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The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

Objective: We conducted a multi-institutional observational study to investigate whether maintenance hormone therapy following primary treatment of low-grade advanced-stage ovarian cancer (LGSOC) is associated with an overall survival advantage., Methods: We included patients with histologically confirmed stage III or IV LGSOC diagnosed between Jan 1, 2004, and Dec 31, 2019, treated in Commission on Cancer-accredited cancer programs in the US. Patients who received hormone therapy within six months of diagnosis were matched to controls who did not initiate hormone therapy during this timeframe by risk-set propensity score matching. The primary outcome was the risk of death from any cause within five years of initiation of HT or observation., Results: There were 296 patients who initiated maintenance hormone therapy within six months of diagnosis and 2805 potential controls. Patients who received hormone therapy were more often treated in academic medical centers (55% vs. 44%), diagnosed later in the study period (62% vs. 23% diagnosed in 2018-2019), and frequently received no chemotherapy during initial treatment (45% vs. 17%). After risk set propensity score matching, we identified 225 patients treated with HT and 225 untreated controls who were otherwise similar with respect to measured covariates. In the matched cohort, hormone therapy was associated with a reduction in the risk of death (hazard ratio 0.60; 95% CI 0.38-0.94), corresponding to a 60-month survival of 75% compared with 65%., Conclusions: Following primary management of LGSOC, maintenance hormone therapy was associated with improved overall survival compared with observation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fungi have historically been the source of numerous important medicinal compounds, but full exploitation of their genetic potential for drug development has been hampered in traditional discovery paradigms. Here we describe a radically different approach, top-down drug discovery (TD 3 ), starting with a massive digital search through a database of over 100,000 fully genomicized fungi to identify loci encoding molecules with a predetermined human target. We exemplify TD 3 by the selection of cyclin-dependent kinases (CDKs) as targets and the discovery of two molecules, 1 and 2 , which inhibit therapeutically important human CDKs. 1 and 2 exhibit a remarkable mechanism, forming a site-selective covalent bond to the CDK active site Lys. We explored the structure-activity relationship via semi- and total synthesis, generating an analog, 43 , with improved kinase selectivity, bioavailability, and efficacy. This work highlights the power of TD 3 to identify mechanistically and structurally novel molecules for the development of new medicines.

Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy., (© 2024. The Author(s).)

With the increasing use of neoadjuvant chemotherapy, it has also become apparent that some patients will require a less extensive interval cytoreductive surgery which could be performed as a minimally invasive procedure. This observation, and expertise with minimally invasive surgery for other indications in gynecologic oncology, has driven surgeons in the United States and other countries to perform an increasing portion of interval cytoreductive surgery using minimally invasive techniques. Further observational and trial data will continue to inform which patients are best suited for this approach., (© 2023 Wiley Periodicals LLC.)

Objective: To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery., Methods: We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control., Results: We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42)., Conclusion: NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate utilization of sentinel lymph node biopsy (SLNB) for early-stage vulvar cancer at minority-serving hospitals and low-volume facilities., Methods: Between 2012-2018, individuals with T1b vulvar squamous cell carcinoma were identified using the National Cancer Database. Patient, facility, and disease characteristics were compared between patients undergoing SLNB or inguinofemoral lymph node dissection (IFLD). Multivariable logistic regression, adjusted for patient, facility, and disease characteristics, was used to evaluate factors associated with SLNB. Kaplan-Meier survival analysis using log rank test and Cox regression was performed., Results: Of the 3,532 patients, 2,406 (68.1%) underwent lymph node evaluation, with 1,704 (48.2%) undergoing IFLD and 702 (19.8%) SLNB. In a multivariable analysis, treatment at minority-serving hospitals (OR 0.39, 95% CI 0.19-0.78) and low-volume hospitals (OR 0.44, 95% CI 0.28-0.70) were associated with significantly lower odds of undergoing SLNB compared to receiving care at non-minority-serving and high-volume hospitals, respectively. While SLNB utilization increased over time for the entire cohort and stratified subgroups, use of the procedure did not increase at minority-serving hospitals. After controlling for patient and tumor characteristics, SLNB was not associated with worse OS compared to IFLD in patients with positive (HR 1.02, 95% CI 0.63-1.66) or negative (HR 0.92, 95% CI 0.70-1.21) nodal pathology., Conclusions: For patients with early-stage vulvar cancer, treatment at minority-serving or low-volume hospitals was associated with significantly decreased odds of undergoing SLNB. Future efforts should be concentrated toward ensuring that all patients have access to advanced surgical techniques regardless of where they receive their care., Competing Interests: Declaration of Competing Interest No financial support was provided for the submitted work. Dr. Eisenhauer has a leadership role on the NCCN Ovarian Cancer Committee. All other co-authors have no Conflicts of Interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To describe the use of National Comprehensive Cancer Network guideline-concordant inguinofemoral lymph node (LN) evaluation in individuals with early-stage vulvar cancer., Methods: This retrospective cohort study identified patients with T1b and T2 vulvar squamous cell carcinoma diagnosed between 2012 and 2018 using the National Cancer Database. Factors associated with LN evaluation were examined using logistic regression analyses, adjusting for patient, disease, and facility-level characteristics. Kaplan-Meier survival analysis using log rank test and Cox regression was performed for the entire cohort and a subgroup of older patients , defined as individuals aged 80 years or older., Results: Of the 5,685 patients with vulvar cancer, 3,756 (66.1%) underwent guideline-concordant LN evaluation. In our adjusted model, age 80 years or older (odds ratio [OR], 0.30; 95% CI 0.22-0.42) and Black race (OR 0.72; 95% CI 0.54-0.95) were associated with lower odds of LN evaluation. High-volume hospitals were associated with increased odds of LN evaluation compared with low-volume hospitals (OR 1.62; 95% CI 1.28-2.05). Older individuals who did not undergo LN evaluation had significantly worse overall survival than those with pathologically negative LNs (hazard ratio [HR] 0.45; 95% CI 0.37-0.55) and similar overall survival as those with pathologically positive LNs (HR 1.05; 95% CI 0.77-1.43)., Conclusion: Guideline-concordant LN evaluation for early-stage vulvar squamous cell carcinoma is low. Lower utilization is associated with older age, Black race, and care at a low-volume hospital., Competing Interests: Financial Disclosure J. Alejandro Rauh-Hain received payment from Schlesinger and Guidepoint. Sara Bouberhan received payment from ImmunoGen. Eric L. Eisenhauer received payment from Seagan. Christina Minami's institution received funding from the American College of Surgeons, American Society of Clinical Oncology, and the National Institute of Aging. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Objective: To describe the quality of life of women at an increased risk of ovarian cancer undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO)., Methods: Patients evaluated in our gynecologic oncology ambulatory practice between January 2018-December 2019 for an increased risk of ovarian cancer were included. Patients received the EORTC QLQ-C30 and PROMIS emotional and instrumental support questionnaires along with a disease-specific measure (PROM). First and last and pre- and post-surgical PROM responses in each group were compared as were PROMs between at-risk patients and patients with other ovarian diseases., Results: 195 patients with an increased risk of ovarian cancer were identified, 155 completed PROMs (79.5%). BRCA1 or BRCA2 mutations were noted in 52.8%. Also included were 469 patients with benign ovarian disease and 455 with ovarian neoplasms. Seventy-two at-risk patients (46.5%) had surgery and 36 had both pre- and post-operative PROMs. Post-operatively, these patients reported significantly less tension (p = 0.011) and health-related worry (p = 0.021) but also decreased levels of health (p = 0.018) and quality of life <7d (0.001), less interest in sex (p = 0.014) and feeling less physically attractive (p = 0.046). No differences in body image or physical/sexual health were noted in at-risk patients who did not have surgery. When compared to patients with ovarian neoplasms, at-risk patients reported lower levels of disease-related life interference and treatment burden, less worry, and better overall health., Conclusions: In patients with an increased risk of ovarian cancer, RRBSO is associated with decreased health-related worry and tension, increased sexual dysfunction and poorer short-term quality of life. Patients with ovarian neoplasms suffer to a greater extent than at-risk patients and report higher levels of treatment burden and disease-related anxiety., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine the proportion of patients with a pre-invasive endometrial lesion who meet Mayo criteria for lymph node dissection on final pathology to determine if the use of sentinel lymph node biopsy in patients with pre-invasive lesions would be warranted., Methods: All women who underwent hysterectomy for a pre-invasive endometrial lesion (atypical hyperplasia or endometrial intra-epithelial neoplasia) between 2009 and 2019 were included for analysis. Relevant statistical tests were utilized to test the associations between patient, operative, and pathologic characteristics., Results: 141 patients met inclusion criteria. 51 patients (36%) had a final diagnosis of cancer, the majority (96%) of which were Stage IA grade 1 endometrioid carcinomas. Seven patients (5%) met Mayo criteria on final pathology (one grade 3, seven size >2 cm, one >50% myoinvasive). Three of these seven patients had lymph nodes assessed of which 0% had metastases. Six of these patients had frozen section performed, and 2 met (33%) Mayo criteria intraoperatively. Of the seven patients in the overall cohort that had lymph node sampling, six had a final diagnosis of cancer and none had positive lymph nodes. Of the 51 patients with cancer, only 10 had cancer diagnosed using frozen section, and only two met intra-operative Mayo criteria. Age > 55 was predictive of meeting Mayo criteria on final pathology (p = 0.007). No patients experienced a cancer recurrence across a median follow up of 24.3 months., Conclusions: Atypical hyperplasia and endometrial intra-epithelial neoplasia portend low risk disease and universal nodal assessment is of limited value., Competing Interests: Declaration of Competing Interest The authors declare no relevant conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

