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Havrilesky, Laura Jean

Overview:

I am interested in using health economic models to inform decisions related to gynecologic cancers. Specific models have addressed the decision to administer intraperitoneal chemotherapy for newly diagnosed advanced ovarian cancer following optimal cytoreduction, the choice of chemotherapy regimen for recurrent platinum-sensitive ovarian cancer, and the exploration of screening strategies for ovarian cancer. The ovarian cancer screening model examines the effects of test cost, sensitivity, specificity, and screen frequency on ovarian cancer mortality, the lifetime false positive rate of testing, the positive predictive value of the test, and its cost effectiveness. This type of model is potentially useful in informing the design trials of novel screening tests for ovarian cancer. I am also conducting a prospective study to quantify the effects of screening for, diagnosis of, and treatment for ovarian cancer on the quality of life of women.

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. 1995

M.D. — Duke University

Residency, Obstetrics And Gynecology

Duke University

Grants:

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
Principal Investigator
Start Date
January 01, 2016
End Date
December 31, 2017

Tissue and Data Acquisition Activity for the Study of Gynecologic Disease

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
Henry M. Jackson Foundation
Role
Principal Investigator
Start Date
August 19, 2016
End Date
February 28, 2017

Ovarian Cancer Patient-Centered Decision Aid

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
University of California - Irvine
Role
Principal Investigator
Start Date
June 17, 2013
End Date
May 31, 2016

A Pilot Study on H.O.P.E: Helping Ovarian Cancer Patients Cope with Disease Recurrence

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
Foundation for Women's Cancer
Role
Co Investigator
Start Date
April 01, 2014
End Date
March 31, 2016

Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer

Administered By
Duke Clinical Research Institute
AwardedBy
Agency for Healthcare Research and Quality
Role
Principal Investigator
Start Date
September 10, 2010
End Date
September 30, 2012

Tissue and Data Acquisition Activity for the Study of Gynecologic Disease

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
United States Army Medical Research and Materiel Command
Role
Principal Investigator
Start Date
November 01, 2010
End Date
May 31, 2011

Decision Analysis on Screening for Cervical Cancer

Administered By
Institutes and Centers
AwardedBy
Agency for Healthcare Research and Quality
Role
Investigator
Start Date
July 25, 2007
End Date
August 31, 2008

Genomics Tests for Ovarian Cancer Detection and Management

Administered By
Institutes and Centers
AwardedBy
Agency for Healthcare Research and Quality
Role
Investigator
Start Date
September 30, 2005
End Date
November 30, 2006

Management of Adnexal Mass

Administered By
Institutes and Centers
AwardedBy
Agency for Healthcare Research and Quality
Role
Investigator
Start Date
September 01, 2004
End Date
July 15, 2006
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Publications:

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

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p=0.01), but multi-day regimens of MTX have higher historic success rates. We assessed the cost-effectiveness of Act-D vs. MTX per GOG 0174 and explored multi-day MTX regimens.A cost effectiveness decision model was constructed with data from GOG 0174. Outcome was cost per first-line treatment success expressed in terms of incremental cost-effectiveness ratio (ICER). Front-line failures were assumed to receive cross-over single agent therapy, second line failures; multi-agent chemotherapy. GOG 0174 had no quality of life (QOL) evaluation, so equal QOL (utility 1.0) was assumed but varied in sensitivity analysis. A second exploratory model included 5-day and 8-day MTX regimens.Act-D ($18,505) was more expensive compared to weekly MTX ($8950) with an ICER of $56,215 per first-line treatment success compared to weekly MTX. Small decreases in QOL dramatically increased the ICER during sensitivity analysis. Models with multi-day MTX regimens were also more cost-effective than Act-D. If effectiveness was redefined as avoidance of multi-agent chemotherapy, weekly MTX was more effective.With a complete cure rate for low-risk GTN regardless of initial agent, our model supports provider hesitation toward first line Act-D for low risk GTN. While Act-D is more effective for first line treatment success, it is more costly, and does not decrease rate of multi-agent chemotherapy use.

Authors
Miller, CR; Chappell, NP; Sledge, C; Leath, CA; Phippen, NT; Havrilesky, LJ; Barnett, JC
MLA Citation
Miller, CR, Chappell, NP, Sledge, C, Leath, CA, Phippen, NT, Havrilesky, LJ, and Barnett, JC. "Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?." Gynecologic oncology 144.1 (January 2017): 125-129.
PMID
27816248
Source
epmc
Published In
Gynecologic Oncology
Volume
144
Issue
1
Publish Date
2017
Start Page
125
End Page
129
DOI
10.1016/j.ygyno.2016.10.038

Definitive Chemoradiotherapy for Vulvar Cancer

Authors
Natesan, D; Susko, M; Havrilesky, L; Chino, J
MLA Citation
Natesan, D, Susko, M, Havrilesky, L, and Chino, J. "Definitive Chemoradiotherapy for Vulvar Cancer." International Journal of Gynecological Cancer 26.9 (November 2016): 1699-1705.
Source
crossref
Published In
International Journal of Gynecological Cancer
Volume
26
Issue
9
Publish Date
2016
Start Page
1699
End Page
1705
DOI
10.1097/IGC.0000000000000811

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

Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors.

Authors
Morgan, RJ; Armstrong, DK; Alvarez, RD; Bakkum-Gamez, JN; Behbakht, K; Chen, L-M; Copeland, L; Crispens, MA; DeRosa, M; Dorigo, O; Gershenson, DM; Gray, HJ; Hakam, A; Havrilesky, LJ; Johnston, C; Lele, S; Martin, L; Matulonis, UA; O'Malley, DM; Penson, RT; Percac-Lima, S; Pineda, M; Plaxe, SC; Powell, MA; Ratner, E; Remmenga, SW; Rose, PG; Sabbatini, P; Santoso, JT; Werner, TL; Burns, J; Hughes, M
MLA Citation
Morgan, RJ, Armstrong, DK, Alvarez, RD, Bakkum-Gamez, JN, Behbakht, K, Chen, L-M, Copeland, L, Crispens, MA, DeRosa, M, Dorigo, O, Gershenson, DM, Gray, HJ, Hakam, A, Havrilesky, LJ, Johnston, C, Lele, S, Martin, L, Matulonis, UA, O'Malley, DM, Penson, RT, Percac-Lima, S, Pineda, M, Plaxe, SC, Powell, MA, Ratner, E, Remmenga, SW, Rose, PG, Sabbatini, P, Santoso, JT, Werner, TL, Burns, J, and Hughes, M. "Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology." Journal of the National Comprehensive Cancer Network : JNCCN 14.9 (September 2016): 1134-1163.
PMID
27587625
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
14
Issue
9
Publish Date
2016
Start Page
1134
End Page
1163

Tumor grade and chemotherapy response in endometrioid endometrial cancer.

The objective of this study is to evaluate the association between tumor grade and response to chemotherapy in patients with endometrioid endometrial adenocarcinoma. Patients with advanced or recurrent endometrioid endometrial adenocarcinoma of known tumor grade who received at least 3 cycles of chemotherapy were retrospectively identified at three institutions. RECIST 1.1 criteria were used to assess response to neoadjuvant, postoperative or salvage chemotherapy. Chi-square testing was used to evaluate the association between tumor grade and chemotherapy response. Ninety-one patients met inclusion criteria: 13 with grade 1, 29 with grade 2 and 49 with grade 3 tumors. Eighty-four percent of patients received chemotherapy for recurrence, 12% for postoperative residual disease, and 4% in the neoadjuvant setting. The majority (85%) received carboplatin and paclitaxel. Forty-six percent (6/13) of grade 1, 72% (21/29) of grade 2 and 43% (21/49) of grade 3 tumors achieved an objective response. Grade 2 tumors were more likely to respond to chemotherapy compared to grade 3 tumors (72% vs. 43%, p = 0.02; Table 2), and specifically more likely to respond to carboplatin/paclitaxel (72% vs. 41%, p = 0.016). Median progression-free survival for patients receiving chemotherapy for recurrence or progression was 9 months for grade 1, 8 months for grade 2, and 5 months for grade 3 tumors. Similar results between grade and treatment response were apparent in the subset of 37 patients with a recently re-assigned tumor grade (G2 88% vs. G3 44%, p = 0.032). In this series of endometrioid endometrial cancers, grade 2 tumors had the best measurable response to chemotherapy.

Authors
Davidson, BA; Foote, J; Clark, LH; Broadwater, G; Ehrisman, J; Gehrig, P; Graybill, W; Alvarez Secord, A; Havrilesky, LJ
MLA Citation
Davidson, BA, Foote, J, Clark, LH, Broadwater, G, Ehrisman, J, Gehrig, P, Graybill, W, Alvarez Secord, A, and Havrilesky, LJ. "Tumor grade and chemotherapy response in endometrioid endometrial cancer." Gynecologic oncology reports 17 (August 2016): 3-6.
PMID
27354990
Source
epmc
Published In
Gynecologic Oncology Reports
Volume
17
Publish Date
2016
Start Page
3
End Page
6
DOI
10.1016/j.gore.2016.04.006

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

A personalized paradigm in the treatment of platinum-resistant ovarian cancer - A cost utility analysis of genomic-based versus cytotoxic therapy.

To assess the cost-effectiveness of a strategy employing genomic-based tumor testing to guide therapy for platinum-resistant ovarian cancer.A decision model was created to compare standard of care (SOC) cytotoxic chemotherapy to a genomic-based treatment strategy. The genomic arm included tumor testing with treatment directed at targets identified. Overall survival was assumed to be similar between strategies; quality of life (QOL) was assumed superior during targeted therapy compared to chemotherapy. Pertinent uncertainties (cost of targeted therapy and genomic testing, response to targeted therapy, probability of a tumor having a targetable alteration, and impact on QOL) were evaluated in a series of one-and two-way sensitivity analyses.The genomic testing strategy was more expensive ($90,271 vs. $74,926) per patient than SOC. The incremental cost-effectiveness ratio (ICER) of the genomic strategy was $479,303 per quality-adjusted life year saved (QALY). Model results were insensitive to the cost of genomic testing, differences in QOL, and the probability of identifying a targetable alteration. However, the model was sensitive to the cost of targeted therapy. For example, when the cost of targeted therapy was reduced to 56% of its current cost (or $6400/cycle), the genomic strategy became more cost-effective with an ICER of $96,612/QALY.Genomic-based tumor testing and targeted therapy in patients with platinum-resistant ovarian cancer is not cost-effective compared with SOC. However, reducing the cost of targeted therapy (independently, or in combination with reducing the cost of the genomic test) provides opportunities for improved value in cancer care.

Authors
Wallbillich, JJ; Forde, B; Havrilesky, LJ; Cohn, DE
MLA Citation
Wallbillich, JJ, Forde, B, Havrilesky, LJ, and Cohn, DE. "A personalized paradigm in the treatment of platinum-resistant ovarian cancer - A cost utility analysis of genomic-based versus cytotoxic therapy." Gynecologic oncology 142.1 (July 2016): 144-149.
PMID
27106017
Source
epmc
Published In
Gynecologic Oncology
Volume
142
Issue
1
Publish Date
2016
Start Page
144
End Page
149
DOI
10.1016/j.ygyno.2016.04.024

Does Routine Posttreatment PET/CT Add Value to the Care of Women With Locally Advanced Cervical Cancer?

The aim of this study was to determine the necessary reduction in recurrence rate that would make postchemoradiation positron emission tomography (PET)/computed tomography (CT) to direct completion hysterectomy for locally advanced cervical cancer (LACC) cost-effective.A decision model evaluated costs and recurrence rates of 2 posttreatment surveillance strategies in LACC: (1) routine surveillance without PET/CT and (2) PET/CT after 3 months to triage to completion hysterectomy. Incremental cost-effectiveness ratios were expressed in dollars per additional cancer recurrence avoided. Model parameters included expected rates of recurrence using each strategy, true- and false-positive rates of posttreatment PET/CT, and major complications of completion hysterectomy. From published data, we modeled an LACC baseline recurrence rate of 32%, PET/CT false-positive rate of 33%, and false-negative rate of 19%. We assumed that PET/CT revealed persistent local cervical cancer in 16% and progressive or distant disease in 6%. Costs of PET/CT, hysterectomy, and treatment for recurrence were based on Medicare reimbursements. A 50% salvage rate with hysterectomy was assumed and varied in sensitivity analysis.Routine use of PET/CT to direct completion hysterectomy was associated with a higher average cost ($16,579 vs $15,450) and a lower recurrence rate (26% vs 32%). The incremental cost-effectiveness ratio of PET was $20,761 per recurrence prevented. When the probability of recurrence after hysterectomy dropped to 25% or less, PET/CT was a dominant strategy.Routine use of PET/CT to determine which patients may benefit from a completion hysterectomy after chemoradiation for LACC has the potential to be highly cost-effective.

Authors
Phippen, NT; Havrilesky, LJ; Barnett, JC; Hamilton, CA; Stany, MP; Lowery, WJ
MLA Citation
Phippen, NT, Havrilesky, LJ, Barnett, JC, Hamilton, CA, Stany, MP, and Lowery, WJ. "Does Routine Posttreatment PET/CT Add Value to the Care of Women With Locally Advanced Cervical Cancer?." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 26.5 (June 2016): 944-950.
PMID
27051057
Source
epmc
Published In
International Journal of Gynecological Cancer
Volume
26
Issue
5
Publish Date
2016
Start Page
944
End Page
950
DOI
10.1097/igc.0000000000000705

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

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.
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

Impact of postoperative nausea and vomiting prophylaxis with dexamethasone on the risk of recurrence of endometrial cancer.

To assess whether antiemetic doses of dexamethasone are associated with an increased risk of cancer recurrence in women who underwent surgery for endometrial cancer.This is a retrospective study at an academic university medical center. Women who underwent surgery for endometrial cancer from 2003 to 2007 were identified from a prospectively collected endometrial cancer database. Perioperative records were reviewed to determine administration of dexamethasone. Patients were divided into two groups: those who received dexamethasone 4-10 mg for postoperative nausea and vomiting prophylaxis and those who did not receive dexamethasone. We collected information on patient demographics, cancer stage, cancer grade, histology, year of surgery, chemotherapy, radiation therapy, duration of surgery, perioperative blood transfusion, receipt of epidural analgesia, dose of dexamethasone given, follow-up time, and co-morbidities.Primary endpoint was recurrence-free survival. Secondary endpoints included progression-free survival and overall survival.Three hundred and nine patients were included in the analysis. There were no significant differences between dexamethasone exposed (n = 107) and non-exposed patients in recurrence-free survival ([5 year estimate (95% CI)] = 71 (62-82) % vs. 71 (64-78) %, p = 1.0), progression-free survival (57 [47-68] % vs. 60 [53-68] %, p = 0.9), or overall survival (68 [59-79] % vs. 71 [64-79] %, p = 1.0). In univariate analysis, significant predictors of recurrence-free survival were tumor stage (p = 0.02), tumor grade (0.003) and receipt of adjuvant chemotherapy (p < 0.001). In the multivariable model, higher tumor grade (hazard ratio [HR] [95% CI] = 2.3 [1.4-3.9], p = 0.002) and receipt of adjuvant chemotherapy (3.2 [1.8-5.8], p < 0.001), but not dexamethasone (0.9 [0.5-1.5], p = 0.7), were significant predictors of recurrence-free survival.Dexamethasone administration was not associated with an increased risk of recurrence in women having surgery for endometrial cancer. Limitations of the study include its retrospective single center design and the fact that administration of dexamethasone was not randomized.

Authors
Merk, BA; Havrilesky, LJ; Ehrisman, JA; Broadwater, G; Habib, AS
MLA Citation
Merk, BA, Havrilesky, LJ, Ehrisman, JA, Broadwater, G, and Habib, AS. "Impact of postoperative nausea and vomiting prophylaxis with dexamethasone on the risk of recurrence of endometrial cancer." Current medical research and opinion 32.3 (January 2016): 453-458.
PMID
26583436
Source
epmc
Published In
Current Medical Research and Opinion
Volume
32
Issue
3
Publish Date
2016
Start Page
453
End Page
458
DOI
10.1185/03007995.2015.1123146

Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: An NRG oncology/gynecologic oncology group study

Authors
Hess, LM; Huang, HQ; Hanlon, AL; Robinson, WR; Johnson, R; Chambers, SK; Mannel, RS; Puls, L; Davidson, SA; Method, M; Lele, S; Havrilesky, L; Nelson, T; Alberts, DS
MLA Citation
Hess, LM, Huang, HQ, Hanlon, AL, Robinson, WR, Johnson, R, Chambers, SK, Mannel, RS, Puls, L, Davidson, SA, Method, M, Lele, S, Havrilesky, L, Nelson, T, and Alberts, DS. "Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: An NRG oncology/gynecologic oncology group study." Gynecologic Oncology 139.3 (December 2015): 541-545.
Source
crossref
Published In
Gynecologic Oncology
Volume
139
Issue
3
Publish Date
2015
Start Page
541
End Page
545
DOI
10.1016/j.ygyno.2015.10.003

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

Benefits and Harms of Breast Cancer Screening: A Systematic Review.

Patients need to consider both benefits and harms of breast cancer screening.To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy.We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO (to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, as well as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes among women at average risk of breast cancer (no known genetic susceptibility, family history, previous breast neoplasia, or chest irradiation). We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews.Across all ages of women at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95% CI, 0.73-0.89]; Canadian Task Force: RR, 0.82 [95% CI, 0.74-0.94]; Cochrane: RR, 0.81 [95% CI, 0.74-0.87]); were greater in a meta-analysis of cohort studies (RR, 0.75 [95% CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, among women 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. For women with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy result was higher (7.0% [95% CI, 6.1%-7.8%]) for annual compared with biennial (4.8% [95% CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive results were lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was low in quality. There was no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE.For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.

Authors
Myers, ER; Moorman, P; Gierisch, JM; Havrilesky, LJ; Grimm, LJ; Ghate, S; Davidson, B; Mongtomery, RC; Crowley, MJ; McCrory, DC; Kendrick, A; Sanders, GD
MLA Citation
Myers, ER, Moorman, P, Gierisch, JM, Havrilesky, LJ, Grimm, LJ, Ghate, S, Davidson, B, Mongtomery, RC, Crowley, MJ, McCrory, DC, Kendrick, A, and Sanders, GD. "Benefits and Harms of Breast Cancer Screening: A Systematic Review." JAMA 314.15 (October 2015): 1615-1634.
PMID
26501537
Source
epmc
Published In
JAMA : the journal of the American Medical Association
Volume
314
Issue
15
Publish Date
2015
Start Page
1615
End Page
1634
DOI
10.1001/jama.2015.13183

Postoperative Pain Scores and Narcotic Use in Robotic-assisted Versus Laparoscopic Hysterectomy for Endometrial Cancer Staging.

To retrospectively evaluate perioperative pain and analgesic and antiemetic use in patients who underwent surgical staging for endometrial cancer using traditional versus robotic-assisted laparoscopy.We identified women in a single institution who underwent minimally hysterectomy for endometrial cancer from 2008 to 2012. Patient characteristics and perioperative outcomes, including analgesic and antiemetic use and pain scores, were analyzed. After univariate analysis, a multivariate linear regression model was generated to determine factors associated with narcotic use in the post anesthesia care unit (PACU) (Canadian Task Force Classification II-3).A single academic institution in the United States from 2008 to 2012.Women undergoing total laparoscopic hysterectomy or robotic-assisted laparoscopic hysterectomy for endometrial cancer.Laparoscopic or robotic-assisted laparoscopic hysterectomy.Three hundred thirty-five women were included (213 laparoscopy and 122 robotic-assisted laparoscopy). There was no difference in pain scores at 0 to 6 and 6 to 12 hours after surgery; at 12 to 24 hours, robotic-assisted surgery was associated with higher median pain scores (5/10 vs 4/10, p = .012). Robotic-assisted surgery was associated with a longer anesthesia time (289 vs 255 minutes, p < .001), similar antiemetic use (p = .40), and lower narcotic use in the postanesthesia care unit (PACU) (1.3 mg vs 2.5 mg morphine equivalents, p = .003). There was no difference in narcotic use on the postoperative floor (p = .46). In multivariate analysis controlling for age, menopausal status, anesthesia duration, and local anesthetic use, hysterectomy type was not a significant predictor of PACU narcotic use (p = .86).In a retrospective analysis, a robotic-assisted approach to endometrial cancer was not associated with reduced PACU narcotic or antiemetic use compared with the traditional laparoscopic approach. Twenty-four-hour narcotic and antiemetic use was also not different between the 2 approaches.

Authors
Turner, TB; Habib, AS; Broadwater, G; Valea, FA; Fleming, ND; Ehrisman, JA; Di Santo, N; Havrilesky, LJ
MLA Citation
Turner, TB, Habib, AS, Broadwater, G, Valea, FA, Fleming, ND, Ehrisman, JA, Di Santo, N, and Havrilesky, LJ. "Postoperative Pain Scores and Narcotic Use in Robotic-assisted Versus Laparoscopic Hysterectomy for Endometrial Cancer Staging." Journal of minimally invasive gynecology 22.6 (September 2015): 1004-1010.
PMID
25967934
Source
epmc
Published In
Journal of Minimally Invasive Gynecology
Volume
22
Issue
6
Publish Date
2015
Start Page
1004
End Page
1010
DOI
10.1016/j.jmig.2015.05.003

Improving NCCN guideline-adherent care for ovarian cancer: Value of an intervention.

To estimate the potential cost-effectiveness of an intervention to improve adherence to National Comprehensive Cancer Network (NCCN) guideline-based care for ovarian cancer.A modified Markov model with a 5-year time horizon estimated the potential cost-effectiveness of an intervention (AD-INT) to improve NCCN-guideline adherence compared to status quo (SQ) levels of adherence. Data were obtained from a population-based analysis of National Cancer Data Base records for ovarian cancer diagnosed from 1998 to 2002 (N=47,160). Cohorts were defined by race and adherence to NCCN guideline-based care. Costs were estimated using 2014 Medicare reimbursements. Incremental cost-effectiveness ratios (ICERs) were calculated in 2014 US dollars per year of life saved (YLS) using the standard threshold of $50,000/YLS. We simulated an AD-INT that reduced non-adherence by 25% and cost at least $100 per patient. One-way sensitivity analyses were performed.Although the individual components of guideline-adherent care are more costly than non-adherent care, a reasonably effective AD-INT is also highly likely to be cost-effective. An AD-INT costing $100 per patient and reducing non-adherence by 25% is cost-effective with an ICER of $22/YLS compared with SQ, while interventions costing over $1000 remain cost-effective, up to a per-patient intervention cost of up to $8000 (targeting only blacks) or $4000 (targeting all patients).An ovarian cancer intervention that moderately decreases racial disparities in NCCN guideline adherent care or improves adherence for all is potentially cost-effective. Further research may determine which modifiable factors may be targeted to help reduce adherence disparities.

Authors
Dottino, JA; Cliby, WA; Myers, ER; Bristow, RE; Havrilesky, LJ
MLA Citation
Dottino, JA, Cliby, WA, Myers, ER, Bristow, RE, and Havrilesky, LJ. "Improving NCCN guideline-adherent care for ovarian cancer: Value of an intervention." Gynecologic oncology 138.3 (September 2015): 694-699.
PMID
26072441
Source
epmc
Published In
Gynecologic Oncology
Volume
138
Issue
3
Publish Date
2015
Start Page
694
End Page
699
DOI
10.1016/j.ygyno.2015.06.013

Consensus in controversy: The modified Delphi method applied to Gynecologic Oncology practice.

To determine the degree of consensus regarding the probabilities of outcomes associated with IP/IV and IV chemotherapy.A survey was administered to an expert panel using the Delphi method. Ten ovarian cancer experts were asked to estimate outcomes for patients receiving IP/IV or IV chemotherapy. The clinical estimates were: 1) probability of completing six cycles of chemotherapy, 2) probability of surviving five years, 3) median survival, and 4) probability of ER/hospital visits during treatment. Estimates for two patients, one with a low comorbidity index (patient 1) and the other with a moderate index (patient 2), were included. The survey was administered in three rounds, and panelists could revise their subsequent responses based on review of the anonymous opinions of their peers.The ranges were smaller for IV compared with IP/IV therapy. Ranges decreased with each round. Consensus converged around outcomes related to IP/IV chemotherapy for: 1) completion of 6 cycles of therapy (type 1 patient, 62%, type 2 patient, 43%); 2) percentage of patients surviving 5 years (type 1 patient, 66%, type 2 patient, 47%); and 3) median survival (type 1 patient, 83 months, type 2 patient, 58 months). The group required three rounds to achieve consensus on the probabilities of ER/hospital visits (type 1 patient, 24%, type 2 patient, 35%).Initial estimates of survival and adverse events associated with IP/IV chemotherapy differ among experts. The Delphi process works to build consensus and may be a pragmatic tool to inform patients of their expected outcomes.

Authors
Cohn, DE; Havrilesky, LJ; Osann, K; Lipscomb, J; Hsieh, S; Walker, JL; Wright, AA; Alvarez, RD; Karlan, BY; Bristow, RE; DiSilvestro, PA; Wakabayashi, MT; Morgan, R; Mukamel, DB; Wenzel, L
MLA Citation
Cohn, DE, Havrilesky, LJ, Osann, K, Lipscomb, J, Hsieh, S, Walker, JL, Wright, AA, Alvarez, RD, Karlan, BY, Bristow, RE, DiSilvestro, PA, Wakabayashi, MT, Morgan, R, Mukamel, DB, and Wenzel, L. "Consensus in controversy: The modified Delphi method applied to Gynecologic Oncology practice." Gynecologic oncology 138.3 (September 2015): 712-716.
PMID
26177553
Source
epmc
Published In
Gynecologic Oncology
Volume
138
Issue
3
Publish Date
2015
Start Page
712
End Page
716
DOI
10.1016/j.ygyno.2015.07.014

Bariatric surgery as a means to decrease mortality in women with type I endometrial cancer - An intriguing option in a population at risk for dying of complications of metabolic syndrome.

