7.0 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $9,909 and identified 2.6 additional VUSs.MGT was associated with a higher additional cost per deleterious mutation identified and a higher ratio of VUS burden to actionable information in women with no family history as compared with women with a family history. Family history should be considered when determining an initial genetic testing platform in women with EOC.

Authors
Foote, JR; Lopez-Acevedo, M; Buchanan, AH; Secord, AA; Lee, PS; Fountain, C; Myers, ER; Cohn, DE; Reed, SD; Havrilesky, LJ
MLA Citation
Foote, JR, Lopez-Acevedo, M, Buchanan, AH, Secord, AA, Lee, PS, Fountain, C, Myers, ER, Cohn, DE, Reed, SD, and Havrilesky, LJ. "Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer." Journal of oncology practice 13.2 (February 2017): e120-e129.
PMID
28045615
Source
epmc
Published In
Journal of Oncology Practice
Volume
13
Issue
2
Publish Date
2017
Start Page
e120
End Page
e129
DOI
10.1200/jop.2016.011866

Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer

Authors
Foote, JR; Lopez-Acevedo, M; Buchanan, AH; Secord, AA; Lee, PS; Fountain, C; Myers, ER; Cohn, DE; Reed, SD; Havrilesky, LJ
MLA Citation
Foote, JR, Lopez-Acevedo, M, Buchanan, AH, Secord, AA, Lee, PS, Fountain, C, Myers, ER, Cohn, DE, Reed, SD, and Havrilesky, LJ. "Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer." Journal of Oncology Practice 13.2 (February 2017): e120-e129.
Source
crossref
Published In
Journal of Oncology Practice
Volume
13
Issue
2
Publish Date
2017
Start Page
e120
End Page
e129
DOI
10.1200/JOP.2016.011866

Disparities in the surgical staging of high-grade endometrial cancer in the United States.

The National Comprehensive Cancer Network (NCCN) and the Society of Gynecologic Oncology (SGO) recommend lymph node sampling (LNS) as a key component in the surgical staging of high-grade endometrial cancer. Our goal was to examine surgical staging patterns for high-grade endometrial cancer in the United States.The National Cancer Data Base (NCDB) was searched for patients who underwent surgery for serous, clear cell, or grade 3 endometrioid endometrial cancer. Outcomes were receipt of LNS and overall survival (OS). Multivariate logistic regression was used to examine receipt of LNS in Stage I-III disease based on race (White vs. Black), income, surgical volume, and distance traveled to care. Multivariate Cox proportional hazards regression modeling was used to assess OS based on stage, race, income, LNS, surgical volume, and distance traveled.Forty-two thousand nine hundred seventy-three patients were identified: 76% White, 53% insured by Medicare/Medicaid, 24% traveled >30 miles, and 33% stage III disease. LNS was similar among White and Black women (81% vs 82%). LNS was more common among >30 miles traveled (84% vs 81%, p < 0.001), higher surgical volume (83% vs 80%, p < 0.001), and academic centers (84% vs 80%, p < 0.001). In multivariate analysis, higher income, higher surgical volume, Charlson-Deyo score, and distance traveled were predictors of LNS. Stage III disease (HR 3.39, 95% CI 3.28-3.50), age (10-year increase; HR 1.63, 95% CI 1.61-1.66), lack of LNS (HR 1.64, 95% CI 1.56-1.69), and low income (HR 1.20, 95% CI 1.14-1.27) were predictors of lower survival.Surgical care for high-grade endometrial cancer in the United States is not uniform. Improved access to high quality care at high volume centers is needed to improve rates of recommended LNS.

Authors
Foote, JR; Gaillard, S; Broadwater, G; Sosa, JA; Davidson, B; Adam, MA; Secord, AA; Jones, MB; Chino, J; Havrilesky, LJ
MLA Citation
Foote, JR, Gaillard, S, Broadwater, G, Sosa, JA, Davidson, B, Adam, MA, Secord, AA, Jones, MB, Chino, J, and Havrilesky, LJ. "Disparities in the surgical staging of high-grade endometrial cancer in the United States." Gynecologic oncology research and practice 4 (January 19, 2017): 1-.
Website
http://hdl.handle.net/10161/14627
PMID
28116108
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
4
Publish Date
2017
Start Page
1
DOI
10.1186/s40661-016-0036-3

Multidisciplinary approach to manage antenatally suspected placenta percreta: updated algorithm and patient outcomes.

Due to the significant morbidity and mortality associated with placenta percreta, alternative management options are needed. Beginning in 2005, our institution implemented a multidisciplinary strategy to patients with suspected placenta percreta. The purpose of this study is to present our current strategy, maternal morbidity and outcomes of patients treated by our approach.From 2005 to 2014, a retrospective cohort study of patients with suspected placenta percreta at an academic tertiary care institution was performed. Treatment modalities included immediate hysterectomy at the time of cesarean section (CHYS), planned delayed hysterectomy (interval hysterectomy 6 weeks after delivery) (DH), and fertility sparing (uterine conservation) (FS). Prognostic factors of maternal morbidity were identified from medical records. Complications directly related to interventional procedures and DH was recorded. Descriptive statistics were utilized.Of the 21 patients with suspected placenta percreta, 7 underwent CHYS, 13 underwent DH, and 1 had FS with uterine preservation. Of the 20 cases that underwent hysterectomy, final pathology showed 11 increta, 7 percreta, and 2 inconclusive. 19/20 cases underwent interventional radiology (IR) procedures. Selective embolization was utilized in 14 cases (2/7 CHYS; 12/13 DH). The median time from cesarean section (CS) to DH was 41 [26-68] days. There were no cases of emergent hysterectomy, delayed hemorrhage, or sepsis in the DH group. Both estimated blood loss and number of packed red blood cell transfusions were significantly higher in the CHYS group. 3/21 cases required massive transfusion (2 CHYS, 1 FS) with median total blood product transfusion of 13 units [12-15]. The four IR-related complications occurred in the DH group. Incidence of postoperative complications was similar between both groups. Median hospital length of stay (LOS) after CHYS was 4 days [3-8] compared to DH cohort: 7 days [3-33] after CS and 4 days [1 -10] after DH. The DH cohort had a higher rate of hospital readmission of 54% (7/13) compared to 14% (1/7) CHYS, most commonly due to pain. There were no maternal deaths.This multidisciplinary strategy may appear feasible; however, further investigation is warranted to evaluate the effectiveness of alternative approaches to cesarean hysterectomy in cases of morbidly adherent placenta.

Authors
Lee, PS; Kempner, S; Miller, M; Dominguez, J; Grotegut, C; Ehrisman, J; Previs, R; Havrilesky, LJ; Broadwater, G; Ellestad, SC; Secord, AA
MLA Citation
Lee, PS, Kempner, S, Miller, M, Dominguez, J, Grotegut, C, Ehrisman, J, Previs, R, Havrilesky, LJ, Broadwater, G, Ellestad, SC, and Secord, AA. "Multidisciplinary approach to manage antenatally suspected placenta percreta: updated algorithm and patient outcomes." Gynecologic oncology research and practice 4 (January 2017): 11-.
Website
http://hdl.handle.net/10161/15582
PMID
28852530
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
4
Publish Date
2017
Start Page
11
DOI
10.1186/s40661-017-0049-6

Does time interval between surgery and intraperitoneal chemotherapy administration in advanced ovarian cancer carry a prognostic impact? An NRG Oncology/Gynecologic Oncology Group study ancillary study.

To determine the relationship of the time from surgery to intraperitoneal (IP) chemotherapy (TSIC) initiation with survival of patients with stage III epithelial ovarian cancer (EOC) patients using ancillary data from cooperative group clinical trials.Data from 420 patients with stage III EOC treated with IP chemotherapy under GOG-0114 and 172 were reviewed. The Cox proportional hazards model was used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on PFS and OS.The median TSIC was 62.5days (interquartile range 28-83). The median TSIC was longer for patients in GOG-0114 vs those in GOG-172 (83 vs 26days, p<0.001). TSIC was significantly associated (p=0.049) with PFS: each 10% increase in TSIC (days) decreases the risk of progression by 3%. TSIC was not significantly associated with OS in this model. In a linear regression model, gross residual disease was significantly associated with shorter TSIC (R2 -0.141, 95%CI -0.217, -0.064, p<0.001). When only data from GOG-172 were considered, no statistical significant association was found between TSIC and PFS or OS.In this ancillary data study, TSIC was not associated with improved OS in patients with stage III epithelial ovarian cancer. TSIC was significantly associated with PFS for the entire cohort, suggesting increase in PFS with longer TSIC. However, this was not found when only data from GOG 172 or GOG 114 were analyzed separately. Hence, the relationship between IP chemotherapy initiation and time from surgery needs to be studied further.

Authors
Garcia-Soto, AE; Java, JJ; Nieves Neira, W; Pearson, JM; Cohn, DE; Lele, SB; Tewari, KS; Walker, JL; Alvarez Secord, A; Armstrong, DK; Copeland, LJ
MLA Citation
Garcia-Soto, AE, Java, JJ, Nieves Neira, W, Pearson, JM, Cohn, DE, Lele, SB, Tewari, KS, Walker, JL, Alvarez Secord, A, Armstrong, DK, and Copeland, LJ. "Does time interval between surgery and intraperitoneal chemotherapy administration in advanced ovarian cancer carry a prognostic impact? An NRG Oncology/Gynecologic Oncology Group study ancillary study." Gynecologic oncology 143.3 (December 2016): 484-489.
PMID
27726923
Source
epmc
Published In
Gynecologic Oncology
Volume
143
Issue
3
Publish Date
2016
Start Page
484
End Page
489
DOI
10.1016/j.ygyno.2016.10.003

Levonorgestrel Intrauterine Device as an Endometrial Cancer Prevention Strategy in Obese Women: A Cost-Effectiveness Analysis.

To estimate the cost-effectiveness of the levonorgestrel intrauterine device (IUD) as an endometrial cancer prevention strategy in obese women.A modified Markov model was used to compare IUD placement at age 50 with usual care among women with a body mass index (BMI, kg/m) 40 or greater or BMI 30 or greater. The effects of obesity on incidence and survival were incorporated. The IUD was assumed to confer a 50% reduction in cancer incidence over 5 years. Costs of IUD and cancer care were included. Clinical outcomes were cancer diagnosis and deaths from cancer. Incremental cost-effectiveness ratios were calculated in 2015 U.S. dollars per year of life saved. One-way and two-way sensitivity analyses and Monte Carlo probabilistic analyses were performed.For a 50 year old with BMI 40 or greater, the IUD strategy is costlier and more effective than usual care with an incremental cost-effectiveness ratio of $74,707 per year of life saved. If the protective effect of the levonorgestrel IUD is assumed to be 10 years, the incremental cost-effectiveness ratio decreases to $37,858 per year of life saved. In sensitivity analysis, a levonorgestrel IUD that reduces cancer incidence by at least 68% in women with BMIs of 40 or greater or costs less than $500 is potentially cost-effective. For BMI 30 or greater, the incremental cost-effectiveness ratio of IUD strategy is $137,223 per year of life saved compared with usual care. In Monte Carlo analysis, IUD placement for BMI 40 or greater is cost-effective in 50% of simulations at a willingness-to-pay threshold of $100,000 per year of life saved.The levonorgestrel IUD is a potentially cost-effective strategy for prevention of deaths from endometrial cancer in obese women.

Authors
Dottino, JA; Hasselblad, V; Secord, AA; Myers, ER; Chino, J; Havrilesky, LJ
MLA Citation
Dottino, JA, Hasselblad, V, Secord, AA, Myers, ER, Chino, J, and Havrilesky, LJ. "Levonorgestrel Intrauterine Device as an Endometrial Cancer Prevention Strategy in Obese Women: A Cost-Effectiveness Analysis." Obstetrics and gynecology 128.4 (October 2016): 747-753.
PMID
27607867
Source
epmc
Published In
Obstetrics & Gynecology (Elsevier)
Volume
128
Issue
4
Publish Date
2016
Start Page
747
End Page
753
DOI
10.1097/aog.0000000000001616

Performance of sentinel lymph node biopsy in high-risk endometrial cancer.

To determine the rate and performance of sentinel lymph node (SLN) mapping among women with high-risk endometrial cancers.Patients diagnosed between 2012 and 2015 with uterine cancer of grade 3 endometrioid, clear cell, serous or carcinosarcoma histology and who underwent SLN mapping prior to full pelvic lymph node dissection were included. Subjects underwent methylene blue or ICG injection for laparoscopic (N = 16) or robotic-assisted laparoscopic (N = 20) staging. Outcomes included SLN mapping rates, SLN and non-SLN positive rates, false negative SLN algorithm rate, and the negative predictive value (NPV) of the SLN algorithm. Fisher's exact test was used to compare mapping and node positivity rates.9/36 (25%) patients with high-risk uterine cancer had at least one metastatic lymph node identified. Successful mapping occurred in 30/36 (83%) patients. SLN mapped to pelvic nodes bilaterally in 20 (56%), unilaterally in 9 (25%), and aortic nodes only in 1 (3%). Malignancy was identified in 14/95 (15%) of all sentinel nodes and 12/775 (1.5%) of all non-sentinel nodes (p < 0.001). The false negative rate of SLN mapping alone was 2/26 (7.7%); the NPV was 92.3%. When the SLN algorithm was applied retrospectively the false negative rate was 0/31 (0%); the NPV was 100%.SLN mapping rates for high-risk cancers are slightly lower than in prior reports of lower risk cancers. The NPV of the SLN mapping alone is 92% and rises to 100% when the SLN algorithm is applied. Such results are acceptable and consistent with larger subsets of lower risk endometrial cancers.

Authors
Ehrisman, J; Secord, AA; Berchuck, A; Lee, PS; Di Santo, N; Lopez-Acevedo, M; Broadwater, G; Valea, FA; Havrilesky, LJ
MLA Citation
Ehrisman, J, Secord, AA, Berchuck, A, Lee, PS, Di Santo, N, Lopez-Acevedo, M, Broadwater, G, Valea, FA, and Havrilesky, LJ. "Performance of sentinel lymph node biopsy in high-risk endometrial cancer." Gynecologic oncology reports 17 (August 2016): 69-71.
PMID
27453926
Source
epmc
Published In
Gynecologic Oncology Reports
Volume
17
Publish Date
2016
Start Page
69
End Page
71
DOI
10.1016/j.gore.2016.04.002

Is Intraperitoneal Chemotherapy Dead?

Authors
Secord, AA; Havrilesky, LJ
MLA Citation
Secord, AA, and Havrilesky, LJ. "Is Intraperitoneal Chemotherapy Dead?." Obstetrics and gynecology 127.6 (June 2016): 983-984.
PMID
27159765
Source
epmc
Published In
Obstetrics & Gynecology (Elsevier)
Volume
127
Issue
6
Publish Date
2016
Start Page
983
End Page
984
DOI
10.1097/aog.0000000000001461

Patient preference-weighted assessments using the ASCO value framework in recurrent, platinum sensitive ovarian cancer

Authors
Foote, J; Liang, M; Secord, AA; Cohn, DE; Havrilesky, LJ
MLA Citation
Foote, J, Liang, M, Secord, AA, Cohn, DE, and Havrilesky, LJ. "Patient preference-weighted assessments using the ASCO value framework in recurrent, platinum sensitive ovarian cancer." May 20, 2016.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
34
Issue
15
Publish Date
2016
DOI
10.1200/JCO.2016.34.15_suppl.6630

Phase II evaluation of nintedanib in the treatment of bevacizumab-resistant persistent/recurrent ovarian, fallopian tube, or primary peritoneal carcinoma.

Authors
Davidson, BA; Squatrito, R; Duska, LR; Havrilesky, LJ; Schwager, N; McCollum, M; Arapovic, S; Secord, AA
MLA Citation
Davidson, BA, Squatrito, R, Duska, LR, Havrilesky, LJ, Schwager, N, McCollum, M, Arapovic, S, and Secord, AA. "Phase II evaluation of nintedanib in the treatment of bevacizumab-resistant persistent/recurrent ovarian, fallopian tube, or primary peritoneal carcinoma." May 20, 2016.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
34
Issue
15
Publish Date
2016
DOI
10.1200/JCO.2016.34.15_suppl.TPS5601

Prognostic and predictive blood-based biomarkers (BMs) in patients (pts) with advanced epithelial ovarian cancer (EOC) treated with carboplatinpaclitaxel (CP) +/- bevacizumab (BEV). Results from GOG-0218.

Authors
Secord, AA; Tritchler, D; Liu, Y; Starr, MD; Brady, JC; Lankes, HA; Hurwitz, H; Mannel, RS; Tewari, KS; O'Malley, DM; Gray, HJ; Bakkum-Gamez, JN; Fujiwara, K; Boente, M; Deng, W; Burger, RA; Birrer, MJ; Nixon, AB
MLA Citation
Secord, AA, Tritchler, D, Liu, Y, Starr, MD, Brady, JC, Lankes, HA, Hurwitz, H, Mannel, RS, Tewari, KS, O'Malley, DM, Gray, HJ, Bakkum-Gamez, JN, Fujiwara, K, Boente, M, Deng, W, Burger, RA, Birrer, MJ, and Nixon, AB. "Prognostic and predictive blood-based biomarkers (BMs) in patients (pts) with advanced epithelial ovarian cancer (EOC) treated with carboplatinpaclitaxel (CP) +/- bevacizumab (BEV). Results from GOG-0218." May 20, 2016.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
34
Issue
15
Publish Date
2016

Epigenetic resensitization to platinum in recurrent, platinum-resistant ovarian cancer (OC) using guadecitabine (SGI-110), a novel hypomethylating agent (HMA): Results of a randomized phase II study.

Authors
Matulonis, UA; Oza, AM; Secord, AA; Roman, LD; Blagden, SP; Banerjee, SN; Elkas, JC; Nemunaitis, JJ; Ghamande, SA; Fleming, GF; Markham, MJ; Hirte, HW; Provencher, DM; Basu, B; Kristeleit, RS; Naim, S; Hao, Y; Keer, HN; Azab, M; Matei, D
MLA Citation
Matulonis, UA, Oza, AM, Secord, AA, Roman, LD, Blagden, SP, Banerjee, SN, Elkas, JC, Nemunaitis, JJ, Ghamande, SA, Fleming, GF, Markham, MJ, Hirte, HW, Provencher, DM, Basu, B, Kristeleit, RS, Naim, S, Hao, Y, Keer, HN, Azab, M, and Matei, D. "Epigenetic resensitization to platinum in recurrent, platinum-resistant ovarian cancer (OC) using guadecitabine (SGI-110), a novel hypomethylating agent (HMA): Results of a randomized phase II study." May 20, 2016.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
34
Issue
15
Publish Date
2016

Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-Grade Endometrial Cancer

Authors
Ehrisman, JA; Abbott, S; Harmon, Z; Secord, AA; Berchuck, A; Lee, PS; Valea, FA; Broadwater, G; Li, X; Havrilesky, LJ; Hall, A
MLA Citation
Ehrisman, JA, Abbott, S, Harmon, Z, Secord, AA, Berchuck, A, Lee, PS, Valea, FA, Broadwater, G, Li, X, Havrilesky, LJ, and Hall, A. "Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-Grade Endometrial Cancer." February 2016.
Source
wos-lite
Published In
Modern Pathology
Volume
29
Publish Date
2016
Start Page
282A
End Page
282A

Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis.

To evaluate the association between body mass index (BMI) and mortality in women with endometrial cancer.A systematic review was performed utilizing a Medline search with Mesh keywords 'endometrial neoplasms' and ('body mass index' or 'obesity') and ('survival analysis' or 'mortality' or 'survivor' or 'survival') for studies published prior to June 2013. Inclusion criteria included studies that assessed associations between BMI and survival in endometrial cancer patients. Two investigators independently reviewed the title and abstract and full-text of articles for inclusion or exclusion decision; discordant decisions were adjudicated by a third reviewer. A random-effects model was constructed that was comparable to the standard random-effects models used in the meta-analysis of odds ratios. The model was fitted using SAS PROC NLMIXED.1451 studies were identified and reviewed in duplicate, 18 met inclusion criteria. A random-effects meta-analysis demonstrated significantly higher odds of mortality with increasing BMI in endometrial cancer patients. Specifically the odds ratios were 1.01, 1.17, 1.26, and 1.66 for BMI categories of 25-29.9, 30-34.9, 35-39.9, and 40+, respectively. The odds ratio for all-cause mortality in endometrial cancer patients with a BMI≥40 compared to those with a BMI<25 was 1.66 (CI: 1.10-2.51, p=0.02). A single dose-response model indicated that a 10% increase in BMI resulted in a 9.2% increase in the odds of all-cause mortality (p=0.007).Increased BMI is significantly associated with increased all-cause mortality in women with endometrial cancer, with the highest risk for those with a BMI≥40.

Authors
Secord, AA; Hasselblad, V; Von Gruenigen, VE; Gehrig, PA; Modesitt, SC; Bae-Jump, V; Havrilesky, LJ
MLA Citation
Secord, AA, Hasselblad, V, Von Gruenigen, VE, Gehrig, PA, Modesitt, SC, Bae-Jump, V, and Havrilesky, LJ. "Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis." Gynecologic oncology 140.1 (January 2016): 184-190. (Review)
PMID
26524722
Source
epmc
Published In
Gynecologic Oncology
Volume
140
Issue
1
Publish Date
2016
Start Page
184
End Page
190
DOI
10.1016/j.ygyno.2015.10.020

Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial.

CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC).Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS).Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07).CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509).NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.

Authors
Gray, HJ; Benigno, B; Berek, J; Chang, J; Mason, J; Mileshkin, L; Mitchell, P; Moradi, M; Recio, FO; Michener, CM; Secord, AA; Tchabo, NE; Chan, JK; Young, J; Kohrt, H; Gargosky, SE; Goh, JC
MLA Citation
Gray, HJ, Benigno, B, Berek, J, Chang, J, Mason, J, Mileshkin, L, Mitchell, P, Moradi, M, Recio, FO, Michener, CM, Secord, AA, Tchabo, NE, Chan, JK, Young, J, Kohrt, H, Gargosky, SE, and Goh, JC. "Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial." Journal for immunotherapy of cancer 4 (January 2016): 34-.
Website
http://hdl.handle.net/10161/15403
PMID
27330807
Source
epmc
Published In
Journal for ImmunoTherapy of Cancer
Volume
4
Publish Date
2016
Start Page
34
DOI
10.1186/s40425-016-0137-x

The role of immune checkpoint inhibition in the treatment of ovarian cancer.

The introduction of immune checkpoint inhibitors has revolutionized treatment of multiple cancers and has bolstered interest in this treatment approach. So far, emerging clinical data show limited clinical efficacy of these agents in ovarian cancer with objective response rates of 10-15% with some durable responses. In this review, we present emerging clinical data of completed trials of immune checkpoint inhibitors and review ongoing studies. In addition we examine the current knowledge of the tumor microenvironment of ovarian cancers with a focus on the significance of PD-L1 expression and tumor-infiltrating lymphocytes on predicting response to immune checkpoint blockade. We evaluate approaches to improve treatment outcomes through the use of predictive biomarkers and patient selection. Finally, we review management considerations including immune related adverse events and response criteria.

Authors
Gaillard, SL; Secord, AA; Monk, B
MLA Citation
Gaillard, SL, Secord, AA, and Monk, B. "The role of immune checkpoint inhibition in the treatment of ovarian cancer." Gynecologic oncology research and practice 3 (January 2016): 11-. (Review)
PMID
27904752
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
3
Publish Date
2016
Start Page
11

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis.

Chemotherapy plays a role in the treatment of endometrioid endometrial cancer (EEC); however, tumor grade may affect response. Our objective was to evaluate associations between tumor grade and in vitro chemoresponse.We conducted an analysis of primary tumor samples from women with EEC undergoing in vitro chemoresponse testing. Results were classified as sensitive (S), intermediate (I), or resistant (R) to each drug tested. Correlations between tumor grade and response were examined.Data was collected from 159 patients: 28 with grade 1 (18%), 52 with grade 2 (32%), and 79 (50%) with grade 3 tumors. Median age of patients was 62 (range 31-92). Most patients were Caucasian (83%) with advanced disease (Stage III: 50.9%; Stage IV: 13.2%). Overall chemoresponse was similar across all grades. Fifty percent, 56 and 51% for grade 1, 2, and 3 tumors, respectively, demonstrated S results to at least 1 agent. There was no association between grade and in vitro response to chemotherapy agents (p > 0.05) except a marginal association between grade and doxorubicin response (p = 0.08). Grade 1 and 2 cancers were more likely to demonstrate R results for doxorubicin compared to grade 3 cancers (G1: 19% vs G2: 25% vs G3: 8%; p = 0.08). In a subset tested for all 7 agents, only one patient tumor was pan-R and 4 were pan-S.Based on our data, grades 1-3 EEC have similar in vitro chemoresponse. These findings suggest that chemotherapy may be useful in advanced low grade EECs, but further clinical correlation is needed.

Authors
Davidson, BA; Foote, J; Brower, SL; Tian, C; Havrilesky, LJ; Secord, AA
MLA Citation
Davidson, BA, Foote, J, Brower, SL, Tian, C, Havrilesky, LJ, and Secord, AA. "Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis." Gynecologic oncology research and practice 3 (January 2016): 13-.
PMID
27980799
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
3
Publish Date
2016
Start Page
13

Conservative management of morbidly adherent placenta: expert review.

Over the last century, the incidence of placenta accreta, increta, and percreta, collectively referred to as morbidly adherent placenta, has risen dramatically. Planned cesarean hysterectomy at the time of cesarean delivery is the standard recommended treatment in the United States. Recently, interest in conservative management has resurged, especially in Europe. The aims of this review are the following: (1) to provide an overview of methods used for conservative management, (2) to discuss clinical implications for both clinicians and patients, and (3) to identify areas in need of further research.

Authors
Fox, KA; Shamshirsaz, AA; Carusi, D; Secord, AA; Lee, P; Turan, OM; Huls, C; Abuhamad, A; Simhan, H; Barton, J; Wright, J; Silver, R; Belfort, MA
MLA Citation
Fox, KA, Shamshirsaz, AA, Carusi, D, Secord, AA, Lee, P, Turan, OM, Huls, C, Abuhamad, A, Simhan, H, Barton, J, Wright, J, Silver, R, and Belfort, MA. "Conservative management of morbidly adherent placenta: expert review." American journal of obstetrics and gynecology 213.6 (December 2015): 755-760. (Review)
PMID
25935779
Source
epmc
Published In
American Journal of Obstetrics & Gynecology
Volume
213
Issue
6
Publish Date
2015
Start Page
755
End Page
760
DOI
10.1016/j.ajog.2015.04.034

Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients.

To compare the efficacy of chemotherapy (C) combined with bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian cancer (EOC).A multicenter analysis of patients treated from 2004 to 2011 was performed. Demographic, treatment, response, and adverse event information were obtained. Progression-free (PFS) and overall survival (OS) were analyzed.Of 277 patients (median age: 58years), the majority had Stage III and IV (86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and 6.7months, and median overall survival (OS) was 14.3 and 10.5months, respectively. The chemotherapeutic agents combined with Bev and the median OS include: pegylated liposomal doxorubicin (n=19, OS of 20.4months), taxanes (n=55, OS of 20.2months), gemcitabine (n=106, OS of 14.1months), topotecan (n=43, OS of 13months), and cyclophosphamide (n=21, OS of 13months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group.This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone.

Authors
Fuh, KC; Secord, AA; Bevis, KS; Huh, W; ElNaggar, A; Blansit, K; Previs, R; Tillmanns, T; Kapp, DS; Chan, JK
MLA Citation
Fuh, KC, Secord, AA, Bevis, KS, Huh, W, ElNaggar, A, Blansit, K, Previs, R, Tillmanns, T, Kapp, DS, and Chan, JK. "Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients." Gynecologic oncology 139.3 (December 2015): 413-418.
PMID
26144600
Source
epmc
Published In
Gynecologic Oncology
Volume
139
Issue
3
Publish Date
2015
Start Page
413
End Page
418
DOI
10.1016/j.ygyno.2015.06.041

A multi-institutional study of outcomes in stage I-III uterine carcinosarcoma.

To evaluate the use of adjuvant therapy after primary surgery for stage I-III uterine carcinosarcoma (CS).A multi-institutional retrospective study of women with stage I-III CS was conducted. Analyses were stratified by stage (I/II and III). Patients were categorized according to adjuvant therapy: observation (OBS), radiation (RT), chemotherapy (CT) or multimodal therapy (CT+RT). Overall survival (OS) and progression-free survival (PFS) were analyzed using log-rank tests and Cox proportional hazards models.303 patients were identified across four institutions: 195 with stage I/II and 108 with stage III disease. In stage I/II disease, 75 (39.9%) received OBS, 33 (17.6%) CT, 37 (19.7%) RT, and 43 (22.9%) CT+RT. OBS was associated with a fourfold increased risk of death compared to CT (adjusted hazard ratio (aHR)=4.48, p=0.003). Patients receiving CT+RT had significantly improved PFS compared to those receiving CT alone (aHR=0.43, p=0.04), but no difference in OS. In the stage III cohort, 16 (15.0%) received OBS, 34 (31.8%) CT, 20 (18.7%) RT, and 37 (34.6%) CT+RT. OBS was associated with worse OS and PFS compared to CT (OS: aHR=2.46, p=0.04; PFS: aHR=2.39, p=0.03, respectively). A potential improvement in PFS was seen for those treated with CT+RT compared to CT alone, however it was not statistically significant (aHR=0.53, p=0.09).Observation after surgery was associated with poor outcomes in uterine CS compared to CT and RT alone. Multimodality therapy for women with stage I/II disease was associated with improved PFS compared to chemotherapy alone. Novel treatment options are needed to improve outcomes in this aggressive disease.

Authors
Dickson, EL; Vogel, RI; Gehrig, PA; Pierce, S; Havrilesky, L; Secord, AA; Dottino, J; Fader, AN; Ricci, S; Geller, MA
MLA Citation
Dickson, EL, Vogel, RI, Gehrig, PA, Pierce, S, Havrilesky, L, Secord, AA, Dottino, J, Fader, AN, Ricci, S, and Geller, MA. "A multi-institutional study of outcomes in stage I-III uterine carcinosarcoma." Gynecologic oncology 139.2 (November 2015): 275-282.
PMID
26348313
Source
epmc
Published In
Gynecologic Oncology
Volume
139
Issue
2
Publish Date
2015
Start Page
275
End Page
282
DOI
10.1016/j.ygyno.2015.09.002

Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma.

To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC).51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105. Associations between mRNA expression levels and overall survival were assessed using rank score statistic. Effect size was estimated as a hazard ratio (HR) under a proportional hazard model. The Storey q-value method was used to account for multiple testing within the false-discovery rate (FDR) framework. Publicly available databases including TCGA and GSE were used for external confirmation.Thirty-one angiogenic-related genes were significantly associated with survival (q≤0.05). Of these 31 genes, 4 were also associated with outcome in the TCGA data: AKT1 (q=0.02; TCGA p=0.01, HR=0.8), CD44 (q=0.003; TCGA p=0.05, HR=0.9), EPHB2 (q=0.01; TCGA p=0.05, HR=1.2), and ERBB2 (q=0.02; TCGA p=0.05, HR=1.2). While 5 were associated with outcome in the GSE database: FLT1 (q=0.03; GSE26712 p=0.01, HR=3.1); PF4 (q=0.02; GSE26712 p=0.01, HR=3.0); NRP1 (q=0.02; GSE26712 p<0.04, HR>1.4); COL4A3 (q=0.04; GSE26712 p=0.03, HR=1.3); and ANGPTL3 (q=0.02; GSE14764 p=0.02, HR=1.5). High AKT1 and CD44 were associated with longer survival. In contrast, high expression of EPHB2, ERBB2, FLT1; PF4, NRP1, COL4A3, and ANGPTL3 were associated with shorter survival. CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression.Thirty-one angiogenic-related genes were associated with survival in advanced HGSC and nine of these genes were confirmed in independent publicly available databases.

Authors
Siamakpour-Reihani, S; Owzar, K; Jiang, C; Turner, T; Deng, Y; Bean, SM; Horton, JK; Berchuck, A; Marks, JR; Dewhirst, MW; Alvarez Secord, A
MLA Citation
Siamakpour-Reihani, S, Owzar, K, Jiang, C, Turner, T, Deng, Y, Bean, SM, Horton, JK, Berchuck, A, Marks, JR, Dewhirst, MW, and Alvarez Secord, A. "Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma." Gynecologic oncology 139.1 (October 2015): 23-29.
PMID
26260910
Source
epmc
Published In
Gynecologic Oncology
Volume
139
Issue
1
Publish Date
2015
Start Page
23
End Page
29
DOI
10.1016/j.ygyno.2015.08.001

Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis.

Type I epithelial ovarian cancers (EOCs) are reported to be relatively chemoresistant. This study sought to compare pretreatment chemoresponse assays in Type I vs. Type II EOCs.383 women with stage III-IV EOC enrolled in an observational study, with known chemoresponse assay results for 7 common therapeutic agents, were included. Type I EOCs were defined as grade 1 serous/endometrioid cancers and all clear cell/mucinous cancers. Type II EOCs were classified as grade 2-3 serous/endometrioid cancers and undifferentiated cancers. Chemotherapy assay responses were classified as sensitive (S), intermediately sensitive (I), or resistant (R). All patients were treated with platinum/taxane therapy following cytoreductive surgery.Thirty (7.8%) tumors were classified as Type I EOC, and 353 (92.2%) as Type II EOC. Type I patients were younger at the time of diagnosis (median age: 57 vs. 62 years, p=0.018) and had longer survival compared to Type II patients (mPFS: 25.8 vs. 16.4 months, HR=1.71, p=0.042). Eighty-six percent of Type I EOC specimens demonstrated a sensitive chemoresponse assay result to at least 1 agent; 35.7% were pan-S to all 7 agents. After adjusting for stage, debulking status, and type of EOC, multi-drug resistance was twice as likely in women with Type I EOC compared to Type II EOC (pan-R, 14.3% vs. 6.8% (p=0.268); pan-S, 35.7% vs. 51.2% (p=0.183)), but did not attain statistical significance.The majority of women with Type I EOC displayed assay sensitivity to at least one agent. Given the small sample size these findings need to be evaluated further.

Authors
Previs, R; Leath, CA; Coleman, RL; Herzog, TJ; Krivak, TC; Brower, SL; Tian, C; Secord, AA
MLA Citation
Previs, R, Leath, CA, Coleman, RL, Herzog, TJ, Krivak, TC, Brower, SL, Tian, C, and Secord, AA. "Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis." Gynecologic oncology 138.2 (August 2015): 267-271.
PMID
26037898
Source
epmc
Published In
Gynecologic Oncology
Volume
138
Issue
2
Publish Date
2015
Start Page
267
End Page
271
DOI
10.1016/j.ygyno.2015.05.038

Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis

Authors
Previs, R; III, LCA; Coleman, RL; Herzog, TJ; Krivak, TC; Brower, SL; Tian, C; Secord, AA
MLA Citation
Previs, R, III, LCA, Coleman, RL, Herzog, TJ, Krivak, TC, Brower, SL, Tian, C, and Secord, AA. "Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis." GYNECOLOGIC ONCOLOGY 138.2 (August 2015): 267-271.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
138
Issue
2
Publish Date
2015
Start Page
267
End Page
271
DOI
10.1016/j.ygyno.2015.05.038

Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer.

The Lumbee Indian tribe is the largest Native American tribe in North Carolina, with about 55,000 enrolled members who mostly reside in southeastern counties. We evaluated whether Lumbee heritage is associated with high-risk histologic subtypes of endometrial cancer.We retrospectively analyzed the available records from IRB-approved endometrial cancer databases at two institutions of patients of Lumbee descent (year of diagnosis range 1980-2014). Each Lumbee case was matched by age, year of diagnosis, and BMI to two non-Lumbee controls. Chi-square test was used to compare categorical associations. Kaplan-Meier methods and log-rank test were used to display and compare disease-free survival (DFS) and overall survival (OS). Multivariate Cox proportional hazards regression was used to adjust for age and BMI while testing cohort as a predictor of DFS and OS.Among 108 subjects, 10/35 (29%) Lumbee and 19/72 (26%) non-Lumbee subjects had high-risk (serous/clear cell/carcinosarcoma) histologic types (p = 0.8). 12/35 (34%) Lumbee and 24/72 (33%) non-Lumbee subjects had grade 3 tumors (p = 0.9). 5/33 (15%) Lumbee and 13/72 (18%) non-Lumbee had advanced stage endometrial cancer at diagnosis (p = 0.7). Lumbee ancestry was not associated with worse survival outcomes. OS (p = 0.054) and DFS (p = 0.01) were both worse in Blacks compared to Lumbee and White subjects.In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes.

Authors
Zhang, C; Roque, D; Ehrisman, JA; DiSanto, N; Broadwater, G; Doll, KM; Gehrig, PA; Secord, AA; Havrilesky, LJ
MLA Citation
Zhang, C, Roque, D, Ehrisman, JA, DiSanto, N, Broadwater, G, Doll, KM, Gehrig, PA, Secord, AA, and Havrilesky, LJ. "Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer." Gynecologic oncology reports 13 (August 2015): 49-52.
PMID
26425722
Source
epmc
Published In
Gynecologic Oncology Reports
Volume
13
Publish Date
2015
Start Page
49
End Page
52
DOI
10.1016/j.gore.2015.06.004

Selective cardiac surveillance in patients with gynecologic cancer undergoing treatment with pegylated liposomal doxorubicin (PLD).

OBJECTIVE: The study objective was to examine the safety and cost savings of selective cardiac surveillance (CS) during treatment with pegylated liposomal doxorubicin (PLD). METHODS: A retrospective, dual institution study of women receiving PLD for the treatment of a gynecologic malignancy was performed. The study period was 2002-2014. At both institutions, a selective strategy for CS was implemented in which only high-risk women with a cardiac history or with symptoms suggestive of cardiac toxicity during PLD treatment underwent a cardiac evaluation. Patient demographics, clinical and treatment history were evaluated. Cost analyses were performed utilizing professional/technical fee rates for echocardiogram and multi-gated acquisition scan for each state. RESULTS: PLD was administered in 184 women. The mean patient age was 62.7years, and 79% were treated for recurrent ovarian or peritoneal carcinoma. The median cumulative administered dose of PLD was 300mg/m(2); 24 received >550mg/m(2). The median follow-up time was 20months. Of the 184 patients, the majority (n=157, 85.3%) did not undergo either an initial cardiac evaluation or surveillance during or post-PLD treatment. Fifty-three patients considered high risk for anthracycline-induced cardiotoxicity underwent CS. Only three patients (1.6%) in the entire cohort developed CHF that was possibly related to PLD treatment; all had significant pre-existing cardiac risk factors. Selective instead of routine use of CS in the study population resulted in a cost savings of $182,552.28. CONCLUSION: Utilizing cardiac surveillance in select women undergoing PLD treatment for gynecologic malignancies resulted in significant health care cost savings without adversely impacting clinical outcomes.

Authors
Kushnir, CL; Angarita, AM; Havrilesky, LJ; Thompson, S; Spahlinger, D; Sinno, AK; Tanner, EJ; Secord, AA; Roche, KL; Stone, RL; Fader, AN
MLA Citation
Kushnir, CL, Angarita, AM, Havrilesky, LJ, Thompson, S, Spahlinger, D, Sinno, AK, Tanner, EJ, Secord, AA, Roche, KL, Stone, RL, and Fader, AN. "Selective cardiac surveillance in patients with gynecologic cancer undergoing treatment with pegylated liposomal doxorubicin (PLD)." Gynecologic oncology 137.3 (June 2015): 503-507.
PMID
25735254
Source
epmc
Published In
Gynecologic Oncology
Volume
137
Issue
3
Publish Date
2015
Start Page
503
End Page
507
DOI
10.1016/j.ygyno.2015.02.020

Patient-reported outcomes as end points and outcome indicators in solid tumours.

Patient-reported outcome (PRO) measures, such as quality of life, have been associated with relevant clinical end points and are prognostic for survival outcomes in a variety of solid cancers in adults. In the past few years, PROs have garnered a greater influence as established and clinically relevant measures that could alter the current paradigm of practice-changing therapeutic advances, as it has been recognized that classic clinical end points do not accurately portray a full appreciation of the benefits, risks and costs of therapy. In this Review, we comprehensively assess the correlation of PROs with treatment response and survival, and explore tumour-related and patient-centric composite end points in patients with cancer participating in clinical trials. Comparisons or composite end points that consider tumour-related and PRO components might help health-care providers, patients with cancer and decision makers to better understand the total clinical benefit of therapeutic interventions.

Authors
Secord, AA; Coleman, RL; Havrilesky, LJ; Abernethy, AP; Samsa, GP; Cella, D
MLA Citation
Secord, AA, Coleman, RL, Havrilesky, LJ, Abernethy, AP, Samsa, GP, and Cella, D. "Patient-reported outcomes as end points and outcome indicators in solid tumours." Nature reviews. Clinical oncology 12.6 (June 2015): 358-370. (Review)
PMID
25754949
Source
epmc
Published In
Nature Reviews Clinical Oncology
Volume
12
Issue
6
Publish Date
2015
Start Page
358
End Page
370
DOI
10.1038/nrclinonc.2015.29

A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P.

Authors
Aghajanian, C; Filiaci, VL; Dizon, DS; Carlson, J; Powell, MA; Secord, AA; Tewari, KS; Bender, D; O'Malley, DM; Stuckey, A; Rotmensch, J; Levine, DA; Lankes, HA; Moore, KN
MLA Citation
Aghajanian, C, Filiaci, VL, Dizon, DS, Carlson, J, Powell, MA, Secord, AA, Tewari, KS, Bender, D, O'Malley, DM, Stuckey, A, Rotmensch, J, Levine, DA, Lankes, HA, and Moore, KN. "A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial.

STUDY OBJECTIVE: To evaluate if the use of Valleylab mode ("V mode") (Covidien, Mansfield, MA) electrothermal energy for colpotomy during total laparoscopic hysterectomy (LH) results in a smaller margin of thermal injury to the upper vagina compared with traditional cut/coagulate (cut/coag) electrothermal energy. DESIGN: Prospective randomized clinical trial (Canadian Task Force classification I). SETTING: University medical center. PATIENTS: A total of 101 subjects who underwent LH between June 2010 and August 2012. INTERVENTIONS: Subjects were randomized to colpotomy by V mode electrothermal energy or cut/coag electrothermal energy. MEASUREMENTS AND MAIN RESULTS: The primary end point was the median depth of thermal injury measured in millimeters. The secondary end points included the proportion of subjects who developed granulation tissue, induration, infection, or dehiscence at the vaginal cuff at 4 weeks, 3 months, or 6 months postoperatively. There was no significant difference in the median depth of thermal injury in the cut/coag and V mode arms (anterior margin: 0.68 mm vs 0.63 mm [p = .94], posterior margin: 0.66 mm vs 0.70 mm [p = .87], respectively). Twenty-seven percent of subjects in each arm developed at least 1 of the clinical end points at 4 weeks, 3 months, or 6 months postoperatively (granulation tissue: 6%-18% vs 8%-21%, induration: 0%-2% vs 4%-5%, infection: 0%-4% vs 0%-10%, dehiscence: 2% vs 0% in the cut/coag and V mode arms, respectively), with no difference between arms (p = 1.0). CONCLUSION: The V mode does not reduce the depth of thermal injury compared with cut/coag electrothermal energy when used for colpotomy incision during total laparoscopic hysterectomy (Clinical Trials.gov ID: NCT02080546).

Authors
Teoh, D; Lowery, WJ; Jiang, X; Ehrisman, J; Halvorson, P; Broadwater, G; Bentley, R; Secord, AA; Sobolewski, C; Berchuck, A; Havrilesky, LJ; Valea, FA; Lee, PS
MLA Citation
Teoh, D, Lowery, WJ, Jiang, X, Ehrisman, J, Halvorson, P, Broadwater, G, Bentley, R, Secord, AA, Sobolewski, C, Berchuck, A, Havrilesky, LJ, Valea, FA, and Lee, PS. "Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial." February 2015.
PMID
25305572
Source
epmc
Published In
Journal of Minimally Invasive Gynecology
Volume
22
Issue
2
Publish Date
2015
Start Page
227
End Page
233
DOI
10.1016/j.jmig.2014.10.002

Vaginal Cuff Thermal Injury by Mode of Colpotomy at Total Laparoscopic Hysterectomy: A Randomized Clinical Trial

Authors
Teoh, D; Lowery, WJ; Jiang, X; Ehrisman, J; Halvorson, P; Broadwater, G; Bentley, R; Secord, AA; Sobolewski, C; Berchuck, A; Havrilesky, LJ; Valea, FA; Lee, PS
MLA Citation
Teoh, D, Lowery, WJ, Jiang, X, Ehrisman, J, Halvorson, P, Broadwater, G, Bentley, R, Secord, AA, Sobolewski, C, Berchuck, A, Havrilesky, LJ, Valea, FA, and Lee, PS. "Vaginal Cuff Thermal Injury by Mode of Colpotomy at Total Laparoscopic Hysterectomy: A Randomized Clinical Trial." JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY 22.2 (February 2015): 227-233.
Source
wos-lite
Published In
Journal of Minimally Invasive Gynecology
Volume
22
Issue
2
Publish Date
2015
Start Page
227
End Page
233
DOI
10.1016/j.jmig.2014.10.002

Adenocarcinoma of Mullerian origin: review of pathogenesis, molecular biology, and emerging treatment paradigms.

Traditionally, epithelial ovarian, tubal, and peritoneal cancers have been viewed as separate entities with disparate origins, pathogenesis, clinical features, and outcomes. Additionally, previous classification systems for ovarian cancer have proposed two primary histologic groups that encompass the standard histologic subtypes. Recent data suggest that these groupings no longer accurately reflect our knowledge surrounding these cancers. In this review, we propose that epithelial ovarian, tubal, and peritoneal carcinomas represent a spectrum of disease that originates in the Mullerian compartment. We will discuss the incidence, classification, origin, molecular determinants, and pathologic analysis of these cancers that support the conclusion they should be collectively referred to as adenocarcinomas of Mullerian origin. As our understanding of the molecular and pathologic profiling of adenocarcinomas of Mullerian origin advances, we anticipate treatment paradigms will shift towards genomic driven therapeutic interventions.

