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The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond., Competing Interests: Declaration of interests PM reports having had an advisory role or received speaker's honoraria (paid to him or to his institution) from GlaxoSmithKline, AstraZeneca, and ImmunoGen. GS reports grants or contracts from MSD, consulting fees from Tesaro Bio Italy and Johnson and Johnson, and payment or honoraria from Clovis Oncology Italy. NRA-R reports grants or contracts from Grail (paid to the institution). FFi reports honoraria from Theramex and Organon, and support for attending and travelling to meetings from Organon, Merck-Serono, and Theramex (paid to the institution). SB reports honoraria from MSD; support for attending and travelling to meetings from Hologic, MSD, and Pfizer; and honoraria for participation on a data safety monitoring board or advisory board from Hologic. CR-J reports payment for lectures (paid to the institution) from Organon and Novartis, speakers bureau (paid to the institution) from Gédéon Richter and Roche, and for manuscript writing (paid to the institution) from Roche. All other authors declare no competing interests., (Copyright © Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: We evaluated the performance of a chatbot compared to the National Comprehensive Cancer Network (NCCN) Guidelines for the management of ovarian cancer., Methods: Using NCCN Guidelines, we generated 10 questions and answers regarding management of ovarian cancer at a single point in time. Questions were thematically divided into risk factors, surgical management, medical management, and surveillance. We asked ChatGPT (GPT-4) to provide responses without prompting (unprompted GPT) and with prompt engineering (prompted GPT). Responses were blinded and evaluated for accuracy and completeness by 5 gynecologic oncologists. A score of 0 was defined as inaccurate, 1 as accurate and incomplete, and 2 as accurate and complete. Evaluations were compared among NCCN, unprompted GPT, and prompted GPT answers., Results: Overall, 48% of responses from NCCN, 64% from unprompted GPT, and 66% from prompted GPT were accurate and complete. The percentage of accurate but incomplete responses was higher for NCCN vs GPT-4. The percentage of accurate and complete scores for questions regarding risk factors, surgical management, and surveillance was higher for GPT-4 vs NCCN; however, for questions regarding medical management, the percentage was lower for GPT-4 vs NCCN. Overall, 14% of responses from unprompted GPT, 12% from prompted GPT, and 10% from NCCN were inaccurate., Conclusions: GPT-4 provided accurate and complete responses at a single point in time to a limited set of questions regarding ovarian cancer, with best performance in areas of risk factors, surgical management, and surveillance. Occasional inaccuracies, however, should limit unsupervised use of chatbots at this time., Competing Interests: Declaration of competing interest Dr. Abu-Rustum reports research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. Dr. Chi reports medical advisory board participation for Verthermia Acquio and Biom ‘Up Inc., speaker fees from AstraZeneca, and stock in BioNTech and Doximity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery., Methods: We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated. Five-fold cross-validation was applied to the multivariate model. Significant variables were assigned a 'BLOODS' (BLood transfusion Over an Ovarian cancer Debulking Surgery) score of +1 if present. A total BLOODS score was calculated for each patient, and the odds of receiving a transfusion was determined for each score., Results: Overall, 1566 patients met eligibility criteria; 800 (51%) underwent a peri-operative blood transfusion. Odds ratios (OR) were statistically significant for American Society of Anesthesiologists scores of 3 and 4 (OR 1.34, 95% confidence interval (95% CI) 1.09 to 1.63), pre-operative levels of cancer antigen 125 (CA125) (OR 2.43, 95% CI 1.98 to 2.99), platelets (OR 1.59, 95% CI 1.45 to 1.74), obesity (OR 0.76, 95% CI 0.60 to 0.96), presence of carcinomatosis (OR 2.45, 95% CI 1.93 to 3.11), bulky upper abdominal disease (OR 2.86, 95% CI 2.32 to 3.54), pre-operative serum albumin level (OR 0.31, 95% CI 0.24 to 0.40), and pre-operative hemoglobin level (OR 0.56, 95% CI 0.51 to 0.61). The corrected AUC was 0.748 (95% CI 0.693 to 0.804). BLOODS scores of 0 and 5 corresponded to 11% and 73% odds, respectively, of receiving a peri-operative blood transfusion., Conclusions: We developed a universal pre-operative scoring system, the BLOODS score, to help identify patients with ovarian cancer who would benefit from surgical planning and blood-saving techniques. The BLOODS score was directly proportional to the American Society of Anesthesiologists score, presence of upper abdominal disease, carcinomatosis, CA125 level, and platelets level. We believe this model can help physicians with surgical planning and can benefit patient outcomes., Competing Interests: Competing interests: NR Abu-Rustum reports grant funding from GRAIL paid to the institution. DS Chi reports personal fees from Apyx Medical, Verthermia Inc, Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc, TransEnterix, Inc, Doximity, Moderna, and BioNTech SE. K Long Roche reports travel support from Intuitive Surgical. A Iasonos reports consulting fees from Mylan. RN Grisham reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. The other authors do not have potential conflicts of interest to declare., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Ovarian cancer with extensive metastatic disease involving pelvic structures often requires rectosigmoid resection for complete gross resection; however, it is associated with increased surgical morbidity. There are limited data, and none in ovarian cancer, on near-infrared assessment of perfusion in rectosigmoid resections with anastomosis., Primary Objective: To compare the rate of pelvic complications (pelvic abscesses, anastomotic leaks, and infections) within 30 days of surgery with and without near-infrared assessment of perfusion at time of rectosigmoid resection and re-anastomosis in patients undergoing cytoreductive surgery for ovarian cancer., Study Hypothesis: We hypothesize the use of near-infrared technology (intravenous indocyanine green and endoscopic near-infrared fluorescence imaging), compared with standard intra-operative assessment, to evaluate anastomotic perfusion at time of rectosigmoid resection and re-anastomosis will result in lower rates of post-operative pelvic complications., Trial Design: This is a planned multicenter randomized controlled trial. Patients who undergo rectosigmoid resection as part of their ovarian cytoreductive surgery will be randomized 1:1 to standard assessment of anastomosis with the surgeon's usual technique (control arm) or assessment with near-infrared angiography using indocyanine green and endoscopic fluorescence imaging (experimental arm). Randomization will occur after rectosigmoid resection has been completed and the surgeon declares their plan to create a diverting ostomy. Randomization will be stratified by plan for diverting ostomy., Major Inclusion/exclusion Criteria: Main inclusion criteria include patients with primary or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are scheduled for cytoreductive surgery with suspected need for low-anterior rectosigmoid resection., Primary Endpoint: Rate of 30-day post-operative pelvic complications., Sample Size: 310 (155 per arm) ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Q2 2027 and Q4 2027, respectively., Trial Registration: NCT04878094., Competing Interests: Competing interests: Dr Leitao reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. Dr Abu-Rustum reports research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. Dr Chi reports personal fees from AstraZeneca, UptoDate, Biom’Up, Apyx Medical Corp, and Verthemia, as well as stock ownership in Doximity., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Although genetic testing (GT) is universally recommended for patients with epithelial ovarian cancer (EOC), rates are low (34%). In 1/2019, we implemented mainstreaming-GT in parallel with tumor testing via MSK-IMPACT within oncology clinics. We sought to determine GT rates pre/post-mainstreaming and patient characteristics associated with GT., Methods: Patients with newly diagnosed EOC seen at our institution from 7/1/2015-3/31/2022 were included. Clinical data were abstracted including social determinants of health (SDOH) variables, race/ethnicity, marital status, insurance, language, comorbidities, employment, and Yost index, a measure of socioeconomic status. GT rates were calculated overall and pre-/post-mainstreaming (1/2019). Logistic regression models were fit to identify variables associated with GT., Results: Of 1742 patients with EOC, 1591 (91%) underwent GT. Rates of GT increased from 87% to 95% after mainstreaming (p < 0.001). Among 151 patients not undergoing GT, major reasons were lack of provider recommendation (n = 76, 50%) and logistical issues (n = 38, 25%) with few declining (n = 14, 9%) or having medical complications preventing GT (n = 7, 4.6%). High-grade serous histology, advanced stage (III/IV), and having a spouse/partner were associated with increased GT uptake (p < 0.01). Among SDOH variables, there were no differences by insurance, Yost score, language, comorbidities, employment, or race/ethnicity. In multivariable models, likelihood of GT increased with mainstreaming, even after adjustment for histology, stage, and marital status (OR 3.77; 95% CI: 2.56-5.66)., Conclusions: Mainstreaming increased the likelihood of GT in patients with EOC. We found lower testing rates in patients without partners/spouses, non-high-grade serous histology, and early-stage disease, representing potential areas for future interventions., Competing Interests: Declaration of competing interest YLL reports research funding from AstraZeneca, GSK and Repare Therapeutics outside of this work. BW reports research funding by Repare Therapeutics, outside the current study. CA has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech. ZS reports an immediate family member who serves as a consultant in Ophthalmology for Adverum, Genentech, Gyroscope Therapeutics Limited, Neurogene, Optos Plc, Outlook Therapeutics, RegenexBio, and Regeneron. DSC reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. NRA reports research funding