To estimate the cost-effectiveness and utility of a strategy of offering weight loss surgery (WLS) to women with low risk stage I endometrial cancer (EC) and BMI≥40kg/m(2).A modified Markov state transition model was designed to compare routine care to WLS for women with low risk stage I endometrioid EC, age<70, with a mean BMI 40. A time horizon of 15years was used to simulate the overall survival (OS) of 96,232 women treated from 1988-2010 from SEER*Stat data. To simulate the effects of WLS on OS, a hazard ratio (0.76, 95% CI 0.59-0.99) representing the OS improvement achieved from this intervention (derived from a prospective trial) was modeled. We assumed that 90% of women undergoing bariatric procedures would experience a reduction in BMI. We assumed that 5% of women not undergoing WLS would achieve weight loss to a BMI of 35. Costs of treatment for obesity-related chronic diseases and quality of life (QOL)-related utilities were modeled from published reports.The mean cost-effectiveness for each strategy was: $69,295 and 8.10 quality-adjusted life years (QALYs) for routine care versus $100,675 and 9.30 QALYs for WLS. WLS had an incremental cost-effectiveness ratio (ICER) of $26,080/QALY compared to routine care. At a willingness to pay threshold of $50,000/QALY, WLS was the strategy of choice in 100% of simulations.WLS is a potentially cost-effective intervention in women with low risk, early stage EC, at least in part due to improved quality of life with weight reduction.

Authors
Neff, R; Havrilesky, LJ; Chino, J; O'Malley, DM; Cohn, DE
MLA Citation
Neff, R, Havrilesky, LJ, Chino, J, O'Malley, DM, and Cohn, DE. "Bariatric surgery as a means to decrease mortality in women with type I endometrial cancer - An intriguing option in a population at risk for dying of complications of metabolic syndrome." Gynecologic oncology 138.3 (September 2015): 597-602.
PMID
26232518
Source
epmc
Published In
Gynecologic Oncology
Volume
138
Issue
3
Publish Date
2015
Start Page
597
End Page
602
DOI
10.1016/j.ygyno.2015.07.002

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

Patient and physician factors associated with participation in cervical and uterine cancer trials: an NRG/GOG247 study.

The aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials.Prospective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial. Odds ratios (OR) and 95% confidence intervals (CI) for significant (p<0.05) results reported.Sixty institutions, 781 patients, and 150 physicians participated, 300/780 (38%) had a trial available, 290/300 had known participation status. Of these, 150 women enrolled (59.5%), 102 eligible did not enroll (35%), 38 (13%) were ineligible. Ethnicity and specialty of physician, practice type, data management availability, and patient age were significantly associated with trial availability. Patients with >4 comorbidities (OR 4.5; CI 1.7-11.8) had higher odds of trial ineligibility. Non-White patients (OR 7.9; CI 1.3-46.2) and patients of Black physicians had greater odds of enrolling (OR 56.5; CI 1.1-999.9) in a therapeutic trial. Significant patient therapeutic trial enrollment factors: belief trial may help (OR 76.9; CI 4.9->1000), concern about care if not on trial (OR12.1; CI 2.1-71.4), pressure to enroll (OR .27; CI 0.12-.64), caregiving without pay (OR 0.13; CI .02-.84). Significant physician beliefs were: patients would not do well on standard therapy (OR 3.6; CI 1.6-8.4), and trial would not be time consuming (OR 3.3; CI 1.3-8.1).Trial availability, patient and physician beliefs were factors identified that if modified could improve enrollment in cancer cooperative group clinical trials.

Authors
Brooks, SE; Carter, RL; Plaxe, SC; Basen-Engquist, KM; Rodriguez, M; Kauderer, J; Walker, JL; Myers, TKN; Drake, JG; Havrilesky, LJ; Van Le, L; Landrum, LM; Brown, CL
MLA Citation
Brooks, SE, Carter, RL, Plaxe, SC, Basen-Engquist, KM, Rodriguez, M, Kauderer, J, Walker, JL, Myers, TKN, Drake, JG, Havrilesky, LJ, Van Le, L, Landrum, LM, and Brown, CL. "Patient and physician factors associated with participation in cervical and uterine cancer trials: an NRG/GOG247 study." Gynecologic oncology 138.1 (July 2015): 101-108.
PMID
25937529
Source
epmc
Published In
Gynecologic Oncology
Volume
138
Issue
1
Publish Date
2015
Start Page
101
End Page
108
DOI
10.1016/j.ygyno.2015.04.033

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

Abstract 10: Does routine post-treatment PET/CT add value to the care of women with locally advanced cervical cancer?

Authors
Phippen, NT; Havrilesky, LJ; Barnett, JC; Hamilton, CA; Stany, M; Lowery, WJ
MLA Citation
Phippen, NT, Havrilesky, LJ, Barnett, JC, Hamilton, CA, Stany, M, and Lowery, WJ. "Abstract 10: Does routine post-treatment PET/CT add value to the care of women with locally advanced cervical cancer?." Gynecologic Oncology 137.3 (June 2015): 594-595.
Source
crossref
Published In
Gynecologic Oncology
Volume
137
Issue
3
Publish Date
2015
Start Page
594
End Page
595
DOI
10.1016/j.ygyno.2015.03.027

Costs, Effectiveness, and Workload Impact of Management Strategies for Women With an Adnexal Mass

Authors
Havrilesky, LJ; Dinan, M; Sfakianos, GP; Curtis, LH; Barnett, JC; Van Gorp, T; Myers, ER
MLA Citation
Havrilesky, LJ, Dinan, M, Sfakianos, GP, Curtis, LH, Barnett, JC, Van Gorp, T, and Myers, ER. "Costs, Effectiveness, and Workload Impact of Management Strategies for Women With an Adnexal Mass." Obstetrical & Gynecological Survey 70.4 (April 2015): 253-255.
Source
crossref
Published In
Obstetrical and Gynecological Survey
Volume
70
Issue
4
Publish Date
2015
Start Page
253
End Page
255
DOI
10.1097/01.ogx.0000464937.42384.2d

A review of relative dose intensity and survival in patients with metastatic solid tumors.

Studies have shown that in the curative setting patients with cancer receiving chemotherapy at higher relative dose intensity (RDI) had better clinical outcomes than those receiving treatment at lower RDI. However, the impact of RDI in advanced/metastatic disease remains unclear. A review of the literature was performed to evaluate the relationship between RDI and survival in patients with metastatic lung, breast, or ovarian cancer receiving chemotherapy. Few studies attempted to specifically associate RDI with survival in a systematic way. Findings from studies that analyzed overall survival with a prespecified RDI threshold support the emerging perception that maintaining an RDI≥85% has a favorable impact on survival. Nonetheless, these studies were limited by their retrospective nature. More studies are needed to further evaluate the impact of maintaining planned chemotherapy dose intensity on outcomes in metastatic solid tumors.

Authors
Havrilesky, LJ; Reiner, M; Morrow, PK; Watson, H; Crawford, J
MLA Citation
Havrilesky, LJ, Reiner, M, Morrow, PK, Watson, H, and Crawford, J. "A review of relative dose intensity and survival in patients with metastatic solid tumors." Critical reviews in oncology/hematology 93.3 (March 2015): 203-210.
PMID
25459671
Source
epmc
Published In
Critical Reviews in Oncology/Hematology
Volume
93
Issue
3
Publish Date
2015
Start Page
203
End Page
210
DOI
10.1016/j.critrevonc.2014.10.006

A cost-utility analysis of NRG Oncology/Gynecologic Oncology Group Protocol 218: Incorporating prospectively collected quality-of-life scores in an economic model of treatment of ovarian cancer

© 2014 Elsevier Inc. All rights reserved.Objective. To estimate quality-of-life (QOL)-adjusted cost-utility with addition of bevacizumab (B) to intravenous paclitaxel/carboplatin (PC) for primary treatment of advanced-stage epithelial ovarian cancer. Methods. A modified Markov state transition model of 3 regimens evaluated in GOG 218 (PC, PC + concurrent B [PCB], and PCB + maintenance B [PCB + B]) was populated by prospectively collected survival, adverse event, and QOL data from GOG 218. Progression-free survival (PFS) and overall survival (OS) were modeled using primary event data. Costs of grade 4 hypertension, grade 3-5 bowel events, and growth factor support were incorporated. QOL scores were converted to utilities and incorporated into the model. Monte Carlo probabilistic sensitivity analysis was performed to account for uncertainty in estimates. Results. PC was the least expensive ($4044) and least effective (mean 1.1 quality-adjusted progression-free years [QA-PFY]) regimen. PCB ($43,703 and 1.13 QA-PFY) was dominated by a combination of PC and PCB + B. PCB + B ($122,700 and 1.25 QA-PFY) was the most expensive regimen with an incremental cost-effectiveness ratio of $792,380/QA-PFY compared to PC. In a model not incorporating QOL, the incremental cost-effectiveness ratio (ICER) of PCB + B was $632,571/PFY compared to PC. Conclusions. In this cost-utility model, incorporation of QOL into an analysis of GOG 218 led to less favorable ICER (by >$150,000/QA-PFY) in regimens containing B compared with those that do not include B. Continued investigation of populations with ovarian cancer in whom the efficacy of treatment with bevacizumab is expected to be increased (or in whom QOL is expected to increase with use) is critical.

Authors
Cohn, DE; Barnett, JC; Wenzel, L; Monk, BJ; Burger, RA; Straughn, JM; Myers, ER; Havrilesky, LJ
MLA Citation
Cohn, DE, Barnett, JC, Wenzel, L, Monk, BJ, Burger, RA, Straughn, JM, Myers, ER, and Havrilesky, LJ. "A cost-utility analysis of NRG Oncology/Gynecologic Oncology Group Protocol 218: Incorporating prospectively collected quality-of-life scores in an economic model of treatment of ovarian cancer." Gynecologic Oncology 136.2 (February 1, 2015): 293-299.
Source
scopus
Published In
Gynecologic Oncology
Volume
136
Issue
2
Publish Date
2015
Start Page
293
End Page
299
DOI
10.1016/j.ygyno.2014.10.020

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

A cost-utility analysis of NRG Oncology/Gynecologic Oncology Group Protocol 218: incorporating prospectively collected quality-of-life scores in an economic model of treatment of ovarian cancer.

To estimate quality-of-life (QOL)-adjusted cost-utility with addition of bevacizumab (B) to intravenous paclitaxel/carboplatin (PC) for primary treatment of advanced-stage epithelial ovarian cancer.A modified Markov state transition model of 3 regimens evaluated in GOG 218 (PC, PC+concurrent B [PCB], and PCB+maintenance B [PCB+B]) was populated by prospectively collected survival, adverse event, and QOL data from GOG 218. Progression-free survival (PFS) and overall survival (OS) were modeled using primary event data. Costs of grade 4 hypertension, grade 3-5 bowel events, and growth factor support were incorporated. QOL scores were converted to utilities and incorporated into the model. Monte Carlo probabilistic sensitivity analysis was performed to account for uncertainty in estimates.PC was the least expensive ($4044) and least effective (mean 1.1 quality-adjusted progression-free years [QA-PFY]) regimen. PCB ($43,703 and 1.13 QA-PFY) was dominated by a combination of PC and PCB+B. PCB+B ($122,700 and 1.25 QA-PFY) was the most expensive regimen with an incremental cost-effectiveness ratio of $792,380/QA-PFY compared to PC. In a model not incorporating QOL, the incremental cost-effectiveness ratio (ICER) of PCB+B was $632,571/PFY compared to PC.In this cost-utility model, incorporation of QOL into an analysis of GOG 218 led to less favorable ICER (by >$150,000/QA-PFY) in regimens containing B compared with those that do not include B. Continued investigation of populations with ovarian cancer in whom the efficacy of treatment with bevacizumab is expected to be increased (or in whom QOL is expected to increase with use) is critical.

Authors
Cohn, DE; Barnett, JC; Wenzel, L; Monk, BJ; Burger, RA; Straughn, JM; Myers, ER; Havrilesky, LJ
MLA Citation
Cohn, DE, Barnett, JC, Wenzel, L, Monk, BJ, Burger, RA, Straughn, JM, Myers, ER, and Havrilesky, LJ. "A cost-utility analysis of NRG Oncology/Gynecologic Oncology Group Protocol 218: incorporating prospectively collected quality-of-life scores in an economic model of treatment of ovarian cancer." Gynecologic oncology 136.2 (February 2015): 293-299.
PMID
25449568
Source
epmc
Published In
Gynecologic Oncology
Volume
136
Issue
2
Publish Date
2015
Start Page
293
End Page
299
DOI
10.1016/j.ygyno.2014.10.020

Lymphatic mapping and sentinel lymph node dissection compared to complete lymphadenectomy in the management of early-stage vulvar cancer: A cost-utility analysis.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) is an acceptable method of evaluating groin lymph nodes in women with vulvar cancer. The purpose of this study is to assess the cost and effectiveness of SLNB compared to universal inguinofemoral lymphadenectomy (LND) for vulvar cancer. METHODS: A modified Markov decision model was generated to compare two surgical approaches for newly diagnosed, early-stage vulvar cancer: (1) radical vulvectomy+LND and (2) radical vulvectomy+SLNB. Published data were used to estimate survival outcomes, probability of positive lymph nodes and lymphedema. Costs of surgery and radiation and lymphedema therapies were estimated from published data. Lymphedema's effect on quality of life (QOL) was extrapolated from other disease sites and assigned a utility score of 0.84. Multiple sensitivity analyses were performed. RESULTS: SLNB was less costly ($13,449 versus $14,261) and more effective (4.16 quality-adjusted life years (QALYs) versus 4.00 QALYs) than LND. The model was sensitive to the impact of lymphedema on QOL. Unless the impact of lymphedema on QOL was minimal (utility score>0.975) SLNB dominated LND. Variations in the rate of positive SLNB and probability of lymphedema over clinically reasonable ranges did not alter the results. CONCLUSIONS: SLNB is a cost-effective strategy for the treatment of newly diagnosed vulvar cancer, mainly due to the impact of lymphedema on QOL.

Authors
McCann, GA; Cohn, DE; Jewell, EL; Havrilesky, LJ
MLA Citation
McCann, GA, Cohn, DE, Jewell, EL, and Havrilesky, LJ. "Lymphatic mapping and sentinel lymph node dissection compared to complete lymphadenectomy in the management of early-stage vulvar cancer: A cost-utility analysis." Gynecologic oncology 136.2 (February 2015): 300-304.
PMID
25478927
Source
epmc
Published In
Gynecologic Oncology
Volume
136
Issue
2
Publish Date
2015
Start Page
300
End Page
304
DOI
10.1016/j.ygyno.2014.11.079

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

A review of relative dose intensity and survival in patients with metastatic solid tumors

© 2014 .Studies have shown that in the curative setting patients with cancer receiving chemotherapy at higher relative dose intensity (RDI) had better clinical outcomes than those receiving treatment at lower RDI. However, the impact of RDI in advanced/metastatic disease remains unclear. A review of the literature was performed to evaluate the relationship between RDI and survival in patients with metastatic lung, breast, or ovarian cancer receiving chemotherapy. Few studies attempted to specifically associate RDI with survival in a systematic way. Findings from studies that analyzed overall survival with a prespecified RDI threshold support the emerging perception that maintaining an RDI. ≥. 85% has a favorable impact on survival. Nonetheless, these studies were limited by their retrospective nature. More studies are needed to further evaluate the impact of maintaining planned chemotherapy dose intensity on outcomes in metastatic solid tumors.

Authors
Havrilesky, LJ; Reiner, M; Morrow, PK; Watson, H; Crawford, J
MLA Citation
Havrilesky, LJ, Reiner, M, Morrow, PK, Watson, H, and Crawford, J. "A review of relative dose intensity and survival in patients with metastatic solid tumors." Critical Reviews in Oncology/Hematology 93.3 (January 1, 2015): 203-210. (Review)
Source
scopus
Published In
Critical Reviews in Oncology/Hematology
Volume
93
Issue
3
Publish Date
2015
Start Page
203
End Page
210
DOI
10.1016/j.critrevonc.2014.10.006

Lymphatic mapping and sentinel lymph node dissection compared to complete lymphadenectomy in the management of early-stage vulvar cancer: A cost-utility analysis

© 2014 Elsevier Inc. All rights reserved.Objective. Sentinel lymph node biopsy (SLNB) is an acceptable method of evaluating groin lymph nodes in women with vulvar cancer. The purpose of this study is to assess the cost and effectiveness of SLNB compared to universal inguinofemoral lymphadenectomy (LND) for vulvar cancer. Methods. A modified Markov decision model was generated to compare two surgical approaches for newly diagnosed, early-stage vulvar cancer: (1) radical vulvectomy + LND and (2) radical vulvectomy + SLNB. Published data were used to estimate survival outcomes, probability of positive lymph nodes and lymphedema. Costs of surgery and radiation and lymphedema therapies were estimated from published data. Lymphedema's effect on quality of life (QOL) was extrapolated from other disease sites and assigned a utility score of 0.84. Multiple sensitivity analyses were performed. Results. SLNB was less costly ($13,449 versus $14,261) and more effective (4.16 quality-adjusted life years (QALYs) versus 4.00 QALYs) than LND. The model was sensitive to the impact of lymphedema on QOL. Unless the impact of lymphedema on QOL was minimal (utility score > 0.975) SLNB dominated LND. Variations in the rate of positive SLNB and probability of lymphedema over clinically reasonable ranges did not alter the results. Conclusions. SLNB is a cost-effective strategy for the treatment of newly diagnosed vulvar cancer, mainly due to the impact of lymphedema on QOL.

Authors
McCann, GA; Cohn, DE; Jewell, EL; Havrilesky, LJ
MLA Citation
McCann, GA, Cohn, DE, Jewell, EL, and Havrilesky, LJ. "Lymphatic mapping and sentinel lymph node dissection compared to complete lymphadenectomy in the management of early-stage vulvar cancer: A cost-utility analysis." Gynecologic Oncology 136.2 (January 1, 2015): 300-304.
Source
scopus
Published In
Gynecologic Oncology
Volume
136
Issue
2
Publish Date
2015
Start Page
300
End Page
304
DOI
10.1016/j.ygyno.2014.11.079

Bevacizumab in recurrent, persistent, or advanced stage carcinoma of the cervix: is it cost-effective?

OBJECTIVE: Evaluate the cost-effectiveness of incorporating bevacizumab into the treatment regimen for recurrent, persistent, or advanced stage carcinoma of the cervix following publication of a recent phase III trial that demonstrated an overall survival (OS) benefit with the addition of bevacizumab. METHODS: A cost-effectiveness decision model was constructed using recently published results from a Gynecologic Oncology Group phase III study, comparing a standard chemotherapy regimen (Chemo) to the experimental regimen (Chemo + Bev) consisting of the standard regimen+bevacizumab. Costs and adverse events were incorporated and sensitivity analyses assessed model uncertainties. RESULTS: The cost of Chemo + Bev was $53,784 compared to $5,688 for the Chemo arm. The 3.7 month OS advantage with Chemo+Bev came at an incremental cost-effectiveness ratio (ICER) of $155K per quality-adjusted life year (QALY). Chemo + Bev becomes cost-effective with an ICER ≤ $100K in sensitivity analysis when the cost of bevacizumab is discounted >37.5% or the dose is reduced from 15 to 7.5 mg/kg, an effective dose in ovarian cancer. CONCLUSIONS: With an ICER of $155K/QALY, the addition of bevacizumab to standard chemotherapy approaches common cost-effectiveness standards. Moderately discounting the cost of bevacizumab or using a smaller dose significantly alters its affordability.

Authors
Phippen, NT; Leath, CA; Havrilesky, LJ; Barnett, JC
MLA Citation
Phippen, NT, Leath, CA, Havrilesky, LJ, and Barnett, JC. "Bevacizumab in recurrent, persistent, or advanced stage carcinoma of the cervix: is it cost-effective?." Gynecologic oncology 136.1 (January 2015): 43-47.
PMID
25448456
Source
epmc
Published In
Gynecologic Oncology
Volume
136
Issue
1
Publish Date
2015
Start Page
43
End Page
47
DOI
10.1016/j.ygyno.2014.11.003

Costs, effectiveness, and workload impact of management strategies for women with an adnexal mass.

BACKGROUND: We compared the estimated clinical outcomes, costs, and physician workload resulting from available strategies for deciding which women with an adnexal mass should be referred to a gynecologic oncologist. METHODS: We used a microsimulation model to compare five referral strategies: 1) American Congress of Obstetricians and Gynecologists (ACOG) guidelines, 2) Multivariate Index Assay (MIA) algorithm, 3) Risk of Malignancy Algorithm (ROMA), 4) CA125 alone with lowered cutoff values to prioritize test sensitivity over specificity, 5) referral of all women (Refer All). Test characteristics and relative survival were obtained from the literature and data from a biomarker validation study. Medical costs were estimated using Medicare reimbursements. Travel costs were estimated using discharge data from Surveillance, Epidemiology and End Results-Medicare and State Inpatient Databases. Analyses were performed separately for pre- and postmenopausal women (60 000 "subjects" in each), repeated 10 000 times. RESULTS: Refer All was cost-effective compared with less expensive strategies in both postmenopausal (incremental cost-effectiveness ratio [ICER] $9423/year of life saved (LYS) compared with CA125) and premenopausal women (ICER $10 644/YLS compared with CA125), but would result in an additional 73 cases/year/subspecialist. MIA was more expensive and less effective than Refer All in pre- and postmenopausal women. If Refer All is not a viable option, CA125 is an optimal strategy in postmenopausal women. CONCLUSIONS: Referral of all women to a subspecialist is an efficient strategy for managing women with adnexal masses requiring surgery, assuming sufficient capacity for additional surgical volume. If a test-based triage strategy is needed, CA125 with lowered cutoff values is a cost-effective strategy.

Authors
Havrilesky, LJ; Dinan, M; Sfakianos, GP; Curtis, LH; Barnett, JC; Van Gorp, T; Myers, ER
MLA Citation
Havrilesky, LJ, Dinan, M, Sfakianos, GP, Curtis, LH, Barnett, JC, Van Gorp, T, and Myers, ER. "Costs, effectiveness, and workload impact of management strategies for women with an adnexal mass." Journal of the National Cancer Institute 107.1 (January 2015): 322-.
PMID
25515232
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
107
Issue
1
Publish Date
2015
Start Page
322
DOI
10.1093/jnci/dju322

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

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

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

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

Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions.

OBJECTIVE: We wished to determine the reduction in the rate of wound complications that would render the use of prophylactic negative pressure wound vacuum therapy (NPWT) cost saving compared to routine incision care (RC) following laparotomy for gynecologic malignancy. METHODS: A decision tree was designed from a payer perspective to compare strategies for incision management following laparotomy for gynecologic malignancy: (1) RC; (2) prophylactic NPWT. Rates of wound complication, antibiotic use, re-hospitalization, re-operation, and home health use were obtained from a published cohort of 431 women who underwent laparotomy for endometrial cancer 2002-2007. Costs were estimated using Medicare reimbursements; cost of NPWT ($200) was obtained from hospital financial department. A 50% reduction in wound complications using NPWT was assigned initially and varied for sensitivity analysis. RESULTS: The mean BMI was 36. The wound complication rate was 31% (37% for BMI>30, 41% for BMI>40). The overall cost of incision care was $104 lower for NPWT than for RC. At the lowest cost of NPWT ($200), the risk of wound complication must be reduced by 33% (relative risk=0.67) for NPWT to achieve cost savings in this cohort. Modeling obese and morbidly obese cohorts, the NPWT resulted in overall cost savings of $163 and $203, respectively, and the risk of wound complication must be reduced by 28% and 25%, respectively, for NPWT to achieve cost savings. CONCLUSION: If the wound complication rate can be reduced by one-third, prophylactic NPWT is potentially cost saving in high-risk women undergoing laparotomy for gynecologic malignancy.

Authors
Lewis, LS; Convery, PA; Bolac, CS; Valea, FA; Lowery, WJ; Havrilesky, LJ
MLA Citation
Lewis, LS, Convery, PA, Bolac, CS, Valea, FA, Lowery, WJ, and Havrilesky, LJ. "Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions." Gynecologic oncology 132.3 (March 2014): 684-689.
PMID
24440649
Source
epmc
Published In
Gynecologic Oncology
Volume
132
Issue
3
Publish Date
2014
Start Page
684
End Page
689
DOI
10.1016/j.ygyno.2014.01.014

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

Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions

Objective We wished to determine the reduction in the rate of wound complications that would render the use of prophylactic negative pressure wound vacuum therapy (NPWT) cost saving compared to routine incision care (RC) following laparotomy for gynecologic malignancy. Methods A decision tree was designed from a payer perspective to compare strategies for incision management following laparotomy for gynecologic malignancy: (1) RC; (2) prophylactic NPWT. Rates of wound complication, antibiotic use, re-hospitalization, re-operation, and home health use were obtained from a published cohort of 431 women who underwent laparotomy for endometrial cancer 2002-2007. Costs were estimated using Medicare reimbursements; cost of NPWT ($200) was obtained from hospital financial department. A 50% reduction in wound complications using NPWT was assigned initially and varied for sensitivity analysis. Results The mean BMI was 36. The wound complication rate was 31% (37% for BMI > 30, 41% for BMI > 40). The overall cost of incision care was $104 lower for NPWT than for RC. At the lowest cost of NPWT ($200), the risk of wound complication must be reduced by 33% (relative risk = 0.67) for NPWT to achieve cost savings in this cohort. Modeling obese and morbidly obese cohorts, the NPWT resulted in overall cost savings of $163 and $203, respectively, and the risk of wound complication must be reduced by 28% and 25%, respectively, for NPWT to achieve cost savings. Conclusion If the wound complication rate can be reduced by one-third, prophylactic NPWT is potentially cost saving in high-risk women undergoing laparotomy for gynecologic malignancy. © 2014 Elsevier Inc.