Authors
Cobb, LP; Gaillard, S; Wang, Y; Shih, I-M; Secord, AA
MLA Citation
Cobb, LP, Gaillard, S, Wang, Y, Shih, I-M, and Secord, AA. "Adenocarcinoma of Mullerian origin: review of pathogenesis, molecular biology, and emerging treatment paradigms." Gynecologic oncology research and practice 2 (January 2015): 1-.
PMID
27231561
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
2
Publish Date
2015
Start Page
1
DOI
10.1186/s40661-015-0008-z

Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma

© 2015 Elsevier Inc. All rights reserved.Objectives To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). Methods 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105. Associations between mRNA expression levels and overall survival were assessed using rank score statistic. Effect size was estimated as a hazard ratio (HR) under a proportional hazard model. The Storey q-value method was used to account for multiple testing within the false-discovery rate (FDR) framework. Publicly available databases including TCGA and GSE were used for external confirmation. Results Thirty-one angiogenic-related genes were significantly associated with survival (q 0.05). Of these 31 genes, 4 were also associated with outcome in the TCGA data: AKT1 (q = 0.02; TCGA p = 0.01, HR = 0.8), CD44 (q = 0.003; TCGA p = 0.05, HR = 0.9), EPHB2 (q = 0.01; TCGA p = 0.05, HR = 1.2), and ERBB2 (q = 0.02; TCGA p = 0.05, HR = 1.2). While 5 were associated with outcome in the GSE database: FLT1 (q = 0.03; GSE26712 p = 0.01, HR = 3.1); PF4 (q = 0.02; GSE26712 p = 0.01, HR = 3.0); NRP1 (q = 0.02; GSE26712 p 0.04, HR 1.4); COL4A3 (q = 0.04; GSE26712 p = 0.03, HR = 1.3); and ANGPTL3 (q = 0.02; GSE14764 p = 0.02, HR = 1.5). High AKT1 and CD44 were associated with longer survival. In contrast, high expression of EPHB2, ERBB2, FLT1; PF4, NRP1, COL4A3, and ANGPTL3 were associated with shorter survival. CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression. Conclusions Thirty-one angiogenic-related genes were associated with survival in advanced HGSC and nine of these genes were confirmed in independent publicly available databases.

Authors
Siamakpour-Reihani, S; Owzar, K; Jiang, C; Turner, T; Deng, Y; Bean, SM; Horton, JK; Berchuck, A; Marks, JR; Dewhirst, MW; Secord, AA
MLA Citation
Siamakpour-Reihani, S, Owzar, K, Jiang, C, Turner, T, Deng, Y, Bean, SM, Horton, JK, Berchuck, A, Marks, JR, Dewhirst, MW, and Secord, AA. "Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma." Gynecologic Oncology 139.1 (2015): 23-29.
Source
scival
Published In
Gynecologic Oncology
Volume
139
Issue
1
Publish Date
2015
Start Page
23
End Page
29
DOI
10.1016/j.ygyno.2015.08.001

Patient preferences in advanced or recurrent ovarian cancer.

The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen.Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer.In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P = .01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate.PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity.

Authors
Havrilesky, LJ; Alvarez Secord, A; Ehrisman, JA; Berchuck, A; Valea, FA; Lee, PS; Gaillard, SL; Samsa, GP; Cella, D; Weinfurt, KP; Abernethy, AP; Reed, SD
MLA Citation
Havrilesky, LJ, Alvarez Secord, A, Ehrisman, JA, Berchuck, A, Valea, FA, Lee, PS, Gaillard, SL, Samsa, GP, Cella, D, Weinfurt, KP, Abernethy, AP, and Reed, SD. "Patient preferences in advanced or recurrent ovarian cancer." Cancer 120.23 (December 2014): 3651-3659.
PMID
25091693
Source
epmc
Published In
Cancer
Volume
120
Issue
23
Publish Date
2014
Start Page
3651
End Page
3659
DOI
10.1002/cncr.28940

The search for biomarkers to direct antiangiogenic treatment in epithelial ovarian cancer.

Antiangiogenic agents have demonstrated improved progression-free survival in women with primary and recurrent epithelial ovarian cancer (EOC). Biomarkers that predict outcomes in patients treated with antiangiogenic agents are being investigated to rationally direct therapy for women most likely to benefit from these agents. Among the most promising plasma-based biomarkers are vascular endothelial growth factor (VEGF)-A, fibroblast growth factor, platelet-derived growth factor, angiopoietin-2, and VEGF receptor-2. While these biomarkers have been correlated with prognosis, they have not been shown to predict benefit, specifically from anti-VEGF therapy, highlighting the need for alternative biomarkers, including molecular and clinical factors, which may be predictive of outcome in women with ovarian cancer treated with antiangiogenic agents. Biomarkers are currently being investigated as secondary outcomes in several ongoing phase II and phase III clinical trials of antiangiogenic agents in patients with EOC. Molecular techniques, such as microarray analyses, and imaging techniques, such as dynamic contrast-enhanced magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, are also being explored in this field. In this review, we provide a comprehensive overview of current biomarker research, with an emphasis on angiogenic biomarkers associated with EOC.

Authors
Secord, AA; Nixon, AB; Hurwitz, HI
MLA Citation
Secord, AA, Nixon, AB, and Hurwitz, HI. "The search for biomarkers to direct antiangiogenic treatment in epithelial ovarian cancer." Gynecologic oncology 135.2 (November 2014): 349-358. (Review)
PMID
25178997
Source
epmc
Published In
Gynecologic Oncology
Volume
135
Issue
2
Publish Date
2014
Start Page
349
End Page
358
DOI
10.1016/j.ygyno.2014.08.033

Abstract 2320: Clinical epigenetic resensitization of platinum-resistant, recurrent ovarian cancer patients with SGI-110, a novel, second-generation, subcutaneously administered hypomethylating agent (HMA)

Authors
Fleming, G; Ghamande, S; Lin, Y; Secord, AA; Nemunaitis, J; Markham, M-J; Nephew, K; Fang, F; Gupta, S; Naim, S; Choy, G; Jueliger, S; Taverna, P; Hao, Y; Keer, H; Azab, M; Matei, D
MLA Citation
Fleming, G, Ghamande, S, Lin, Y, Secord, AA, Nemunaitis, J, Markham, M-J, Nephew, K, Fang, F, Gupta, S, Naim, S, Choy, G, Jueliger, S, Taverna, P, Hao, Y, Keer, H, Azab, M, and Matei, D. "Abstract 2320: Clinical epigenetic resensitization of platinum-resistant, recurrent ovarian cancer patients with SGI-110, a novel, second-generation, subcutaneously administered hypomethylating agent (HMA)." October 1, 2014.
Source
crossref
Published In
Cancer Research
Volume
74
Issue
19 Supplement
Publish Date
2014
Start Page
2320
End Page
2320
DOI
10.1158/1538-7445.AM2014-2320

Modifizierter doppelt gestielter VRAM-Lappen zur simultanen Rekonstruktion eines Perineum- und posterioren vaginalen Defekts

Authors
Kokosis, G; Schmitz, R; Secord, AA; Havrilesky, LJ; Berchuck, A; Mantyh, CR; Erdmann, D
MLA Citation
Kokosis, G, Schmitz, R, Secord, AA, Havrilesky, LJ, Berchuck, A, Mantyh, CR, and Erdmann, D. "Modifizierter doppelt gestielter VRAM-Lappen zur simultanen Rekonstruktion eines Perineum- und posterioren vaginalen Defekts." Der Gynäkologe 47.10 (October 2014): 784-787.
Source
crossref
Published In
Der Gynäkologe
Volume
47
Issue
10
Publish Date
2014
Start Page
784
End Page
787
DOI
10.1007/s00129-014-3448-3

SGO guidance document for clinical trial designs in ovarian cancer: a changing paradigm.

To explore and facilitate the multifaceted process of drug development and regulatory approval in ovarian cancer.The Society of Gynecologic Oncology (SGO) recently sought and received input from multiple stakeholders including the National Cancer Institute's (NCI) Clinical Therapy Evaluation Program (CTEP), the Food and Drug Administration (FDA), pharmaceutical industry, and patient advocates. This whitepaper is the work product and opinion solely of the SGO.This document summarizes the SGO's interpretation of these meetings and the current regulatory environment where there has been a paucity of recent approvals in the United States. It provides guidance in clinical trial design with the express purpose of encouraging novel drug development in ovarian cancer. Points of emphasis include: ovarian cancer heterogeneity (histologic subtypes and molecular genetic alterations), clinical trial design elements, surrogate as well as composite endpoints, and the four principles of clinical drug development (unmet medical need, discovery, safety, and efficacy).There has been an evolution in the acceptance of surrogate endpoints depending upon the clinical setting in ovarian cancer. While overall survival (OS) remains the most objective clinical trial endpoint, there is now realization that demanding OS as the primary endpoint has many obstacles. Ovarian cancer is a heterogeneous disease that is now divided by histologic subtypes. Future registration strategies will need to address disease heterogeneity. The exploration of currently acceptable clinical trial endpoints and alternative regulatory strategies will hopefully stimulate interest in novel drug development for patients with ovarian cancer.

Authors
Herzog, TJ; Alvarez, RD; Secord, A; Goff, BA; Mannel, RS; Monk, BJ; Coleman, RL
MLA Citation
Herzog, TJ, Alvarez, RD, Secord, A, Goff, BA, Mannel, RS, Monk, BJ, and Coleman, RL. "SGO guidance document for clinical trial designs in ovarian cancer: a changing paradigm." Gynecologic oncology 135.1 (October 2014): 3-7.
PMID
25124162
Source
epmc
Published In
Gynecologic Oncology
Volume
135
Issue
1
Publish Date
2014
Start Page
3
End Page
7
DOI
10.1016/j.ygyno.2014.08.004

A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer.

OBJECTIVE: Recurrence following primary platinum-based chemotherapy remains a challenge in the treatment of patients with advanced-stage epithelial ovarian cancer. This study examines whether a chemoresponse assay can identify patients who are platinum-resistant prior to treatment. STUDY DESIGN: Women (n = 276) with International Federation of Gynecology and Obstetrics stage III-IV ovarian, fallopian, and peritoneal cancer were enrolled in an observational study, and the responsiveness of their tumors was evaluated using a chemoresponse assay. All patients were treated with a platinum/taxane regimen following cytoreductive surgery. Assay responses to carboplatin or paclitaxel were classified as sensitive, intermediate sensitive (IS), or resistant. Association of assay response with progression-free survival (PFS) was analyzed using the Kaplan-Meier method and a Cox regression model. RESULTS: Patients whose tumors were resistant to carboplatin were at increased risk of disease progression compared to those with nonresistant (sensitive + IS) tumors (median PFS: 11.8 vs 16.6 months, respectively, P < .001), and the association was confirmed after adjusting for other clinical factors (hazard ratio, 1.71; 95% confidence interval, 1.12-2.62; P = .013). Association of assay response to paclitaxel with PFS trended in multivariate analysis (hazard ratio, 1.28; 95% confidence interval, 0.84-1.95; P = .245). For tumors resistant to carboplatin, 59% were sensitive or IS to at least 1 other commonly used agent, demonstrating the ability of the assay to inform treatment decisions beyond the standard platinum/taxane regimen. CONCLUSION: Assay resistance to carboplatin is strongly associated with shortened PFS among advanced-stage epithelial ovarian cancer patients treated with carboplatin + paclitaxel therapy, supporting use of this assay to identify patients likely to experience early recurrence on standard platinum-based therapy.

Authors
Krivak, TC; Lele, S; Richard, S; Secord, AA; Leath, CA; Brower, SL; Tian, C; Moore, RG
MLA Citation
Krivak, TC, Lele, S, Richard, S, Secord, AA, Leath, CA, Brower, SL, Tian, C, and Moore, RG. "A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer." American journal of obstetrics and gynecology 211.1 (July 2014): 68.e1-68.e8.
PMID
24530815
Source
epmc
Published In
American Journal of Obstetrics & Gynecology
Volume
211
Issue
1
Publish Date
2014
Start Page
68.e1
End Page
68.e8
DOI
10.1016/j.ajog.2014.02.009

Relative influence of factors determining a woman's preference for treatment options in ovarian cancer.

Authors
Havrilesky, LJ; Secord, AA; Ehrisman, JA; Berchuck, A; Valea, FA; Lee, PS; Gaillard, S; Celia, D; Weinfurt, K; Abernethy, AP; Reed, SD
MLA Citation
Havrilesky, LJ, Secord, AA, Ehrisman, JA, Berchuck, A, Valea, FA, Lee, PS, Gaillard, S, Celia, D, Weinfurt, K, Abernethy, AP, and Reed, SD. "Relative influence of factors determining a woman's preference for treatment options in ovarian cancer." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Endometrial cancer outcomes in hypertensive women treated with beta-blocker

Authors
Roque, DR; Pierce, S; Doll, KM; Davidson, B; Jackson, AL; Ko, EM; Moore, DT; Gehrig, PA; Secord, AA; Havrilesky, LJ; Bae-Jump, VL
MLA Citation
Roque, DR, Pierce, S, Doll, KM, Davidson, B, Jackson, AL, Ko, EM, Moore, DT, Gehrig, PA, Secord, AA, Havrilesky, LJ, and Bae-Jump, VL. "Endometrial cancer outcomes in hypertensive women treated with beta-blocker." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Laparoscopy compared to laparotomy in the management of granulosa cell tumors of the ovary

Authors
Nakayama, J; Edwards, J; Stine, JE; Pelkofski, E; Gehrlg, PA; Secord, AA; Duska, LR
MLA Citation
Nakayama, J, Edwards, J, Stine, JE, Pelkofski, E, Gehrlg, PA, Secord, AA, and Duska, LR. "Laparoscopy compared to laparotomy in the management of granulosa cell tumors of the ovary." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

A randomized phase II trial of bevacizumab (BV) plus oral everolimus (EV) versus bevacizumab alone for recurrent or persistent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal cancer (PPC).

Authors
Tew, WP; Sill, M; McMeekin, DS; Secord, AA; Bonebrake, AJ; Schilder, J; Stuckey, A; Rice, L; Tewari, KS; Aghajanian, C
MLA Citation
Tew, WP, Sill, M, McMeekin, DS, Secord, AA, Bonebrake, AJ, Schilder, J, Stuckey, A, Rice, L, Tewari, KS, and Aghajanian, C. "A randomized phase II trial of bevacizumab (BV) plus oral everolimus (EV) versus bevacizumab alone for recurrent or persistent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal cancer (PPC)." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway

In the majority of cases, endometrial cancer is localized and highly curable through surgery and adjuvant radiotherapy. However, for patients with advanced or metastatic disease, prognosis is poor. Systemic treatments such as cytotoxic chemotherapy or hormonal therapy can cause significant toxicities including chemotherapy-related gastrointestinal, neurologic, and immunosuppressive toxicities and hormone-related hypertension, increased blood sugar, thrombosis, and pulmonary emboli. In addition, these therapies rarely lead to sustained disease control. Novel therapies with greater efficacy and reduced toxicity are needed. Recent progress in the identification of genetic abnormalities in cell signaling proteins has spurred the development of targeted agents for the treatment of patients with endometrial cancer. The fibroblast growth factor receptor (FGFR) pathway is one of several signaling pathways that have been implicated in the pathogenesis and progression of endometrial cancer. The activity of novel FGFR-targeted agents in preclinical endometrial cancer models and clinical trials will be reviewed. © 2013 Elsevier Ltd.

Authors
Lee, PS; Secord, AA
MLA Citation
Lee, PS, and Secord, AA. "Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway." Cancer Treatment Reviews 40.4 (May 1, 2014): 507-512. (Review)
Source
scopus
Published In
Cancer Treatment Reviews
Volume
40
Issue
4
Publish Date
2014
Start Page
507
End Page
512
DOI
10.1016/j.ctrv.2013.11.004

Targeting molecular pathways in endometrial cancer: a focus on the FGFR pathway.

In the majority of cases, endometrial cancer is localized and highly curable through surgery and adjuvant radiotherapy. However, for patients with advanced or metastatic disease, prognosis is poor. Systemic treatments such as cytotoxic chemotherapy or hormonal therapy can cause significant toxicities including chemotherapy-related gastrointestinal, neurologic, and immunosuppressive toxicities and hormone-related hypertension, increased blood sugar, thrombosis, and pulmonary emboli. In addition, these therapies rarely lead to sustained disease control. Novel therapies with greater efficacy and reduced toxicity are needed. Recent progress in the identification of genetic abnormalities in cell signaling proteins has spurred the development of targeted agents for the treatment of patients with endometrial cancer. The fibroblast growth factor receptor (FGFR) pathway is one of several signaling pathways that have been implicated in the pathogenesis and progression of endometrial cancer. The activity of novel FGFR-targeted agents in preclinical endometrial cancer models and clinical trials will be reviewed.

Authors
Lee, PS; Secord, AA
MLA Citation
Lee, PS, and Secord, AA. "Targeting molecular pathways in endometrial cancer: a focus on the FGFR pathway." Cancer Treat Rev 40.4 (May 2014): 507-512. (Review)
PMID
24332498
Source
pubmed
Published In
Cancer Treatment Reviews
Volume
40
Issue
4
Publish Date
2014
Start Page
507
End Page
512
DOI
10.1016/j.ctrv.2013.11.004

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients.

The aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer.We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement.LVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03).Minimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.

Authors
Zhang, C; Havrilesky, LJ; Broadwater, G; Di Santo, N; Ehrisman, JA; Lee, PS; Berchuck, A; Alvarez Secord, A; Bean, S; Bentley, RC; Valea, FA
MLA Citation
Zhang, C, Havrilesky, LJ, Broadwater, G, Di Santo, N, Ehrisman, JA, Lee, PS, Berchuck, A, Alvarez Secord, A, Bean, S, Bentley, RC, and Valea, FA. "Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients." Gynecologic oncology 133.2 (May 2014): 211-215.
PMID
24582867
Source
epmc
Published In
Gynecologic Oncology
Volume
133
Issue
2
Publish Date
2014
Start Page
211
End Page
215
DOI
10.1016/j.ygyno.2014.02.025

Obesity is associated with worse overall survival in women with low-grade papillary serous epithelial ovarian cancer.

The objective of this study was to evaluate prognostic risk factors for survival in women with low-grade serous epithelial ovarian cancer (LGSC).A multicenter retrospective analysis of patients with LGSC was conducted. Potential epidemiologic risk factors evaluated included obesity, age, parity, race, smoking, oral contraceptive pill and/or hormonal replacement therapy use, and previous hysterectomy or surgery on fallopian tubes and/or ovaries. Additional factors included stage, extent of debulking, residual disease, and disease status.Eighty-one patients were identified, and pathologic diagnosis was independently confirmed. Median age at diagnosis was 56 years (range, 21-86 years). Thirty-four percent were obese, and 80% had optimally debulked disease. Forty-six percent were alive, 14% with disease, whereas 25% were dead of disease, 2% died of intercurrent disease, and 27% had an unknown status. In a univariate analysis, optimal surgical debulking was associated with improved progression-free survival (P = 0.01), disease-specific survival (P = 0.03), and overall survival (OS) (P < 0.001) and body mass index with worse OS (P = 0.05). On multivariate analysis, obesity (hazard ratio, 2.8; 95% confidence interval, 1.05-7.3; P = 0.04) and optimal tumor debulking (hazard ratio, 0.05; 95% confidence interval, 0.008-0.29; P = 0.001) were a significant predictor of OS.In a multivariate analysis, obesity and optimal tumor cytoreduction were significant predictors of OS. However, obesity was not associated with worse disease-specific survival, suggesting that mortality of obese patients with LGSC may result from other comorbidities. Interventions addressing obesity may improve survival for women diagnosed with LGSC, and further study is warranted to address the role of obesity in LGSC.

Authors
Previs, RA; Kilgore, J; Craven, R; Broadwater, G; Bean, S; Wobker, S; DiFurio, M; Bae-Jump, V; Gehrig, PA; Secord, AA
MLA Citation
Previs, RA, Kilgore, J, Craven, R, Broadwater, G, Bean, S, Wobker, S, DiFurio, M, Bae-Jump, V, Gehrig, PA, and Secord, AA. "Obesity is associated with worse overall survival in women with low-grade papillary serous epithelial ovarian cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 24.4 (May 2014): 670-675.
PMID
24614825
Source
epmc
Published In
International Journal of Gynecological Cancer
Volume
24
Issue
4
Publish Date
2014
Start Page
670
End Page
675
DOI
10.1097/igc.0000000000000109

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: A single institution study of 458 patients

Authors
Zhang, C; Havrilesky, LJ; Broadwater, G; Di Santo, N; Ehrisman, JA; Lee, PS; Berchuck, A; Alvarez Secord, A; Bean, S; Bentley, RC; Valea, FA
MLA Citation
Zhang, C, Havrilesky, LJ, Broadwater, G, Di Santo, N, Ehrisman, JA, Lee, PS, Berchuck, A, Alvarez Secord, A, Bean, S, Bentley, RC, and Valea, FA. "Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: A single institution study of 458 patients." Gynecologic Oncology 133.2 (May 2014): 211-215.
Source
crossref
Published In
Gynecologic Oncology
Volume
133
Issue
2
Publish Date
2014
Start Page
211
End Page
215
DOI
10.1016/j.ygyno.2014.02.025

RELATIVE INFLUENCE OF FACTORS DETERMINING A WOMAN'S PREFERENCE FOR TREATMENT OPTIONS IN OVARIAN CANCER: A DISCRETE CHOICE EXPERIMENT

Authors
Havrilesky, LJ; Secord, AA; Ehrisman, J; Berchuck, A; Valea, FA; Lee, PS; Cella, D; Weinfurt, K; Abernethy, AP; Reed, SD
MLA Citation
Havrilesky, LJ, Secord, AA, Ehrisman, J, Berchuck, A, Valea, FA, Lee, PS, Cella, D, Weinfurt, K, Abernethy, AP, and Reed, SD. "RELATIVE INFLUENCE OF FACTORS DETERMINING A WOMAN'S PREFERENCE FOR TREATMENT OPTIONS IN OVARIAN CANCER: A DISCRETE CHOICE EXPERIMENT." VALUE IN HEALTH 17.3 (May 2014): A93-A93.
Source
wos-lite
Published In
Value in Health
Volume
17
Issue
3
Publish Date
2014
Start Page
A93
End Page
A93

The complex triad of obesity, diabetes and race in Type I and II endometrial cancers: prevalence and prognostic significance.

BACKGROUND: We examined the distribution of obesity, diabetes, and race in Type I and Type II endometrial cancers (EC) and their associations with clinical outcomes. METHODS: A multi-institutional retrospective analysis of Type I and II EC cases from January 2005 to December 2010 was conducted. Type I (endometrioid), Type II (serous and clear cell), low grade (LG) (grade 1 and 2 endometrioid), and high grade (HG) (grade 3 endometrioid, serous, clear cell) cohorts were compared. Univariate and multivariate analyses were used to determine time-to-recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS). RESULTS: Type I EC patients were more frequently obese than Type II (66% versus 51%, p<0.0001) and had similar rates of diabetes (25% versus 23%, p=0.69). African-Americans (AA) had higher median BMI than Caucasians in both Type I (p<0.001) and II (p<0.001) ECs, and were twice as likely to have diabetes (p<0.001). In Type I EC, DM was associated with worse RFS and OS in unadjusted and adjusted models (RFS HR 1.38, 95%CI 1.01-1.89; OS HR 1.86, 95%CI 1.30-2.67), but not with TTR. BMI was associated with improved TTR in the adjusted analysis for Type I EC (HR 0.98, 95%CI 0.95-1.0), but not with RFS or OS. There was no association between DM or BMI and outcomes in Type II or HG EC. AA race was not associated with RFS or OS on adjusted analyses in any group. CONCLUSIONS: Obesity and diabetes are highly prevalent in Type I and II ECs, especially in AA. DM was associated with worse RFS and OS in Type I EC. Neither DM nor BMI was associated with outcomes in Type II or HG EC.

Authors
Ko, EM; Walter, P; Clark, L; Jackson, A; Franasiak, J; Bolac, C; Havrilesky, L; Secord, AA; Moore, DT; Gehrig, PA; Bae-Jump, VL
MLA Citation
Ko, EM, Walter, P, Clark, L, Jackson, A, Franasiak, J, Bolac, C, Havrilesky, L, Secord, AA, Moore, DT, Gehrig, PA, and Bae-Jump, VL. "The complex triad of obesity, diabetes and race in Type I and II endometrial cancers: prevalence and prognostic significance." Gynecologic oncology 133.1 (April 2014): 28-32.
PMID
24680588
Source
epmc
Published In
Gynecologic Oncology
Volume
133
Issue
1
Publish Date
2014
Start Page
28
End Page
32
DOI
10.1016/j.ygyno.2014.01.032

A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy.

OBJECTIVE: To develop a nomogram to predict overall survival (OS) in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy. METHODS: A multicenter retrospective study was conducted. Potential prognostic variables included age; stage; grade; histology; performance status; residual disease; presence of ascites and/or pleural effusions; number of chemotherapy regimens, treatment-free interval (TFI) prior to bevacizumab administration, and platinum sensitivity. Multivariate analysis was performed using Cox proportional hazards regression. The predictive model was developed into a nomogram to predict five-year OS. RESULTS: 312 women with recurrent ovarian cancer treated with bevacizumab and chemotherapy were identified; median age was 59 (range: 19-85); 86% women had advanced stage (III-IV) disease. The majority had serous histology (74%), high grade cancers (93.5%), and optimal cytoreductions (69.5%). Fifty-one percent of women received greater than two prior chemotherapeutic regimens. TFI (AHR=0.98, 95% CI 0.97-1.00, p=0.022) was the only statistically significant predictor in a multivariate progression-free survival (PFS) analysis. In a multivariate OS analysis, prior number of chemotherapy regimens, TFI, platinum sensitivity, and presence of ascites were significant. A nomogram to predict five-year OS was constructed and internally validated (bootstrap-corrected concordance index=0.737). CONCLUSION: Our multivariate model identified prior number of chemotherapy regimens, TFI, platinum sensitivity, and the presence of ascites as prognostic variables for OS in women with recurrent ovarian cancer treated with bevacizumab combined with chemotherapy. Our nomogram to predict five-year OS may be used to identify women who may benefit from bevacizumab and chemotherapy, but further validation is needed.

Authors
Previs, RA; Bevis, KS; Huh, W; Tillmanns, T; Perry, L; Moore, K; Chapman, J; McClung, C; Kiet, T; Java, J; Chan, J; Secord, AA
MLA Citation
Previs, RA, Bevis, KS, Huh, W, Tillmanns, T, Perry, L, Moore, K, Chapman, J, McClung, C, Kiet, T, Java, J, Chan, J, and Secord, AA. "A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy." Gynecologic oncology 132.3 (March 2014): 531-536.
PMID
24472410
Source
epmc
Published In
Gynecologic Oncology
Volume
132
Issue
3
Publish Date
2014
Start Page
531
End Page
536
DOI
10.1016/j.ygyno.2014.01.036

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube.

To determine the safety and efficacy of the novel combination of docetaxel, oxaliplatin, and bevacizumab as first-line treatment of advanced cancer of the ovary, peritoneum or fallopian tube after initial debulking surgery.Eligible patients (stage IB-IV) were treated with 6 cycles of oxaliplatin (85 mg/m(2)), docetaxel (75 mg/m(2)), and bevacizumab (15 mg/kg) every 3 weeks, followed by single-agent bevacizumab 15 mg/kg every 3 weeks to complete one year of therapy. The primary endpoint was 12-month progression-free survival (PFS).A total of 132 patients (80 with measurable disease at baseline; 52 with non-measurable, evaluable disease at baseline) enrolled and received study treatment. At diagnosis, 76.5% of patients had stage III disease and 20% had stage IV. 62.9% were optimally cytoreduced. The most common grade 3/4 adverse events were neutropenia (42.4%), leukopenia (13.6%), hypertension (8.3%), fatigue (6.1%), and nausea (6.1%). One patient (0.8%) had a fatal gastrointestinal perforation. The best overall confirmed response rate (complete response+partial response [measurable disease subgroup]) was 58.6% (95% CI 49%, 67%). CA-125 response rates for the measurable and non-measurable disease subgroups were 83.0% and 81.5%, respectively. The 12-month PFS rate for the measurable disease subgroup was 65.7% (95% CI 53.4%, 76.7%); median PFS was 16.3 (95% CI 12.6, 19.6) months. Median overall survival was 47.3 (95% CI 34.1, upper limit not applicable) months.This novel treatment regimen may provide a promising therapeutic approach for women with ovarian, primary peritoneal, or fallopian tube carcinoma. No unanticipated safety concerns were identified.

Authors
Herzog, TJ; Monk, BJ; Rose, PG; Braly, P; Hines, JF; Bell, MC; Wenham, RM; Secord, AA; Roman, LD; Einstein, MH; Drake, RD; Childs, BH
MLA Citation
Herzog, TJ, Monk, BJ, Rose, PG, Braly, P, Hines, JF, Bell, MC, Wenham, RM, Secord, AA, Roman, LD, Einstein, MH, Drake, RD, and Childs, BH. "A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube." Gynecologic oncology 132.3 (March 2014): 517-525.
PMID
24476788
Source
epmc
Published In
Gynecologic Oncology
Volume
132
Issue
3
Publish Date
2014
Start Page
517
End Page
525
DOI
10.1016/j.ygyno.2014.01.035

Metformin is associated with improved survival in endometrial cancer

Objective Preclinical evidence suggests that metformin exhibits anti-tumorigenic effects in endometrial cancer. We sought to investigate the association of metformin on endometrial cancer outcomes. Methods A multi-institutional IRB-approved retrospective cohort analysis was conducted comparing endometrial cancer patients with diabetes mellitus who used metformin (based on medication review at the time of diagnosis) to those who did not use metformin from 2005 to 2010. Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling. Results 24% (363/1495) endometrial cancer patients were diabetic, of whom 54% used metformin. Metformin users were younger and heavier than non-users, though nearly all were postmenopausal and obese. 75% of both groups had endometrioid histology. Stage, grade, and adjuvant therapy distributions were similar. Metformin users had improved RFS and OS. Non-metformin users had 1.8 times worse RFS (95% CI: 1.1-2.9, p = 0.02) and 2.3 times worse OS (95% CI: 1.3-4.2, p = 0.005) after adjusting for age, stage, grade, histology and adjuvant treatment. Metformin use was not associated with TTR. Conclusion Metformin use was associated with improved RFS and OS but not TTR, most likely due to improving all-cause mortality. Its role in modifying cancer recurrence remains unclear. Prospective studies that capture metformin exposure prior to, during and post endometrial cancer treatment may help define the role of metformin upon cancer specific and overall health outcomes. © 2013 Elsevier Inc. All rights reserved.

Authors
Ko, EM; Walter, P; Jackson, A; Clark, L; Franasiak, J; Bolac, C; Havrilesky, LJ; Secord, AA; Moore, DT; Gehrig, PA; Bae-Jump, V
MLA Citation
Ko, EM, Walter, P, Jackson, A, Clark, L, Franasiak, J, Bolac, C, Havrilesky, LJ, Secord, AA, Moore, DT, Gehrig, PA, and Bae-Jump, V. "Metformin is associated with improved survival in endometrial cancer." Gynecologic Oncology 132.2 (February 1, 2014): 438-442.
Source
scopus
Published In
Gynecologic Oncology
Volume
132
Issue
2
Publish Date
2014
Start Page
438
End Page
442
DOI
10.1016/j.ygyno.2013.11.021

Metformin is associated with improved survival in endometrial cancer.

OBJECTIVE: Preclinical evidence suggests that metformin exhibits anti-tumorigenic effects in endometrial cancer. We sought to investigate the association of metformin on endometrial cancer outcomes. METHODS: A multi-institutional IRB-approved retrospective cohort analysis was conducted comparing endometrial cancer patients with diabetes mellitus who used metformin (based on medication review at the time of diagnosis) to those who did not use metformin from 2005 to 2010. Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling. RESULTS: 24% (363/1495) endometrial cancer patients were diabetic, of whom 54% used metformin. Metformin users were younger and heavier than non-users, though nearly all were postmenopausal and obese. 75% of both groups had endometrioid histology. Stage, grade, and adjuvant therapy distributions were similar. Metformin users had improved RFS and OS. Non-metformin users had 1.8 times worse RFS (95% CI: 1.1-2.9, p = 0.02) and 2.3 times worse OS (95% CI: 1.3-4.2, p = 0.005) after adjusting for age, stage, grade, histology and adjuvant treatment. Metformin use was not associated with TTR. CONCLUSION: Metformin use was associated with improved RFS and OS but not TTR, most likely due to improving all-cause mortality. Its role in modifying cancer recurrence remains unclear. Prospective studies that capture metformin exposure prior to, during and post endometrial cancer treatment may help define the role of metformin upon cancer specific and overall health outcomes.

Authors
Ko, EM; Walter, P; Jackson, A; Clark, L; Franasiak, J; Bolac, C; Havrilesky, LJ; Secord, AA; Moore, DT; Gehrig, PA; Bae-Jump, V
MLA Citation
Ko, EM, Walter, P, Jackson, A, Clark, L, Franasiak, J, Bolac, C, Havrilesky, LJ, Secord, AA, Moore, DT, Gehrig, PA, and Bae-Jump, V. "Metformin is associated with improved survival in endometrial cancer." Gynecol Oncol 132.2 (February 2014): 438-442.
PMID
24269517
Source
pubmed
Published In
Gynecologic Oncology
Volume
132
Issue
2
Publish Date
2014
Start Page
438
End Page
442
DOI
10.1016/j.ygyno.2013.11.021

Dasatinib (BMS-35482) interacts synergistically with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells with high SRC pathway activation and protein expression.

PURPOSE: This study aimed to explore the activity of dasatinib in combination with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells. METHODS: Cells with previously determined SRC pathway and protein expression (SRC pathway/SRC protein IGROV1, both high; SKOV3, both low) were treated with dasatinib in combination with the cytotoxic agents. SRC and paxillin protein expression were determined pretreatment and posttreatment. Dose-response curves were constructed, and the combination index (CI) for drug interaction was calculated. RESULTS: In the IGROV1 cells, dasatinib alone reduced phospho-SRC/total SRC 71% and p-paxillin/t-paxillin ratios 77%. Phospho-SRC (3%-33%; P = 0.002 to 0.04) and p-paxicillin (6%-19%; P = 0.01 to 0.05) levels were significantly reduced with dasatinib in combination with each cytotoxic agent. The combination of dasatinib and docetaxel, gemcitabine, or topotecan had a synergistic antiproliferative effect (CI, 0.49-0.68), whereas dasatinib combined with doxorubicin had an additive effect (CI, 1.08).In SKOV3 cells, dasatinib resulted in less pronounced reductions of phospho-SRC/total SRC (49%) and p-paxillin/t-paxillin (62%). Phospho-SRC (18%; P < 0.001) and p-paxillin levels (18%; P = 0.001; 9%; P = 0.007) were significantly decreased when dasatinib was combined with docetaxel and topotecan (p-paxillin only). Furthermore, dasatinib combined with the cytotoxics in the SKOV3 cells produced an antagonistic interaction on the proliferation of these cells (CI, 1.49-2.27). CONCLUSIONS: Dasatinib in combination with relapse chemotherapeutic agents seems to interact in a synergistic or additive manner in cells with high SRC pathway activation and protein expression. Further evaluation of dasatinib in combination with chemotherapy in ovarian cancer animal models and exploration of the use of biomarkers to direct therapy are warranted.

Authors
Secord, AA; Teoh, D; Jia, J; Nixon, AB; Grace, L; Adams, DJ; Murphy, SK
MLA Citation
Secord, AA, Teoh, D, Jia, J, Nixon, AB, Grace, L, Adams, DJ, and Murphy, SK. "Dasatinib (BMS-35482) interacts synergistically with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells with high SRC pathway activation and protein expression." Int J Gynecol Cancer 24.2 (February 2014): 218-225.
PMID
24407585
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
24
Issue
2
Publish Date
2014
Start Page
218
End Page
225
DOI
10.1097/IGC.0000000000000056

Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: A case report

We describe clinicopathologic and immunohistochemical features of an unusual case of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy postcoital vaginal bleeding 4 months after starting oral contraceptives and was found to have a cervical mass. She underwent a loop electrosurgical excision of the mass, and microscopic examination revealed a florid endocervical proliferation, extending to the margins. This lesion was initially interpreted as an invasive, well-differentiated endocervical adenocarcinoma. However, on subsequent review, the lesion was found to have a low rate of proliferation, no evidence of an infiltrative growth pattern, and abundant acute inflammation. Given these findings and the absence of any residual endocervical lesion on a subsequent cold knife conization, we determined that this was a benign, likely reactive, lesion. This case, together with previous studies, suggests that women with cystic fibrosis can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development. © 2013 International Society of Gynecological Pathologists.

Authors
Previs, RA; Edwards, JM; Secord, AA; Nucci, MR; Bentley, RC; Hall, AHS
MLA Citation
Previs, RA, Edwards, JM, Secord, AA, Nucci, MR, Bentley, RC, and Hall, AHS. "Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: A case report." International Journal of Gynecological Pathology 33.1 (January 1, 2014): 100-104.
Source
scopus
Published In
International Journal of Gynecological Pathology
Volume
33
Issue
1
Publish Date
2014
Start Page
100
End Page
104
DOI
10.1097/PGP.0b013e318278b832

A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy

Objective To develop a nomogram to predict overall survival (OS) in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy. Methods A multicenter retrospective study was conducted. Potential prognostic variables included age; stage; grade; histology; performance status; residual disease; presence of ascites and/or pleural effusions; number of chemotherapy regimens, treatment-free interval (TFI) prior to bevacizumab administration, and platinum sensitivity. Multivariate analysis was performed using Cox proportional hazards regression. The predictive model was developed into a nomogram to predict five-year OS. Results 312 women with recurrent ovarian cancer treated with bevacizumab and chemotherapy were identified; median age was 59 (range: 19-85); 86% women had advanced stage (III-IV) disease. The majority had serous histology (74%), high grade cancers (93.5%), and optimal cytoreductions (69.5%). Fifty-one percent of women received greater than two prior chemotherapeutic regimens. TFI (AHR = 0.98, 95% CI 0.97-1.00, p = 0.022) was the only statistically significant predictor in a multivariate progression-free survival (PFS) analysis. In a multivariate OS analysis, prior number of chemotherapy regimens, TFI, platinum sensitivity, and presence of ascites were significant. A nomogram to predict five-year OS was constructed and internally validated (bootstrap-corrected concordance index = 0.737). Conclusion Our multivariate model identified prior number of chemotherapy regimens, TFI, platinum sensitivity, and the presence of ascites as prognostic variables for OS in women with recurrent ovarian cancer treated with bevacizumab combined with chemotherapy. Our nomogram to predict five-year OS may be used to identify women who may benefit from bevacizumab and chemotherapy, but further validation is needed. © 2014 Elsevier Inc.

Authors
Previs, RA; Bevis, KS; Huh, W; Tillmanns, T; Perry, L; Moore, K; Chapman, J; McClung, C; Kiet, T; Java, J; Chan, J; Secord, AA
MLA Citation
Previs, RA, Bevis, KS, Huh, W, Tillmanns, T, Perry, L, Moore, K, Chapman, J, McClung, C, Kiet, T, Java, J, Chan, J, and Secord, AA. "A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy." Gynecologic Oncology 132.3 (January 1, 2014): 531-536.
Source
scopus
Published In
Gynecologic Oncology
Volume
132
Issue
3
Publish Date
2014
Start Page
531
End Page
536
DOI
10.1016/j.ygyno.2014.01.036

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube

Objective To determine the safety and efficacy of the novel combination of docetaxel, oxaliplatin, and bevacizumab as first-line treatment of advanced cancer of the ovary, peritoneum or fallopian tube after initial debulking surgery. Methods Eligible patients (stage IB-IV) were treated with 6 cycles of oxaliplatin (85 mg/m 2 ), docetaxel (75 mg/m 2 ), and bevacizumab (15 mg/kg) every 3 weeks, followed by single-agent bevacizumab 15 mg/kg every 3 weeks to complete one year of therapy. The primary endpoint was 12-month progression-free survival (PFS). Results A total of 132 patients (80 with measurable disease at baseline; 52 with non-measurable, evaluable disease at baseline) enrolled and received study treatment. At diagnosis, 76.5% of patients had stage III disease and 20% had stage IV. 62.9% were optimally cytoreduced. The most common grade 3/4 adverse events were neutropenia (42.4%), leukopenia (13.6%), hypertension (8.3%), fatigue (6.1%), and nausea (6.1%). One patient (0.8%) had a fatal gastrointestinal perforation. The best overall confirmed response rate (complete response + partial response [measurable disease subgroup]) was 58.6% (95% CI 49%, 67%). CA-125 response rates for the measurable and non-measurable disease subgroups were 83.0% and 81.5%, respectively. The 12-month PFS rate for the measurable disease subgroup was 65.7% (95% CI 53.4%, 76.7%); median PFS was 16.3 (95% CI 12.6, 19.6) months. Median overall survival was 47.3 (95% CI 34.1, upper limit not applicable) months. Conclusions This novel treatment regimen may provide a promising therapeutic approach for women with ovarian, primary peritoneal, or fallopian tube carcinoma. No unanticipated safety concerns were identified. © 2014 Elsevier Inc.

Authors
Herzog, TJ; Monk, BJ; Rose, PG; Braly, P; Hines, JF; Bell, MC; Wenham, RM; Secord, AA; Roman, LD; Einstein, MH; Drake, RD; Childs, BH
MLA Citation
Herzog, TJ, Monk, BJ, Rose, PG, Braly, P, Hines, JF, Bell, MC, Wenham, RM, Secord, AA, Roman, LD, Einstein, MH, Drake, RD, and Childs, BH. "A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube." Gynecologic Oncology 132.3 (January 1, 2014): 517-525.
Source
scopus
Published In
Gynecologic Oncology
Volume
132
Issue
3
Publish Date
2014
Start Page
517
End Page
525
DOI
10.1016/j.ygyno.2014.01.035

A modified bipedicle VRAM flap for simultaneous reconstruction of a perineal and posterior vaginal defect

© 2014, Springer-Verlag Berlin Heidelberg. The management of locally advanced pelvic tumors regularly requires radical surgical resection. The resection results in significant intrinsic and extrinsic pelvic defects. The advent of composite flaps has revolutionized vaginal and perineal reconstruction. Flaps provide bulky tissue to obliterate dead space, recruit vascularized tissue to an irradiated area and facilitate the skin closure. The authors present a modified vertical rectus abdominis myocutaneous (VRAM) flap for simultaneous reconstruction of a perineal and posterior vaginal defect following radical pelvic and abdominoperineal resection, based on two individual perforators off the inferior epigastric artery and vein with an excellent outcome. The English full-text version of this article is available at SpringerLink (under supplemental).

Authors
Kokosis, G; Schmitz, R; Secord, AA; Havrilesky, LJ; Berchuck, A; Mantyh, CR; Erdmann, D
MLA Citation
Kokosis, G, Schmitz, R, Secord, AA, Havrilesky, LJ, Berchuck, A, Mantyh, CR, and Erdmann, D. "A modified bipedicle VRAM flap for simultaneous reconstruction of a perineal and posterior vaginal defect." Gynakologe 47.10 (January 1, 2014): 784-787.
Source
scopus
Published In
Der Gynäkologe
Volume
47
Issue
10
Publish Date
2014
Start Page
784
End Page
787
DOI
10.1007/s00129-014-3448-3

Patient preferences in advanced or recurrent ovarian cancer

© 2014 American Cancer Society. BACKGROUND: The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen. METHODS: Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer. RESULTS: In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, a nd 24 months of PFS versus 15 months of PFS were 1.5 (P5.01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate. CONCLUSIONS: PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity.

Authors
Havrilesky, LJ; Secord, AA; Ehrisman, JA; Berchuck, A; Valea, FA; Lee, PS; Gaillard, SL; Samsa, GP; Cella, D; Weinfurt, KP; Abernethy, AP; Reed, SD
MLA Citation
Havrilesky, LJ, Secord, AA, Ehrisman, JA, Berchuck, A, Valea, FA, Lee, PS, Gaillard, SL, Samsa, GP, Cella, D, Weinfurt, KP, Abernethy, AP, and Reed, SD. "Patient preferences in advanced or recurrent ovarian cancer." Cancer 120.23 (January 1, 2014): 3651-3659.
Source
scopus
Published In
Cancer
Volume
120
Issue
23
Publish Date
2014
Start Page
3651
End Page
3659
DOI
10.1002/cncr.28940

Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: a case report.

We describe clinicopathologic and immunohistochemical features of an unusual case of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy postcoital vaginal bleeding 4 months after starting oral contraceptives and was found to have a cervical mass. She underwent a loop electrosurgical excision of the mass, and microscopic examination revealed a florid endocervical proliferation, extending to the margins. This lesion was initially interpreted as an invasive, well-differentiated endocervical adenocarcinoma. However, on subsequent review, the lesion was found to have a low rate of proliferation, no evidence of an infiltrative growth pattern, and abundant acute inflammation. Given these findings and the absence of any residual endocervical lesion on a subsequent cold knife conization, we determined that this was a benign, likely reactive, lesion. This case, together with previous studies, suggests that women with cystic fibrosis can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development.

Authors
Previs, RA; Edwards, JM; Secord, AA; Nucci, MR; Bentley, RC; Hall, AHS
MLA Citation
Previs, RA, Edwards, JM, Secord, AA, Nucci, MR, Bentley, RC, and Hall, AHS. "Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: a case report." International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 33.1 (January 2014): 100-104.
PMID
24300542
Source
epmc
Published In
International Journal of Gynecological Pathology
Volume
33
Issue
1
Publish Date
2014
Start Page
100
End Page
104
DOI
10.1097/pgp.0b013e318278b832

Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Recently, clinical trials have focused on novel antiangiogenic agents in combination with chemotherapy or alone in women with primary and recurrent ovarian cancer. Antiangiogenic agents include monoclonal antibodies, tyrosine-kinase inhibitors, and peptibodies. Many of these agents, including bevacizumab, pazopanib, nintedanib, cediranib, and trebananib, have been evaluated in randomized Phase III clinical trials, and all have demonstrated a progression-free survival (PFS) benefit. Specifically, maintenance pazopanib was shown to improve PFS in women with newly diagnosed EOC. Pazopanib, an oral TKI, inhibits several kinase receptors, including those for vascular endothelial growth factor (-1,-2,-3), platelet-derived growth factor (-α and -β), and fibroblast growth factor. It also targets stem cell-factor receptor (c-kit), interleukin 2-inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase, and colony-stimulating factor 1 receptor. Pazopanib has been investigated in several Phase II and III clinical trials, with results indicating a potential role in the management of EOC. This article provides an overview of pazopanib in the treatment of EOC.

