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Objectives: Although non-inferior overall survival and reduced surgical morbidity with neoadjuvant therapy (NAC) compared to primary debulking surgery, upfront debulking surgery remains the treatment of choice for newly diagnosed advanced stage ovarian cancer (OC) in the US. This can be partially attributed to the association of aggressive surgical treatment with long term survival (LTS) demonstrated in high grade serous OC (HGSOC). On the contrary, NAC has been shown to lower the odds for LTS. We aimed to identify clinico-pathologic factors associated with LTS in advanced epithelial OC (EOC) treated with NAC. Methods: This is a retrospective case-control study. Women with FIGO stage III-IV high grade epithelial cancer of the ovary, fallopian tube or peritoneum diagnosed and treated with NAC prior to 2013 were extracted from consecutive patient records of the Tel-Aviv Sourasky Medical Center. Women surviving longer than 7 years from diagnosis (defined as long-term survivors, LTS) were compared to women surviving 6-24 months from diagnosis (defined as short-term survivors, STS). Patients with low grade or low malignant potential tumors were excluded. Results: We identified 190 women with stage III/IV epithelial OC. Seventy-eight patients (41%) survived longer than 5 years from diagnosis and 47 (24%) survived longer than 7 years from diagnosis, significantly higher proportions compared to previous reports. Thirty-nine patients (20%) survived 6-24 months, similar to previous reports. Clinicopathologic and treatment characteristics of both groups are displayed in Table 1. CA125 pre-treatment or after 4 courses of chemotherapy and the number of adjuvant and total chemotherapy courses administered were similar between the groups. LTS were significantly younger than STS at diagnosis, with a mean age of 60.05 years vs 65.95 years, respectively (p=0.008). The majority of LTS received 3 courses of NAC or less compared to STS (59.6% vs 33.4%), implying a smaller disease burden or better response to NAC. LTS had a significantly longer disease-free interval (80.49 months vs 3.65 months, p Download : Download high-res image (404KB) Download : Download full-size image Conclusions: Our analysis, to the best of our knowledge, is the first to demonstrate that NAC does not compromise the odds of long-term survivorship in women with advanced EOC, further strengthening NAC as an equivalent alternative to primary debulking surgery. In addition, we identified basic clinicpathologic and treatment-related factors associated with long term survival of epithelial OC patients treated with NAC. Further investigation is needed to determine which factors should be integrated into treatment-related decisions.

Objective This study sought to evaluate the incidence, risk factors, and estimated cost associated with venous thromboembolism (VTE) following robotic surgery for endometrial cancer. Methods The study included all consecutive patients with newly diagnosed endometrial cancer who underwent robotic surgery, excluding patients with a previous history of VTE (3%), those taking long-term warfarin (3%), and patients with conversions to laparotomy (3%). The incidence of postoperative symptomatic VTE within 90 days was analyzed. Direct and indirect medical costs were estimated using a linked billing database for standardized, inflation-adjusted costs. Results A total of 558 cases were identified. Median BMI was 29 kg/m2 (range, 17–85 kg/m2), median operative time was 227 minutes (range, 75–419 minutes), and median blood loss was 30 mL (range, 3–400 mL). All patients received thromboprophylaxis with intraoperative subcutaneous heparin and sequential pneumatic compression devices. Extended postoperative prophylaxis for 28 days was administered to 88 (17.2%) patients with high-risk factors. A total of eight patients (1.6%) developed symptomatic VTE, and all eight were in the group that did not receive extended prophylaxis. The number needed to treat to prevent one VTE was 52.8, with an absolute risk reduction 1.89% (95% CI 0.59% to 3.19%). The average cost for treatment of a VTE was $7653 (range, $4396–$12 211), equivalent to the cost of treating 21 patients with extended prophylaxis ($356 per patient). Conclusion The incidence of VTE in patients with endometrial cancer who underwent robotic-assisted surgery was low (1.6%), and none of the VTEs occurred in the cohort of high-risk patients who received extended thromboprophylaxis.

Objective The expression of homologous recombination (HR) genes in high grade ovarian cancer (HGOC) samples from debulking surgeries were correlated to outcomes in patients selected for chemotherapy treatment regimens. Study design RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naive patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist, and cancer cell content was further confirmed using a percent tumor content covariate, and mutation score covariate analysis. Gene expression analysis was performed using a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression models were used to assess the associations between the expression of 19 HR genes and survival. Results In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB, RAD50) was associated with improved outcome, in contrast to the NACT group where four HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and only one HR gene (RAD51) remained significantly associated with survival in PDS and NACT groups, respectively. Conclusion Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naive patients.