Authors
Lewis, LS; Convery, PA; Bolac, CS; Valea, FA; Lowery, WJ; Havrilesky, LJ
MLA Citation
Lewis, LS, Convery, PA, Bolac, CS, Valea, FA, Lowery, WJ, and Havrilesky, LJ. "Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions." Gynecologic Oncology 132.3 (January 1, 2014): 684-689.
Source
scopus
Published In
Gynecologic Oncology
Volume
132
Issue
3
Publish Date
2014
Start Page
684
End Page
689
DOI
10.1016/j.ygyno.2014.01.014

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, and 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

Palliative services enhance the quality and value of gynecologic cancer care.

Authors
Havrilesky, LJ
MLA Citation
Havrilesky, LJ. "Palliative services enhance the quality and value of gynecologic cancer care." Gynecologic oncology 132.1 (January 2014): 1-2.
PMID
24444679
Source
epmc
Published In
Gynecologic Oncology
Volume
132
Issue
1
Publish Date
2014
Start Page
1
End Page
2
DOI
10.1016/j.ygyno.2013.12.035

Can we maximize both value and quality in gynecologic cancer care? A work in progress.

Value is defined as desirable health outcomes achieved per monetary unit spent. Comparative effectiveness research and cost-effectiveness research are methods that have been developed to quantify effectiveness and value to inform management decisions. In this article we review the comparative and cost-effectiveness literature in the field of ovarian cancer treatment. Studies have shown that improved ovarian cancer survival is associated with complete primary surgical cytoreduction, with treatment at high volume facilities by subspecialist providers (gynecologic oncologists) and with National Comprehensive Cancer Network (NCCN) guideline-adherent care in both surgical staging and chemotherapy regimens. Intraperitoneal/intravenous chemotherapy (compared with intravenous alone) has been associated with improved survival and cost-effectiveness. Bevacizumab for primary and maintenance therapy has been found to not be cost-effective (even in selective subsets) despite a small progression-free survival (PFS) advantage. For platinum-sensitive recurrent ovarian cancer, secondary cytoreduction and platinum-based combinations are associated with improved overall survival (OS); several platinum-based combinations have also been found cost-effective. For platinum-resistant recurrence, single agent therapy and supportive care are cost-effective compared with combination therapies. Although little prospective clinical research has been done around end-of-life care, one study reported that for platinum-resistant ovarian cancer, palliative intervention would potentially reduce costs and increase quality adjusted life years compared with usual care (based on improvement in quality of life [QOL]). Overall, cost comparisons of individual chemotherapy regimens are highly dependent on market prices of novel therapeutic agents.

Authors
Havrilesky, LJ; Fountain, C
MLA Citation
Havrilesky, LJ, and Fountain, C. "Can we maximize both value and quality in gynecologic cancer care? A work in progress." American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting (January 2014): e268-e275. (Review)
PMID
24857112
Source
epmc
Published In
American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting
Publish Date
2014
Start Page
e268
End Page
e275
DOI
10.14694/edbook_am.2014.34.e268

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. © 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

Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis.

PURPOSE: To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. METHODS: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. RESULTS: From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. CONCLUSION: Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

Authors
Moorman, PG; Havrilesky, LJ; Gierisch, JM; Coeytaux, RR; Lowery, WJ; Peragallo Urrutia, R; Dinan, M; McBroom, AJ; Hasselblad, V; Sanders, GD; Myers, ER
MLA Citation
Moorman, PG, Havrilesky, LJ, Gierisch, JM, Coeytaux, RR, Lowery, WJ, Peragallo Urrutia, R, Dinan, M, McBroom, AJ, Hasselblad, V, Sanders, GD, and Myers, ER. "Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis." J Clin Oncol 31.33 (November 20, 2013): 4188-4198. (Review)
PMID
24145348
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
31
Issue
33
Publish Date
2013
Start Page
4188
End Page
4198
DOI
10.1200/JCO.2013.48.9021

Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review.

Oral contraceptives may influence the risk of certain cancers. As part of the AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, we conducted a systematic review to estimate associations between oral contraceptive use and breast, cervical, colorectal, and endometrial cancer incidence. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews. Study inclusion criteria were women taking oral contraceptives for contraception or ovarian cancer prevention; includes comparison group with no oral contraceptive use; study reports quantitative associations between oral contraceptive exposure and relevant cancers; controlled study or pooled patient-level meta-analyses; sample size for nonrandomized studies ≥100; peer-reviewed, English-language; published from January 1, 2000 forward. Random-effects meta-analyses were conducted by estimating pooled ORs with 95% confidence intervals (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial cancers studies. Breast cancer incidence was slightly but significantly increased in users (OR, 1.08; CI, 1.00-1.17); results show a higher risk associated with more recent use of oral contraceptives. Risk of cervical cancer was increased with duration of oral contraceptive use in women with human papillomavirus infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86; CI, 0.79-0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43-0.77) were significantly reduced by oral contraceptive use. Compared with never use, ever use of oral contraceptives is significantly associated with decreases in colorectal and endometrial cancers and increases in breast cancers. Although elevated breast cancer risk was small, relatively high incidence of breast cancers means that oral contraceptives may contribute to a substantial number of cases.

Authors
Gierisch, JM; Coeytaux, RR; Urrutia, RP; Havrilesky, LJ; Moorman, PG; Lowery, WJ; Dinan, M; McBroom, AJ; Hasselblad, V; Sanders, GD; Myers, ER
MLA Citation
Gierisch, JM, Coeytaux, RR, Urrutia, RP, Havrilesky, LJ, Moorman, PG, Lowery, WJ, Dinan, M, McBroom, AJ, Hasselblad, V, Sanders, GD, and Myers, ER. "Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review." Cancer Epidemiol Biomarkers Prev 22.11 (November 2013): 1931-1943. (Review)
PMID
24014598
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
22
Issue
11
Publish Date
2013
Start Page
1931
End Page
1943
DOI
10.1158/1055-9965.EPI-13-0298

In reply.

Authors
Havrilesky, LJ; Myers, ER; Thomas, WL
MLA Citation
Havrilesky, LJ, Myers, ER, and Thomas, WL. "In reply." Obstet Gynecol 122.5 (November 2013): 1114-. (Letter)
PMID
24150023
Source
pubmed
Published In
Obstetrics and Gynecology
Volume
122
Issue
5
Publish Date
2013
Start Page
1114
DOI
10.1097/01.AOG.0000435077.65209.72

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

Ovarian Cancer, Version 2.2013 Featured Updates to the NCCN Guidelines

Authors
Jr, MRJ; Alvarez, RD; Armstrong, DK; Burger, RA; Chen, L-M; Copeland, L; Crispens, MA; Gershenson, DM; Gray, HJ; Hakam, A; Havrilesky, LJ; Johnston, C; Lele, S; Martin, L; Matulonis, UA; O'Malley, DM; Penson, RT; Powell, MA; Remmenga, SW; Sabbatini, P; Santoso, JT; Schink, JC; Teng, N; Werner, TL; Dwyer, MA; Hughes, M
MLA Citation
Jr, MRJ, Alvarez, RD, Armstrong, DK, Burger, RA, Chen, L-M, Copeland, L, Crispens, MA, Gershenson, DM, Gray, HJ, Hakam, A, Havrilesky, LJ, Johnston, C, Lele, S, Martin, L, Matulonis, UA, O'Malley, DM, Penson, RT, Powell, MA, Remmenga, SW, Sabbatini, P, Santoso, JT, Schink, JC, Teng, N, Werner, TL, Dwyer, MA, and Hughes, M. "Ovarian Cancer, Version 2.2013 Featured Updates to the NCCN Guidelines." JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK 11.10 (October 2013): 1199-1209.
Source
wos-lite
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
10
Publish Date
2013
Start Page
1199
End Page
1209

How much is another randomized trial of lymph node dissection in endometrial cancer worth? A value of information analysis.

OBJECTIVE: This study aimed to assess the value of a randomized controlled trial (RCT) of lymph node dissection (LND) at the time of hysterectomy for high-risk subsets of women with endometrial cancer. METHODS: A modified Markov decision model compared routine LND to no LND for women with grade 3 or grades 2-3 endometrial cancer. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity and value of information (VOI) analyses. Survival without LND was modeled from Surveillance, Epidemiology and End Results program data. A hazard ratio (HR) describing survival in the high-risk group undergoing LND (estimate 0.9, 95% CI 0.6-1.1), adverse event rates, probability and type of adjuvant therapy were modeled from published RCTs. Costs were obtained from national reimbursement data. VOI estimated the value of reducing uncertainty regarding the survival benefit of LND. RESULTS: For grade 3, LND had an incremental cost-effectiveness ratio of $40,183/quality-adjusted life year (QALY) compared to no LND. Acceptability curves revealed considerable uncertainty, with an expected value of perfect information of $4,195 per patient at societal willingness to pay of $50,000/QALY. The estimated value of partial perfect information regarding the HR was $3,702 per patient. Assuming 8,000 individuals annually with grade 3 endometrial cancer in the US, the upper limit of VOI for the HR was $29.6 million annually. For grades 2 and 3 combined, analysis revealed a much lower likelihood of finding LND cost-effective. CONCLUSION: A clinical trial defining the survival effect of LND in women with grade 3 endometrial cancer is a worthwhile use of resources.

Authors
Havrilesky, LJ; Chino, JP; Myers, ER
MLA Citation
Havrilesky, LJ, Chino, JP, and Myers, ER. "How much is another randomized trial of lymph node dissection in endometrial cancer worth? A value of information analysis." Gynecol Oncol 131.1 (October 2013): 140-146.
PMID
23800699
Source
pubmed
Published In
Gynecologic Oncology
Volume
131
Issue
1
Publish Date
2013
Start Page
140
End Page
146
DOI
10.1016/j.ygyno.2013.06.025

Palliative and hospice care in gynecologic cancer: a review.

Despite the increasing availability of palliative care, oncology providers often misunderstand and underutilize these resources. The goals of palliative care are relief of suffering and provision of the best possible quality of life for both the patient and her family, regardless of where she is in the natural history of her disease. Lack of understanding and awareness of the services provided by palliative care physicians underlie barriers to referral. Oncologic providers spend a significant amount of time palliating the symptoms of cancer and its treatment; involvement of specialty palliative care providers can assist in managing the complex patient. Patients with gynecologic malignancies remain an ideal population for palliative care intervention. This review of the literature explores the current state of palliative care in the treatment of gynecologic cancers and its implications for the quality and cost of this treatment.

Authors
Lopez-Acevedo, M; Lowery, WJ; Lowery, AW; Lee, PS; Havrilesky, LJ
MLA Citation
Lopez-Acevedo, M, Lowery, WJ, Lowery, AW, Lee, PS, and Havrilesky, LJ. "Palliative and hospice care in gynecologic cancer: a review." Gynecol Oncol 131.1 (October 2013): 215-221. (Review)
PMID
23774302
Source
pubmed
Published In
Gynecologic Oncology
Volume
131
Issue
1
Publish Date
2013
Start Page
215
End Page
221
DOI
10.1016/j.ygyno.2013.06.012

Cost analysis of colposcopy for abnormal cytology in post-treatment surveillance for cervical cancer.

OBJECTIVE: The aim of this study was to estimate cost and outcomes associated with colposcopy following abnormal Pap for women with a history of cervical cancer. METHODS: Decision models compared the costs and number of isolated local recurrences (ILR) detected using two strategies, colposcopy and no colposcopy, for women with a history of cervical cancer and low grade or high grade Pap. Clinical data for input were derived from a cohort of women with a history of cervical cancer undergoing surveillance Paps at 2 institutions. Costs were obtained using national reimbursement data. RESULTS: Five hundred fifty-six patients underwent 2900 surveillance Paps. Twenty-seven of 50 women with a low grade Pap underwent colposcopy. One of 3 recurrences in the colposcopy group was an ILR diagnosed colposcopically. Colposcopy following low grade Pap costs $354 more and resulted in a lower rate of diagnosis of ILR compared to no colposcopy (3.7% vs 8.6%). Sixty of 78 women with a high grade Pap underwent colposcopy. Three of 15 recurrences in the colposcopy group were ILR diagnosed colposcopically. Colposcopy following high grade Pap costs $623 more than no colposcopy but resulted in a higher rate of diagnosis of ILR (5% vs 0%; $7481 per additional ILR). CONCLUSIONS: Colposcopy following low or high grade surveillance Pap smear adds substantial cost to the management of women with cervical cancer. Only colposcopy following a high grade Pap is associated with a higher probability that cervical cancer recurrence will be detected when salvageable. These findings support withholding colposcopy for abnormal surveillance Pap tests less than high grade.

Authors
Tergas, AI; Havrilesky, LJ; Fader, AN; Guntupalli, SR; Huh, WK; Massad, LS; Rimel, BJ
MLA Citation
Tergas, AI, Havrilesky, LJ, Fader, AN, Guntupalli, SR, Huh, WK, Massad, LS, and Rimel, BJ. "Cost analysis of colposcopy for abnormal cytology in post-treatment surveillance for cervical cancer." Gynecol Oncol 130.3 (September 2013): 421-425.
PMID
23747836
Source
pubmed
Published In
Gynecologic Oncology
Volume
130
Issue
3
Publish Date
2013
Start Page
421
End Page
425
DOI
10.1016/j.ygyno.2013.05.037

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." Gynecologic oncology 130.3 (September 2013): 426-430.
PMID
23769759
Source
epmc
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

Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis.

To estimate the risk of venous thromboembolism, stroke, or myocardial infarction (MI) associated with the use of oral contraceptive pills (OCPs) and to describe how these risks vary by dose or formulation. We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published from January 1995 through June 2012 that evaluated the association between OCP use and risk of venous thromboembolism, stroke, or MI. We reviewed 6,476 citations. We included English-language, controlled studies with human participants reporting a quantitative association between exposure to OCPs and outcomes of venous thromboembolism, stroke, or MI. Two investigators independently reviewed articles for inclusion or exclusion; discordant decisions were resolved by team review and consensus. Random-effects meta-analysis was used to generate summary odds ratios (ORs). Fifty studies met inclusion criteria. There were no randomized clinical trials. We found threefold increased odds of venous thromboembolism among current compared with noncurrent OCP users (14 studies; OR 2.97, 95% confidence interval [CI] 2.46-3.59). We found twofold increased odds of ischemic stroke (seven studies; OR 1.90, 95% CI 1.24-2.91). There was no evidence of increased risk of hemorrhagic stroke (four studies; OR 1.03, 95% CI 0.71-1.49) or MI (eight studies; OR 1.34, 95% CI 0.87-2.08). Current use of combined OCPs is associated with increased odds of venous thromboembolism and ischemic stroke but not hemorrhagic stroke or MI.

Authors
Peragallo Urrutia, R; Coeytaux, RR; McBroom, AJ; Gierisch, JM; Havrilesky, LJ; Moorman, PG; Lowery, WJ; Dinan, M; Hasselblad, V; Sanders, GD; Myers, ER
MLA Citation
Peragallo Urrutia, R, Coeytaux, RR, McBroom, AJ, Gierisch, JM, Havrilesky, LJ, Moorman, PG, Lowery, WJ, Dinan, M, Hasselblad, V, Sanders, GD, and Myers, ER. "Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis." Obstetrics and gynecology 122.2 Pt 1 (August 1, 2013): 380-389. (Review)
Source
scopus
Published In
Obstetrics and Gynecology
Volume
122
Issue
2 Pt 1
Publish Date
2013
Start Page
380
End Page
389

Are supportive care-based treatment strategies preferable to standard chemotherapy in recurrent cervical cancer?

OBJECTIVE: Recurrent cervical cancer has a poor prognosis despite aggressive treatment. We evaluate the comparative-effectiveness of four management strategies in recurrent cervix cancer incorporating risk prognostication categories derived from pooled collaborative group trials: 1) standard doublet chemotherapy; 2) selective chemotherapy (home hospice with no chemotherapy for poorest prognosis patients with remainder receiving standard doublet chemotherapy); 3) single-agent chemotherapy with home hospice; and 4) home hospice. METHODS: A cost-effectiveness decision model was constructed. Survival reduction of 24% was assumed for single-agent chemotherapy and 40% for hospice only compared to standard doublet chemotherapy. Overall survival and strategy cost for each arm were modeled as follows: standard doublet chemotherapy 8.9 months ($33K); selective chemotherapy 8.7 months ($29K); single-agent chemotherapy with home hospice 6.7 months ($16K); and home hospice alone 5.3 months ($11K). Base case analysis assumed equal quality of life (QOL). Sensitivity analyses assessed model uncertainties. RESULTS: Standard doublet chemotherapy for all is not cost-effective compared to selective chemotherapy with an incremental cost-effectiveness ratio (ICER) of $276K per quality-adjusted life-year (QALY). Sensitivity analysis predicted that a 90% improvement in survival is required before standard doublet chemotherapy is cost-effective in the poorest prognosis patients. Selective chemotherapy is the most cost-effective strategy compared to single-agent chemotherapy with home hospice with an ICER of $78K/QALY. Chemotherapy containing regimens become cost-prohibitive with small decreases in QOL. CONCLUSIONS: Supportive care based treatment strategies are potentially more cost-effective than the current standard of doublet chemotherapy for all patients with recurrent cervical cancer and warrant prospective evaluation.

Authors
Phippen, NT; Leath, CA; Miller, CR; Lowery, WJ; Havrilesky, LJ; Barnett, JC
MLA Citation
Phippen, NT, Leath, CA, Miller, CR, Lowery, WJ, Havrilesky, LJ, and Barnett, JC. "Are supportive care-based treatment strategies preferable to standard chemotherapy in recurrent cervical cancer?." Gynecol Oncol 130.2 (August 2013): 317-322.
PMID
23707667
Source
pubmed
Published In
Gynecologic Oncology
Volume
130
Issue
2
Publish Date
2013
Start Page
317
End Page
322
DOI
10.1016/j.ygyno.2013.05.019

Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis.

OBJECTIVE: To estimate the risk of venous thromboembolism, stroke, or myocardial infarction (MI) associated with the use of oral contraceptive pills (OCPs) and to describe how these risks vary by dose or formulation. DATA SOURCES: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published from January 1995 through June 2012 that evaluated the association between OCP use and risk of venous thromboembolism, stroke, or MI. METHODS OF STUDY SELECTION: We reviewed 6,476 citations. We included English-language, controlled studies with human participants reporting a quantitative association between exposure to OCPs and outcomes of venous thromboembolism, stroke, or MI. Two investigators independently reviewed articles for inclusion or exclusion; discordant decisions were resolved by team review and consensus. Random-effects meta-analysis was used to generate summary odds ratios (ORs). TABULATION, INTEGRATION, AND RESULTS: Fifty studies met inclusion criteria. There were no randomized clinical trials. We found threefold increased odds of venous thromboembolism among current compared with noncurrent OCP users (14 studies; OR 2.97, 95% confidence interval [CI] 2.46-3.59). We found twofold increased odds of ischemic stroke (seven studies; OR 1.90, 95% CI 1.24-2.91). There was no evidence of increased risk of hemorrhagic stroke (four studies; OR 1.03, 95% CI 0.71-1.49) or MI (eight studies; OR 1.34, 95% CI 0.87-2.08). CONCLUSION: Current use of combined OCPs is associated with increased odds of venous thromboembolism and ischemic stroke but not hemorrhagic stroke or MI.

Authors
Peragallo Urrutia, R; Coeytaux, RR; McBroom, AJ; Gierisch, JM; Havrilesky, LJ; Moorman, PG; Lowery, WJ; Dinan, M; Hasselblad, V; Sanders, GD; Myers, ER
MLA Citation
Peragallo Urrutia, R, Coeytaux, RR, McBroom, AJ, Gierisch, JM, Havrilesky, LJ, Moorman, PG, Lowery, WJ, Dinan, M, Hasselblad, V, Sanders, GD, and Myers, ER. "Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis." Obstet Gynecol 122.2 Pt 1 (August 2013): 380-389. (Review)
PMID
23969809
Source
pubmed
Published In
Obstetrics and Gynecology
Volume
122
Issue
2 Pt 1
Publish Date
2013
Start Page
380
End Page
389
DOI
10.1097/AOG.0b013e3182994c43

Preference-based utility scores for adverse events associated with the treatment of gynecologic cancers.

Our goals were to (1) define a set of descriptive health states related to adverse events (AEs) associated with gynecologic cancer treatment with radical surgery and chemoradiation and (2) derive a set of quality of life-related utility scores corresponding to these health states. We developed a list of health states for grade 3/4 AEs related to gynecologic cancer treatment. Using the visual analog scale score and time trade-off (TTO) methods, valuation of each health state was obtained through interviews of 60 volunteers (15 cervical cancer survivors treated with surgery and/or chemoradiation and 45 women without a cancer diagnosis). Health states were ranked by mean/median TTO scores. Wilcoxon rank sum test was used to compare central tendencies related to patient and volunteer characteristics. Patients and volunteers agreed on their preference rankings, with highest preference given to infection (median TTO = 1.0) and thrombosis (median TTO = 0.97). Lowest preference was assigned to radiation proctitis (median TTO = 0.87) and gastrointestinal fistula formation (median TTO = 0.83). Utility scores for the majority of health states were not significantly associated with age, race, parity, patient or volunteer status, history of abnormal Pap smear, stage of cervical cancer diagnosis, or personal experience of a serious treatment-related AE. This study helps establish preferences and quality-of-life utility scores for health states related to toxicities from surgery, radiation, and chemotherapy for gynecologic cancer treatment. Such information can be used to inform medical decision making/counseling and may be applied to future comparative effectiveness models in which radical surgery and/or chemoradiation are considered.

Authors
Jewell, EL; Smrtka, M; Broadwater, G; Valea, F; Davis, DM; Nolte, KC; Valea, R; Myers, ER; Havrilesky, LJ
MLA Citation
Jewell, EL, Smrtka, M, Broadwater, G, Valea, F, Davis, DM, Nolte, KC, Valea, R, Myers, ER, and Havrilesky, LJ. "Preference-based utility scores for adverse events associated with the treatment of gynecologic cancers." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 23.6 (July 1, 2013): 1158-1166.
Source
scopus
Published In
International Journal of Gynecological Cancer
Volume
23
Issue
6
Publish Date
2013
Start Page
1158
End Page
1166

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

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

Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To estimate the overall reduction in ovarian cancer risk associated with the use of oral contraceptive pills (OCPs) and whether reduction in risk is affected by specifics of OCP use, such as formulation or duration of use. DATA SOURCES: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published from January 1990 to June 2012, with primary analysis of studies published since January 2000. METHODS OF STUDY SELECTION: We reviewed 6,476 citations. We included English-language controlled studies with human participants reporting a quantitative association between exposure to OCPs (in which the explicit or implicit indication for OCP use was prevention of pregnancy or ovarian cancer) compared with no use of OCPs. Two investigators independently reviewed the title and abstract and full-text of articles for inclusion or exclusion decision; discordant decisions were resolved by team review and consensus. TABULATION, INTEGRATION, AND RESULTS: Fifty-five studies met inclusion criteria. A random-effects meta-analysis of 24 case-control and cohort studies showed significant reduction in ovarian cancer incidence in ever-users compared with never-users (odds ratio 0.73, 95% confidence interval 0.66-0.81). There was a significant duration-response relationship, with reduction in incidence of more than 50% among women using OCPs for 10 or more years. The lifetime reduction in ovarian cancer attributable to the use of OCPs is approximately 0.54% for a number-needed-to-treat of approximately 185 for a use period of 5 years. CONCLUSION: Significant duration-dependent reductions in ovarian cancer incidence in the general population are associated with OCP use.

Authors
Havrilesky, LJ; Moorman, PG; Lowery, WJ; Gierisch, JM; Coeytaux, RR; Urrutia, RP; Dinan, M; McBroom, AJ; Hasselblad, V; Sanders, GD; Myers, ER
MLA Citation
Havrilesky, LJ, Moorman, PG, Lowery, WJ, Gierisch, JM, Coeytaux, RR, Urrutia, RP, Dinan, M, McBroom, AJ, Hasselblad, V, Sanders, GD, and Myers, ER. "Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis." Obstet Gynecol 122.1 (July 2013): 139-147. (Review)
PMID
23743450
Source
pubmed
Published In
Obstetrics and Gynecology
Volume
122
Issue
1
Publish Date
2013
Start Page
139
End Page
147
DOI
10.1097/AOG.0b013e318291c235

Preference-based utility scores for adverse events associated with the treatment of gynecologic cancers.