Authors
Davidson, BA; Secord, AA
MLA Citation
Davidson, BA, and Secord, AA. "Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer." International journal of women's health 6 (January 2014): 289-300. (Review)
Website
http://hdl.handle.net/10161/15735
PMID
24648773
Source
epmc
Published In
International Journal of Women's Health
Volume
6
Publish Date
2014
Start Page
289
End Page
300
DOI
10.2147/ijwh.s49781

Differential Angiogenic Gene Expression in TP53 Wild-Type and Mutant Ovarian Cancer Cell Lines.

Underlying mechanisms regulating angiogenesis in ovarian cancer have not been completely elucidated. Evidence suggests that the TP53 tumor suppressor pathway and tumor microenvironment play integral roles. We utilized microarray technology to study the interaction between TP53 mutational status and hypoxia on angiogenic gene expression.Affymetrix U133A arrays were analyzed for angiogenic gene expression in 19 ovarian cancer cell lines stratified both by TP53 mutation status and A2780 wild-type (wt) TP53 vs. mutated (m) TP53 cell lines after treatment under hypoxic conditions or with ionizing radiation.Twenty-eight differentially expressed angiogenic genes were identified in the mTP53 cell lines compared to wtTP53 lines. Five genes were upregulated in mTP53 cells: 40% involved in extracellular matrix (ECM) degradation [matrix metalloproteinase 10 (MMP10)/15] and 60% in angiogenesis (fibroblast growth factor receptor 3/VEGFA/ephrin receptor-B4). Twenty-three genes were upregulated in wtTP53: nearly 22% were ECM constituents or involved in ECM degradation; over 40% were growth factors or mediators of angiogenesis. Five genes were upregulated in the A2780mTP53 cells: 40% involved in ECM remodeling (MMP10, ADAMTS1), 40% with pro-angiogenic activity (EFNB2, factor 2 receptor), and 20% with anti-angiogenic properties (ADAMTS1). Three genes were upregulated in hypoxia treated cells compared to controls: one with anti-angiogenic activity (angiopoietin-like 4) and two with pro-angiogenic activity (VEGFA, EFNA3). No significant gene fold changes were noted after exposure to radiation. Four genes continued to demonstrate significant differential expression (p ≤ 0.05) after adjusting for multiple comparisons. These genes included endoglin upregulation in wt lines (pro-angiogenesis) and upregulation of FGF20 (growth factor), ADAMTS1 (anti-angiogenesis) and MMP10 (ECM degradation) in mTP53 cell lines.Our exploratory findings indicate that non-overlapping angiogenic pathways may be altered by TP53 mutations and hypoxic conditions in the tumor microenvironment. Further evaluation is needed for confirmation.

Authors
Davidson, BA; Rubatt, JM; Corcoran, DL; Teoh, DK; Bernardini, MQ; Grace, LA; Soper, WJ; Berchuck, A; Siamakpour-Reihani, S; Chen, W; Owzar, K; Murphy, SK; Secord, AA
MLA Citation
Davidson, BA, Rubatt, JM, Corcoran, DL, Teoh, DK, Bernardini, MQ, Grace, LA, Soper, WJ, Berchuck, A, Siamakpour-Reihani, S, Chen, W, Owzar, K, Murphy, SK, and Secord, AA. "Differential Angiogenic Gene Expression in TP53 Wild-Type and Mutant Ovarian Cancer Cell Lines." Frontiers in oncology 4 (January 2014): 163-.
PMID
24999452
Source
epmc
Published In
Frontiers in Oncology
Volume
4
Publish Date
2014
Start Page
163
DOI
10.3389/fonc.2014.00163

Dasatinib (BMS-35482) potentiates the activity of gemcitabine and docetaxel in uterine leiomyosarcoma cell lines.

To explore the activity of dasatinib alone and in combination with gemcitabine and docetaxel in uterine leiomyosarcoma (uLMS) cell lines, and determine if dasatinib inhibits the SRC pathway.SK-UT-1 and SK-UT-1B uLMS cells were treated with gemcitabine, docetaxel and dasatinib individually and in combination. SRC and paxcillin protein expression were determined pre- and post-dasatinib treatment using Meso Scale Discovery (MSD) multi-array immunogenicity assay. Dose-response curves were constructed and the coefficient of drug interaction (CDI) and combination index (CI) for drug interaction calculated.Activated phosphorylated levels of SRC and paxillin were decreased after treatment with dasatinib in both cell lines (p < 0.001). The addition of a minimally active concentration of dasatinib (IC25) decreased the IC50 of each cytotoxic agent by 2-4 fold. The combination of gemcitabine-docetaxel yielded a synergistic effect in SK-UT-1 (CI = 0.59) and an antagonistic effect in SK-UT-1B (CI = 1.36). Dasatinib combined with gemcitabine or docetaxel revealed a synergistic anti-tumor effect (CDI < 1) in both cell lines. The triple drug combination and sequencing revealed conflicting results with a synergistic effect in SK-UT-1B and antagonistic in SK-UT-1.Dasatinib inhibits the SRC pathway and yields a synergistic effect with the two-drug combination with either gemcitabine or docetaxel. The value of adding dasatinib to gemcitabine and docetaxel in a triple drug combination is uncertain, but may be beneficial in select uLMS cell lines. Based on our pre-clinical data and known activity of gemcitabine and docetaxel, further evaluation of dasatinib in combination with these agents for the treatment of uLMS is warranted.

Authors
Lopez-Acevedo, M; Grace, L; Teoh, D; Whitaker, R; Adams, DJ; Jia, J; Nixon, AB; Secord, AA
MLA Citation
Lopez-Acevedo, M, Grace, L, Teoh, D, Whitaker, R, Adams, DJ, Jia, J, Nixon, AB, and Secord, AA. "Dasatinib (BMS-35482) potentiates the activity of gemcitabine and docetaxel in uterine leiomyosarcoma cell lines." Gynecologic oncology research and practice 1 (January 2014): 2-.
Website
http://hdl.handle.net/10161/12496
PMID
27231555
Source
epmc
Published In
Gynecologic Oncology Research and Practice
Volume
1
Publish Date
2014
Start Page
2
DOI
10.1186/2053-6844-1-2

Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway

Authors
Lee, PS; Secord, AA
MLA Citation
Lee, PS, and Secord, AA. "Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway." Cancer Treatment Reviews 40.4 (2014): 507-512.
Source
scopus
Published In
Cancer Treatment Reviews
Volume
40
Issue
4
Publish Date
2014
Start Page
507
End Page
512

A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer

Objective Recurrence following primary platinum-based chemotherapy remains a challenge in the treatment of patients with advanced-stage epithelial ovarian cancer. This study examines whether a chemoresponse assay can identify patients who are platinum-resistant prior to treatment. Study Design Women (n = 276) with International Federation of Gynecology and Obstetrics stage III-IV ovarian, fallopian, and peritoneal cancer were enrolled in an observational study, and the responsiveness of their tumors was evaluated using a chemoresponse assay. All patients were treated with a platinum/taxane regimen following cytoreductive surgery. Assay responses to carboplatin or paclitaxel were classified as sensitive, intermediate sensitive (IS), or resistant. Association of assay response with progression-free survival (PFS) was analyzed using the Kaplan-Meier method and a Cox regression model. Results Patients whose tumors were resistant to carboplatin were at increased risk of disease progression compared to those with nonresistant (sensitive + IS) tumors (median PFS: 11.8 vs 16.6 months, respectively, P <.001), and the association was confirmed after adjusting for other clinical factors (hazard ratio, 1.71; 95% confidence interval, 1.12-2.62; P =.013). Association of assay response to paclitaxel with PFS trended in multivariate analysis (hazard ratio, 1.28; 95% confidence interval, 0.84-1.95; P =.245). For tumors resistant to carboplatin, 59% were sensitive or IS to at least 1 other commonly used agent, demonstrating the ability of the assay to inform treatment decisions beyond the standard platinum/taxane regimen. Conclusion Assay resistance to carboplatin is strongly associated with shortened PFS among advanced-stage epithelial ovarian cancer patients treated with carboplatin + paclitaxel therapy, supporting use of this assay to identify patients likely to experience early recurrence on standard platinum-based therapy. © 2014 Mosby, Inc. All rights reserved.

Authors
Krivak, TC; Lele, S; Richard, S; Secord, AA; Leath, CA; Brower, SL; Tian, C; Moore, RG
MLA Citation
Krivak, TC, Lele, S, Richard, S, Secord, AA, Leath, CA, Brower, SL, Tian, C, and Moore, RG. "A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer." American Journal of Obstetrics and Gynecology 211.1 (2014): 68.e1-68.e8.
Source
scival
Published In
American Journal of Obstetrics & Gynecology
Volume
211
Issue
1
Publish Date
2014
Start Page
68.e1
End Page
68.e8
DOI
10.1016/j.ajog.2014.02.009

SGO guidance document for clinical trial designs in ovarian cancer: A changing paradigm

© 2014 Elsevier Inc.Objective. To explore and facilitate themultifaceted process of drug development and regulatory approval in ovarian cancer.Methods. The Society of Gynecologic Oncology (SGO) recently sought and received input from multiple stakeholders including the National Cancer Institute's (NCI) Clinical Therapy Evaluation Program (CTEP), the Food and Drug Administration (FDA), pharmaceutical industry, and patient advocates. This whitepaper is the work product and opinion solely of the SGO.Results. This document summarizes the SGO's interpretation of these meetings and the current regulatory environment where there has been a paucity of recent approvals in the United States. It provides guidance in clinical trial design with the express purpose of encouraging novel drug development in ovarian cancer. Points of emphasis include: ovarian cancer heterogeneity (histologic subtypes and molecular genetic alterations), clinical trial design elements, surrogate as well as composite endpoints, and the four principles of clinical drug development (unmet medical need, discovery, safety, and efficacy).Conclusions. There has been an evolution in the acceptance of surrogate endpoints depending upon the clinical setting in ovarian cancer. While overall survival (OS) remains the most objective clinical trial endpoint, there is now realization that demanding OS as the primary endpoint has many obstacles. Ovarian cancer is a heterogeneous disease that is now divided by histologic subtypes. Future registration strategies will need to address disease heterogeneity. The exploration of currently acceptable clinical trial endpoints and alternative regulatory strategies will hopefully stimulate interest in novel drug development for patients with ovarian cancer.

Authors
Herzog, TJ; Alvarez, RD; Secord, A; Goff, BA; Mannel, RS; Monk, BJ; Coleman, RL
MLA Citation
Herzog, TJ, Alvarez, RD, Secord, A, Goff, BA, Mannel, RS, Monk, BJ, and Coleman, RL. "SGO guidance document for clinical trial designs in ovarian cancer: A changing paradigm." Gynecologic Oncology 135.1 (2014): 3-7.
Source
scival
Published In
Gynecologic Oncology
Volume
135
Issue
1
Publish Date
2014
Start Page
3
End Page
7
DOI
10.1016/j.ygyno.2014.08.004

Does adjuvant chemotherapy improve survival for women with early-stage uterine leiomyosarcoma?

Objectives To examine whether adjuvant therapy after primary surgery for treatment o f early-stage uterine leiomyosarcoma (LMS) improves recurrence and survival rates. Methods A multisite, retrospective study of women diagnosed with stage I-II high grade LMS from 1990-2010 was performed. All patients (pts) underwent primary surgery followed by observation (OBS), radiotherapy (RT), or chemotherapy (CT) postoperatively. Results One hundred eight patients were identified with long-term follow-up; 94 pts (87.0%) had stage I and 14 (13.0%) had stage II disease. The mean patient age was 55.4 years and mean BMI was 28.0. Thirty-four (31.5%) patients underwent OBS, 35 (32.4%) received RT, and 39 (36.1%) received chemotherapy. After a median follow-up of 41.8 months, a recurrence was diagnosed in 70.8%. Recurrence was evident in 25/34 (73.5%) OBS, 23/35 (65.7%) RT, and 28/39 (71.8%) of CT cohorts and was not different based on treatment (p = 0.413). However, extra-pelvic recurrences were significantly higher in the RT (95.2%) than in the OBS (60%) or CT (64.3%) cohorts (p = 0.012). Additionally, recurrences were more likely to be successfully treated or palliated in those who initially received CT (p = 0.031). On multivariate analysis, stage (p < 0.001) and chemotherapy (p = 0.045) were associated with overall survival. Conclusions Women with early-stage, high grade uterine LMS experience high recurrence rates and poor survival outcomes, irrespective of adjuvant therapy. These rates are higher than previously reported in the literature. Although women treated with CT had similar recurrence rates as those treated with OBS or RT, treatment with adjuvant chemotherapy may decrease the risk of extra-pelvic recurrence and improve survival. © 2013 Elsevier Inc.

Authors
Ricci, S; Giuntoli, RL; Eisenhauer, E; Lopez, MA; Krill, L; Tanner, EJ; Gehrig, PA; Havrilesky, LJ; Secord, AA; Levinson, K; Frasure, H; Celano, P; Fader, AN
MLA Citation
Ricci, S, Giuntoli, RL, Eisenhauer, E, Lopez, MA, Krill, L, Tanner, EJ, Gehrig, PA, Havrilesky, LJ, Secord, AA, Levinson, K, Frasure, H, Celano, P, and Fader, AN. "Does adjuvant chemotherapy improve survival for women with early-stage uterine leiomyosarcoma?." Gynecologic Oncology 131.3 (December 1, 2013): 629-633.
Source
scopus
Published In
Gynecologic Oncology
Volume
131
Issue
3
Publish Date
2013
Start Page
629
End Page
633
DOI
10.1016/j.ygyno.2013.08.037

Does adjuvant chemotherapy improve survival for women with early-stage uterine leiomyosarcoma?

OBJECTIVES: To examine whether adjuvant therapy after primary surgery for treatment of early-stage uterine leiomyosarcoma (LMS) improves recurrence and survival rates. METHODS: A multisite, retrospective study of women diagnosed with stage I-II high grade LMS from 1990-2010 was performed. All patients (pts) underwent primary surgery followed by observation (OBS), radiotherapy (RT), or chemotherapy (CT) postoperatively. RESULTS: One hundred eight patients were identified with long-term follow-up; 94 pts (87.0%) had stage I and 14 (13.0%) had stage II disease. The mean patient age was 55.4 years and mean BMI was 28.0. Thirty-four (31.5%) patients underwent OBS, 35 (32.4%) received RT, and 39 (36.1%) received chemotherapy. After a median follow-up of 41.8 months, a recurrence was diagnosed in 70.8%. Recurrence was evident in 25/34 (73.5%) OBS, 23/35 (65.7%) RT, and 28/39 (71.8%) of CT cohorts and was not different based on treatment (p=0.413). However, extra-pelvic recurrences were significantly higher in the RT (95.2%) than in the OBS (60%) or CT (64.3%) cohorts (p=0.012). Additionally, recurrences were more likely to be successfully treated or palliated in those who initially received CT (p=0.031). On multivariate analysis, stage (p<0.001) and chemotherapy (p=0.045) were associated with overall survival. CONCLUSIONS: Women with early-stage, high grade uterine LMS experience high recurrence rates and poor survival outcomes, irrespective of adjuvant therapy. These rates are higher than previously reported in the literature. Although women treated with CT had similar recurrence rates as those treated with OBS or RT, treatment with adjuvant chemotherapy may decrease the risk of extra-pelvic recurrence and improve survival.

Authors
Ricci, S; Giuntoli, RL; Eisenhauer, E; Lopez, MA; Krill, L; Tanner, EJ; Gehrig, PA; Havrilesky, LJ; Secord, AA; Levinson, K; Frasure, H; Celano, P; Fader, AN
MLA Citation
Ricci, S, Giuntoli, RL, Eisenhauer, E, Lopez, MA, Krill, L, Tanner, EJ, Gehrig, PA, Havrilesky, LJ, Secord, AA, Levinson, K, Frasure, H, Celano, P, and Fader, AN. "Does adjuvant chemotherapy improve survival for women with early-stage uterine leiomyosarcoma?." Gynecol Oncol 131.3 (December 2013): 629-633.
PMID
24016408
Source
pubmed
Published In
Gynecologic Oncology
Volume
131
Issue
3
Publish Date
2013
Start Page
629
End Page
633
DOI
10.1016/j.ygyno.2013.08.037

Cost effectiveness of alternative strategies for incorporating bevacizumab into the primary treatment of ovarian cancer.

BACKGROUND: The objective of this study was to evaluate the comparative effectiveness of strategies that incorporated bevacizumab into the primary platinum-based treatment of ovarian cancer: 1) no bevacizumab; 2) concurrent and maintenance bevacizumab for all; 3) bevacizumab for suboptimally debulked stage III and stage IV disease (high-risk cohort); and the evaluation of an alternative exploratory strategy of 4) directed bevacizumab therapy based on a predictive test for bevacizumab responsiveness. METHODS: A modified Markov state transition model with a 3-year time horizon that simulated publically available International Collaboration on Ovarian Neoplasms (ICON7) trial outcomes was used to evaluate the cost effectiveness of each strategy. Costs and adverse events were incorporated. An alternative strategy was used to model the impact on overall survival of a genetic-based predictive test. A Monte Carlo simulation simultaneously accounted for uncertainty in key parameters. RESULTS: The incorporation of bevacizumab for high-risk patients had an incremental cost-effectiveness ratio of $168,000 per quality-adjusted life-year (QALY) saved compared with chemotherapy alone and dominated a strategy of giving bevacizumab to all patients with ovarian cancer. Monte Carlo simulation acceptability curves indicated that, at a willingness-to-pay threshold of $200,000 per QALY, the treatment of high-risk women with bevacizumab was the strategy of choice in 84% of simulations. A predictive test had an incremental cost-effectiveness ratio of $129,000 per QALY compared with chemotherapy alone and dominated other bevacizumab treatment strategies. CONCLUSIONS: The selective treatment of women with suboptimal and/or stage IV ovarian cancer was a more cost-effective use of bevacizumab than universal treatment but still did not fall within the limits of common willingness-to-pay thresholds. Continued investigation of potentially cost-effective strategies, such as a predictive test, is necessary to optimize the use of this expensive treatment.

Authors
Barnett, JC; Alvarez Secord, A; Cohn, DE; Leath, CA; Myers, ER; Havrilesky, LJ
MLA Citation
Barnett, JC, Alvarez Secord, A, Cohn, DE, Leath, CA, Myers, ER, and Havrilesky, LJ. "Cost effectiveness of alternative strategies for incorporating bevacizumab into the primary treatment of ovarian cancer." Cancer 119.20 (October 15, 2013): 3653-3661.
PMID
23921967
Source
pubmed
Published In
Cancer
Volume
119
Issue
20
Publish Date
2013
Start Page
3653
End Page
3661
DOI
10.1002/cncr.28283

A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer

Authors
Krivak, T; Secord, AA; Richard, S; III, LC; Moore, R; Coleman, R; Fiorica, J; Barter, J; Downey, G; Tian, C; Lele, S
MLA Citation
Krivak, T, Secord, AA, Richard, S, III, LC, Moore, R, Coleman, R, Fiorica, J, Barter, J, Downey, G, Tian, C, and Lele, S. "A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer." GYNECOLOGIC ONCOLOGY 131.1 (October 2013): 276-276.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
131
Issue
1
Publish Date
2013
Start Page
276
End Page
276
DOI
10.1016/j.ygyno.2013.07.076

Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels.

PURPOSE: CA-125 has been a valuable marker for detecting ovarian cancer, however, it is not sensitive enough to detect early-stage disease and not specific to ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific to ovarian cancer regardless of CA-125 levels. METHODS: Top-down and iTRAQ quantitative proteomics methods were used to identify high-frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers. RESULTS: The proteomics methodologies identified more than 60 potential high-frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high-frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels. CONCLUSIONS: Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant to early detection of ovarian cancer.

Authors
Karabudak, AA; Hafner, J; Shetty, V; Chen, S; Secord, AA; Morse, MA; Philip, R
MLA Citation
Karabudak, AA, Hafner, J, Shetty, V, Chen, S, Secord, AA, Morse, MA, and Philip, R. "Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels." J Cancer Res Clin Oncol 139.10 (October 2013): 1757-1770.
PMID
23999876
Source
pubmed
Published In
Journal of Cancer Research and Clinical Oncology
Volume
139
Issue
10
Publish Date
2013
Start Page
1757
End Page
1770
DOI
10.1007/s00432-013-1501-6

Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer.

OBJECTIVE: To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective. METHODS: A decision model with a 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, and ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (ORs) for potential reductions in hospitalization (OR 0.69), chemotherapy (OR 0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies. RESULTS: EPC was associated with a cost savings of $1285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) <$50,000/QALY, unless the cost of outpatient EPC exceeded $2400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER $37,440/QALY. CONCLUSION: Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer.

Authors
Lowery, WJ; Lowery, AW; Barnett, JC; Lopez-Acevedo, M; Lee, PS; Secord, AA; Havrilesky, L
MLA Citation
Lowery, WJ, Lowery, AW, Barnett, JC, Lopez-Acevedo, M, Lee, PS, Secord, AA, and Havrilesky, L. "Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer." Gynecol Oncol 130.3 (September 2013): 426-430.
PMID
23769759
Source
pubmed
Published In
Gynecologic Oncology
Volume
130
Issue
3
Publish Date
2013
Start Page
426
End Page
430
DOI
10.1016/j.ygyno.2013.06.011

Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer.

OBJECTIVES: (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures. METHODS: A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, >1 hospitalization in the last 30 days, >1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤3 days. RESULTS: One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p=0.003), >1 hospitalization in the last 30 days (p<0.001), ICU admission in the last 30 days (p=0.005), dying in acute care setting (p=0.01), admitted to hospice ≤3 days (p=0.02). EOL discussion as outpatient was associated with fewer patients hospitalized >1 in the last 30days of life (p<0.001). CONCLUSIONS: End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions.

Authors
Lopez-Acevedo, M; Havrilesky, LJ; Broadwater, G; Kamal, AH; Abernethy, AP; Berchuck, A; Alvarez Secord, A; Tulsky, JA; Valea, F; Lee, PS
MLA Citation
Lopez-Acevedo, M, Havrilesky, LJ, Broadwater, G, Kamal, AH, Abernethy, AP, Berchuck, A, Alvarez Secord, A, Tulsky, JA, Valea, F, and Lee, PS. "Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer." Gynecol Oncol 130.1 (July 2013): 156-161.
PMID
23587882
Source
pubmed
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
156
End Page
161
DOI
10.1016/j.ygyno.2013.04.010

Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer.

OBJECTIVE: We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix. METHODS: Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy. RESULTS: Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities. CONCLUSION: The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.

Authors
Zighelboim, I; Wright, JD; Gao, F; Case, AS; Massad, LS; Mutch, DG; Powell, MA; Thaker, PH; Eisenhauer, EL; Cohn, DE; Valea, FA; Alvarez Secord, A; Lippmann, LT; Dehdashti, F; Rader, JS
MLA Citation
Zighelboim, I, Wright, JD, Gao, F, Case, AS, Massad, LS, Mutch, DG, Powell, MA, Thaker, PH, Eisenhauer, EL, Cohn, DE, Valea, FA, Alvarez Secord, A, Lippmann, LT, Dehdashti, F, and Rader, JS. "Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer." Gynecol Oncol 130.1 (July 2013): 64-68.
PMID
23591400
Source
pubmed
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
64
End Page
68
DOI
10.1016/j.ygyno.2013.04.009

A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy.

OBJECTIVES: The efficacy and safety of bevacizumab and docetaxel were evaluated in women who developed recurrent epithelial ovarian, fallopian, or peritoneal cancer within 12 months of platinum-based therapy. METHODS: Patients received docetaxel (40 mg/m(2)) on days 1 and 8 and bevacizumab (15 mg/kg) on day 1 of a 21-daycycle. Primary endpoint was 6-month progression-free survival (PFS). RESULTS: Forty-one patients were evaluable for PFS and 38 for best response; 46% had platinum-free intervals (PFI) of <6 months and 54% between 6 and 12 months. The 6-month PFS was 43.9% (95% confidence interval (CI(95%))=28.6-58.2%). Median PFS (months) was 5.2 (CI(95%)=4.4-7.2) for all patients, 6.2 (CI(95%)=4.1-7.4) for patients with PFI <6 months, and 5.1 (CI(95%)=3.0-7.2) for those with PFI ≥ 6 months. Twenty-two patients showed overall response (CR+PR) (57.9%; CI(95%)=40.8-73.7%), and 32 showed clinical benefit (CR+PR+SD) (84.2%; CI(95%)=68.8-94.0%). For those with complete or partial responses, median duration of response was 4.8 months (0.7-14.5). Median overall survival was 12.4 months (CI(95%)=10.0-21.9). The most common grade 3/4 adverse events (AEs) were neutropenia (14.6% of patients), followed by leukopenia, fatigue, metabolic, and gastrointestinal, with 66% showing any grade 3/4 toxicity. Most common AEs of any grade were gastrointestinal (93%), fatigue (73%), and pain (73%). Four (10%) patients developed hypertension, 1 a gastrointestinal perforation, and another a colovesicular fistula. CONCLUSIONS: Bevacizumab and docetaxel administered in patients with recurrent ovarian cancer is an active regimen without new unanticipated toxicities. This combination should be an option for further study or clinical use in recurrent ovarian cancer.

Authors
Wenham, RM; Lapolla, J; Lin, H-Y; Apte, SM; Lancaster, JM; Judson, PL; Gonzalez-Bosquet, J; Herschberger, A; Havrilesky, LJ; Secord, AA
MLA Citation
Wenham, RM, Lapolla, J, Lin, H-Y, Apte, SM, Lancaster, JM, Judson, PL, Gonzalez-Bosquet, J, Herschberger, A, Havrilesky, LJ, and Secord, AA. "A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy." Gynecol Oncol 130.1 (July 2013): 19-24.
PMID
23623830
Source
pubmed
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
19
End Page
24
DOI
10.1016/j.ygyno.2013.04.049

Cost-effectiveness of BRCA1 and BRCA2 mutation testing to target PARP inhibitor use in platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: (1) To determine whether use of a PARP inhibitor or (2) BRCA1/2 mutation testing followed by a PARP inhibitor for test positives is potentially cost-effective for maintenance treatment of platinum-sensitive recurrent high-grade serous ovarian cancer. METHODS: A modified Markov decision analysis compared 3 strategies: (1) observe; (2) olaparib to progression; (3) BRCA1/2 mutation testing; treat mutation carriers with olaparib to progression. Progression-free survival and rates of adverse events were derived from a phase 2 randomized trial. Key assumptions are as follows: (1) 14% of patients harbor a BRCA1/2 mutation; (2) progression-free survival of individuals treated with olaparib is improved for BCRA1/2 carriers compared with noncarriers (estimated hazard ratio, approximately 0.4). Costs derived from national data were assigned to treatments, adverse events, and BRCA1/2 test. Monte Carlo probabilistic sensitivity analysis was performed. RESULTS: Global olaparib was the most effective strategy, followed by BRCA1/2 testing and no olaparib. BRCA1/2 testing had an incremental cost-effectiveness ratio (ICER) of $193,442 per progression-free year of life saved (PF-YLS) compared to no olaparib, whereas global olaparib had an ICER of $234,128 per PF-YLS compared to BRCA1/2 testing. At a 52% lower-than-baseline olaparib cost estimate of $3000 per month, BRCA1/2 testing became potentially cost-effective compared with observation, with an ICER of $100,000 per PF-YLS. When strategy (1) was removed from the analysis, BRCA1/2 testing was the preferred strategy. CONCLUSIONS: The use of maintenance olaparib in women with high-grade serous ovarian cancer is not cost-effective regardless of whether BRCA1/2 testing is used to direct treatment. However, BRCA1/2 testing is a preferred strategy compared to global maintenance olaparib alone.

Authors
Secord, AA; Barnett, JC; Ledermann, JA; Peterson, BL; Myers, ER; Havrilesky, LJ
MLA Citation
Secord, AA, Barnett, JC, Ledermann, JA, Peterson, BL, Myers, ER, and Havrilesky, LJ. "Cost-effectiveness of BRCA1 and BRCA2 mutation testing to target PARP inhibitor use in platinum-sensitive recurrent ovarian cancer." Int J Gynecol Cancer 23.5 (June 2013): 846-852.
PMID
23666017
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
23
Issue
5
Publish Date
2013
Start Page
846
End Page
852
DOI
10.1097/IGC.0b013e31829527bd

The impact of diabetes and obesity on endometrial cancer outcomes

Authors
Ko, EM; Walter, P; Clark, LH; Jackson, AL; Franasiak, J; Havrilesky, LJ; Secord, AA; Moore, DT; Gehrig, PA; Bae-Jump, VL
MLA Citation
Ko, EM, Walter, P, Clark, LH, Jackson, AL, Franasiak, J, Havrilesky, LJ, Secord, AA, Moore, DT, Gehrig, PA, and Bae-Jump, VL. "The impact of diabetes and obesity on endometrial cancer outcomes." May 20, 2013.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

Recurrence rates in patients with uterine papillary serous cancer with and without breast cancer.

Authors
Stine, JE; Pierce, S; Gehrig, PA; Nakayama, J; Havrilesky, LJ; Secord, AA; Chiu, WK; Moore, DT; Kim, KH
MLA Citation
Stine, JE, Pierce, S, Gehrig, PA, Nakayama, J, Havrilesky, LJ, Secord, AA, Chiu, WK, Moore, DT, and Kim, KH. "Recurrence rates in patients with uterine papillary serous cancer with and without breast cancer." May 20, 2013.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

Invasion, metastasis, and angiogenesis

Authors
Romano-Fitzgerald, S; De Meritens, AB; Secord, AA; Kohn, EC
MLA Citation
Romano-Fitzgerald, S, De Meritens, AB, Secord, AA, and Kohn, EC. "Invasion, metastasis, and angiogenesis." Principles and Practice of Gynecologic Oncology: Sixth Edition. May 8, 2013. 72-88.
Source
scopus
Publish Date
2013
Start Page
72
End Page
88

Abstract 330A: Differential expression of angiogenic genes in invasive high grade serous ovarian carcinomas.

Authors
Siamakpour- Reihani, S; Jiang, C; Turner, T; Owzar, K; Berchuck, A; Dewhirst, M; Alvarez Secord, A
MLA Citation
Siamakpour- Reihani, S, Jiang, C, Turner, T, Owzar, K, Berchuck, A, Dewhirst, M, and Alvarez Secord, A. "Abstract 330A: Differential expression of angiogenic genes in invasive high grade serous ovarian carcinomas." April 15, 2013.
Source
crossref
Published In
Cancer Research
Volume
73
Issue
8 Supplement
Publish Date
2013
Start Page
330A
End Page
330A
DOI
10.1158/1538-7445.AM2013-330A

Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer.

OBJECTIVE: There is limited information concerning the role of relative dose intensity (RDI) on clinical outcomes in solid tumors. The objectives of our study were to evaluate the prognostic significance of RDI and predictors of reduced RDI in women with newly diagnosed advanced stage epithelial ovarian carcinoma (EOC) treated with platinum-based chemotherapy. METHODS: A multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy between 1995 and 2009 was conducted. Data were obtained to include the first four chemotherapy cycles administered. Outcomes included: (1) planned and delivered relative dose intensity (RDI), (2) progression-free (PFS) and overall (OS) survival. Survival estimates were based on Kaplan and Meier method, and multivariate analyses were based on logistic regression and Cox proportional hazards regression. RESULTS: Evaluable subjects included 325 women. With median follow-up of 34 months (range, 0.4-170), progression or recurrence was recorded in 241 (73.9%) and death in 179 (54.9%). In multivariate analysis, predictors of reduced planned RDI were: treatment off research protocols (odds ratio [OR]=4.3; P<0.001) and BSA >2m(2) (OR=6.14; P<0.001); predictors of reduced delivered RDI were: BMI over 30 kg/m(2) (OR=2.35; P=0.008) and use of carboplatin (OR=2.71; P=0.008). In multivariate analysis, the following factors were independently associated with OS: delivered RDI <85% (hazard ratio [HR]=1.71; P=0.003) and elevated CA-125 at cycle 1 (HR=2.29; P=0.017). CONCLUSION: In this retrospective analysis, reduced chemotherapy RDI for ovarian cancer was associated with lower OS, but not PFS, despite adjustment for established prognostic factors.

Authors
Hanna, RK; Poniewierski, MS; Laskey, RA; Lopez, MA; Shafer, A; Van Le, L; Crawford, J; Dale, DC; Gehrig, PA; Secord, AA; Havrilesky, LJ; Lyman, GH
MLA Citation
Hanna, RK, Poniewierski, MS, Laskey, RA, Lopez, MA, Shafer, A, Van Le, L, Crawford, J, Dale, DC, Gehrig, PA, Secord, AA, Havrilesky, LJ, and Lyman, GH. "Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer." Gynecol Oncol 129.1 (April 2013): 74-80.
PMID
23262376
Source
pubmed
Published In
Gynecologic Oncology
Volume
129
Issue
1
Publish Date
2013
Start Page
74
End Page
80
DOI
10.1016/j.ygyno.2012.12.017

A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer.

OBJECTIVE: To determine if there is an advantage to combination chemotherapy and radiation for optimally resected stage IIIC endometrial cancer (EC). METHODS: A multicenter retrospective analysis of patients with EC from 1991 to 2008 was conducted. Inclusion criteria were lymph node assessment and optimally resected disease. Recurrence-free (RFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: 265 patients with optimally resected stage IIIC EC were identified. Postoperative therapies included radiotherapy in 17% (n=45), chemotherapy in 17% (n=46), and both chemotherapy and radiation in 61% (n=161). Three-year RFS was 56% for chemotherapy alone, compared to 73% for radiation alone, and 73% for combination therapy (p=0.12). Those receiving chemotherapy alone had the worst 3-year OS (78%) compared to either radiotherapy alone (95%) or combination therapy (90%) (p=0.005). After adjustment for stage and grade those treated with chemotherapy alone were at a 2.2 fold increased risk of recurrence (95% CI, 1.2 to 4.2; p=0.02) and 4.0 fold increased risk of death (95% CI, 1.6 to 10.0; p=0.004) compared to those treated with chemotherapy and radiation. In contrast there was no significant difference in RFS [HR=1.0 (95% CI, 0.5 to 2.0; p=0.92)] or OS [HR=1.1 (95% CI, 0.3 to 3.6; p=0.91)] for those treated with radiation alone compared to those treated with chemotherapy and radiation. CONCLUSION: Adjuvant therapy with either radiation alone or chemotherapy and radiation was associated with improved outcomes for patients with optimally resected stage IIIC EC compared to those treated with chemotherapy only.

Authors
Secord, AA; Geller, MA; Broadwater, G; Holloway, R; Shuler, K; Dao, N-Y; Gehrig, PA; O'Malley, DM; Finkler, N; Havrilesky, LJ
MLA Citation
Secord, AA, Geller, MA, Broadwater, G, Holloway, R, Shuler, K, Dao, N-Y, Gehrig, PA, O'Malley, DM, Finkler, N, and Havrilesky, LJ. "A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer." Gynecol Oncol 128.1 (January 2013): 65-70.
PMID
23085460
Source
pubmed
Published In
Gynecologic Oncology
Volume
128
Issue
1
Publish Date
2013
Start Page
65
End Page
70
DOI
10.1016/j.ygyno.2012.10.010

BRCA1 immunohistochemistry in a molecularly characterized cohort of ovarian high-grade serous carcinomas.

BRCA1 and BRCA2 dysfunction, frequently seen in high-grade serous ovarian carcinomas, often results from germline mutations, somatic mutations, and promoter methylation. Identification of tumors with BRCA defects has therapeutic and prognostic implications. Identifying germline BRCA mutations is also important given the increased risk for hereditary breast and ovarian carcinoma. Our goal was to assess whether immunohistochemical analysis (IHC) for BRCA1 is an effective method for the detection of BRCA1 dysfunction in molecularly characterized high-grade ovarian serous carcinoma. We identified 43 high-grade ovarian serous carcinomas with known events in BRCA1 and BRCA2 included in The Cancer Genome Atlas Project. BRCA1 stain was first assessed without knowledge of the BRCA status, and a semiquantitative assessment for intensity and amount of staining was performed. The stains were reevaluated and divided into 3 categories (retained, loss, and equivocal) on the basis of correlation with genotyping data. Presence of retained BRCA staining was considered normal, whereas the other patterns, including equivocal staining or loss of staining, were considered abnormal. Two pathologists, blinded to the BRCA status, then scored 2 sets of validation cases selected on the basis of available molecular data-1 with only germline mutation status available (n=31) and 1 with comprehensive genomic data (n=39). The pathologists agreed 88% of the time in the training set and 91% in the validation sets. In the training set, abnormal BRCA staining was seen in 24 cases, of which 21 (87%) showed BRCA1 genetic abnormalities, 1 showed BRCA2 mutations, and 2 showed no BRCA abnormalities. Abnormal BRCA1 staining was noted in all 5 cases with BRCA1 germline mutations, in 3 (60%) of 5 with BRCA1 somatic mutations, and in 13 (93%) of 14 with BRCA1 promoter methylation. The 2 validation sets included 70 additional patients, and all cases with germline BRCA1 mutations (n=11) showed abnormal BRCA1 staining. Tumors with BRCA1 promoter methylation also showed abnormal staining in 6 (86%) of 7 cases. In the entire study, no cases with BRCA1 germline mutation showed intact immunostaining (negative predictive value=100%). This study shows that BRCA1 IHC is well correlated with molecular events in ovarian carcinoma. Considering the high negative predictive value for germline mutations, BRCA1 IHC appears to be an effective approach to stratify patients for germline genetic testing and to detect other mechanisms of BRCA1 dysfunction in high-grade serous ovarian carcinomas.

Authors
Garg, K; Levine, DA; Olvera, N; Dao, F; Bisogna, M; Secord, AA; Berchuck, A; Cerami, E; Schultz, N; Soslow, RA
MLA Citation
Garg, K, Levine, DA, Olvera, N, Dao, F, Bisogna, M, Secord, AA, Berchuck, A, Cerami, E, Schultz, N, and Soslow, RA. "BRCA1 immunohistochemistry in a molecularly characterized cohort of ovarian high-grade serous carcinomas." Am J Surg Pathol 37.1 (January 2013): 138-146.
PMID
23232854
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
37
Issue
1
Publish Date
2013
Start Page
138
End Page
146
DOI
10.1097/PAS.0b013e31826cabbd

Cost effectiveness of alternative strategies for incorporating bevacizumab into the primary treatment of ovarian cancer

BACKGROUND The objective of this study was to evaluate the comparative effectiveness of strategies that incorporated bevacizumab into the primary platinum-based treatment of ovarian cancer: 1) no bevacizumab; 2) concurrent and maintenance bevacizumab for all; 3) bevacizumab for suboptimally debulked stage III and stage IV disease (high-risk cohort); and the evaluation of an alternative exploratory strategy of 4) directed bevacizumab therapy based on a predictive test for bevacizumab responsiveness. METHODS A modified Markov state transition model with a 3-year time horizon that simulated publically available International Collaboration on Ovarian Neoplasms (ICON7) trial outcomes was used to evaluate the cost effectiveness of each strategy. Costs and adverse events were incorporated. An alternative strategy was used to model the impact on overall survival of a genetic-based predictive test. A Monte Carlo simulation simultaneously accounted for uncertainty in key parameters. RESULTS The incorporation of bevacizumab for high-risk patients had an incremental cost-effectiveness ratio of 168,000 per quality-adjusted life-year (QALY) saved compared with chemotherapy alone and dominated a strategy of giving bevacizumab to all patients with ovarian cancer. Monte Carlo simulation acceptability curves indicated that, at a willingness-to-pay threshold of 200,000 per QALY, the treatment of high-risk women with bevacizumab was the strategy of choice in 84% of simulations. A predictive test had an incremental cost-effectiveness ratio of 129,000 per QALY compared with chemotherapy alone and dominated other bevacizumab treatment strategies. CONCLUSIONS The selective treatment of women with suboptimal and/or stage IV ovarian cancer was a more cost-effective use of bevacizumab than universal treatment but still did not fall within the limits of common willingness-to-pay thresholds. Continued investigation of potentially cost-effective strategies, such as a predictive test, is necessary to optimize the use of this expensive treatment. Cancer 2013;119:3653-3661. © 2013 American Cancer Society.

Authors
Barnett, JC; Secord, AA; Cohn, DE; II, CAL; Myers, ER; Havrilesky, LJ
MLA Citation
Barnett, JC, Secord, AA, Cohn, DE, II, CAL, Myers, ER, and Havrilesky, LJ. "Cost effectiveness of alternative strategies for incorporating bevacizumab into the primary treatment of ovarian cancer." Cancer 119.20 (2013): 3653-3661.
Source
scival
Published In
Cancer
Volume
119
Issue
20
Publish Date
2013
Start Page
3653
End Page
3661
DOI
10.1002/cncr.28283

A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer

Objective: To determine if there is an advantage to combination chemotherapy and radiation for optimally resected stage IIIC endometrial cancer (EC). Methods: A multicenter retrospective analysis of patients with EC from 1991 to 2008 was conducted. Inclusion criteria were lymph node assessment and optimally resected disease. Recurrence-free (RFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. Results: 265 patients with optimally resected stage IIIC EC were identified. Postoperative therapies included radiotherapy in 17% (n = 45), chemotherapy in 17% (n = 46), and both chemotherapy and radiation in 61% (n = 161). Three-year RFS was 56% for chemotherapy alone, compared to 73% for radiation alone, and 73% for combination therapy (p = 0.12). Those receiving chemotherapy alone had the worst 3-year OS (78%) compared to either radiotherapy alone (95%) or combination therapy (90%) (p = 0.005). After adjustment for stage and grade those treated with chemotherapy alone were at a 2.2 fold increased risk of recurrence (95% CI, 1.2 to 4.2; p = 0.02) and 4.0 fold increased risk of death (95% CI, 1.6 to 10.0; p = 0.004) compared to those treated with chemotherapy and radiation. In contrast there was no significant difference in RFS [HR = 1.0 (95% CI, 0.5 to 2.0; p = 0.92)] or OS [HR = 1.1 (95% CI, 0.3 to 3.6; p = 0.91)] for those treated with radiation alone compared to those treated with chemotherapy and radiation. Conclusion: Adjuvant therapy with either radiation alone or chemotherapy and radiation was associated with improved outcomes for patients with optimally resected stage IIIC EC compared to those treated with chemotherapy only. © 2012 Elsevier B.V.

Authors
Secord, AA; Geller, MA; Broadwater, G; Holloway, R; Shuler, K; Dao, N-Y; Gehrig, PA; O'Malley, DM; Finkler, N; Havrilesky, LJ
MLA Citation
Secord, AA, Geller, MA, Broadwater, G, Holloway, R, Shuler, K, Dao, N-Y, Gehrig, PA, O'Malley, DM, Finkler, N, and Havrilesky, LJ. "A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer." Gynecologic Oncology 128.1 (2013): 65-70.
Source
scival
Published In
Gynecologic Oncology
Volume
128
Issue
1
Publish Date
2013
Start Page
65
End Page
70
DOI
10.1016/j.ygyno.2012.10.010

Image-guided Brachytherapy for Gynecologic Surgeons

Brachytherapy is a fundamental component of the definitive treatment of many advanced gynecologic malignancies, most notably cancers of the uterine corpus and cervix, and allows high radiation doses to be delivered to the target while minimizing the normal tissue dose. However, dose specification has been based primarily on points visible on plain radiographs, with limited correlation to a patient's anatomy and extent of disease. Recent advances have allowed more customized volume-based specification of dose, which has allowed improvements in outcomes. This article reviews these advances using cervical cancer as a model, and looks to future directions with this promising treatment. © 2013 Elsevier Inc. All rights reserved.

Authors
Chino, J; Secord, AA
MLA Citation
Chino, J, and Secord, AA. "Image-guided Brachytherapy for Gynecologic Surgeons." Surgical Oncology Clinics of North America (2013).
PMID
23622076
Source
scival
Published In
Surgical Oncology Clinics of North America
Publish Date
2013
DOI
10.1016/j.soc.2013.02.002

Summary of the 44th Annual Meeting on Women's Cancers

Authors
Secord, AA; Walsh, CS
MLA Citation
Secord, AA, and Walsh, CS. "Summary of the 44th Annual Meeting on Women's Cancers." Gynecologic Oncology 129.2 (2013): 273-276.
PMID
23582582
Source
scival
Published In
Gynecologic Oncology
Volume
129
Issue
2
Publish Date
2013
Start Page
273
End Page
276
DOI
10.1016/j.ygyno.2013.03.028

Image-guided Brachytherapy for Gynecologic Surgeons

Brachytherapy is a fundamental component of the definitive treatment of many advanced gynecologic malignancies, most notably cancers of the uterine corpus and cervix, and allows high radiation doses to be delivered to the target while minimizing the normal tissue dose. However, dose specification has been based primarily on points visible on plain radiographs, with limited correlation to a patient's anatomy and extent of disease. Recent advances have allowed more customized volume-based specification of dose, which has allowed improvements in outcomes. This article reviews these advances using cervical cancer as a model, and looks to future directions with this promising treatment. © 2013 Elsevier Inc.