paid to the institution by GRAIL. MSK also has equity in GRAIL. All other authors have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the theoretical impact of regionalizing cytoreductive surgery for ovarian cancer (OC) to high-volume facilities on patient travel., Methods: We retrospectively identified patients with OC who underwent cytoreduction between 1/1/2004-12/31/2018 from the New York State Cancer Registry and Statewide Planning and Research Cooperative System. Hospitals were stratified by low-volume (<21 cytoreductive surgical procedures for OC annually) and high-volume centers (≥21 procedures annually). A simulation was performed; outcomes of interest were driving distance and time between the centroid of the patient's residence zip code and the treating facility zip code., Results: Overall, 60,493 patients met inclusion criteria. Between 2004 and 2018, 210 facilities were performing cytoreductive surgery for OC in New York; 159 facilities (75.7%) met low-volume and 51 (24.3%) met high-volume criteria. Overall, 10,514 patients (17.4%) were treated at low-volume and 49,979 (82.6%) at high-volume facilities. In 2004, 78.2% of patients were treated at high-volume facilities, which increased to 84.6% in 2018 (P < .0001). Median travel distance and time for patients treated at high-volume centers was 12.2 miles (IQR, 5.6-25.5) and 23.0 min (IQR, 15.2-37.0), and 8.2 miles (IQR, 3.7-15.9) and 16.8 min (IQR, 12.4-26.0) for patients treated at low-volume centers. If cytoreductive surgery was centralized to high-volume centers, median distance and time traveled for patients originally treated at low-volume centers would be 11.2 miles (IQR, 3.8-32.3; P < .001) and 20.2 min (IQR, 13.6-43.0; P < .001)., Conclusions: Centralizing cytoreductive surgery for OC to high-volume centers in New York would increase patient travel burden by negligible amounts of distance and time for most patients., Competing Interests: Declaration of competing interest Outside the submitted work, D. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. N.R. Abu-Rustum reports research funding paid to the institution by GRAIL. E.L. Jewell reports personal fees from Covidien/Medtronic. K. Long Roche reports travel support from Intuitive Surgical. The other authors do not have potential conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We sought to investigate the safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism among women who undergo neoadjuvant chemotherapy for the treatment of advanced ovarian cancer., Methods: A retrospective study using data extrapolated from a prospectively maintained institutional database was used to identify all patients with ovarian cancer who underwent neoadjuvant chemotherapy from April 2015 through September 2018 at our institution. All patients who received therapeutic anticoagulation for newly diagnosed venous thromboembolism at initial diagnosis or during neoadjuvant chemotherapy were included., Results: Of 290 patients who underwent neoadjuvant chemotherapy for advanced ovarian cancer during the study period, 67 (23%) had newly diagnosed venous thromboembolism at the time of initial diagnosis or developed venous thromboembolism during neoadjuvant chemotherapy. Of these 67 patients, 64 (96%) received therapeutic anticoagulation. A total of 13 (20%) of 64 patients who underwent therapeutic anticoagulation experienced a bleeding episode while on anticoagulation; 4 (31%) of the 13 events were of major severity. Three patients developed major internal bleeding in the peritoneal cavity, and one patient suffered from a major vaginal bleeding episode. All four patients were hospitalized (range, 5-11 days) and received ≥2 units of red blood cells for anemia. None of these patients died from fatal bleeding or had to delay starting chemotherapy. Of note, all four patients received low-molecular-weight heparin via subcutaneous injection. Overall, 13 (20%) of 64 patients required an anticoagulant dose reduction, mostly due to weight loss or new bleeding episodes., Conclusion: Therapeutic anticoagulation in this setting appeared safe, with a low risk of major bleeding complications. Furthermore, anticoagulation did not result in delay of chemotherapy or cytoreductive surgery., Competing Interests: Competing interests: Outside the submitted work, YLL reports research funding from GSK, REPARE Therapeutics, and AstraZeneca; RG reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER; DSC reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE; NRA-R reports research funding paid to the institution by GRAIL; and EJ reports personal fees from Covidien/Medtronic., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the impact of short-term postoperative complications on oncologic outcomes for patients with epithelial ovarian cancer undergoing primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) with intestinal resection., Methods: A retrospective chart review was performed for patients with ovarian cancer who underwent PCS or ICS with at least one intestinal resection at our institution from 1/1/2015 to 12/31/2020. Progression-free survival (PFS) and overall survival (OS) were analyzed for the PCS and ICS cohorts separately. Short-term complications within 30 days of surgery (surgical secondary events [SSEs]) were graded by a validated institutional SSE system., Results: Among 437 patients who underwent intestinal resections during PCS (n = 289) or ICS (n = 148), 183 (42%) had one, 180 (41%) had two, and 74 (17%) had three intestinal resections. Six (1.4%) of 437 patients experienced an anastomotic leak postoperatively. There were no perioperative deaths. There was no difference in PFS and OS for patients who underwent PCS with any SSE vs. no SSE within 30 days of surgery (HR, 1.05; 95% CI: 0.76-1.47; p = 0.75 and HR, 0.79; 95% CI: 0.49-1.26; p = 0.32, respectively). There was no difference in PFS and OS for patients who underwent ICS with any SSE vs. no SSE within 30 days of surgery (HR, 1.43; 95% CI: 0.99-2.07; p = 0.055 and HR. 1.18; 95% CI: 0.72-1.93; p = 0.52, respectively., Conclusion: Short-term postoperative morbidity for patients who underwent intestinal surgery during primary surgical management for advanced ovarian cancer did not impact oncologic outcomes., Competing Interests: Declaration of Competing Interest Outside the submitted work, N.R. Abu-Rustum reports research grants from GRAIL, Inc. paid to the institution; MSK also has equity in GRAIL, Inc. A. Iasonos reports consulting fees from Mylan. M.M. Leitao is an ad-hoc speaker for Intuitive Surgical, Inc., has served on advisory boards for JnJ/Ethicon and Immunogen, and reports consulting fees from Medtronic. D.S. Chi reports fees from AstraZeneca, UptoDate, and Biom'Up, has stock in Doximity, and has served on advisory boards for Apyx Medical Corp, Biom'Up, and Verthemia. The remaining authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Next-generation sequencing (NGS) studies have demonstrated that co-occurring sporadic endometrioid endometrial carcinoma (EEC) and endometrioid ovarian carcinoma (EOC) are clonally related, suggesting that they originate from a single primary tumor. Despite clonality, synchronous EEC and EOC when diagnosed at early stage behave indolently, similar to isolated primary EEC or isolated primary EOC. In the present study, we compared the DNA methylation signatures of co-occurring EEC and EOC with those of isolated primary EEC and isolated primary EOC. We also performed targeted NGS to assess the clonal relatedness of 7 co-occurring EEC and EOC (4 synchronous EEC and EOC and 3 metastatic EEC based on pathologic criteria). NGS confirmed a clonal relationship in all co-occurring EEC and EOC. DNA methylation profiling showed distinct epigenetic signatures of isolated primary EEC and isolated primary EOC. Endometrial tumors from co-occurring EEC and EOC clustered with isolated primary EEC while their ovarian counterparts clustered with isolated primary EOC. Three co-occurring EEC and EOC cases with peritoneal lesions showed a closer epigenetic signature and copy number variation profile between the peritoneal lesion and EOC than EEC. In conclusion, synchronous sporadic EEC and EOC are clonally related but demonstrate a shift in DNA methylation signatures between ovarian and endometrial tumors as well as epigenetic overlap between ovarian and peritoneal tumors. Our results suggest that tumor microenvironment in the ovary may play a role in epigenetic modulation of metastatic EEC., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate rates of germline pathogenic/likely pathogenic variants (PVs) and genetic counseling by ancestry in patients with epithelial ovarian cancer (EOC)., Methods: Patients with pathologically confirmed EOC who underwent clinical tumor-normal sequencing from January 1, 2015, to December 31, 2020, inclusive of germline analysis of ≥76 genes were included. Patients with newly identified PVs were referred for Clinical Genetics Service (CGS) counseling. Ancestry groups were defined using self-reported race/ethnicity and Ashkenazi Jewish (AJ) heritage. Genetic ancestry was inferred computationally using validated algorithms. Logistic regression models were built., Results: Of 1,266 patients, self-reported ancestry (AJ, 17%; Asian, 10%; Black/African American, 5.4%; Hispanic, 6.2%; non-Hispanic White, 57%; other, 0.16%; unknown, 4.0%) correlated with genetic ancestry (AJ ancestry, 18%; admixed, 10%; African, 4%; East Asian [EAS], 6%; European, 56%; Native American, 0.2%; South Asian [SAS], 4%; unknown, 2%). Germline PVs were observed in 313 (25%) patients, including 195 (15%) with PVs in EOC-associated genes. Those with PVs were younger at diagnosis (59 v 62 years; P < .001) and more likely to have high-grade serous ovarian cancer (83% v 72%; P = .009). PV prevalence varied between ancestry groups ( P < .001), with highest rates in the AJ (39.9%) and Asian (26.5%) groups and similar rates (>10%) across other ancestry groups. Use of genetic ancestry demonstrated similar findings and further characterized high rates of PV in EAS/SAS groups. Younger age, high-grade serous histology, and self-reported AJ or Asian ancestry were associated with PV in an EOC-associated gene. Rates of CGS counseling for newly identified PVs were high (80%) across ancestry groups., Conclusion: Rates of PV, particularly in EOC-associated genes, were high regardless of ancestry, with similar rates of counseling between groups, emphasizing the importance of universal genetic testing in all patients with EOC.