OBJECTIVE: Our goals were to (1) define a set of descriptive health states related to adverse events (AEs) associated with gynecologic cancer treatment with radical surgery and chemoradiation and (2) derive a set of quality of life-related utility scores corresponding to these health states. METHODS: We developed a list of health states for grade 3/4 AEs related to gynecologic cancer treatment. Using the visual analog scale score and time trade-off (TTO) methods, valuation of each health state was obtained through interviews of 60 volunteers (15 cervical cancer survivors treated with surgery and/or chemoradiation and 45 women without a cancer diagnosis). Health states were ranked by mean/median TTO scores. Wilcoxon rank sum test was used to compare central tendencies related to patient and volunteer characteristics. RESULTS: Patients and volunteers agreed on their preference rankings, with highest preference given to infection (median TTO = 1.0) and thrombosis (median TTO = 0.97). Lowest preference was assigned to radiation proctitis (median TTO = 0.87) and gastrointestinal fistula formation (median TTO = 0.83). Utility scores for the majority of health states were not significantly associated with age, race, parity, patient or volunteer status, history of abnormal Pap smear, stage of cervical cancer diagnosis, or personal experience of a serious treatment-related AE. CONCLUSIONS: This study helps establish preferences and quality-of-life utility scores for health states related to toxicities from surgery, radiation, and chemotherapy for gynecologic cancer treatment. Such information can be used to inform medical decision making/counseling and may be applied to future comparative effectiveness models in which radical surgery and/or chemoradiation are considered.

Authors
Jewell, EL; Smrtka, M; Broadwater, G; Valea, F; Davis, DM; Nolte, KC; Valea, R; Myers, ER; Havrilesky, LJ
MLA Citation
Jewell, EL, Smrtka, M, Broadwater, G, Valea, F, Davis, DM, Nolte, KC, Valea, R, Myers, ER, and Havrilesky, LJ. "Preference-based utility scores for adverse events associated with the treatment of gynecologic cancers." Int J Gynecol Cancer 23.6 (July 2013): 1158-1166.
PMID
23792609
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
23
Issue
6
Publish Date
2013
Start Page
1158
End Page
1166
DOI
10.1097/IGC.0b013e318299e2a6

Oral contraceptive use for the primary prevention of ovarian cancer.

To estimate the overall balance of harms and benefits from the potential use of oral contraceptives (OCs) for the primary prevention of ovarian cancerWe searched PubMed®, Embase®, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for English-language studies published from January 1990 to June 2012 that evaluated the potential benefits (reduction in ovarian, colorectal, and endometrial cancers) and harms (increase in breast and cervical cancer, and vascular complications) of OC use.Two investigators screened each abstract and full-text article for inclusion; the investigators abstracted data, and they performed quality ratings, applicability ratings, and evidence grading. Random-effects models were used to compute summary estimates of effects. A simulation model was used to estimate the effects of OC use on the overall balance of benefits and harms.We reviewed 55 studies relevant to ovarian cancer outcomes, 66 relevant to other cancers, and 50 relevant to vascular events. Ovarian cancer incidence was significantly reduced in OC users (OR [odds ratio], 0.73; 95% CI [confidence interval], 0.66 to 0.81), with greater reductions seen with longer duration of use. Breast cancer incidence was slightly but significantly increased in OC users (OR, 1.08; 95% CI, 1.00 to 1.17), with a significant reduction in risk as time since last use increased. The risk of cervical cancer was significantly increased in women with persistent human papillomavirus infection who used OCs, but heterogeneity prevented a formal meta-analysis. Incidences of both colorectal cancer (OR, 0.86; 95% CI, 0.79 to 0.95) and endometrial cancer (OR, 0.57; 95% CI, 0.43 to 0.76) were significantly reduced by OC use. The risk of vascular events was increased in current OC users compared with nonusers, although the increase in myocardial infarction was not statistically significant. The overall strength of evidence for ovarian cancer prevention was moderate to low, primarily because of the lack of randomized trials and inconsistent reporting of important characteristics of use, such as duration. The simulation model predicted that the combined increase in risk of breast and cervical cancers and vascular events was likely to be equivalent to or greater than the decreased risk in ovarian cancer, although the harm/benefit ratio was much more favorable when protection against endometrial and colorectal cancers was added, resulting in net gains in life expectancy of approximately 1 month.There is insufficient evidence to recommend for or against the use of OCs solely for the primary prevention of ovarian cancer. Although the net effects of the current patterns of OC use likely result in increased life expectancy when other noncontraceptive benefits are included, the harm/benefit ratio for ovarian cancer prevention alone is uncertain, particularly when the potential quality-of-life impact of breast cancer and vascular events are considered.

Authors
Havrilesky, LJ; Gierisch, JM; Moorman, PG; Coeytaux, RR; Urrutia, RP; Lowery, WJ; Dinan, M; McBroom, AJ; Wing, L; Musty, MD; Lallinger, KR; Hasselblad, V; Sanders, GD; Myers, ER
MLA Citation
Havrilesky, LJ, Gierisch, JM, Moorman, PG, Coeytaux, RR, Urrutia, RP, Lowery, WJ, Dinan, M, McBroom, AJ, Wing, L, Musty, MD, Lallinger, KR, Hasselblad, V, Sanders, GD, and Myers, ER. "Oral contraceptive use for the primary prevention of ovarian cancer." Evidence report/technology assessment 212 (June 2013): 1-514.
PMID
24423062
Source
epmc
Published In
Evidence report/technology assessment
Issue
212
Publish Date
2013
Start Page
1
End Page
514

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

Comparative effectiveness research in gynecologic oncology

Authors
Havrilesky, LJ; Kulasingam, SL; Jewell, EL; Cohn, DE
MLA Citation
Havrilesky, LJ, Kulasingam, SL, Jewell, EL, and Cohn, DE. "Comparative effectiveness research in gynecologic oncology." Principles and Practice of Gynecologic Oncology: Sixth Edition. May 8, 2013. 503-517.
Source
scopus
Publish Date
2013
Start Page
503
End Page
517

The impact of postoperative nausea and vomiting prophylaxis with dexamethasone on postoperative wound complications in patients undergoing laparotomy for endometrial cancer.

BACKGROUND: Dexamethasone is widely used for postoperative nausea and vomiting (PONV) prophylaxis. However, there are limited data on the risk of wound complications associated with single-dose dexamethasone use for this purpose. We performed this retrospective study to determine whether intraoperative dexamethasone for PONV prevention increases the risk or severity of postoperative wound complications. METHODS: Women who underwent laparotomy for endometrial cancer between 2002 and 2007 were identified from a tumor registry. Perioperative records were reviewed to determine dexamethasone administration. Medical records were reviewed to identify wound complications including cellulitis, superficial surgical site infection, wound separation, and fascial dehiscence. Wound care needs and time to complete wound healing were compared based on dexamethasone exposure. The rate of wound complications was also compared based on dexamethasone dose. Baseline characteristics and perioperative details were evaluated for independent associations with wound complications. Logistic regression analyses were performed to predict the occurrence of wound complications. RESULTS: Four hundred thirty-one patients met inclusion criteria; 192 (44.6%) received dexamethasone (4-12 mg) and 31.1% developed a wound complication. In unadjusted analysis, there was no difference in the risk of developing a wound complication based on dexamethasone exposure; 53 of 192 patients (27.6%) who received dexamethasone developed a wound complication, compared with 81 of 239 (33.9%) who did not receive dexamethasone: odds ratio (OR) (95% confidence interval [CI]) = 0.74 (0.49, 1.13), P = 0.16. There was no difference in the distribution of wound complication types based on receipt of dexamethasone (P = 0.71), or in the incidence of wound complications based on the dose of dexamethasone (P = 0.48). Of patients who developed a wound complication, there was no difference in the need for IV antibiotics, vacuum-assisted wound closure, or in the rate of fascial dehiscence based on dexamethasone exposure. The time to complete wound healing was not different between the 2 cohorts (P = 0.48). In univariate analysis, higher body mass index (BMI), higher estimated blood loss, smoking, and longer duration of surgery were predictors of wound complications. Smoking (OR [95% CI]: 2.0 [1.3, 3.2], P = 0.003) and BMI (OR [95% CI]: 1.2 [1.1, 1.3], P = 0.0003) were the only significant predictors of wound complications in the multivariate model, whereas dexamethasone remained a nonsignificant predictor (OR [95% CI]: 0.7 [0.5, 1.1], P = 0.12). CONCLUSION: Intraoperative dexamethasone for PONV prophylaxis does not seem to increase the rate or severity of postoperative wound complications in women undergoing laparotomy for endometrial cancer. BMI and smoking were significant predictors of wound complications in this patient population.

Authors
Bolac, CS; Wallace, AH; Broadwater, G; Havrilesky, LJ; Habib, AS
MLA Citation
Bolac, CS, Wallace, AH, Broadwater, G, Havrilesky, LJ, and Habib, AS. "The impact of postoperative nausea and vomiting prophylaxis with dexamethasone on postoperative wound complications in patients undergoing laparotomy for endometrial cancer." Anesth Analg 116.5 (May 2013): 1041-1047.
PMID
23337415
Source
pubmed
Published In
Anesthesia and Analgesia
Volume
116
Issue
5
Publish Date
2013
Start Page
1041
End Page
1047
DOI
10.1213/ANE.0b013e318276cf58

Screening for cervical cancer: a modeling study for the US Preventive Services Task Force.

OBJECTIVE: This study addresses the following 3 questions posed by the US Preventive Services Task Force: (1) at what age should screening for cervical cancer begin; (2) at what age should screening for cervical cancer end; and (3) how do the benefits and potential harms of screening strategies that use human papillomavirus DNA testing in conjunction with cytology (cotesting) compare with those strategies that use cytology only? MATERIALS AND METHODS: A Markov model was updated and used to quantify clinical outcomes (i.e., colposcopies, cancers, and life expectancy) associated with different screening strategies. RESULTS: Screening in the teenaged years is associated with a high number of colposcopies (harms), small differences in cancers detected and, as a result, small gains in life expectancy (benefits). Screening women beginning in the early 20s provides a reasonable balance of the harms and benefits of screening. Among women who have been screened according to the current recommendations for cervical cancer (beginning at age 21 years and conducted every 3 years with cytology), screening beyond 65 years is associated with small additional gains in life expectancy but large increases in colposcopies. For cotesting, a strategy of cytology only conducted every 3 years, followed by cotesting conducted every 5 years (for women ≥30 years), is associated with fewer colposcopies and greater gains in life expectancy compared with screening with cytology only conducted every 3 years. CONCLUSIONS: The results of this modeling study support current US Preventive Services Task Force recommendations for cervical cancer screening.

Authors
Kulasingam, SL; Havrilesky, LJ; Ghebre, R; Myers, ER
MLA Citation
Kulasingam, SL, Havrilesky, LJ, Ghebre, R, and Myers, ER. "Screening for cervical cancer: a modeling study for the US Preventive Services Task Force." J Low Genit Tract Dis 17.2 (April 2013): 193-202.
PMID
23519288
Source
pubmed
Published In
Journal of Lower Genital Tract Disease
Volume
17
Issue
2
Publish Date
2013
Start Page
193
End Page
202
DOI
10.1097/LGT.0b013e3182616241

We need a new paradigm in gynecologic cancer care: SGO proposes solutions for delivery, quality and reimbursement policies.

Authors
Alvarez, RD; Gray, HJ; Timmins, PF; Gibb, RK; Edelson, M; Fowler, JM; Havrilesky, LJ; McCauley, DL; Nash, JD; Rahaman, J; Rash, JK; Rodabaugh, KJ; Powell, MA; Bristow, RE; Brown, JV; Tewari, D; Cliby, WA; Anastasia, P; Robinson, WR; Shahin, MS; Cantrell, LA; Cloven, NG; Gold, MA; Hope, JM; Muntz, HG; Sorosky, JI; Elkas, JC; Frumovitz, MM; Jewell, E; Spillman, MA; Naumann, RW
MLA Citation
Alvarez, RD, Gray, HJ, Timmins, PF, Gibb, RK, Edelson, M, Fowler, JM, Havrilesky, LJ, McCauley, DL, Nash, JD, Rahaman, J, Rash, JK, Rodabaugh, KJ, Powell, MA, Bristow, RE, Brown, JV, Tewari, D, Cliby, WA, Anastasia, P, Robinson, WR, Shahin, MS, Cantrell, LA, Cloven, NG, Gold, MA, Hope, JM, Muntz, HG, Sorosky, JI, Elkas, JC, Frumovitz, MM, Jewell, E, Spillman, MA, and Naumann, RW. "We need a new paradigm in gynecologic cancer care: SGO proposes solutions for delivery, quality and reimbursement policies." Gynecol Oncol 129.1 (April 2013): 3-4.
PMID
23638463
Source
pubmed
Published In
Gynecologic Oncology
Volume
129
Issue
1
Publish Date
2013
Start Page
3
End Page
4

Quality of life in ICON7: need for patients' perspectives.

Authors
Havrilesky, LJ; Abernethy, AP
MLA Citation
Havrilesky, LJ, and Abernethy, AP. "Quality of life in ICON7: need for patients' perspectives." Lancet Oncol 14.3 (March 2013): 183-185.
PMID
23333118
Source
pubmed
Published In
The Lancet Oncology
Volume
14
Issue
3
Publish Date
2013
Start Page
183
End Page
185
DOI
10.1016/S1470-2045(12)70590-9

Comparison of methods to estimate health state utilities for ovarian cancer using quality of life data: a Gynecologic Oncology Group study.

BACKGROUND: Cost-effectiveness/cost-utility analyses are increasingly needed to inform decisions about care. Algorithms have been developed using the Functional Assessment of Cancer Therapy (FACT) quality of life instrument to estimate utility weights for cost analyses. This study was designed to compare these algorithms in the setting of ovarian cancer. METHODS: GOG-0152 was a 550-patient randomized phase III trial of interval cytoreduction, and GOG-0172 was a 415-patient randomized phase III trial comparing intravenous versus intraperitoneal therapy among women with advanced ovarian cancer. QOL data were collected via the FACT at four time points in each study. Two published mapping algorithms (Cheung and Dobrez) and a linear transformation method were applied to these data. The agreement between measures was assessed by the concordance correlation coefficient (r(CCC)), and paired t-tests were used to compare means. RESULTS: While agreement between the estimation algorithms was good (ranged from 0.72 to 0.81), there were statistically significant (p<0.001) and clinically meaningful differences between the scores: mean scores were higher with Dobrez than with Cheung or the linear transformation method. Scores were also statistically significantly different (p<0.001) between studies. CONCLUSIONS: In the absence of prospectively collected utility data, the use of mapping algorithms is feasible, however, the optimal algorithm is not clear. There were significant differences between studies, which highlight the need for validation of these algorithms in specific settings. If cost analyses incorporate mapping algorithms to obtain utility estimates, investigators should take the variability into account.

Authors
Hess, LM; Brady, WE; Havrilesky, LJ; Cohn, DE; Monk, BJ; Wenzel, L; Cella, D
MLA Citation
Hess, LM, Brady, WE, Havrilesky, LJ, Cohn, DE, Monk, BJ, Wenzel, L, and Cella, D. "Comparison of methods to estimate health state utilities for ovarian cancer using quality of life data: a Gynecologic Oncology Group study." Gynecol Oncol 128.2 (February 2013): 175-180.
PMID
23123576
Source
pubmed
Published In
Gynecologic Oncology
Volume
128
Issue
2
Publish Date
2013
Start Page
175
End Page
180
DOI
10.1016/j.ygyno.2012.10.024

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

How much is another randomized trial of lymph node dissection in endometrial cancer worth? A value of information analysis

Objective. This study aimed to assess the value of a randomized controlled trial (RCT) of lymph node dissection (LND) at the time of hysterectomy for high-risk subsets of women with endometrial cancer. Methods. A modified Markov decision model compared routine LND to no LND for women with grade 3 or grades 2-3 endometrial cancer. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity and value of information (VOI) analyses. Survival without LND was modeled from Surveillance, Epidemiology and End Results program data. A hazard ratio (HR) describing survival in the high-risk group undergoing LND (estimate 0.9, 95% CI 0.6-1.1), adverse event rates, probability and type of adjuvant therapy were modeled from published RCTs. Costs were obtained from national reimbursement data. VOI estimated the value of reducing uncertainty regarding the survival benefit of LND. Results. For grade 3, LND had an incremental cost-effectiveness ratio of $40,183/quality-adjusted life year (QALY) compared to no LND. Acceptability curves revealed considerable uncertainty, with an expected value of perfect information of $4,195 per patient at societal willingness to pay of $50,000/QALY. The estimated value of partial perfect information regarding the HR was $3,702 per patient. Assuming 8,000 individuals annually with grade 3 endometrial cancer in the US, the upper limit of VOI for the HR was $29.6 million annually. For grades 2 and 3 combined, analysis revealed a much lower likelihood of finding LND cost-effective. Conclusion. A clinical trial defining the survival effect of LND in women with grade 3 endometrial cancer is a worthwhile use of resources. © 2013 Elsevier Inc. All rights reserved.

Authors
Havrilesky, LJ; Chino, JP; Myers, ER
MLA Citation
Havrilesky, LJ, Chino, JP, and Myers, ER. "How much is another randomized trial of lymph node dissection in endometrial cancer worth? A value of information analysis." Gynecologic Oncology 131.1 (2013): 140-146.
Source
scival
Published In
Gynecologic Oncology
Volume
131
Issue
1
Publish Date
2013
Start Page
140
End Page
146
DOI
10.1016/j.ygyno.2013.06.025

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

Palliative and hospice care in gynecologic cancer: A review

Despite the increasing availability of palliative care, oncology providers often misunderstand and underutilize these resources. The goals of palliative care are relief of suffering and provision of the best possible quality of life for both the patient and her family, regardless of where she is in the natural history of her disease. Lack of understanding and awareness of the services provided by palliative care physicians underlie barriers to referral. Oncologic providers spend a significant amount of time palliating the symptoms of cancer and its treatment; involvement of specialty palliative care providers can assist in managing the complex patient. Patients with gynecologic malignancies remain an ideal population for palliative care intervention. This review of the literature explores the current state of palliative care in the treatment of gynecologic cancers and its implications for the quality and cost of this treatment. © 2013 Elsevier Inc. All rights reserved.

Authors
Lopez-Acevedo, M; Lowery, WJ; Lowery, AW; Lee, PS; Havrilesky, LJ
MLA Citation
Lopez-Acevedo, M, Lowery, WJ, Lowery, AW, Lee, PS, and Havrilesky, LJ. "Palliative and hospice care in gynecologic cancer: A review." Gynecologic Oncology 131.1 (2013): 215-221.
Source
scival
Published In
Gynecologic Oncology
Volume
131
Issue
1
Publish Date
2013
Start Page
215
End Page
221
DOI
10.1016/j.ygyno.2013.06.012

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, NY; Gehrig, PA; O'Malley, DM; Finkler, N; Havrilesky, LJ
MLA Citation
Secord, AA, Geller, MA, Broadwater, G, Holloway, R, Shuler, K, Dao, NY, 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

Comparison of methods to estimate health state utilities for ovarian cancer using quality of life data: A Gynecologic Oncology Group study

Background: Cost-effectiveness/cost-utility analyses are increasingly needed to inform decisions about care. Algorithms have been developed using the Functional Assessment of Cancer Therapy (FACT) quality of life instrument to estimate utility weights for cost analyses. This study was designed to compare these algorithms in the setting of ovarian cancer. Methods: GOG-0152 was a 550-patient randomized phase III trial of interval cytoreduction, and GOG-0172 was a 415-patient randomized phase III trial comparing intravenous versus intraperitoneal therapy among women with advanced ovarian cancer. QOL data were collected via the FACT at four time points in each study. Two published mapping algorithms (Cheung and Dobrez) and a linear transformation method were applied to these data. The agreement between measures was assessed by the concordance correlation coefficient (rCCC), and paired t-tests were used to compare means. Results: While agreement between the estimation algorithms was good (ranged from 0.72 to 0.81), there were statistically significant (p < 0.001) and clinically meaningful differences between the scores: mean scores were higher with Dobrez than with Cheung or the linear transformation method. Scores were also statistically significantly different (p < 0.001) between studies. Conclusions: In the absence of prospectively collected utility data, the use of mapping algorithms is feasible, however, the optimal algorithm is not clear. There were significant differences between studies, which highlight the need for validation of these algorithms in specific settings. If cost analyses incorporate mapping algorithms to obtain utility estimates, investigators should take the variability into account. © 2012 Elsevier Inc. All rights reserved.

Authors
Hess, LM; Brady, WE; Havrilesky, LJ; Cohn, DE; Monk, BJ; Wenzel, L; Cella, D
MLA Citation
Hess, LM, Brady, WE, Havrilesky, LJ, Cohn, DE, Monk, BJ, Wenzel, L, and Cella, D. "Comparison of methods to estimate health state utilities for ovarian cancer using quality of life data: A Gynecologic Oncology Group study." Gynecologic Oncology 128.2 (2013): 175-180.
Source
scival
Published In
Gynecologic Oncology
Volume
128
Issue
2
Publish Date
2013
Start Page
175
End Page
180
DOI
10.1016/j.ygyno.2012.10.024

The impact of postoperative nausea and vomiting prophylaxis with dexamethasone on postoperative wound complications in patients undergoing laparotomy for endometrial cancer

BACKGROUND:: Dexamethasone is widely used for postoperative nausea and vomiting (PONV) prophylaxis. However, there are limited data on the risk of wound complications associated with single-dose dexamethasone use for this purpose. We performed this retrospective study to determine whether intraoperative dexamethasone for PONV prevention increases the risk or severity of postoperative wound complications. METHODS:: Women who underwent laparotomy for endometrial cancer between 2002 and 2007 were identified from a tumor registry. Perioperative records were reviewed to determine dexamethasone administration. Medical records were reviewed to identify wound complications including cellulitis, superficial surgical site infection, wound separation, and fascial dehiscence. Wound care needs and time to complete wound healing were compared based on dexamethasone exposure. The rate of wound complications was also compared based on dexamethasone dose. Baseline characteristics and perioperative details were evaluated for independent associations with wound complications. Logistic regression analyses were performed to predict the occurrence of wound complications. RESULTS:: Four hundred thirty-one patients met inclusion criteria; 192 (44.6%) received dexamethasone (4-12 mg) and 31.1% developed a wound complication. In unadjusted analysis, there was no difference in the risk of developing a wound complication based on dexamethasone exposure; 53 of 192 patients (27.6%) who received dexamethasone developed a wound complication, compared with 81 of 239 (33.9%) who did not receive dexamethasone: odds ratio (OR) (95% confidence interval [CI]) = 0.74 (0.49, 1.13), P = 0.16. There was no difference in the distribution of wound complication types based on receipt of dexamethasone (P = 0.71), or in the incidence of wound complications based on the dose of dexamethasone (P = 0.48). Of patients who developed a wound complication, there was no difference in the need for IV antibiotics, vacuum-assisted wound closure, or in the rate of fascial dehiscence based on dexamethasone exposure. The time to complete wound healing was not different between the 2 cohorts (P = 0.48). In univariate analysis, higher body mass index (BMI), higher estimated blood loss, smoking, and longer duration of surgery were predictors of wound complications. Smoking (OR [95% CI]: 2.0 [1.3, 3.2], P = 0.003) and BMI (OR [95% CI]: 1.2 [1.1, 1.3], P = 0.0003) were the only significant predictors of wound complications in the multivariate model, whereas dexamethasone remained a nonsignificant predictor (OR [95% CI]: 0.7 [0.5, 1.1], P = 0.12). CONCLUSION:: Intraoperative dexamethasone for PONV prophylaxis does not seem to increase the rate or severity of postoperative wound complications in women undergoing laparotomy for endometrial cancer. BMI and smoking were significant predictors of wound complications in this patient population. Copyright © 2013 International Anesthesia Research Society.

Authors
Bolac, CS; Wallace, AH; Broadwater, G; Havrilesky, LJ; Habib, AS
MLA Citation
Bolac, CS, Wallace, AH, Broadwater, G, Havrilesky, LJ, and Habib, AS. "The impact of postoperative nausea and vomiting prophylaxis with dexamethasone on postoperative wound complications in patients undergoing laparotomy for endometrial cancer." Anesthesia and Analgesia 116.5 (2013): 1041-1047.
Source
scival
Published In
Anesthesia and Analgesia
Volume
116
Issue
5
Publish Date
2013
Start Page
1041
End Page
1047
DOI
10.1213/ANE.0b013e318276cf58

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, HY; Apte, SM; Lancaster, JM; Judson, PL; Gonzalez-Bosquet, J; Herschberger, A; Havrilesky, LJ; Secord, AA
MLA Citation
Wenham, RM, Lapolla, J, Lin, HY, 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

Are supportive care-based treatment strategies preferable to standard chemotherapy in recurrent cervical cancer?

Objective Recurrent cervical cancer has a poor prognosis despite aggressive treatment. We evaluate the comparative-effectiveness of four management strategies in recurrent cervix cancer incorporating risk prognostication categories derived from pooled collaborative group trials: 1) standard doublet chemotherapy; 2) selective chemotherapy (home hospice with no chemotherapy for poorest prognosis patients with remainder receiving standard doublet chemotherapy); 3) single-agent chemotherapy with home hospice; and 4) home hospice. Methods A cost-effectiveness decision model was constructed. Survival reduction of 24% was assumed for single-agent chemotherapy and 40% for hospice only compared to standard doublet chemotherapy. Overall survival and strategy cost for each arm were modeled as follows: standard doublet chemotherapy 8.9 months ($33 K); selective chemotherapy 8.7 months ($29 K); single-agent chemotherapy with home hospice 6.7 months ($16 K); and home hospice alone 5.3 months ($11 K). Base case analysis assumed equal quality of life (QOL). Sensitivity analyses assessed model uncertainties. Results Standard doublet chemotherapy for all is not cost-effective compared to selective chemotherapy with an incremental cost-effectiveness ratio (ICER) of $276 K per quality-adjusted life-year (QALY). Sensitivity analysis predicted that a 90% improvement in survival is required before standard doublet chemotherapy is cost-effective in the poorest prognosis patients. Selective chemotherapy is the most cost-effective strategy compared to single-agent chemotherapy with home hospice with an ICER of $78 K/QALY. Chemotherapy containing regimens become cost-prohibitive with small decreases in QOL. Conclusions Supportive care based treatment strategies are potentially more cost-effective than the current standard of doublet chemotherapy for all patients with recurrent cervical cancer and warrant prospective evaluation. © 2013 Elsevier Inc. All rights reserved.