Authors
Chino, J; Secord, AA
MLA Citation
Chino, J, and Secord, AA. "Image-guided Brachytherapy for Gynecologic Surgeons." Surgical Oncology Clinics of North America 22.3 (2013): 495-509.
Source
scival
Published In
Surgical Oncology Clinics of North America
Volume
22
Issue
3
Publish Date
2013
Start Page
495
End Page
509
DOI
10.1016/j.soc.2013.02.002

Metastatic adenocarcinoma after laparoscopic supracervical hysterectomy with morcellation: A case report

Authors
Turner, T; Secord, AA; Lowery, WJ; Sfakianos, G; Lee, PS
MLA Citation
Turner, T, Secord, AA, Lowery, WJ, Sfakianos, G, and Lee, PS. "Metastatic adenocarcinoma after laparoscopic supracervical hysterectomy with morcellation: A case report." Gynecologic Oncology Case Reports 5 (2013): 19-21.
PMID
24371686
Source
scival
Published In
Gynecologic Oncology Reports
Volume
5
Publish Date
2013
Start Page
19
End Page
21
DOI
10.1016/j.gynor.2013.03.002

Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer

Objectives (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures. Methods A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, > 1 hospitalization in the last 30 days, > 1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤ 3 days. Results One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p = 0.003), > 1 hospitalization in the last 30 days (p < 0.001), ICU admission in the last 30 days (p = 0.005), dying in acute care setting (p = 0.01), admitted to hospice ≤ 3 days (p = 0.02). EOL discussion as outpatient was associated with fewer patients hospitalized > 1 in the last 30 days of life (p < 0.001). Conclusions End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions. © 2013 Elsevier Inc.

Authors
Lopez-Acevedo, M; Havrilesky, LJ; Broadwater, G; Kamal, AH; Abernethy, AP; Berchuck, A; Secord, AA; Tulsky, JA; Valea, F; Lee, PS
MLA Citation
Lopez-Acevedo, M, Havrilesky, LJ, Broadwater, G, Kamal, AH, Abernethy, AP, Berchuck, A, Secord, AA, Tulsky, JA, Valea, F, and Lee, PS. "Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer." Gynecologic Oncology 130.1 (2013): 156-161.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
156
End Page
161
DOI
10.1016/j.ygyno.2013.04.010

A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy

Objectives The efficacy and safety of bevacizumab and docetaxel were evaluated in women who developed recurrent epithelial ovarian, fallopian, or peritoneal cancer within 12 months of platinum-based therapy. Methods Patients received docetaxel (40 mg/m2) on days 1 and 8 and bevacizumab (15 mg/kg) on day 1 of a 21-day cycle. Primary endpoint was 6-month progression-free survival (PFS). Results Forty-one patients were evaluable for PFS and 38 for best response; 46% had platinum-free intervals (PFI) of < 6 months and 54% between 6 and 12 months. The 6-month PFS was 43.9% (95% confidence interval (CI95%) = 28.6-58.2%). Median PFS (months) was 5.2 (CI95% = 4.4-7.2) for all patients, 6.2 (CI95% = 4.1-7.4) for patients with PFI < 6 months, and 5.1 (CI95% = 3.0-7.2) for those with PFI ≥ 6 months. Twenty-two patients showed overall response (CR + PR) (57.9%; CI 95% = 40.8-73.7%), and 32 showed clinical benefit (CR + PR + SD) (84.2%; CI95% = 68.8-94.0%). For those with complete or partial responses, median duration of response was 4.8 months (0.7-14.5). Median overall survival was 12.4 months (CI95% = 10.0-21.9). The most common grade 3/4 adverse events (AEs) were neutropenia (14.6% of patients), followed by leukopenia, fatigue, metabolic, and gastrointestinal, with 66% showing any grade 3/4 toxicity. Most common AEs of any grade were gastrointestinal (93%), fatigue (73%), and pain (73%). Four (10%) patients developed hypertension, 1 a gastrointestinal perforation, and another a colovesicular fistula. Conclusions Bevacizumab and docetaxel administered in patients with recurrent ovarian cancer is an active regimen without new unanticipated toxicities. This combination should be an option for further study or clinical use in recurrent ovarian cancer. © 2013 Elsevier Inc.

Authors
Wenham, RM; Lapolla, J; Lin, H-Y; Apte, SM; Lancaster, JM; Judson, PL; Gonzalez-Bosquet, J; Herschberger, A; Havrilesky, LJ; Secord, AA
MLA Citation
Wenham, RM, Lapolla, J, Lin, H-Y, Apte, SM, Lancaster, JM, Judson, PL, Gonzalez-Bosquet, J, Herschberger, A, Havrilesky, LJ, and Secord, AA. "A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy." Gynecologic Oncology 130.1 (2013): 19-24.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
19
End Page
24
DOI
10.1016/j.ygyno.2013.04.049

Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer

Objective We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix. Methods Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m 2 day 1, topotecan 0.75 mg/m2 days 1, 2 and 3 and bevacizumab 15 mg/kg day 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy. Results Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities. Conclusion The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity. © 2013 Elsevier Inc.

Authors
Zighelboim, I; Wright, JD; Gao, F; Case, AS; Massad, LS; Mutch, DG; Powell, MA; Thaker, PH; Eisenhauer, EL; Cohn, DE; Valea, FA; Secord, AA; Lippmann, LT; Dehdashti, F; Rader, JS
MLA Citation
Zighelboim, I, Wright, JD, Gao, F, Case, AS, Massad, LS, Mutch, DG, Powell, MA, Thaker, PH, Eisenhauer, EL, Cohn, DE, Valea, FA, Secord, AA, Lippmann, LT, Dehdashti, F, and Rader, JS. "Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer." Gynecologic Oncology 130.1 (2013): 64-68.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
64
End Page
68
DOI
10.1016/j.ygyno.2013.04.009

Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer

Objective To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective. Methods A decision model with a 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, and ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (ORs) for potential reductions in hospitalization (OR 0.69), chemotherapy (OR 0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies. Results EPC was associated with a cost savings of $1285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) < $50,000/QALY, unless the cost of outpatient EPC exceeded $2400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER $37,440/QALY. Conclusion Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer. © 2013 Elsevier Inc. All rights reserved.

Authors
Lowery, WJ; Lowery, AW; Barnett, JC; Lopez-Acevedo, M; Lee, PS; Secord, AA; Havrilesky, L
MLA Citation
Lowery, WJ, Lowery, AW, Barnett, JC, Lopez-Acevedo, M, Lee, PS, Secord, AA, and Havrilesky, L. "Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer." Gynecologic Oncology 130.3 (2013): 426-430.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
3
Publish Date
2013
Start Page
426
End Page
430
DOI
10.1016/j.ygyno.2013.06.011

Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels

Purpose: CA-125 has been a valuable marker for detecting ovarian cancer, however, it is not sensitive enough to detect early-stage disease and not specific to ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific to ovarian cancer regardless of CA-125 levels. Methods: Top-down and iTRAQ quantitative proteomics methods were used to identify high-frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers. Results: The proteomics methodologies identified more than 60 potential high-frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high-frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels. Conclusions: Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant to early detection of ovarian cancer. © 2013 Springer-Verlag Berlin Heidelberg.

Authors
Karabudak, AA; Hafner, J; Shetty, V; Chen, S; Secord, AA; Morse, MA; Philip, R
MLA Citation
Karabudak, AA, Hafner, J, Shetty, V, Chen, S, Secord, AA, Morse, MA, and Philip, R. "Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels." Journal of Cancer Research and Clinical Oncology 139.10 (2013): 1757-1770.
Source
scival
Published In
Journal of Cancer Research and Clinical Oncology
Volume
139
Issue
10
Publish Date
2013
Start Page
1757
End Page
1770
DOI
10.1007/s00432-013-1501-6

TP53 Status is Associated with Thrombospondin1 Expression In vitro.

OBJECTIVES: To elucidate the association between thrombospondin1 (THBS1) expression and TP53 status and THBS1 promoter methylation in epithelial ovarian cancer (EOC). METHODS: Epithelial ovarian cancer cell lines with known TP53 status were analyzed for THBS1 gene expression using Affymetrix U133 microarrays and promoter methylation by pyrosequencing. THBS1 mRNA expression was obtained pre- and post-exposure to radiation and hypoxia treatment in A2780 parent wild-type (wt) and mutant (m)TP53 cells. THBS1 expression was compared to tumor growth properties. RESULTS: THBS1 gene expression was higher in cells containing a wtTP53 gene or null TP53 mutation (p = 0.005) and low or absent p53 protein expression (p = 0.008) compared to those harboring a missense TP53 gene mutation and exhibiting high p53 protein expression. Following exposure to radiation, there was a 3.4-fold increase in THBS1 mRNA levels in the mTP53 versus wtTP53 A2780 cells. After exposure to hypoxia, THBS1 mRNA levels increased approximately fourfold in both wtTP53 and mTP53 A2780 cells. Promoter methylation levels were low (median = 8.6%; range = 3.5-88.8%). There was a non-significant inverse correlation between THBS1 methylation and transcript levels. There was no association between THBS1 expression and population doubling time, invasive capacity, or anchorage-independent growth. CONCLUSION: THBS1 expression may be regulated via the TP53 pathway, and induced by hypoxic tumor microenvironment conditions. Overall low levels of THBS1 promoter methylation imply that methylation is not the primary driver of THBS1 expression in EOC.

Authors
Alvarez Secord, A; Bernardini, MQ; Broadwater, G; Grace, LA; Huang, Z; Baba, T; Kondoh, E; Sfakianos, G; Havrilesky, LJ; Murphy, SK
MLA Citation
Alvarez Secord, A, Bernardini, MQ, Broadwater, G, Grace, LA, Huang, Z, Baba, T, Kondoh, E, Sfakianos, G, Havrilesky, LJ, and Murphy, SK. "TP53 Status is Associated with Thrombospondin1 Expression In vitro. (Published online)" Front Oncol 3 (2013): 269-.
PMID
24195060
Source
pubmed
Published In
Frontiers in Oncology
Volume
3
Publish Date
2013
Start Page
269
DOI
10.3389/fonc.2013.00269

Predictors of failure to perform pelvic peritoneal cytology in endometrial cancer staging surgery

Authors
Lopez-Acevedo, M; Zhang, C; Secord, AA; Lee, PS; Havrilesky, LJ; Berchuck, A
MLA Citation
Lopez-Acevedo, M, Zhang, C, Secord, AA, Lee, PS, Havrilesky, LJ, and Berchuck, A. "Predictors of failure to perform pelvic peritoneal cytology in endometrial cancer staging surgery." JOURNAL OF CLINICAL ONCOLOGY 30.34 (December 1, 2012).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
34
Publish Date
2012

Predictors of failure to perform pelvic peritoneal cytology in endometrial cancer staging surgery.

201 Background: The Federation of Gynecology and Obstetrics (FIGO) staging system and the National Comprehensive Cancer Network (NCCN) guidelines for endometrial cancer recommend performing pelvic peritoneal cytology to look for the presence of cancer cells in the peritoneal cavity in patients who are undergoing surgical staging of apparent non-metastatic disease. About 10% of cases have positive cytology and this information is used in formulating plans for adjuvant therapy. However, adherence to the guidelines recommending that cytology be performed is not universal. In this study, we sought to identify factors associated with failure to perform pelvic peritoneal cytology at the time of endometrial cancer staging surgery.We performed a retrospective study of women with FIGO stage I/II endometrial adenocarcinoma who underwent endometrial cancer staging surgery at our institution from 1993-2007. Predictors of failure to perform cytology that were investigated included: surgeon, presence of adhesions, intraoperative blood loss and conversion from laparoscopy to laparotomy.Among 1,112 cases, peritoneal cytology was not performed in 76 (6.8%). In 30 cases cytology was not performed for valid reasons including 15 in which the surgery was performed vaginally, 10 in which the diagnosis of endometrial cancer was not known prior to surgery and 5 in which gross evidence of stage III/IV disease was found at surgery. Of the remaining 46 cases, 11 (23.9%) had surgery that was converted from laparoscopy to laparotomy, 16 (34.8%) had dense pelvic adhesions and 40 (87.0%) had an estimated blood loss greater than 100 ml. The frequency of these and other risk factors will be compared to that seen in a matched cohort of patients who did have pelvic peritoneal cytology performed.Our analysis will investigate predictors of failure to perform pelvic peritoneal cytology. Increased awareness of these factors has the potential to improve compliance with this accepted procedure that plays a role in planning adjuvant therapy for early stage endometrial cancer.

Authors
Zhang, C; Secord, AA; Lee, PS; Havrilesky, LJ; Berchuck, A
MLA Citation
Zhang, C, Secord, AA, Lee, PS, Havrilesky, LJ, and Berchuck, A. "Predictors of failure to perform pelvic peritoneal cytology in endometrial cancer staging surgery." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30.34_suppl (December 2012): 201-.
PMID
28147010
Source
epmc
Published In
Journal of Clinical Oncology
Volume
30
Issue
34_suppl
Publish Date
2012
Start Page
201

A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer.

PURPOSE: We conducted a phase I study of dasatinib, an oral SRC-family tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in the treatment of advanced and recurrent epithelial ovarian cancer. EXPERIMENTAL DESIGN: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included defining toxicity, response rate (RR), pharmacokinetics, and pharmacodynamics. Using a "3+3" design, cohorts of three to six patients received paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) every 3 weeks with escalating doses of dasatinib (100, 120, and 150 mg daily), followed by an eight-patient expansion cohort. RESULTS: Twenty patients were enrolled between June 2007 and December 2009. The median age was 61 years (range: 42-82) with a median of 2 prior regimens (range: 0-6), and 71% had platinum-sensitive disease. There were three to six patients in each cohort, and eight in the expansion cohort. Pharmacokinetics were observed over the first two cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia). Other toxicities in all cycles included neutropenia (95% grade 3-4; 91% in the 150 mg dosing cohort), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 40% [three complete responses, (15%); five partial responses, (25%)],10 patients (50%) had stable disease, and two were not evaluable. The PFS(6-month) actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. CONCLUSIONS: Due to the high incidence of myelosuppression with subsequent cycles, the recommended phase II dose of dasatinib is 150 mg daily in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity.

Authors
Secord, AA; Teoh, DK; Barry, WT; Yu, M; Broadwater, G; Havrilesky, LJ; Lee, PS; Berchuck, A; Lancaster, J; Wenham, RM
MLA Citation
Secord, AA, Teoh, DK, Barry, WT, Yu, M, Broadwater, G, Havrilesky, LJ, Lee, PS, Berchuck, A, Lancaster, J, and Wenham, RM. "A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer." Clin Cancer Res 18.19 (October 1, 2012): 5489-5498.
PMID
22837181
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
19
Publish Date
2012
Start Page
5489
End Page
5498
DOI
10.1158/1078-0432.CCR-12-0507

A multi-institutional cohort study of adjuvant therapy in stage I-II uterine carcinosarcoma.

OBJECTIVE: To evaluate the impact of adjuvant post-operative therapy in women with early stage uterine carcinosarcoma. METHODS: After IRB approval was obtained at all sites, a multi-center retrospective study of women with FIGO stage I-II uterine carcinosarcoma diagnosed from 1997 to 2007 was conducted. Post-operative treatment included observation (OBS), radiation (RT), chemotherapy (CT) alone or with RT (CT+RT). Data analyzed included demographic and pathologic factors, adjuvant therapy outcomes, and time-to-event information. The Kaplan-Meier method was used to estimate time-to-event functions. Cox regression modeling was used to examine the impact of selected covariates on progression free survival (PFS), and overall survival (OS). RESULTS: 111 women were identified: 94 (85%) had stage I and 17 (15%) had stage II uterine carcinosarcoma. Forty-four women (40%) did not receive adjuvant therapy (OBS), 29 (26%) women had adjuvant CT, 23 (20%) women underwent RT and 15 (14%) women underwent RT+CT. Seventy-three patients were alive without disease and 38 had progressed or died at the close of data collection. In multivariate analysis, CT (p=0.003), LVSI (p<0.0001) and a pre-existing cancer (p=0.004) were most predictive of PFS. LVSI was predictive of shortened OS (p=0.01). CONCLUSIONS: In women with FIGO stage I-II uterine carcinosarcoma, adjuvant chemotherapy is associated with improved PFS compared to radiation or observation alone. Ongoing clinical trials will clarify the role of chemotherapy in women with this disease.

Authors
Cantrell, LA; Havrilesky, L; Moore, DT; O'Malley, D; Liotta, M; Secord, AA; Nagel, CI; Cohn, DE; Fader, AN; Wallace, AH; Rose, P; Gehrig, PA
MLA Citation
Cantrell, LA, Havrilesky, L, Moore, DT, O'Malley, D, Liotta, M, Secord, AA, Nagel, CI, Cohn, DE, Fader, AN, Wallace, AH, Rose, P, and Gehrig, PA. "A multi-institutional cohort study of adjuvant therapy in stage I-II uterine carcinosarcoma." Gynecol Oncol 127.1 (October 2012): 22-26.
PMID
22727985
Source
pubmed
Published In
Gynecologic Oncology
Volume
127
Issue
1
Publish Date
2012
Start Page
22
End Page
26
DOI
10.1016/j.ygyno.2012.06.020

Iniparib plus paclitaxel and carboplatin as initial treatment of advanced or recurrent uterine carcinosarcoma: a Gynecologic Oncology Group Study.

OBJECTIVE: To estimate the activity and tolerability of iniparib plus paclitaxel and carboplatin as initial therapy of uterine carcinosarcoma. METHODS: Eligible patients had advanced, persistent or recurrent carcinosarcoma of the uterus, measurable disease and no prior chemotherapy. Patients received paclitaxel 175 mg/m(2) IV over 3h followed by carboplatin area under the curve (AUC)=six over 30 min on day one of 21 day cycles plus iniparib 4 mg/kg IV over 1h twice weekly beginning on day one. Treatment continued until disease progression or adverse effects prohibited further therapy. Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to grade adverse events. The primary endpoint was tumor response. The study was conducted with a 2-stage group sequential design, targeting 20 and 25 patients in each stage. The study was designed to distinguish between 45% versus 65% responding with alpha=10% and 90% power. RESULTS: Twenty-two patients were entered onto the study with five excluded from analysis, leaving 17 evaluable for analysis. Treatment resulted in the expected hematologic and non-hematologic toxicities of the paclitaxel-carboplatin backbone. The observed proportion responding was 23.5% (4/17 patients). The two-sided, 90% confidence interval for the true probability of response was 8.5-46.1%. The required minimal number of responses to proceed to second stage was eight. CONCLUSIONS: Iniparib plus paclitaxel and carboplatin did not show significant activity to warrant further study. The rate of exclusion upon central pathology review (23%) suggests that review of pathology slides for confirmation of eligibility is important in this tumor type.

Authors
Aghajanian, C; Sill, MW; Secord, AA; Powell, MA; Steinhoff, M
MLA Citation
Aghajanian, C, Sill, MW, Secord, AA, Powell, MA, and Steinhoff, M. "Iniparib plus paclitaxel and carboplatin as initial treatment of advanced or recurrent uterine carcinosarcoma: a Gynecologic Oncology Group Study." Gynecol Oncol 126.3 (September 2012): 424-427.
PMID
22634397
Source
pubmed
Published In
Gynecologic Oncology
Volume
126
Issue
3
Publish Date
2012
Start Page
424
End Page
427
DOI
10.1016/j.ygyno.2012.05.024

Physical strain and urgent need for ergonomic training among gynecologic oncologists who perform minimally invasive surgery.

OBJECTIVES: There is limited data regarding physical strain and minimally invasive gynecologic surgery (MIS). We sought to evaluate ergonomic strain among gynecologic oncologists. METHODS: An online survey was sent to all physician members of the Society of Gynecologic Oncology in North America in 2010. The survey contained 42 questions and data was analyzed using univariate and bivariate analyses with summary statistics, t-tests, and chi-squared test. RESULTS: There were 260 respondents (31.2%) to the survey. Case mix was 26% benign and 64% oncologic surgery. Over 52% of respondents had been in practice for greater than 11 years and 52% practice in an academic setting. Physical discomfort related to MIS was reported in 88% (216/244) of surgeons with 52% reporting persistent pain. Increased pain symptoms were associated with surgeon's height, glove size, age and female gender. Patient body mass index (BMI) was associated with pain symptoms in surgeons performing conventional laparoscopic surgery, but not robotic surgery. To decrease pain, surgeons changed positions (78%), limited the number of cases per day (14%), spread cases throughout the week (6%), or limited the total number of cases (3%). Only 29% had received treatment at any time for pain symptoms. Treatment included physical therapy (59%), medical management (28%), surgery (13%), and time off (1%). Only 16% of those with pain symptoms had received formal ergonomic training. CONCLUSION: Physical strain rates of 88% are far greater than previously reported. Such prevalent occupational strain presents a growing problem in the face of increasing demand for MIS.

Authors
Franasiak, J; Ko, EM; Kidd, J; Secord, AA; Bell, M; Boggess, JF; Gehrig, PA
MLA Citation
Franasiak, J, Ko, EM, Kidd, J, Secord, AA, Bell, M, Boggess, JF, and Gehrig, PA. "Physical strain and urgent need for ergonomic training among gynecologic oncologists who perform minimally invasive surgery." Gynecol Oncol 126.3 (September 2012): 437-442.
PMID
22613351
Source
pubmed
Published In
Gynecologic Oncology
Volume
126
Issue
3
Publish Date
2012
Start Page
437
End Page
442
DOI
10.1016/j.ygyno.2012.05.016

Minimally invasive surgery versus laparotomy in women with high grade endometrial cancer: a multi-site study performed at high volume cancer centers.

OBJECTIVE: The study aim was to compare outcomes in women with high-grade endometrial cancer (EC) who underwent surgical staging via minimally invasive surgery (MIS) versus laparotomy. METHODS: This is a retrospective, multi-institutional cohort study of patients with high-grade EC who were comprehensively surgically staged by either MIS or laparotomy. Demographic, surgical variables, complications, and survival were analyzed. RESULTS: Three hundred and eighty-three patients met criteria: 191 underwent laparotomy and 192 MIS (65% robotic, 35% laparoscopy). Subgroups were well matched by age (mean 66 years), stage, body mass index, histology and adjuvant therapies. Median operative time was longer in the MIS group (191 vs. 135 min; p<.001). However, the MIS cohort had a higher mean lymph node count (39.0 vs. 34.0; p=.03), shorter hospital stay (1 vs. 4 days) and significantly fewer complications (8.4% vs. 31.3%; p<.001). There was no significant difference in lymph node count with laparoscopic versus robotic staging. With a median follow-up time of 44 months, progression-free (PFS) and overall survival were not significantly different between the surgical cohorts. On multivariable analysis, stage, treatment were associated with PFS. CONCLUSIONS: Women with high grade endometrial cancers staged by minimally invasive techniques experienced fewer complications and similar survival outcomes compared to those staged by laparotomy. As this population is elderly and most will receive adjuvant therapies, minimization of surgical morbidity is of interest. When managed by expert laparoscopists or robotic surgeons, a high-risk histologic subtype is not a contraindication to minimally invasive surgery in women with apparent early-stage disease.

Authors
Fader, AN; Seamon, LG; Escobar, PF; Frasure, HE; Havrilesky, LA; Zanotti, KM; Secord, AA; Boggess, JF; Cohn, DE; Fowler, JM; Skafianos, G; Rossi, E; Gehrig, PA
MLA Citation
Fader, AN, Seamon, LG, Escobar, PF, Frasure, HE, Havrilesky, LA, Zanotti, KM, Secord, AA, Boggess, JF, Cohn, DE, Fowler, JM, Skafianos, G, Rossi, E, and Gehrig, PA. "Minimally invasive surgery versus laparotomy in women with high grade endometrial cancer: a multi-site study performed at high volume cancer centers." Gynecol Oncol 126.2 (August 2012): 180-185.
PMID
22555102
Source
pubmed
Published In
Gynecologic Oncology
Volume
126
Issue
2
Publish Date
2012
Start Page
180
End Page
185
DOI
10.1016/j.ygyno.2012.04.028

Obesity: Too big a problem to ignore.

Authors
Secord, AA; Gehrig, PA
MLA Citation
Secord, AA, and Gehrig, PA. "Obesity: Too big a problem to ignore." Gynecol Oncol 126.2 (August 2012): 274-276.
PMID
22555101
Source
pubmed
Published In
Gynecologic Oncology
Volume
126
Issue
2
Publish Date
2012
Start Page
274
End Page
276
DOI
10.1016/j.ygyno.2012.04.033

A multicenter, randomized, phase 2 clinical trial to evaluate the efficacy and safety of combination docetaxel and carboplatin and sequential therapy with docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer.

BACKGROUND: The aim of this randomized clinical trial was to evaluate the efficacy and safety of combination (cDC) and sequential (sDC) weekly docetaxel and carboplatin in women with recurrent platinum-sensitive epithelial ovarian cancer (EOC). METHODS: Participants were randomized to either weekly docetaxel 30 mg/m(2) on days 1 and 8 and carboplatin area under the curve (AUC) = 6 on day 1, every 3 weeks or docetaxel 30 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles followed by carboplatin AUC = 6 on day 1, every 3 weeks for 6 cycles or until disease progression. The primary endpoint was measurable progression-free survival (PFS). RESULTS: Between January 2004 and March 2007, 150 participants were enrolled. The response rate was 55.4% and 43.2% for those treated with cDC and sDC, respectively. The median PFS was 13.7 months (95% confidence interval [CI], 9.9-16.8) for cDC and 8.4 months (95% CI, 7.1-11.0) for sDC. On the basis of an exploratory analysis, patients treated with sDC were at a 62% increased risk of disease progression compared to those treated with cDC (hazard ratio = 1.62; 95% CI, 1.08-2.45; P = .02). The median overall survival time was similar in both groups (33.2 and 30.1 months, P = .2). The incidence of grade 2 or 3 neurotoxicity and grade 3 or 4 neutropenia was higher with cDC than with sDC (11.7% vs 8.5%; 36.8% vs 11.3%). The sDC group demonstrated significant improvements in the Functional Assessment for Cancer Therapy-Ovarian, Quality of Life Trial Outcome Index scores compared with the combination cohort (P = .013). CONCLUSIONS: Both cDC and sDC regimens have activity in recurrent platinum-sensitive EOC with acceptable toxicity profiles. The cDC regimen may provide a PFS advantage over sDC.

Authors
Alvarez Secord, A; Berchuck, A; Higgins, RV; Nycum, LR; Kohler, MF; Puls, LE; Holloway, RW; Lewandowski, GS; Valea, FA; Havrilesky, LJ
MLA Citation
Alvarez Secord, A, Berchuck, A, Higgins, RV, Nycum, LR, Kohler, MF, Puls, LE, Holloway, RW, Lewandowski, GS, Valea, FA, and Havrilesky, LJ. "A multicenter, randomized, phase 2 clinical trial to evaluate the efficacy and safety of combination docetaxel and carboplatin and sequential therapy with docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer." Cancer 118.13 (July 1, 2012): 3283-3293.
PMID
22072307
Source
pubmed
Published In
Cancer
Volume
118
Issue
13
Publish Date
2012
Start Page
3283
End Page
3293
DOI
10.1002/cncr.26610

Surgical staging for endometrial cancer in the elderly - is there a role for lymphadenectomy?

OBJECTIVES: We sought to evaluate the effect of systematic lymphadenectomy (LND) on endometrial cancer-specific survival in an elderly population. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2006. Women who underwent primary hysterectomy for non-serous, non-clear cell endometrial carcinoma were included. Women were stratified by age (<70, 70-79, and ≥ 80) and disease-specific survival (DSS) was analyzed via the Kaplan-Meier method and stratified by postoperative grade. Cohorts were compared using the log-rank test. In a simulated population, the disease-specific survival of women with pre-operative grade 1 endometrial carcinoma was calculated using a weighted average survival accounting for those upgraded at final pathology. RESULTS: Endometrial cancer was identified in 5759 women ≥ 80 years old. Disease specific survival at 5 years for the LND and no LND groups was 93.4% and 94.5% (p=0.36) for grade 1, 84.4% and 85% (p=0.97) for grade 2, and 65.9% and 60.9% (p=0.002) for grade 3. In the simulated pre-operative grade 1 group, 5 year disease-specific survival (DSS) was 91% in the LND group and 92% in the no LND group. CONCLUSION: In women older than 80, systematic lymphadenectomy is associated with improved DSS for high grade, but similar DSS for low grade endometrial cancer, consistent with what is seen with younger women. As there is no clear survival benefit to lymphadenectomy in elderly women presenting with low grade disease, the surgeon should carefully weigh the surgical risks and benefits in this patient population, which may be at higher risk for morbidity.

Authors
Lowery, WJ; Gehrig, PA; Ko, E; Secord, AA; Chino, J; Havrilesky, LJ
MLA Citation
Lowery, WJ, Gehrig, PA, Ko, E, Secord, AA, Chino, J, and Havrilesky, LJ. "Surgical staging for endometrial cancer in the elderly - is there a role for lymphadenectomy?." Gynecol Oncol 126.1 (July 2012): 12-15.
PMID
22588178
Source
pubmed
Published In
Gynecologic Oncology
Volume
126
Issue
1
Publish Date
2012
Start Page
12
End Page
15
DOI
10.1016/j.ygyno.2012.05.003

A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors.

PURPOSE: Preclinical data suggest concurrent inhibition of VEGF, mTOR and EGFR pathways may augment antitumor and antiangiogenic effects compared to inhibition of each pathway alone. This study evaluated the maximum tolerated dose/recommended phase II dose and safety and tolerability of bevacizumab, everolimus and panitumumab drug combination. METHODS: Subjects with advanced solid tumors received escalating doses of everolimus and flat dosing of panitumumab at 4.8 mg/kg and bevacizumab at 10 mg/kg every 2 weeks. Dose-limiting toxicities (DLTs) were assessed in cycle 1; toxicity evaluation was closely monitored throughout treatment. Treatment continued until disease progression or undesirable toxicity. RESULTS: Thirty-two subjects were evaluable for toxicity; 31 subjects were evaluable for tumor response. DLTs were observed in cohorts with everolimus at 10 and 5 mg daily and included grade 3 mucositis, skin rash and thrombocytopenia. Therefore, everolimus was dose-reduced to 5 mg three times weekly, which improved the tolerability of the treatment regimen. Common adverse events were skin rash/pruritus (91 %), mucositis/stomatitis (75 %), hypomagnesemia (72 %), hypocalcemia (56 %) and hypokalemia (50 %). There were 3 partial responses; an additional 10 subjects had stable disease ≥6 months. Three subjects with ovarian cancer and one with endometrial cancer achieved prolonged disease control ranging from 11 to >40 months. CONCLUSIONS: The recommended phase II dose is everolimus at 5 mg three times weekly plus panitumumab at 4.8 mg/kg and bevacizumab at 10 mg/kg every 2 weeks. This dosing regimen has an acceptable safety and tolerability profile and appears to have moderate the clinical activity in refractory tumors.

Authors
Vlahovic, G; Meadows, KL; Uronis, HE; Morse, MA; Blobe, GC; Riedel, RF; Zafar, SY; Alvarez-Secord, A; Gockerman, J; Starodub, AN; Ready, NE; Anderson, EL; Bendell, JC; Hurwitz, HI
MLA Citation
Vlahovic, G, Meadows, KL, Uronis, HE, Morse, MA, Blobe, GC, Riedel, RF, Zafar, SY, Alvarez-Secord, A, Gockerman, J, Starodub, AN, Ready, NE, Anderson, EL, Bendell, JC, and Hurwitz, HI. "A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors." Cancer Chemother Pharmacol 70.1 (July 2012): 95-102.
PMID
22638798
Source
pubmed
Published In
Cancer Chemotherapy and Pharmacology
Volume
70
Issue
1
Publish Date
2012
Start Page
95
End Page
102
DOI
10.1007/s00280-012-1889-8

Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer.

OBJECTIVE: To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy. METHODS: Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC]<500/mm(3)) and febrile neutropenia (FN; ANC<1000/mm(3) and temperature>38.1°C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression. RESULTS: Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area<2.0m(2) (p=0.03), body mass index (BMI)<30 kg/m(2) (p<0.01), Caucasian race (p<0.01), treatment on research protocols (p<0.01), non-carboplatin-containing regimens (p<0.01), and planned relative dose intensity (RDI)>85% of standard (p=0.02). Women over age 60 were more likely to develop FN (p=0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p<0.01), Caucasian race (HR 2.13; p=0.01), and planned RDI>85% (HR 1.69; p=0.05); predictors of FN were age>60 (HR 2.84; p=0.05) and non-carboplatin containing regimens (HR 4.06; p<0.01). CONCLUSION: While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.

Authors
Laskey, RA; Poniewierski, MS; Lopez, MA; Hanna, RK; Secord, AA; Gehrig, PA; Lyman, GH; Havrilesky, LJ
MLA Citation
Laskey, RA, Poniewierski, MS, Lopez, MA, Hanna, RK, Secord, AA, Gehrig, PA, Lyman, GH, and Havrilesky, LJ. "Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer." Gynecol Oncol 125.3 (June 2012): 625-630.
PMID
22426251
Source
pubmed
Published In
Gynecologic Oncology
Volume
125
Issue
3
Publish Date
2012
Start Page
625
End Page
630
DOI
10.1016/j.ygyno.2012.03.015

Phase II trial of topotecan, cisplatin, and bevacizumab for recurrent or persistent cervical cancer

Authors
Zighelboim, I; Wright, JD; Gao, F; Case, AS; Massad, LS; Mutch, DG; Powell, MA; Thaker, PH; Eisenhauer, EL; Cohn, DE; Valea, FA; Secord, AA; Lippmann, LT; Rader, JS
MLA Citation
Zighelboim, I, Wright, JD, Gao, F, Case, AS, Massad, LS, Mutch, DG, Powell, MA, Thaker, PH, Eisenhauer, EL, Cohn, DE, Valea, FA, Secord, AA, Lippmann, LT, and Rader, JS. "Phase II trial of topotecan, cisplatin, and bevacizumab for recurrent or persistent cervical cancer." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

The influence of radiation modality and lymph node dissection on survival in early-stage endometrial cancer.

BACKGROUND: The appropriate uses of lymph node dissection (LND) and adjuvant radiation therapy (RT) for Stage I endometrial cancer are controversial. We explored the impact of specific RT modalities (whole pelvic RT [WPRT], vaginal brachytherapy [VB]) and LND status on survival. MATERIALS AND METHODS: The Surveillance Epidemiology and End Results dataset was queried for all surgically treated International Federation of Gynecology and Obstetrics (FIGO) Stage I endometrial cancers; subjects were stratified into low, intermediate and high risk cohorts using modifications of Gynecologic Oncology Group (GOG) protocol 99 and PORTEC (Postoperative Radiation Therapy in Endometrial Cancer) trial criteria. Five-year overall survival was estimated, and comparisons were performed via the log-rank test. RESULTS: A total of 56,360 patients were identified: 70.4% low, 26.2% intermediate, and 3.4% high risk. A total of 41.6% underwent LND and 17.6% adjuvant RT. In low-risk disease, LND was associated with higher survival (93.7 LND vs. 92.7% no LND, p < 0.001), whereas RT was not (91.6% RT vs. 92.9% no RT, p = 0.23). In intermediate-risk disease, LND (82.1% LND vs. 76.5% no LND, p < 0.001) and RT (80.6% RT vs. 74.9% no RT, p < 0.001) were associated with higher survival without differences between RT modalities. In high-risk disease, LND (68.8% LND vs. 54.1% no LND, p < 0.001) and RT (66.9% RT vs. 57.2% no RT, p < 0.001) were associated with increased survival; if LND was not performed, VB alone was inferior to WPRT (p = 0.01). CONCLUSION: Both WPRT and VB alone are associated with increased survival in the intermediate-risk group. In the high-risk group, in the absence of LND, only WPRT is associated with increased survival. LND was also associated with increased survival.

Authors
Chino, JP; Jones, E; Berchuck, A; Secord, AA; Havrilesky, LJ
MLA Citation
Chino, JP, Jones, E, Berchuck, A, Secord, AA, and Havrilesky, LJ. "The influence of radiation modality and lymph node dissection on survival in early-stage endometrial cancer." Int J Radiat Oncol Biol Phys 82.5 (April 1, 2012): 1872-1879.
PMID
21640502
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
82
Issue
5
Publish Date
2012
Start Page
1872
End Page
1879
DOI
10.1016/j.ijrobp.2011.03.054

Minimally invasive surgery for endometrial cancer: the horse is already out of the barn.

Authors
Berchuck, A; Secord, AA; Havrilesky, LJ
MLA Citation
Berchuck, A, Secord, AA, and Havrilesky, LJ. "Minimally invasive surgery for endometrial cancer: the horse is already out of the barn." J Clin Oncol 30.7 (March 1, 2012): 681-682.
PMID
22291090
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
30
Issue
7
Publish Date
2012
Start Page
681
End Page
682
DOI
10.1200/JCO.2011.40.5506

Antiangiogenic agents in combination with chemotherapy for the treatment of epithelial ovarian cancer.

OBJECTIVE: The purpose of this review was to provide an overview of angiogenesis, including the rationale for targeting angiogenesis as a treatment strategy for epithelial ovarian cancer (EOC) and to discuss available clinical trial data with antiangiogenic agents in EOC, with a focus on combinations with chemotherapy. METHODS: This was a literature review of clinical studies evaluating select antiangiogenic agents in combination with traditional cytotoxic chemotherapy for the treatment of EOC. RESULTS: Several therapies that target angiogenesis-specific pathways are undergoing clinical development for EOC. Although some of these agents have demonstrated single-agent activity for EOC, there is considerable interest in combining this treatment strategy with chemotherapy in an effort to potentially improve treatment benefits in this patient population. Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, is the most studied antiangiogenic agent in EOC and has shown efficacy as monotherapy and combined with chemotherapy in both the relapsed/recurrent and first-line settings. However, results from recent phase 3 trials raise questions regarding patient selection and optimal dose, schedule, and duration of bevacizumab therapy. Other agents in various phases of testing include aflibercept (VEGF Trap), a fusion protein that binds all isoforms of VEGF; multitargeted antiangiogenic tyrosine kinase inhibitors (eg, BIBF 1120, cediranib, pazopanib, sorafenib); and AMG 386, a selective angiopoietin inhibitor. Toxicities associated with VEGF inhibition are also a concern with antiangiogenic therapy, including hypertension, proteinuria, thromboses, and gastrointestinal perforation. CONCLUSIONS: Results from recently completed and ongoing clinical trials combining antiangiogenic agents with chemotherapy are awaited in hopes of expanding therapeutic options for patients with EOC.

Authors
Teoh, D; Secord, AA
MLA Citation
Teoh, D, and Secord, AA. "Antiangiogenic agents in combination with chemotherapy for the treatment of epithelial ovarian cancer." Int J Gynecol Cancer 22.3 (March 2012): 348-359. (Review)
PMID
22266932
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
22
Issue
3
Publish Date
2012
Start Page
348
End Page
359
DOI
10.1097/IGC.0b013e31823c6efd

Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of platinum-sensitive, recurrent ovarian cancer.

BACKGROUND: In a randomized controlled trial (RCT) of patients with recurrent, platinum-sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. METHODS: An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. RESULTS: The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations. CONCLUSIONS: Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with platinum-sensitive ovarian cancer, even when accounting for slightly lower QoL during treatment.

Authors
Havrilesky, LJ; Pokrzywinski, R; Revicki, D; Higgins, RV; Nycum, LR; Kohler, MF; Berchuck, A; Myers, ER; Secord, AA
MLA Citation
Havrilesky, LJ, Pokrzywinski, R, Revicki, D, Higgins, RV, Nycum, LR, Kohler, MF, Berchuck, A, Myers, ER, and Secord, AA. "Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of platinum-sensitive, recurrent ovarian cancer." Cancer 118.2 (January 15, 2012): 386-391.
PMID
21598242
Source
pubmed
Published In
Cancer
Volume
118
Issue
2
Publish Date
2012
Start Page
386
End Page
391
DOI
10.1002/cncr.26199

Quinary debulking for epithelial ovarian cancer.

We report a case of optimal quinary debulking for recurrent papillary serous carcinoma of the ovary involving the liver parenchyma through the full thickness of the diaphragm into the lung parenchyma. Multiple debulking procedures for ovarian cancer are controversial, especially when there is extensive upper abdominal or thoracic disease. Selection criteria for such extensive surgery include: good functional status, long disease-free interval, and absence of other systemic disease. Our patient tolerated her procedure well without evidence of residual disease over 6 months postoperatively.

Authors
Edwards, JM; Lowery, WJ; Secord, AA
MLA Citation
Edwards, JM, Lowery, WJ, and Secord, AA. "Quinary debulking for epithelial ovarian cancer." Journal of surgical case reports 2012.7 (January 2012): 7-.
PMID
24960732
Source
epmc
Published In
Journal of Surgical Case Reports
Volume
2012
Issue
7
Publish Date
2012
Start Page
7
DOI
10.1093/jscr/2012.7.7

Surgical staging for endometrial cancer in the elderly - Is there a role for lymphadenectomy?

Authors
Lowery, WJ; Gehrig, PA; Ko, E; Secord, AA; Chino, J; Havrilesky, LJ
MLA Citation
Lowery, WJ, Gehrig, PA, Ko, E, Secord, AA, Chino, J, and Havrilesky, LJ. "Surgical staging for endometrial cancer in the elderly - Is there a role for lymphadenectomy?." Obstetrical and Gynecological Survey 67.11 (2012): 702-703.
Source
scival
Published In
Obstetrical and Gynecological Survey
Volume
67
Issue
11
Publish Date
2012
Start Page
702
End Page
703
DOI
10.1097/OGX.0b013e31827681f1

Health-related quality of life outcomes of docetaxel/carboplatin combination therapy vs. sequential therapy with docetaxel then carboplatin in patients with relapsed, platinum-sensitive ovarian cancer: results from a randomized clinical trial.

OBJECTIVES: A phase II clinical trial compared docetaxel in combination with carboplatin to sequential single agent docetaxel followed by carboplatin for treatment of recurrent platinum-sensitive ovarian, peritoneal, or tubal cancer. This manuscript reports prospectively collected health-related quality of life (HRQL). METHODS: Participants were randomized to either weekly docetaxel 30 mg/m(2)/days 1 and 8 and carboplatin AUC 6/day 1 every 3 weeks (cDC) or docetaxel 30 mg/m(2)/days 1 and 8, repeated every 3 weeks for 6 cycles followed by carboplatin AUC 6/day 1 every 3 weeks for 6 cycles or until disease progression (sDC). The primary HRQL endpoint was the trial outcome index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, and was assessed as an intent-to-treat analysis. The secondary HRQL endpoints included the FACT-O total score, the FACT-General, and several domain scores of the FACT-O instrument (physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and the ovarian cancer specific (OCS) module). The FACT-O was administered at randomization, prior to each of 6 cycles of treatment, and at study endpoint. RESULTS: One hundred forty-eight participants were randomized to each group. Sequential docetaxel followed by carboplatin (sDC) was associated with significant improvements in the FACT-O TOI (p=0.013), FACT-O total score (p=0.033), and OCS (p=0.029) compared to the combination docetaxel and carboplatin group (cDC). CONCLUSIONS: Sequential single agent docetaxel followed by carboplatin is associated with improved HRQL when compared to cDC. The improved progression-free survival observed with cDC should be weighed against lower quality of life during treatment.

Authors
Pokrzywinski, R; Secord, AA; Havrilesky, LJ; Puls, LE; Holloway, RW; Lewandowski, GS; Higgins, RV; Nycum, LR; Kohler, MF; Revicki, DA
MLA Citation
Pokrzywinski, R, Secord, AA, Havrilesky, LJ, Puls, LE, Holloway, RW, Lewandowski, GS, Higgins, RV, Nycum, LR, Kohler, MF, and Revicki, DA. "Health-related quality of life outcomes of docetaxel/carboplatin combination therapy vs. sequential therapy with docetaxel then carboplatin in patients with relapsed, platinum-sensitive ovarian cancer: results from a randomized clinical trial." Gynecol Oncol 123.3 (December 2011): 505-510.
PMID
21945310
Source
pubmed
Published In
Gynecologic Oncology
Volume
123
Issue
3
Publish Date
2011
Start Page
505
End Page
510
DOI
10.1016/j.ygyno.2011.08.015

The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study.

OBJECTIVES: To elucidate the regulation of MASPIN expression in epithelial ovarian cancer (EOC) and associations with p53 status and MASPIN promoter methylation. METHODS: Seven EOC cell lines and 110 advanced stage EOC specimens were analyzed for MASPIN promoter methylation. The cell lines were treated with 5-azacytidine (5-azaC) and evaluated for MASPIN promoter methylation, protein, and mRNA expression. Wild-type (wt) p53 was transiently transfected into the mutant p53 (m p53) SKOV3 cells which were treated with 5-azaC. Phosphor imager analysis quantified the percent methylation of the MASPIN promoter. RESULTS: Of the 3 MASPIN-low m p53 cell lines 2 had greater than 5% MASPIN methylation whereas only 1 of 4 MASPIN-high wt p53 cell lines had greater than 5% MASPIN methylation. Despite the presence of aberrant MASPIN promoter methylation in SKOV3 cells, wt p53-transfection alone resulted in a 3.3-fold increase in MASPIN mRNA. The combination of 5-azaC and wt p53-transfection produced a 36% reduction in MASPIN promoter methylation and 4.5-fold increase in MASPIN transcription. Among the 110 ovarian cancer specimens analyzed for methylation of the MASPIN promoter, 81.8% were weakly methylated, 14.5% were heavily methylated and 3.6% were fully methylated. There was no relationship between promoter methylation and p53 status or MASPIN protein expression. However, MASPIN protein was 6 times more likely to be detected in cancer specimens that harbor a p53 mutation relative to cancer specimens with a wt p53 gene. CONCLUSION: The regulation of MASPIN is a complex multifactorial process that may be controlled by both p53-dependent and -independent epigenetic mechanisms.

Authors
Alvarez Secord, A; Darcy, KM; Hutson, A; Huang, Z; Lee, PS; Jewell, EL; Havrilesky, LJ; Markman, M; Muggia, F; Murphy, SK
MLA Citation
Alvarez Secord, A, Darcy, KM, Hutson, A, Huang, Z, Lee, PS, Jewell, EL, Havrilesky, LJ, Markman, M, Muggia, F, and Murphy, SK. "The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study." Gynecol Oncol 123.2 (November 2011): 314-319.
PMID
21903246
Source
pubmed
Published In
Gynecologic Oncology
Volume
123
Issue
2
Publish Date
2011
Start Page
314
End Page
319
DOI
10.1016/j.ygyno.2011.08.003

Retrospective review of an intraoperative algorithm to predict lymph node metastasis in low-grade endometrial adenocarcinoma.