Objectives: To describe the prevalence of germline pathogenic variants (gPVs) in endometrial and ovarian carcinosarcomas and determine if gPVs are drivers of carcinosarcoma., Methods: Patients with endometrial or ovarian carcinosarcomas who underwent clinical tumor-normal sequencing from 1/1/2015 to 6/1/2021 and consented to germline assessment of ≥76 cancer predisposition genes were included. In patients with gPVs, biallelic inactivation was identified through analysis of loss of heterozygosity and somatic pathogenic alterations., Results: Of 216 patients identified, 167 (77%) were diagnosed with endometrial carcinosarcoma and 49 (23%) with ovarian carcinosarcoma. Overall, 33 gPVs were observed in 29 patients (13%); 20 gPVs (61%) had biallelic loss in tumors. The rate of high-penetrance gPVs overall was 7% (16 of 216); 88% of high-penetrance gPVs had biallelic loss. In the endometrial carcinosarcoma cohort, 22 gPVs were found in 19 (11%) of 167 patients; 12 gPVs (55%) had biallelic loss in tumors, including 8 (89%) of 9 in high-penetrance gPVs. Among the ovarian carcinosarcoma cohort, 11 gPVs were found in 10 (20%) of 49 patients; 8 gPVs (73%) had biallelic loss in tumors, and all evaluable high-penetrance gPVs (n = 6) had biallelic loss. All gPVs in homologous recombination (BRCA1, BRCA2, RAD51C) and Lynch syndrome (MSH2, MSH6) genes had biallelic loss in tumors (n = 15)., Conclusions: gPVs in genes affecting homologous recombination- or Lynch-associated mismatch repair exhibited biallelic inactivation within tumors, suggesting likely drivers of gynecologic carcinosarcoma. Our data support germline testing for patients with gynecologic carcinosarcomas, given implications for treatment and risk-reduction in patients and at-risk family members., Competing Interests: Declaration of Competing Interest B.Weigelt reports research funding and scientific advisory board participation from Repare Therapeutics, outside the submitted work. K. Offit is a founder and shareholder of AnaNeo Therapeutics Incorporated. Z.K. Stadler has an immediate family member who serves as a consultant in Ophthalmology for Alcon, Adverum, Gyroscope Therapeutics Ltd., Neurogene and RegenexBio, outside the submitted work. M.F. Berger reports receiving research funding from GRAIL and advisory board activities for Eli Lilly, AstraZeneca, and PetDx. Y.L. Liu reports research funding from AstraZeneca, GSK, and Repare Therapeutics. N.R. Abu-Rustum reports research funding paid to the institution from GRAIL. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). D.S. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. R.N. Grisham reports personal fees from AstraZeneca, Corcept, GlaxoSmithKline, MJH Life Sciences, Natera, PER, and SpringWorks. M.M. Leitao Jr. reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, Inc., and advisory board participation for JnJ/Ethicon and Takeda. V. Makker reports advisory board participation (unpaid) for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. R.E. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences, Curio, R-Pharm, GOG Foundation, and Onclive/PER. M. Rubinstein reports research funding from Merk, Zentalis, and AstraZeneca. M.L. Hensley reports advisory board participation at Aadi Bioscience, GSK, Thrive Bioscience, and Lilly; has an immediate family member who is employed by Sanofi; and served as a CME faculty speaker for Research to Practice. All other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer., Methods: We conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006-9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded., Results: Among 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7-61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%-56.2%). Median OS was 81.3 months (95% CI: 68.9-103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P < .001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P = .003)., Conclusions: Intrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS., Competing Interests: Declaration of Competing Interest Outside of the submitted work, REO reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences, and Curio. AI reports consulting fees from Mylan. NAR reports grant funding from GRAIL paid to the institution. RG reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. DC reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. DJ reports consulting fees from AstraZeneca and serves on a clinical trial steering committee at Merck. BJP reports consulting fees from Intuitive Surgical, AstraZenenca, Medtronic, and CEEVRA. All other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and assessed it in female patients with germ cell tumors (GCTs). We sought to validate these modified IGCCCG (mIGCCCG) models in a new cohort., Methods: We queried institutional databases for female patients with GCTs treated at Memorial Sloan Kettering Cancer Center from 1/1/1990-6/1/2020. The mIGCCCG model classifies patients with non-dysgerminomas as good, intermediate, or poor risk based on tumor markers using male IGCCCG cutoffs and absence/presence of non-pulmonary/peritoneal visceral metastasis. In dysgerminomas, good- and intermediate-risk groups are defined by absence/presence of non-pulmonary/peritoneal visceral metastasis. Progression-free survival (PFS) and overall survival (OS) were estimated for each group in the validation and combined original and validation cohorts. Associations between individual clinical factors and outcomes were evaluated., Results: Among 183 female patients with GCTs, clinical characteristics and outcomes were similar between the original (n = 93) and validation (n = 90) cohorts. In multivariable models, higher stage, older age, and non-dysgerminoma histology predicted worse PFS and OS (p < 0.05). Among 162 patients who received chemotherapy, preoperative and pre-chemotherapy mIGCCCG models were significantly associated with PFS and OS (p < 0.001 for all groups). With the preoperative model, 3-year PFS rates were 94%, 76%, and 50% in the good-, intermediate-, and poor-risk patients, respectively; OS rates were 96%, 86%, and 52%, respectively. Even within stage groups, mIGCCCG risk classifications were associated with clinical outcomes., Conclusions: A female-specific mIGCCCG risk model effectively stratifies patients and should be incorporated into clinical trials., Competing Interests: Conflict of Interest Statement Outside the submitted work, YL reports research funding from GSK, REPARE Therapeutics, and AstraZeneca; DF is a consultant/advisor for Cigna Research, and reports research funding from Decibel Therapeutics, Astellas Pharma, and Telix Pharmaceuticals; SF has received research support from AstraZeneca, Genentech/Roche, is a consultant/advisory board member for Merck, and owns stock in Urogen, Allogene Therapeutics, Neogene Therapeutics, Kronos Bio, ByHeart, 76Bio, Vida Ventures, and Inconovir; JM reports research funding from Seagen, Sermonix, Pfizer, and Olema Pharmaceuticals, and has consulted for Seagen, Pfizer, Novartis, Sanofi, Genzyme, AstraZeneca, and GlaxoSmithKline in the past 2 years; RO reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences and Curio; RG reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER; CA has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech; DC reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE; and NAR reports research funding paid to the institution by GRAIL. The other authors do not have potential conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years., Methods: We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001-12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S(x + y)/S(x). Confidence intervals were estimated using a variation of Greenwood's formula., Results: Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25-95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%-32%)-75% (95% CI: 68%-82%) for stage I/II disease, 22% (95% CI: 19%-26%) for stage III, and 6.9% (95% CI: 3.9%-12%) for stage IV. For patients <65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%-70%); for those ≥65 years, it was 48% (95% CI: 38%-57%). For patients <65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%-94%); stage III, 58% (95% CI: 50%-66%); and stage IV, 26% (95% CI: 12%-42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%-91%), 42% (95% CI: 30%-53%), and 29% (95% CI: 7%-56%), respectively., Conclusions: For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods., Competing Interests: Declaration of Competing Interest R.E.O. reports personal fees from Tesaro/GSK, personal fees from Regeneron, personal fees from Seattle Genetics, other from AstraZeneca Pharmaceuticals, personal fees from Fresenius Kabi, personal fees from Gynecologic Oncology Foundation, personal fees from Bayer, personal fees from Curio, advisor for Carina Biotech outside the submitted work; and non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK), ARTISTRY7 (Arkemes) and DUO-O (AstraZeneca) studies. Her institute receives funding for clinical research from Bayer/Celgene/Juno, Tesaro/GSK, Ludwig Cancer Institute, Abbvie/StemCentrx, Merck, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma, Gynecologic Oncology Foundation. N.A.R. reports research funding paid to the institution by GRAIL. R.N.G. reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER; D.S·C reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE; The other authors do not have potential conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: We sought to describe clinicopathologic and treatment factors associated with oncologic outcomes in patients with early-stage