Authors
Phippen, NT; III, CAL; Miller, CR; Lowery, WJ; Havrilesky, LJ; Barnett, JC
MLA Citation
Phippen, NT, III, CAL, Miller, CR, Lowery, WJ, Havrilesky, LJ, and Barnett, JC. "Are supportive care-based treatment strategies preferable to standard chemotherapy in recurrent cervical cancer?." Gynecologic Oncology 130.2 (2013): 317-322.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
2
Publish Date
2013
Start Page
317
End Page
322
DOI
10.1016/j.ygyno.2013.05.019

Oral contraceptive pills as primary prevention for ovarian cancer: A systematic review and meta-analysis

OBJECTIVE:: To estimate the overall reduction in ovarian cancer risk associated with the use of oral contraceptive pills (OCPs) and whether reduction in risk is affected by specifics of OCP use, such as formulation or duration of use. DATA SOURCES:: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published from January 1990 to June 2012, with primary analysis of studies published since January 2000. METHODS OF STUDY SELECTION:: We reviewed 6,476 citations. We included English-language controlled studies with human participants reporting a quantitative association between exposure to OCPs (in which the explicit or implicit indication for OCP use was prevention of pregnancy or ovarian cancer) compared with no use of OCPs. Two investigators independently reviewed the title and abstract and full-text of articles for inclusion or exclusion decision; discordant decisions were resolved by team review and consensus. TABULATION, INTEGRATION, AND RESULTS:: Fifty-five studies met inclusion criteria. A random-effects meta-analysis of 24 case-control and cohort studies showed significant reduction in ovarian cancer incidence in ever-users compared with never-users (odds ratio 0.73, 95% confidence interval 0.66-0.81). There was a significant duration-response relationship, with reduction in incidence of more than 50% among women using OCPs for 10 or more years. The lifetime reduction in ovarian cancer attributable to the use of OCPs is approximately 0.54% for a number-needed-to-treat of approximately 185 for a use period of 5 years. CONCLUSION:: Significant duration-dependent reductions in ovarian cancer incidence in the general population are associated with OCP use. © 2013 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

Authors
Havrilesky, LJ; Moorman, PG; Lowery, WJ; Gierisch, JM; Coeytaux, RR; Urrutia, RP; Dinan, M; McBroom, AJ; Hasselblad, V; Sanders, GD; Myers, ER
MLA Citation
Havrilesky, LJ, Moorman, PG, Lowery, WJ, Gierisch, JM, Coeytaux, RR, Urrutia, RP, Dinan, M, McBroom, AJ, Hasselblad, V, Sanders, GD, and Myers, ER. "Oral contraceptive pills as primary prevention for ovarian cancer: A systematic review and meta-analysis." Obstetrics and Gynecology 122.1 (2013): 139-147.
Source
scival
Published In
Obstetrics & Gynecology (Elsevier)
Volume
122
Issue
1
Publish Date
2013
Start Page
139
End Page
147
DOI
10.1097/AOG.0b013e318291c235

Cost analysis of colposcopy for abnormal cytology in post-treatment surveillance for cervical cancer

Objective The aim of this study was to estimate cost and outcomes associated with colposcopy following abnormal Pap for women with a history of cervical cancer. Methods Decision models compared the costs and number of isolated local recurrences (ILR) detected using two strategies, colposcopy and no colposcopy, for women with a history of cervical cancer and low grade or high grade Pap. Clinical data for input were derived from a cohort of women with a history of cervical cancer undergoing surveillance Paps at 2 institutions. Costs were obtained using national reimbursement data. Results Five hundred fifty-six patients underwent 2900 surveillance Paps. Twenty-seven of 50 women with a low grade Pap underwent colposcopy. One of 3 recurrences in the colposcopy group was an ILR diagnosed colposcopically. Colposcopy following low grade Pap costs $354 more and resulted in a lower rate of diagnosis of ILR compared to no colposcopy (3.7% vs 8.6%). Sixty of 78 women with a high grade Pap underwent colposcopy. Three of 15 recurrences in the colposcopy group were ILR diagnosed colposcopically. Colposcopy following high grade Pap costs $623 more than no colposcopy but resulted in a higher rate of diagnosis of ILR (5% vs 0%; $7481 per additional ILR). Conclusions Colposcopy following low or high grade surveillance Pap smear adds substantial cost to the management of women with cervical cancer. Only colposcopy following a high grade Pap is associated with a higher probability that cervical cancer recurrence will be detected when salvageable. These findings support withholding colposcopy for abnormal surveillance Pap tests less than high grade. © 2013 Elsevier Inc. All rights reserved.

Authors
Tergas, AI; Havrilesky, LJ; Fader, AN; Guntupalli, SR; Huh, WK; Massad, LS; Rimel, BJ
MLA Citation
Tergas, AI, Havrilesky, LJ, Fader, AN, Guntupalli, SR, Huh, WK, Massad, LS, and Rimel, BJ. "Cost analysis of colposcopy for abnormal cytology in post-treatment surveillance for cervical cancer." Gynecologic Oncology 130.3 (2013): 421-425.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
3
Publish Date
2013
Start Page
421
End Page
425
DOI
10.1016/j.ygyno.2013.05.037

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

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
Front Oncol
Volume
3
Publish Date
2013
Start Page
269
DOI
10.3389/fonc.2013.00269

A branching process model of ovarian cancer.

Ovarian cancer is usually diagnosed at an advanced stage, rendering the possibility of cure unlikely. To date, no cost-effective screening test has proven effective for reducing mortality. To estimate the window of opportunity for ovarian cancer screening, we develop a branching process model for ovarian cancer growth and progression accounting for three cell populations: Primary (cells in the ovary or fallopian tube), Peritoneal (viable cells in peritoneal fluid), and Metastatic (cells implanted on other intra-abdominal surfaces). Growth and migration parameters were chosen to match results of clinical studies. Using these values, our model predicts a window of opportunity of 2.9 years, indicating that one would have to screen at least every other year to be effective. The model can be used to inform future efforts in designing improved screening and treatment strategies.

Authors
Danesh, K; Durrett, R; Havrilesky, LJ; Myers, E
MLA Citation
Danesh, K, Durrett, R, Havrilesky, LJ, and Myers, E. "A branching process model of ovarian cancer." J Theor Biol 314 (December 7, 2012): 10-15.
PMID
22959913
Source
pubmed
Published In
Journal of Theoretical Biology
Volume
314
Publish Date
2012
Start Page
10
End Page
15
DOI
10.1016/j.jtbi.2012.08.025

Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multiagent 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 34months (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; P2m(2) (OR=6.14; P

Authors
Hanna, RK; Poniewierski, MS; Laskey, RA; Lopez, MA; Shafer, A; Le, LV; Crawford, J; Dale, DC; Gehrig, PA; Secord, AA; Havrilesky, LJ; Lyman, GH
MLA Citation
Hanna, RK, Poniewierski, MS, Laskey, RA, Lopez, MA, Shafer, A, Le, LV, 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 multiagent chemotherapy for epithelial ovarian cancer." Gynecologic oncology (December 2012). (Academic Article)
PMID
23262376
Source
manual
Published In
Gynecologic Oncology
Publish Date
2012
DOI
10.1016/j.ygyno.2012.12.017

Cost effectiveness of concurrent gemcitabine and cisplatin with radiation followed by adjuvant gemcitabine and cisplatin in patients with stages IIB to IVA carcinoma of the cervix.

OBJECTIVE: A recent phase III trial reported gemcitabine with cisplatin chemoradiation followed by 2 cycles of gemcitabine and cisplatin (G) significantly improved progression-free (PFS) and overall survival (OS) compared to standard cisplatin chemoradiation (C) for locally advanced cervix cancer. We evaluate the cost effectiveness (CE) of these treatment regimens. METHODS: A modified Markov model was constructed comparing CE between treatment arms using the published trial's five-year OS and treatment-related toxicity rates. Quality of life (QOL) utility scores during treatment were obtained from published literature and modeled for sensitivity analysis. Cost data was obtained from Medicare reimbursement figures and the Healthcare Cost and Utilization Project. One-way sensitivity analyses assessed variations in cost and adverse events. RESULTS: Mean cost was $41,330 (US$) for C versus $60,974 for G. Incremental cost-effectiveness ratio (ICER) for G compared to C was $33,080 per quality-adjusted life year (QALY). In sensitivity analyses (SA), the ICER increased to common willingness-to-pay thresholds of 50 K and 100 K when QOL utility scores during G active treatment declined to 0.64 and 0.53 (baseline 0.76), respectively. The model was insensitive to changes in adverse event rates, costs of treatment, or adverse event hospitalization costs. CONCLUSIONS: Gemcitabine with cisplatin chemoradiation followed by 2 cycles of adjuvant gemcitabine and cisplatin is a cost effective treatment for locally advanced cervix cancer compared to standard cisplatin chemoradiation. Common willingness to pay thresholds are exceeded during sensitivity analyses with realistic declines in QOL. Our results support ongoing investigations of novel adjuvants to standard cisplatin chemoradiation with potentially less toxicity.

Authors
Phippen, NT; Leath, CA; Chino, JP; Jewell, EL; Havrilesky, LJ; Barnett, JC
MLA Citation
Phippen, NT, Leath, CA, Chino, JP, Jewell, EL, Havrilesky, LJ, and Barnett, JC. "Cost effectiveness of concurrent gemcitabine and cisplatin with radiation followed by adjuvant gemcitabine and cisplatin in patients with stages IIB to IVA carcinoma of the cervix." Gynecol Oncol 127.2 (November 2012): 267-272.
PMID
22892361
Source
pubmed
Published In
Gynecologic Oncology
Volume
127
Issue
2
Publish Date
2012
Start Page
267
End Page
272
DOI
10.1016/j.ygyno.2012.08.002

Beyond mere obesity: effect of increasing obesity classifications on hysterectomy outcomes for uterine cancer/hyperplasia.

OBJECTIVE: To assess the impact of obesity severity on hysterectomy outcomes for uterine hyperplasia/cancer. METHODS: The data from women undergoing hysterectomies for endometrial hyperplasia/uterine cancer with a BMI≥30 kg/m(2) were abstracted from records at the University of Virginia and Duke University following IRB approval. Univariate and multivariate statistical analyses were performed. RESULTS: Mean age of the 659 patients was 58.1 yrs; mean body mass index (BMI) was 43 kg/m(2). Women were grouped based on BMI: 39.6% (261) were obese (30-39 kg/m(2)), 41.7% (275) were morbidly obese (40-49 kg/m(2)) and 18.7% (123) were super obese (≥50 kg/m(2)). Minimally invasive surgical procedures (MIS) were attempted in 280 patients with a conversion rate of 16.1%; BMI was higher in the converted group (47.3 vs. 40.6 kg/m(2); p<0.001). As obesity group increased, there was a decreased frequency of lymphadenectomy (63.8% vs. 37.1% vs. 20.3%; p<0.001), increased blood loss (242 vs. 281 vs. 378 mL; p<0.001) and fewer nodes removed (p<0.001). On multivariate analysis, type of surgery (open vs. MIS) and obesity classification were independently and significantly associated with wound complications (p<0.001) and the presence of postoperative complications (p<0.001, p=0.003). Surgical staging with lymphadenectomy was significantly associated with obesity (p<0.001) but not procedure type (p=0.11). Blood transfusion (p<0.001), hospital readmission (p=0.025), and ileus (p<0.001) were significantly associated with open procedures but not obesity. There were no significant differences in progression-free or disease-specific survival based on obesity group. CONCLUSION: Women with BMI's exceeding 40 kg/m(2) have worse surgical outcomes than their less obese counterparts.

Authors
Giugale, LE; Di Santo, N; Smolkin, ME; Havrilesky, LJ; Modesitt, SC
MLA Citation
Giugale, LE, Di Santo, N, Smolkin, ME, Havrilesky, LJ, and Modesitt, SC. "Beyond mere obesity: effect of increasing obesity classifications on hysterectomy outcomes for uterine cancer/hyperplasia." Gynecol Oncol 127.2 (November 2012): 326-331.
PMID
22910692
Source
pubmed
Published In
Gynecologic Oncology
Volume
127
Issue
2
Publish Date
2012
Start Page
326
End Page
331
DOI
10.1016/j.ygyno.2012.08.014

Ovarian Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines

Authors
Jr, MRJ; Alvarez, RD; Armstrong, DK; Burger, RA; Castells, M; Chen, L-M; Copeland, L; Crispens, MA; Gershenson, D; Gray, H; Hakam, A; Havrilesky, LJ; Johnston, C; Lele, S; Martin, L; Matulonis, UA; O'Malley, DM; Penson, RT; Remmenga, SW; Sabbatini, P; Santoso, JT; Schilder, RJ; Schink, J; Teng, N; Werner, TL; Hughes, M; Dwyer, MA
MLA Citation
Jr, MRJ, Alvarez, RD, Armstrong, DK, Burger, RA, Castells, M, Chen, L-M, Copeland, L, Crispens, MA, Gershenson, D, Gray, H, Hakam, A, Havrilesky, LJ, Johnston, C, Lele, S, Martin, L, Matulonis, UA, O'Malley, DM, Penson, RT, Remmenga, SW, Sabbatini, P, Santoso, JT, Schilder, RJ, Schink, J, Teng, N, Werner, TL, Hughes, M, and Dwyer, MA. "Ovarian Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines." JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK 10.11 (November 2012): 1339-1349.
Source
wos-lite
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
11
Publish Date
2012
Start Page
1339
End Page
1349

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

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

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

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

Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer.

OBJECTIVE: To determine the potential economic impact of a paclitaxel drug shortage in patients with newly diagnosed, untreated ovarian cancer. METHODS: A modified Markov state transition model with a 6 cycle time horizon compared two scenarios: (1) Standard treatment (STD): paclitaxel 175 mg/m2/carboplatin AUC 5 × 6 cycles; (2) Paclitaxel drug shortage (DS): docetaxel 75 mg/m2/carboplatin AUC 5 × 6 cycles. Adverse events, quality of life, and costs of chemotherapy, neuropathy, febrile neutropenia, and anemia were incorporated. Key assumptions: (1) Costs and consequences were assigned only to grade 2+ neuropathy, febrile neutropenia, and grade 3-4 anemia; (2) Grade 2+ neuropathy prompted a switch from paclitaxel/carboplatin to docetaxel/carboplatin or from docetaxel/carboplatin to carboplatin alone; (3) Febrile neutropenia resulted in inpatient hospitalization followed by G-CSF prophylaxis. RESULTS: The mean cost of 6 cycles of chemotherapy was $4939 in the STD and $16,107 in the DS scenario, for a cost difference of $11,168 per patient over 6 cycles of treatment. STD was the dominant strategy (less expensive and more effective than the drug shortage scenario). In sensitivity analysis, DS was more costly over a wide range of clinical estimates in each arm. A drug shortage that affects approximately 50% of women initiating chemotherapy is expected to impact 779 women and cost third party payers an additional $8,699,872 monthly. CONCLUSIONS: Our model indicates that chemotherapy drug shortages can have a significant negative impact on the average cost of primary treatment for ovarian cancer and have the potential to negatively impact health system costs.

Authors
Havrilesky, LJ; Garfield, CF; Barnett, JC; Cohn, DE
MLA Citation
Havrilesky, LJ, Garfield, CF, Barnett, JC, and Cohn, DE. "Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer." Gynecol Oncol 125.3 (June 2012): 631-634.
PMID
22446408
Source
pubmed
Published In
Gynecologic Oncology
Volume
125
Issue
3
Publish Date
2012
Start Page
631
End Page
634
DOI
10.1016/j.ygyno.2012.03.028

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

Robotic-assisted surgery in gynecologic oncology: a Society of Gynecologic Oncology consensus statement. Developed by the Society of Gynecologic Oncology's Clinical Practice Robotics Task Force.

Authors
Ramirez, PT; Adams, S; Boggess, JF; Burke, WM; Frumovitz, MM; Gardner, GJ; Havrilesky, LJ; Holloway, R; Lowe, MP; Magrina, JF; Moore, DH; Soliman, PT; Yap, S
MLA Citation
Ramirez, PT, Adams, S, Boggess, JF, Burke, WM, Frumovitz, MM, Gardner, GJ, Havrilesky, LJ, Holloway, R, Lowe, MP, Magrina, JF, Moore, DH, Soliman, PT, and Yap, S. "Robotic-assisted surgery in gynecologic oncology: a Society of Gynecologic Oncology consensus statement. Developed by the Society of Gynecologic Oncology's Clinical Practice Robotics Task Force." Gynecol Oncol 124.2 (February 2012): 180-184.
PMID
22079679
Source
pubmed
Published In
Gynecologic Oncology
Volume
124
Issue
2
Publish Date
2012
Start Page
180
End Page
184
DOI
10.1016/j.ygyno.2011.11.006

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

Cost analysis of abdominal, laparoscopic, and robotic-assisted myomectomies.

STUDY OBJECTIVE: To perform a cost-minimization analysis of abdominal, traditional laparoscopic and robotic-assisted myomectomy. DESIGN: Cost analysis (Canadian Task Force Classification III). SETTING: Academic medical center. PATIENTS: Women undergoing myomectomy by various surgical approaches. INTERVENTIONS: We developed a decision model to compare the costs ($2009) of different approaches to myomectomy from a healthcare system perspective. The model included operative time, conversion risk, transfusion risk, and length of stay (LOS) for each modality. Baseline estimates and ranges were based on reported values extracted from existing literature. We analyzed two different models: #1) Existing Robot model and #2) Robot Purchase model. MEASUREMENTS AND MAIN RESULTS: In the baseline analysis for the Existing Robot model, abdominal myomectomy (AM) was the least expensive at $4937 compared with laparoscopic myomectomy (LM) at $6219 and robotic-assisted laparoscopic myomectomy (RM) at $7299. The abdominal route remained the least expensive when varying all parameters and costs except for two cases in which LM became least expensive: 1) If AM length of stay was greater than 4.6 days, and 2) If the surgeon's fee for AM was greater than $2410. When comparing LM to RM, the cost of RM was consistently higher unless the robotic disposable equipment costs were less than $1400. In the Robot Purchase model, only the RM costs increased while AM and LM costs remained the same. CONCLUSION: In this cost-minimization analysis, abdominal myomectomy is the least expensive approach when compared to laparoscopy and robotic-assisted laparoscopy.

Authors
Behera, MA; Likes, CE; Judd, JP; Barnett, JC; Havrilesky, LJ; Wu, JM
MLA Citation
Behera, MA, Likes, CE, Judd, JP, Barnett, JC, Havrilesky, LJ, and Wu, JM. "Cost analysis of abdominal, laparoscopic, and robotic-assisted myomectomies." J Minim Invasive Gynecol 19.1 (January 2012): 52-57.
PMID
22100443
Source
pubmed
Published In
Journal of Minimally Invasive Gynecology
Volume
19
Issue
1
Publish Date
2012
Start Page
52
End Page
57
DOI
10.1016/j.jmig.2011.09.007

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 economics of screening for gynaecological cancers

In this chapter, we summarise findings from recent cost-effectiveness analyses of screening for cervical cancer and ovarian cancer. We begin with a brief summary of key issues that affect the cost-effectiveness of screening, including disease burden, and availability and type of screening tests. For cervical cancer, we discuss the potential effect of human papilloma virus vaccines on screening. Outstanding epidemiological and cost-effectiveness issues are included. For cervical cancer, this includes incorporating the long-term effect of treatment (including adverse birth outcomes in treated women who are of reproductive age) into cost-effectiveness models using newly available trial data to identify the best strategy for incorporating human papilloma virus tests. A second issue is the need for additional data on human papilloma virus vaccines, such as effectiveness of reduced cancer incidence and mortality, effectiveness in previously exposed women and coverage. Definitive data on these parameters will allow us to update model-based analyses to include more realistic estimates, and also potentially dramatically alter our approach to screening. For ovarian cancer, outstanding issues include confirming within the context of a trial that screening is effective for reducing mortality and incorporating tests with high specificity into screening into screening algorithms for ovarian cancer. © 2011 Elsevier Ltd. All rights reserved.

Authors
Kulasingam, S; Havrilesky, L
MLA Citation
Kulasingam, S, and Havrilesky, L. "Health economics of screening for gynaecological cancers." Best Practice and Research: Clinical Obstetrics and Gynaecology 26.2 (2012): 163-173.
PMID
22138003
Source
scival
Published In
Best Practice & Research: Clinical Obstetrics & Gynaecology
Volume
26
Issue
2
Publish Date
2012
Start Page
163
End Page
173
DOI
10.1016/j.bpobgyn.2011.10.013

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

Preoperative screening strategies for bacterial vaginosis prior to elective hysterectomy: a cost comparison study.

OBJECTIVE: The purpose of this study is to compare costs of 3 strategies for women undergoing hysterectomy: (1) test all patients for bacterial vaginosis; treat if positive; (2) treat all patients for bacterial vaginosis; (3) neither test nor treat patients for bacterial vaginosis. For comparison purposes, a fourth strategy is examined: (4) no surgical site infection prophylaxis or bacterial vaginosis treatment. STUDY DESIGN: A cost minimization model was created using estimates obtained from the published literature, Medicare reimbursement data, and wholesale drug costs. RESULTS: In the base case, the optimal strategy was to treat all patients for bacterial vaginosis, with a cuff infection rate of 4.0% and mean cost of $593. The "test all patients for bacterial vaginosis; treat if positive" strategy was also inexpensive, with a mean cost of $623 and 4.2% cuff infection rate. "Neither test nor treat patients for bacterial vaginosis" and "no surgical site infection prophylaxis or bacterial vaginosis treatment" were more expensive and less effective than other strategies. CONCLUSION: This model suggests that consideration should be given to adding metronidazole to standard surgical site infection prophylaxis before hysterectomy.

Authors
McElligott, KA; Havrilesky, LJ; Myers, ER
MLA Citation
McElligott, KA, Havrilesky, LJ, and Myers, ER. "Preoperative screening strategies for bacterial vaginosis prior to elective hysterectomy: a cost comparison study." Am J Obstet Gynecol 205.5 (November 2011): 500.e1-500.e7.
PMID
21944221
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
205
Issue
5
Publish Date
2011
Start Page
500.e1
End Page
500.e7
DOI
10.1016/j.ajog.2011.07.012

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

Utility scores and treatment preferences for clinical early-stage cervical cancer.

OBJECTIVES: To determine utility scores for health states relevant to the treatment of early-stage, high-risk cervical cancer. METHODS: Seven descriptive health states incorporating the physical and emotional aspects of medical treatment, recovery, and prognosis were developed. Forty-five female volunteers valuated each health state using the visual analogue score (VAS) and time trade off (TTO) methods. Treatment options were ranked by mean and median TTO scores. The 95% confidence intervals were calculated to determine the statistical significance of ranking preferences. The Wilcoxon rank-sum test was used to compare central tendencies related to age, race, parity, and subject history of abnormal cervical cytology. RESULTS: VAS and TTO scores were highly correlated. Volunteers ranked minimally invasive radical hysterectomy with low-risk features as most preferred (mean TTO = 0.96; median TTO = 1.00) and aborted radical hysterectomy followed by chemoradiation as least preferred (mean TTO = 0.69; median TTO = 0.83). Health states that included radical surgery were ranked higher than those that included chemoradiation, either in the adjuvant or primary setting. When survival was comparable, volunteers rated radical hysterectomy with high-risk pathology followed by adjuvant chemoradiation (mean TTO = 0.78; median TTO = 0.92; 95% CI: 0.69-0.87) similarly to chemoradiation alone (mean TTO = 0.76; median TTO 0.90; 95% CI: 0.66-0.86; p = NS). Utility scores for the majority of health states were not significantly associated with age, race, parity, or subject history of abnormal cervical cytology. CONCLUSION: Subjects consistently preferred surgical excision to treat early-stage, high-risk cervical cancer and chose a minimally invasive approach. Such utility scores can be used to incorporate quality-of-life effects into comparative-effectiveness models for cervical cancer.

Authors
Jewell, EL; Smrtka, M; Broadwater, G; Valea, F; Davis, DM; Nolte, KC; Valea, R; Myers, ER; Samsa, G; Havrilesky, LJ
MLA Citation
Jewell, EL, Smrtka, M, Broadwater, G, Valea, F, Davis, DM, Nolte, KC, Valea, R, Myers, ER, Samsa, G, and Havrilesky, LJ. "Utility scores and treatment preferences for clinical early-stage cervical cancer." Value Health 14.4 (June 2011): 582-586.
PMID
21669383
Source
pubmed
Published In
Value in Health
Volume
14
Issue
4
Publish Date
2011
Start Page
582
End Page
586
DOI
10.1016/j.jval.2010.11.017

Development of an ovarian cancer screening decision model that incorporates disease heterogeneity: implications for potential mortality reduction.