OBJECTIVE: To validate the Mayo algorithm to intraoperatively identify women with endometrial cancer in whom lymphadenectomy may be safely omitted. METHODS: A multi-center retrospective chart review 1977-2010 was completed using two independent institutional endometrial cancer databases. Eligibility criteria were grade 1 or 2 endometrial carcinoma, low-risk histology, and myometrial invasion ≤ 50% on intraoperative pathology consultation; patients were considered to satisfy the Mayo criteria if, in addition to these, tumor diameter on the final pathology report was ≤ 2 cm. Analysis of nodal metastases, recurrent disease, and progression-free survival (PFS) using the Kaplan-Meier method was performed. RESULTS: Six hundred and two patients met inclusion criteria for the study. Of 110 patients satisfying the Mayo algorithm with an adequate lymphadenectomy, 2 (1.8%) were diagnosed with lymph node metastasis and 4 (3.6%) subsequently developed recurrent disease. The Mayo algorithm identified with a 98.2% negative predictive value women who would not benefit from a lymphadenectomy. There was no significant difference in recurrence rate or PFS between women who underwent lymphadenectomy and those who did not when the Mayo algorithm was satisfied. CONCLUSIONS: The Mayo algorithm intraoperatively identifies tumor characteristics of low-risk disease in endometrial carcinoma that predict a very low likelihood of nodal metastasis and recurrence. Although a small number of patients with advanced stage disease may be missed when applying the Mayo criteria, there is no apparent survival benefit to lymphadenectomy for patients satisfying this algorithm, and these data support its use at other institutions.

Authors
Convery, PA; Cantrell, LA; Di Santo, N; Broadwater, G; Modesitt, SC; Secord, AA; Havrilesky, LJ
MLA Citation
Convery, PA, Cantrell, LA, Di Santo, N, Broadwater, G, Modesitt, SC, Secord, AA, and Havrilesky, LJ. "Retrospective review of an intraoperative algorithm to predict lymph node metastasis in low-grade endometrial adenocarcinoma." Gynecol Oncol 123.1 (October 2011): 65-70.
PMID
21742369
Source
pubmed
Published In
Gynecologic Oncology
Volume
123
Issue
1
Publish Date
2011
Start Page
65
End Page
70
DOI
10.1016/j.ygyno.2011.06.025

Cost comparison of strategies for the management of venous thromboembolic event risk following laparotomy for ovarian cancer.

OBJECTIVE: To evaluate the costs and effectiveness of thromboprophylaxis strategies following laparotomy for ovarian cancer. METHODS: We constructed a decision model to evaluate six strategies for management of postoperative venous thromboembolism (VTE) risk: (1) no thromboprophylaxis; (2) inpatient sequential compression device (SCD); (3) inpatient unfractionated heparin (UFH) 5000 units TID; (4) inpatient low molecular weight heparin (LMWH) 40 mg daily; (5) UFH 5000 units TID×1 month; (6) LMWH 40 mg daily×1 month. Rates of VTE, heparin-induced thrombocytopenia, and significant bleeding for each strategy were obtained from published literature. Costs were based on institutional charges or obtained from the Agency for Healthcare Research and Quality Nationwide Inpatient Sample database for 2008 and average wholesale pricing. Sensitivity analyses were performed to account for uncertainty in estimates. RESULTS: In the base case, UFH×1 month was the least expensive (mean cost $1611) and most effective (VTE risk 1.9%) strategy. LMWH×1 month was equally effective but more expensive ($2197). Inpatient UFH, inpatient LMWH, and SCDs were less effective and more expensive than UFH×1 month. In the sensitivity analysis, cost rankings remained unchanged unless the baseline probability of VTE was assumed <6.5%, the cost of VTE treatment was <$20,000, or the cost of bleeding was >$4500. LMWH×1 month became least expensive when cost was decreased 38%. CONCLUSION: Based on current evidence, extended prophylaxis with UFH is the least expensive and most effective strategy to prevent postoperative VTE following laparotomy for ovarian cancer.

Authors
Teoh, D; Berchuck, A; Alvarez Secord, A; Lee, PS; Lowery, WJ; Sfakianos, GP; Valea, FA; Myers, ER; Havrilesky, LJ
MLA Citation
Teoh, D, Berchuck, A, Alvarez Secord, A, Lee, PS, Lowery, WJ, Sfakianos, GP, Valea, FA, Myers, ER, and Havrilesky, LJ. "Cost comparison of strategies for the management of venous thromboembolic event risk following laparotomy for ovarian cancer." Gynecol Oncol 122.3 (September 2011): 467-472.
PMID
21752434
Source
pubmed
Published In
Gynecologic Oncology
Volume
122
Issue
3
Publish Date
2011
Start Page
467
End Page
472
DOI
10.1016/j.ygyno.2011.06.014

Adverse events associated with laparoscopy vs laparotomy in the treatment of endometrial cancer.

OBJECTIVE: The objective of the study was to compare adverse event rates between laparoscopic vs open surgery for endometrial cancer. STUDY DESIGN: This was a retrospective cohort study comparing 107 women who underwent laparoscopy with 269 age- and body mass index-matched women who underwent laparotomy for treatment of endometrial cancer. RESULTS: Adverse event rates were similar between cohorts (37% laparoscopy vs 43% laparotomy, P=.248). Laparotomies had higher rates of cellulitis (16% vs 7%, P=.018) and open wound infection (9% vs 2%, P=.02), whereas laparoscopy had higher rates of sensory peripheral nerve deficit (5% vs 0%, P=.008) and lymphedema (7% vs 1%, P=.003). Laparoscopy was associated with longer mean operating room times but with shorter hospital stays and lower mean blood loss. CONCLUSION: Laparoscopy was associated with decreased rates of surgical site infections but had an increased risk of peripheral sensory nerve deficits and lymphedema when compared with laparotomy.

Authors
Barnett, JC; Havrilesky, LJ; Bondurant, AE; Fleming, ND; Lee, PS; Secord, AA; Berchuck, A; Valea, FA
MLA Citation
Barnett, JC, Havrilesky, LJ, Bondurant, AE, Fleming, ND, Lee, PS, Secord, AA, Berchuck, A, and Valea, FA. "Adverse events associated with laparoscopy vs laparotomy in the treatment of endometrial cancer." Am J Obstet Gynecol 205.2 (August 2011): 143.e1-143.e6.
PMID
21514921
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
205
Issue
2
Publish Date
2011
Start Page
143.e1
End Page
143.e6
DOI
10.1016/j.ajog.2011.03.012

Relationship between relative dose intensity and mortality in women receiving combination chemotherapy for stage III-IV epithelial ovarian cancer.

Authors
Havrilesky, LJ; Hanna, RK; Poniewierski, MS; Laskey, R; Secord, AA; Gehrig, PA; Lopez, MA; Shafer, A; Van Le, L; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Havrilesky, LJ, Hanna, RK, Poniewierski, MS, Laskey, R, Secord, AA, Gehrig, PA, Lopez, MA, Shafer, A, Van Le, L, Dale, DC, Crawford, J, and Lyman, GH. "Relationship between relative dose intensity and mortality in women receiving combination chemotherapy for stage III-IV epithelial ovarian cancer." May 20, 2011.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
15
Publish Date
2011

MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.

PURPOSE: The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans. EXPERIMENTAL DESIGN: Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancer-associated peptides were used to activate naive T cells to generate antigen-specific T cells that could recognize ovarian and breast cancers in vitro. Combinations of these peptides (0.3 mg of each peptide or 1 mg of each peptide) were formulated into vaccines in conjunction with Montanide ISA-51 and granulocyte monocyte colony stimulating factor which were used to vaccinate patients with ovarian and breast cancer without evidence of clinical disease in parallel pilot clinical trials. RESULTS: T cells specific for individual peptides could be generated in vitro by using mixtures of peptides, and these T cells recognized ovarian and breast cancers but not nonmalignant cells. Patient vaccinations were well tolerated with the exception of local erythema and induration at the injection site. Nine of the 14 vaccinated patients responded immunologically to their vaccine by inducing peptide-specific T-cell responses that were capable of recognizing HLA-matched breast and ovarian cancer cells. CONCLUSION: Mixtures of specific peptides identified as naturally presented on cancer cells and capable of activating tumor-specific T cells in vitro also initiate or augment immune responses toward solid tumors in cancer patients.

Authors
Morse, MA; Secord, AA; Blackwell, K; Hobeika, AC; Sinnathamby, G; Osada, T; Hafner, J; Philip, M; Clay, TM; Lyerly, HK; Philip, R
MLA Citation
Morse, MA, Secord, AA, Blackwell, K, Hobeika, AC, Sinnathamby, G, Osada, T, Hafner, J, Philip, M, Clay, TM, Lyerly, HK, and Philip, R. "MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer." Clin Cancer Res 17.10 (May 15, 2011): 3408-3419.
PMID
21300761
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
10
Publish Date
2011
Start Page
3408
End Page
3419
DOI
10.1158/1078-0432.CCR-10-2614

Relationship between relative dose intensity and mortality in women receiving combination chemotherapy for stage III-IV epithelial ovarian cancer.

5084 Background: Although considerable progress has been made in the treatment of advanced ovarian cancer, complications of both disease and treatment limit long term survival. Further research is needed on specific patient- and treatment-related factors that are associated with increased mortality in this population.A multicenter retrospective study of women with surgical FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy between 1995 and 2008 was conducted. Data were obtained from each institution's tumor registry and medical records to include the first four cycles of chemotherapy administered. Outcomes included: (1) Chemotherapy relative dose intensity (RDI), defined as actual delivered dose intensity over the course of chemotherapy in comparison with standard ovarian cancer regimens based on literature review; (2) Overall survival. Survival estimates were based on the method of Kaplan and Meier and multivariate analysis was based on the proportion hazards regression method of Cox.Evaluable patients included 327 women with stage III or IV ovarian cancer. With median followup of 26 months (range, 1-170), progression or recurrence was noted in 246 patients (74.3%) and death was recorded in 180 (54.4%). Median time to recurrence or progression was 18 months while median time to death was 48 months. Factors associated with overall survival included disease stage, baseline CA 125 and chemotherapy RDI. In multivariate regression analysis, the following factors were independently associated with overall survival: Noncaucasian race (HR=1.46; P=0.045); Stage IV (HR=1.38; P=0.035); Elevated baseline CA 125 (HR=2.41; P=0.007) and RDI <85% (HR=1.52; P=0.011). Age, type of treatment and comorbidities did not appear to influence overall survival after adjustment for the above prognostic factors.Women who receive reduced relative dose intensity of primary chemotherapy for ovarian cancer have lower survival even after adjustment for race, stage and baseline CA-125. These data suggest that women with ovarian cancer should be treated with target RDI whenever possible.

Authors
Havrilesky, LJ; Hanna, RK; Poniewierski, MS; Laskey, R; Secord, AA; Gehrig, PA; Lopez, MA; Shafer, A; Van Le, L; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Havrilesky, LJ, Hanna, RK, Poniewierski, MS, Laskey, R, Secord, AA, Gehrig, PA, Lopez, MA, Shafer, A, Van Le, L, Dale, DC, Crawford, J, and Lyman, GH. "Relationship between relative dose intensity and mortality in women receiving combination chemotherapy for stage III-IV epithelial ovarian cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.15_suppl (May 2011): 5084-.
PMID
28023655
Source
epmc
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
5084

Dasatinib (BMS-35482) has synergistic activity with paclitaxel and carboplatin in ovarian cancer cells.

PURPOSE: To explore the activity of dasatinib alone and in combination with paclitaxel and carboplatin in ovarian cancer cells and to determine if dasatinib activity can be predicted based on evaluation of the SRC pathway. EXPERIMENTAL DESIGN: Microarray analysis was performed for IGROV1, OVCAR3, A2780 and SKOV3 ovarian cancer cells and the status of the genomic SRC signature pathway was determined. Cells were treated with carboplatin, paclitaxel and dasatinib individually and in combination. Pre- and post-treatment phospho-SRC (pSRC) and SRC protein expression was determined. Dose-response curves were constructed, and drug interaction was assessed by the Combination Index (CI) method. RESULTS: SRC protein expression levels reflected the SRC pathway genomic signature in the cell lines with the lowest (SKOV3) and highest (IGROV1) pathway expression, but not in those with intermediate expression (OVCAR3, A2780). Dasatinib treatment caused loss of pSRC in all cell lines, with 50% growth inhibition for IGROV1 at 70 nM, OVCAR3 at 34 nM, A2780 at 4.1 μM and SKOV3 at 530 nM. Dasatinib combined with cytotoxics yielded a synergistic effect (CI=0.46 to 0.79) in all cell lines except SKOV3. CONCLUSION: Dasatinib in combination with standard chemotherapeutic agents appears to interact in a synergistic manner in some ovarian cancer cell lines. Further research is needed to evaluate tumor cell characteristics which predict response to dasatinib.

Authors
Teoh, D; Ayeni, TA; Rubatt, JM; Adams, DJ; Grace, L; Starr, MD; Barry, WT; Berchuck, A; Murphy, SK; Secord, AA
MLA Citation
Teoh, D, Ayeni, TA, Rubatt, JM, Adams, DJ, Grace, L, Starr, MD, Barry, WT, Berchuck, A, Murphy, SK, and Secord, AA. "Dasatinib (BMS-35482) has synergistic activity with paclitaxel and carboplatin in ovarian cancer cells." Gynecol Oncol 121.1 (April 2011): 187-192.
PMID
21208651
Source
pubmed
Published In
Gynecologic Oncology
Volume
121
Issue
1
Publish Date
2011
Start Page
187
End Page
192
DOI
10.1016/j.ygyno.2010.11.017

ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers.

Selection of suitable antigens is critical for the development of cancer vaccines. Most desirable are over-expressed cell surface proteins that may serve as targets for both antibodies and T cells, thus maximizing a concerted immune response. Towards this goal, we characterized the relevance of tumour necrosis factor-α-converting enzyme (ADAM17) for such targeted therapeutics. ADAM17 is one of the several metalloproteinases that play a key role in epidermal growth factor receptor (EGFR) signalling and has recently emerged as a new therapeutic target in several tumour types. In the present study, we analysed the expression profile of ADAM17 in a variety of normal and cancer cells of human origin and found that this protein is over-expressed on the surface of several types of cancer cells compared to the normal counterparts. Furthermore, we analysed the presentation of a human leucocyte antigen (HLA)-A2-restricted epitope from ADAM17 protein to specific T cells established from normal donors as well as ovarian cancer patients. Our analysis revealed that the HLA-A2-restricted epitope is processed efficiently and presented by various cancer cells and not by normal cells. Tumour-specific T cell activation results in the secretion of both interferon-γ and granzyme B that can be blocked by HLA-A2 specific antibodies. Collectively, our data present evidence that ADAM17 can be a potential target antigen to devise novel immunotherapeutic strategies against ovarian, breast and prostate cancer.

Authors
Sinnathamby, G; Zerfass, J; Hafner, J; Block, P; Nickens, Z; Hobeika, A; Secord, AA; Lyerly, HK; Morse, MA; Philip, R
MLA Citation
Sinnathamby, G, Zerfass, J, Hafner, J, Block, P, Nickens, Z, Hobeika, A, Secord, AA, Lyerly, HK, Morse, MA, and Philip, R. "ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers." Clin Exp Immunol 163.3 (March 2011): 324-332.
PMID
21175594
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
163
Issue
3
Publish Date
2011
Start Page
324
End Page
332
DOI
10.1111/j.1365-2249.2010.04298.x

Antiangiogenic therapies in epithelial ovarian cancer.

BACKGROUND: Angiogenesis is a critical component of tumor development and proliferation, and increased angiogenesis has been associated with a worse clinical outcome in a number of solid tumors, including ovarian cancer. Therefore, agents that target the angiogenic process are of considerable interest in the treatment of ovarian cancer. METHODS: Studies evaluating the efficacy of antiangiogenic agents in ovarian cancer are reported. Antiangiogenic agents examined include vascular endothelial growth factor (VEGF) pathway inhibitors, including monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and a soluble receptor decoy, as well as inhibitors of other angiogenic factors and vascular disrupting agents. RESULTS: The VEGF inhibitor bevacizumab has been shown to have efficacy in ovarian cancer in phase II trials and a progression-free survival advantage in one phase III trial. TKIs block the VEGF receptors and secondary angiogenic pathways and have shown activity in phase I and II trials. Alternative angiogenesis inhibitors include EphA2 inhibitors and a selective angiopoietin 1/2-neutralizing peptibody. Another strategy is to destroy the existing tumor vasculature, and a number of vascular disrupting agents are being studied in preclinical and phase I trials. Antiangiogenic agents have a unique side effect profile, likely due to inhibition of normal physiologic angiogenesis. CONCLUSIONS: Phase II and early phase III trials have demonstrated that antiangiogenic therapies have significant activity in ovarian cancer. The results of phase III trials in the front-line and recurrent settings will determine the extent of clinical benefit of antiangiogenic therapies in combination with chemotherapy. Antiangiogenic agents have a distinct side effect profile, and further studies are necessary to evaluate how to minimize the incidence of these events and to identify women most likely to benefit from these therapies.

Authors
Teoh, DGK; Secord, AA
MLA Citation
Teoh, DGK, and Secord, AA. "Antiangiogenic therapies in epithelial ovarian cancer." Cancer Control 18.1 (January 2011): 31-43. (Review)
PMID
21273978
Source
pubmed
Published In
Cancer control : journal of the Moffitt Cancer Center
Volume
18
Issue
1
Publish Date
2011
Start Page
31
End Page
43

Recurrent granulosa cell tumor presenting with spontaneous retroperitoneal hemorrhage: A case report

Authors
Zani, S; Stoecker, M; Cox, MW; Secord, AA; Blazer, DG
MLA Citation
Zani, S, Stoecker, M, Cox, MW, Secord, AA, and Blazer, DG. "Recurrent granulosa cell tumor presenting with spontaneous retroperitoneal hemorrhage: A case report." Gynecologic Oncology Case Reports 1.1 (2011): 14-16.
PMID
24371592
Source
scival
Published In
Gynecologic Oncology Reports
Volume
1
Issue
1
Publish Date
2011
Start Page
14
End Page
16
DOI
10.1016/j.gynor.2011.09.003

Severe ulceration over mandibular torus in an ovarian cancer patient receiving bevacizumab therapy

Authors
Teoh, D; Won, JS; Eisberg, R; Nolte, K; Secord, AA
MLA Citation
Teoh, D, Won, JS, Eisberg, R, Nolte, K, and Secord, AA. "Severe ulceration over mandibular torus in an ovarian cancer patient receiving bevacizumab therapy." Gynecologic Oncology Case Reports 1.1 (2011): 20-21.
PMID
24371594
Source
scival
Published In
Gynecologic Oncology Reports
Volume
1
Issue
1
Publish Date
2011
Start Page
20
End Page
21
DOI
10.1016/j.gynor.2011.09.001

Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: A gynecologic oncology group study

Purpose: There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN). Patients and Methods: Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma. Results: Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m2 was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m 2 (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated. Conclusion: The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease. © 2011 by American Society of Clinical Oncology.

Authors
Osborne, RJ; Filiaci, V; Schink, JC; Mannel, RS; Secord, AA; Kelley, JL; Provencher, D; Miller, DS; Covens, AL; Lage, JM
MLA Citation
Osborne, RJ, Filiaci, V, Schink, JC, Mannel, RS, Secord, AA, Kelley, JL, Provencher, D, Miller, DS, Covens, AL, and Lage, JM. "Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: A gynecologic oncology group study." Journal of Clinical Oncology 29.7 (2011): 825-831.
PMID
21263100
Source
scival
Published In
Journal of Clinical Oncology
Volume
29
Issue
7
Publish Date
2011
Start Page
825
End Page
831
DOI
10.1200/JCO.2010.30.4386

A phase II evaluation of weekly gemcitabine and docetaxel for second-line treatment of recurrent carcinosarcoma of the uterus: a gynecologic oncology group study.

BACKGROUND: The objective of this study was to estimate antitumor activity and toxicity of weekly docetaxel and gemcitabine as second-line chemotherapy for patients with recurrent uterine carcinosarcoma. METHODS: Patients with recurrent carcinosarcoma of the uterus who had failed one regimen of chemotherapy, had a Gynecologic Oncology Group (GOG) performance status of 0-2 and had measurable disease were included. Treatment consisted of gemcitabine 600 mg/m(2) and docetaxel 35 mg/m(2) intravenously on days 1, 8 and 15 of a 28-day cycle until disease progression or intolerable adverse effects. This study employed an optimal but flexible two-stage design with an early stopping rule. If more than 3 out of 22-24 or more than 4 out of 25-29 patients responded, accrual to the second stage was to be initiated. RESULTS: Twenty-eight patients were enlisted. Three patients were not eligible after pathology review. One patient was never treated. Twenty-four patients were evaluable. Nine patients had previous radiation therapy. There were no complete responses. Partial responses were seen in two patients (8.3%), stable disease in eight (33.3%) and progressive disease in 12 patients (50%). Two patients were not evaluable (8.3%). The median progression-free survival was 1.8 months. The median survival was 4.9 months. The treatment caused myelosuppression, mainly neutropenia, but also thrombocytopenia and anemia. Dose modifications became necessary in the majority of patients. In five patients, treatment was discontinued due to toxicity. CONCLUSIONS: This regimen of docetaxel and gemcitabine is not active in patients with recurrent carcinosarcoma of the uterus as second-line chemotherapy.

Authors
Miller, BE; Blessing, JA; Stehman, FB; Shahin, MS; Yamada, SD; Secord, AA; Warshal, DP; Abulafia, O; Richards, WE; Van Le, L
MLA Citation
Miller, BE, Blessing, JA, Stehman, FB, Shahin, MS, Yamada, SD, Secord, AA, Warshal, DP, Abulafia, O, Richards, WE, and Van Le, L. "A phase II evaluation of weekly gemcitabine and docetaxel for second-line treatment of recurrent carcinosarcoma of the uterus: a gynecologic oncology group study." Gynecol Oncol 118.2 (August 1, 2010): 139-144.
PMID
20452658
Source
pubmed
Published In
Gynecologic Oncology
Volume
118
Issue
2
Publish Date
2010
Start Page
139
End Page
144
DOI
10.1016/j.ygyno.2010.03.024

Expression signatures of TP53 mutations in serous ovarian cancers.

BACKGROUND: Mutations in the TP53 gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease. METHODS: The TP53 coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage. RESULTS: Missense or chain terminating (null) mutations in TP53 were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict TP53 status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers. CONCLUSIONS: This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.

Authors
Bernardini, MQ; Baba, T; Lee, PS; Barnett, JC; Sfakianos, GP; Secord, AA; Murphy, SK; Iversen, E; Marks, JR; Berchuck, A
MLA Citation
Bernardini, MQ, Baba, T, Lee, PS, Barnett, JC, Sfakianos, GP, Secord, AA, Murphy, SK, Iversen, E, Marks, JR, and Berchuck, A. "Expression signatures of TP53 mutations in serous ovarian cancers. (Published online)" BMC Cancer 10 (May 26, 2010): 237-.
Website
http://hdl.handle.net/10161/4356
PMID
20504346
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
237
DOI
10.1186/1471-2407-10-237

A randomized, open-label phase IIb study of maintenence therapy with a MUC-1 dendritic cell vaccine in patients with epithelial ovarian cancer in first or second remission

Authors
Gray, HJ; Secord, AA; Anderson, ML; DelPriore, G; Tchabo, NE; Berek, JS
MLA Citation
Gray, HJ, Secord, AA, Anderson, ML, DelPriore, G, Tchabo, NE, and Berek, JS. "A randomized, open-label phase IIb study of maintenence therapy with a MUC-1 dendritic cell vaccine in patients with epithelial ovarian cancer in first or second remission." May 20, 2010.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Phase II trial of topotecan, cisplatin, and bevacizurnab for recurrent or persistent cervical cancer

Authors
Zighelboim, I; Wright, JD; Powell, MA; Case, AS; Eisenhauer, EL; Cohn, DE; Valea, FA; Secord, AA; Lippmann, LT; Rader, JS
MLA Citation
Zighelboim, I, Wright, JD, Powell, MA, Case, AS, Eisenhauer, EL, Cohn, DE, Valea, FA, Secord, AA, Lippmann, LT, and Rader, JS. "Phase II trial of topotecan, cisplatin, and bevacizurnab for recurrent or persistent cervical cancer." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer.

We previously found that the gene encoding the Myelin and Lymphocyte protein, MAL, was among the most highly expressed genes in serous ovarian cancers from short-term survivors (<3 years) relative to those of long-term survivors (>7 years). In the present study, we have found that this difference in expression is partially attributable to differences in DNA methylation at a specific region within the MAL promoter CpG island. While MAL was largely unmethylated at the transcription start site (Region 1; -48 to +73 bp) in primary serous ovarian cancers, methylation of an upstream region (Region 2; -452 to -266 bp) was inversely correlated with MAL transcription in the primary cancers (R = -0.463) and ovarian cancer cell lines (R = -0.444). Following treatment of the OVCA432 cell line with 5-azacytidine, methylation of Region 2 decreased from 73.3% to 34.7% (p = 0.007) while Region 1 was unaffected. This was accompanied by a 10-fold increase in MAL expression. Since MAL transcripts are elevated in tumors from short-term survivors, all of whom were treated with platinum-based therapy, MAL may have a role in cisplatin response. We therefore determined the 50% growth inhibitory dose of cisplatin in 30 ovarian cancer cell lines and compared this to MAL expression. MAL transcript levels were higher in the resistant ovarian cell lines (p = 0.04). MAL methylation status may therefore serve as a marker of platinum sensitivity while MAL protein may be a target for development of novel therapies aimed at enhancing sensitivity to platinum-based drugs in ovarian cancer.

Authors
Lee, PS; Teaberry, VS; Bland, AE; Huang, Z; Whitaker, RS; Baba, T; Fujii, S; Secord, AA; Berchuck, A; Murphy, SK
MLA Citation
Lee, PS, Teaberry, VS, Bland, AE, Huang, Z, Whitaker, RS, Baba, T, Fujii, S, Secord, AA, Berchuck, A, and Murphy, SK. "Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer." International journal of cancer 126.6 (March 2010): 1378-1389.
PMID
19642140
Source
epmc
Published In
International Journal of Cancer
Volume
126
Issue
6
Publish Date
2010
Start Page
1378
End Page
1389
DOI
10.1002/ijc.24797

Stage I, grade 3 endometrioid adenocarcinoma of the endometrium: an analysis of clinical outcomes and patterns of recurrence.

OBJECTIVE: To study patterns of recurrence and survival outcomes in patients with surgical stage I, grade 3 endometrioid adenocarcinoma of the endometrium (EA) treated with various treatment modalities. METHODS: A retrospective multi-institutional study of surgical stage I, grade 3 EA patients diagnosed between 1988 and 2006 was performed. Demographic, clinicopathologic, treatment and outcome data were collected. After surgery, patients were treated with either observation or radiotherapy (vaginal brachytherapy, whole pelvic or both). RESULTS: One hundred seventy-six patients were collected with a median age of 68 years. Twenty-six (15%) were stage IA, 96 (54%) IB and 54 (31%) IC. Sixty-one patients (35%) had lymphovascular space invasion (LVSI) and a mean of 18.9 lymph nodes (LNs) was removed. Seventy-eight patients (44%) were observed while 98 (56%) were treated with radiotherapy, the majority (n=51) receiving brachytherapy. After a median follow-up of 58 months, 20 recurrences (11%) were noted. Ninety percent of recurrences occurred in Stage IB/IC patients. The median time to recurrence was 22.5 months (5-74.5) and 80% of recurrences were extra-pelvic. There was no significant difference in recurrence based upon treatment modality or LVSI. Majority of recurrences were not salvaged as 75% (12/16) died of their disease with a median time of recurrence to death of 8 months. CONCLUSIONS: Patients with stage IB/IC, grade 3 endometrioid adenocarcinoma have a significant risk for extra-pelvic recurrence. Most patients will not be salvaged and will succumb to their disease, suggesting that current loco-regional adjuvant treatment strategies are not optimal and evaluation of more systemic therapies is warranted.

Authors
Rasool, N; Fader, AN; Seamon, L; Neubauer, NL; Shahin, FA; Alexander, HA; Moore, K; Moxley, K; Secord, AA; Kunos, C; Rose, PG; O'Malley, DM
MLA Citation
Rasool, N, Fader, AN, Seamon, L, Neubauer, NL, Shahin, FA, Alexander, HA, Moore, K, Moxley, K, Secord, AA, Kunos, C, Rose, PG, and O'Malley, DM. "Stage I, grade 3 endometrioid adenocarcinoma of the endometrium: an analysis of clinical outcomes and patterns of recurrence." Gynecol Oncol 116.1 (January 2010): 10-14.
PMID
19875158
Source
pubmed
Published In
Gynecologic Oncology
Volume
116
Issue
1
Publish Date
2010
Start Page
10
End Page
14
DOI
10.1016/j.ygyno.2009.10.043

Association between the N-terminally truncated (DeltaN) p63alpha (DeltaNp63alpha) isoform and debulking status, VEGF expression and progression-free survival in previously untreated, advanced stage epithelial ovarian cancer: A Gynecologic Oncology Group study.

OBJECTIVES: The Gynecologic Oncology Group (GOG) examined the association between the relative expression of the DeltaNp63alpha isoform and clinicopathologic variables, p53 status, angiogenic markers, progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC). METHODS: Immunoblot analysis was used to determine the relative expression of DeltaNp63alpha to beta-actin in lysates of frozen primary tumor from women with previously untreated, advanced stage EOC who participated in a GOG specimen banking protocol and a randomized phase III treatment protocol. RESULTS: DeltaNp63alpha was detected in 49/56 (87.5%) cases with relative expression ranging from 0 to 4.55 (median=0.325). A correlation was observed between the relative expression of DeltaNp63alpha and debulking status (Spearman's correlation coefficient=0.303; p=0.025) and the relative expression of vascular endothelial growth factor (VEGF) (Spearman's correlation coefficient=0.303; p=0.045), but not with p53 status (overexpression or mutation), immunoblot expression of MASPIN, or the relative expression of thrombospondin-1, basic fibroblast growth factor or VEGF receptor-1. A 1.4-fold increase was observed in the risk of disease progression for each unit increase in the relative expression of DeltaNp63alpha using an unadjusted (hazard ratio [HR]=1.459; 95% confidence interval [CI]=1.096-1.942; p=0.010), a full (HR=1.483; 95% CI=1.060-2.076; p=0.021) and a reduced (HR=1.387; 95% CI=1.025-1.877; p=0.034) Cox regression model. The relative expression of DeltaNp63alpha was not associated with OS using an unadjusted, a full or a reduced Cox model. CONCLUSIONS: The relative expression DeltaNp63alpha appears to be associated with debulking status and the relative expression of VEGF and PFS, and to be an independent prognostic factor for disease progression in EOC.

Authors
Jewell, EL; Darcy, KM; Hutson, A; Lee, PS; Havrilesky, LJ; Grace, LA; Berchuck, A; Secord, AA
MLA Citation
Jewell, EL, Darcy, KM, Hutson, A, Lee, PS, Havrilesky, LJ, Grace, LA, Berchuck, A, and Secord, AA. "Association between the N-terminally truncated (DeltaN) p63alpha (DeltaNp63alpha) isoform and debulking status, VEGF expression and progression-free survival in previously untreated, advanced stage epithelial ovarian cancer: A Gynecologic Oncology Group study." Gynecol Oncol 115.3 (December 2009): 424-429.
PMID
19767063
Source
pubmed
Published In
Gynecologic Oncology
Volume
115
Issue
3
Publish Date
2009
Start Page
424
End Page
429
DOI
10.1016/j.ygyno.2009.07.035

An updated clinicopathologic study of early-stage uterine papillary serous carcinoma (UPSC).

OBJECTIVES: Stage I-II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC. METHODS: A retrospective, multi-institution analysis of surgically staged I-II UPSC patients was performed. Patients were treated by various adjuvant modalities. Age, race, sub-stage, percentage UPSC histology, lymphvascular space invasion (LVSI), tumor size and adjuvant treatment modality were evaluated for their effect on recurrence and survival outcomes. RESULTS: We identified 206 patients. Forty patients (19.4%) had 5-49% UPSC, 55 (26.7%) had 50-99% and 111 patients (53.9%) had 100% UPSC in their respective uterine specimens. Twenty one percent of patients experienced a primary recurrence. On univariate analysis, age, increasing %UPSC, LVSI, and tumor size were not significantly associated with recurrence or progression-free survival (PFS). However, substage (p=0.005) and treatment with platinum/taxane-based chemotherapy (p=0.001) were associated with recurrence/PFS. On multivariate analysis, only chemotherapy (p=0.01) was a significant factor affecting PFS, whereas age (p=0.05), substage (p=0.05), and chemotherapy (p=0.02) were associated with overall survival. CONCLUSIONS: Traditional risk factors for recurrence and survival in patients with early-stage endometrial cancer may not be relevant in patients with UPSC. Patients with any percentage UPSC in their uterine specimens are at a significant risk for recurrence and poor survival outcomes. Given that current clinicopathologic data does not accurately identify women most likely to benefit from adjuvant therapy, alternative prognostic markers based on novel techniques should be explored.

Authors
Fader, AN; Starks, D; Gehrig, PA; Secord, AA; Frasure, HE; O'Malley, DM; Tuller, ER; Rose, PG; Havrilesky, LJ; Moore, KN; Huh, WK; Axtell, AE; Kelley, JL; Zanotti, KM; UPSC Consortium,
MLA Citation
Fader, AN, Starks, D, Gehrig, PA, Secord, AA, Frasure, HE, O'Malley, DM, Tuller, ER, Rose, PG, Havrilesky, LJ, Moore, KN, Huh, WK, Axtell, AE, Kelley, JL, Zanotti, KM, and UPSC Consortium, . "An updated clinicopathologic study of early-stage uterine papillary serous carcinoma (UPSC)." Gynecol Oncol 115.2 (November 2009): 244-248.
PMID
19712966
Source
pubmed
Published In
Gynecologic Oncology
Volume
115
Issue
2
Publish Date
2009
Start Page
244
End Page
248
DOI
10.1016/j.ygyno.2009.07.030

A Phase II evaluation of weekly topotecan as a single agent second line therapy in persistent or recurrent carcinoma of the cervix: a Gynecologic Oncology Group study.

PURPOSE: To estimate antitumor activity and toxicity of weekly topotecan hydrochloride in patients with persistent or recurrent cervical carcinoma who failed prior treatment. PATIENTS AND METHODS: Women entered on study had or failed one prior chemotherapy regimen in addition to radiosensitizing chemotherapy, performance status less than 3, and adequate hematologic, renal, hepatic, and neurological function. Topotecan was infused at 3.0 mg/m(2) on days 1, 8, and 15 every 28 days. RESULTS: Twenty-seven patients were enrolled onto this study with 25 evaluable. Twenty-two patients had received radiation and chemotherapy prior to study. A median of two and mean of three courses of chemotherapy was given (range, one to eight courses). The most frequently severe adverse events were grade 3 anemia (28%) and grade 4 (4%) along with grade 3 neutropenia (8%) and grade 4 (8%). Two patients had grade 4 thrombocytopenia. There were no complete or partial responders. Ten patients (40%) had stable disease, twelve (48%) had increasing disease, and response could not be assessed in three (12%). The median progression-free survival was 2.4 months for the patients with increasing disease and 6.2 months (3.5-8.8 months) for those with stable disease. Disease location was equally divided within and outside the irradiated field. The 12 patients with increasing disease were more likely to have disease outside the pelvic radiation field. CONCLUSION: There were no complete or partial responders to weekly topotecan among the 25 patients in this study.

Authors
Fiorica, JV; Blessing, JA; Puneky, LV; Secord, AA; Hoffman, JS; Yamada, SD; Buekers, TE; Bell, J; Schilder, JM; Gynecologic Oncology Group,
MLA Citation
Fiorica, JV, Blessing, JA, Puneky, LV, Secord, AA, Hoffman, JS, Yamada, SD, Buekers, TE, Bell, J, Schilder, JM, and Gynecologic Oncology Group, . "A Phase II evaluation of weekly topotecan as a single agent second line therapy in persistent or recurrent carcinoma of the cervix: a Gynecologic Oncology Group study." Gynecol Oncol 115.2 (November 2009): 285-289.
PMID
19726073
Source
pubmed
Published In
Gynecologic Oncology
Volume
115
Issue
2
Publish Date
2009
Start Page
285
End Page
289
DOI
10.1016/j.ygyno.2009.07.024

Priming and activation of human ovarian and breast cancer-specific CD8+ T cells by polyvalent Listeria monocytogenes-based vaccines.

Immunotherapeutic vaccine is potentially an effective strategy to combat cancer. Essential components of an effective vaccine must include antigens that are processed by the major histocompatibility complex class I pathway, presented by the tumor major histocompatibility complex molecules, and an effective antigen delivery platform that is capable of breaking self-tolerance. In this study, we characterized a set of ovarian cancer-specific T-cell epitopes delivered by live-attenuated recombinant Listeria monocytogenes (Lm DeltaactADeltainlB) as a vaccine vector. We present data that peptide-specific T cells recognize the human monocytic cell line THP-1 infected with recombinant Lm DeltaactADeltainlB encoding the epitopes. Furthermore, we demonstrate that recombinant L. monocytogenes (Lm)-infected antigen-presenting cells can prime and expand epitope-specific CD8 T cells in vitro and such CD8 T cells recognize not only peptide-loaded targets but also ovarian and breast tumor cells presenting endogenous epitopes. Finally, peptide-specific T cells generated using peripheral blood mononuclear cell from ovarian cancer patients recognize target cells infected with recombinant Lm DeltaactADeltainlB encoding the epitopes. Our results demonstrate that live-attenuated recombinant Lm can be used effectively as a vehicle to deliver cancer peptide antigens singly or as a multiepitope construct. Thus, the use of recombinant live-attenuated Lm strains encoding endogenously processed and presented tumor epitopes/antigens represents an attractive strategy for active cancer immunotherapy in a clinical setting.

Authors
Sinnathamby, G; Lauer, P; Zerfass, J; Hanson, B; Karabudak, A; Krakover, J; Secord, AA; Clay, TM; Morse, MA; Dubensky, TW; Brockstedt, DG; Philip, R; Giedlin, M
MLA Citation
Sinnathamby, G, Lauer, P, Zerfass, J, Hanson, B, Karabudak, A, Krakover, J, Secord, AA, Clay, TM, Morse, MA, Dubensky, TW, Brockstedt, DG, Philip, R, and Giedlin, M. "Priming and activation of human ovarian and breast cancer-specific CD8+ T cells by polyvalent Listeria monocytogenes-based vaccines." J Immunother 32.8 (October 2009): 856-869.
PMID
19752748
Source
pubmed
Published In
Journal of Immunotherapy
Volume
32
Issue
8
Publish Date
2009
Start Page
856
End Page
869
DOI
10.1097/CJI.0b013e3181b0b125

Robotic-assisted laparoscopic gynecologic procedures in a fellowship training program.

BACKGROUND AND OBJECTIVE: The robotic surgical platform is an alternative technique to traditional laparoscopy and requires the development of new surgical skills for both the experienced surgeon and trainee. Our goal was to perform an early evaluation of the feasibility of training fellows in robotic-assisted gynecologic procedures at the outset of our incorporation of this technology into clinical practice. METHODS: A systematic approach to fellow training included (1) didactic and hands-on training with the robotic system, (2) instructional videos, (3) assistance at the operating table, and (4) performance of segments of gynecologic procedures in tandem with the attending physician. Time to complete the entire procedure, individual segments, rate of conversion to laparotomy, and complications were recorded. RESULTS: Twenty-one robotic-assisted gynecologic procedures were performed from April 2006 to January 2007. Fellows participated as the console surgeon in 14/21 cases. Thirteen patients (62%) had prior abdominal surgery. Median values with ranges were age 51 years (range, 33 to 90); BMI 28 (range, 19.4 to 43.8); EBL 25 mL (range, 25 to 250); and hospital stay 1 day (range, 1 to 4). No significant difference existed between fellow and attending mean total operative and individual segment times. One conversion to laparotomy was necessary. No major surgical complications occurred. CONCLUSION: These data suggest that it is feasible to incorporate a systematic approach to robotic-assisted laparoscopic training for trainees at the outset of incorporation of this technology into current practice.

Authors
Lee, PS; Bland, A; Valea, FA; Havrilesky, LJ; Berchuck, A; Secord, AA
MLA Citation
Lee, PS, Bland, A, Valea, FA, Havrilesky, LJ, Berchuck, A, and Secord, AA. "Robotic-assisted laparoscopic gynecologic procedures in a fellowship training program." JSLS 13.4 (October 2009): 467-472.
PMID
20202385
Source
pubmed
Published In
JSLS : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons
Volume
13
Issue
4
Publish Date
2009
Start Page
467
End Page
472
DOI
10.4293/108680809X12589998403921

Indwelling catheters for the management of refractory malignant ascites: a systematic literature overview and retrospective chart review.

The safety and efficacy of indwelling intraperitoneal (IP) catheters for the management of refractory malignant ascites is unclear. A systematic literature overview and retrospective chart review of patients with malignant refractory ascites who underwent indwelling IP catheter placement was performed. Standardized literature abstraction and chart review templates were used to ensure that consistent information was collected. Fifteen publications met literature search criteria, representing 221 patients. Tenckhoff (Quinton Instrument Company, Seattle, WA, USA), Pleurex (Denver Biomedical Inc., Golden, CO, USA), and peritoneal catheters were used, along with IP ports. A median 5.9% of cases (range: 2.5%-34%) had documented peritonitis. In the literature, untunneled catheters were most commonly associated with infections. Our chart review added 19 cases from two academic institutions to this literature (median age: 60 years [range: 31-85]; females: 17 [89%]; gynecological malignancies: 14 [73%]). Palliative management before catheter placement included diuretics (n=4 [21%]) and multiple paracenteses (n=11 [58%] had two or more taps [range: 2-8]). Median time from diagnosis to catheter placement was 25 months (range: 1-77). Interventions were: French pigtail catheters (n=16 [84%]), Tenckhoff catheter (n=1 [5%]), and Port-A-Caths (Smith Medical MD, St. Paul, MN, USA) (n=2; 11%). Four (21%) catheters were tunneled. Prophylactic antibiotics were prescribed in six cases (32%). Two cases (11%) had documented infections, seven catheters (37%) became occluded, and two leaked (11%). The median time from catheter until death was 36 days (range: 4-660). Nine patients (47%) were admitted to hospice. In these retrospective studies, indwelling IP catheters appear to be a safe and effective palliative strategy to manage refractory malignant ascites, without overwhelming infection rates.

Authors
Fleming, ND; Alvarez-Secord, A; Von Gruenigen, V; Miller, MJ; Abernethy, AP
MLA Citation
Fleming, ND, Alvarez-Secord, A, Von Gruenigen, V, Miller, MJ, and Abernethy, AP. "Indwelling catheters for the management of refractory malignant ascites: a systematic literature overview and retrospective chart review." J Pain Symptom Manage 38.3 (September 2009): 341-349. (Review)
PMID
19328648
Source
pubmed
Published In
Journal of Pain and Symptom Management
Volume
38
Issue
3
Publish Date
2009
Start Page
341
End Page
349
DOI
10.1016/j.jpainsymman.2008.09.008

A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer.

OBJECTIVES: The appropriate sequencing of chemotherapy and radiation for the treatment of advanced endometrial cancer has not yet been determined. We sought to evaluate the outcome and adverse effects in patients with advanced stage endometrial cancer treated with postoperative chemotherapy and radiation to determine whether there was an advantage to a particular sequencing modality. METHODS: A multicenter retrospective analysis of patients with surgical stages III and IV endometrial cancer from 1993 to 2007 was conducted. Inclusion criteria were comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, +/- selective pelvic/aortic lymphadenectomy, and treatment with adjuvant chemotherapy and radiation. Differences in frequencies of adverse events were tested with Pearson's chi-square test for comparing proportions. OS and PFS rates were calculated using Kaplan-Meier estimates. Hazard Ratios (HR) were estimated from multivariate Cox proportional hazards models. RESULTS: One hundred and nine patients with advanced stage endometrial cancer were identified who received postoperative adjuvant therapies; 41% (n=45) chemotherapy followed by radiation and then further chemotherapy (CRC), 17% (n=18) radiation followed by chemotherapy (RC), and 42% (n=46) chemotherapy followed by radiation (CR). The median age was 62 years (range: 35-83); 48% had endometrioid tumors; and 90% underwent optimal cytoreduction. There was no difference in the frequency of adverse effects due to either chemotherapy (p=0.35) or radiotherapy (p=0.14); dose modifications (p=0.055); or delays (p=0.80) between the various sequencing modalities. There was a significant difference between adjuvant treatment groups for both OS (log rank p=0.011) and PFS (log rank p=0.025), with those receiving CRC having a superior 3-year OS (88%) and PFS (69%) compared to RC (54% and 47%) or CR (57% and 52%). After adjusting for stage, age, grade, race, histology and cytoreduction status the OS HR for therapy was 5.74 (95% CI, 1.96 to 16.77) for RC and 2.60 (95% CI, 1.01 to 6.71) for CR, compared to CRC, p=0.003. When the analysis was restricted to optimally cytoreduced patients, those who were treated with RC were at higher risk for disease progression [HR=3.53 (95% CI, 1.29 to 9.71)], p=0.024, and death [HR=7.24 (95% CI, 2.25 to 23.37)], p=0.001, than patients who received sequential CRC. CONCLUSIONS: Sequential CRC was associated with improved survival in women with advanced stage disease compared to other sequencing modalities with a similar adverse effect profile. Future clinical trials are needed to prospectively evaluate appropriate sequencing and types of adjuvant chemotherapy and radiotherapy for the treatment of advanced stage endometrial cancer.