ovarian clear cell carcinoma undergoing complete staging and in a sub-set of these patients undergoing fertility-conserving surgery., Methods: We retrospectively identified patients with ovarian clear cell carcinoma initially treated at our institution from January 1, 1996 to March 31, 2020. Survival was estimated using Kaplan-Meier curves and compared by log-rank test. Survival-associated variables were identified by Cox proportional hazards regression., Results: Of 182 patients, mismatch repair and p53 protein expression were assessed by immunohistochemistry on 82 and 66 samples, respectively. There were no significant differences in progression-free survival or overall survival between mismatch repair-deficient (n=6, including 4 patients with Lynch syndrome; 7.3%) and mismatch repair-proficient patients, whereas aberrant p53 expression (n=3; 4.5%) was associated with worse progression-free (p<0.001) and overall survival (p=0.01). Patients with stage IA/IC1 disease had a 95% 5-year overall survival rate (95% CI 88% to 98%); patients with stage IC2/IC3 disease had a similar 5-year overall survival rate (76%; 95% CI 54% to 88%) to that of patients with stage IIA/IIB disease (82%; 95% CI 54% to 94%). There was no difference in 5-year overall survival in patients with stage IA/IC1 undergoing chemotherapy versus observation (94% vs 100%). Nine patients underwent fertility-sparing surgery and none experienced recurrence. Of five patients who pursued fertility, all had successful pregnancies., Conclusions: In patients with completely staged ovarian clear cell carcinoma, those with stage IA/IC1 disease have an excellent prognosis, regardless of chemotherapy. Aberrant p53 expression may portend worse outcomes. Additional investigation is warranted on the safety of fertility conservation in patients with stage IA/IC1 disease., Competing Interests: Competing interests: AI has served as a consultant for Mylan. DSC has provided speaking services for AstraZeneca, served on advisory boards for Apyx Medical and Biom’Up, and holds or has held stock or stock options in Moderna, BioNTech, Doximity, and Apyx Medical. CAA has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech. NRA-R has received research grants from GRAIL and Stryker/Novadaq. ML has received research grant(s) from KCI/Acelity, provided speaking services for Intuitive Surgical, and served on advisory boards for Johnson & Johnson/Ethicon and Takeda. MMR has received research grants from AstraZeneca, Merck, and Zentalis. BW has served on a scientific advisory board for Repare Therapeutics. RG has consulted for AstraZeneca, Corcept, GlaxoSmithKline, MJH Life Sciences, Natera, PER, and SpringWorks. All research grants were awarded to and administered by the institution., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability 1-4 patterned by distinct mutational processes 5,6 , tumour heterogeneity 7-9 and intraperitoneal spread 7,8,10 . Immunotherapies have had limited efficacy in HGSOC 11-13 , highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC. Homologous recombination-deficient HRD-Dup (BRCA1 mutant-like) and HRD-Del (BRCA2 mutant-like) tumours harboured inflammatory signalling and ongoing immunoediting, reflected in loss of HLA diversity and tumour infiltration with highly differentiated dysfunctional CD8 + T cells. By contrast, foldback-inversion-bearing tumours exhibited elevated immunosuppressive TGFβ signalling and immune exclusion, with predominantly naive/stem-like and memory T cells. Phenotypic state associations were specific to anatomical sites, highlighting compositional, topological and functional differences between adnexal tumours and distal peritoneal foci. Our findings implicate anatomical sites and mutational processes as determinants of evolutionary phenotypic divergence and immune resistance mechanisms in HGSOC. Our study provides a multi-omic cellular phenotype data substrate from which to develop and interpret future personalized immunotherapeutic approaches and early detection research., (© 2022. The Author(s).)

Objective: To determine the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin on the transcriptomic profiles of normal and ovarian cancer (OC) tissues., Methods: Normal and tumor samples from four OCs were prospectively collected pre- and immediately post-HIPEC treatment and subjected to RNA-sequencing. Differential gene expression, gene ontology enrichment and pathway analyses were performed. Heat shock protein and immune-response protein expression was assessed using protein arrays and western blotting., Results: RNA-sequencing revealed 4231 and 322 genes significantly differentially expressed between pre- and post-treatment normal and OC tissues, respectively (both adjusted p-value <0.05). Gene enrichment analyses demonstrated that the most significantly upregulated genes in normal tissues played a role in immune as well as heat shock response (both adjusted p < 0.001). In contrast, HIPEC induced an increased expression of primarily heat shock response and protein folding-related genes in tumor tissues (both adjusted p < 0.001). HIPEC-induced heat shock protein (HSP) expression changes, including in HSP90, HSP40, HSP60, and HSP70, were also observed at the protein level in both normal and tumor tissues., Conclusions: HIPEC with carboplatin resulted in an upregulation of heat shock-related genes in both normal and tumor tissue, with an additional immune response gene induction in normal and protein folding in tumor tissue. The findings of our exploratory study provide evidence to suggest that HIPEC administration may suffice to induce gene expression changes in residual tumor cells and raises a biological basis for the consideration of combinatorial treatments with HSP inhibitors., Competing Interests: Declaration of Competing Interest G. Zoppoli reports receiving travel grants from Roche, Novartis, and Pfizer, consultation fees from Pfizer, reagents from ThermoFisher Scientific and Cytiva Life Sciences, outside the submitted work. N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution, outside the current study. J.S. Reis-Filho reports receiving personal/consultancy fees from Goldman Sachs, REPARE Therapeutics and Paige.AI, membership of the scientific advisory boards of VolitionRx, REPARE Therapeutics and Paige.AI, membership of the Board of Directors of Grupo Oncoclinicas, and ad hoc membership of the scientific advisory boards of Roche Tissue Diagnostics, Ventana Medical Systems, Novartis, Genentech and InVicro, outside the scope of this study. J.S. Reis-Filho has stocks or stock options with REPARE Therapeutics and Paige.AI. D.S. Chi reports membership of the medical advisory boards of Bovie Medical Co. (now Apyx Medical), Verthermia Inc. and Biom ‘Up, to have/had stock options of Bovie Medical Co. (now Apyx Medical), Verthermia Inc., Intuitive Surgical Inc. and TransEnterix Inc., and to be the Chief Editor and shareholder of C Surgeries. D. Zamarin reports personal/consulting fees from Agenus, Hookipa Biotech, Western Oncolytics, Synthekine, Mana Therapeutics, Xencor, Memgen and Takeda, grants and personal fees from Merck and from Astra Zeneca, grants and non-financial support from Genentech, grants from Plexxikon and stock options from Calidi Biotherapeutics, outside the submitted work. D. Zamarin has a patent for use of Newcastle Disease Virus for cancer therapy, outside the submitted work. Dr. Aghajanian reports membership of advisory boards/personal fees from Tesaro, Eisai/Merck, Mersana Therapeutics, Roche/Genentech, Abbvie, AstraZeneca/Merck, Repare Therapeutics, and grants from Clovis, Genentech, AbbVie, Astra Zeneca, all outside the submitted work. R.E. O'Cearbhaill reports receiving honoraria/consulting/advisory role from GlaxoSmithKline, Fresenius, Seagen Inc., Carina Biotech and institutional research funding: Juno Therapeutics, Sellas Life Sciences, Ludwig Institute for Cancer Research, Stem CentRx, TapImmune Inc., TCR2 Therapeutics, Regeneron, Genmab, Atara Biotherapeutics, GlaxoSmithKline, AstraZeneca/Merck, Syndax, Genentech, Kite/Gilead, Gynecologic Oncology Group Foundation. Meal from AstraZeneca. B. Weigelt reports ad hoc membership of the scientific advisory board of Repare Therapeutics. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ovarian metastases from endocervical adenocarcinomas (EAs) are rare but well-described. Silva Pattern A tumors have been reported to pose essentially no risk of lymph node metastases or recurrence. We describe a cohort of patients with Silva Pattern A EAs with ovarian metastases, as well as involvement of other sites. Eight pattern A EAs with ovarian metastases (4 synchronous, 4 metachronous) were identified from our institution's pathologic archives (2008-2021). Clinicopathologic and molecular features for each case were recorded. All patients were treated by hysterectomy; in each case, the entire tumor was submitted for histologic evaluation. The synchronous metastases were all clinically suspected to be ovarian primary tumors; EAs with metachronous ovarian involvement were confined to the uterus at initial diagnosis, with ovarian metastasis occurring 5 to 171 months after hysterectomy. Morphologically, all tumors were predominantly gland-forming, 5/8 (63%) displayed prominent mucinous differentiation, and 5/8 (63%) involved the corpus. All EAs were either noninvasive (exophytic/papillary/more complex than adenocarcinoma in situ) or showed nondestructive cervical stromal invasion to a depth of 5 mm or less. In the 5 tumors tested by next-generation sequencing, ARID1A, GNAS, and KRAS mutations were detected in 2 (40%), 3 (60%), and 4 (80%) cases, respectively. All 6 patients with follow-up (range, 32 to 181 mo; median, 99.5 mo) had at least 1 recurrence. All but one are without evident disease at last clinical assessment. In an otherwise typical Silva Pattern A EA, corpus involvement, mucinous differentiation, and certain gene mutations may be associated with risk for synchronous or metachronous ovarian metastases., Competing Interests: Conflicts of Interest and Source of Funding: Supported in part by the National Institutes of Health/National Cancer Institute Cancer Center Core Grant No. P30-CA008748. N.R.A.