BACKGROUND: Pathologic and genetic data suggest that epithelial ovarian cancer may consist of indolent and aggressive phenotypes. The objective of the current study was to estimate the impact of a 2-phenotype paradigm of epithelial ovarian cancer on the mortality reduction achievable using available screening technologies. METHODS: The authors modified a Markov model of ovarian cancer natural history (the 1-phenotype model) to incorporate aggressive and indolent phenotypes (the 2-phenotype model) based on histopathologic criteria. Stage distribution, incidence, and mortality were calibrated to data from the Surveillance, Epidemiology, and End Results Program of the US National Cancer Institute. For validation, a Monte Carlo microsimulation (1000,000 events) of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) multimodality prevalence screen was performed. Mortality reduction and positive predictive value (PPV) were estimated for annual screening. RESULTS: In validation against UKCTOCS data, the model-predicted percentage of screen-detected cancers diagnosed at stage I and II was 41% compared with 47% (UKCTOCS data), and the model-predicted PPV of screening was 27% compared with 35% (UKCTOCS data). The model-estimated PPV of a strategy of annual population-based screening in the United States at ages 50 to 85 years was 14%. The mortality reduction using annual postmenopausal screening was 14.7% (1-phenotype model) and 10.9% (2-phenotype model). Mortality reduction was lower with the 2-phenotype model than with the 1-phenotype model regardless of screening frequency or test sensitivity; 68% of cancer deaths are accounted for by the aggressive phenotype. CONCLUSIONS: The current analysis suggested that reductions in ovarian cancer mortality using available screening technologies on an annual basis are likely to be modest. A model that incorporated 2 clinical phenotypes of ovarian carcinoma into its natural history predicted an even smaller potential reduction in mortality because of the more frequent diagnosis of indolent cancers at early stages.

Authors
Havrilesky, LJ; Sanders, GD; Kulasingam, S; Chino, JP; Berchuck, A; Marks, JR; Myers, ER
MLA Citation
Havrilesky, LJ, Sanders, GD, Kulasingam, S, Chino, JP, Berchuck, A, Marks, JR, and Myers, ER. "Development of an ovarian cancer screening decision model that incorporates disease heterogeneity: implications for potential mortality reduction." Cancer 117.3 (February 1, 2011): 545-553.
PMID
21254049
Source
pubmed
Published In
Cancer
Volume
117
Issue
3
Publish Date
2011
Start Page
545
End Page
553
DOI
10.1002/cncr.25624

Analgesic and antiemetic needs following minimally invasive vs open staging for endometrial cancer.

OBJECTIVE: We sought to assess perioperative outcomes of minimally invasive vs open endometrial cancer staging procedures. STUDY DESIGN: A total of 181 consecutive patients underwent open or minimally invasive hysterectomy with or without lymphadenectomy. Perioperative outcomes, analgesic, and antiemetic use were compared. RESULTS: In all, 97 and 84 women underwent open and minimally invasive staging procedures, respectively. In the open staging group, median anesthesia time was shorter (197 vs 288 minutes; P < .0001), but recovery room stay (168 vs 140 minutes; P = .01) and hospital stay (4 vs 1 day; P < .0001) were longer. Median narcotic (13 vs 43 mg morphine equivalents; P < .0001) and antiemetic (43% vs 25%; P = .01) use were lower for minimally invasive surgery in the first 24 hours postoperatively. Median estimated blood loss was lower for minimally invasive procedures (100 vs 300 mL; P < .0001). CONCLUSION: Minimally invasive staging for endometrial cancer is associated with lower use of narcotics and antiemetics, and shorter hospital stay compared to open procedures.

Authors
Fleming, ND; Havrilesky, LJ; Valea, FA; Allen, TK; Broadwater, G; Bland, A; Habib, AS
MLA Citation
Fleming, ND, Havrilesky, LJ, Valea, FA, Allen, TK, Broadwater, G, Bland, A, and Habib, AS. "Analgesic and antiemetic needs following minimally invasive vs open staging for endometrial cancer." Am J Obstet Gynecol 204.1 (January 2011): 65.e1-65.e6.
PMID
20869036
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
204
Issue
1
Publish Date
2011
Start Page
65.e1
End Page
65.e6
DOI
10.1016/j.ajog.2010.08.020

Epithelial ovarian cancer.

Authors
Morgan, RJ; Alvarez, RD; Armstrong, DK; Boston, B; Burger, RA; Chen, L-M; Copeland, L; Crispens, MA; Gershenson, D; Gray, HJ; Grigsby, PW; Hakam, A; Havrilesky, LJ; Johnston, C; Lele, S; Matulonis, UA; O'Malley, DM; Penson, RT; Remmenga, SW; Sabbatini, P; Schilder, RJ; Schink, JC; Teng, N; Werner, TL; National Comprehensive Cancer Network,
MLA Citation
Morgan, RJ, Alvarez, RD, Armstrong, DK, Boston, B, Burger, RA, Chen, L-M, Copeland, L, Crispens, MA, Gershenson, D, Gray, HJ, Grigsby, PW, Hakam, A, Havrilesky, LJ, Johnston, C, Lele, S, Matulonis, UA, O'Malley, DM, Penson, RT, Remmenga, SW, Sabbatini, P, Schilder, RJ, Schink, JC, Teng, N, Werner, TL, and National Comprehensive Cancer Network, . "Epithelial ovarian cancer." J Natl Compr Canc Netw 9.1 (January 2011): 82-113.
PMID
21233246
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
1
Publish Date
2011
Start Page
82
End Page
113

A review of cost-effectiveness studies in ovarian cancer.

BACKGROUND: Ovarian cancer is the fifth leading cause of all cancer-related deaths among women. While the costs of diagnosis and treatment impact the affected individual and the health system, the most important costs for the patient are often the pain and suffering associated with ovarian cancer. The quality of life associated with any management decision should be closely examined. Cost-effectiveness models take into account costs, effects, and quality of life and provide clinicians with useful tools to aid in making these difficult decisions. METHODS: A comprehensive review of cost-effectiveness analyses was undertaken concerning screening for and treatment of ovarian cancer. RESULTS: Screening methods to detect ovarian cancer are unproven, and the majority of women present with advanced-stage disease. Multimodal screening strategies with high specificities targeted at the highest-risk individuals are the most likely strategies to be cost-effective. Primary treatment with intravenous paclitaxel and platinum regimens has proven to be cost-effective in multiple studies. Studies evaluating intraperitoneal chemotherapy show that this strategy is potentially cost-effective over a long-term time horizon. A cost-effectiveness analysis of the management of recurrent platinum-sensitive ovarian cancer showed that treatment with carboplatin and paclitaxel is cost-effective compared to single-agent therapy. However, the preferred option for patients with recurrent platinum-resistant ovarian cancer appears to be supportive care (no chemotherapy) or single-agent therapy. CONCLUSIONS: Many therapeutic choices are cost-effective in the treatment of ovarian cancer. Cost-effectiveness models offer one way to examine options in the management of a disease. The quality of life of the patient should be the most important factor in any management decision and is incorporated into well-designed studies on cost-effectiveness.

Authors
Sfakianos, GP; Havrilesky, LJ
MLA Citation
Sfakianos, GP, and Havrilesky, LJ. "A review of cost-effectiveness studies in ovarian cancer." Cancer Control 18.1 (January 2011): 59-64. (Review)
PMID
21273981
Source
pubmed
Published In
Cancer control : journal of the Moffitt Cancer Center
Volume
18
Issue
1
Publish Date
2011
Start Page
59
End Page
64

Projecting the need for gynecologic oncologists for the next 40 years.

OBJECTIVE: To estimate the ratio of gynecologic cancer cases to practicing gynecologic oncologists in the United States over the next 40 years. METHODS: Using population projections from the U.S. Census Bureau and incidence and mortality rates from Surveillance, Epidemiology and End Results surveys, we estimated the annual number of new gynecologic cancer cases through 2050; the effects of human papillomavirus (HPV) vaccination was included in cervical cancer estimates. The number of practicing gynecologic oncologists was projected through 2050 using data from the 2005 Society of Gynecologic Oncologists Practice Survey, current Society of Gynecologic Oncologists membership information, American Board of Obstetrics and Gynecology and Gynecologic Oncology oral examination results, and mortality estimates from U.S. life tables. Projected time in practice was sex-dependent based on Society of Gynecologic Oncologists Practice Survey. For sensitivity analyses, we varied annual number and sex distribution of fellowship graduates, HPV vaccination coverage rates, and future incidence of overweight and obesity. RESULTS: At constant training rates, the annual number of new cancer cases per practicing gynecologic oncologist will rise from 112 in 2010 to 133 in 2050, a 19% increase. If the annual number of fellowship graduates increases by 25%, the ratio of cancer cases per gynecologic oncologist will decrease to 106, a 5% decrease. Projections are more sensitive to changes in physician demographics than to changes in HPV vaccination coverage rates. CONCLUSION: The gynecologic cancer caseload of practicing gynecologic oncologists will increase by almost 20% over the next 40 years at constant training rates. Changes in the projected sex distribution of fellowship graduates and their time in practice affect these projections.

Authors
Wallace, AH; Havrilesky, LJ; Valea, FA; Barnett, JC; Berchuck, A; Myers, ER
MLA Citation
Wallace, AH, Havrilesky, LJ, Valea, FA, Barnett, JC, Berchuck, A, and Myers, ER. "Projecting the need for gynecologic oncologists for the next 40 years." Obstet Gynecol 116.6 (December 2010): 1366-1372.
PMID
21099604
Source
pubmed
Published In
Obstetrics and Gynecology
Volume
116
Issue
6
Publish Date
2010
Start Page
1366
End Page
1372
DOI
10.1097/AOG.0b013e3181fc3a22

Cost comparison among robotic, laparoscopic, and open hysterectomy for endometrial cancer.

OBJECTIVE: To use decision modeling to compare the costs associated with robotic, laparoscopic, and open hysterectomy for the treatment of endometrial cancer. METHODS: Three separate models were used, each with sensitivity analysis: 1) a societal perspective model, which included inpatient hospital costs, robotic expenses, and lost wages and caregiver costs; 2) a hospital perspective plus robot costs model, which was identical to the societal perspective model but excluded lost wages and caregiver costs; and 3) a hospital perspective without robot costs model, which was identical to the hospital perspective plus robot costs model except that it excluded initial cost of the robot. RESULTS: The societal perspective model predicted laparoscopy ($10,128) as the least expensive approach followed by robotic and ($11,476) and open hysterectomy ($12,847). Societal perspective model sensitivity analyses predicted robotic hysterectomy to be least expensive when robotic disposable equipment cost less than $1,046 per case (baseline cost $2,394). In the hospital perspective plus robot costs model, laparoscopy was least expensive ($6,581) followed by open ($7,009) and robotic hysterectomy ($8,770); however, if hospital stay after open surgery was less than 2.9 days, open hysterectomy was least expensive. In the hospital perspective without robot costs model, laparoscopy remained least expensive, but robotic surgery became least expensive if the cost of robotic disposable equipment was reduced to less than $1,496 per case. CONCLUSION: Laparoscopy is the least expensive surgical approach for the treatment of endometrial cancer. Robotic is less costly than abdominal hysterectomy when the societal costs associated with recovery time are accounted for and is most economically attractive if disposable equipment costs can be minimized. LEVEL OF EVIDENCE: III.

Authors
Barnett, JC; Judd, JP; Wu, JM; Scales, CD; Myers, ER; Havrilesky, LJ
MLA Citation
Barnett, JC, Judd, JP, Wu, JM, Scales, CD, Myers, ER, and Havrilesky, LJ. "Cost comparison among robotic, laparoscopic, and open hysterectomy for endometrial cancer." Obstet Gynecol 116.3 (September 2010): 685-693.
PMID
20733453
Source
pubmed
Published In
Obstetrics and Gynecology
Volume
116
Issue
3
Publish Date
2010
Start Page
685
End Page
693
DOI
10.1097/AOG.0b013e3181ee6e4d

Impact of a chemoresponse assay on treatment costs for recurrent ovarian cancer.

OBJECTIVE: We sought to estimate mean costs of chemotherapy treatment for recurrent ovarian cancer with or without use of a chemoresponse assay. STUDY DESIGN: We estimated mean costs for 3 groups: (1) assay assisted: 75 women who received oncologist's choice of chemotherapy following chemoresponse testing (65% adherence to test results), (2) assay adherent: modeled group assuming 100% adherence to assay results, and (3) empiric: modeled from market share data on most frequently utilized chemotherapy regimens. Cost estimates were based on commercial claims database reimbursements. RESULTS: The most common chemotherapy regimens used were topotecan, doxorubicin, and carboplatin/paclitaxel. Mean chemotherapy costs for 6 cycles were $48,758 (empiric), $33,187 (assay assisted), and $23,986 (assay adherent). The cost savings related to the assay were associated with a shift from higher- to lower-cost chemotherapy regimens and lower use of supportive drugs such as hematopoiesis-stimulating agents. CONCLUSION: Assay-assisted chemotherapy for recurrent ovarian cancer may result in reduced costs compared to empiric therapy.

Authors
Havrilesky, LJ; Krivak, TC; Mucenski, JW; Myers, ER
MLA Citation
Havrilesky, LJ, Krivak, TC, Mucenski, JW, and Myers, ER. "Impact of a chemoresponse assay on treatment costs for recurrent ovarian cancer." Am J Obstet Gynecol 203.2 (August 2010): 160.e1-160.e7.
PMID
20417480
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
203
Issue
2
Publish Date
2010
Start Page
160.e1
End Page
160.e7
DOI
10.1016/j.ajog.2010.02.054

Cost-minimization analysis of robotic-assisted, laparoscopic, and abdominal sacrocolpopexy.

STUDY OBJECTIVE: To perform a cost-minimization analysis comparing robotic-assisted, laparoscopic, and abdominal sacrocolpopexy. DESIGN: Cost-minimization analysis using a micro-costing approach (Canadian Task Force classification III). MEASUREMENTS AND MAIN RESULTS: A decision model was developed to compare the costs (2008 US dollars) of robotic, laparoscopic, and abdominal sacrocolpopexy. Our model included operative time, risk of conversion, risk of transfusion, and length of stay (LOS) for each method. Respective baseline estimates for robotic, laparoscopic, and abdominal sacrocolpopexy procedures included operative time (328, 269, and 170 minutes), conversion (1.4%, 1.8%, and 0%), transfusion (1.4%, 1.8%, 3.8%), and LOS (1.0, 1.8, and 2.7 days). Two models were used, the Robot Existing model, that is, current hospital ownership of a robotic system, and the Robot Purchase model, that is, initial hospital purchase of a robotic system, with purchase and maintenance costs amortized and distributed across robotic procedures. Sensitivity analyses were performed to assess the effect of varying each parameter through its range. For the Robot Existing robot model, robotic sacrocolpopexy was the most expensive, $8508 per procedure compared with laparoscopic sacrocolpopexy at $7353 and abdominal sacrocolpopexy at $5792. Robotic and laparoscopic sacrocolpopexy became cost-equivalent only when robotic operative time was reduced to 149 minutes, robotic disposables costs were reduced to $2132, or laparoscopic disposable costs were increased to $3413. Laparoscopic and abdominal sacrocolpopexy became cost-equivalent only when laparoscopic disposable costs were reduced to $668, mean LOS for abdominal sacrocolpopexy was increased to 5.6 days, or surgeon reimbursement for abdominal sacrocolpopexy exceeded $2213. The addition of robotic purchase and maintenance costs resulted in an incremental increase of $581, $865, and $1724 per procedure when these costs were distributed over 60, 40, and 20 procedures per month, respectively. CONCLUSION: Robotic sacrocolpopexy was more expensive compared with the laparoscopic or abdominal routes under the baseline assumptions.

Authors
Judd, JP; Siddiqui, NY; Barnett, JC; Visco, AG; Havrilesky, LJ; Wu, JM
MLA Citation
Judd, JP, Siddiqui, NY, Barnett, JC, Visco, AG, Havrilesky, LJ, and Wu, JM. "Cost-minimization analysis of robotic-assisted, laparoscopic, and abdominal sacrocolpopexy." J Minim Invasive Gynecol 17.4 (July 2010): 493-499.
PMID
20621010
Source
pubmed
Published In
Journal of Minimally Invasive Gynecology
Volume
17
Issue
4
Publish Date
2010
Start Page
493
End Page
499
DOI
10.1016/j.jmig.2010.03.011

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

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

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

Evaluation of two management strategies for preoperative grade 1 endometrial cancer.

OBJECTIVE: To compare the practices, adjuvant treatment, and outcomes of patients with preoperatively assessed grade 1 endometrioid endometrial cancer between two academic gynecologic oncology centers that use different treatment strategies. METHODS: A retrospective analysis was performed at Duke University Medical Center (Duke) and the Toronto Sunnybrook Regional Cancer Center (Sunnybrook) between 1991 and 2007. Patients at Duke generally underwent surgical staging unless intraoperative assessment identified a negligible risk of nodal disease. Patients at Sunnybrook generally did not undergo surgical staging. RESULTS: A total of 494 patients (272 from Duke and 222 from Sunnybrook were identified with preoperative, central-review-confirming, grade 1, endometrioid, endometrial cancer. Groups were similar in grade, final histology, type of hysterectomy, and length of hospital stay. Patients from Sunnybrook were older (aged 62 years compared with 59 years, P=.001) and were more likely to have capillary lymphatic space involvement (18.2% compared with 8.3%, P=.003) and cervical involvement (12.2% compared with 3.7%, P<.001). Approximately 2% of cases were upgraded to high grade on final specimen. Lymphadenectomy was performed on 49.4% of patients at Duke compared with 11.7% of patients at Sunnybrook. Overall 3-year survival was 96% at Duke and 96% at Sunnybrook (P=.217). Three-year recurrence-free survival was 96% at Duke and 95% at Sunnybrook (P=.327). CONCLUSION: Despite differences in practice and slight differences in patient populations, the recurrence-free and overall survival of women with preoperative centrally reviewed grade 1 endometrial cancer is excellent and without statistically significant difference between the two centers. LEVEL OF EVIDENCE: III

Authors
Bernardini, MQ; May, T; Khalifa, MA; Bland, AE; Nofech-Mozes, S; Berchuck, A; Covens, A; Havrilesky, L
MLA Citation
Bernardini, MQ, May, T, Khalifa, MA, Bland, AE, Nofech-Mozes, S, Berchuck, A, Covens, A, and Havrilesky, L. "Evaluation of two management strategies for preoperative grade 1 endometrial cancer." Obstet Gynecol 114.1 (July 2009): 7-15.
PMID
19546752
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
114
Issue
1
Publish Date
2009
Start Page
7
End Page
15
DOI
10.1097/AOG.0b013e3181aa97fc

Cost-effectiveness analysis of annual screening strategies for endometrial cancer.

OBJECTIVE: The objective of the study was to determine the cost-effectiveness of annual screening tests for endometrial cancer. STUDY DESIGN: Markov state transition model of the natural history of endometrial cancer used as the design for the study. Incidence was modeled for the general population and high risk groups (obese, body mass index [BMI] of >or= 30 kg/m(2); tamoxifen users). Strategies evaluated were no screening, annual endometrial biopsy, annual endovaginal ultrasound, and annual serum screening. Serum screening was based on a recently described biomarker panel (sensitivity of 0.98, specificity of 0.98). RESULTS: In the general population model, no screening was least expensive, whereas annual serum screening age at 50-75 years had incremental cost-effectiveness ratio (ICER) of $60,363 per year of life saved (YLS) compared with no screening. In a high-risk population (obesity, BMI of >or= 30 kg/m(2)), annual serum screening at age 45-80 years had ICER of $41,226 per YLS compared with no screening. Annual endometrial biopsy and annual transvaginal ultrasound were dominated. CONCLUSION: Annual serum screening for endometrial cancer has the potential to be cost effective when applied to high-risk populations.

Authors
Havrilesky, LJ; Maxwell, GL; Myers, ER
MLA Citation
Havrilesky, LJ, Maxwell, GL, and Myers, ER. "Cost-effectiveness analysis of annual screening strategies for endometrial cancer." Am J Obstet Gynecol 200.6 (June 2009): 640.e1-640.e8.
PMID
19380121
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
200
Issue
6
Publish Date
2009
Start Page
640.e1
End Page
640.e8
DOI
10.1016/j.ajog.2009.02.022

Platinum/taxane-based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma.

BACKGROUND: A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients. METHODS: A retrospective, multi-institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (OBS); radiotherapy alone (RT); or platinum/taxane-based chemotherapy (CT) +/- RT. RESULTS: The authors identified 142 patients with a median follow-up of 37 months (range, 7-144 months). Thirty-three patients were observed, 20 received RT alone, and 89 received CT +/- RT. Twenty-five recurrences (17.6%) were diagnosed, and 60% were extrapelvic. Chemotherapy-treated patients experienced significantly fewer recurrences than those treated without chemotherapy (P = .013). Specifically, CT +/- RT patients had a lower risk of recurrence (11.2%) compared with patients who received RT alone (25%, P = .146) or OBS (30.3%, P = .016). This effect was most pronounced in stage IB/IC (P = .007). CT- and CT + RT-treated patients experienced similar recurrence. After multivariate analysis, treatment with chemotherapy was associated with a decreased risk of recurrence (P = .047). The majority of recurrences (88%) were not salvageable. Progression-free survival (PFS) and cause-specific survival (CSS) for chemotherapy-treated patients were more favorable than for those who did not receive chemotherapy (P = .013 and .081). Five-year PFS and CSS rates were 81.5% and 87.6% in CT +/- RT, 64.1% and 59.5% in RT alone, and 64.7% and 70.2% for OBS. CONCLUSIONS: Stage I UPSC patients have significant risk for extrapelvic recurrence and poor survival. Recurrence and survival outcomes are improved in well-staged patients treated with platinum/taxane-based chemotherapy. This multi-institutional study is the largest to support systemic therapy for early stage UPSC patients.

Authors
Fader, AN; Drake, RD; O'Malley, DM; Gibbons, HE; Huh, WK; Havrilesky, LJ; Gehrig, PA; Tuller, E; Axtell, AE; Zanotti, KM; Uterine Papillary Serous Carcinoma (UPSC) Consortium,
MLA Citation
Fader, AN, Drake, RD, O'Malley, DM, Gibbons, HE, Huh, WK, Havrilesky, LJ, Gehrig, PA, Tuller, E, Axtell, AE, Zanotti, KM, and Uterine Papillary Serous Carcinoma (UPSC) Consortium, . "Platinum/taxane-based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma." Cancer 115.10 (May 15, 2009): 2119-2127.
PMID
19306417
Source
pubmed
Published In
Cancer
Volume
115
Issue
10
Publish Date
2009
Start Page
2119
End Page
2127
DOI
10.1002/cncr.24247

Determination of quality of life-related utilities for health states relevant to ovarian cancer diagnosis and treatment.

OBJECTIVES: (1) To define a set of health state descriptions related to screening, diagnosis, prognosis, and toxicities relevant to ovarian cancer; (2) To derive a set of quality of life-related utilities to be used for cost-effectiveness analyses. METHODS: A comprehensive list of health states was developed to represent the experiences of diagnostic testing for ovarian cancer, natural history of ovarian cancer (e.g., newly diagnosed early stage ovarian cancer, recurrent progressive ovarian cancer) and the most common chemotherapy-related toxicities (e.g. alopecia, peripheral neuropathy, pain, neutropenia, fatigue). Valuation of each health state was obtained through individual interviews of 13 ovarian cancer patients and 37 female members of the general public. Interviews employed visual analog score (VAS) and time trade off (TTO) methods of health state valuation. RESULTS: Mean TTO-derived utilities were higher than VAS-derived utilities by 0.118 U (p<0.0001). Mean VAS-derived utilities for screening tests were 0.83 and 0.81 for true negative blood test and ultrasound; 0.79 and 0.78 for false negative blood test and ultrasound, respectively. Patients and volunteers generally agreed in their preference ranking of chemotherapy-associated states, with lowest rankings being given to febrile neutropenia, grades 3-4 fatigue, and grades 3-4 nausea/vomiting. For 55% of chemotherapy-associated health states, the average utility assigned was higher for patients than for volunteers. CONCLUSIONS: This study establishes societal preferences for a number of health states related to screening, diagnosis and treatment of ovarian cancer that can be used for assessing the cost-effectiveness of different ovarian cancer screening and treatment regimens.

Authors
Havrilesky, LJ; Broadwater, G; Davis, DM; Nolte, KC; Barnett, JC; Myers, ER; Kulasingam, S
MLA Citation
Havrilesky, LJ, Broadwater, G, Davis, DM, Nolte, KC, Barnett, JC, Myers, ER, and Kulasingam, S. "Determination of quality of life-related utilities for health states relevant to ovarian cancer diagnosis and treatment." Gynecol Oncol 113.2 (May 2009): 216-220.
PMID
19217148
Source
pubmed
Published In
Gynecologic Oncology
Volume
113
Issue
2
Publish Date
2009
Start Page
216
End Page
220
DOI
10.1016/j.ygyno.2008.12.026

Cost-effectiveness of botulinum toxin a versus anticholinergic medications for idiopathic urge incontinence.