Authors
Secord, AA; Havrilesky, LJ; O'Malley, DM; Bae-Jump, V; Fleming, ND; Broadwater, G; Cohn, DE; Gehrig, PA
MLA Citation
Secord, AA, Havrilesky, LJ, O'Malley, DM, Bae-Jump, V, Fleming, ND, Broadwater, G, Cohn, DE, and Gehrig, PA. "A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer." Gynecol Oncol 114.3 (September 2009): 442-447.
PMID
19560193
Source
pubmed
Published In
Gynecologic Oncology
Volume
114
Issue
3
Publish Date
2009
Start Page
442
End Page
447
DOI
10.1016/j.ygyno.2009.06.005

Multicenter analysis of recurrence and survival in stage IIIA endometrial cancer.

OBJECTIVE: To determine factors related to recurrence and survival in women with stage IIIA endometrial cancer; to examine outcomes of women with IIIA1 disease. METHODS: Multi-institutional analysis of women with stage IIIA endometrial carcinoma undergoing hysterectomy, bilateral salpingo-oophorectomy, lymphadenectomy, and pelvic cytology between 1980 and 2008. Overall survival (OS) and recurrence-free disease specific survival (RFDSS) were compared using Kaplan-Meier method, univariate and multivariate analyses. RESULTS: 98 women underwent surgical staging for stage IIIA endometrial carcinoma. Pelvic washings were positive in 53%, serosa in 18%, and adnexae in 45%. Forty were IIIA1; 58 were IIIA2 (adnexal/serosal involvement). Median number of lymph nodes was 19 (range 1-73). Adjuvant treatment was given to 88%: radiotherapy--21%, chemotherapy - 19%, chemotherapy and radiotherapy--19%, hormonal therapy--16%, and intraperitoneal P-32 - 11%. Five-year OS and RFDSS for IIIA1 were 77% and 76%, respectively; and for IIIA2 were 75% and 73%, respectively (p=NS for both). Patients with IIIA1 disease were less likely to receive chemotherapy or radiotherapy than those with IIIA2 disease (p=0.0035). Older age (Hazard ratio 1.24; 95% CI 1.00-1.54), non-Caucasian race (HR 5.35; 95% CI 1.96-14.5), and cervical metastases (HR 3.3; 95% CI 1.3-8.7) predicted lower RFDSS in multivariate analysis. Among 24 patients meeting NCCN's observation criteria (IIIA1, non-serous, and FIGO grade 1-2), 0/12 receiving adjuvant treatment recurred, while 1/12 not receiving adjuvant treatment recurred. CONCLUSIONS: Surgically assessed stage IIIA endometrial adenocarcinoma recurs in approximately 20-25% of cases. A subset of stage IIIA1 with very low risk factors may be appropriate candidates for observation.

Authors
Havrilesky, LJ; Secord, AA; O'Malley, DM; Broadwater, G; Bae-Jump, V; Cohn, DE; Gehrig, PA
MLA Citation
Havrilesky, LJ, Secord, AA, O'Malley, DM, Broadwater, G, Bae-Jump, V, Cohn, DE, and Gehrig, PA. "Multicenter analysis of recurrence and survival in stage IIIA endometrial cancer." Gynecol Oncol 114.2 (August 2009): 279-283.
PMID
19446319
Source
pubmed
Published In
Gynecologic Oncology
Volume
114
Issue
2
Publish Date
2009
Start Page
279
End Page
283
DOI
10.1016/j.ygyno.2009.04.030

Improved outcomes in advanced stage uterine carcinosarcoma (mixed mullerian tumor [MMT])

Authors
O'Malley, DM; Nagel, C; Cantrell, LA; Havrilesky, L; Liotta, M; Secord, AA; Nickles, A; Cohn, DE; Wallace, A; Rose, P; Gehrig, P
MLA Citation
O'Malley, DM, Nagel, C, Cantrell, LA, Havrilesky, L, Liotta, M, Secord, AA, Nickles, A, Cohn, DE, Wallace, A, Rose, P, and Gehrig, P. "Improved outcomes in advanced stage uterine carcinosarcoma (mixed mullerian tumor [MMT])." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Effect of treatment of patients with early-stage uterine carcinosarcoma

Authors
Cantrell, LA; Havrilesky, L; O'Malley, D; Liotta, M; Secord, AA; Nagel, C; Fader, AN; Wallace, A; Rose, P; Gehrig, PA
MLA Citation
Cantrell, LA, Havrilesky, L, O'Malley, D, Liotta, M, Secord, AA, Nagel, C, Fader, AN, Wallace, A, Rose, P, and Gehrig, PA. "Effect of treatment of patients with early-stage uterine carcinosarcoma." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Effect of treatment of patients with early-stage uterine carcinosarcoma.

5516 Background: The treatment of early stage uterine carcinosarcoma is controversial. We sought to retrospectively review factors that influence progression and survival.A retrospective, multi-institution study of women diagnosed from 1997-2007 was performed. Postoperative treatment included either observation (OBS), RT (brachytherapy, whole pelvic, or combination), chemotherapy (CT) alone or with RT (CT+RT). Data collected included time to recurrence, overall survival, and sites of recurrence. Statistics included ANOVA and Kaplan Meier.One hundred and forty-six patients were diagnosed with early stage (stages 1 and 2) uterine carcinocarcoma. The median age at diagnosis was 68 years (range:40-91). The majority (62%) were Caucasian, 49 (34%) were African-American and the remainder were other ethnicities. One hundred and seventeen had stage 1 disease and 29 had stage 2. The majority of patients (N = 54, 37 %) were observed, 36 (25%) were treated with CT, 31 (21%) were treated with RT and 17 (12%) were treated with CT + RT. The median progression free survival (PFS) for patients diagnosed with early stage disease was 16.7 months for the OBS cohort and 38.2 months for the CT cohort (p < 0.01). Median overall survival was 23 months for the OBS cohort and 39.3 months for the CT cohort (p = 0.02). The cohorts that underwent RT or CT+RT had improved median progression free (29.9, 20 months) and overall survival (31.7, 20.8 months) as compared to the OBS cohort, however this was not a statistically significant difference.We report on the largest experience in the literature on early stage uterine carcinosarcoma and the first to show that women with early stage disease may benefit from adjuvant chemotherapy. The role of radiation therapy or combination chemotherapy and radiation could not be adequately assessed from this retrospective analysis, but a trend toward improved survival was present. Prospective trials evaluating the best treatment for patients with early stage carcinosarcoma of the uterus should be undertaken to better answer this question. No significant financial relationships to disclose.

Authors
Cantrell, LA; Havrilesky, L; O'Malley, D; Liotta, M; Secord, AA; Nagel, C; Fader, AN; Wallace, A; Rose, P; Gehrig, PA
MLA Citation
Cantrell, LA, Havrilesky, L, O'Malley, D, Liotta, M, Secord, AA, Nagel, C, Fader, AN, Wallace, A, Rose, P, and Gehrig, PA. "Effect of treatment of patients with early-stage uterine carcinosarcoma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): 5516-.
PMID
27962460
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
5516

Uterine Neoplasms Clinical Practice Guidelines in Oncology

Authors
Greer, BE; Koh, W-J; Abu-Rustum, N; Bookman, MA; Bristow, RE; Campos, SM; Cho, KR; Copeland, L; Crispens, MA; Eifel, PJ; Huh, WK; Jaggernauth, W; Kapp, DS; Kavanagh, JJ; III, LJR; Morgan, M; Jr, MRJ; Powell, CB; Remmenga, SW; Reynolds, RK; Secord, AA; Jr, SW; Teng, N
MLA Citation
Greer, BE, Koh, W-J, Abu-Rustum, N, Bookman, MA, Bristow, RE, Campos, SM, Cho, KR, Copeland, L, Crispens, MA, Eifel, PJ, Huh, WK, Jaggernauth, W, Kapp, DS, Kavanagh, JJ, III, LJR, Morgan, M, Jr, MRJ, Powell, CB, Remmenga, SW, Reynolds, RK, Secord, AA, Jr, SW, and Teng, N. "Uterine Neoplasms Clinical Practice Guidelines in Oncology." JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK 7.5 (May 2009): 496-531.
Source
wos-lite
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
7
Issue
5
Publish Date
2009
Start Page
496
End Page
531

Microarray analysis of early stage serous ovarian cancers shows profiles predictive of favorable outcome.

PURPOSE: Although few women with advanced serous ovarian cancer are cured, detection of the disease at an early stage is associated with a much higher likelihood of survival. We previously used gene expression array analysis to distinguish subsets of advanced cancers based on disease outcome. In the present study, we report on gene expression of early-stage cancers and validate our prognostic model for advanced-stage cancers. EXPERIMENTAL DESIGN: Frozen specimens from 39 stage I/II, 42 stage III/IV, and 20 low malignant potential cancers were obtained from four different sites. A linear discriminant model was used to predict survival based upon array data. RESULTS: We validated the late-stage survival model and show that three of the most differentially expressed genes continue to be predictive of outcome. Most early-stage cancers (38 of 39 invasive, 15 of 20 low malignant potential) were classified as long-term survivors (median probabilities 0.97 and 0.86). MAL, the most differentially expressed gene, was further validated at the protein level and found to be an independent predictor of poor survival in an unselected group of advanced serous cancers (P = 0.0004). CONCLUSIONS: These data suggest that serous ovarian cancers detected at an early stage generally have a favorable underlying biology similar to advanced-stage cases that are long-term survivors. Conversely, most late-stage ovarian cancers seem to have a more virulent biology. This insight suggests that if screening approaches are to succeed it will be necessary to develop approaches that are able to detect these virulent cancers at an early stage.

Authors
Berchuck, A; Iversen, ES; Luo, J; Clarke, JP; Horne, H; Levine, DA; Boyd, J; Alonso, MA; Secord, AA; Bernardini, MQ; Barnett, JC; Boren, T; Murphy, SK; Dressman, HK; Marks, JR; Lancaster, JM
MLA Citation
Berchuck, A, Iversen, ES, Luo, J, Clarke, JP, Horne, H, Levine, DA, Boyd, J, Alonso, MA, Secord, AA, Bernardini, MQ, Barnett, JC, Boren, T, Murphy, SK, Dressman, HK, Marks, JR, and Lancaster, JM. "Microarray analysis of early stage serous ovarian cancers shows profiles predictive of favorable outcome." Clin Cancer Res 15.7 (April 1, 2009): 2448-2455.
PMID
19318476
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
7
Publish Date
2009
Start Page
2448
End Page
2455
DOI
10.1158/1078-0432.CCR-08-2430

Attitudes regarding the use of hematopoietic colony-stimulating factors and maintenance of relative dose intensity among gynecologic oncologists.

OBJECTIVE: To assess the attitudes regarding the use of colony-stimulating factor (CSF) and the maintenance of relative dose intensity (RDI) by gynecologic oncologists during the administration of chemotherapy to patients with epithelial ovarian cancer. METHODS: A nationwide survey of 608 gynecologic oncologists was performed using a 19-point questionnaire. The questionnaire assessed the following domains: (1) demographic information, (2) patterns of CSF use during first-line and relapse chemotherapies for patients with epithelial ovarian cancer, and (3) use of CSFs to maintain RDI. RESULTS: The response rate to the survey was 42% (n = 255). Eighty-six percent (220/255) of the respondents routinely administer chemotherapy. In the first-line setting, 67% of physicians who routinely administer chemotherapy preferred to use CSFs for secondary prophylaxis after a neutropenic complication, whereas only 2% would use CSFs for primary prophylaxis. In the recurrent disease setting, physicians were more likely to administer a regimen with minimal myelosuppression (74% reported "likely" or "very likely"), to dose delay or modify if neutropenic complications occur (78%), or to administer CSFs for secondary prophylaxis (85%) than to dose attenuate upon initiation of chemotherapy (49%) or to administer CSFs for primary prophylaxis (46%). Most physicians would administer CSFs to maintain RDI in both the first-line (75%) and palliative settings (62%), and 49% would strive to maintain a dose intensity of more than 85%. CONCLUSIONS: Most gynecologic oncologists use CSFs as secondary prophylaxis for neutropenic complications rather than as primary prophylaxis. Most gynecologic oncologists monitor RDI and use CSFs to maintain RDI in their patients with ovarian carcinoma.

Authors
Alvarez Secord, A; Bae-Jump, V; Havrilesky, LJ; Calingaert, B; Clarke-Pearson, DL; Soper, JT; Gehrig, PA
MLA Citation
Alvarez Secord, A, Bae-Jump, V, Havrilesky, LJ, Calingaert, B, Clarke-Pearson, DL, Soper, JT, and Gehrig, PA. "Attitudes regarding the use of hematopoietic colony-stimulating factors and maintenance of relative dose intensity among gynecologic oncologists." Int J Gynecol Cancer 19.3 (April 2009): 447-454.
PMID
19407573
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
19
Issue
3
Publish Date
2009
Start Page
447
End Page
454
DOI
10.1111/IGC.0b013e3181a1a6c9

Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study.

OBJECTIVES: The aims of this study were to examine prognostic significance of microvessel density (MVD) in previously-untreated, advanced epithelial ovarian cancer (EOC) and explore associations between MVD and factors that affect angiogenesis. METHODS: MVD was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG randomized phase III trials. Average MVD hotspots were quantified by light microscopy at high power (x400) and categorized as low (or=upper quartile). Immunoblot expression of MASPIN, THBS-1, bFGF, VEGF, VEGFR-1 and p53 status (mutation and overexpression) was previously determined. RESULTS: Of 106 evaluable cases, 25% exhibited high CD31-MVD (>24.25 vessels/high power field [HPF]) or high CD105-MVD (>19.25 vessels/HPF). After adjusting for age and stratifying by GOG performance status, stage, cell type, grade, debulking status and treatment regimen, high versus low CD105-MVD was associated with increased risk of disease progression (hazard ratio [HR]=1.873; 95% confidence interval [CI]: 1.102-3.184; p=0.020), but not death (HR=1.125; 95% CI: 0.654-1.935; p=0.670) whereas CD31-MVD was not associated with risk of disease progression (HR=1.578; 95% CI=0.918-2.711; p=0.099) or death (HR=1.678; 95% CI=0.957-2.943; p=0.071). CD31-MVD was correlated with CD105-MVD (p=0.001) and MASPIN (p=0.016). Neither CD31-MVD nor CD105-MVD was associated with p53 status, THBS-1, bFGF, VEGF or VEGFR-1. CONCLUSIONS: High MVD assessed using CD105, a marker of proliferating endothelial cells and neoangiogenesis, but not CD31 a pan-endothelial marker, appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates.

Authors
Rubatt, JM; Darcy, KM; Hutson, A; Bean, SM; Havrilesky, LJ; Grace, LA; Berchuck, A; Secord, AA
MLA Citation
Rubatt, JM, Darcy, KM, Hutson, A, Bean, SM, Havrilesky, LJ, Grace, LA, Berchuck, A, and Secord, AA. "Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study." Gynecol Oncol 112.3 (March 2009): 469-474.
PMID
19135712
Source
pubmed
Published In
Gynecologic Oncology
Volume
112
Issue
3
Publish Date
2009
Start Page
469
End Page
474
DOI
10.1016/j.ygyno.2008.11.030

The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma.

OBJECTIVE: We sought to assess the accuracy of a preoperative grade 1 designation and role of lymphadenectomy in women with preoperative grade 1 endometrial cancer. METHODS: A retrospective analysis of patients diagnosed with preoperative grade 1 endometrial cancer from 1970 to 2006 was conducted. Inclusion criteria were preoperative grade 1 disease and hysterectomy with or without surgical staging. RESULTS: 581 patients who underwent surgery for preoperative grade 1 cancer were identified. Lymphadenectomy was performed in 46%. Pelvic and aortic node metastases were identified in 5.4% and 3.2% patients who underwent lymphadenectomy. 9.7% were upgraded intraoperatively and 25% were upgraded on final pathology with 22% having grade 2 and 3% grade 3 disease. 22.5% with grade 1 disease intraoperatively were upgraded on final pathology, with 21.1% having grade 2 and 1.4% grade 3 disease. 9% had advanced stage disease. 20% of patients with disease limited to the uterus had adverse features including high risk histologic variants, grade 3 disease, myometrial invasion >1/2, and/or cervical involvement. After adjusting for risk factors there was no significant difference in OS (HR 1.00, p=0.992) or PFS (HR 0.96, p=0.815) between the patients who did or did not undergo surgical staging. CONCLUSION: A substantial number of patients with grade 1 endometrial cancer based on preoperative and intraoperative assessments have higher grade disease on final pathology. Although lymphadenectomy does not affect survival in this group it may identify patients with advanced disease and assist in tailoring adjuvant therapy for those with adverse risk factors.

Authors
Neubauer, NL; Havrilesky, LJ; Calingaert, B; Bulusu, A; Bernardini, MQ; Fleming, ND; Bland, AE; Secord, AA
MLA Citation
Neubauer, NL, Havrilesky, LJ, Calingaert, B, Bulusu, A, Bernardini, MQ, Fleming, ND, Bland, AE, and Secord, AA. "The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma." Gynecol Oncol 112.3 (March 2009): 511-516.
PMID
19144394
Source
pubmed
Published In
Gynecologic Oncology
Volume
112
Issue
3
Publish Date
2009
Start Page
511
End Page
516
DOI
10.1016/j.ygyno.2008.11.012

Stage II uterine papillary serous carcinoma: Carboplatin/paclitaxel chemotherapy improves recurrence and survival outcomes.

OBJECTIVES: To determine recurrence patterns and survival outcomes of stage II uterine papillary serous carcinoma (UPSC) patients treated by various modalities with an emphasis on carboplatin/paclitaxel-based chemotherapy (CT)+/-radiotherapy (RT). METHODS: A retrospective, multi-institution study of women with stage II UPSC diagnosed from 1992 to 2006 was performed. All patients underwent comprehensive surgical staging. Treatment included observation (OBS), RT (vaginal brachytherapy, whole pelvic and/or whole abdominal therapy), or >or=3 cycles carboplatin/paclitaxel alone or with RT. Recurrence and survival outcomes were determined. RESULTS: We identified 55 subjects: 10 treated with OBS, 26 with RT alone and 19 with CT+/-RT. After a median follow-up of 33 mos (range, 10-119), 20 recurrences (36%) were observed. There was an overall difference in recurrence based upon treatment (p=.013). Specifically, all CT+/-RT treated patients had a lower risk of recurrence (11%) compared to patients treated by RT alone (50%) or OBS (50%). No patients treated with both CT+RT (n=12) experienced a recurrence. Treatment with CT was also associated with a decreased risk of recurrence on multivariate analysis (p=.015). Most recurrences were extra-pelvic (70%), occurred within 2 years (85%) and were not salvageable (84%). Five-year progression-free survival was 86% in chemotherapy-treated patients versus 41% in those not receiving chemotherapy (p=.010); overall survival was 88% in chemotherapy-treated patients versus 64% in those not receiving chemotherapy (p=.115). CONCLUSIONS: Stage II UPSC patients have a significant risk for unsalvageable, extra-pelvic recurrence. However, treatment with platinum/taxane therapy+/-RT appears to reduce this risk and is associated with improved progression free survival outcomes.

Authors
Fader, AN; Nagel, C; Axtell, AE; Zanotti, KM; Kelley, JL; Moore, KN; Secord, AA; Walsh, CS; Huh, WK; Gehrig, PA; Gibbons, H; Rose, PG; Havrilesky, LJ; Tuller, E; Drake, RD; Bottsford-Miller, J; O'Malley, DM; UPSC Consortium,
MLA Citation
Fader, AN, Nagel, C, Axtell, AE, Zanotti, KM, Kelley, JL, Moore, KN, Secord, AA, Walsh, CS, Huh, WK, Gehrig, PA, Gibbons, H, Rose, PG, Havrilesky, LJ, Tuller, E, Drake, RD, Bottsford-Miller, J, O'Malley, DM, and UPSC Consortium, . "Stage II uterine papillary serous carcinoma: Carboplatin/paclitaxel chemotherapy improves recurrence and survival outcomes." Gynecol Oncol 112.3 (March 2009): 558-562.
PMID
19118888
Source
pubmed
Published In
Gynecologic Oncology
Volume
112
Issue
3
Publish Date
2009
Start Page
558
End Page
562
DOI
10.1016/j.ygyno.2008.11.016

The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma

Authors
Secord, AA; Neubauer, N; Havrilesky, LJ; Calingaert, B; Bernardini, M; Bland, A; Fleming, N
MLA Citation
Secord, AA, Neubauer, N, Havrilesky, LJ, Calingaert, B, Bernardini, M, Bland, A, and Fleming, N. "The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma." February 2009.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
112
Issue
2
Publish Date
2009
Start Page
S91
End Page
S92

Improved survival with consolidation chemotherapy after adjuvant paclitaxel and carboplatin in advanced epithelial ovarian cancer

Authors
Shafer, A; Ayeni, TA; Deal, AM; Secord, AA; Soper, JT; Havrilesky, LJ; Van Le, L; Gehrig, PA
MLA Citation
Shafer, A, Ayeni, TA, Deal, AM, Secord, AA, Soper, JT, Havrilesky, LJ, Van Le, L, and Gehrig, PA. "Improved survival with consolidation chemotherapy after adjuvant paclitaxel and carboplatin in advanced epithelial ovarian cancer." February 2009.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
112
Issue
2
Publish Date
2009
Start Page
S135
End Page
S136

Multicenter analysis of recurrence and survival in stage IIIA endometrial cancer

Authors
Havrilesky, LJ; Secord, AA; O'Malley, DM; Bae-Jump, V; Broadwater, G; Tatagari, J; Hamamci, N; Gehrig, PA
MLA Citation
Havrilesky, LJ, Secord, AA, O'Malley, DM, Bae-Jump, V, Broadwater, G, Tatagari, J, Hamamci, N, and Gehrig, PA. "Multicenter analysis of recurrence and survival in stage IIIA endometrial cancer." February 2009.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
112
Issue
2
Publish Date
2009
Start Page
S81
End Page
S81

Early-stage uterine papillary serous carcinoma (UPSC): percentage UPSC, lymphvascular invasion and tumor size are not independent predictors of recurrence

Authors
Fader, AN; Starks, D; Rose, PG; Tuller, ER; Gibbons, H; Gehrig, PA; Huh, WK; Havrilesky, LJ; Moore, KN; Axtell, AE; Secord, AA; Kelley, JL; O'Malley, DM; Walsh, C; Drake, RD; Bottsford-Miller, J; Zanotti, KM
MLA Citation
Fader, AN, Starks, D, Rose, PG, Tuller, ER, Gibbons, H, Gehrig, PA, Huh, WK, Havrilesky, LJ, Moore, KN, Axtell, AE, Secord, AA, Kelley, JL, O'Malley, DM, Walsh, C, Drake, RD, Bottsford-Miller, J, and Zanotti, KM. "Early-stage uterine papillary serous carcinoma (UPSC): percentage UPSC, lymphvascular invasion and tumor size are not independent predictors of recurrence." February 2009.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
112
Issue
2
Publish Date
2009
Start Page
S72
End Page
S73

A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer

Authors
Secord, AA; Havrilesky, LJ; O'Malley, DM; Bae-Jump, V; Fleming, ND; Broadwater, G; Cohn, DE; Gehrig, PA
MLA Citation
Secord, AA, Havrilesky, LJ, O'Malley, DM, Bae-Jump, V, Fleming, ND, Broadwater, G, Cohn, DE, and Gehrig, PA. "A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer." February 2009.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
112
Issue
2
Publish Date
2009
Start Page
S12
End Page
S13

MiRNA patterns in ovarian cancer cell lines: Correlation with serum studies

Authors
Resnick, KE; Alder, H; Secord, AA; Whitaker, R; Richardson, DL; Heaphy, C; Murphy, SK; Baba, T; Croce, C; Colin, DE
MLA Citation
Resnick, KE, Alder, H, Secord, AA, Whitaker, R, Richardson, DL, Heaphy, C, Murphy, SK, Baba, T, Croce, C, and Colin, DE. "MiRNA patterns in ovarian cancer cell lines: Correlation with serum studies." GYNECOLOGIC ONCOLOGY 112.2 (February 2009): S115-S116.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
112
Issue
2
Publish Date
2009
Start Page
S115
End Page
S116

Relationship between tamoxifen use and high risk endometrial cancer histologic types.

OBJECTIVES: We wished to determine whether a pre-existing diagnosis of breast cancer or the use of tamoxifen among patients with pre-existing breast cancer influences the histologic type of subsequently diagnosed endometrial carcinoma, the interval between these diagnoses, or survival. METHODS: A single institution retrospective review was performed of all patients who underwent primary surgery for endometrial carcinoma from 1995-2005. We compared the histologic type of endometrial carcinoma among patients with a prior history of breast cancer to those without. Patients with a previous diagnosis of breast cancer were further analyzed by comparing histologic type, progression-free and overall survival between tamoxifen users and non-users. RESULTS: Among 732 women with endometrial carcinoma, 59 patients (8%) had a previous diagnosis of breast cancer, of whom 29 (49%) had used tamoxifen. Women with a history of breast cancer were more likely to have a high risk uterine histologic type (grade 3 endometrioid, papillary serous, or clear cell) (18/59; 31%) than those without this prior malignancy (120/670, 18%; p=0.024). Breast cancer survivors whose endometrial carcinoma was of a high risk histologic type had a longer median duration of prior tamoxifen use compared to those with lower risk histologic types (60 versus 46 months, p=0.034). CONCLUSIONS: Among women with endometrial carcinoma, those with a history of breast cancer are more likely to harbor a high risk uterine histologic subtype. Tamoxifen use of at least 60 months is associated with high risk uterine histologic subtypes when compared to no tamoxifen use. This study adds to existing data suggesting a relationship between tamoxifen use and development of endometrial carcinoma of more aggressive histologic types.

Authors
Bland, AE; Calingaert, B; Secord, AA; Lee, PS; Valea, FA; Berchuck, A; Soper, JT; Havrilesky, L
MLA Citation
Bland, AE, Calingaert, B, Secord, AA, Lee, PS, Valea, FA, Berchuck, A, Soper, JT, and Havrilesky, L. "Relationship between tamoxifen use and high risk endometrial cancer histologic types." Gynecol Oncol 112.1 (January 2009): 150-154.
PMID
18937966
Source
pubmed
Published In
Gynecologic Oncology
Volume
112
Issue
1
Publish Date
2009
Start Page
150
End Page
154
DOI
10.1016/j.ygyno.2008.08.035

In response to "The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma"

Authors
Secord, AA; Neubauer, NL
MLA Citation
Secord, AA, and Neubauer, NL. "In response to "The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma"." Gynecologic Oncology 115.2 (2009): 317--.
Source
scival
Published In
Gynecologic Oncology
Volume
115
Issue
2
Publish Date
2009
Start Page
317-
DOI
10.1016/j.ygyno.2009.07.012

Uterine neoplasms

Adenocarcinoma of the endometrium is the most common malignancy of the female genital tract in the United States. Conversely, uterine sarcomas, also included in these guidelines, are uncommon malignancies. Many physicians believe that adenocarcinoma of the endometrium is a relatively benign disease because of the early symptoms of irregular vaginal bleeding, the often-localized nature of the disease, and the generally high survival rate. However, the estimated number of deaths from endometrial cancer continues to increase, indicating the need for a critical reassessment of the guidelines for managing it. Updates of the uterine neoplasms guidelines for 2009 include expanded recommendations for systemic therapy for recurrent, metastatic, and high-risk endometrial disease; updated recommendations for systemic therapy for uterine sarcoma; and new principles of radiation therapy in both endometrial carcinoma and uterine sarcoma. © Journal of the National Comprehensive Cancer Network.

Authors
Greer, BE; Koh, W-J; Abu-Rustum, N; Bookman, MA; Bristow, RE; Campos, SM; Cho, KR; Copeland, L; Crispens, MA; Eifel, PJ; Huh, WK; Jaggernauth, W; Kapp, DS; Kavanagh, JJ; III, JRL; Morgan, M; Jr, RJM; Powell, CB; Remmenga, SW; Reynolds, RK; Secord, AA; Jr, WS; Teng, N
MLA Citation
Greer, BE, Koh, W-J, Abu-Rustum, N, Bookman, MA, Bristow, RE, Campos, SM, Cho, KR, Copeland, L, Crispens, MA, Eifel, PJ, Huh, WK, Jaggernauth, W, Kapp, DS, Kavanagh, JJ, III, JRL, Morgan, M, Jr, RJM, Powell, CB, Remmenga, SW, Reynolds, RK, Secord, AA, Jr, WS, and Teng, N. "Uterine neoplasms." JNCCN Journal of the National Comprehensive Cancer Network 7.5 (2009): 498-531.
PMID
19460278
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
7
Issue
5
Publish Date
2009
Start Page
498
End Page
531

A phase II trial of paclitaxel poliglumex in recurrent or persistent ovarian or primary peritoneal cancer (EOC): a Gynecologic Oncology Group Study.

OBJECTIVES: To estimate the anti-tumor activity and toxicity of paclitaxel poliglumex (PPX) in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer (EOC) in second or third line treatment. METHOD: Twenty-five patients received PPX at 235 mg/m(2) every 21 days (Cohort 1). At a planned analysis following first stage accrual, the dose was reduced to 175 mg/m(2) Cohort 2) for additional accrual to 78 patients. RECIST and CTC toxicity criteria were used. RESULTS: Patients received PPX in the second line (15%) and third line (85%) setting. In cohort 2, 25 out of 47 determined cases (53%) were platinum resistant and 17 out of 43 determined cases (40%) were taxane-resistant. The overall response rates for cohort 2 were 0/49 (0%) CR, 8/49 (16%) PR, and 20/49 (41%) SD. The median progression-free survival (PFS) was 2.8 months (95% CI 1.48-4.8 months) and median overall survival (OS) was 15.4 months. The most frequent grade III or IV toxicities in cohort 2 were: neutropenia (24%/20%), constitutional (8%/0%), gastrointestinal (6%/0%), and neuropathy (24%/0%). CONCLUSION: PPX at 175 mg/m(2) every 21 days has a modest activity of limited duration when given as second or third line therapy in patients with epithelial ovarian or primary peritoneal cancer. The incidence of neuropathy using this dose in recurrent ovarian cancer is higher than predicted from studies in other tumors with PPX. The Gynecology Oncology Group (GOG) is currently exploring its use at 135 mg/m(2) every 28 days in a randomized trial evaluating maintenance chemotherapy in first remission.

Authors
Sabbatini, P; Sill, MW; O'Malley, D; Adler, L; Secord, AA; Gynecologic Oncology Group Study,
MLA Citation
Sabbatini, P, Sill, MW, O'Malley, D, Adler, L, Secord, AA, and Gynecologic Oncology Group Study, . "A phase II trial of paclitaxel poliglumex in recurrent or persistent ovarian or primary peritoneal cancer (EOC): a Gynecologic Oncology Group Study." Gynecol Oncol 111.3 (December 2008): 455-460.
PMID
18829087
Source
pubmed
Published In
Gynecologic Oncology
Volume
111
Issue
3
Publish Date
2008
Start Page
455
End Page
460
DOI
10.1016/j.ygyno.2008.07.049

Cost effectiveness of intraperitoneal compared with intravenous chemotherapy for women with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: To determine the cost effectiveness of intraperitoneal versus intravenous regimens for adjuvant treatment of optimally resected stage III ovarian cancer. PATIENTS AND METHODS: A decision model was developed to compare the cost effectiveness at 7-, 11.5-, and 35-year horizons of intravenous carboplatin and paclitaxel (IV-CARBO/PAC), intravenous cisplatin and paclitaxel (IV-CIS/PAC), or intravenous paclitaxel followed by intraperitoneal cisplatin and paclitaxel (IP-CIS/PAC). Survival data were from women participating in representative Gynecologic Oncology Group (GOG) protocols. Medicare reimbursement rates and the Agency for Healthcare Research and Quality Database were used to estimate costs for treatment regimens and grade 3 to 4 adverse effects, respectively. RESULTS: Median predicted survival was 66, 57, 51, and 48 months for IP-CIS/PAC, IV-CARBO/PAC, IV-CIS/PAC (GOG 172), or IV-CIS/PAC (GOG 158), respectively. Across a range of analyses, IV-CIS/PAC was more costly and had lower life expectancy than IV-CARBO/PAC. Compared with IV-CARBO/PAC, IP-CIS/PAC had an incremental cost-effectiveness ratio (ICER) of $180,022 per quality-adjusted life year (QALY) saved at a 7-year time horizon, $71,835/QALY at 11.5 years, and $32,053/QALY over a lifetime. Extending the survival advantage of IP-CIS/PAC over 11.5 years and a lifetime results in ICERs of $26,249 and $23,973, respectively. Assuming IP-CIS/PAC and IV-CIS/PAC were equally effective when administered on an outpatient basis, the ICER of IP-CIS/PAC compared with IV-CARBO/PAC was $26,311. CONCLUSION: Inpatient IP-CIS/PAC, while not cost effective compared with IV-CARBO/PAC at 7 years, becomes cost effective if a longer time horizon is modeled and/or a survival benefit can be assumed to persist longer than currently available data. Outpatient IP-CIS/PAC may also be cost effective compared with IV-CARBO/PAC if proven as effective as inpatient IP-CIS/PAC.

Authors
Havrilesky, LJ; Secord, AA; Darcy, KM; Armstrong, DK; Kulasingam, S; Gynecologic Oncology Group,
MLA Citation
Havrilesky, LJ, Secord, AA, Darcy, KM, Armstrong, DK, Kulasingam, S, and Gynecologic Oncology Group, . "Cost effectiveness of intraperitoneal compared with intravenous chemotherapy for women with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study." J Clin Oncol 26.25 (September 1, 2008): 4144-4150.
PMID
18757328
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
25
Publish Date
2008
Start Page
4144
End Page
4150
DOI
10.1200/JCO.2007.13.1961

Medical and surgical treatment of placenta percreta to optimize bladder preservation.

BACKGROUND: Placenta percreta is associated with significant morbidity and mortality. Interventions are dictated by hemodynamic stability, desire to retain future fertility, and efforts to reduce surgical morbidity at time of delivery. CASES: Two cases of antenatally diagnosed placenta percreta with bladder invasion are presented. Conservative management was used, including endovascular interventions, leaving the placenta in situ, methotrexate, and delayed hysterectomy. Postoperative outcomes were acceptable, with no significant hemorrhagic complications or need for extensive bladder reconstruction. CONCLUSION: Antenatal diagnosis of placenta percreta with bladder invasion is essential in the multidisciplinary management of this potentially catastrophic condition. A comprehensive approach including delayed hysterectomy after medical management resulted in an excellent clinical outcome.

Authors
Lee, PS; Bakelaar, R; Fitpatrick, CB; Ellestad, SC; Havrilesky, LJ; Alvarez Secord, A
MLA Citation
Lee, PS, Bakelaar, R, Fitpatrick, CB, Ellestad, SC, Havrilesky, LJ, and Alvarez Secord, A. "Medical and surgical treatment of placenta percreta to optimize bladder preservation." Obstet Gynecol 112.2 Pt 2 (August 2008): 421-424.
PMID
18669749
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
112
Issue
2 Pt 2
Publish Date
2008
Start Page
421
End Page
424
DOI
10.1097/AOG.0b013e31817e7966

Desmoplastic small round cell tumor masquerading as advanced ovarian cancer.

Desmoplastic small round cell tumor (DSRCT) is a rare abdominal malignancy usually diagnosed in young adult males. Most patients have widespread disease at presentation, with an organ of origin difficult to ascertain. A 33-year-old female presented to her gynecologist with complaints of suprapubic pressure, abdominal pain, and increased abdominal girth. She had a large intraabdominal tumor on ultrasound, thought to be ovarian cancer. She underwent surgical exploration, which confirmed a malignancy, but the exact etiology was uncertain. Final pathology was consistent with DSRCT. DSRCT is a rare malignancy that can mimic other more commonly seen tumors such as lymphoma and ovarian cancer. When encountering an extensive intraabdominal malignancy of uncertain etiology, DSRCT should be in the differential diagnosis.

Authors
Bland, AE; Shah, AA; Piscitelli, JT; Bentley, RC; Secord, AA
MLA Citation
Bland, AE, Shah, AA, Piscitelli, JT, Bentley, RC, and Secord, AA. "Desmoplastic small round cell tumor masquerading as advanced ovarian cancer." Int J Gynecol Cancer 18.4 (July 2008): 847-850.
PMID
18081791
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
18
Issue
4
Publish Date
2008
Start Page
847
End Page
850
DOI
10.1111/j.1525-1438.2007.01110.x

A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer.

While bevacizumab has shown activity in recurrent ovarian cancer, a higher than expected incidence of bowel perforations has been reported in recent trials. We sought to determine factors associated with toxicity and tumor response in patients with relapsed ovarian cancer treated with bevacizumab. A retrospective review of patients with recurrent ovarian cancer treated with bevacizumab was undertaken. Response was determined radiographically and through CA125 measurements. Statistical analysis to determine factors associated with toxicity and response was performed. Sixty-two eligible patients were identified. The cohort had received a median of 5 prior chemotherapy regimens. Single-agent bevacizumab was administered to 12 (19%), while 50 (81%) received the drug in combination with a cytotoxic agent. Grade 3-5 toxicities occurred in 15 (24%) patients, including grade 3-4 hypertension in 4 (7%), gastrointestinal perforations in 7%, and chylous ascites in 5%. Development of chylous ascites and gastrointestinal perforations appeared to correlate with tumor response. The overall response rate was 36% (4 complete response, 17 partial response), with stable disease in 40%. A higher objective response rate was seen in the bevacizumab combination group compared to single-agent treatment (43% vs 10%) (P = 0.07). However, 29 grade 3-5 toxic episodes were seen in the combination group vs only 1 in the single-agent bevacizumab cohort (P = 0.071). We conclude that bevacizumab demonstrates promising activity in recurrent ovarian cancer. The addition of a cytotoxic agent to bevacizumab improved response rates at the cost of increased toxicity. Gastrointestinal perforations occurred in 7%. The perforations occurred in heavily pretreated patients who were responding to therapy.

Authors
Wright, JD; Secord, AA; Numnum, TM; Rocconi, RP; Powell, MA; Berchuck, A; Alvarez, RD; Gibb, RK; Trinkaus, K; Rader, JS; Mutch, DG
MLA Citation
Wright, JD, Secord, AA, Numnum, TM, Rocconi, RP, Powell, MA, Berchuck, A, Alvarez, RD, Gibb, RK, Trinkaus, K, Rader, JS, and Mutch, DG. "A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer." Int J Gynecol Cancer 18.3 (May 2008): 400-406.
PMID
17645510
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
18
Issue
3
Publish Date
2008
Start Page
400
End Page
406
DOI
10.1111/j.1525-1438.2007.01027.x

Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: a Gynecologic Oncology Group study.

PURPOSE: This phase II trial assessed the activity and tolerability of cetuximab (C225, Erbitux) in combination with carboplatin in patients with relapsed platinum-sensitive ovarian or primary peritoneal carcinoma. PATIENTS AND METHODS: Patients were to receive combination therapy with cetuximab (initial dose of 400 mg/m2 intravenously on cycle 1, day 1, followed by weekly infusions of 250 mg/m2) and carboplatin (AUC of 6 on day 1 and every 3 weeks). The primary objectives of this trial were to estimate the anti-tumor activity and adverse events of this combination therapy. Immunohistochemical expression of EGFR was evaluated in tumor specimens from patients enrolled in this trial. RESULTS: Of the 29 patients, 28 (97%) were eligible and evaluable for analysis of the efficacy and toxicity of cetuximab administered in combination with carboplatin. Of the evaluable entries, 26 had EGFR-positive tumors and the response rate in this group of patients was as follows: 9 demonstrated an objective response (3 CR; 6 PR) and 8 had stable disease. The response rate did not meet criteria for opening a second stage of accrual. The median time to progression was 9.4+ months (range: .9-22.2+). The most commonly observed adverse events were dermatologic toxicity (grade 3 in 32%), thrombocytopenia (grade 3 in 14%), and hypersensitivity reactions (grade 3 and 4 in 18%). CONCLUSIONS: Cetuximab administered in combination with carboplatin had modest activity in screened patients with EGFR-positive, relapsed platinum-sensitive ovarian or primary peritoneal carcinoma. Cetuximab was associated with an acneiform rash in a majority of patients and occasional serious hypersensitivity reactions.

Authors
Secord, AA; Blessing, JA; Armstrong, DK; Rodgers, WH; Miner, Z; Barnes, MN; Lewandowski, G; Mannel, RS; Gynecologic Oncology Group,
MLA Citation
Secord, AA, Blessing, JA, Armstrong, DK, Rodgers, WH, Miner, Z, Barnes, MN, Lewandowski, G, Mannel, RS, and Gynecologic Oncology Group, . "Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: a Gynecologic Oncology Group study." Gynecol Oncol 108.3 (March 2008): 493-499.
PMID
18191993
Source
pubmed
Published In
Gynecologic Oncology
Volume
108
Issue
3
Publish Date
2008
Start Page
493
End Page
499
DOI
10.1016/j.ygyno.2007.11.029

Prognostic relevance of microvessel density in previously untreated, advanced-stage epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study

Authors
Rubatt, JM; Darcy, KM; Hutson, A; Bean, SM; Havrilesky, LJ; Lee, PS; Grace, LA; Berchuck, A; Secord, AA
MLA Citation
Rubatt, JM, Darcy, KM, Hutson, A, Bean, SM, Havrilesky, LJ, Lee, PS, Grace, LA, Berchuck, A, and Secord, AA. "Prognostic relevance of microvessel density in previously untreated, advanced-stage epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study." GYNECOLOGIC ONCOLOGY 108.3 (March 2008): S20-S20.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
108
Issue
3
Publish Date
2008
Start Page
S20
End Page
S20

Regulation of angiogenic gene expression in p53 wild type and mutant ovarian cancer cells by hypoxia and radiation

Authors
Rubatt, JM; Secord, AA; Iversen, E; Grace, L; Soper, W; Berchuck, A
MLA Citation
Rubatt, JM, Secord, AA, Iversen, E, Grace, L, Soper, W, and Berchuck, A. "Regulation of angiogenic gene expression in p53 wild type and mutant ovarian cancer cells by hypoxia and radiation." GYNECOLOGIC ONCOLOGY 108.3 (March 2008): S84-S84.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
108
Issue
3
Publish Date
2008
Start Page
S84
End Page
S84

MAL, a gene associated with survival in epithelial ovarian cancer, is epigenetically regulated

Authors
Lee, PS; Teaberry, V; Bland, AE; Huang, Z; Secord, AA; Berchuck, A; Murphy, SK
MLA Citation
Lee, PS, Teaberry, V, Bland, AE, Huang, Z, Secord, AA, Berchuck, A, and Murphy, SK. "MAL, a gene associated with survival in epithelial ovarian cancer, is epigenetically regulated." GYNECOLOGIC ONCOLOGY 108.3 (March 2008): S125-S125.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
108
Issue
3
Publish Date
2008
Start Page
S125
End Page
S125

Surgical cytoreduction and dose intensity of adjuvant paclitaxel and carboplatin chemotherapy in advanced epithelial ovarian cancer

Authors
Shafer, A; Rubatt, JM; Ayeni, T; Deal, AM; Secord, AA; Soper, JT; Havrilesky, LJ; Van Le, L; Gehring, PA
MLA Citation
Shafer, A, Rubatt, JM, Ayeni, T, Deal, AM, Secord, AA, Soper, JT, Havrilesky, LJ, Van Le, L, and Gehring, PA. "Surgical cytoreduction and dose intensity of adjuvant paclitaxel and carboplatin chemotherapy in advanced epithelial ovarian cancer." March 2008.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
108
Issue
3
Publish Date
2008
Start Page
S55
End Page
S56

Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer.

Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR), distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

Authors
Kirkpatrick, JP; Rabbani, ZN; Bentley, RC; Hardee, ME; Karol, S; Meyer, J; Oosterwijk, E; Havrilesky, L; Secord, AA; Vujaskovic, Z; Dewhirst, MW; Jones, EL
MLA Citation
Kirkpatrick, JP, Rabbani, ZN, Bentley, RC, Hardee, ME, Karol, S, Meyer, J, Oosterwijk, E, Havrilesky, L, Secord, AA, Vujaskovic, Z, Dewhirst, MW, and Jones, EL. "Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer. (Published online)" Biomark Insights 3 (February 1, 2008): 45-55.
PMID
19578493
Source
pubmed
Published In
Biomarker Insights
Volume
3
Publish Date
2008
Start Page
45
End Page
55

Cervical cancer.

Authors
Greer, BE; Koh, W-J; Abu-Rustum, N; Bookman, MA; Bristow, RE; Campos, S; Cho, KR; Copeland, L; Eifel, P; Huh, WK; Jaggernauth, W; Kapp, DS; Kavanagh, J; Lipscomb, GH; Lurain, JR; Morgan, M; Morgan, RJ; Powell, CB; Remmenga, SW; Reynolds, RK; Secord, AA; Small, W; Teng, N; National Comprehensive Cancer Network,
MLA Citation
Greer, BE, Koh, W-J, Abu-Rustum, N, Bookman, MA, Bristow, RE, Campos, S, Cho, KR, Copeland, L, Eifel, P, Huh, WK, Jaggernauth, W, Kapp, DS, Kavanagh, J, Lipscomb, GH, Lurain, JR, Morgan, M, Morgan, RJ, Powell, CB, Remmenga, SW, Reynolds, RK, Secord, AA, Small, W, Teng, N, and National Comprehensive Cancer Network, . "Cervical cancer." J Natl Compr Canc Netw 6.1 (January 2008): 14-36.
PMID
18267056
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
1
Publish Date
2008
Start Page
14
End Page
36

Primary surgery versus chemoradiation in the treatment of IB2 cervical carcinoma: a cost effectiveness analysis.