-R. reports the following, outside the submitted work: grant from Stryker/Novadaq (paid to institution); grant from Olympus (paid to institution); grant from GRAIL (paid to institution). Memorial Sloan Kettering Cancer Center (MSK) has financial interests relative to GRAIL. As a result of these interests, MSK could ultimately potentially benefit financially from the outcomes of this research. For the remaining authors none were declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1 / 2 , the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1 /2 as well as BRIP1 and RAD51C / D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2 , RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points., Competing Interests: Ying L. LiuResearch Funding: AstraZeneca, Tesaro/GSK Kelsey BreenStock and Other Ownership Interests: Imago Pharma, Isabl TechnologiesConsulting or Advisory Role: DarwinHealth, Imago Pharma, Karyopharm Therapeutics, EmendoPatents, Royalties, Other Intellectual Property: Royalty from licensing agreements with MI Bioresearch Alicia LathamOther Relationship: Conquer Cancer Foundation Rachel N. GrishamConsulting or Advisory Role: Mateon Therapeutics, Clovis Oncology, Regeneron, GlaxoSmithKline, AstraZeneca, SignateraResearch Funding: Context TherapeuticsTravel, Accommodations, Expenses: EMD SeronoOther Relationship: Prime Oncology, MCM Education, OncLive, Aptitude HealthUncompensated Relationships: Verastem Melissa K. FreyResearch Funding: Invitae Dennis S. ChiLeadership: CSurgeriesStock and Other Ownership Interests: Bovie Medical, Verthermia, Intuitive Surgical, TransenterixHonoraria: Biom'UpConsulting or Advisory Role: Bovie Medical, Verthermia, Biom'UpTravel, Accommodations, Expenses: Biom'Up Nadeem Abu-RustumHonoraria: Prime OncologyResearch Funding: Stryker/Novadaq, GRAILTravel, Accommodations, Expenses: Prime Oncology Carol AghajanianConsulting or Advisory Role: Mersana, Eisai, Roche, AbbVie, Eisai, AstraZeneca/Merck, Roche/Genentech, Repare TherapeuticsResearch Funding: Genentech/Roche, AbbVie, Clovis Oncology, AstraZeneca Zsofia K. StadlerConsulting or Advisory Role: Allergan, Genentech/Roche, Regeneron, Optos, Adverum, Novartis, Regenxbio, Gyroscope, NeurogeneNo other potential conflicts of interest were reported.

Purpose: To determine the incidence of venous thromboembolism (VTE) and define clinical risk factors associated with the development of new-onset VTE in patients receiving neoadjuvant chemotherapy (NACT) for ovarian cancer (OC)., Methods: An institutional ovarian cancer database was used to identify all OC patients receiving NACT from 04/2015-09/2018. VTE events were recorded and included clinically diagnosed deep venous thrombosis (DVT) and/or pulmonary embolism (PE). The incidence of VTE events was categorized according to treatment phases (P): P0) First visit/prior to induction of NACT; P1) during NACT before interval debulking surgery (IDS); P2) intraoperative through day 28 post-IDS; P3) during adjuvant chemotherapy., Results: A total of 290 patients were identified during the study period. Seventy-five (25.9%) developed a VTE at some point from time of presentation through the peri-operative period. Forty (13.8%) presented with VTE prior to initiation of NACT. An additional 27 (11.6%) developed a VTE during NACT (P1); 6 (3.9%) during the intraoperative and 28-day post-operative period (P2); and 2 (1.3%) during the adjuvant period (P3). The overall VTE rate was 25.9% (n = 75). FIGO stage IV disease was the only factor associated with increased risk for a new-onset VTE [Odds Ratio (OR): 3.9 (95% Confidence Interval [CI] = 1.2-13.6; p = 0.03]., Conclusions: Patients receiving NACT for advanced OC are at extremely high risk for developing thromboembolic events, either at initial presentation or during induction of NACT, a treatment phase that is traditionally without use of prophylactic anticoagulation. Since Khorana scoring is not predictive in this population, clinicians might need to consider increased screening or use of prophylactic anticoagulation in patients receiving NACT for OC, particularly in advanced metastatic disease., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: We sought to describe clinicopathologic and surgical factors associated with oncologic outcomes in patients undergoing tertiary cytoreduction and to present a clinical model to identify patients with high-grade serous ovarian cancer (HGSOC) who may benefit most from tertiary cytoreduction., Methods: We retrospectively identified patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who underwent tertiary cytoreduction at our institution from 1/1/1990-1/1/2019. Kaplan-Meier curves were used to estimate survival and compared using the log-rank test. Cox-proportional hazards regression was used to detect variables associated with survival., Results: Of 114 patients who met inclusion criteria, 79 (69.2%) had high-grade serous tumors. Of patients with available genetic testing (n = 66), 22 (33%) harbored germline or somatic BRCA mutations. Fifty-eight women (50.9%) died of disease. Complete gross resection (CGR) at tertiary cytoreduction, treatment-free interval (TFI), and platinum sensitivity were all significantly associated with disease-specific survival (DSS) and maintained significance on multivariate analysis (HR 3.71, 95% CI: 1.59-8.70; HR 0.49, 95% CI: 0.28-0.85; and HR 2.94, 95% CI: 1.22-7.07, respectively). Postoperative treatment was not associated with a survival difference. Patients with HGSOC and a single site of recurrence who were ≥2 years from secondary cytoreduction had the longest survival after tertiary cytoreduction (median DSS, 79.5 months)., Conclusions: Proper patient selection for tertiary cytoreduction is essential. Those who achieve CGR likely derive the greatest benefit from tertiary surgery. Platinum sensitivity and prolonged TFI are also associated with improved DSS. Patients with HGSOC and single-site recurrence who were ≥2 years out from secondary cytoreduction had the longest DSS., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Leitao reports personal fees from JnJ/Ethicon and Intuitive Surgical, Inc. Dr. O'Cearbhaill reports personal fees from Tesaro, GlaxoSmithKline, Regeneron, and Seattle Genetics; she is also a non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies. Her institution receives funding for clinical research from Bayer/Celgene/Juno, Tesaro/GSK, Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma, and the Gynecologic Oncology Foundation. Dr. Abu-Rustum reports grants from Stryker/Novadaq, Olympus, and GRAIL. Dr. Chi reports personal fees from Bovie Medical Co., Verthermia Inc. (now Apyx Medical Corp.), Biom ‘Up, and C Surgeries, as well as other from Intuitive Surgical, Inc., and TransEnterix, Inc. The other authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine if the mutational landscapes and genomic features of homologous recombination DNA repair defects (HRD) vary between younger and older patients with high-grade serous ovarian cancer (HGSOC)., Methods: Younger and older women were defined as bottom and top age quartiles, respectively. HGSOCs from 15 younger (median 49 years, range 35-53) and 15 older women (median 72 years, range 70-87) were subjected to whole-exome sequencing (WES). For validation, HGSOC WES data were obtained from The Cancer Genome Atlas (TCGA), including 38 younger (median 45 years, range 34-50) and 30 older women (median 74 years, range 68-84). Mutational profiles, BRCA1/2 status, genomic HRD features, and for TCGA cases RNA-sequencing-based HRD transcriptomic signatures were assessed., Results: In the institutional cohort, pathogenic germline BRCA1/2 mutations were more frequent in younger (5/15) than older women (0/15, p = 0.042). No somatic BRCA1/2 mutations were identified. HGSOCs from older patients preferentially displayed aging-related mutational signatures and, in contrast to younger patients, harbored CCNE1 amplifications (3/15, 20%). In the TCGA cohort, pathogenic germline BRCA1 (younger 8/38, older 0/30, p = 0.007) but not BRCA2 mutations (young 3/38, older 4/30, p = 0.691) were more frequent in younger patients. Again, no somatic BRCA1/2 mutations were identified. HGSOCs from younger women more frequently displayed genomic features of HRD (all, p < 0.05), a significant HRD gene-signature enrichment, but less frequently CCNE1 amplification (p = 0.05). Immunoreactive CLOVAR subtypes were more common in HGSOCs from younger women, and proliferative subtypes in HGSOCs from older women (p = 0.041)., Conclusions: HGSOC patients diagnosed at an older age less frequently harbor pathogenic BRCA1 germline mutations and genomic features of HRD than younger women. Individualized treatment options, particularly pertaining to use of PARP inhibitors, in older women may be warranted., Competing Interests: Declaration of Competing Interest N.R. reports research support/ grants from Pfizer, BMS and REPARE Therapeutics as well as honoraria from REPARE Therapeutics and Illumina, outside the scope of this study. D.S.C. reports membership of the medical advisory boards and stock options of Bovie Medical Co (now Apyx Medical) and Verthermia Inc., Chief Editor and Shareholder of C Surgeries, and ad hoc membership of the medical advisory board of Biom ‘Up, outside the scope of the submitted work. N.R.A.