Objective: Our goal was to pragmatically describe patient reported outcomes (PROs) in a typical clinic population of vulvar cancer patients, as prior studies of vulvar cancer PROs have examined clinical trial participants., Methods: A prospective PRO program was implemented in the Gynecologic Oncology clinic of a tertiary academic institution in January 2018. Vulvar cancer patients through September 2019 were administered the European Organization for the Research and Treatment of Cancer Quality of life Questionnaire, the Patient Reported Outcome Measurement Information System Instrumental and Emotional Support Scales, and the Functional Assessment of Cancer Therapy-Vulvar questionnaire. Binary logistic regressions were performed to determine adjusted odds ratios for adverse responses to individual questions by insurance, stage, age, time since diagnosis, recurrence, radiation, and surgical radicality., Results: Seventy vulvar cancer patients responded to PROs (85.4% response rate). Seventy-one percent were > 1 year since diagnosis, 61.4% had stage I disease, and 28.6% recurred. Publicly insured women had less support and worse quality of life (QOL, aOR 4.15, 95% CI 1.00-17.32, p = 0.05). Women who recurred noted more interference with social activities (aOR 4.45, 95% CI 1.28-15.41, p = 0.019) and poorer QOL (aOR 5.22 95% CI 1.51-18.10, p = 0.009). There were no major differences by surgical radicality. Those >1 year since diagnosis experienced less worry (aOR 0.17, 95% CI 0.04-0.63, p = 0.008)., Conclusions: Surgical radicality does not affect symptoms or QOL in vulvar cancer patients, whereas insurance, recurrence, and time since diagnosis do. This data can improve counseling and awareness of patient characteristics that would benefit from social services referral., Competing Interests: Declaration of Competing Interest There are no conflicts of interest for any of the authors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin + /anti-CD45 - cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0-18) and, at 36 days posttreatment, was 4 (range, 0-17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79-0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32-1.03) and PFS (HR, 0.59; 95% CI, 0.36-0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker., (©2020 American Association for Cancer Research.)

Ovarian cancer cells evade the immune system as well as chemotherapeutic and/or biologic treatments through inherent or acquired mechanisms of survival and drug resistance. Depending on the cell type and the stimuli, this threshold can range from external forces such as blunt trauma to programmed processes such as apoptosis, autophagy, or necroptosis. This review focuses on apoptosis, which is one form of programmed cell death. It highlights the multiple signaling pathways that promote or inhibit apoptosis and reviews current clinical therapies that target apoptotic pathways in ovarian cancer.

In the era of advanced cancer genomics, our recognition of hereditary cancer mutations continues to increase. Two of these conditions, which carry an increased risk of female cancers including endometrial, ovarian, breast, are hereditary breast and ovarian cancer syndrome and Lynch syndrome. Risk-reducing surgery, such as mastectomy, salpingo-oophorectomy, and hysterectomy may decrease cancer risk for mutation carriers. Background, indications, techniques, and consequences of these surgical procedures are reviewed., (© 2019 Wiley Periodicals, Inc.)