OBJECTIVES: To estimate the relative cost-effectiveness of treatments for patients with FIGO stage IB2 cervical cancer and no evidence of metastasis as determined by combination of positron emission tomography/computed tomography (PET/CT). METHODS: A Markov state transition model was constructed to compare two strategies: (1) radical hysterectomy and pelvic lymphadenectomy with tailored adjuvant therapy (RH+TA); (2) primary chemoradiation (CR). Five-year survival estimates for FIGO stage IB2 cervical cancer were obtained from literature. Medicare reimbursement rates and Agency for Healthcare Research and Quality database were used to obtain costs of treatment regimens and grades 3-5 adverse events. Strategies were compared using incremental cost per year of life saved (YLS). Extensive sensitivity analyses were performed. RESULTS: Overall survival estimates were 78.9% for CR; 79.6% for RH+TA. Mean cost for CR at 5 years was $21,403 compared to $27,840 for RH+TA. RH+TA cost $63,689 per additional year of life saved (YLS) compared to CR. Results were most sensitive to survival estimates and the costs associated with high dose rate (HDR) versus low dose rate (LDR) brachytherapy. If 90% of patients with intermediate pathologic risk factors at surgery were assumed to receive adjuvant CR, the ICER of RH+TA rose to $100,000 per YLS compared to CR. CONCLUSIONS: RH+TA is potentially cost effective when compared to CR for patients with stage IB2 cervical cancer without metastatic disease by PET/CT imaging. Key factors in the cost-effectiveness of treatments include physician's expected recommendation of adjuvant therapy, brachytherapy modality employed for primary CR and quality of life related to both treatment and its complications.

Authors
Jewell, EL; Kulasingam, S; Myers, ER; Alvarez Secord, A; Havrilesky, LJ
MLA Citation
Jewell, EL, Kulasingam, S, Myers, ER, Alvarez Secord, A, and Havrilesky, LJ. "Primary surgery versus chemoradiation in the treatment of IB2 cervical carcinoma: a cost effectiveness analysis." Gynecol Oncol 107.3 (December 2007): 532-540.
PMID
17900674
Source
pubmed
Published In
Gynecologic Oncology
Volume
107
Issue
3
Publish Date
2007
Start Page
532
End Page
540
DOI
10.1016/j.ygyno.2007.08.056

The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer.

OBJECTIVE: : The optimal adjuvant therapy for women with stages III and IV endometrial cancer following surgical staging and cytoreductive surgery is controversial. We sought to determine the outcome of patients with advanced stage endometrial cancer treated with postoperative chemotherapy+/-radiation to determine whether there was an advantage to combining treatment modalities. METHODS: : A retrospective analysis of patients with surgical stages III and IV endometrial cancer from 1975 to 2006 was conducted at Duke University and the University of North Carolina. Inclusion criteria were comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, +/-selective pelvic/aortic lymphadenectomy, surgical debulking, and treatment with adjuvant chemotherapy and/or radiotherapy. Progression-free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: : 356 Patients with advanced stage endometrial cancer were identified who received postoperative adjuvant therapies; 48% (n=171) radiotherapy alone, 29% (n=102) chemotherapy alone, 23% (n=83) chemotherapy and radiation. The median age was 66 years; 38% had endometrioid tumors; and 83% were optimally debulked. There was a significant difference between the adjuvant treatment groups for both OS and PFS (p<0.001), with those receiving chemotherapy alone having poorer 3-year OS (33%) and PFS (19%) compared to either radiotherapy alone (70% and 59%) or combination therapy (79% and 62%). After adjusting for stage, age, grade, and debulking status the hazard ratio (HR) for OS was 1.60 (95% CI, 0.88 to 2.89; p=0.122) for chemotherapy alone and 2.01 (95% CI, 1.17 to 3.48; p=0.012) for radiotherapy alone, compared to combination therapy. When the analysis was restricted to optimally debulked patients the adjusted HR for patients who were treated with either chemotherapy or radiation alone indicated a significantly higher risk for disease progression [HR=1.84 (95% CI, 1.03 to 3.27; p=0.038); HR=1.80 (95% CI, 1.10 to 2.95; p=0.020)] and death [HR=2.33 (95% CI, 1.12 to 4.86; p=0.024); HR=2.64 (95% CI, 1.38 to 5.07; p=0.004)], respectively, compared to patients who received combination therapy. CONCLUSION: : Combined adjuvant chemotherapy and radiation was associated with improved survival in patients with advanced stage disease compared to either modality alone. Future clinical trials are needed to prospectively evaluate multi-modality adjuvant therapy in women with advanced staged endometrial cancer to determine the appropriate sequencing and types of chemotherapy and radiation.

Authors
Alvarez Secord, A; Havrilesky, LJ; Bae-Jump, V; Chin, J; Calingaert, B; Bland, A; Rutledge, TL; Berchuck, A; Clarke-Pearson, DL; Gehrig, PA
MLA Citation
Alvarez Secord, A, Havrilesky, LJ, Bae-Jump, V, Chin, J, Calingaert, B, Bland, A, Rutledge, TL, Berchuck, A, Clarke-Pearson, DL, and Gehrig, PA. "The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer." Gynecol Oncol 107.2 (November 2007): 285-291.
PMID
17688923
Source
pubmed
Published In
Gynecologic Oncology
Volume
107
Issue
2
Publish Date
2007
Start Page
285
End Page
291
DOI
10.1016/j.ygyno.2007.06.014

Management of platinum-sensitive recurrent ovarian cancer: a cost-effectiveness analysis.

OBJECTIVE: We wished to compare the cost-effectiveness of three chemotherapy regimens for treatment of recurrent platinum-sensitive ovarian cancer. METHODS: A Markov decision tree was constructed comparing three chemotherapy regimens: (1) carboplatin alone (C); (2) paclitaxel/carboplatin (PC); (3) gemcitabine/carboplatin (GC). Progression-free survival (PFS) and adverse event rates were estimated from published randomized controlled trials (RCTs). Costs of treatment and adverse events were obtained using Medicare reimbursement data. RESULTS: Estimated mean and median progression-free survival were 8.0 and 6.0 months for C, 10.1 and 7.8 months for PC, 10.5 and 8.4 months for GC, respectively. C was the least expensive strategy, costing $501 per progression-free month (PFM). PC had an incremental cost-effectiveness ratio (ICER) of $1297 per additional PFM ($15,564 per additional progression-free year (PFY)) compared to C. GC had an ICER of $23,199 per additional PFM ($278,388 per additional PFY) compared to PC. Results were insensitive to variation in the rates and costs of toxicities over clinically reasonable ranges. The model was sensitive to changes in PFS estimates. When the PFS of GC was assumed to be equivalent to that of PC, GC was strongly dominated (more expensive and no more effective) by PC due to the additional costs. Adjustment for neurotoxicity-associated quality of life (QoL) did not change rankings of strategies. CONCLUSIONS: PC appears to be relatively cost-effective compared to C for the treatment of recurrent platinum-sensitive ovarian cancer. GC appears to be less cost-effective compared to PC, with an ICER ten times higher.

Authors
Havrilesky, LJ; Secord, AA; Kulasingam, S; Myers, E
MLA Citation
Havrilesky, LJ, Secord, AA, Kulasingam, S, and Myers, E. "Management of platinum-sensitive recurrent ovarian cancer: a cost-effectiveness analysis." Gynecol Oncol 107.2 (November 2007): 211-218.
PMID
17870150
Source
pubmed
Published In
Gynecologic Oncology
Volume
107
Issue
2
Publish Date
2007
Start Page
211
End Page
218
DOI
10.1016/j.ygyno.2007.06.029

Cost-effectiveness of adjuvant radiotherapy in intermediate risk endometrial cancer.

OBJECTIVES: Endometrial cancer is the most common gynecologic malignancy in the United States. Adjuvant radiotherapy in patients with intermediate risk disease (stage IB, IC, and occult stage II) is controversial. Despite no proven survival advantage, a significant number of women undergo this treatment annually. The purpose of this study was to compare the estimated health and economic outcomes for adjuvant whole pelvic radiotherapy to no treatment with salvage therapy for recurrence. METHODS: A decision analytic model was created to estimate the costs of adjuvant pelvic radiotherapy versus no adjuvant radiotherapy in patients with intermediate risk endometrial cancer. Data used was gathered from published literature and institutional data on costs. The model incorporates complications, recurrence rates, treatment of recurrence, and survival in each group. RESULTS: In the base case analysis, adjuvant pelvic radiation reduced the recurrence rate by 50%. Cost-effectiveness as measured by cost per recurrence prevented was highly sensitive to the probability of recurrence and the efficacy of adjuvant therapy. In our model the mean costs of Strategy 1 with observation and treatment reserved until the time of recurrence would be $5016. In contrast the mean cost of Strategy 2 which incorporated adjuvant radiotherapy would be $21,159. Cost per recurrence prevented based on the incremental cost-effectiveness is thus $225,215. In the highest risk subgroup, using the upper limit of the 90% confidence limit of efficacy seen in GOG Protocol 99, cost/recurrence prevented was approximately $50,000. Results did not differ when using parameters solely from GOG 99 or PORTEC. CONCLUSIONS: Although adjuvant pelvic radiation does not appear to improve survival for intermediate risk endometrial cancer patients, it does prevent recurrences, at a net positive cost compared to no therapy. Data are not currently available to incorporate quality of life information into cost-effectiveness analyses. Obtaining such data would allow cost/quality-adjusted life year gained to be estimated. This information is necessary to determine if the extra costs of adjuvant radiotherapy in patients with intermediate risk endometrial cancer are acceptable by current health care policy standards.

Authors
Rankins, NC; Secord, AA; Jewell, E; Havrilesky, LJ; Soper, JT; Myers, E
MLA Citation
Rankins, NC, Secord, AA, Jewell, E, Havrilesky, LJ, Soper, JT, and Myers, E. "Cost-effectiveness of adjuvant radiotherapy in intermediate risk endometrial cancer." Gynecol Oncol 106.2 (August 2007): 388-393.
PMID
17509672
Source
pubmed
Published In
Gynecologic Oncology
Volume
106
Issue
2
Publish Date
2007
Start Page
388
End Page
393
DOI
10.1016/j.ygyno.2007.04.015

Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer.

PURPOSE: Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. PATIENTS AND METHODS: Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. RESULTS: In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. CONCLUSION: Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

Authors
Mutch, DG; Orlando, M; Goss, T; Teneriello, MG; Gordon, AN; McMeekin, SD; Wang, Y; Scribner, DR; Marciniack, M; Naumann, RW; Secord, AA
MLA Citation
Mutch, DG, Orlando, M, Goss, T, Teneriello, MG, Gordon, AN, McMeekin, SD, Wang, Y, Scribner, DR, Marciniack, M, Naumann, RW, and Secord, AA. "Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer." J Clin Oncol 25.19 (July 1, 2007): 2811-2818.
PMID
17602086
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
19
Publish Date
2007
Start Page
2811
End Page
2818
DOI
10.1200/JCO.2006.09.6735

Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study.

OBJECTIVES: The aim of this study was to explore the co-expression and prognostic relevance of thrombospondin-1 (THBS-1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1) in epithelial ovarian cancer (EOC). METHODS: Frozen tumor specimens with defined p53 status were obtained from 67 patients with previously untreated advanced-stage EOC who participated in a Gynecologic Oncology Group specimen-banking protocol and a phase III treatment protocol. Relative expression of the angiogenic markers was quantified by immunoblot analysis and categorized at the median angiogenic marker/actin ratio. p-values are provided as an indication of confidence in the results and to prioritize further testing. RESULTS: An association was observed between categorized VEGF and p53 overexpression (p=0.022), and between VEGFR-1 and race (p=0.027) or histologic subtype (p=0.007). Unadjusted Cox regression analyses indicated that high compared with low THBS-1, but not VEGF or VEGFR-1, was associated with an increased risk of disease progression (hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.29-3.71; p=0.004) and death (HR=1.93; 95% CI=1.12-3.32; p=0.018) whereas bFGF was associated with a reduced risk of disease progression (HR=0.60; 95% CI=0.36-0.99; p=0.046) and death (HR=0.54; 95% CI=0.32-0.93; p=0.026). After adjusting for prognostic factors including clinical characteristics and p53 overexpression, THBS-1 but not bFGF, VEGF or VEGFR-1 was associated with progression-free and overall survival. CONCLUSIONS: These data suggest that high THBS-1 is an independent predictor of worse progression-free and overall survival in women with advanced-stage EOC. A larger prospective study is warranted for validation of these findings.

Authors
Secord, AA; Darcy, KM; Hutson, A; Lee, PS; Havrilesky, LJ; Grace, LA; Berchuck, A; Gynecologic Oncology Group study,
MLA Citation
Secord, AA, Darcy, KM, Hutson, A, Lee, PS, Havrilesky, LJ, Grace, LA, Berchuck, A, and Gynecologic Oncology Group study, . "Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study." Gynecol Oncol 106.1 (July 2007): 221-232.
PMID
17481705
Source
pubmed
Published In
Gynecologic Oncology
Volume
106
Issue
1
Publish Date
2007
Start Page
221
End Page
232
DOI
10.1016/j.ygyno.2007.03.021

Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer: a multiinstitutional experience.

The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.

Authors
Huh, WK; Straughn, JM; Mariani, A; Podratz, KC; Havrilesky, LJ; Alvarez-Secord, A; Gold, MA; McMeekin, DS; Modesitt, S; Cooper, AL; Powell, MA; Mutch, DG; Nag, S; Alvarez, RD; Cohn, DE
MLA Citation
Huh, WK, Straughn, JM, Mariani, A, Podratz, KC, Havrilesky, LJ, Alvarez-Secord, A, Gold, MA, McMeekin, DS, Modesitt, S, Cooper, AL, Powell, MA, Mutch, DG, Nag, S, Alvarez, RD, and Cohn, DE. "Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer: a multiinstitutional experience." Int J Gynecol Cancer 17.4 (July 2007): 886-889.
PMID
17309665
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
17
Issue
4
Publish Date
2007
Start Page
886
End Page
889
DOI
10.1111/j.1525-1438.2007.00858.x

Outcomes in surgical stage I uterine papillary serous carcinoma.

OBJECTIVE: The optimal management of patients with stage I uterine papillary serous carcinoma (UPSC) is unclear. We sought to determine whether outcomes of women with surgical stage I UPSC differ with and without adjuvant therapy. METHODS: Retrospective multi-institution analysis of women with stage I UPSC surgically staged from 1976 to 2006. INCLUSION CRITERIA: comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, selective pelvic/aortic lymphadenectomy, peritoneal cytology. Recurrence and survival were analyzed using Kaplan-Meier method. RESULTS: Of 83 women with stage I UPSC, 36 (43%) received adjuvant therapies (23% radiotherapy, 3% chemotherapy, 15% chemotherapy and radiotherapy, 2% progestins). Three-year overall (OS) and progression-free survival (PFS) were 80% and 68%, respectively. Three-year OS and PFS by adjuvant treatment were observation (N=47) 86% and 78%, radiotherapy (N=17) 63% and 44%, chemotherapy with or without radiotherapy (N=17) 92% and 76%, respectively. Of the 18 recurrences, 9 (50%) included an extrapelvic component. Local recurrence was 2/30 (7%) following adjuvant radiotherapy and 7/53 (13%) without radiotherapy (p=0.48). Recurrence was higher in stage IB/IC (15/51, 29%) compared to stage IA (3/32, 9%). There has been one recurrence (5%) among the 22 women observed with stage IA disease. CONCLUSION: In this largest reported series of women with surgical stage I UPSC, the high recurrence (29%) among patients with stage IB/IC disease highlights the need for clinical trials to test new therapeutic approaches. Surgically staged patients with IA disease had good prognosis. These data suggest that radiotherapy alone is not effective, that systemic therapy is needed, and that observation could be considered in patients with stage IA disease.

Authors
Havrilesky, LJ; Secord, AA; Bae-Jump, V; Ayeni, T; Calingaert, B; Clarke-Pearson, DL; Berchuck, A; Gehrig, PA
MLA Citation
Havrilesky, LJ, Secord, AA, Bae-Jump, V, Ayeni, T, Calingaert, B, Clarke-Pearson, DL, Berchuck, A, and Gehrig, PA. "Outcomes in surgical stage I uterine papillary serous carcinoma." Gynecol Oncol 105.3 (June 2007): 677-682.
PMID
17355889
Source
pubmed
Published In
Gynecologic Oncology
Volume
105
Issue
3
Publish Date
2007
Start Page
677
End Page
682
DOI
10.1016/j.ygyno.2007.01.041

Most early-stage serous ovarian cancers have gene expression profiles predictive of long-term survival

Authors
Berchuck, A; Lancaster, JM; Iversen, ES; Luo, J; Levine, DA; Boyd, J; Secord, AA; Marks, JR; Nevins, JR; Dressman, H
MLA Citation
Berchuck, A, Lancaster, JM, Iversen, ES, Luo, J, Levine, DA, Boyd, J, Secord, AA, Marks, JR, Nevins, JR, and Dressman, H. "Most early-stage serous ovarian cancers have gene expression profiles predictive of long-term survival." March 2007.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
104
Issue
3
Publish Date
2007
Start Page
S15
End Page
S16

The role of multimodality adjuvant chemotherapy and radiation in women with advanced-stage endometrial cancer

Authors
Alvarez Secord, A; Gehrig, PA; Havrilesky, LJ; Bae-Jump, V; Chin, J; Calingaert, B; Bland, A; Rutledge, T; Berchuck, A; Clarke-Pearson, DL
MLA Citation
Alvarez Secord, A, Gehrig, PA, Havrilesky, LJ, Bae-Jump, V, Chin, J, Calingaert, B, Bland, A, Rutledge, T, Berchuck, A, and Clarke-Pearson, DL. "The role of multimodality adjuvant chemotherapy and radiation in women with advanced-stage endometrial cancer." GYNECOLOGIC ONCOLOGY 104.3 (March 2007): S6-S6.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
104
Issue
3
Publish Date
2007
Start Page
S6
End Page
S6

Phase II study of cetuximab in combination with carboplatin in patients with relapsed platinum-sensitive ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor immunohistochemical expression: A Gynecologic Oncology Group study

Authors
Secord, AA; Blessing, JA; Armstrong, D; III, BMN; Lewandowski, G; Mannel, RS
MLA Citation
Secord, AA, Blessing, JA, Armstrong, D, III, BMN, Lewandowski, G, and Mannel, RS. "Phase II study of cetuximab in combination with carboplatin in patients with relapsed platinum-sensitive ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor immunohistochemical expression: A Gynecologic Oncology Group study." March 2007.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
104
Issue
3
Publish Date
2007
Start Page
S32
End Page
S32

Weekly low-dose paclitaxel and carboplatin in the treatment of advanced or recurrent cervical and endometrial cancer.

BACKGROUND: The purpose of this study was to evaluate the toxicity profile of weekly low-dose paclitaxel and carboplatin in patients with gynecologic malignancies. METHODS: Patients had measurable disease defined by clinical examination or radiographic studies. Each cycle of treatment consisted of carboplatin at an AUC of 2 and paclitaxel at 80 mg/m2 on days 1, 8, and 15 of a 28-day cycle. RESULTS: Twenty-eight patients with advanced or recurrent cervical and endometrial cancers were included in this study. The overall response rate (ORR) was 39% (2 CR, 9 PR). Among the 15 cervical cancers the ORR was 20%, while the 13 endometrial cancers had a 62% ORR. Median time to progression and overall survival was 3.4 and 7.6 months for those with cervical cancer and 5.5 and 15.4 months for those with endometrial cancer. Grade 3 or 4 hematologic toxicity was uncommon (7% grade 3 anemia, 21% grade 3 or 4 neutropenia, 7% grade 3 or 4 thrombocytopenia). CONCLUSION: A regimen of weekly low-dose paclitaxel and carboplatin has an acceptable toxicity profile that is easily managed by dose adjustment and the use of erythropoietic therapy. This regimen appears to have activity in advanced or recurrent endometrial cancer which warrants further evaluation.

Authors
Secord, AA; Havrilesky, LJ; Carney, ME; Soper, JT; Clarke-Pearson, DL; Rodriguez, GC; Berchuck, A
MLA Citation
Secord, AA, Havrilesky, LJ, Carney, ME, Soper, JT, Clarke-Pearson, DL, Rodriguez, GC, and Berchuck, A. "Weekly low-dose paclitaxel and carboplatin in the treatment of advanced or recurrent cervical and endometrial cancer." Int J Clin Oncol 12.1 (February 2007): 31-36.
PMID
17380438
Source
pubmed
Published In
International Journal of Clinical Oncology
Volume
12
Issue
1
Publish Date
2007
Start Page
31
End Page
36
DOI
10.1007/s10147-006-0619-9

The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer.

OBJECTIVE: The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment. METHODS: Retrospective single institution analysis of patients surgically staged for IIIA endometrial cancer at Duke University Medical Center from 1973 to 2002. Stage IIIA patients were stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae or uterine serosa (group IIIA2, n=20). Comparison was made with previously reported group of 467 patients with surgical stage I/II disease. Recurrence and survival were analyzed using Kaplan-Meier estimations and Cox proportional hazards model. RESULTS: Mean age of 57 patients with stage IIIA endometrial cancer was 63. Adjuvant therapies were administered to 89% patients (74% radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively. Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32 84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included extrapelvic component. In multivariable analysis of stage I-IIIA patients (n=517), positive cytology but not adnexal/serosal metastasis was predictive of death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07-2.71). CONCLUSION: Among patients with stage IIIA endometrial cancer, metastasis to adnexae or serosa does not appear to confer worse prognosis than positive cytology alone. Positive cytology is an independent predictor of prognosis among patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for these groups remains unclear, recurrence patterns suggest that systemic therapies are appropriate.

Authors
Havrilesky, LJ; Cragun, JM; Calingaert, B; Alvarez Secord, A; Valea, FA; Clarke-Pearson, DL; Berchuck, A; Soper, JT
MLA Citation
Havrilesky, LJ, Cragun, JM, Calingaert, B, Alvarez Secord, A, Valea, FA, Clarke-Pearson, DL, Berchuck, A, and Soper, JT. "The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer." Gynecol Oncol 104.2 (February 2007): 401-405.
PMID
17014898
Source
pubmed
Published In
Gynecologic Oncology
Volume
104
Issue
2
Publish Date
2007
Start Page
401
End Page
405
DOI
10.1016/j.ygyno.2006.08.027

Comparison of gracilis and rectus abdominis myocutaneous flap neovaginal reconstruction performed during radical pelvic surgery: flap-specific morbidity.

To compare flap-specific complications of gracilis myocutaneous (GM) and rectus abdominis myocutaneous (RAM) flap neovaginal reconstructions after radical pelvic surgery. The study was a single-institution retrospective review of patients undergoing concurrent radical pelvic surgery with GM or RAM neovaginal reconstructions performed on a gynecological oncology service, 1978-2003. Flap-specific complications were compared between the techniques. Forty-four GM and 32 RAM neovaginal reconstructions were analyzed: plastic surgeons developed 12 (27%) GM and 4 (13%) RAM flaps, with all other flaps performed by gynecological oncologists. Primary procedures included 54 (71%) total pelvic exenterations, with partial exenterations or radical vulvovaginectomies in 16 (21%) and 6 (8%) patients, respectively. Forty (53%) patients had received radiation and 28 (36%) received chemoradiation before radical surgery. There were no significant differences in patient characteristics, other than more frequent use of continent urinary conduits (P < 0.001) and a trend for more frequent sidewall radiation (P < 0.1) in the RAM group, reflecting use in more recent patients (P < 0.001). Median follow-up is 28 months (range: 2 weeks to 216 months), with 5% acute operative mortality. Flap-specific complications were significantly increased in GM patients (P < 0.03). Overall flap loss was significantly increased in GM patients (P < 0.02). Thirty (59%) of 51 patients surviving for more than 12 months reported coitus, with no significant difference between the groups. Because of lower overall incidence of flap-specific complications and significantly lower incidence of flap loss compared with GM flap, RAM flap has become our technique of choice for neovaginal reconstruction concurrent with radical pelvic surgery.

Authors
Soper, JT; Secord, AA; Havrilesky, LJ; Berchuck, A; Clarke-Pearson, DL
MLA Citation
Soper, JT, Secord, AA, Havrilesky, LJ, Berchuck, A, and Clarke-Pearson, DL. "Comparison of gracilis and rectus abdominis myocutaneous flap neovaginal reconstruction performed during radical pelvic surgery: flap-specific morbidity." Int J Gynecol Cancer 17.1 (January 2007): 298-303.
PMID
17291272
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
17
Issue
1
Publish Date
2007
Start Page
298
End Page
303
DOI
10.1111/j.1525-1438.2007.00784.x

Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology.

OBJECTIVE: To determine whether pelvic lymph node count is associated with patterns of recurrence or survival in patients with FIGO stage I and II endometrial cancer. METHODS: Single institution retrospective study of 467 patients with FIGO stage I and II endometrial cancer treated with primary surgery including lymph node dissection. Analysis included pelvic lymph node count, histology, stage, age, race, BMI, year of surgery, depth of myometrial invasion, and adjuvant radiation. Kaplan-Meier life-tables were used to calculate survival; the Cox proportional hazards model was used to identify prognostic factors independently associated with survival. RESULTS: Mean pelvic lymph node count was 12.6 (SD +/- 8). Distant recurrence was associated with decreased pelvic lymph node count, high-risk histology, and postoperative pelvic radiation. Pelvic lymph node count was not associated with survival by univariate analysis, however, overall (OS) and progression-free (PFS) survival were significantly better with pelvic lymph node counts >or=12 among women with high-risk histology (P < 0.001), but not among women with low-risk histology. Multivariable Cox proportional hazards regression identified increasing age, non-Caucasian race, and high-risk histology as independent negative prognostic factors for both OS and PFI. Among patients with high-risk histology, pelvic lymph node count remained an independent prognostic factor for both overall (OS) and progression-free survival (PFS) in the model, with hazard ratios of 0.28 and 0.29, respectively, when >or=12 pelvic lymph nodes were identified. Pelvic lymph node count had no association with OS or PFS in women with low-risk histology. CONCLUSION: Pelvic lymph node count >or=12 is an important prognostic variable in patients with FIGO stage I and II endometrial cancer who have high-risk histology. Most likely, the association of survival and lymph node count in this group is the result of improved staging among patients with higher pelvic lymph node counts.

Authors
Lutman, CV; Havrilesky, LJ; Cragun, JM; Secord, AA; Calingaert, B; Berchuck, A; Clarke-Pearson, DL; Soper, JT
MLA Citation
Lutman, CV, Havrilesky, LJ, Cragun, JM, Secord, AA, Calingaert, B, Berchuck, A, Clarke-Pearson, DL, and Soper, JT. "Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology." Gynecol Oncol 102.1 (July 2006): 92-97.
PMID
16406063
Source
pubmed
Published In
Gynecologic Oncology
Volume
102
Issue
1
Publish Date
2006
Start Page
92
End Page
97
DOI
10.1016/j.ygyno.2005.11.032

A comparison of combination docetaxel/carboplatin versus sequential docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer.

Authors
Secord, AA; Havrilesky, LJ; Higgins, RV; Nycum, LR; Kohler, MF; Puls, LE; Holloway, R; Soper, JT; Valea, FA; Berchuck, A
MLA Citation
Secord, AA, Havrilesky, LJ, Higgins, RV, Nycum, LR, Kohler, MF, Puls, LE, Holloway, R, Soper, JT, Valea, FA, and Berchuck, A. "A comparison of combination docetaxel/carboplatin versus sequential docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer." June 20, 2006.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
24
Issue
18
Publish Date
2006
Start Page
278S
End Page
278S

Maspin expression in epithelial ovarian cancer and associations with poor prognosis: a Gynecologic Oncology Group study.

OBJECTIVE: This study examined MASPIN expression in human ovarian cancer, and explored the association between MASPIN and prognosis in patients with advanced stage disease treated with first-line cisplatin, carboplatin and/or paclitaxel. METHODS: Frozen primary tumors were obtained from 68 women with previously untreated, advanced stage epithelial ovarian cancer who participated in a specimen banking protocol and a phase III treatment trial conducted by the Gynecologic Oncology Group. Immunoblot analysis was performed in lysates prepared from these tumor specimens to quantify the relative expression of MASPIN/beta-actin. RESULTS: MASPIN was expressed at detected levels in 49 (72%) cases with relative expression ranging from 0.02 to 7.7 (median = 0.2), and was not detected in 19 (28%) of the primary tumors tested. Non-detectable levels of this class II tumor suppressor gene product and inhibitor of angiogenesis were associated with suboptimally-debulked disease (P = 0.034) but not with patient age, FIGO stage, tumor grade, or histologic subtype. After adjusting for prognostic variables for disease progression or death, non-detectable MASPIN expression predicted an increased risk of disease progression (hazard ratio [HR] = 1.89; 95% confidence interval [CI]: 1.04-3.45; P = 0.038) and death (HR = 1.99; 95% CI: 1.07-3.69; P = 0.030). CONCLUSIONS: In advanced stage epithelial ovarian cancer, non-detectable MASPIN appears to be associated with suboptimally-debulked disease and be an independent predictor of an increased risk of progression and death. Further studies are needed to validate these exploratory findings, determine the molecular mechanism controlling MASPIN expression as well as down-regulation and loss in ovarian cancer, and determine if MASPIN can prevent progression of this disease.

Authors
Gynecologic Oncology Group, ; Secord, AA; Lee, PS; Darcy, KM; Havrilesky, LJ; Grace, LA; Marks, JR; Berchuck, A
MLA Citation
Gynecologic Oncology Group, , Secord, AA, Lee, PS, Darcy, KM, Havrilesky, LJ, Grace, LA, Marks, JR, and Berchuck, A. "Maspin expression in epithelial ovarian cancer and associations with poor prognosis: a Gynecologic Oncology Group study." Gynecol Oncol 101.3 (June 2006): 390-397.
PMID
16551475
Source
pubmed
Published In
Gynecologic Oncology
Volume
101
Issue
3
Publish Date
2006
Start Page
390
End Page
397
DOI
10.1016/j.ygyno.2006.02.014

Use of trastuzumab in the treatment of metastatic endometrial cancer.

Systemic therapy of metastatic endometrial cancer is relatively ineffective. Response rates to chemotherapy and hormonal therapy in published studies range from 11% to 57%, but most responses are partial and of limited duration. In this case, we present a 76-year-old woman with stage IIIA endometrial adenocarcinoma who was initially treated with surgery and pelvic radiation. She developed multiple pulmonary metastases. She was treated with weekly paclitaxel chemotherapy. Immunostaining revealed that the primary endometrial cancer overexpressed HER-2/neu. Trastuzumab was added to the regimen, and a dramatic partial response was achieved. After a second pulmonary relapse following discontinuation of prior therapy, she was again successfully treated with trastuzumab in combination with paclitaxel and then docetaxel. Therefore, trastuzumab may be a useful adjuvant to taxane-based chemotherapy in some patients with metastatic endometrial cancers that overexpress HER-2/neu.

Authors
Jewell, E; Secord, AA; Brotherton, T; Berchuck, A
MLA Citation
Jewell, E, Secord, AA, Brotherton, T, and Berchuck, A. "Use of trastuzumab in the treatment of metastatic endometrial cancer." Int J Gynecol Cancer 16.3 (May 2006): 1370-1373.
PMID
16803532
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
16
Issue
3
Publish Date
2006
Start Page
1370
End Page
1373
DOI
10.1111/j.1525-1438.2006.00543.x

Intra-peritoneal cisplatin and whole abdomen hyperthermia for relapsed ovarian carcinoma.

The study was designed to determine the maximum tolerated dose (MTD) of IP cisplatin [CDDP] combined with intravenous thiosulphate and concurrent whole abdomen hyperthermia for advanced, recurrent or progressive ovarian carcinoma. Between September 1991 and November 1998, 41 patients with advanced epithelial ovarian cancer received escalating doses of IP (IP) cisplatin (six cycles given every 3-4 weeks) and whole abdomen hyperthermia with intravenous thiosulphate as second line treatment. Whole abdomen hyperthermia was administrated using a BSD-2000 annular phased array system. Forty-one patients were enrolled in the phase I/II portions of the study. Forty-four per cent (18/41) had undergone sub-optimal cytoreductive surgery and 15% (6/41) had been optimally debulked of their disease. Ninety per cent (37/41) had platinum-resistant disease and 10% (4/41) had platinum-sensitive disease. No DLTs occurred in the phase I testing and the recommended dose for this combination schedule was 180 mg m-2 of IP cisplatin with thiosulphate and whole abdomen hyperthermia. The overall response rate was 44% (10 CR, 8 PR) and the median survival for all patients from protocol entry was 30 months (range 2-107 months). Median duration and survival of those achieving a pathologic CR was 14 months (range 2-27 months) and 35 months (range 14-71 months, 95% CI 16-54 months), respectively. Salvage platinum based IP cisplatin with hyperthermia did achieve pathologic CR in selected patients and was well tolerated. These promising results suggest a role for the use of adjuvant whole abdomen hyperthermia as a means of augmenting chemosensitization.

Authors
Jones, E; Alvarez Secord, A; Prosnitz, LR; Samulski, TV; Oleson, JR; Berchuck, A; Clarke-Pearson, D; Soper, J; Dewhirst, MW; Vujaskovic, Z
MLA Citation
Jones, E, Alvarez Secord, A, Prosnitz, LR, Samulski, TV, Oleson, JR, Berchuck, A, Clarke-Pearson, D, Soper, J, Dewhirst, MW, and Vujaskovic, Z. "Intra-peritoneal cisplatin and whole abdomen hyperthermia for relapsed ovarian carcinoma." Int J Hyperthermia 22.2 (March 2006): 161-172.
PMID
16754599
Source
pubmed
Published In
International Journal of Hyperthermia (Informa)
Volume
22
Issue
2
Publish Date
2006
Start Page
161
End Page
172
DOI
10.1080/02656730500515270

Targeted bio weapons in the war against gynecologic cancers

Will biological warfare revolutionize the battle against gynecologic cancers? Two experts share the latest molecular tactics using "special" agents. Lethal weapons like Herceptin can throw up some roadblocks, even when they can't always destroy a tumor.

Authors
Secord, AA; Berchuck, A
MLA Citation
Secord, AA, and Berchuck, A. "Targeted bio weapons in the war against gynecologic cancers." Contemporary Ob/Gyn 51.10 (2006): 48-54.
Source
scival
Published In
Contemporary ob/gyn
Volume
51
Issue
10
Publish Date
2006
Start Page
48
End Page
54

Tissue transglutaminase expression in early-stage cervical cancer

Authors
Rabbani, ZN; Kirkpatrick, JP; Salahuddin, FK; Bentley, RC; Secord, AA; Greenberg, CS; Havrilesky, LJ; Vujaskovic, Z; Jones, E; Dewhirst, MW
MLA Citation
Rabbani, ZN, Kirkpatrick, JP, Salahuddin, FK, Bentley, RC, Secord, AA, Greenberg, CS, Havrilesky, LJ, Vujaskovic, Z, Jones, E, and Dewhirst, MW. "Tissue transglutaminase expression in early-stage cervical cancer." 2006.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S167
End Page
S167
DOI
10.1016/j.ijrobp.2006.07.331

Combined PET/DCT for evaluation of newly diagnosed endometrial cancer: Implications for radiation therapy

Authors
Jones, EL; Havrilesky, LJ; Secord, AA; Clarke-Pearson, DL; Soper, JT; Valea, F; Coleman, RE; Wong, TZ
MLA Citation
Jones, EL, Havrilesky, LJ, Secord, AA, Clarke-Pearson, DL, Soper, JT, Valea, F, Coleman, RE, and Wong, TZ. "Combined PET/DCT for evaluation of newly diagnosed endometrial cancer: Implications for radiation therapy." 2006.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S40
End Page
S40
DOI
10.1016/j.ijrobp.2006.07.098

Resection of lymph node metastases influences survival in stage IIIC endometrial cancer.

OBJECTIVE: Surgical staging of endometrial cancer identifies those patients with microscopic metastatic disease most likely to benefit from adjuvant therapy and may also confer therapeutic benefit. Our objective was to compare survival of patients who underwent resection of grossly positive lymph nodes (LN) to those with microscopically positive LN. METHODS: Patients had stage IIIC endometrial cancer with pelvic and/or aortic LN metastases and underwent surgery between 1973 and 2002. Exclusion criteria included pre-surgical radiation and second primary cancer. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Mean age of 96 patients with stage IIIC endometrial cancer was 64. There were 45 cases with microscopic LN involvement and 51 with grossly enlarged LN. Overall, 41% had disease in aortic LN, which in 18% represented isolated aortic LN metastasis. Adjuvant therapies were given to 92% of patients (85% radiotherapy, 10% chemotherapy, 10% progestins). Among those with grossly involved LN, 86% were completely resected. Five-year disease-specific survival (DSS) was 63% in 45 patients with microscopic metastatic disease compared to 50% in 44 patients with grossly positive LN completely resected and 43% in 7 with residual macroscopic disease. In multivariable analyses, gross nodal disease not debulked (HR=6.85, P=0.009), serosal/adnexal involvement (HR=2.24, P=0.036), diagnosis prior to 1989 (HR=4.33, P<0.001), older age (HR=1.09, P<0.001), and >2 positive lymph nodes (HR=3.12, P=0.007) were associated with lower DSS. CONCLUSION: Grossly involved LN can often be completely resected in patients with stage IIIC endometrial cancer. These retrospective data provide evidence suggestive of a therapeutic benefit for lymphadenectomy in endometrial cancer.

Authors
Havrilesky, LJ; Cragun, JM; Calingaert, B; Synan, I; Secord, AA; Soper, JT; Clarke-Pearson, DL; Berchuck, A
MLA Citation
Havrilesky, LJ, Cragun, JM, Calingaert, B, Synan, I, Secord, AA, Soper, JT, Clarke-Pearson, DL, and Berchuck, A. "Resection of lymph node metastases influences survival in stage IIIC endometrial cancer." Gynecol Oncol 99.3 (December 2005): 689-695.
PMID
16126261
Source
pubmed
Published In
Gynecologic Oncology
Volume
99
Issue
3
Publish Date
2005
Start Page
689
End Page
695
DOI
10.1016/j.ygyno.2005.07.014

Randomized phase III trial of gemcitabine (GEM) versus pegylated liposomal doxorubicin (PLDOX) for patients (pts.) with platinum-resistant (pt-r) ovarian cancer (oc) undergoing second or third-line chemotherapy (ct)

Authors
Mutch, D; Orlando, M; Teneriello, T; Gordon, A; McMeekin, S; Goss, T; Scribner, D; Naumann, R; Secord, AA; Wang, Y
MLA Citation
Mutch, D, Orlando, M, Teneriello, T, Gordon, A, McMeekin, S, Goss, T, Scribner, D, Naumann, R, Secord, AA, and Wang, Y. "Randomized phase III trial of gemcitabine (GEM) versus pegylated liposomal doxorubicin (PLDOX) for patients (pts.) with platinum-resistant (pt-r) ovarian cancer (oc) undergoing second or third-line chemotherapy (ct)." October 2005.
Source
wos-lite
Published In
European Journal of Cancer Supplements
Volume
3
Issue
2
Publish Date
2005
Start Page
262
End Page
262

Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer.

PURPOSE: Selective lymphadenectomy is widely accepted in the management of endometrial cancer. Purported benefits are individualization of adjuvant therapy based on extent of disease and resection of occult metastases. Our goal was to assess effects of the extent of selective lymphadenectomy on outcomes in women with apparent stage I endometrial cancer at laparotomy. PATIENTS AND METHODS: Patients with endometrial cancer who received primary surgical treatment between 1973 and 2002 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/IIA disease and procedure including hysterectomy and selective lymphadenectomy (pelvic or pelvic + aortic). Exclusion criteria included presurgical radiation, grossly positive lymph nodes, or extrauterine metastases at laparotomy. Recurrence and survival were analyzed using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: Among 509 patients, the median number of lymph nodes removed was 15 (median pelvic, 11; median aortic, three). Pelvic and aortic node metastases were found in 24 (5%) of 509 patients and 11 (3%) of 373 patients, respectively. Patients with poorly differentiated cancers having more than 11 pelvic nodes removed had improved overall survival (hazard ratio [HR], 0.25; P < .0001) and progression-free survival (HR, 0.26; P < .0001) compared with patients having poorly differentiated cancers with 11 or fewer nodes removed. Number of nodes removed was not predictive of survival among patients with cancers of grade 1 to 2. Performance of aortic selective lymphadenectomy was not associated with survival. Three (27%) of 11 patients with microscopic aortic nodal metastasis are alive without recurrence. CONCLUSION: These data add to the literature documenting the possible therapeutic benefit of selective lymphadenectomy in management of patients with apparent early-stage endometrial cancer.

Authors
Cragun, JM; Havrilesky, LJ; Calingaert, B; Synan, I; Secord, AA; Soper, JT; Clarke-Pearson, DL; Berchuck, A
MLA Citation
Cragun, JM, Havrilesky, LJ, Calingaert, B, Synan, I, Secord, AA, Soper, JT, Clarke-Pearson, DL, and Berchuck, A. "Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer." J Clin Oncol 23.16 (June 1, 2005): 3668-3675.
PMID
15738538
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
16
Publish Date
2005
Start Page
3668
End Page
3675
DOI
10.1200/JCO.2005.04.144

Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer.

OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects. PATIENTS AND METHODS: Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle. RESULTS: Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy. CONCLUSIONS: Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.

Authors
Alvarez Secord, A; Jones, EL; Hahn, CA; Petros, WP; Yu, D; Havrilesky, LJ; Soper, JT; Berchuck, A; Spasojevic, I; Clarke-Pearson, DL; Prosnitz, LR; Dewhirst, MW
MLA Citation
Alvarez Secord, A, Jones, EL, Hahn, CA, Petros, WP, Yu, D, Havrilesky, LJ, Soper, JT, Berchuck, A, Spasojevic, I, Clarke-Pearson, DL, Prosnitz, LR, and Dewhirst, MW. "Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer." Int J Hyperthermia 21.4 (June 2005): 333-347.
PMID
16019859
Source
pubmed
Published In
International Journal of Hyperthermia (Informa)
Volume
21
Issue
4
Publish Date
2005
Start Page
333
End Page
347
DOI
10.1080/02656730500110155

Prospective assessment of quality of life in ovarian cancer patients receiving whole abdomen hyperthermia and liposomal doxorubicin.

PURPOSE: Prospective assessment of quality of life (QoL) in patients with refractory, residual or recurrent ovarian cancer receiving whole abdomen hyperthermia and intravenous liposomal doxorubicin chemotherapy. METHODS: Treatment consisted of six cycles of intravenous liposomal doxorubicin at 40 mg m2 followed by whole abdomen hyperthermia with each cycle delivered every 4 weeks. QoL assessment was performed at baseline, prior to each cycle of chemotherapy and every 3 months during follow-up using self-administered questionnaires. Global QoL was rated on a seven-point scale and specific domains of QoL, disease related symptoms and treatment related toxicity were rated on a four-point scale. RESULTS: Thirty-two patients were enrolled on the study and 129 QoL questionnaires were completed. Average age was 57.9 (range 45-76); nine patients had persistent and 23 recurrent disease. Ten patients completed six cycles of therapy. Three patients returned follow-up surveys. Subjects rated their overall QoL and health at baseline as above average with mean scores 5.10 (95% CI=4.62-5.58) and 4.66 (95% CI=4.23-5.08), respectively. No significant change in overall QoL was found between baseline and cycles 4-6 of therapy. Mean ratings of overall health and subject reported differences in QoL between cycles were not significantly changed during therapy. Limited follow-up data were available, but scores suggest possible improvement in QoL for patients completing all therapy. Subjects rated the greatest negative impact on QoL in areas of role functioning and social functioning, where the mean (SD) over all cycles was 2.00 (0.67) and 1.98 (0.70), respectively. For physical symptoms, fatigue and sleep disturbance had the most negative impact on QoL with means (SD) of 2.26 (0.62) and 1.91 (0.70). The moderate treatment related toxicity seen in this study did not significantly impact patients reported QoL. CONCLUSIONS: Patients with unfavourable ovarian cancer responding to intravenous liposomal doxorubicin and whole abdomen hyperthermia maintained above average QoL during therapy. Limited data on patients completing protocol therapy demonstrated possible improvement in QoL.

Authors
Hahn, CA; Jones, EL; Blivin, JL; Sanders, LL; Yu, D; Dewhirst, MW; Secord, AA; Prosnitz, LR
MLA Citation
Hahn, CA, Jones, EL, Blivin, JL, Sanders, LL, Yu, D, Dewhirst, MW, Secord, AA, and Prosnitz, LR. "Prospective assessment of quality of life in ovarian cancer patients receiving whole abdomen hyperthermia and liposomal doxorubicin." Int J Hyperthermia 21.4 (June 2005): 349-357.
PMID
16019860
Source
pubmed
Published In
International Journal of Hyperthermia (Informa)
Volume
21
Issue
4
Publish Date
2005
Start Page
349
End Page
357
DOI
10.1080/02656730400022260

Rectus abdominis myocutaneous flaps for neovaginal reconstruction after radical pelvic surgery.

The objective of this article is to compare the flap-specific complications associated with vertical (VRAM) and transverse (TRAM) rectus abdominis myocutaneous flap vaginal reconstructions performed during radical pelvic procedures. A retrospective chart review was performed to identify all patients who underwent VRAM and TRAM neovaginal reconstructions performed on the Gynecologic Oncology Service at Duke University Medical Center. Flap-specific complications were compared between the two techniques. From 1988 to 2003, 14 VRAM and 18 TRAM flap neovaginal reconstructions were performed on 32 women during the course of 22 (68%) total pelvic exenterations, 8 (25%) partial exenterations, and 2 (6%) radical vulvovaginectomies. Twenty-eight (88%) patients had been previously treated with radiation therapy or concurrent chemoradiation. Associated procedures included continent urinary conduit in 21 (66%), rectosigmoid reanastomosis in 8 (25%), and intraoperative or postoperative sidewall radiation therapy in 7 (22%) of patients. Overall median survival was 14 months (range: 2-week postoperative death to 65 months), with two (6%) acute postoperative mortalities. Fifteen flap-specific complications occurred in 12 (38%) patients, with no significant differences in flap type. Abdominal wound complications included four (12%) superficial wound separations, while one (3%) patient had a fascial dehiscence associated with complex fistulas that contributed to her death, but no patient developed incisional hernia. One patient each developed > 50% flap loss after TRAM and < 50% flap loss after VRAM flap, respectively. Four (12%) patients developed vaginal stricture or stenosis, two (6%) required percutaneous drainage of pelvic abscess or hematoma, and two (6%) developed rectovaginal fistula. Univariate analysis revealed a trend for increasing flap loss with body mass index > 35 (P = 0.056, Fisher exact two-tailed test), but there were no significant associations with other patient characteristics or flap-specific complications. Thirteen (62%) of 21 patients who survived >12 months reported coitus. Both VRAM and TRAM are reliable techniques for neovaginal reconstructions after radical pelvic surgery and have a similar distribution of flap-specific complications involving the donor and recipient sites.

