Faculty Bibliography

The carboplatin/paclitaxel doublet remains the chemotherapy backbone for the initial treatment of ovarian cancer. This two-drug regimen, with carboplatin dosed using the Calvert formula, yielded convincing noninferior outcomes when compared with the prior, more toxic, regimen of cisplatin/paclitaxel. Carboplatin's dose-limiting toxicity is thrombocytopenia; however, when this drug is properly dosed and combined with paclitaxel, the doublet's cycle 1 dose in chemotherapy-naive women is generally safe. Carboplatin (unlike cisplatin) contributes minimally to the cumulative sensory neuropathy of paclitaxel, thus ensuring noticeable reversibility of neuropathy symptoms following completion of 6 cycles and only occasionally requiring cessation or substitution of the taxane. Paclitaxel is responsible for the hair loss associated with the carboplatin/paclitaxel doublet; preventive measures must be considered for patients who would otherwise refuse treatment. Several first-line phase III trials, as well as ongoing trials for which only preliminary results have been published, have fueled debates on the optimal dose and schedule; these have focused not only on weekly vs q3-weeks paclitaxel, but also on other modifications and the advisability of adding bevacizumab. Our view is that results of this doublet in the first-line treatment of ovarian cancer are driven primarily by carboplatin, given that ovarian cancer is a platinum-sensitive disease. Consequently, the roles of the accompanying paclitaxel dose and schedule and the addition of bevacizumab are currently unsettled, and questions regarding these issues should be decided based on patient tolerance and comorbidities until additional data are available.

PURPOSE/OBJECTIVE:To evaluate the outcomes of intraperitoneal chemotherapy (IP) compared with those of intravenous chemotherapy (IV) in patients with advanced ovarian cancer after neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS). METHODS:Patients with advanced epithelial ovarian carcinoma treated with PDS or NACT and IDS from 2006 to 2015 were identified. Comparative statistics were used to evaluate covariates, and survival rates were calculated using the Kaplan-Meier method and compared with log-rank tests. RESULTS:Sixty-six patients received NACT followed by IDS with residual disease of ≤ 1 cm; 42 of these patients (63.6%) received IP therapy; and 24 patients (36.3%) had IV therapy only after IDS. The median progression-free survival (PFS) was 16.0 months in the IP group and 13.5 months in the IV group (p = 0.13). The estimated median overall survival (OS) was 64.0 months with IP and 50.0 months with IV (p = 0.44). During the same study period, 149 patients underwent optimal PDS after which 93 patients (62.4%) received IP and 56 patients (37.6%) were given IV chemotherapy. Patients after IP demonstrated improved survival outcomes when compared to patients after IV therapy. The median PFS was 28.0 months after IP and 16.5 months after IV (p = 0.0006), and the median OS was not reached for IP and 50.0 months after IV (p < 0.0001). CONCLUSIONS:Although IP chemotherapy after PDS is associated with improved survival, IP therapy after NACT and IDS, despite high rates of completion, may not have the same degree of survival advantage over IV therapy.

Background Although the lifetime risk of both ovarian cancer (oc) and breast cancer (bca) is a high in BRCA mutation carriers (61%-79% bca risk, and 11%-53% oc risk), synchronous cancers, defined as the diagnosis of both cancers in the same patient within 6 months of each other, are rare, with only a few cases being reported in the literature. In 2008, we reported a case series of 8 BRCA-mutated patients who had both bca and oc, and we highlighted the unusual features and variable management of both synchronous and metachronous cancers. We now focus on synchronous presentations. Methods 6 patients with BRCA germline mutations and synchronous diagnoses of bca and oc were identified at New York University Langone Medical Center and Tel Aviv Sourasky Medical Center. Their clinical presentations and outcomes to date were analyzed. Results In 3 of 6 patients, the diagnoses of synchronous bca and oc were a result of risk-reducing surgeries or initial staging imaging. The bcas were all early-stage disease (i and ii); the ocs were high-grade, primarily serous, and advanced even if detected incidentally during the bca work-up. All 6 patients received chemotherapy with platinum and a taxane initially, aregimen that doubled as adjuvant or neoadjuvant treatment for bca. All 6 patients had excellent local and systemic control of bca, but the eventual progression in their oc or the occurrence of another primary cancer resulted in unfavourable outcomes. Conclusions Synchronous bca and oc diagnoses in BRCA-mutated women might become more common because of widespread genetic testing, use of staging imaging, and prophylactic surgeries. Platinum- and taxane-based chemotherapy directed at oc, coupled with local and systemic treatments, appears to adequately deal with bca, but long-term outlook is driven primarily by risk of oc recurrence or unrelated cancers. Dual primaries might provide a further rationale for consolidation with parp inhibitors

Health care in the United States is in the midst of a significant transformation from a "fee for service" to a "fee for value" based model. The Medicare Access and CHIP Reauthorization Act of 2015 has only accelerated this transition. Anticipating these reforms, the Society of Gynecologic Oncology developed the Future of Physician Payment Reform Task Force (PPRTF) in 2015 to develop strategies to ensure fair value based reimbursement policies for gynecologic cancer care. The PPRTF elected as a first task to develop an Alternative Payment Model for thesurgical management of low risk endometrial cancer. The history, rationale, and conceptual framework for the development of an Endometrial Cancer Alternative Payment Model are described in this white paper, as well as directions forfuture efforts.