Background: Based primarily on studies concerning early-stage tumours (treated surgically), and locally advanced disease (treated with chemoradiation), the prognosis for women with adenocarcinoma (AC) or adenosquamous (AS) carcinoma has been reported to be poorer than those with squamous cell carcinoma (SCCA) of the cervix. It is unclear whether differences in prognosis also persist in the setting of recurrent or metastatic disease treated using chemotherapy doublets with or without bevacizumab., Methods: Cases were pooled from three Gynaecologic Oncology Group randomised phase III trials of chemotherapy doublets. Pearson's test was used to evaluate response rate (RR) of AC/AS vs SCCA, Kaplan-Meier method to estimate progression-free survival (PFS) and overall survival (OS), and Cox proportional hazards model to estimate the impact of histology on PFS and OS., Results: Of 781 evaluable patients, 77% (N=599) had SCCA and 23% (N=182) AC/AS. There were no significant differences in RRs between histologic subgroups. The adjusted hazard ratio (HR) for death for SCCA vs AC/AS was 1.13 (95% CI 0.93, 1.38 P=0.23). When comparing SC/AS (N=661, 85%) to AC alone (N=120, 15%), the adjusted HR for death was 1.23 (95% CI 0.97, 1.57, P=0.09)., Conclusions: AC/AS and SCCA have similar survival in recurrent or metastatic cervical carcinoma when treated with chemotherapy doublets.

We sought to identify how gynecologic oncologists approach reproductive counseling for their fertile, reproductive age patients, and their experience with unplanned pregnancies. Members of the Society of Gynecologic Oncology (SGO) were surveyed electronically regarding consistency of counseling patterns of contraception and fertility concerns, most and least common contraceptive methods utilized, referral patterns, and incidence of unplanned pregnancy. Of the 1424 SGO members identified, 261 participated in the questionnaire, yielding a response rate of 18%. Eighty-two percent of respondents agreed unplanned pregnancy is a potential problem, but only 57% believed their patients understood unplanned pregnancy is possible during treatment. Half of respondents report "always" in terms of frequency that contraception is addressed among their high-risk patients. After adjustment for gender, we found that the odds of reporting providing fertility counseling were nearly three times higher among attendings as compared to fellows [AOR = 2.72; 95% CI = (1.44, 5.12), three times higher in women as compared to men [AOR = 2.80; 95% CI = (1.46, 5.38)], as well as in individuals 50 + years as compared to those < 40 years old [AOR = 4.91; 95% CI = (2.05, 11.74)]. Ninety-six percent reported < 5 unplanned pregnancies, to their knowledge, in the previous five years of clinical practice. Most providers acknowledge that unplanned pregnancy is a potential risk in fertile gynecologic oncology patients, but only half believe their patients understand an unplanned pregnancy is possible. An opportunity exists to provide more directed counseling regarding fertility during and after cancer therapy, and to educate patients and providers regarding more reliable, long acting contraceptive methods.

Objective: The objective of this prospective pilot study was to assess the clinical and histologic effects of topical imiquimod therapy on recurrent extramammary Paget's disease of the vulva., Methods: Patients with biopsy-proven recurrent extramammary Paget's disease presenting to the gynecology outpatient services at two participating institutions were recruited for conservative treatment with 5% imiquimod cream from 2007 to 2011. The topical cream was to be applied 3 times per week for 12weeks. Punch biopsy and photography were performed at baseline and at the 12-week time point., Results: Eight patients from two institutions were enrolled. Complete clinical and histologic response was achieved in 6 (75%) patients by the 12-week follow-up appointment. Of the two remaining patients, one had a complete clinical response but no significant histologic response; the other patient was removed from the study protocol secondary to intolerable local irritation. Two patients continue to have no evidence of disease after a median follow-up of 35months. Five are alive with disease. No patients progressed to invasive cancer while receiving therapy., Conclusion: Topical 5% imiquimod cream is a safe and feasible option for women suffering from recurrent extramammary Paget's disease of the vulva, and should be considered as a viable alternative to surgical management. Given the rare nature of this disease, additional multi-institutional prospective studies should be conducted to explore the efficacy of this treatment regime., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Objective: To measure and compare postoperative pain and patient satisfaction in patients undergoing either robotic or open laparotomy for surgical staging of endometrial cancer., Design: Prospective, comparative study (Canadian Task Force classification II)., Setting: University hospital., Patients: A total of 142 patients undergoing either robotic or open laparotomy for surgical staging of endometrial cancer., Interventions: Patients scheduled for surgical staging of endometrial cancer at a single institution were identified. The patients underwent either robotic or open hysterectomy for staging of endometrial cancer. The choice of operative approach (robotic vs laparotomy) was made by the faculty physician before enrollment. Patients participated in the study for up to 48 hours for pain assessments and up to 10 ± 3 days postoperatively for quality of recovery assessments., Measurements and Main Results: The following measurements were performed: postoperative pain with the visual analog scale (VAS), 24-hour opioid consumption, and quality of recovery using the Quality of Recovery Questionnaire (QoR-40). The study was terminated owing to futility, given the lack of open procedures at our institution. Despite that lack of statistically significant difference between VAS scores at rest and with leg extension, there was a significant decrease in 24-hour opioid consumption in the robotic group. In addition, the QoR-40 showed an increased perception of recovery in patients within the robotic group compared with the laparotomy group., Conclusion: Patients with endometrial cancer who underwent robotic surgery had decreased postoperative opioid consumption and improved quality of recovery compared with those who underwent surgery via laparotomy., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to describe pregnancy risk assessment, reproductive goals, and incidence of pregnancy among the reproductive age population seen by gynecologic oncologists at a tertiary care center., Methods: A retrospective chart review was conducted among 18- to 45-year-old women evaluated by a gynecologic oncologist from January 2000 to December 2011. Data abstracted included the following: diagnosis, cancer treatment, parity, pregnancy risk factors (eg, menstrual patterns, sexual activity, and use of contraception), reproductive goals, type of referral, and pregnancy. Descriptive statistics were used to describe the characteristics of the population., Results: Five hundred seventeen women were eligible and included in the review. Median age was 31 years with most common diagnoses being cervical cancer, endometrial cancer, and premalignant disease. Most patients are multiparous. Seventy percent were treated surgically, with 58% experiencing surgical sterility. Completeness of reproductive data documented at initial visit included the following: 47% with a contraception plan, 54% sexual activity/practices, and 37% with personal reproductive goals reviewed. Fifteen patients were pregnant at the initial visit, and 21 patients pregnant during follow-up, representing 43 pregnancies (9 patients had more than 1 pregnancy). For those maintaining fertility after the initial visit, there was a median (range) of 2 (0-25) visits with 32% documenting a contraception plan at follow-up visits., Conclusions: A patient's reproductive goals and risk factors for pregnancy are inconsistently addressed during initial consultation with the gynecologic oncologist. This lack of consistency potentially increases patients' risk for unplanned pregnancy during evaluation and treatment of a gynecologic cancer diagnosis and potentially results in a missed opportunity for fertility preservation. Planned and unplanned pregnancy occurs in this population at a rate similar to that of US women of reproductive age, underscoring the need for reproductive counseling in this population.