Objective Pilot study to assess the value of weekly paclitaxel plus carboplatin every 3weeks (dose dense regimen, DD) compared to the standard 3-weekly protocol in the adjuvant setting for endometrial cancer. Methods Retrospective cohort study comparing consecutive patients with high and intermediate-high risk endometrial cancer, undergoing DD protocol (from 2011 to 2015) to a non-overlapping historical cohort with similar characteristics who received treatment every three weeks (2008–2011). Results 122 patients with endometrial cancer were included in the study, of these, 61 patients received the dose dense protocol and 61 were treated with the standard 3-weekly protocol. After a median follow-up of 61.6months in the 3-weekly cohort, compared with 41.6months in the DD cohort, 40 progressions were recorded. 29 progressions were observed in women treated in the standard protocol, with a three years progression free survival (PFS) of 57.4%, compared to 11 progressions observed in patients in the DD schedule, with a three years PFS of 79.5% ( P =0.03). Patients who were treated with the DD protocol were less likely to have progression events compared to the standard cohort with a hazard ratio of 0.4 on multivariate analysis (CI 95%, 0.2–0.8, P =0.01), had significantly less distant metastases ( P =0.01), and had improved overall survival when diagnosed with advanced stage disease ( P =0.02). Complaints of musculoskeletal pain were more frequent in the standard cohort ( n =17, 27.9%) compared to the dose dense cohort ( n =4, 6.6%), P =0.005. Conclusion Preliminary data suggests that dose dense chemotherapy might be a reasonable and superior option for adjuvant treatment of endometrial cancer, compared to standard chemotherapy.

Objective To evaluate clinical outcome in patients selected to receive neoadjuvant chemotherapy (NACT) compared to primary debulking surgery (PDS). Methods Retrospective study including all consecutive patients diagnosed and treated for advanced (stages III-IV) ovarian cancers between the years 2003–2015. Results 263 women were included in the study, of these, 127 patients were selected to receive NACT and 136 were treated with PDS followed by adjuvant chemotherapy. PDS was associated with longer OS in stage IIIc disease (median OS: 60.2 vs. 48.8months; p -value 0.039) compared with NACT. Patients achieved higher rates of complete cytoreduction in the NACT group compared to the PDS group (65.9% vs. 40.2%; p =0.001). Patients attaining complete cytoreduction after PDS had the best survival, (median OS 106months) followed by those with complete cytoreduction after NACT (median OS 71months), followed by those with residual disease after PDS (median OS 55months). Patients with residual disease following interval debulking after NACT had the worst outcome (median OS 36months). Platinum sensitivity following first line and second line chemotherapy was similar whether patients received neoadjuvant chemotherapy or not. Conclusion PDS was associated with improved outcome. NACT appears to improve survival outcome in patients that would have had residual disease after PDS, and attain complete cytoreduction at the time of interval cytoreduction. This treatment option can be used in selected patients that are not candidates for complete cytoreduction at PDS.

Background Metformin has been associated with reduced cancer risk. The mechanisms underlying this cancer protective effect remain unknown. Methods "Window of opportunity" study of metformin in women with operable endometrial cancer (EC). Eleven newly diagnosed, untreated, non-diabetic patients with EC received metformin 500mg tid from diagnostic biopsy to surgery. Fasting plasma insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 1 (IGFBP-1) and insulin-like growth factor binding protein 7 (IGFBP-7) measurements were taken before and after metformin treatment. Ki-67, pAMPK, and pS6 immunohistochemistry staining was performed on the endometrial cancer before and after metformin treatment and was compared to a control group of 10 women with EC who did not receive metformin. Results Metformin was administered for a mean of 36.6days. None of the patients suffered side effects requiring withdrawal from the study. The study group comprised 8 patients with endometrioid EC, and 3 non-endometrioid EC, with a mean follow-up time of 57months. Mean plasma insulin ( p =0.0005), IGF-1 ( p =0.001), and IGFBP-7 ( p =0.0098) were significantly reduced after metformin treatment. A clear reduction in ki-67 and pS6 expression was observed by both conventional light microscope analysis and digital image analysis with a significant mean reduction in percentage of cells staining for ki-67 (9.7%, P =0.02) and pS6 (31%, P =0.03). In the non-treated control group expression was similar between the biopsy and the surgical specimens. Conclusions This pilot trial presents biological evidence consistent with anti-proliferative effects of metformin in women with EC in the clinical setting.