-R. reports institutional grants from GRAIL and Stryker, outside the scope of this study. D.Z. reports personal/consultancy fees from Merck, Genentech, Synlogic Therapeutics, Biomed Valley Discoveries, Trieza Therapeutics, Tesaro, and Agenus, and institutional research support from Genentech, Astra Zeneca, and Plexxikon, all outside of the scope of the submitted work. J.S.R.-F. reports receiving personal/consultancy fees and is a member of the scientific advisory board of Repare Therapeutics. J.S.R.-F. also declares receiving personal/consultancy fees from Goldman Sachs and Paige.AI, membership of the scientific advisory boards of VolitionRx and Paige.AI, membership of the Board of Directors of Grupo Oncoclinicas, and ad hoc membership of the scientific advisory boards of Roche Tissue Diagnostics, Ventana Medical Systems, Novartis, Genentech and InVicro, all outside the scope of this study. B.W. reports membership of the ad hoc scientific advisory board of Repare Therapeutics, outside the scope of the submitted work. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Prior data suggested that women with incidentally detected occult invasive ovarian cancer (OIOC) at the time of risk-reducing salpingo-oophorectomy (RRSO) for BRCA mutation may have poorer prognoses than would be expected based on disease stage. We sought to evaluate prevalence and outcomes of patients with OIOC in a tertiary referral center., Methods: Patients with BRCA mutation undergoing RRSO from 01/2005 to 05/2017 were identified, and their records reviewed. Women with incidentally detected OIOC were included; those with clinical features raising preoperative suspicion for malignancy were excluded., Results: 548 patients with BRCA mutation who underwent RRSO were identified. 26 (4.7%) had an OIOC (median age 55 years; range 42-75); 15(58%) patients, BRCA1; 9(34%), BRCA2; 2(8%) had a mutation in both genes. All OIOCs were high-grade serous: 10 (38%) Stage I; 8 (31%) Stage II; 8(31%) Stage III. 24(92%) patients received adjuvant platinum/taxane therapy. Of Stage III patients, 4 (50%) were identified intraoperatively; the remaining 4 (50%) had microscopic nodal disease on final pathology only. At median follow-up of 67.3 months (28-166) no Stage I patients have recurred; 2 Stage II and 6 Stage III patients recurred. 5-year progression-free survival (PFS) was 72% (95%CI, 50.2-85.7%); median PFS for the cohort was 129 months (95%CI, 75.3-not estimable). 5-year disease-specific survival (DSS) was 96% (95%CI, 76-99%); median DSS not reached., Conclusion: Consistent with prior reports, almost 5% of patients had an OIOC at RRSO. The majority with early-stage disease had excellent PFS and DSS outcomes, as would be expected based on disease stage., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sporadic synchronous endometrial (ECs) and ovarian cancers (OCs), although clinically considered to be independent primaries, have been shown to be clonally related and likely constitute metastases from each other. We sought to define whether synchronous ECs/OCs in patients with DNA mismatch repair (MMR)-deficiency syndromes would be clonally related. We subjected synchronous ECs/OCs from four patients (LS3-LS6) with clinically confirmed Lynch syndrome (LS) and one patient with constitutional mismatch repair-deficiency syndrome (CMMRD) to massively parallel sequencing targeting 468 cancer-related genes. Somatic mutations, copy number alterations (CNAs), clonal relatedness and clonal decomposition analyses were performed using previously described bioinformatics methods. All synchronous ECs/OCs analyzed were considered independent primaries based on clinicopathologic criteria. Sequencing analysis revealed that the ECs/OCs of three cases (LS2-CMMRD, L3, L4) harbored similar repertoires of somatic mutations and CNAs and were clonally related. In these three cases, a subset of subclonal mutations in the EC became clonal in the OC, suggesting that the EC was likely the substrate from which the OC developed. LS5's EC/OC had distinct mutational profiles but shared specific CNAs. In contrast, LS6's EC/OC harbored distinct somatic mutations and lacked CNAs, consistent with each tumor constituting an independent primary lesion. In LS5 and LS6, PTEN mutations and PTEN loss of protein expression were found to be restricted to the EC. Finally, re-analysis of sequencing data of sporadic synchronous ECs/OCs supported the observations made in the current study that the directionality of progression is likely from the endometrium to the ovary. In conclusion, contrary to sporadic synchronous ECs/OCs, which are almost invariably clonally related, ECs/OCs simultaneously involving the uterus and ovary in LS patients may represent distinct primary tumors. A subset of MMR-deficiency syndrome-related synchronous ECs/OCs, however, may originate from a single primary tumor at variance with their clinical diagnosis, with the endometrium being the likeliest site of origin.

Objective: To evaluate the clinical significance and genomic associations of concurrent serous tubal intraepithelial carcinoma (STIC) with high-grade serous carcinoma (HGSC) of the ovary in women undergoing primary debulking surgery (PDS)., Methods: All patients who underwent PDS for HGSC between 01/2015 and 12/2018 were captured in a prospectively maintained institutional database. Patients were categorized based on the presence or absence of concurrent STIC noted on final pathology. Demographic, perioperative, and outcomes data were collected, and groups were compared using standard statistical tests. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. For comparison of differences in somatic alterations between the two cohorts, specimens were sequenced using MSK-IMPACT., Results: Of 306 eligible patients, 87 (28%) had a concurrent STIC lesion (+STIC) and 219 (72%) did not (no-STIC). Demographics and clinicopathological factors were similar between the two cohorts, except for a significantly higher median preoperative CA-125 level in the no-STIC group (423 U/mL vs. 321 U/mL; p=0.029). There were no significant differences in median PFS (22.7 months [95%CI: 18.9-28.4] vs. 27.7 months [95%CI: 25.5-30.5]; p=0.126) and 3- year OS rate (81% [95%CI: 70-88%] vs. 85% [95%CI: 78-90%]; p=0.392) between +STIC and no-STIC patients, respectively. Targeted DNA-sequencing via MSK-IMPACT showed a similar distribution of driver mutations or structural genetic alterations, and affected genetic signaling pathways were similar between the cohorts., Conclusions: There were no identifiable clinical and genetic differences in patients with HGSC and concurrent STIC. These data suggest a comparable, if not identical, disease process., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Iasonos reports personal fees from Mylan. Dr. Grisham reports personal fees from Clovis, Mateon, Regeneron, Verastem, Amgen, and Medscape, as well as a Conquer Cancer Foundation Career Development Grant (CDA) supported by Amgen; she has also received academic grants from Cycle for Survival, OCRFA, and Kaleidoscope of Hope. Dr. Aghajanian reports personal fees from Tesaro, Immunogen, Abbvie, Roche/Genentech, Eisai/Merck, Mersana Therapeutics, Clovis, and AstraZeneca, as well as grants from Genentech, AbbVie, and AstraZeneca. Dr. O'Cearbhaill reports personal fees from Tesaro, GlaxoSmithKline, Regeneron, and Genmab Therapeutics, as well as other (meal) from Genentech USA; she is also a non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies; she also reports funding to her institution for clinical research from Celgene/Juno, Tesaro/GSK, Ludwig Cancer Institute, Abbvie, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma, and the Gynecologic Oncology Foundation. Dr. Chi reports personal fees from Bovie Medical Co., Verthermia Inc. (now Apyx Medical Corp.), C Surgeries, and Biom ‘Up. He also reports previous stock ownership in Intuitive Surgical, Inc. and TransEnterix, Inc. Dr. Abu-Rustum reports grants from Stryker/Novadaq, Olympus, and GRAIL. Memorial Sloan Kettering Cancer Center (MSK) has financial interests relative to GRAIL. As a result of these interests, MSK could ultimately potentially benefit financially from the outcomes of this research. The other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To describe oncologic outcomes after using acute normovolemic hemodilution (ANH) to reduce requirement for allogenic red blood cell transfusions (ABT) in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer., Methods: We performed a post-hoc analysis of a recent prospective trial investigating the safety and feasibility of ANH during PDS for advanced ovarian cancer. We report long-term survival outcomes. We compared demographics, clinicopathological characteristics, survival outcomes in this cohort of Stage IIIB-IVB high-grade serous ovarian cancer patients undergoing ANH (ANH group), with a retrospective cohort of all other patients (standard group) undergoing PDS during the same time period (01/2012-04/2017). Standard statistical tests were used., Results: There were no demographic or clinicopathological differences between ANH (n = 33) and standard groups (n = 360), except for higher median age at diagnosis (57 vs. 62 years, respectively; p = 0.044) and shorter operative time (357 vs. 446 min, respectively; p < 0.001) in the standard