Introduction: Patients with epithelial ovarian cancer (EOC) have a high rate of recurrence, and overall survival remains at ∼ 25%. There is a need for new treatments that can increase progression free survival and quality of life. Recent clinical trials focus on angiogenesis, VEGFs, and tyrosine kinase inhibitors that play a role in recurrence, metastasis, and ascites in EOC., Areas Covered: This review summarizes clinical rationale, mechanisms of action, and clinical data for angiogenesis inhibitors under evaluation in Phase II and III trials for EOC. Anti-angiogenesis agents reviewed in this paper include aflibercept, bevacizumab, cediranib, fosbretabulin, imatinib, nintedanib, pazopanib, saracatinib, sorafenib, sunitinib, and trebananib., Expert Opinion: These agents have particular rationale for potential use in EOC due to the molecular changes associated with EOC tumorigenesis, namely a significant increase in angiogenic activity. Due to the costs and toxicities associated with anti-angiogenics, biomarker or molecular signature selection strategy for patients who will most benefit would be ideal but no such strategy has been validated to date.

Objective: To estimate the rate of inpatient stay and the factors predicting inpatient status after robotic surgery for endometrial cancer following the change in the Medicare definition of "inpatient" to include hospitalization spanning 2 midnights., Design: Retrospective chart review (Canadian Task Force classification II-1)., Setting: Academic hospital., Patients: All patients (n = 395) with endometrial cancer who underwent robotic surgical management between 2006 and 2010., Intervention: The outpatient stay group with hospitalization spanning 1 midnight was compared with the inpatient stay group with hospitalization spanning 2 midnights or longer through estimation of the adjusted relative risk (aRR) for various characteristics of interest., Results: Ninety-six of 395 patients (24.3%) stayed at least 2 midnights and thus were deemed inpatients. Clinical factors associated with inpatient stay were increasing age, history of myocardial infarction (aRR, 2.0; 95% confidence interval [CI], 1.0-3.7), surgery start time at or after 12 noon (aRR, 1.7; 95% CI, 1.2-2.4), perioperative blood transfusion (aRR, 3.2; 95% CI, 2.3-4.5), and surgery performed in the year 2010 (aRR, 0.5; 95% CI, 0.3-0.7). Age ≥ 60 years was associated with at least a 2-fold adjusted risk of prolonged hospitalization. Body mass index, other medical comorbidities, operative duration, estimated blood loss, and performance of lymphadenectomy or additional surgical procedures were not identified as significant risk factors., Conclusion: Approximately 75% of the patients undergoing robotic surgery for endometrial cancer were discharged as outpatients. Recognition of factors predicting inpatient stay can improve hospital resource allocation and throughput in women undergoing robotic surgery for endometrial cancer., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

Cancer genomics has increased our recognition of specific hereditary cancer mutations. Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome are two such entities in which women carrying specific mutations may be at high risk for developing breast, ovarian, and/or endometrial cancers. Risk reducing surgery such as prophylactic mastectomy, oophorectomy, and/or hysterectomy may allow women to decrease these risks after completing childbearing. Background, indications, and consequences of these procedures are reviewed., (© 2014 Wiley Periodicals, Inc.)

Objective: To determine whether intra-operative radiation therapy (IORT) at the time of pelvic exenteration (PE) or laterally extended endopelvic resection (LEER) improves progression-free survival (PFS) in patients with recurrent, previously irradiated gynecologic cancers., Methods: We conducted a single institution retrospective review of patients who had undergone a complete PE for locally recurrent gynecologic cancer. Demographic and clinicopathologic data were collected., Results: 32 patients were identified (2000-2012); 21 (66%) cervical cancer, 8 (25%) vaginal, and 3 (9%) vulvar cancer. All patients were previously irradiated. Twenty-one (66%) received IORT. Mean age was 51. Eight patients had a LEER, all with IORT. Median PFS and OS, respectively, for those with PE alone was 33 and 41 vs. 10 and 10 months for PE+IORT compared to 9 and 17 months for LEER+IORT (P=.04). Increasing tumor size negatively impacted PFS (hazard ratio 1.3; 95%CI 1.12-1.52). Margin status was not associated with survival. No patients undergoing LEER+IORT recurred only locally whereas 62% recurred with a distant component (+/- local). Patients with PE alone had mainly local (36%) and few (9%) distant recurrences compared to 31% local and 38% distant (+/- local) recurrences for those with PE+IORT., Conclusions: We failed to demonstrate that IORT changes survival and recurrence outcomes. However, patients with clinical indications for IORT at the time of PE have worse prognosis compared to those who do not require IORT. If the need for IORT is anticipated, the surgeon may consider performing a LEER to decrease local recurrence if cure is the goal or consider palliative treatment options., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The doublet gemcitabine and carboplatin is effective for the treatment of recurrent ovarian cancer, while multi-agent chemotherapy with bevacizumab may add additional benefit. This phase II study tested the efficacy and safety of a biweekly gemcitabine, carboplatin, and bevacizumab combination in patients with platinum-sensitive recurrent ovarian, peritoneal, or tubal cancer (ROC)., Patients and Methods: Eligible patients received concurrent gemcitabine 1000 mg/m(2), carboplatin area under the curve 3, and bevacizumab 10 mg/kg administered intravenously on days 1 and 15 every 28 days for six cycles or up to 24 cycles if clinical benefit occurred. The primary end points were progression-free survival (PFS) by RECIST, and safety; the secondary end points were objective response rates and overall survival., Results: Overall, 45 patients were enrolled. The median PFS was 13.3 months (95% CI, 11.3 to 15.3). The objective response rate was 69%. Grade 4 hematologic toxicities included neutropenia (27%) and thrombocytopenia (2%). Grades 3 and 4 non-hematologic toxicities included fatigue (18%), pain (9%), and nausea/vomiting (4%). There were 2 episodes of cerebrovascular accidents, 2 noted DVTs, and no episodes of bowel perforation. Median OS was 36.1 months (95% CI, 26.7 to 45.5)., Conclusion: Biweekly gemcitabine, carboplatin, and bevacizumab were an effective regimen in recurrent ovarian cancer, with comparable toxicity to recently reported day 1 gemcitabine, carboplatin, bevacizumab, and day 8 gemcitabine. Response rate and PFS are improved from reported outcomes of the gemcitabine carboplatin doublet. The degree to which biweekly dosing may present a more rationale schedule for this triplet should be evaluated further., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine a dosing schedule of neoadjuvant chemotherapy using carboplatin, paclitaxel, and bevacizumab in women with advanced ovarian cancer, evaluating feasibility and outcomes from interval cytoreductive surgery (ICS)., Methods: Using a "3+3" design, eligible patients received carboplatin (area under the curve, 5) and bevacizumab (15 mg/kg) every 3 weeks with escalating doses of weekly paclitaxel (60, 70, and 80 mg/m) for 3 cycles. Patients then received 1 cycle of chemotherapy without bevacizumab followed by ICS. The primary objective was to determine a feasible dosing schedule. Secondary objectives included defining toxicity, response rates based on imaging, and surgical outcomes defined by residual disease following ICS and 30-day postoperative outcomes., Results: Nine patients were enrolled with a median age of 64 years. There were no dose-limiting toxicities, and weekly paclitaxel 80 mg/m was deemed feasible. During chemotherapy treatment, there were a total of 7 attributable grade 3 toxicities, which most commonly included neutropenia and thromboembolism. All patients demonstrated a response on imaging before surgery, with a median reduction in disease of 56.4% (range, 36.9%-100%). Optimal ICS was performed in all patients, and 78% had no gross residual tumor. There were no intraoperative complications; however, 1 patient experienced an anastomotic leak (grade 4) 10 days after surgery requiring repeat operation., Conclusions: A 4-cycle neoadjuvant regimen of carboplatin area under the curve of 5, weekly paclitaxel 80 mg/m, and bevacizumab 15 mg/kg for cycles 1 to 3, followed by interval cytoreduction, was feasible. Optimal ICS was achieved in all patients, and surgery was associated with acceptable morbidity.