OBJECTIVES/OBJECTIVE:Black race has been associated with increased 30-day morbidity and mortality following surgery for endometrial cancer. Black women are also less likely to undergo laparoscopy when compared to white women. With the development of improved laparoscopic techniques and equipment, including the robotic platform, we sought to evaluate whether there has been a change in surgical approach for black women, and in turn, improvement in perioperative outcomes. METHODS:Using the American College of Surgeons' National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for endometrial cancer from 2010 to 2015 were identified. Comparative analyses stratified by race and hysterectomy approach were performed to assess the relationship between race and perioperative outcomes. RESULTS:A total of 17,692 patients were identified: of these, 13,720 (77.5%) were white and 1553 (8.8%) were black. Black women were less likely to undergo laparoscopic hysterectomy compared to white women (49.3% vs 71.3%, p<0.0001). Rates of laparoscopy in both races increased over the 6-year period; however these consistently remained lower in black women each year. Black women had higher 30-day postoperative complication rates compared to white women (22.5% vs 13.6%, p<0.0001). When laparoscopic hysterectomies were isolated, there was no difference in postoperative complication rates between black and white women (9.2% vs 7.5%, p=0.1). CONCLUSIONS:Overall black women incur more postoperative complications compared to white women undergoing hysterectomy for endometrial cancer. However, laparoscopy may mitigate this disparity. Efforts should be made to maximize the utilization of minimally invasive surgery for the surgical management of endometrial cancer.

BACKGROUND/BACKGROUND:Risk-reducing bilateral salpingo-oophorectomy (RRBSO) increases survival in patients at high risk of developing ovarian cancer. While many general gynecologists perform this procedure, some argue it should be performed exclusively by specialists. In this retrospective observational study, we identified how often optimal techniques were used and whether surgeons' training impacted implementation. METHODS/METHODS:We used the ACOG guidelines highlighting various aspects of the procedure to determine which elements were consistent with best practices to maximize surgical prophylaxis. All cases of RRBSO from 2006 to 2010 were identified. We abstracted data from the operative and pathology reports to review the techniques employed. Fisher's exact test and chi-square were utilized to compare differences between groups (InStat, La Jolla, CA). RESULTS/RESULTS:Among 263 RRBSOs, 22 were performed by general gynecologists and 241 by gynecologic oncologists. Gynecologic oncologists were more likely to perform pelvic washings-217/241 vs. 10/22 (p < .0001). They were more likely to include a description of the upper abdomen-220/241 vs. 12/22 (p < .0001). Oncologists were more likely to utilize a retroperitoneal approach to skeletonize the infundibulopelvic ligaments-157/241 vs. 3/22 (p < .0001). When operations were performed by oncologists, the specimens were more often completely sectioned-217/241 vs. 16/22 (p = .003). The use of a retroperitoneal approach among gynecologic oncologists increased over the study period (chi-square for trend, p < .0001). There was no visible trend in performance improvement in any other area when looking at either group. CONCLUSION/CONCLUSIONS:Gynecologic oncologists are more likely to adhere to best practice techniques when performing RRBSO, though there was room for improvement for both groups.

OBJECTIVE: To evaluate the results of multigene panel testing among Ashkenazi Jewish compared with non-Ashkenazi Jewish patients. METHODS: We reviewed the medical records for all patients who underwent multigene panel testing and targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical actionability for identified pathogenic mutations was characterized based on the National Comprehensive Cancer Network (NCCN) guidelines and consensus statements and expert opinion for genes not addressed by these guidelines. RESULTS: Four hundred and fifty-four patients underwent multigene panel screening, including 138 Ashkenazi Jewish patients. The median patient age was fifty-two years. Three hundred and fifty-four patients (78%) had a personal history of cancer. Two hundred and fifty-one patients had breast cancer, 49, ovarian cancer, 26, uterine cancer and 20, colorectal cancer. We identified 62 mutations in 56 patients and 291 variants of uncertain significance in 196 patients. Among the 56 patients with mutations, 51 (91%) had actionable mutations. Twenty mutations were identified by multigene panels among Ashkenazi Jewish patients, 18 of which were in genes other than BRCA1/2. A review of targeted BRCA1/2 testing performed over the same study period included 103 patients and identified six mutations in BRCA1/2, all of which occurred in Ashkenazi Jewish patients. Among all Ashkenazi Jewish patients undergoing genetic testing, 25/183 (14%) had a mutation, 24/25 of which were actionable (96%) and 17/25 patients (68%) had mutations in non BRCA1/2 genes. CONCLUSIONS: With the rapid acceptance of multigene panels there is a pressing need to understand how this testing will affect patient management. While traditionally many Ashkenazi Jewish patients have undergone targeted BRCA1/2 testing, our data suggest consideration of multigene panels in this population as the majority of the results are clinically actionable and often in genes other than BRCA1/2.