group. Cytoreductive outcomes (ANH vs. standard): 0 mm, 69.7 vs. 63.9%; gross residual disease (RD) ≤1 cm, 21.2 vs. 26.9%; >1 cm, 9.1 vs. 9.2% (p = 0.78). RD after PDS was the only independent factor associated with worse progression-free survival (PFS) on multivariable analysis (p < 0.001). Patients with BRCA mutations trended towards improved PFS (p = 0.057). Significant factors for overall survival (OS) on multivariable analysis: preoperative CA125 (p = 0.004), ascites (p = 0.018), RD after PDS (p = 0.04), BRCA mutation status (p < 0.001). After adjustment for potential confounders, ANH was not independently associated with PFS or OS [PFS: HR 0.928 (0.618-1.395); p = 0.721; OS: HR 0.588 (95%CI: 0.317-1.092); p = 0.093]., Conclusions: ANH is an innovative approach in intraoperative management. It was previously proven to decrease need for ABT while maintaining the ability to achieve complete gross resection and associated benefits., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Although trials of neoadjuvant chemotherapy in ovarian cancer use 3 neoadjuvant cycles, real-world practice varies. We sought to evaluate the influence of increasing pre-operative cycles on survival, accounting for surgical outcomes., Methods: We identified 199 women with newly diagnosed ovarian cancer recommended for neoadjuvant chemotherapy who underwent interval debulking surgery from July 2015 to December 2018. Non-parametric tests were used to compare clinical characteristics by neoadjuvant cycles. The Kaplan-Meier method was used to estimate differences in progression-free and overall survival. The log-rank test was used to assess the relationship of covariates to outcome., Results: The median number of neoadjuvant cycles was 4 (range 3-8), with 56 (28%) women receiving ≥5 cycles. Compared with those receiving 3 or 4, women with ≥5 neoadjuvant cycles received fewer or no post-operative cycles (p<0.001) but had no other differences in clinical factors (p>0.05). Complete gross resection rates were similar among those receiving 3, 4, and ≥5 neoadjuvant cycles (68.5%, 70%, and 71.4%, respectively, p=0.96). There were no significant differences in progression-free or overall survival when comparing 3 versus 4 neoadjuvant cycles. However, more cycles (≥5 vs 4) were associated with worse progression-free survival, even after adjustment for BRCA status and complete gross resection (HR 2.20, 95% CI 1.45 to 3.33, p<0.001), and worse overall survival, even after adjustment for histology, response on imaging, and complete gross resection rates (HR 2.78, 95% CI 1.37 to 5.63, p=0.016). The most common reason for receiving ≥5 cycles was extent of disease requiring more neoadjuvant chemotherapy., Conclusions: Despite maximal cytoreduction, patients receiving ≥ 5 neoadjuvant cycles have a poorer prognosis than those receiving 3-4 cycles. Future studies should focus on reducing surgical morbidity and optimizing novel therapies in this high-risk group., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We sought to evaluate whether provider volume or other factors are associated with chemotherapy guideline compliance in elderly patients with epithelial ovarian cancer (EOC)., Methods: We queried the SEER-Medicare database for patients ≥66 years, diagnosed with FIGO stage II-IV EOC from 2004 to 2013 who underwent surgery and received chemotherapy within 7 months of diagnosis. We compared NCCN guideline compliance (6 cycles of platinum-based doublet) and chemotherapy-related toxicities across provider volume tertiles. Factors associated with guideline compliance and chemotherapy-related toxicities were assessed using logistic regression. Overall survival (OS) was compared across volume tertiles and Cox proportional-hazards model was created to adjust for case-mix., Results: 1924 patients met inclusion criteria. The overall rate of guideline compliance was 70.3% with a significant association between provider volume and compliance (64.5% for low-volume, 72.2% for medium-volume, 71.7% for high-volume, p = .02). In the multivariate model, treatment by low-volume providers and patient age ≥ 80 years were independently associated with worse chemotherapy-guideline compliance. In the survival analysis, there was a significant difference in median OS across provider volume tertiles with median survival of 32.8 months (95%CI 29.6, 36.4) low-volume, 41.9 months (95%CI 37.5, 46.7) medium-volume, 42.1 months (95%CI 38.8, 44.2) high-volume providers, respectively (p < .01). After adjusting for case-mix, low-volume providers were independently associated with higher rates of mortality (aHR 1.25, 95%CI: 1.08, 1.43)., Conclusions: In a modern cohort of elderly Medicare patients with advanced EOC, we found higher rates of non-compliant care and worse survival associated with treatment by low-volume Medicare providers. Urgent efforts are needed to address this volume-outcomes disparity., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: We assessed the utility of video-assisted thoracic surgery (VATS) in defining extent of intrathoracic disease in advanced ovarian carcinoma with moderate-to-large pleural effusions., Methods: Beginning in 2001, VATS was performed on all patients with suspected advanced ovarian carcinoma and moderate-to-large pleural effusions, evaluating for macroscopic intrathoracic disease. The algorithm recommended primary debulking surgery (PDS) for ≤1 cm, neoadjuvant chemotherapy (NACT)/interval debulking surgery (IDS) for >1 cm intrathoracic disease. We reviewed records of patients undergoing VATS from 10/01-01/19. Differences between treatment groups were tested using standard statistical techniques., Results: One-hundred patients met eligibility criteria (median age, 60; median CA-125 level, 1158 U/mL; medium serum albumin, 3.8 g/dL). Macroscopic pleural disease was found in 70 (70%). After VATS, 50 (50%) underwent attempted PDS (PDS group), 50 (50%) received NACT (NACT/IDS group). Forty-seven (94%) underwent IDS. Median overall survival (OS) for the entire cohort (n = 100) was 44.5 months (95% CI: 37.8-51.7). The PDS group had significantly longer survival than the NACT/IDS group [45.8 (95% CI: 40.5-87.8) vs. 37.4 months (95% CI: 33.3-45.2); p = .016]. On multivariable analysis, macroscopic intrathoracic disease (HR 2.18, 95% CI: 1.14-4.18; p = .019) and age ≥ 65 (HR 1.98, 95% CI: 1.16-3.40; p = .013) were independently associated with elevated death risk. Patients with the best outcome had no macroscopic disease at VATS and underwent PDS (median OS, 87.8 months)., Conclusions: VATS is useful in therapeutic decision-making for PDS vs. NACT/IDS in advanced ovarian cancer with moderate-to-large pleural effusions., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To describe outcomes using a multimodal algorithm to triage patients with advanced epithelial ovarian cancer (EOC) to primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT)., Methods: All patients with EOC treated at our institution from 04/2015-08/2018 were identified. We included patients without contraindication to PDS who underwent prospective calculation of a Resectability (R)-score. A low risk score for suboptimal cytoreduction was defined as ≤6, and a high risk score ≥7. Patients were triaged to laparotomy/PDS, laparoscopic evaluation of resectability (LSC), or NACT depending on R-score., Results: Among 299 participants, 226 (76%) had a low risk score and 73 (24%) a high risk score. For patients with a low risk score, management included laparotomy/PDS, 181 (80%); LSC, 43 (19%) (with subsequent triage: PDS, 31; NACT, 12); and NACT, 2 (1%). For patients with a high risk score, management included laparotomy/PDS, 9 (12%); LSC, 51 (70%) (with subsequent triage: PDS, 28; NACT, 23); and NACT, 13 (18%). Overall, 83% underwent PDS, with a 75% CGR rate and 94% optimal cytoreduction rate. Use of the algorithm resulted in a 31% LSC rate and a 6% rate of suboptimal PDS., Conclusions: The multimodal algorithm led to excellent surgical results; 94% of patients achieved an optimal resection, with a very low rate of suboptimal cytoreduction., Competing Interests: Declaration of competing interest Outside the submitted work, Dr. Straubhar has a patent W02019195097A1 perineal heating device issued. Dr. Lakhman is a shareholder of Y-mAbs Therapeutics, Inc. Dr. Abu-Rustum reports grants from Stryker/Novadaq, Olympus, and GRAIL. Dr. Chi reports personal fees from Bovie Medical Co. (now Apyx Medical), Verthermia Inc., C Surgeries, and Biom Up, as well as other from Intuitive Surgical, Inc. and TransEnterix, Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sclerosing stromal tumor (SST) of the ovary is a rare type of sex cord-stromal tumor (SCST), whose genetic underpinning is currently unknown. Here, using whole-exome, targeted capture and RNA-sequencing, we report recurrent FHL2-GLI2 fusion genes in 65% (17/26) of SSTs and other GLI2 rearrangements in additional 15% (4/26) SSTs, none of which are detected in other types of SCSTs (n = 48) or common cancer types (n = 9,950). The FHL2-GLI2 fusions result in transcriptomic activation of the Sonic Hedgehog (SHH) pathway in SSTs. Expression of the FHL2-GLI2 fusion in vitro leads to the acquisition of phenotypic characteristics of SSTs, increased proliferation, migration and colony formation, and SHH pathway activation. Targeted inhibition of the SHH pathway results in reversal of these oncogenic properties, indicating its role in the pathogenesis of SSTs. Our results demonstrate that the FHL2-GLI2 fusion is likely the oncogenic driver of SSTs, defining a genotypic-phenotypic correlation in ovarian neoplasms.