Objective: Primary cytoreductive surgery in patients with stage IIIC-IV epithelial ovarian cancer frequently includes diaphragm peritonectomy or resection, which can lead to symptomatic pleural effusions when the resection specimen is ≥ 10 cm. Our objective was to evaluate whether the placement of an intraoperative thoracostomy tube decreased the incidence of symptomatic pleural effusions in these cases., Methods: We identified 156 patients who underwent primary debulking surgery involving diaphragm peritonectomy or resection for stage III-IV ovarian cancer from 1/01-12/09. Using standard statistical tests, the incidence of symptomatic pleural effusions and other variables were compared between patients who did and did not have intraoperative chest tubes placed., Results: Forty-nine patients had a resected diaphragm specimen ≥ 10 cm in largest dimension; 28 (57%) did not undergo chest tube placement (NCT group) while 21 (43%) did (CT group). Mediastinal lymph node dissection (0% vs 19%, P = 0.028) and liver resections (11% vs 38%, P = 0.037) were higher in the CT group. Postoperatively, 57% of the NCT group developed a moderate or large pleural effusion compared to 19% of the CT group (P = 0.007). Thirteen patients (46%) in the NCT group developed respiratory symptoms requiring either placement of a postoperative chest tube or thoracentesis compared to 3 patients (14%) in the CT group (P = 0.018)., Conclusions: Diaphragm peritonectomy or resection can often lead to moderate or large pleural effusions that may become symptomatic. In these patients, intraoperative chest tube placement may be considered to decrease the incidence of symptomatic effusions and the need for postoperative chest tube placement or thoracentesis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To describe readmission patterns after robotic surgery for endometrial cancer and identify risk factors for readmission within 90 days of discharge., Methods: Patients with endometrial cancer who underwent robotic surgical management at an academic institution from 2006 to 2010 were identified. Patient characteristics, intraoperative data, and postoperative complications were analyzed. Student's t-test and Fisher's exact test were used to compare patients readmitted within 90 days to those who were not., Results: Three hundred ninety-five patients were included. Thirty (7.6%) were readmitted within 90 days of surgical discharge. Length of stay greater than one day (40.0% vs. 23.0%, p=0.04) and postoperative complication (63.3% vs. 13.4%, p<0.01) were associated with readmission. The median interval to readmission was 9.5 days and median duration of subsequent hospitalization was 2.5 days. Fever (31.3%) and workup for vaginal drainage (25.0%) were the most common reasons for readmission. Only 2 of the 10 patients readmitted with fever had culture-proven infection, and no patients readmitted for vaginal drainage had a confirmed urinary tract injury. Of the 30 patients readmitted, 5 required a second operation - 3 for vaginal cuff dehiscence and 2 for port site hernia., Conclusions: Robotic surgery for endometrial cancer was associated with a 7.6% readmission rate. The most common reasons for readmission, fever and evaluation for urinary tract injury, were frequently not associated with severe illness. This supports additional education to consider raising the threshold for readmission by using more widespread outpatient evaluation for the potential complications of robotic endometrial cancer surgery., (© 2013.)

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

Objective: The optimal role of bevacizumab (Bev) in the treatment of ovarian cancer has not yet been established. Furthermore, it is unclear whether there is a benefit of Bev after progression on a Bev-containing regimen in ovarian cancer. The objective of this study was to compare response rates, progression-free survival (PFS), and overall survival between patients who were treated with chemotherapy and Bev after progression on Bev (BAB) versus patients who were treated with chemotherapy without Bev (CWOB)., Methods: We conducted a retrospective chart review of all patients who received treatment with Bev (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution. Patients who received additional therapy after progression while on Bev were included., Results: Forty-six patients were included (16 CWOB group and 30 BAB). The median number of previous chemotherapy regimens was 2.5 for CWOB compared with 4 for BAB (P = 0.11). Fifty-two percent of patients had an objective response to the first Bev regimen before progressing on Bev. Response rates for the regimen after progression on Bev were 19% (3/16) in the CWOB group and 23% (7/30) in the BAB group (P = 1). Twenty-five percent of the patients who responded to the first Bev regimen and 18% of those who did not respond to the first Bev regimen responded to the second Bev regimen (P = 0.72). The median PFS for patients in the CWOB group was 2.6 months (95% confidence interval [CI], 1.3-5 months), compared with 5.0 months (95% CI, 3.5-7.3 months) for patients in the BAB group (P = 0.01). Overall survival was similar, 9.4 months (95% CI, 5.0-12.0 months) for CWOB versus 8.6 months (95% CI, 5.8-15.5 months) for BAB (P = 0.19). One patient in the BAB group died of a bowel perforation., Conclusions: In patients previously treated with Bev for recurrent ovarian cancer, the subsequent addition of Bev to cytotoxic chemotherapy increased the PFS compared with patients not receiving a second course of Bev, but did so without an impact on overall survival. The response to the first Bev regimen did not predict whether a patient would respond again to the next Bev regimen. Randomized, larger studies will have to be performed to confirm this observation.