Authors
Soper, JT; Havrilesky, LJ; Secord, AA; Berchuck, A; Clarke-Pearson, DL
MLA Citation
Soper, JT, Havrilesky, LJ, Secord, AA, Berchuck, A, and Clarke-Pearson, DL. "Rectus abdominis myocutaneous flaps for neovaginal reconstruction after radical pelvic surgery." Int J Gynecol Cancer 15.3 (May 2005): 542-548.
PMID
15882183
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
15
Issue
3
Publish Date
2005
Start Page
542
End Page
548
DOI
10.1111/j.1525-1438.2005.15322.x

Rectus abdominis myocutaneous and myoperitoneal flaps for neovaginal reconstruction after radical pelvic surgery: comparison of flap-related morbidity.

PURPOSE: To compare flap-specific complications of rectus abdominis myocutaneous (RAM) and myoperitoneal (RAMP) flap neovagina reconstructions performed concurrently with radical pelvic procedures. MATERIALS AND METHODS: Retrospective single institution chart review of all patients with RAM or RAMP flap neovaginal reconstructions performed on a Gynecologic Oncology service, 1988-2003. Analysis for associations with flap-specific morbidity was performed. RESULTS: Neovaginal reconstructions comprised 32 RAM and 7 RAMP flaps. Twenty-two (69%) RAM patients underwent total pelvic exenteration compared to 1 (14%) RAMP patient (P < 0.013). Overall, 33 (85%) of the patient population had previously been treated with radiation. Flap-specific complications developed in 12 (32%) RAM versus 4 (57%) of the RAMP patients (P > 0.1). Donor site complications and incisional hernias were increased in RAMP patients (both P < 0.03), with trends for increasing risk of vaginal stricture/stenosis and superficial wound separations (both P < 0.1). Complete vaginal stenosis developed in only 1 (3%) RAM versus 3 (43%) RAMP patients. Furthermore, 3 RAMP patients developed complete stenosis when the vaginal defect was circumferential and involved >65% of the vagina while this did not occur in 22 similar RAM patients (P < 0.0005). Only patients with partial longitudinal defects maintained vaginal patency after RAMP flap. Fifteen (58%) of 26 patients surviving >12 months reported coitus, with no significant difference between the groups. CONCLUSIONS: When there is circumferential loss of the upper 2/3 of the vagina. RAMP flaps are not suitable for neovaginal reconstruction after radical pelvic surgery because of an increased risk of vaginal stenosis compared to RAM flaps. Patients with partial longitudinal vaginal defects, however, may have successful neovaginal reconstruction with RAMP flaps.

Authors
Soper, JT; Secord, AA; Havrilesky, LJ; Berchuck, A; Clarke-Pearson, DL
MLA Citation
Soper, JT, Secord, AA, Havrilesky, LJ, Berchuck, A, and Clarke-Pearson, DL. "Rectus abdominis myocutaneous and myoperitoneal flaps for neovaginal reconstruction after radical pelvic surgery: comparison of flap-related morbidity." Gynecol Oncol 97.2 (May 2005): 596-601.
PMID
15863165
Source
pubmed
Published In
Gynecologic Oncology
Volume
97
Issue
2
Publish Date
2005
Start Page
596
End Page
601
DOI
10.1016/j.ygyno.2005.01.032

Vascular endothelial growth factor, persistent disease, and survival in ovarian cancer - Reply

Authors
Secord, AA
MLA Citation
Secord, AA. "Vascular endothelial growth factor, persistent disease, and survival in ovarian cancer - Reply." GYNECOLOGIC ONCOLOGY 96.1 (January 2005): 265-266.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
96
Issue
1
Publish Date
2005
Start Page
265
End Page
266
DOI
10.1016/j.ygyno.2004.10.008

Vascular endothelial growth factor, persistent disease, and survival in ovarian cancer [2] (multiple letters)

Authors
Ferrero, S; Ragni, N; Secord, AA
MLA Citation
Ferrero, S, Ragni, N, and Secord, AA. "Vascular endothelial growth factor, persistent disease, and survival in ovarian cancer [2] (multiple letters)." Gynecologic Oncology 96.1 (2005): 265-266.
PMID
15589618
Source
scival
Published In
Gynecologic Oncology
Volume
96
Issue
1
Publish Date
2005
Start Page
265
End Page
266
DOI
10.1016/j.ygyno.2004.09.032

Phase I/II trial of combination topotecan and vinorelbine in patients with refractory gynecologic cancer.

Authors
Berchuck, A; Secord, AA; Havrilesky, LJ; Wenham, R; Soper, JT; Clarke-Pearson, DL
MLA Citation
Berchuck, A, Secord, AA, Havrilesky, LJ, Wenham, R, Soper, JT, and Clarke-Pearson, DL. "Phase I/II trial of combination topotecan and vinorelbine in patients with refractory gynecologic cancer." July 15, 2004.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
22
Issue
14
Publish Date
2004
Start Page
487S
End Page
487S

Phase I/II trial of intravenous liposomal doxorubicin and whole abdomen hyperthermia in patients with refractory ovarian cancer.

Authors
Secord, AA; Jones, E; Hahn, CA; Havrilesky, LJ; Soper, JT; Berchuck, A; Clarke-Pearson, DL; Prosnitz, LR
MLA Citation
Secord, AA, Jones, E, Hahn, CA, Havrilesky, LJ, Soper, JT, Berchuck, A, Clarke-Pearson, DL, and Prosnitz, LR. "Phase I/II trial of intravenous liposomal doxorubicin and whole abdomen hyperthermia in patients with refractory ovarian cancer." July 15, 2004.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
22
Issue
14
Publish Date
2004
Start Page
471S
End Page
471S

Phase I/II trial of intravenous liposomal doxorubicin and whole abdomen hyperthermia in patients with refractory ovarian cancer.

5089 Background: A phase I/II study of liposomal doxorubicin combined with whole abdominal hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase liposomal extravasation into tumor xenografts resulting in enhanced cytotoxic effects.Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) liposomal doxorubicin 40 mg/m2 as a 1-hour infusion followed by whole abdominal hyperthermia. Quality of life (QOL) was performed at baseline, prior to each cycle, and every 3 months following treatment.All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and 6 patients had been previously treated with liposomal doxorubicin. There were 3 partial responses for a response rate of 10% and 8 patients (27%) had disease stabilization. The median time to progression was 3.4 months (range, 1.3 to 20.7) and the median survival was 10.8 months (range, 2.7 to 27.2). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only 4 (13%) experienced grade 3/4 PPE toxicity. None of the patients had grade 3/4 thermal toxicity due to hyperthermia. QOL was stable in patients responding to therapy.Therapy with intravenous doxorubicin and whole abdominal hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer has modest activity and stabilized quality of life. Whole abdomen hyperthermia was well tolerated in this population. Work supported by a grant from the NIH CA42745. [Table: see text].

Authors
Secord, AA; Jones, E; Hahn, CA; Havrilesky, LJ; Soper, JT; Berchuck, A; Clarke-Pearson, DL; Prosnitz, LR; Dewhirst, MW
MLA Citation
Secord, AA, Jones, E, Hahn, CA, Havrilesky, LJ, Soper, JT, Berchuck, A, Clarke-Pearson, DL, Prosnitz, LR, and Dewhirst, MW. "Phase I/II trial of intravenous liposomal doxorubicin and whole abdomen hyperthermia in patients with refractory ovarian cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22.14_suppl (July 2004): 5089-.
PMID
28015342
Source
epmc
Published In
Journal of Clinical Oncology
Volume
22
Issue
14_suppl
Publish Date
2004
Start Page
5089

Phase I/II trial of combination topotecan and vinorelbine in patients with refractory gynecologic cancer.

5152 Background: Topotecan (T) and vinorelbine (V) have shown efficacy in recurrent ovarian and cervical cancer. The purpose of this trial was to determine the recommended dose of combination T and V and to assess its efficacy in patients with refractory gynecologic cancer.Sixteen patients with measurable disease and advanced gynecologic malignancies were enrolled. The phase I study evaluated the toxicity of combining T (0.75-1.25 mg/m2) administered as a 30 minute infusion on days 1,2, and 3 and V (20-22.5 mg/m2) IVP on days 1 and 8 of a 21 day cycle. The phase II study evaluated 8 patients treated with T (0.75 mg/m2) on days 1,2, and 3 followed by V(20 mg/m2) IVP on days 1 and 8.Five DLTs appeared during the first 8 cycles in levels 1 and 2. The MTD was reached and the recommended dose for this combination schedule was T: 0.75 mg/m2 on days #1, 2, and 3 combined with V: 22.5 mg/m2 on days # 1 and 8. Phase II: 8 patients have been enrolled at the recommended dose (median age 60 [35-74]; median PS 0) and have received 29 courses. The median number of prior chemotherapeutic regimens was 2 (range 1-5) and 1 patient had previously been treated with topotecan. All patients had platinum/paclitaxel resistant disease. There were 3 responses (1 CR, 2 PR) for a response rate of 37.5%. The median time to progression was 2.1 months (range, 1.3 to 7.4) and the median survival has not been reached. The predominant toxicity was hematologic and the toxicities were: grade 4 neutropenia (3/8; 37.5%), febrile neutropenia (3/8; 37.5%), and grade 2 anemia (4/8; 50%). Hematologic toxicity resulted in dose delays in 50% (4/8), dose modifications in 37.5% (3/8) and the use of granulocyte colony-stimulating factor in 25% (2/8) of patients.Therapy with combination topotecan and vinorelbine in patients with platinum/paclitaxel resistant ovarian cancer is active, but has significant hematologic toxicity. [Table: see text].

Authors
Berchuck, A; Secord, AA; Havrilesky, LJ; Wenham, R; Soper, JT; Clarke-Pearson, DL
MLA Citation
Berchuck, A, Secord, AA, Havrilesky, LJ, Wenham, R, Soper, JT, and Clarke-Pearson, DL. "Phase I/II trial of combination topotecan and vinorelbine in patients with refractory gynecologic cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22.14_suppl (July 2004): 5152-.
PMID
28016786
Source
epmc
Published In
Journal of Clinical Oncology
Volume
22
Issue
14_suppl
Publish Date
2004
Start Page
5152

The role of optimal debulking in advanced stage serous carcinoma of the uterus.

OBJECTIVE: To evaluate the role of optimal surgical cytoreduction and postoperative therapy in women with advanced uterine serous carcinoma (USC). METHODS: A multi-institutional, retrospective review identified 52 women with stage IV USC. Patient factors, surgical findings, and follow-up data were collected. Differences in demographics, surgical treatments, and adjuvant therapies administered were assessed with Fisher's exact test. Analysis of survival was performed using Kaplan-Meier and comparisons of survival were made using the log-rank test. RESULTS: Twenty-six women were optimally debulked ( 0.05). Median survival was longer in the optimal group (15 vs. 8 m), however, this did not reach statistical significance (P > 0.05). Women who received adjuvant platinum-based chemotherapy had a longer median survival than those who did not receive platinum chemotherapy (21 vs. 2 m) (P < 0.0001). Optimal cytoreduction combined with adjuvant therapy demonstrated a trend toward prolonged survival when compared to suboptimal cytoreduction combined with adjuvant therapy. However, the results did not achieve statistical significance (P > 0.05). CONCLUSION: Although no clear survival advantage is shown in the women who underwent optimal versus suboptimal debulking, there was a trend towards longer median survival in those who were maximally cytoreduced. Adjuvant platinum-based chemotherapy is associated with significantly longer survival in all women, regardless of amount of residual disease.

Authors
Moller, KA; Gehrig, PA; Van Le, L; Secord, AA; Schorge, J
MLA Citation
Moller, KA, Gehrig, PA, Van Le, L, Secord, AA, and Schorge, J. "The role of optimal debulking in advanced stage serous carcinoma of the uterus." Gynecol Oncol 94.1 (July 2004): 170-174.
PMID
15262137
Source
pubmed
Published In
Gynecologic Oncology
Volume
94
Issue
1
Publish Date
2004
Start Page
170
End Page
174
DOI
10.1016/j.ygyno.2004.03.040

The relationship between serum vascular endothelial growth factor, persistent disease, and survival at second-look laparotomy in ovarian cancer.

OBJECTIVE: To assess if the angiogenic factors vascular endothelial growth factor (VEGF) and D-dimer are predictive of persistent disease, early relapse, and survival in patients with ovarian cancer who achieve a complete clinical remission after first-line chemotherapy. METHODS: Serum levels of VEGF and D-dimer were assessed by ELISA in 62 patients who completed first-line chemotherapy and underwent second-look laparotomy at Duke University Medical Center. Cox Proportional Hazards Modeling was utilized to determine if VEGF and/or D-dimer levels could predict disease-free and overall survival. The Kaplan-Meier method was used to estimate median survival. The Wilcoxon test was used to determine if a significant difference existed in median VEGF and D-dimer levels between patients with positive and negative second-look operations. RESULTS: Forty (65%) of the 62 women who underwent second-look laparotomy had persistent disease. The median VEGF levels were 264 pg/ml (range 109-896 pg/ml) in the group with negative second looks compared to 390 pg/ml (range 99-1011 pg/ml) in those with positive second-looks (P = 0.1). High levels of VEGF were marginally associated with the presence of persistent (P = 0.10) and gross (P = 0.07) disease at the time of second look laparotomy. After adjusting for CA125, women with high VEGF serum levels had a worse overall survival (P = 0.004). CONCLUSIONS: This study suggests that serum VEGF may be a clinically important marker for persistent disease and is predictive of survival in ovarian cancer patients after first-line chemotherapy.

Authors
Alvarez Secord, A; Sayer, R; Snyder, SA; Broadwater, G; Rodriguez, GC; Berchuck, A; Blackwell, K
MLA Citation
Alvarez Secord, A, Sayer, R, Snyder, SA, Broadwater, G, Rodriguez, GC, Berchuck, A, and Blackwell, K. "The relationship between serum vascular endothelial growth factor, persistent disease, and survival at second-look laparotomy in ovarian cancer." Gynecol Oncol 94.1 (July 2004): 74-79.
PMID
15262122
Source
pubmed
Published In
Gynecologic Oncology
Volume
94
Issue
1
Publish Date
2004
Start Page
74
End Page
79
DOI
10.1016/j.ygyno.2004.03.043

Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer.

OBJECTIVE: We wished to evaluate survival and adverse outcomes of patients with stage IB2 cervical cancer treated primarily with radical hysterectomy and lymphadenectomy. METHODS: A review was performed of all patients undergoing primary radical hysterectomy for stage IB2 cervical cancer at two institutions from 1987 to 2002. Patients were stratified into low, intermediate (Gynecologic Oncology Group protocol 92 criteria), and high-risk (positive nodes, margins, or parametria) groups. Survival and progression-free interval were analyzed using the Kaplan-Meier method and multivariate analysis. RESULTS: Seventy-two patients underwent primary type III radical hysterectomy and lymphadenectomy (72 pelvic, 58 pelvic and paraaortic). Patients were classified as low (n = 6), intermediate (n = 49), or high (n = 17) risk for recurrence. Adjuvant therapy was administered to 94%, 12%, and 0% of the high-, intermediate-, and low-risk groups, respectively. Five-year survival was 72%, while 5-year progression-free survival was 63%. Five-year overall and progression-free survival by risk group were 47% and 40% (high-risk), 80% and 66% (intermediate-risk), 100% and 100% (low-risk). Predictors of survival in multivariate analysis were Caucasian race (P = 0.001), older age (P = 0.017), inner 2/3 cervical wall invasion (P = 0.045), and absence of lymph-vascular invasion (P < 0.001). Major complications were experienced by 10/72 (13.9%) patients. Among 34 patients who received radiation therapy, two (5.9%) experienced complications attributable to radiation. CONCLUSIONS: Radical hysterectomy and lymphadenectomy followed by tailored adjuvant therapy is a reasonable alternative to primary radiotherapy for stage IB2 cervical cancer. Patients with low- and intermediate-risk factors have satisfactory results after primary surgical management. A prospective randomized trial will clarify the optimal mode of initial therapy for patients with stage IB2 disease.

Authors
Havrilesky, LJ; Leath, CA; Huh, W; Calingaert, B; Bentley, RC; Soper, JT; Alvarez Secord, A
MLA Citation
Havrilesky, LJ, Leath, CA, Huh, W, Calingaert, B, Bentley, RC, Soper, JT, and Alvarez Secord, A. "Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer." Gynecol Oncol 93.2 (May 2004): 429-434.
PMID
15099957
Source
pubmed
Published In
Gynecologic Oncology
Volume
93
Issue
2
Publish Date
2004
Start Page
429
End Page
434
DOI
10.1016/j.ygyno.2004.01.038

High dose rate intraoperative radiotherapy for recurrent cervical cancer and nodal disease.

BACKGROUND: Patients with pelvic sidewall recurrences of cervical cancer have a dismal prognosis. Intraoperative radiation therapy (IORT) has demonstrated encouraging results. Patients have traditionally been excluded from IORT if they had distant metastases. CASE: A patient underwent radical tumor resection and high dose rate (HDR) IORT for a pelvic sidewall recurrence of cervical cancer. She also had metastatic disease in a para-aortic node. The patient has been followed for >20 months with no evidence of disease recurrence. CONCLUSIONS: HDR-IORT may be offered to select patients with recurrent cervical cancer and isolated metastatic para-aortic lymph nodes.

Authors
Roth, TM; Secord, AA; Havrilesky, LJ; Jones, E; Clarke-Pearson, DL
MLA Citation
Roth, TM, Secord, AA, Havrilesky, LJ, Jones, E, and Clarke-Pearson, DL. "High dose rate intraoperative radiotherapy for recurrent cervical cancer and nodal disease." Gynecol Oncol 91.1 (October 2003): 258-260.
PMID
14529691
Source
pubmed
Published In
Gynecologic Oncology
Volume
91
Issue
1
Publish Date
2003
Start Page
258
End Page
260

A pilot Phase II trial of concurrent radiotherapy, chemotherapy, and hyperthermia for locally advanced cervical carcinoma.

BACKGROUND: Five randomized studies have demonstrated a benefit derived from adding cisplatin (CDDP)-based chemotherapy to radiotherapy (RT) for treatment of cervical carcinoma. The Dutch Phase III pelvic tumor trial demonstrated a survival and local control benefit due to the addition of hyperthermia (HT) to RT. The authors evaluated response and toxicity in patients with locally advanced cervical carcinoma (LACC) who were treated with concurrent weekly CDDP, HT, and RT (whole pelvis [n=7] and whole pelvis and paraaortic nodes [n=5]). METHODS: From August 1998 through December 2000, 12 patients with LACC or locally recurrent cervical carcinoma (LRCC) following hysterectomy were enrolled on a pilot study combining weekly CDDP, HT, and RT. RESULTS: Ten patients were treated at initial diagnosis. All achieved clinical complete response and durable local control. Two of the 10 experienced recurrence outside the pelvis; 1 of these patients had pulmonary metastasis, and the other had isolated paraaortic nodal involvement. Two patients treated for LRCC experienced local and systemic progression and died of disease within 6 months. CONCLUSIONS: In this small series, trimodality therapy resulted in an excellent clinical response and was well tolerated. The addition of HT to chemoradiotherapy represents a promising new strategy that warrants multiinstitutional collaborative efforts to confirm its efficacy.

Authors
Jones, EL; Samulski, TV; Dewhirst, MW; Alvarez-Secord, A; Berchuck, A; Clarke-Pearson, D; Havrilesky, LJ; Soper, J; Prosnitz, LR
MLA Citation
Jones, EL, Samulski, TV, Dewhirst, MW, Alvarez-Secord, A, Berchuck, A, Clarke-Pearson, D, Havrilesky, LJ, Soper, J, and Prosnitz, LR. "A pilot Phase II trial of concurrent radiotherapy, chemotherapy, and hyperthermia for locally advanced cervical carcinoma." Cancer 98.2 (July 15, 2003): 277-282.
PMID
12872345
Source
pubmed
Published In
Cancer
Volume
98
Issue
2
Publish Date
2003
Start Page
277
End Page
282
DOI
10.1002/cncr.11475

The role of PET scanning in the detection of recurrent cervical cancer.

OBJECTIVES: [(18)F] Fluoro-2-deoxyglucose positron emission tomography (FDG PET) has recently been established as a sensitive and specific method of detecting lymph node metastases in newly diagnosed cervical cancer. Little is known about the efficacy of PET for detecting recurrent disease. We evaluated the potential role of FDG PET in the context of suspected recurrent cervical cancer. METHODS: The records of patients undergoing PET scan to evaluate for cervical cancer recurrence between July 1998 and February 2002 were reviewed. Radiographic findings were classified as negative, suspicious, or equivocal. PET scan findings were compared to available clinical data to classify each PET result as a true positive, true negative, false positive, or false negative. Clinical proof of recurrence consisted of a tissue biopsy revealing recurrent cancer within 3 months of the PET scan. Clinical proof of no evidence of disease consisted of a negative tissue biopsy within 3 months or no clinical evidence of recurrence within 6 months after the PET scan. RESULTS: Twenty-eight patients underwent 37 PET scans. Twenty-nine cases among 22 patients were clinically evaluable for recurrence status. Median age was 42, and stage distribution was IB 1 (n = 3), IB2 (n = 4), IIA (n = 1), IIB (n = 10), IIIB (n = 9), IVB (n = 1). Histologic types included squamous (n = 23) adenocarcinoma (n = 4) and unknown (n = 1). There were 12 true positive PET scans, 13 true negatives, 2 false positives, and 2 false negatives. The sensitivity and specificity of FDG PET for detecting recurrent cervical cancer were 85.7 and 86.7%, respectively. The positive and negative predictive values were 85.7 and 86.7%, respectively. CONCLUSIONS: Whole-body FDG PET is a sensitive and specific tool for the detection of recurrent cervical cancer in patients who have clinical findings suspicious for recurrence. A larger prospective trial will determine whether this modality should be used routinely in conjunction with, or in lieu of, other imaging studies to detect recurrent disease in a broader population of cervical cancer patients.

Authors
Havrilesky, LJ; Wong, TZ; Secord, AA; Berchuck, A; Clarke-Pearson, DL; Jones, EL
MLA Citation
Havrilesky, LJ, Wong, TZ, Secord, AA, Berchuck, A, Clarke-Pearson, DL, and Jones, EL. "The role of PET scanning in the detection of recurrent cervical cancer." Gynecol Oncol 90.1 (July 2003): 186-190.
PMID
12821362
Source
pubmed
Published In
Gynecologic Oncology
Volume
90
Issue
1
Publish Date
2003
Start Page
186
End Page
190

Weekly low-dose carboplatin and paclitaxel in the treatment of recurrent ovarian and peritoneal cancer.

OBJECTIVES: Weekly paclitaxel alone has moderate activity in the salvage treatment of recurrent ovarian cancer and is associated with a favorable toxicity profile. Combination paclitaxel and carboplatin is a well-established first-line regimen for ovarian cancer. The purpose of this study was to evaluate weekly low-dose paclitaxel and carboplatin in recurrent ovarian or peritoneal cancer. METHODS: Patients with recurrent ovarian or peritoneal cancer previously treated with between one and four chemotherapeutic regimens were eligible. Patients had measurable or assessable disease defined by clinical exam, radiographic studies, or serum CA-125 greater than 75 U/ml. One cycle of treatment consisted of carboplatin at an area under the curve of 2 and paclitaxel at 80 mg/m(2) on days 1, 8, and 15 on a 28-day cycle. Clinical responses were defined by established criteria. RESULTS: Twenty-nine patients were included in this intent-to-treat study. The median number of prior treatment regimens was 2 (range 1 to 4). The overall response rate was 82.8% (16 complete clinical responses, 8 partial responses). Among 8 platinum-refractory patients, the response rate was 37.5%, while 21 platinum-sensitive patients had a 100% response rate. Median time to progression was 13.7 months among platinum-sensitive patients and 3.2 months among platinum-refractory patients. Overall median time to progression was 11.5 months and median-duration of response was 9.9 months. Hematologic toxicity was common (32% grade 3 neutropenia, no grade 4 neutropenia, 14.2% grade 3 or 4 thrombocytopenia) and managed by treatment delay, dose reduction of paclitaxel, or discontinuation of carboplatin. CONCLUSION: Weekly low-dose carboplatin and paclitaxel has significant activity in both platinum-sensitive and platinum-resistant recurrent ovarian cancer with acceptable toxicity that is easily managed by dose adjustment.

Authors
Havrilesky, LJ; Alvarez, AA; Sayer, RA; Lancaster, JM; Soper, JT; Berchuck, A; Clarke-Pearson, DL; Rodriguez, GC; Carney, ME
MLA Citation
Havrilesky, LJ, Alvarez, AA, Sayer, RA, Lancaster, JM, Soper, JT, Berchuck, A, Clarke-Pearson, DL, Rodriguez, GC, and Carney, ME. "Weekly low-dose carboplatin and paclitaxel in the treatment of recurrent ovarian and peritoneal cancer." Gynecologic oncology 88.1 (January 2003): 51-57.
PMID
12504627
Source
epmc
Published In
Gynecologic Oncology
Volume
88
Issue
1
Publish Date
2003
Start Page
51
End Page
57
DOI
10.1006/gyno.2002.6859

Platinum-Resistant and Refractory Ovarian Cancer

Authors
Alvarez, AA; Clarke-Pearson, DL
MLA Citation
Alvarez, AA, and Clarke-Pearson, DL. "Platinum-Resistant and Refractory Ovarian Cancer." American Journal of Cancer 2.1 (2003): 1-13.
Source
crossref
Published In
American Journal of Cancer
Volume
2
Issue
1
Publish Date
2003
Start Page
1
End Page
13
DOI
10.2165/00024669-200302010-00001

Abdominal pain and bloating in two 20-something patients

Authors
Berchuck, A; Alvarez, AA; Stout, JE
MLA Citation
Berchuck, A, Alvarez, AA, and Stout, JE. "Abdominal pain and bloating in two 20-something patients." Contemporary Ob/Gyn 48.1 (2003): 51-58.
Source
scival
Published In
Contemporary ob/gyn
Volume
48
Issue
1
Publish Date
2003
Start Page
51
End Page
58

Loss of expression of the p16 tumor suppressor gene is more frequent in advanced ovarian cancers lacking p53 mutations.

OBJECTIVE: The aim of this study was to test the hypothesis that p53 mutations are less frequent in ovarian cancers with alterations in other genes that regulate G1 progression. METHODS: Expression of G1 stimulatory (cyclins D1 and E, cdk4, Ki67) and inhibitory (p16, Rb, p27, p14) genes was analyzed using Western blots in 84 primary ovarian cancers and seven cell lines of known p53 mutation status. Expression of p16 and Rb also was determined using immunohistochemistry and the p16 gene was examined for homozygous deletions and mutations. RESULTS: Loss of p16 protein was more frequent in ovarian cancers with wild-type p53. All four cell lines with wild-type p53 had lost p16 compared to only one of three with mutant p53 genes. p16 expression was absent in 34% (28/82) of primary ovarian cancers, and this was significantly more common in cases with wild-type p53 (14/28, 50%) compared to those with p53 mutations (14/54, 26%, P = 0.03). Homozygous deletion of the p16 gene was found in cell lines lacking p16, but not in any primary cancers. p16 loss was more common in serous (21/52, 40%) than nonserous cancers (4/23, 17%, P = 0.07). Cases that expressed p16 were more likely to express high levels of Rb (47/55, 85%) than p16-negative cases (12/28, 43%, P < 0.001). Loss of Rb occurred in 5/30 (17%) ovarian cancers lacking p53 mutations compared to 5/54 (9%) cases with p53 mutations (P = 0.48). Expression of G1 stimulatory proteins (cyclins D1 and E, cdk4, Ki67) did not correlate with p53 mutation status. CONCLUSIONS: Loss of expression of the p16 tumor suppressor occurs more often in ovarian cancers lacking p53 mutations. These data are consistent with the paradigm that inactivation of p53 is less of a requisite event in ovarian carcinogenesis when another G1 regulatory gene such as p16 already has been inactivated.

Authors
Havrilesky, LJ; Alvarez, AA; Whitaker, RS; Marks, JR; Berchuck, A
MLA Citation
Havrilesky, LJ, Alvarez, AA, Whitaker, RS, Marks, JR, and Berchuck, A. "Loss of expression of the p16 tumor suppressor gene is more frequent in advanced ovarian cancers lacking p53 mutations." Gynecologic oncology 83.3 (December 2001): 491-500.
PMID
11733961
Source
epmc
Published In
Gynecologic Oncology
Volume
83
Issue
3
Publish Date
2001
Start Page
491
End Page
500
DOI
10.1006/gyno.2001.6464

Mycobacterium bovis peritonitis mimicking ovarian cancer in a young woman.

We describe a 27-year-old woman with peritonitis due to Mycobacterium bovis that initially appeared to be ovarian cancer. Clinicians should include this disease in the differential diagnosis of ovarian cancer and should consider laparoscopic diagnosis in the appropriate epidemiologic setting.

Authors
Stout, JE; Woods, CW; Alvarez, AA; Berchuck, A; Dukes Hamilton, C
MLA Citation
Stout, JE, Woods, CW, Alvarez, AA, Berchuck, A, and Dukes Hamilton, C. "Mycobacterium bovis peritonitis mimicking ovarian cancer in a young woman." Clin Infect Dis 33.4 (August 15, 2001): E14-E16.
PMID
11462205
Source
pubmed
Published In
Clinical Infectious Diseases
Volume
33
Issue
4
Publish Date
2001
Start Page
E14
End Page
E16
DOI
10.1086/321908

Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients.

OBJECTIVE: The regulation of the metastatic process in epithelial ovarian cancer has not been well defined. Similar to other tumor types, the angiogenic phenotype in ovarian cancer strongly influences clinical outcome, suggesting that the acquisition of a pro-angiogenic environment is essential to the process of ovarian cancer proliferation and metastasis. Thrombospondin-1 (TSP-1) is a potent peptide shown in other tumor systems to be associated with angiogenesis and possibly regulated by p53, a gene which is mutated in as high as 50% of advanced ovarian cancers. The purpose of this study was to investigate TSP-1 expression in invasive epithelial ovarian cancer and to examine the relationship between TSP-1 expression and the degree of angiogenesis. In addition, we examined whether TSP-1 expression was associated with overexpression of p53. METHODS: Frozen sections obtained from 85 patients with invasive epithelial ovarian cancer were examined immunohistochemically for expression of TSP-1 and p53. The sections were examined microscopically by two investigators, who were blinded to the clinicopathologic variables. Outcome variables included the correlation among TSP-1, angiogenesis, and p53, as well as the association between TSP-1 expression and survival. RESULTS: The majority (62%) of cases demonstrated high levels (3+) of TSP-1 expression; 7% demonstrated no TSP-1 expression. p53 was overexpressed in 55% of cases, and expression was inversely correlated with TSP-1 staining. Thirteen cancers had 0 or 1+ TSP-1 staining; 12 (92%) of these overexpressed the p53 protein. In contrast, only 49% of tumors with high expression of TSP-1 have overexpression of p53 (P = 0.02). TSP-1 was suggestive for improved survival in patients with advanced disease; high TSP-1 expression was associated with a median survival of 2.4 years compared to 1.5 years for patients with tumors having a lower degree of TSP-1 expression (P = 0.06). CONCLUSION: These data suggest that TSP-1 may possess a tumor inhibitory function in patients with advanced epithelial ovarian carcinoma. The reduction of TSP-1 expression associated with overexpression of p53 may be coupled with the development of a pro-angiogenic environment and malignant phenotype.

Authors
Alvarez, AA; Axelrod, JR; Whitaker, RS; Isner, PD; Bentley, RC; Dodge, RK; Rodriguez, GC
MLA Citation
Alvarez, AA, Axelrod, JR, Whitaker, RS, Isner, PD, Bentley, RC, Dodge, RK, and Rodriguez, GC. "Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients." Gynecologic oncology 82.2 (August 2001): 273-278.
PMID
11531279
Source
epmc
Published In
Gynecologic Oncology
Volume
82
Issue
2
Publish Date
2001
Start Page
273
End Page
278
DOI
10.1006/gyno.2001.6287

Allele loss on chromosome 1p36 in epithelial ovarian cancers.

OBJECTIVES: Prior studies have shown that allelic loss on chromosome 1p36 occurs frequently in ovarian as well as several other types of cancer. This suggests that inactivation of gene(s) in this region may play a role in the pathogenesis of these cancers. The aim of this study was to further delineate the region of loss on chromosome 1p36 in ovarian cancers and to identify associated patient or tumor characteristics. METHODS: Paired normal/cancer DNA samples from 75 ovarian cancers (21 early stage I/II and 54 advanced stage III/IV) were analyzed using microsatellite markers. RESULTS: Forty-nine of 75 (65%) ovarian cancers had loss of at least one marker. The marker demonstrating the most frequent loss was D1S1597, which was lost in 29/57 (51%) informative cases. Allele loss on 1p36 was significantly more common in poorly differentiated ovarian cancers (73%) relative to well or moderately differentiated cases (48%) (P = 0.03). Evidence was obtained for two common regions of deletion: one flanked by D1S1646/D1S244 and another more proximally by D1S244/D1S228. CONCLUSION: These findings further delineate regions on chromosome 1p36 proposed to contain tumor suppressor gene(s) that may play a role in the development and/or progression of epithelial ovarian carcinoma. Allele loss on 1p36 is associated with poor histologic grade.

Authors
Alvarez, AA; Lambers, AR; Lancaster, JM; Maxwell, GL; Ali, S; Gumbs, C; Berchuck, A; Futreal, PA
MLA Citation
Alvarez, AA, Lambers, AR, Lancaster, JM, Maxwell, GL, Ali, S, Gumbs, C, Berchuck, A, and Futreal, PA. "Allele loss on chromosome 1p36 in epithelial ovarian cancers." Gynecologic oncology 82.1 (July 2001): 94-98.
PMID
11426968
Source
epmc
Published In
Gynecologic Oncology
Volume
82
Issue
1
Publish Date
2001
Start Page
94
End Page
98
DOI
10.1006/gyno.2001.6175

Favorable survival associated with microsatellite instability in endometrioid endometrial cancers.

OBJECTIVE: To determine whether microsatellite instability in endometrioid endometrial cancer is associated with favorable survival. METHODS: Microsatellite instability analysis was performed in 131 patients with endometrioid endometrial cancer using three polymorphic markers in paired cancer and normal DNA. Logistic regression and multivariable analyses calculated the relation between microsatellite instability, clinical features, and survival. RESULTS: Microsatellite instability was detected in 29 of 131 (22%) endometrioid endometrial cancers. There was no correlation between microsatellite instability and age, race, grade, stage, or depth of myometrial invasion. Microsatellite instability was associated with better survival in univariate and multivariable analyses after controlling for confounding influences (P =.03). The 5-year survival rate of those with microsatellite instability was 77% (95% confidence interval 55%, 90%) compared with only 48% (95% confidence interval 39%, 57%) in other cases. Microsatellite instability was associated with other molecular features that predict favorable outcome including PTEN mutation (P =.002) and the absence of p53 overexpression (P =.01). CONCLUSION: Microsatellite instability is a molecular alteration associated with favorable outcome in endometrioid endometrial cancers, even when accounting for other prognostic factors. This association might be explained by the finding that the pathway of molecular carcinogenesis characterized by loss of DNA mismatch repair favors alteration of genes that result in a less virulent clinical phenotype.

Authors
Maxwell, GL; Risinger, JI; Alvarez, AA; Barrett, JC; Berchuck, A
MLA Citation
Maxwell, GL, Risinger, JI, Alvarez, AA, Barrett, JC, and Berchuck, A. "Favorable survival associated with microsatellite instability in endometrioid endometrial cancers." Obstet Gynecol 97.3 (March 2001): 417-422.
PMID
11239648
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
97
Issue
3
Publish Date
2001
Start Page
417
End Page
422

Vacuum-assisted closure for cutaneous gastrointestinal fistula management.

BACKGROUND: Cutaneous gastrointestinal (GI) fistulas are a challenging complication in the oncologic patient population. The fistulous effluent is difficult to manage and adversely alters quality of life. Nonsurgical management of enteric fistulas is successful in 30% of cases, requiring at least 4 to 6 weeks. Recently a new technology has been developed to expedite wound healing. The Vacuum-Assisted Closure (VAC) method is a subatmospheric pressure technique that has been demonstrated in laboratory and clinical studies to significantly improve wound healing. Here we report its use in the successful medical management of a cutaneous GI fistula. CASE: A 63-year-old woman with advanced ovarian cancer developed an extensive complex cutaneous GI fistula in an open healing wound. She was treated with total parental nutrition and the VAC device, which resulted in complete closure of the fistula. CONCLUSION: We propose that the VAC device may be a useful adjunct for the medical management of cutaneous GI fistulas.

Authors
Alvarez, AA; Maxwell, GL; Rodriguez, GC
MLA Citation
Alvarez, AA, Maxwell, GL, and Rodriguez, GC. "Vacuum-assisted closure for cutaneous gastrointestinal fistula management." Gynecologic oncology 80.3 (March 2001): 413-416.
PMID
11263943
Source
epmc
Published In
Gynecologic Oncology
Volume
80
Issue
3
Publish Date
2001
Start Page
413
End Page
416
DOI
10.1006/gyno.2000.6092

K-ras mutations in Müllerian inclusion cysts associated with serous borderline tumors of the ovary.

OBJECTIVE: Müllerian inclusion cysts (MIC) are small benign appearing glands that are occasionally noted in lymph nodes and peritoneal biopsies. They occur most frequently in women with serous ovarian tumors, with borderline tumors (SBOT) having a higher incidence than invasive cancers. The aim of this study was to examine whether MIC and SBOT have identical K-ras mutations, which would suggest that they are related. Methods. Six patients in whom adequate tissue was available from SBOT, MIC, and normal tissue were identified from a consecutive series of patients with SBOT who underwent lymph node sampling from 1992 to 1997 at Duke University Medical Center. DNA extraction was performed using laser capture microdissection. Exon 1 of the K-ras gene was amplified using PCR and subjected to single-strand conformation analysis to screen for mutations. Shifted bands were sequenced to confirm the presence of mutations. RESULTS: Mutations in codon 12 of K-ras were found in three of six (50%) SBOT. In two of these three cases, the identical mutation was found in the SBOT and the MIC (gly to val in both cases), but not in the corresponding normal DNA. In one case, a mutation was seen in the ovarian tumor (gly to asp), but not in the corresponding MIC. CONCLUSIONS: Mutations in codon 12 of the K-ras gene are a hallmark of serous borderline tumors. The presence of identical K-ras mutations in some SBOT and their associated MIC suggests that they are related processes. Both may arise due to a field effect, or alternatively some MIC may represent metastases from the primary ovarian tumor.

Authors
Alvarez, AA; Moore, WF; Robboy, SJ; Bentley, RC; Gumbs, C; Futreal, PA; Berchuck, A
MLA Citation
Alvarez, AA, Moore, WF, Robboy, SJ, Bentley, RC, Gumbs, C, Futreal, PA, and Berchuck, A. "K-ras mutations in Müllerian inclusion cysts associated with serous borderline tumors of the ovary." Gynecologic oncology 80.2 (February 2001): 201-206.
PMID
11161860
Source
epmc
Published In
Gynecologic Oncology
Volume
80
Issue
2
Publish Date
2001
Start Page
201
End Page
206
DOI
10.1006/gyno.2000.6066

Racial disparity in the frequency of PTEN mutations, but not microsatellite instability, in advanced endometrial cancers.

Survival of African Americans with endometrial cancer is significantly worse than that of whites. Mutation of the PTEN tumor suppressor gene and microsatellite instability occur in some endometrial cancers, and they are associated with favorable prognostic features. The aim of this study was to determine whether there is a racial disparity in the frequency of these molecular alterations that contributes to differences in outcome in advanced endometrial cancer. We screened 140 stage III/IV endometrial adenocarcinomas (78 Caucasian, 62 African American) for mutations in the PTEN gene. Paired DNA samples were available in 100 cases and were analyzed for microsatellite instability using three polymorphic markers. African-American women had cancers with significantly higher stage and grade that were more often nonendometrioid. In addition, median survival of African Americans (1.0 years) was worse than that of whites (2.5 years; P = 0.02). PTEN mutation was seen in 20 of 140 (14%) cancers and was associated with endometrioid histology and more favorable survival. The frequency of PTEN mutations was significantly higher in whites (17 of 78; 22%) than in African Americans (3 of 62; 5%; P = 0.006). Microsatellite instability was found in 15% of cancers, exclusively in endometrioid cases, and was associated with favorable survival (P = 0.01). There was no racial difference in the frequency of microsatellite instability. We conclude that mutation of the PTEN tumor suppressor gene is associated with favorable survival in advanced endometrial cancer and is 4-fold more frequent in Caucasians relative to African Americans. This suggests that differences in the frequency of PTEN mutations contribute to the racial disparity in endometrial cancer survival.

Authors
Maxwell, GL; Risinger, JI; Hayes, KA; Alvarez, AA; Dodge, RK; Barrett, JC; Berchuck, A
MLA Citation
Maxwell, GL, Risinger, JI, Hayes, KA, Alvarez, AA, Dodge, RK, Barrett, JC, and Berchuck, A. "Racial disparity in the frequency of PTEN mutations, but not microsatellite instability, in advanced endometrial cancers." Clinical cancer research : an official journal of the American Association for Cancer Research 6.8 (August 2000): 2999-3005.
PMID
10955777
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
6
Issue
8
Publish Date
2000
Start Page
2999
End Page
3005

Prognosis of BRCA1 and 2-associated ovarian cancers

About 10% of epithelial ovarian cancers have a hereditary basis. Germline mutations in the BRCA1 and BRCA2 breast/ovarian cancer susceptibility genes are thought to be responsible for most hereditary ovarian cancers. In contrast, about 90% of ovarian cancers arise due to accumulation of somatic mutations. In sporadic ovarian cancers, it has been shown that alterations in the p53 tumor suppressor gene and the HER-2/neu oncogene are associated with advanced stage and poor outcome. Other genetic alterations, such as microsatellite instability have been associated with favorable prognosis in colon and endometrial cancers. In view of this, it is plausible that BRCA1 and 2-associated ovarian cancers might also have a characteristic clinical phenotype. Clinical studies of BRCA1 and 2-associated ovarian cancer have been difficult to perform because no single institution has identified a large number of cases. It appears that the strongest clinical correlate of BRCA1 mutation in ovarian cancer is papillary serous histology. Although most BRCA1-associated ovarian cancers present at an advanced stage, in some studies survival of BRCA1 mutation carriers has been relatively favorable compared to controls. Other studies have not confirmed this association, however. The relative prognosis of ovarian cancers with BRCA2 mutations remains essentially unstudied. Larger collaborative studies are needed to characterize better the clinical features and prognosis of BRCA1 and 2-associated ovarian cancers.

Authors
Berchuck, A; Alvarez, A; Futreal, PA
MLA Citation
Berchuck, A, Alvarez, A, and Futreal, PA. "Prognosis of BRCA1 and 2-associated ovarian cancers." CME Journal of Gynecologic Oncology 4.1 (December 1, 1999): 108-111. (Review)
Source
scopus
Published In
CME Journal of Gynecologic Oncology
Volume
4
Issue
1
Publish Date
1999
Start Page
108
End Page
111

The prognostic significance of angiogenesis in epithelial ovarian carcinoma.

The molecular biology underlying the metastatic process in ovarian carcinoma remains poorly understood. For other neoplasms, the induction of angiogenesis by malignant cells has been shown to play a pivotal role in the process of tumor proliferation and metastasis. The purpose of this study was to characterize the degree of angiogenesis in epithelial ovarian malignancies and to determine whether the degree of neovascularization has prognostic significance for survival. Tissue sections obtained from 88 ovarian cancer patients were examined immunohistochemically for angiogenesis after staining with anti-human endothelial cell antibodies to von Willebrand factor and CD31. Light microscopy was performed, and individual microvessel counts were quantified at high power (x400). A chart review was completed, collating data regarding age, stage, grade, status of disease, and survival. Statistical exploratory methods were used to find potentially useful prognostic cutpoints for marker values of angiogenesis. Of the total 88 patients, tissue microvessel counts from 85 were evaluated via antibodies to von Willebrand factor and 87 for CD31. Overall, median survival was 2.7 years in women with cancers containing high microvessel counts versus 7.9 years in those with low microvessel counts (P = 0.03). A low microvessel count was associated with better 5-year survival in both early stage (I and II) and advanced stage (III and IV) disease. Our data suggest that the degree of neovascularization may have prognostic significance in epithelial ovarian carcinoma, especially for women with early-stage disease. In this group of women, the degree of angiogenesis may allow the selection of women at high risk for recurrence who may benefit from aggressive adjuvant therapy.

Authors
Alvarez, AA; Krigman, HR; Whitaker, RS; Dodge, RK; Rodriguez, GC
MLA Citation
Alvarez, AA, Krigman, HR, Whitaker, RS, Dodge, RK, and Rodriguez, GC. "The prognostic significance of angiogenesis in epithelial ovarian carcinoma." Clinical cancer research : an official journal of the American Association for Cancer Research 5.3 (March 1999): 587-591.
PMID
10100710
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
5
Issue
3
Publish Date
1999
Start Page
587
End Page
591

Mutations in the PTEN tumor suppressor gene in cervical carcinomas

Authors
Maxwell, ; Risinger, ; Shaw, ; Alvarez, ; Barrett, ; Futreal, ; Berchuck,
MLA Citation
Maxwell, , Risinger, , Shaw, , Alvarez, , Barrett, , Futreal, , and Berchuck, . "Mutations in the PTEN tumor suppressor gene in cervical carcinomas." International Journal of Gynecological Cancer 8.6 (November 1998): 489-493.
Source
crossref
Published In
International Journal of Gynecological Cancer
Volume
8
Issue
6
Publish Date
1998
Start Page
489
End Page
493
DOI
10.1046/j.1525-1438.1998.98102.x
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