PURPOSE: We assessed the cost-effectiveness of botulinum toxin A injection compared to anticholinergic medications for the treatment of idiopathic urge incontinence. MATERIALS AND METHODS: A Markov decision analysis model was developed to compare the costs in 2008 U. S. dollars and effectiveness in quality adjusted life-years of botulinum toxin A injection and anticholinergic medications. The analysis was conducted from a societal perspective with a 2-year time frame using 3-month cycles. The primary outcome was the incremental cost-effectiveness ratio, defined as the difference in cost (botulinum toxin A cost--anticholinergic cost) divided by the difference in effectiveness (botulinum toxin A quality adjusted life-years--anticholinergic quality adjusted life-years). RESULTS: While the botulinum strategy was more expensive ($4,392 vs $2,563) it was also more effective (1.63 vs 1.50 quality adjusted life-years) compared to the anticholinergic regimen. The calculated incremental cost-effectiveness ratio was $14,377 per quality adjusted life-year, meaning that botulinum toxin A cost $14,377 per quality adjusted life-year gained. A strategy is often considered cost-effective when the incremental cost-effectiveness ratio is less than $50,000 per quality adjusted life-year. Given this definition botulinum toxin A is cost-effective compared to anticholinergics. To determine if there are situations in which anticholinergics would become cost-effective we performed sensitivity analyses. Anticholinergics become cost-effective if compliance exceeds 75% (33% in the base case) and if the botulinum toxin A procedure cost exceeds $3,875 ($1,690 in the base case). For the remainder of the sensitivity analyses botulinum toxin A remained cost-effective. CONCLUSIONS: Botulinum toxin A injection was cost-effective compared to anticholinergic medications for the treatment of refractory urge incontinence. Anticholinergics become cost-effective if patients are highly compliant with medications or if the botulinum procedure costs increase substantially.

Authors
Wu, JM; Siddiqui, NY; Amundsen, CL; Myers, ER; Havrilesky, LJ; Visco, AG
MLA Citation
Wu, JM, Siddiqui, NY, Amundsen, CL, Myers, ER, Havrilesky, LJ, and Visco, AG. "Cost-effectiveness of botulinum toxin a versus anticholinergic medications for idiopathic urge incontinence." J Urol 181.5 (May 2009): 2181-2186.
PMID
19296983
Source
pubmed
Published In
The Journal of Urology
Volume
181
Issue
5
Publish Date
2009
Start Page
2181
End Page
2186
DOI
10.1016/j.juro.2009.01.037

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

Cost effectiveness of a test to detect metastases for endometrial cancer.

OBJECTIVE: To estimate the potential cost-effectiveness of a hypothetical test to screen for lymph node metastases in women with newly diagnosed, apparent early stage endometrial cancer. METHODS: A decision model was constructed to inform a choice between the following strategies: (1) Usual care, in which the probability of undergoing full surgical staging (29%) is based on literature review; (2) Non-invasive diagnostic testing for metastasis (Testing), in which patients with abnormal test results undergo full surgical staging; (3) 100% referral, in which all patients are referred for full surgical staging. Survival was modeled using Surveillance Epidemiology and End Results (SEER) database. Base case diagnostic test characteristic estimates (sensitivity 0.90, specificity 0.90) were varied for sensitivity analysis. Cost of the diagnostic test was set at $500 and varied; costs of treatment for endometrial cancer (surgery, adjuvant therapies, diagnosis of recurrence, salvage therapies and palliative care) were incorporated. RESULTS: Usual care was the least expensive strategy, while Testing was more expensive and more effective, with an incremental cost-effectiveness ratio (ICER) of $18,785 per year of life saved (YLS) compared to Usual care. 100% referral was the most expensive and most effective strategy, with an ICER of $35,358 per YLS compared to Testing. Results are relatively sensitive to variation in test characteristics and the cost of the diagnostic test but insensitive to cost of treatment and probability of adjuvant therapies. Testing remains cost-effective compared to Usual care unless the usual rate of referral to a Gynecologic Oncologist for full staging exceeds 90%. CONCLUSIONS: Given the current low rates of full surgical staging and/or referral to a Gynecologic Oncologist, a diagnostic test to detect nodal metastasis for endometrial cancer has potential to be cost-effective when compared to usual care. Testing is also potentially cost-effective compared to 100% referral at very high test sensitivities and at the lower range of test costs.

Authors
Havrilesky, LJ; Maxwell, GL; Chan, JK; Myers, ER
MLA Citation
Havrilesky, LJ, Maxwell, GL, Chan, JK, and Myers, ER. "Cost effectiveness of a test to detect metastases for endometrial cancer." Gynecol Oncol 112.3 (March 2009): 526-530.
PMID
19100608
Source
pubmed
Published In
Gynecologic Oncology
Volume
112
Issue
3
Publish Date
2009
Start Page
526
End Page
530
DOI
10.1016/j.ygyno.2008.11.017

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

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

Reducing ovarian cancer mortality through screening: Is it possible, and can we afford it?

OBJECTIVE: Ovarian cancer is a leading cause of cancer-related deaths among women. Given the low prevalence of this disease, the effectiveness of screening strategies has not been established. We wished to estimate the clinical impact and cost-effectiveness of potential screening strategies for ovarian cancer using population-specific data. METHODS: A Markov state transition model to simulate the natural history of ovarian cancer in a cohort of women age 20 to 100. Age-specific incidence and mortality rates were obtained from SEER. Base-case characteristics of a potential screening test were sensitivity 85%, specificity 95%, and cost $50. Outcome measures were mortality reduction, lifetime number of false positive screening tests, positive predictive value, years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (ICER, in cost/YLS). RESULTS: Model-predicted lifetime risk of ovarian cancer (1.38%), lifetime risk of death from ovarian cancer (0.95%), and stage distribution (stage I-19%; stage II-7%; stage III, IV, or unstaged - 74%) closely approximated SEER data. Annual screening resulted in 43% reduction in ovarian cancer mortality, with ICER of $73,469/YLS (base case) and $36,025/YLS (high-risk population) compared to no screening. In the base case, the average lifetime number of false positive tests is 1.06. Cost-effectiveness of screening is most sensitive to test frequency, specificity and cost. CONCLUSIONS: Annual screening for ovarian cancer has the potential to be cost effective, particularly in high-risk populations. Clinically acceptable positive predictive values are achieved if specificity exceeds 99%. Mortality reduction above 50% may not be achievable without screening intervals less than 12 months.

Authors
Havrilesky, LJ; Sanders, GD; Kulasingam, S; Myers, ER
MLA Citation
Havrilesky, LJ, Sanders, GD, Kulasingam, S, and Myers, ER. "Reducing ovarian cancer mortality through screening: Is it possible, and can we afford it?." Gynecol Oncol 111.2 (November 2008): 179-187.
PMID
18722004
Source
pubmed
Published In
Gynecologic Oncology
Volume
111
Issue
2
Publish Date
2008
Start Page
179
End Page
187
DOI
10.1016/j.ygyno.2008.07.006

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

Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence.

OBJECTIVE: To determine the utility of novel combinations of biomarkers, using both a one-step and two-step assay format, to distinguish serum of early ovarian cancer patients from that of healthy controls and to discern the utility of these biomarkers in a monitoring capacity. METHODS: For ovarian cancer detection, HE4, Glycodelin, MMP7, SLPI, Plau-R, MUC1, Inhibin A, PAI-1, and CA125 were evaluated in a cohort of 200 women with ovarian cancer and 396 healthy age-matched controls. Each biomarker was assessed by serum-based immunoassays utilizing novel monoclonal antibody pairs or commercial kits. For detection of disease recurrence, HE4, Glycodelin, MMP7 and CA125 were evaluated in 260 samples from 30 patients with OC monitored longitudinally after diagnosis. RESULTS: Based upon ROC curve analysis, the sensitivity/specificity of specific biomarker combination algorithms ranged from 59.0%/99.7% to 80.5%/96.5% for detection of early stage ovarian cancer and 76.9%/99.7% to 89.2%/97.2% for detection of late stage cancer. In monitoring evaluation of 27 patients who experienced recurrence of OC, sensitivity for predicting recurrence was 100% for the biomarker panel and 96% for CA125. At least one of the panel biomarkers was elevated earlier (range 6-69 weeks) than CA125 and prior to clinical evidence of recurrence in 14/27 (52%) patients. CONCLUSIONS: We have developed and demonstrated the utility of several one- and two-step multi-marker combinations with acceptable test characteristics for possible use in an ovarian cancer screening population. A subset of this panel may also provide adjunctive information to rising CA125 levels in disease monitoring.

Authors
Havrilesky, LJ; Whitehead, CM; Rubatt, JM; Cheek, RL; Groelke, J; He, Q; Malinowski, DP; Fischer, TJ; Berchuck, A
MLA Citation
Havrilesky, LJ, Whitehead, CM, Rubatt, JM, Cheek, RL, Groelke, J, He, Q, Malinowski, DP, Fischer, TJ, and Berchuck, A. "Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence." Gynecol Oncol 110.3 (September 2008): 374-382.
PMID
18584856
Source
pubmed
Published In
Gynecologic Oncology
Volume
110
Issue
3
Publish Date
2008
Start Page
374
End Page
382
DOI
10.1016/j.ygyno.2008.04.041

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

Endometrial cancer: multiplexed Luminex approaches for early detection.

BACKGROUND: Endometrial carcinoma is the most common gynecologic cancer. Despite the advances that have been made in other cancers, both the annual incidence of and the death rate associated with endometrial cancer appear to be rising, both in the US and around the world. In the US, ∼ 41,000 cases are diagnosed and about 7000 women die from the disease each year. Adenocarcinoma, which originates in surface cells of the endometrium, accounts for ∼ 90% of cases of endometrial cancer. At this time, there are no early detection tests or exams that can find endometrial cancer early in women without symptoms. OBJECTIVE: There is growing interest in the use of biomarker approaches for the early detection of endometrial cancer. Endometrial cancer has been linked to altered growth factor signaling, immune inflammatory responses and angiogenesis. This article provides an overview of endometrial cancer and outlines the rationale and need for the clinical application of multiplexed ELISA-based assays for the early detection of cancer. Although endometrial cancer has a generally favorable long-term outcome, its screening and diagnosis pose a challenge in women without symptoms. METHOD: An extensive literature review of biomarker approaches to endometrial cancer detection has been performed. Also, several studies conducted by the present team at the University of Pittsburgh Cancer Institute were reviewed. CONCLUSION: In the authors' published studies, it was hypothesized that an expanded panel of biomarkers comprised of cytokines, chemokines, growth factors and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination, especially in the case of endometrial cancer detection. It was also discovered that prolactin may be very important for endometrial cancer detection. In this article, the potential clinical role for using multimarker testing in the early detection of endometrial cancer and for tumor surveillance to permit early identification of recurrence in patients with recurrent disease is discussed. Additionally, the role of lifestyle factors in the endometrial cancer development and prevention is discussed.

Authors
Linkov, F; Yurkovetsky, Z; Taioli, E; Havrilesky, LJ; Maxwell, GL; Lokshin, A
MLA Citation
Linkov, F, Yurkovetsky, Z, Taioli, E, Havrilesky, LJ, Maxwell, GL, and Lokshin, A. "Endometrial cancer: multiplexed Luminex approaches for early detection." Expert Opin Med Diagn 2.5 (May 2008): 527-537.
PMID
23495741
Source
pubmed
Published In
Expert Opinion on Medical Diagnostics
Volume
2
Issue
5
Publish Date
2008
Start Page
527
End Page
537
DOI
10.1517/17530059.2.5.527

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
Biomark Insights
Volume
3
Publish Date
2008
Start Page
45
End Page
55

Ovarian cancer

Authors
Jr, RJM; Alvarez, RD; Armstrong, DK; Boston, B; Chen, L-M; Copeland, L; Fowler, J; Gaffney, DK; Gershenson, D; Greer, BE; Grigsby, PW; Havrilesky, LJ; Johnston, C; Lancaster, JM; Lele, S; Matulonis, U; O'Malley, D; Ozols, RF; Remmenga, SW; Sabbatini, P; Schink, J; Teng, N
MLA Citation
Jr, RJM, Alvarez, RD, Armstrong, DK, Boston, B, Chen, L-M, Copeland, L, Fowler, J, Gaffney, DK, Gershenson, D, Greer, BE, Grigsby, PW, Havrilesky, LJ, Johnston, C, Lancaster, JM, Lele, S, Matulonis, U, O'Malley, D, Ozols, RF, Remmenga, SW, Sabbatini, P, Schink, J, and Teng, N. "Ovarian cancer." JNCCN Journal of the National Comprehensive Cancer Network 6.8 (2008): 766-794.
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
8
Publish Date
2008
Start Page
766
End Page
794

Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer.

OBJECTIVE: Currently available tumor markers for ovarian cancer are still inadequate in both sensitivity and specificity to be used for population-based screening. Artificial neural network (ANN) as a modeling tool has demonstrated its ability to assimilate information from multiple sources and to detect subtle and complex patterns. In this paper, an ANN model was evaluated for its performance in detecting early stage epithelial ovarian cancer using multiple serum markers. METHODS: Serum specimens collected at four institutions in the US, The Netherlands and the United Kingdom were analyzed for CA 125II, CA 72-4, CA 15-3 and macrophage colony stimulating factor (M-CSF). The four tumor marker values were then used as inputs to an ANN derived using a training set from 100 apparently healthy women, 45 women with benign conditions arising from the ovary and 55 invasive epithelial ovarian cancer patients (including 27 stage I/II cases). A separate validation set from 27 apparently healthy women, 56 women with benign conditions and 35 women with various types of malignant pelvic masses was used to monitor the ANN's performance during training. An independent test data set from 98 apparently healthy women and 52 early stage epithelial ovarian cancer patients (38 stage I and 4 stage II invasive cases and 10 stage I borderline ovarian tumor cases) was used to evaluate the ANN. RESULTS: ROC analysis confirmed the overall superiority of the ANN-derived composite index over CA 125II alone (p=0.0333). At a fixed specificity of 98%, the sensitivities for ANN and CA 125II alone were 71% (37/52) and 46% (24/52) (p=0.047), respectively, for detecting early stage epithelial ovarian cancer, and 71% (30/42) and 43% (18/42) (p=0.040), respectively, for detecting invasive early stage epithelial ovarian cancer. CONCLUSIONS: The combined use of multiple tumor markers through an ANN improves the overall accuracy to discern healthy women from patients with early stage ovarian cancer. Analysis of multiple markers with an ANN may be a better choice than the use of CA 125II alone in a two-step approach for population screening in which a secondary test such as ultrasound is used to keep the overall specificity at an acceptable level.

Authors
Zhang, Z; Yu, Y; Xu, F; Berchuck, A; van Haaften-Day, C; Havrilesky, LJ; de Bruijn, HWA; van der Zee, AGJ; Woolas, RP; Jacobs, IJ; Skates, S; Chan, DW; Bast, RC
MLA Citation
Zhang, Z, Yu, Y, Xu, F, Berchuck, A, van Haaften-Day, C, Havrilesky, LJ, de Bruijn, HWA, van der Zee, AGJ, Woolas, RP, Jacobs, IJ, Skates, S, Chan, DW, and Bast, RC. "Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer." Gynecol Oncol 107.3 (December 2007): 526-531.
PMID
17920110
Source
pubmed
Published In
Gynecologic Oncology
Volume
107
Issue
3
Publish Date
2007
Start Page
526
End Page
531
DOI
10.1016/j.ygyno.2007.08.009

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

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

Clinical and pathologic correlates in surgical stage II endometrial carcinoma.

OBJECTIVE: To identify the surgical, pathologic, and therapeutic factors that influence outcome in patients with surgical stage II endometrial adenocarcinoma. METHODS: All patients with comprehensively staged stage II endometrial adenocarcinoma were identified. Data regarding preoperative, surgical, pathologic, adjuvant therapy, and outcomes were collected. Factors were compared with the chi(2) test, and survival curves were generated and compared with the log rank test. RESULTS: Of 162 patients with surgical stage II endometrial cancer, the median age was 65 years, and the median body mass index was 31.2 kg/m(2). An extrafascial hysterectomy was performed in 75% of cases, whereas 25% of patients underwent radical hysterectomy. At least 10 nodes were recovered in more than 90% of cases. Stage IIA disease was present in 52% of cases, whereas stage IIB accounted for the remaining 48%. After staging, 48% of patients had adjuvant radiation therapy (16% with brachytherapy alone). The remainder received no adjuvant therapy. At a median follow-up of 26 months, 17% experienced disease recurrence. Five-year overall survival rate was 88% and disease-free survival rate was 81%. A significantly better 5-year disease-free survival rate was seen in patients undergoing radical hysterectomy compared with extrafascial hysterectomy (94% compared with 76%, P=.05). Adjuvant radiation did not lead to improved survival. CONCLUSION: In this large series of surgical stage II endometrial cancer cases, improved survival was noted relative to historical controls and in particular with radical compared with extrafascial hysterectomy.

Authors
Cohn, DE; Woeste, EM; Cacchio, S; Zanagnolo, VL; Havrilesky, LJ; Mariani, A; Podratz, KC; Huh, WK; Whitworth, JM; McMeekin, DS; Powell, MA; Boyd, E; Phillips, GS; Fowler, JM
MLA Citation
Cohn, DE, Woeste, EM, Cacchio, S, Zanagnolo, VL, Havrilesky, LJ, Mariani, A, Podratz, KC, Huh, WK, Whitworth, JM, McMeekin, DS, Powell, MA, Boyd, E, Phillips, GS, and Fowler, JM. "Clinical and pathologic correlates in surgical stage II endometrial carcinoma." Obstet Gynecol 109.5 (May 2007): 1062-1067.
PMID
17470583
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
109
Issue
5
Publish Date
2007
Start Page
1062
End Page
1067
DOI
10.1097/01.AOG.0000260871.87607.25

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

Genomic tests for ovarian cancer detection and management.

OBJECTIVES: To assess the evidence that the use of genomic tests for ovarian cancer screening, diagnosis, and treatment leads to improved outcomes. DATA SOURCES: PubMed and reference lists of recent reviews. REVIEW METHODS: We evaluated tests for: (a) single gene products; (b) genetic variations affecting risk of ovarian cancer; (c) gene expression; and (d) proteomics. For tests covered in recent evidence reports (cancer antigen 125 [CA-125] and breast cancer genes 1 and 2 [BRCA1/2]), we added studies published subsequent to the reports. We sought evidence on: (a) the analytic performance of tests in clinical laboratories; (b) the sensitivity and specificity of tests in different patient populations; (c) the clinical impact of testing in asymptomatic women, women with suspected ovarian cancer, and women with diagnosed ovarian cancer; (d) the harms of genomic testing; and (e) the impact of direct-to-consumer and direct-to-physician advertising on appropriate use of tests. We also constructed a computer simulation model to test the impact of different assumptions about ovarian cancer natural history on the relative effectiveness of different strategies. RESULTS: There are reasonable data on the clinical laboratory performance of most radioimmunoassays, but the majority of the data on other genomic tests comes from research laboratories. Genomic test sensitivity/specificity estimates are limited by small sample sizes, spectrum bias, and unrealistically large prevalences of ovarian cancer; in particular, estimates of positive predictive values derived from most of the studies are substantially higher than would be expected in most screening or diagnostic settings. We found no evidence relevant to the question of the impact of genomic tests on health outcomes in asymptomatic women. Although there is a relatively large literature on the association of test results and various clinical outcomes, the clinical utility of changing management based on these results has not been evaluated. We found no evidence that genomic tests for ovarian cancer have unique harms beyond those common to other tests for genetic susceptibility or other tests used in screening, diagnosis, and management of ovarian cancer. Studies of a direct-to-consumer campaign for BRCA1/2 testing suggest increased utilization, but the effect on "appropriateness" was unclear. Model simulations suggest that annual screening, even with a highly sensitive test, will not reduce ovarian cancer mortality by more than 50 percent; frequent screening has a very low positive predictive value, even with a highly specific test. CONCLUSIONS: Although research remains promising, adaptation of genomic tests into clinical practice must await appropriately designed and powered studies in relevant clinical settings.

Authors
Myers, ER; Havrilesky, LJ; Kulasingam, SL; Sanders, GD; Cline, KE; Gray, RN; Berchuck, A; McCrory, DC
MLA Citation
Myers, ER, Havrilesky, LJ, Kulasingam, SL, Sanders, GD, Cline, KE, Gray, RN, Berchuck, A, and McCrory, DC. "Genomic tests for ovarian cancer detection and management." Evid Rep Technol Assess (Full Rep) 145 (October 2006): 1-100. (Review)
PMID
17764207
Source
pubmed
Published In
Evidence report/technology assessment
Issue
145
Publish Date
2006
Start Page
1
End Page
100

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

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

Management of adnexal mass.

OBJECTIVES: To assess diagnostic strategies for distinguishing benign from malignant adnexal masses. DATA SOURCES: MEDLINE(R) and reference lists of recent reviews; discharge data from the Nationwide Inpatient Sample. REVIEW METHODS: The major diagnostic methods evaluated were bimanual pelvic examination, ultrasound (morphology and Doppler velocimetry), MRI, CT, FDG-PET, CA-125, and scoring systems that incorporated multiple clinical, laboratory, and radiologic findings. Meta-analysis using a random-effects model was used to estimate pooled sensitivity and specificity for discriminating benign from malignant. We reviewed evidence for followup strategies for masses considered benign, and for adverse outcomes of diagnostic surgery. We also reviewed published models of the natural history of ovarian cancer and compared the impact of assumptions about natural history on outcomes. RESULTS: The majority of studies did not describe whether patients presented with asymptomatic masses detected through screening or with symptoms. Prevalence of malignant masses in a U.S. postmenopausal screening population was approximately 0.1 percent, while benign masses were found in 0.8 to 1.8 percent of women. Pooled (a) sensitivity and (b) specificity were: bimanual exam (a) 0.45, (b) 0.90; ultrasound morphology scores (a) 0.86 to 0.91, (b) 0.68 to 0.83; Doppler resistive index (a) 0.72, (b) 0.90; pulsatility index (a) 0.80, (b) 0.73; maximum systolic velocity (a) 0.74, (b) 0.81; presence of vessels (a) 0.88, (b) 0.78; combined morphology and Doppler (a) 0.86, (b) 0.91; MRI (a) 0.91, (b) 0.88; CT (a) 0.90, (b) 0.75; FDG-PET (a) 0.67, (b) 0.79; and CA-125 (a) 0.78, (b) 0.78. Both sensitivity and specificity of CA-125 were better in postmenopausal than in premenopausal women. In modeled outcomes, combinations of imaging and CA-125 were both more sensitive and more specific than either alone. Performance of scoring systems in validation studies was consistently worse than in development studies; the highest demonstrated specificity observed was 0.91, with a concurrent sensitivity of 0.74. Evidence on followup strategies was sparse, although one large study provided good evidence for safely following unilocular cysts less than 10 cm in diameter. Overall complication rates in studies of surgically managed adnexal masses were low, but important clinical information was not reported. CONCLUSIONS: All diagnostic modalities showed trade-offs between sensitivity and specificity, but the available literature does not provide sufficient detail on relevant characteristics of study populations to allow confident estimation of the results of alternative diagnostic strategies. Although modeling studies may prove useful in evaluating diagnostic algorithms, further work is needed to explore the implications of uncertainty about the natural history of ovarian cancer.

Authors
Myers, ER; Bastian, LA; Havrilesky, LJ; Kulasingam, SL; Terplan, MS; Cline, KE; Gray, RN; McCrory, DC
MLA Citation
Myers, ER, Bastian, LA, Havrilesky, LJ, Kulasingam, SL, Terplan, MS, Cline, KE, Gray, RN, and McCrory, DC. "Management of adnexal mass." Evid Rep Technol Assess (Full Rep) 130 (February 2006): 1-145. (Review)
PMID
17854238
Source
pubmed
Published In
Evidence report/technology assessment
Issue
130
Publish Date
2006
Start Page
1
End Page
145

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

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

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

FDG-PET for management of cervical and ovarian cancer.

OBJECTIVE: To assess the diagnostic performance of Positron Emission Tomography using fluorodeoxyglucose (FDG-PET) in comparison to conventional imaging modalities in the assessment of patients with cervical and ovarian cancer. METHODS: Studies published between 1966 and 2003 were identified using an OVID search of the MEDLINE database. Inclusion criteria were use of a dedicated scanner, resolution specified, >/=12 human subjects, clinical follow-up >/=6 months or histopathology as reference standard, and sufficient data provided to construct a two-by-two table. Two reviewers independently abstracted data regarding sensitivity and specificity of PET. RESULTS: 25 studies (15 cervical cancer, 10 ovarian cancer) met inclusion criteria for full text review. For cervical cancer, pooled sensitivity and specificity of PET for aortic node metastasis are 0.84 (95% CI 0.68-0.94) and 0.95 (0.89-0.98). Pooled sensitivity and specificity for detection of pelvic node metastasis are: PET, 0.79 (0.65-0.90) and 0.99 (0.96-0.99); MRI, 0.72 (0.53-0.87) and 0.96 (0.92-0.98). Pooled sensitivity for CT is 0.47 (0.21-0.73) (pooled specificity not available). Pooled sensitivity and specificity of PET for recurrent cervical cancer with clinical suspicion are 0.96 (0.87-0.99) and 0.81 (0.58-0.94). For ovarian cancer, pooled sensitivity and specificity to detect recurrence with clinical suspicion are: PET, 0.90 (0.82-0.95) and 0.86 (0.67-0.96); conventional imaging, 0.68 (0.49-0.83) and 0.58 (0.33-0.80); CA-125, 0.81 (0.62-0.92) and 0.83 (0.58-0.96). When conventional imaging and CA-125 are negative, pooled sensitivity and specificity of PET are 0.54 (0.39-0.69) and 0.73 (0.56-0.87), respectively. When CA-125 is rising and conventional imaging is negative, the pooled sensitivity and specificity of PET are 0.96 (0.88-0.99) and 0.80 (0.44-0.97). CONCLUSIONS: There is good evidence that PET is useful for the pre-treatment detection of retroperitoneal nodal metastasis in cervical cancer. There is fair evidence that PET is useful for the detection of recurrent cervical cancer. PET is less useful for the detection of microscopic residual ovarian cancer but has fair sensitivity to detect recurrence in the setting of a rising CA-125 and negative conventional imaging studies. Available studies are limited by low numbers of patients and wide confidence intervals.