Objective: The objective of this study was to evaluate peri-operative and survival outcomes of ovarian cancer patients undergoing percutaneous upper gastrointestinal decompression for malignant bowel obstruction (MBO)., Methods: Retrospective chart review was used to identify patients with ovarian, peritoneal, or fallopian tube cancer who underwent palliative decompressive treatment for MBO from 1/2002 to 12/2010. Kaplan-Meier methods were used to estimate the median survival (MS) and multivariate analysis used to determine if any variables were associated with the hazard of death., Results: Fifty-three patients met inclusion criteria. Median length of diagnosis prior to intervention was 21 months. Fifteen (28.3%) patients experienced complications and 9 required revision. Forty-nine (92.5%) experienced relief of symptoms after placement, and 91% tolerated some form of oral intake. Following placement, 19 (36%) patients received additional chemotherapy and 21(41%) patients received total parental nutrition (TPN). Thirty-five patients were discharged home/outpatient facility, 16 to hospice care, and 2 died prior to discharge. MS for all patients was 46 days. Patients who received chemotherapy had a MS of 169 days compared to 33 days (p<0.001). We failed to find an association between survival and TPN or performance status., Conclusions: Malignant bowel obstruction is a common complication of ovarian cancer. Management is palliative; risks and benefits of any therapy must be considered. Percutaneous decompressive therapy provides relief from associated symptoms, and allows patients to be discharged home. Median survival in this group is limited, and decisions regarding aggressive therapy should be individualized., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Neuroendocrine carcinomas (NECs) of the cervix comprise only 2% of all cervical cancers. Prospective data is limited and treatment guidelines rely on retrospective reviews and literature from lung NEC. The objective of this study was to report our experience in the management of this rare disease., Methods: This was an IRB-approved retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990 and 2012. Demographic, treatment and survival data was collected. Progression free survival (PFS) and overall survival (OS) were assessed., Results: Twenty-six patients met inclusion criteria. Advanced-stage disease (II-IV) was diagnosed in 58% (n=15) of patients. Of the eleven patients with stage I disease, five were treated with platinum-based neoadjuvant chemotherapy (NACT), six with initial radical surgery, and seven received adjuvant therapy including chemotherapy and/or radiation. Nine patients (82%) are currently without evidence of disease (NED). Patients with stage I disease had significantly improved PFS and OS compared to stages II-IV with a median OS that was not reached and 12.1 months, respectively (p=0.0013). The majority of stage I patients with lymph node metastasis and large tumors achieved durable remission with triple-modality therapy including NACT and surgery followed by adjuvant therapy., Conclusions: Cervical NEC is an aggressive disease associated with a high mortality rate. Patients with advanced-stage disease have a poor prognosis regardless of therapy. However, multimodality with consideration of triple-modality therapy in early-stage disease has the potential for complete response and long-term survival, supporting the goal of curative intent in these patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: While it is known that positive surgical margins increase the risk of cervical cancer recurrence, little is known about the effect of close surgical margins (CSM). Therefore, we set out to determine the impact of margin status on recurrence and survival in patients with early-stage cervical cancer., Methods: A retrospective review was conducted of patients undergoing radical hysterectomy from 2000 to 2010 with Stage IA2-IIA cervical cancer. CSM were defined as ≤5mm; association with other clinicopathologic factors as well as recurrence and survival was evaluated., Results: Of the 119 patients, 75 (63%) with CSM had a recurrence rate of 24% compared to 9% without CSM. Though not independently associated with recurrence, CSM were significantly associated with positive lymph nodes (44% vs. 18%), positive parametria (33.3% vs. 2.3%), larger tumors (3.5 vs. 2.5cm), greater depth of stromal invasion (DOI) (84% vs. 33%), and lymphovascular space invasion (LVSI) (61.3% vs. 34.1%). We failed to find an association between adjuvant therapy and recurrence in those with CSM. Exploratory analysis revealed that a surgical margin of ≤2mm was significantly associated with an increased risk of overall recurrence (36% vs. 9%, p=0.009) as well as loco-regional recurrence (22% vs. 4%, p=0.0034)., Conclusions: Surgical margins of ≤5mm on radical hysterectomy specimens are often associated with other high or intermediate risk factors for recurrence. While not a proven independent risk factor, the distance to surgical margin may warrant further investigation as an intermediate risk factor along with tumor size, DOI and LVSI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess complications associated with double-barreled wet colostomy (DBWC) in the first six months after pelvic exenteration as compared to separate urinary and fecal diversion (SUD)., Methods: A single institution retrospective chart review was conducted of all patients who underwent a pelvic exenteration between 2000 and 2011. Patients were included if the procedure involved at least a urinary diversion and a perineal phase. Patient demographics and complications in the first 6months after surgery were recorded., Results: Thirty-three patients met inclusion criteria (12 DBWC and 21 SUD). The majority of patients had recurrent cervical cancer (58%) followed by vaginal, vulva, and endometrial cancer. All patients had previously received radiation. 10/12 patients with a DBWC and 67% of SUD had pelvic reconstruction. Median length of stay (LOS) was shorter for DBWC (14.5 vs. 20days, p=.01). Median operating times were shorter for DBWC (610 vs. 702minutes, p=.04). No urinary conduit or anastomotic bowel leaks occurred in the DBWC group compared to 5 (24%) and 2 (9.5%), respectively, in the SUD group (p=.06 for any leak). 58% of the DBWC and 62% of the SUD group required re-operation, and there were no 30-day peri-operative deaths., Conclusions: DBWC can be performed safely at the time of pelvic exenteration. We found reduced operating times, shorter LOS, and a trend toward fewer urinary conduit and/or bowel anastomotic leaks in DBWC exenteration patients. DBWC may be favorable over more technically challenging SUD in this heavily radiated population that generally has a limited overall survival., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Hematologic, gastrointestinal, and neurologic complications are common side effects of the platinum and taxane-based chemotherapy used in the primary treatment of epithelial ovarian cancer (EOC). These side effects and the impact of the resultant chemotherapy dose modification on disease free interval have not been extensively studied. The goal of this study was to determine the effect of chemotherapy delays and dose reductions on progression free survival (PFS) and overall survival (OS)., Methods: A review of patients with primary epithelial ovarian, peritoneal, and fallopian tube carcinoma treated between 1/2000 and 12/2007 was performed. Inclusion criteria were advanced stage disease and first line chemotherapy with a platinum and taxane regimen. Cox proportional hazard models were used to determine the effect of chemotherapy reductions and delays on PFS and OS., Results: One hundred and fifty seven patients met the inclusion criteria. Patients were divided into four groups: no delays or reductions (48%), delay only (27%), reduction only (8%), and both delay and reduction (18%). The mean number of delays/reductions per patient was 1.1 (range=0-5) and therapy was delayed a mean of 8 days. The most common reasons for delays/reductions were neutropenia (n=51), thrombocytopenia (n=45), and neuropathy (n=18). There were no differences detected in PFS or OS between groups., Conclusions: There were no differences detected in survival between patients who required dose adjustments and treatment delays and those who did not. The lack of association between survival and chemotherapy alterations suggests that in specific circumstances patients with advanced ovarian cancer should have individualized treatment plans., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Intraperitoneal chemotherapy has shown a survival advantage over intravenous chemotherapy for women with newly diagnosed optimally debulked epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. However, significant toxicity has limited its acceptance. In an effort to reduce toxicity, the Gynecologic Oncology Group conducted a Phase I study to evaluate the feasibility of day 1 intravenous (IV) paclitaxel and intraperitoneal (IP) cisplatin followed by day 8 IP paclitaxel on an every 21-day cycle., Methods: Patients with Stage IIB-IV epithelial ovarian, fallopian tube, primary peritoneal carcinomas or carcinosarcoma received paclitaxel 135mg/m(2) IV over 3h followed by cisplatin 75mg/m(2) IP on day 1 and paclitaxel 60 mg/m(2) IP on day 8 of a 21 day cycle with 6 cycles planned. Dose-limiting toxicity (DLT) was defined as febrile neutropenia or dose-delay of greater than 2 weeks due to failure to recover counts, or Grade 3-5 non-hematologic toxicity occurring within the first 4 cycles of treatment., Results: Twenty of 23 patients enrolled were evaluable and nineteen (95%) completed all six cycles of therapy. Three patients experienced a DLT consisting of infection with normal absolute neutrophil count, grade 3 hyperglycemia, and grade 4 abdominal pain., Conclusions: This modified IP regimen which administers both IV paclitaxel and IP cisplatin on day one, followed by IP paclitaxel on day eight, of a twenty-one day cycle appears feasible and is an attractive alternative to the intraperitoneal treatment regimen administered in GOG-0172., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Weekly paclitaxel has been shown to be an effective cytotoxic regimen for recurrent epithelial ovarian cancer (EOC), and may act through inhibition of angiogenesis. Bevacizumab, a potent angiogenesis inhibitor, has also been shown to have activity in patients with EOC. Therefore, we sought to determine if the addition of bevacizumab to weekly paclitaxel led to an increased survival compared to weekly paclitaxel alone., Methods: A single institutional review was conducted for patients with recurrent EOC treated with weekly paclitaxel (60-70mg/m(2)) on days 1, 8, 15, and 22 of a 28day cycle and those treated with weekly paclitaxel and bevacizumab (10-15mg/kg on day 1 and 15). Response rates (RR) were calculated, and progression-free survival (PFS), and overall survival (OS) were compared using Kaplan-Meier survival analysis., Results: Twenty-nine patients treated with weekly paclitaxel and 41 patients treated with paclitaxel/bevacizumab were identified. The groups were similar in demographics, initial optimal cytoreduction, stage, histology, grade, platinum sensitivity, and median number of previous regimens (4 vs. 4, p=0.69).The overall response rate (ORR) was 63% (complete response (CR) 34% and partial response (PR) 29%) for paclitaxel/bevacizumab and 48% (CR 17% and PR 31%) for weekly paclitaxel (p=0.23). Improvement in PFS was seen in those treated with paclitaxel/bevacizumab in comparison to weekly paclitaxel alone (median PFS 13.2 vs. 6.2months, p<.01). There was a trend towards improved OS for paclitaxel/bevacizumab (median OS 20.6 vs. 9.1months; p=0.12). Toxicities were similar between the two regimens although more bowel perforations (2 vs. 0) were seen in the paclitaxel/bevacizumab group., Conclusion: A significant increase in PFS with a trend towards improved OS was demonstrated in this heavily pretreated population treated with paclitaxel/bevacizumab as compared to weekly paclitaxel alone. This data should be helpful in guiding future trials to determine the optimal care for women with recurrent EOC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Define subgroups of patients at highest risk for major morbidity and mortality after a traditional approach of maximal surgical efforts followed by chemotherapy for advanced ovarian cancer (AOC)., Methods: Preoperative health, intra-operative findings and outcomes were assessed in consecutive patients with primary AOC from 4 centers. Initial tumor dissemination was stratified into 3 groups based on volume of disease. Surgery was categorized using a previously described surgical complexity score (SCS). Statistical analysis was directed toward validating a multivariable risk-adjusted model., Results: 576 patients with stage IIIC (N=447, 77.6%) or IV AOC (N=129, 22.4%) were analyzed. Age (HR (per year): 1.02; 95%CI: 1.01-1.03), high tumor dissemination (HTD) (HR: 1.73; 95%CI: 1.19-2.56), residual disease (RD) >1 cm (HR: 2.46; 95%CI: 1.74-3.53), and stage IV (HR: 1.93; 95% CI: 1.51-2.45), independently correlated with OS. We identified a small subgroup of patients who comprised a high-risk group (N=38, 6.6%) characterized by all of the following characteristics: high initial tumor dissemination (HTD) or stage IV plus poor performance or nutritional status plus age ≥ 75. In this group, high SCS to achieve low RD was associated with morbidity of 63.6% and limited survival benefit., Conclusions: Optimal management of AOC requires accurate, risk-adjusted predictors of outcomes allowing a tailored approach starting with primary therapy. Complex surgical procedures to render low RD improve survival, and in the majority of cases, the benefits of such surgery appear to outweigh the morbidity. However careful analysis identifies a subgroup of patients in whom an alternative approach may be the better strategy., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To compare the survival impact of diagnosing recurrent disease by routine surveillance testing versus clinical symptomatology in patients with recurrent epithelial ovarian cancer (EOC) who have achieved a complete response following primary therapy., Methods: We identified all patients who underwent primary surgery for EOC at two institutions between 1/1997 and 12/2004 and were diagnosed with recurrent disease following a complete clinical response to primary chemotherapy. Survival and post-recurrence management were compared between asymptomatic patients in which recurrent disease was diagnosed at a scheduled visit by routine surveillance testing and symptomatic patients in which recurrent disease was diagnosed based on clinical symptomatology at an unscheduled office visit or hospitalization., Results: Of the 121 patients that met inclusion criteria, 22 (18.2%) were diagnosed with a symptomatic recurrence. Median primary PFS was similar for asymptomatic and symptomatic patients (24.8 versus 22.6 months, P = 0.36); however, post-recurrence survival was significantly greater in asymptomatic patients (45.0 versus 29.4 months, P = 0.006). Secondary cytoreductive surgery (SCRS) was attempted equally in both groups (41% versus 32%, P = NS); however, optimal residual disease (

