Faculty Bibliography

Objective: Obesity is a significant risk factor for perioperative morbidity and mortality. Outcomes can be improved with standardized protocols including preventive measures and specialized surgical equipment and personnel. We sought to evaluate the outcomes of a surgical safety protocol for all patients with a body mass index (BMI) of >=40 undergoing planned gynecologic surgery.
Method(s): The high BMI pathway (HBP) was developed by a multidisciplinary team of gynecologic oncologists (GO), anesthesiologists, and ancillary surgical and nursing staff based on the most current recommendations from the literature and instituted as a quality improvement project. It was implemented for all morbidly obese patients undergoing planned surgery by a GO. Patients who underwent robotic hysterectomies (RH) on the HBP from 2016 to 2018 were compared with consecutive historical controls who had RHs from 2014 to 2015 prior to HBP implementation. Standard two-sided statistical analyses were performed.
Result(s): Of the 80 patients who successfully completed surgery on the HBP, 55 patients (68.8%) underwent RH and were included in this analysis. These patients were compared to 48 historical controls prior to HBP initiation. There were no significant differences in patient factors or perioperative times between pre- and post-HBP groups (Table 1). Since implementing HBP, there were fewer anesthesia-related complications (ARC) in HBP patients after RH compared to pre-HBP patients (0.0% vs 12.5%, P = 0.02). Among the control patients with ARC, two had respiratory distress requiring pharmacologic intervention, two had increased postoperative nausea and vomiting, and two had intractable postoperative pain. There was also an increase in same-day discharges among patients who underwent RH (65.5% vs 41.7%, P = 0.03), but no difference in hospital readmission rates. There were no differences in intraoperative and 30-day postoperative complications.
Conclusion(s): A HBP to improve perioperative safety for morbidly obese patients undergoing RH resulted in fewer ARCs and increased rates of same-day discharge without increasing perioperative times or intraoperative and postoperative complications. [Figure presented]
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Objective: The Gynecologic Oncology Group (GOG) study 240 demonstrated a 3.5-month improvement in overall survival when bevacizumab (bev) was added to a combination chemotherapy regimen. This study established a bev-containing regimen as standard therapy for women with recurrent, persistent, or metastatic cervical cancer (CC). Gastrointestinal fistula (GIF) formation is a known complication of bev, and the long-term data of GOG 240 reported that a GIF rate of 15% in women who were treated with bev compared to 1% in the control group women. We sought to evaluate our experience with women treated with bev for CC and to identify associated risk factors for GIF formation.
Method(s): All patients who have received bev for CC from 2012 to 2018 at two academic institutions were identified, and their records were reviewed. Standard two-sided statistical analyses were performed.
Result(s): A total of 43 women were treated with a bev-containing chemotherapy regimen; among them, 34 (79.1%) were treated for CC recurrence, and the remaining were treated for metastatic disease at initial presentation or persistent disease following primary treatment. Thirty-three women (76.6%) received prior radiation therapy (RT); of these, 10 (32.3%) received external beam radiation therapy (EBRT), and 21 (67.7%) had prior EBRT and brachytherapy (BT). The median dose of bev was 15 mg/kg for both EBRT only and EBRT and BT groups. Eleven women developed GIF after bev treatment (11/43, 25.6%). All 11 (100%) had been previously treated with RT, and six (54.5%) had received EBRT plus BT. This resulted in rates of 33.3% (11/33) for GIF formation among women who received EBRT, and 28.6% (6/21) for GIF formation among women who received EBRT plus BT. The median number of bev cycles prior to GIF development was 8 (1-29), and 7 (7/11, 63.6%) received the dose of bev (15 mg/kg) as prescribed in GOG 240. See Table 1.
Conclusion(s): In our cohort of women with CC who were treated with bev, over 25% developed GIF. This is more than expected based on the 15% seen in GOG 240. Notably almost all who developed GIF had recurrent disease and were treated with prior RT. A third of women treated with RT followed by bev formed GIF, representing a considerable proportion of the cohort. GIF development and the possibility of requiring a colostomy should be a part of counseling prior to bev initiation especially in those who have had prior RT. [Figure presented]
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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