Authors
Havrilesky, LJ; Kulasingam, SL; Matchar, DB; Myers, ER
MLA Citation
Havrilesky, LJ, Kulasingam, SL, Matchar, DB, and Myers, ER. "FDG-PET for management of cervical and ovarian cancer." Gynecol Oncol 97.1 (April 2005): 183-191.
PMID
15790456
Source
pubmed
Published In
Gynecologic Oncology
Volume
97
Issue
1
Publish Date
2005
Start Page
183
End Page
191
DOI
10.1016/j.ygyno.2004.12.007

Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions.

PURPOSE: In CA-125-based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only 40%. This study aims to increase preoperative sensitivity for early-stage ovarian cancer while maintaining the annual referral rate to ultrasound at 2% by combining information across CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor (M-CSF). For direct comparisons between marker panels, all sensitivity results correspond to a 98% fixed first-line specificity (referral rate 2%). PATIENTS AND METHODS: Logistic regression, classification tree, and mixture discriminant analysis (MDA) models were fit to a training data set of preoperative serum measurements (63 patients, 126 healthy controls) from one center. Estimates from the training set applied to an independent validation set (60 stage I to II patients, 98 healthy controls) from two other centers provided unbiased estimates of sensitivity. RESULTS: Preoperative sensitivities for early-stage disease of the optimal panels were 45% for CA-125II; 67% for CA-125II and CA 72-4; 70% for CA-125II, CA 72-4, and M-CSF; and 68% for all four markers (latter two results using MDA). CONCLUSION: Efficiently combining information on CA-125II, CA 72-4, and M-CSF significantly increased preoperative early-stage sensitivity from 45% with CA-125II alone to 70%, while maintaining 98% first-line specificity. Screening trials with these markers using MDA followed by referral to ultrasound may maintain previously high levels of specificity and PPV, while significantly increasing early-stage screening sensitivity. MDA is a useful, biologically justified method for combining biomarkers.

Authors
Skates, SJ; Horick, N; Yu, Y; Xu, F-J; Berchuck, A; Havrilesky, LJ; de Bruijn, HWA; van der Zee, AGJ; Woolas, RP; Jacobs, IJ; Zhang, Z; Bast, RC
MLA Citation
Skates, SJ, Horick, N, Yu, Y, Xu, F-J, Berchuck, A, Havrilesky, LJ, de Bruijn, HWA, van der Zee, AGJ, Woolas, RP, Jacobs, IJ, Zhang, Z, and Bast, RC. "Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions." J Clin Oncol 22.20 (October 15, 2004): 4059-4066.
PMID
15381683
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
20
Publish Date
2004
Start Page
4059
End Page
4066
DOI
10.1200/JCO.2004.03.091

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

Gene expression patterns that characterize advanced stage serous ovarian cancers.

OBJECTIVE: To identify gene expression patterns that characterize advanced stage serous ovarian cancers by using microarray expression analysis. METHODS: Using genome-wide expression analysis, we compared a series of 31 advanced stage (III or IV) serous ovarian cancers from patients who survived either less than 2 years or more than 7 years with three normal ovarian epithelial samples. Array findings were validated by analysis of expression of the insulin-like growth factor binding protein 2 (IGFBP2) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genes using quantitative real-time polymerase chain reaction (QRT-PCR). RESULTS: Hierarchical clustering identified patterns of gene expression that distinguished cancer from normal ovarian epithelium. We also identified gene expression patterns that distinguish cancers on the basis of patient survival. These genes include many that are associated with immune function. Expression of IGFBP2 and TRAIL genes measured by array and QRT-PCR analysis demonstrated correlation coefficients of 0.63 and 0.78, respectively. CONCLUSION: Global expression analysis can identify expression patterns and individual genes that contribute to ovarian cancer development and outcome. Many of the genes that determine ovarian cancer survival are associated with the immune response, suggesting that immune function influences ovarian cancer virulence. With the generation of newer arrays with more transcripts, larger studies are possible to fully characterize genetic signatures that predict survival that may ultimately be used to guide therapeutic decision-making.

Authors
Lancaster, JM; Dressman, HK; Whitaker, RS; Havrilesky, L; Gray, J; Marks, JR; Nevins, JR; Berchuck, A
MLA Citation
Lancaster, JM, Dressman, HK, Whitaker, RS, Havrilesky, L, Gray, J, Marks, JR, Nevins, JR, and Berchuck, A. "Gene expression patterns that characterize advanced stage serous ovarian cancers." J Soc Gynecol Investig 11.1 (January 2004): 51-59.
PMID
14706684
Source
pubmed
Published In
Journal of the Society for Gynecologic Investigation (Elsevier)
Volume
11
Issue
1
Publish Date
2004
Start Page
51
End Page
59

Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study.

PURPOSE: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol. PATIENTS AND METHODS: Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. RESULTS: There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P =.014) and a 60% reduction in risk of disease progression (P =.014) for women with such mutations. However, these striking risk reductions increased over time (P <.02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome. CONCLUSION: Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome.

Authors
Havrilesky, L; Darcy, KM; Hamdan, H; Priore, RL; Leon, J; Bell, J; Berchuck, A; Gynecologic Oncology Group Study,
MLA Citation
Havrilesky, L, Darcy, KM, Hamdan, H, Priore, RL, Leon, J, Bell, J, Berchuck, A, and Gynecologic Oncology Group Study, . "Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study." J Clin Oncol 21.20 (October 15, 2003): 3814-3825.
PMID
14551300
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
20
Publish Date
2003
Start Page
3814
End Page
3825
DOI
10.1200/JCO.2003.11.052

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

The Genetic Etiology of Sporadic Ovarian Cancer

Epithelial ovarian cancer is known to be the deadliest gynecologic malignancy and is a leading cause of cancer death in women. Genetic alterations disrupt regulation of proliferation, programmed cell death, and senescence thus causing malignant transformation of a normal ovarian epithelial cell. Ovarian cancers exhibit a high degree of genetic disruption significantly evident at both the chromosomal and molecular levels. The vast majority of tumors resulting from the accumulation of genetic damage over the course of a lifetime is referred to as sporadic cancers. This chapter illustrates the genetic etiology of sporadic ovarian cancer. Initial phases of the human genome project have provided the framework for studies that lead to an increase in understanding of the complex ovarian cancer. Significant advances in research can lead to the development of new approaches to early diagnosis, treatment, and prevention that will ultimately decrease ovarian cancer mortality. © 2004 Elsevier Inc. All rights reserved.

Authors
Lancaster, JM; Havrilesky, LJ; Berchuck, A
MLA Citation
Lancaster, JM, Havrilesky, LJ, and Berchuck, A. "The Genetic Etiology of Sporadic Ovarian Cancer." (September 1, 2003): 139-155. (Chapter)
Source
scopus
Publish Date
2003
Start Page
139
End Page
155
DOI
10.1016/B978-012053642-9/50016-8

Predictors of clinical outcomes in the laparoscopic management of adnexal masses.

OBJECTIVE: Laparoscopy has become an accepted approach in the management of adnexal masses. We evaluated clinical outcomes of laparoscopic management of adnexal masses thought to be benign preoperatively. METHODS: We performed a retrospective study of patients undergoing laparoscopic evaluation of adnexal masses over a 7-year period. Regression models evaluated predictors of blood loss, length of stay, complications, mass rupture, conversion to laparotomy, and operating time. Preoperative predictors of malignant and borderline disease were evaluated using a separate model. RESULTS: Complications occurred in 8% of 396 patients undergoing laparoscopic evaluation of adnexal masses and were associated with concurrent hysterectomy (P =.01) and smaller mass (P =.01). Conversion to laparotomy occurred in 25% and was associated with larger mass (P =.001), prior hysterectomy (P =.002), and younger age (P =.002). Mass rupture occurred in 25% and was associated with prior (P <.001) or concurrent (P =.003) hysterectomy and younger age (P =.001). Blood loss greater than 500 mL was associated with concurrent hysterectomy (P <.001). Length of stay was associated with concurrent (P <.001) and prior (P <.001) hysterectomy, larger mass (P =.01), prior abdominal surgery (P =.009), and medical comorbidities (P =.007). Malignancy occurred in 2%, and laparoscopic management was not associated with adverse outcomes. CONCLUSION: Adnexal masses thought to be benign preoperatively were successfully managed laparoscopically in three fourths of cases and clinical outcomes were acceptable. To a great extent, adverse events were attributable to concurrent hysterectomy rather than removal of the adnexal mass.

Authors
Havrilesky, LJ; Peterson, BL; Dryden, DK; Soper, JT; Clarke-Pearson, DL; Berchuck, A
MLA Citation
Havrilesky, LJ, Peterson, BL, Dryden, DK, Soper, JT, Clarke-Pearson, DL, and Berchuck, A. "Predictors of clinical outcomes in the laparoscopic management of adnexal masses." Obstet Gynecol 102.2 (August 2003): 243-251.
PMID
12907095
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
102
Issue
2
Publish Date
2003
Start Page
243
End Page
251

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

OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma: a critical appraisal.

BACKGROUND: Ovarian carcinoma remains the leading cause of death from gynecologic malignancy in Australia, the Netherlands, and the United States. CA-125-II, the most widely used serum marker, has limited sensitivity and specificity for detecting small-volume, early-stage disease. Therefore, a panel of three serum tumor markers-OVX1, CA-125-II, and macrophage-colony stimulating factor (M-CSF)-has been used to evaluate the sensitivity and specificity of multiple markers for the detection of early-stage ovarian carcinoma. METHODS: Preoperative serum levels of OVX1, CA-125-II, and M-CSF were measured in 281 patients with primary ovarian epithelial tumors of different histotypes. Among these tumors, 175 were malignant, 29 were of borderline malignancy, and 77 were benign. The three markers also were measured in sera from 117 apparently healthy women. Marker levels were considered abnormal at CA-125-II > 35 U/mL, OVX1 > 7.2 U/mL, and M-CSF > 3.5 ng/mL. RESULTS: Among 175 women with malignant ovarian tumors, at least one of the three serum markers was elevated in 85%, whereas CA-125-II was elevated in 80% (P = 0.008). In 58 patients with Stage I ovarian carcinoma, at least one of the three serum markers was elevated in 76%, whereas CA-125 levels were elevated in 66% (P = 0.04). For patients with borderline and benign tumors, a combination of the three antigens had slightly higher sensitivity compared with CA-125-II, but the differences were not statistically significant. Among 117 apparently healthy women, CA-125-II was elevated in 4%, and one of the three markers was positive in 17%. CONCLUSIONS: The sensitivity of a combination of three serum markers was significantly greater than the sensitivity of the CA-125-II assay alone in patients with primary ovarian epithelial tumors of different histotypes. This was true for all stages, including early-stage, potentially curable disease. When used as single markers, however, only the CA-125-II assay could distinguish invasive Stage I tumors from apparently healthy women.

Authors
van Haaften-Day, C; Shen, Y; Xu, F; Yu, Y; Berchuck, A; Havrilesky, LJ; de Bruijn, HW; van der Zee, AG; Bast, RC; Hacker, NF
MLA Citation
van Haaften-Day, C, Shen, Y, Xu, F, Yu, Y, Berchuck, A, Havrilesky, LJ, de Bruijn, HW, van der Zee, AG, Bast, RC, and Hacker, NF. "OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma: a critical appraisal." Cancer 92.11 (December 1, 2001): 2837-2844.
PMID
11753957
Source
pubmed
Published In
Cancer
Volume
92
Issue
11
Publish Date
2001
Start Page
2837
End Page
2844

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." Gynecol Oncol 83.3 (December 2001): 491-500.
PMID
11733961
Source
pubmed
Published In
Gynecologic Oncology
Volume
83
Issue
3
Publish Date
2001
Start Page
491
End Page
500
DOI
10.1006/gyno.2001.6464

Relationship between expression of coactivators and corepressors of hormone receptors and resistance of ovarian cancers to growth regulation by steroid hormones.

OBJECTIVE: To determine whether aberrant expression of hormone receptor corepressors or coactivators or defects in estrogen receptor-mediated transcription might underlie resistance of ovarian cancers to hormonal therapy. METHODS: Northern analysis, Western analysis, and polymerase chain reaction were used to examine expression of estrogen receptor (ER), progesterone receptor (PR), the nuclear receptor corepressors N-CoR and SMRT, and the steroid receptor coactivator BRG-1 in ovarian cancer cell lines and primary cancers. The effect of BRG-1 transfection on ER-mediated transcription was examined. We also determined the effect of estrogen and the pure estrogen antagonist ICI 182,780 on cell cycle profile and expression of ER. Finally, we examined the ability of estrogen to upregulate expression of known estrogen-responsive genes. RESULTS: Among primary ovarian cancers, 18 of 52 (35%) expressed N-CoR, and 37 of 52 (71%) expressed SMRT, but there was no correlation between expression of corepressors and hormone receptor status. All of the primary ovarian cancers and cell lines expressed BRG-1. Estrogen stimulation of two cell lines expressing ER (SKOV3, OVCA 432) elicited low levels of ER-mediated transcription that was not enhanced by BRG-1 transfection. ICI 182,780 did not induce cell cycle arrest in these cell lines, but there was evidence of downregulation of ER, indicating a ligand-receptor interaction. However, estrogen did not elicit increased transcription of estrogen-responsive genes (PR, myc, fos, pS2). CONCLUSION: Inappropriate expression of the nuclear corepressors N-CoR and SMRT or the coactivator BRG-1 does not underlie the resistance of ovarian cancers to hormonal therapy. Further studies are needed to elucidate the mechanisms underlying the inability of ovarian cancers to undergo ER-mediated transcription if we hope to understand their resistance to hormonal therapy.

Authors
Havrilesky, LJ; McMahon, CP; Lobenhofer, EK; Whitaker, R; Marks, JR; Berchuck, A
MLA Citation
Havrilesky, LJ, McMahon, CP, Lobenhofer, EK, Whitaker, R, Marks, JR, and Berchuck, A. "Relationship between expression of coactivators and corepressors of hormone receptors and resistance of ovarian cancers to growth regulation by steroid hormones." J Soc Gynecol Investig 8.2 (March 2001): 104-113.
PMID
11336882
Source
pubmed
Published In
Journal of the Society for Gynecologic Investigation (Elsevier)
Volume
8
Issue
2
Publish Date
2001
Start Page
104
End Page
113

OVXL, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma a critical appraisal

BACKGROUND. Ovarian carcinoma remains the leading cause of death from gynecologic malignancy in Australia, the Netherlands, and the United States. CA-125-II, the most widely used serum marker, has limited sensitivity and specificity for detecting small-volume, early-stage disease. Therefore, a panel of three serum tumor markers-OVX1, CA-125-II, and macrophage-colony stimulating factor (MCSF)-has been used to evaluate the sensitivity and specificity of multiple markers for the detection of early-stage ovarian carcinoma. METHODS. Preoperative serum levels of OVX1, CA-125-II, and M-CSF were measured in 281 patients with primary ovarian epithelial tumors of different histotypes. Among these tumors, 175 were malignant, 29 were of borderline malignancy, and 77 were benign. The three markers also were measured in sera from 117 apparently healthy women. Marker levels were considered abnormal at CA-125-II > 35 U/mL, OVX1 > 7.2 U/mL, and M-CSF > 3.5 ng/mL. RESULTS, Among 175 women with malignant ovarian tumors, at least one of the three serum markers was elevated in 85%, whereas CA-125-II was elevated in 80% (P = 0.008). In 58 patients with Stage I ovarian carcinoma, at least one of the three serum markers was elevated in 76%, whereas CA-125 levels were elevated in 66% (P = 0.04). For patients with borderline and benign tumors, a combination of the three antigens had slightly higher sensitivity compared with CA-125-II, but the differences were not statistically significant. Among 117 apparently healthy women, CA-125-II was elevated in 4%, and one of the three markers was positive in 17%. CONCLUSIONS. The sensitivity of a combination of three serum markers was significantly greater than the sensitivity of the CA-125-II assay alone in patients with primary ovarian epithelial tumors of different histotypes. This was true for all stages, including early-stage, potentially curable disease. When used as single markers, however, only the CA-125-II assay could distinguish invasive Stage I tumors from apparently healthy women. © 2001 American Cancer Society.

Authors
Haaften-Day, CV; Shen, Y; Xu, F; Yu, Y; Berchuck, A; Havrilesky, LJ; Bruijn, HWAD; Zee, AGJVD; Jr, RCB; Hacker, NF
MLA Citation
Haaften-Day, CV, Shen, Y, Xu, F, Yu, Y, Berchuck, A, Havrilesky, LJ, Bruijn, HWAD, Zee, AGJVD, Jr, RCB, and Hacker, NF. "OVXL, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma a critical appraisal." Cancer 92.11 (2001): 2837-2844.
Source
scival
Published In
Cancer
Volume
92
Issue
11
Publish Date
2001
Start Page
2837
End Page
2844
DOI
10.1002/1097-0142(20011201)92:11<2837::AID-CNCR10093>3.0.CO;2-5

Chemotherapy-induced apoptosis in epithelial ovarian cancers.

OBJECTIVE: To determine whether chemotherapy drugs elicit programmed cell death (apoptosis) in ovarian cancer cells. METHODS: Monolayers of immortalized ovarian cancer cell lines and primary ovarian cancer cells obtained from ascites were grown in the presence of cisplatin, 4-hydroxyperoxy-cyclophosphamide (the active metabolite of cyclophosphamide) or paclitaxel. Next, DNA was extracted from the cells and subjected to electrophoresis to determine if DNA laddering characteristic of apoptosis was present. RESULTS: In three of six immortalized cell lines (OVCA 420, 429, and 433), apoptosis was not seen in response to any of the three drugs. In contrast, in OVCAR-3 and OVCA 432, DNA laddering consistent with apoptosis was observed in response to all three drugs. In the DOV 13 cell line, apoptosis was seen only with 4-hydroxyperoxycyclophosphamide. Among three primary ovarian cancers, cisplatin elicited apoptosis in one case. Both cell lines with mutant p53 genes (OVCAR-3 and OVCA 432) underwent apoptosis in response to all three drugs, whereas among three cell lines known to have normal p53 genes, one underwent apoptosis in response to 4-hydroxyperoxycyclophosphamide and two were unaffected. CONCLUSION: Ovarian cancer cell death in response to commonly used chemotherapeutic drugs involves the induction of a genetically programmed sequence of events (apoptosis) rather than simply necrosis.

Authors
Havrilesky, LJ; Elbendary, A; Hurteau, JA; Whitaker, RS; Rodriguez, GC; Berchuck, A
MLA Citation
Havrilesky, LJ, Elbendary, A, Hurteau, JA, Whitaker, RS, Rodriguez, GC, and Berchuck, A. "Chemotherapy-induced apoptosis in epithelial ovarian cancers." Obstet Gynecol 85.6 (June 1995): 1007-1010.
PMID
7770245
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
85
Issue
6
Publish Date
1995
Start Page
1007
End Page
1010

Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta.

Previously, we found that transforming growth factor beta (TGF-beta) inhibits proliferation of normal human ovarian epithelial cells. In addition, although only 1 of 5 immortalized ovarian cancer cell lines was inhibited, TGF-beta inhibited proliferation of 19 of 20 primary epithelial ovarian cancers. In this study, we examined whether TGF-beta induces apoptosis in normal and malignant ovarian epithelial cells. Among 5 immortalized cell lines, only OVCA 420 is markedly growth inhibited by TGF-beta, and this was the only cell line in which TGF-beta elicited DNA fragmentation characteristic of apoptosis. Induction of apoptosis in OVCA 420 was time and concentration dependent and could be partially inhibited by concurrent treatment with an anti-TGF-beta mAb. Although apoptosis was not seen in normal ovarian epithelial cells (n = 7), [3H]thymidine incorporation was inhibited in all cases [mean = 61.2 +/- 7.2% (SD) of untreated control; P < 0.01]. Similarly, TGF-beta inhibited [3H]thymidine incorporation in all 10 primary ovarian cancers (mean = 40.4 +/- 7.1% of control; P < 0.01), but only 3 of 10 (30%) were found to undergo apoptosis when treated with TGF-beta. There was no relationship between p53 status of the ovarian cancers and the ability of TGF-beta to elicit apoptosis. In conclusion, TGF-beta inhibits proliferation but does not induce apoptosis in normal human ovarian epithelial cells. In contrast, some ovarian cancers that are growth inhibited by TGF-beta also undergo apoptosis. These data are consistent with the hypothesis that malignant cells are more susceptible to apoptosis than their normal nontransformed counterparts.

Authors
Havrilesky, LJ; Hurteau, JA; Whitaker, RS; Elbendary, A; Wu, S; Rodriguez, GC; Bast, RC; Berchuck, A
MLA Citation
Havrilesky, LJ, Hurteau, JA, Whitaker, RS, Elbendary, A, Wu, S, Rodriguez, GC, Bast, RC, and Berchuck, A. "Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta." Cancer Res 55.4 (February 15, 1995): 944-948.
PMID
7531618
Source
pubmed
Published In
Cancer Research
Volume
55
Issue
4
Publish Date
1995
Start Page
944
End Page
948

Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells.

Transforming growth factor beta (TGF beta) is an important regulator of cellular proliferation. In normal ovarian epithelial cells, TGF beta acts to inhibit growth. However, in ovarian cancer cell lines, this effect is usually lost. Although the regulatory pathway of TGF beta remains unclear, TGF beta-treated cells arrest late in G1. This inhibition appears to involve blocking of the cyclin-dependent kinase phosphorylation of the retinoblastoma protein. Recently, a general inhibitor of cyclin-dependent kinases, CIP1/WAF1/p21, was identified. Expression of CIP1 is positively regulated by binding of wild-type p53 to a consensus response element upstream of the CIP1 gene. Overexpression of the CIP1 protein causes growth suppression, analogous to TGF beta and wild-type p53. We have examined the induction of CIP1 by TGF beta 1 in ovarian cancer cell lines that have been previously characterized for their proliferative response to TGF beta 1. OVCA420, a cell line that is dramatically growth inhibited by TGF beta 1, significantly induced CIP1 expression in response to TGF beta 1. CIP1 induction was accompanied by a decrease in cdk2 kinase activity and cdk2 protein levels. In three other cell lines that respond weakly to TGF beta 1, CIP1 expression was not induced. To determine if TGF beta 1 induction occurs via p53, regulation of p53 RNA and protein was examined. No differences in p53 transcription, steady-state protein level, de novo synthesis, phosphorylation, or subcellular accumulation were noted. Furthermore, TGF beta 1 could not induce transcription from a consensus p53 DNA binding site in the TGF beta 1-response cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Elbendary, A; Berchuck, A; Davis, P; Havrilesky, L; Bast, RC; Iglehart, JD; Marks, JR
MLA Citation
Elbendary, A, Berchuck, A, Davis, P, Havrilesky, L, Bast, RC, Iglehart, JD, and Marks, JR. "Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells." Cell Growth Differ 5.12 (December 1994): 1301-1307.
PMID
7696178
Source
pubmed
Published In
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
Volume
5
Issue
12
Publish Date
1994
Start Page
1301
End Page
1307

Pathogenesis of ovarian cancers.

OBJECTIVE: To review our current understanding of the molecular genetic events involved in the development of epithelial ovarian cancers. METHODS: Molecular biologic techniques have been used to examine the role of growth-stimulatory genes (oncogenes) and -inhibitory genes (tumor suppressors) in ovarian cancer. RESULTS: A number of different peptide growth factors and their receptors are expressed by normal and malignant ovarian epithelial cells. However, the role, if any, of growth factors in ovarian carcinogenesis or maintenance of the transformed phenotype remains unknown. Amplification and overexpression of the HER-2/neu and c-myc oncogenes occur in a significant fraction of epithelial ovarian cancers (20-30%). Overexpression of HER-2/neu has correlated with poor survival in some studies, whereas c-myc amplification is more common in serous cancers. Mutation of the K-ras oncogene frequently occurs in borderline ovarian tumors, but is less common in invasive epithelial ovarian cancers. Mutation of the p53 tumor suppressor gene occurs in approximately half of advanced (stage III/IV) ovarian cancers and in 15% of early (stage IA/IB) cases. Most recently, preliminary studies have focused on the role of other tumor suppressor genes, cyclins, WAF1, and DNA mismatch repair genes. CONCLUSIONS: An understanding of the molecular events involved in the pathogenesis of epithelial ovarian cancer is beginning to evolve. Improvements in early diagnosis, treatment, and prevention of this deadly disease are dependent on further progress in this area.

Authors
Berchuck, A; Elbendary, A; Havrilesky, L; Rodriguez, GC; Bast, RC
MLA Citation
Berchuck, A, Elbendary, A, Havrilesky, L, Rodriguez, GC, and Bast, RC. "Pathogenesis of ovarian cancers." J Soc Gynecol Investig 1.3 (July 1994): 181-190.
PMID
9419769
Source
pubmed
Published In
Journal of the Society for Gynecologic Investigation (Elsevier)
Volume
1
Issue
3
Publish Date
1994
Start Page
181
End Page
190
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