Objective: To determine the impact on progression-free survival (PFS) and overall survival (OS) of a programmatic change in surgical approach to advanced epithelial ovarian cancer., Methods: Two groups of patients with stage IIIC and IV ovarian, tubal, and peritoneal carcinoma were compared. Group 1, the control group, consisted of all 168 patients who underwent primary cytoreduction from 1/96 to 12/99. Group 2, the study group, consisted of all 210 patients who underwent primary surgery from 1/01 to 12/04, during which time a more comprehensive debulking of upper abdominal disease was utilized., Results: There were no differences between the groups in age, primary site of disease, surgical stage, tumor grade, American Society of Anesthesiologists class, preoperative serum CA-125 and platelet levels, percentage with or amount of ascites, size or location of largest tumor mass, or type of postoperative chemotherapy. Patients in Group 2 vs Group 1 more frequently had extensive upper abdominal procedure(s) (38% vs 0%, respectively; P<0.001) and cytoreduction to residual disease <1 cm (80% vs 46%, respectively; P<0.01). Five-year PFS and OS rates were significantly improved in Group 2. For Group 2 vs Group 1 patients, 5-year PFS rates were 31% vs 14%, respectively (hazard ratio, 0.757; 95% CI, 0.601-0.953; P=0.01]; and 5-year OS rates were 47% vs 35%, respectively (HR, 0.764; 95% CI, 0.592-0.987; P=0.03]., Conclusion: The incorporation of extensive upper abdominal procedures resulted in increased optimal cytoreduction rates and significantly improved PFS and OS. A paradigm shift toward more complete primary cytoreduction can improve survival for patients with advanced ovarian, tubal, and peritoneal carcinomas.

Objective: To determine the incidence, management, and outcome of patients diagnosed with a pancreatic leak after a distal pancreatectomy during primary surgical cytoreduction for ovarian, peritoneal, or tubal cancer., Methods: We performed a retrospective chart review of all patients who had a distal pancreatectomy at the time of primary surgery. Charts were reviewed to identify those patients who developed a persistent left upper quadrant abdominal fluid collection with elevated amylase levels., Results: A total of 17 patients had a distal pancreatectomy; of these, 4 patients (24%) developed a postoperative pancreatic leak. In these patients, persistent leukocytosis prompted evaluation with a computed tomography scan, which subsequently revealed a fluid collection. The median time from surgery to drainage of this collection was 9 days (range, 8-66). The drain remained in situ for a median of 29 days (range, 22-82). The median amylase level of the fluid was 22,945 U/L (range, 763-47,250). The median length of hospital stay for those patients with a leak was 33 days (range, 25-44), which was longer than those without a leak. However, the median time from surgery to treatment with systemic chemotherapy was 31 days (range, 16-43), which was equivalent to those without a pancreatic leak., Conclusion: Twenty-four percent of patients who had undergone a distal pancreatectomy developed a pancreatic leak. This complication, which usually presents early in the postoperative period, can be managed conservatively with percutaneous drainage. Oral intake may be resumed, and total parenteral nutrition is not needed in the majority of cases. Systemic chemotherapy can be administered without significant delay.

Objective: We previously reported that preoperative CA-125 may predict primary cytoreductive outcome in patients with stage III ovarian carcinoma (OC). The objective of this study was to perform a contemporary analysis of the ability of CA-125 to predict cytoreductive outcome in advanced OC since our programmatic change in surgical approach that currently incorporates the utilization of extensive upper abdominal procedures, as needed, to achieve maximal cytoreduction., Methods: We reviewed the records of all patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at our institution between 1/01 and 4/05., Results: The study cohort included 277 patients. Primary disease sites were: ovary, 232 (84%); tubal, 9 (3%); and peritoneum, 36 (13%). Stages were: IIIA, 6 (2%); IIIB, 12 (4%); IIIC, 215 (78%); and IV, 44 (16%). Tumor grades were: grade 1, 6 (2%); grade 2, 30 (11%); grade 3, 233 (84%), and undifferentiated, 8 (3%). Cytoreductive outcomes were: no gross residual disease (RD), 68 (25%); cm RD, 56 (20%). There was no threshold CA-125 level that accurately predicted cytoreductive outcome. However, with CA-125 values >500 U/mL, 50% (57/113) of patients required extensive upper abdominal surgery to achieve RD 500 U/mL, extensive upper abdominal procedures were necessary in 50% of cases to achieve residual disease

Patients with advanced-stage ovarian cancer often have metastatic disease in the upper abdominal region. In particular, metastases to the diaphragm are exceedingly common in these patients. A comprehensive approach to surgical cytoreduction, which has been associated with improved survival in patients with advanced ovarian cancer, should incorporate upper abdominal resection.

Objective: In advanced ovarian cancer, patients cytoreduced to no visible disease appear to have improved survival compared to patients with visible residual tumor < or = 10 mm. It remains unresolved whether this is due to better chemotherapy response and/or simply "re-setting the clock," such that patients with less residual disease take longer to recur and succumb to their disease., Methods: We reviewed the records of all patients who had primary surgery for stage IIIC-IV ovarian cancer at our institution from 1998-2004, followed by intravenous platinum-taxane chemotherapy. Primary outcome measures were complete response (CR) to initial chemotherapy, platinum resistance at 6 months, progression-free (PFS), and overall survival (OS)., Results: A total of 296 patients met study criteria, of whom 64 (22%) had cytoreduction to no visible disease, 145 (49%) had 1-10 mm residual disease, and 87 (29%) had > 10 mm residual disease. After multivariate analyses, patients cytoreduced to no visible disease demonstrated significant improvements in rates of initial complete response and incidence of platinum resistance, as well as subsequent improvement in PFS and OS, compared to the other two groups. Similarly, patients with 1-10 mm residual disease had improved outcomes compared to patients with > 10 mm residual disease for each endpoint., Conclusions: In ovarian cancer patients with < 10 mm residual disease who began platinum-taxane therapy, maximal cytoreduction to no visible residual disease was associated with improved initial chemotherapy response, less platinum resistance, and improved survival. Maximal cytoreduction may improve survival through increased sensitivity to initial chemotherapy and should be the goal of initial surgery in these patients.