Objective: Disparities exist between population subgroups in the use of gynecologic oncologists and high-volume hospitals. The objectives of this study were to explore the experiences of black women obtaining ovarian cancer (OC) care at a high-volume center (HVC) and to identify patient-, provider-, and systems-related factors affecting their access to and use of this level of care., Materials and Methods: Twenty-one semistructured interviews were conducted as part of an institutional review board-approved protocol with women who self-identified as black or African American, treated for OC at a single HVC from January 2013 to May 2017. Recurring themes were identified in transcribed interviews through the process of independent and collaborative thematic content analysis., Results: Five themes were identified: (1) internal attributes contributing to black women's ability/desire to be treated at an HVC, (2) pathways to high- and low-volume centers, (3) obstacles to obtaining care, (4) potential barriers for black women interested in treatment at an HVC, and (5) suggestions for improving HVC use by black women. Study participants who successfully accessed care were comfortable navigating the health care system, understood the importance of self-advocacy, and valued the expertise of an HVC. Barriers to obtaining care at an HVC included lack of knowledge about the HVC, lack of referral, transportation difficulties, and lack of insurance coverage., Conclusion: In this qualitative study, black women treated at an HVC shared attributes and experiences that helped them access care. There is a need to collaborate with black communities and establish interventions to reduce barriers, facilitate access, and disseminate information about the value of receiving care for OC at an HVC.

Objective: Endometrioid ovarian carcinomas (EOCs) comprise 5-10% of all ovarian cancers and commonly co-occur with synchronous endometrioid endometrial cancer (EEC). We sought to examine the molecular characteristics of pure EOCs in patients without concomitant EEC., Methods: EOCs and matched normal samples were subjected to massively parallel sequencing targeting 341-468 cancer-related genes (n = 8) or whole-genome sequencing (n = 28). Mutational frequencies of EOCs were compared to those of high-grade serous ovarian cancers (HGSOCs; n = 224) and EECs (n = 186) from The Cancer Genome Atlas, and synchronous EOCs (n = 23)., Results: EOCs were heterogeneous, frequently harboring KRAS, PIK3CA, PTEN, CTNNB1, ARID1A and TP53 mutations. EOCs were distinct from HGSOCs at the mutational level, less frequently harboring TP53 but more frequently displaying KRAS, PIK3CA, PIK3R1, PTEN and CTNNB1 mutations. Compared to synchronous EOCs and pure EECs, pure EOCs less frequently harbored PTEN, PIK3R1 and ARID1A mutations. Akin to EECs, EOCs could be stratified into the four molecular subtypes: 3% POLE (ultramutated), 19% MSI (hypermutated), 17% copy-number high (serous-like) and 61% copy-number low (endometrioid). In addition to microsatellite instability, a subset of EOCs harbored potentially targetable mutations, including AKT1 and ERBB2 hotspot mutations. EOCs of MSI (hypermutated) subtype uniformly displayed a good outcome., Conclusions: EOCs are heterogeneous at the genomic level and harbor targetable genetic alterations. Despite the similarities in the repertoire of somatic mutations between pure EOCs, synchronous EOCs and EECs, the frequencies of mutations affecting known driver genes differ. Further studies are required to define the impact of the molecular subtypes on the outcome and treatment of EOC patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Epidurals are associated with improved outcomes in some solid tumors, presumably due to their effect on surgical stress response. There are limited data on the prognostic significance of epidural anesthesia in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer. We sought to assess the impact of epidural anesthesia on the survival outcomes of patients undergoing PDS for advanced ovarian cancer., Methods: In this retrospective study, consecutive patients with stage IIIB-IV epithelial ovarian, fallopian tube, or peritoneal carcinoma who underwent PDS at our institution from 01/2005-12/2013 were identified. Progression-free survival (PFS) and overall survival (OS) with regard to epidural use were analyzed., Results: Of 648 patients, 435 received an epidural and 213 did not. Patients in the former group were more likely to have higher stage disease (stage IV disease, 26% vs. 16%, respectively; P = .005), carcinomatosis (87% vs. 80%, respectively; P = .027), and bulky upper abdominal disease (66% vs. 58%, respectively; P = .046). Complete gross resection was achieved in 48% and 32%, respectively (P < .001). For the epidural vs. non-epidural groups, median PFS was 20.8 months and 13.9 months, respectively (P = .021); median OS was 62.4 months and 41.9 months, respectively (P < .001). After controlling for confounding factors, including residual disease, epidural use was independently associated with a decreased risk of progression (HR = 1.327; 95% CI, 1.066-1.653) and death (HR = 1.588; 95% CI, 1.224-2.06)., Conclusions: Perioperative epidural use was independently associated with improved PFS and OS in these patients. Epidural anesthesia at the time of PDS may be warranted in this setting., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To assess complete gross resection (CGR) rates and survival outcomes in patients with advanced ovarian cancer who underwent primary debulking surgery (PDS) during a 13-year period in which specific changes to surgical paradigm were implemented., Methods: We identified all patients with stage IIIB-IV high-grade ovarian carcinoma who underwent PDS at our institution, with the intent of maximal cytoreduction, from 1/2001-12/2013. Patients were categorized by year of PDS based on the implementation of surgical changes to our approach to ovarian cancer debulking (Group 1, 2001-2005; Group 2, 2006-2009; Group 3, 2010-2013)., Results: Among 978 patients, 78% had stage IIIC disease and 89% had disease of serous histology. Carcinomatosis was found in 81%, and 60% had bulky upper abdominal disease (UAD). Compared to Group 1, those who underwent PDS during the latter 2 time periods had higher ASA scores (p < 0.001), higher-stage disease (p < 0.001), and more often had carcinomatosis (p = 0.015) and bulky UAD (p = 0.009). CGR rates for Groups 1-3 increased from 29% to 40% to 55%, respectively (p < 0.001). Five-year progression-free survival (PFS) rates increased over time (15%, 16%, and 20%, respectively; p = 0.199), as did 5-year overall survival (OS) rates (40%, 44%, and 56%, respectively; p < 0.001). On multivariable analysis, CGR was independently associated with PFS (p < 0.001) and OS (p < 0.001)., Conclusions: Despite higher-stage disease and greater tumor burden, CGR rates, PFS and OS for patients who underwent PDS increased over a 13-year period. Surgical paradigm shifts implemented specifically to achieve more complete surgical cytoreduction are likely the reason for these improvements., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer resistant to standard chemotherapy regimens. We sought to characterize the repertoire of somatic mutations in MOCs and to define the contribution of massively parallel sequencing to the classification of tumors diagnosed as primary MOCs., Methods: Following gynecologic pathology and chart review, DNA samples obtained from primary MOCs and matched normal tissues/blood were subjected to whole-exome (n = 9) or massively parallel sequencing targeting 341 cancer genes (n = 15). Immunohistochemical analysis of estrogen receptor, progesterone receptor, PTEN, ARID1A/BAF250a, and the DNA mismatch (MMR) proteins MSH6 and PMS2 was performed for all cases. Mutational frequencies of MOCs were compared to those of high-grade serous ovarian cancers (HGSOCs) and mucinous tumors from other sites., Results: MOCs were heterogeneous at the genetic level, frequently harboring TP53 (75%) mutations, KRAS (71%) mutations and/or CDKN2A/B homozygous deletions/mutations (33%). Although established criteria for diagnosis were employed, four cases harbored mutational and immunohistochemical profiles similar to those of endometrioid carcinomas, and one case for colorectal or endometrioid carcinoma. Significant differences in the frequencies of KRAS, TP53, CDKN2A, FBXW7, PIK3CA and/or APC mutations between the confirmed primary MOCs (n = 19) and HGSOCs, mucinous gastric and/or mucinous colorectal carcinomas were found, whereas no differences in the 341 genes studied between MOCs and mucinous pancreatic carcinomas were identified., Conclusions: Our findings suggest that the assessment of mutations affecting TP53, KRAS, PIK3CA, ARID1A and POLE, and DNA MMR protein expression may be used to further aid the diagnosis and treatment decision-making of primary MOC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes., Methods: This was a retrospective review spanning 1976-2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed., Results: Two hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy-55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%-85%) for patients with stage I to II disease and 17% (95% CI, 8%-29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%-86%) for patients who underwent fertility-preserving surgery., Conclusions: Most patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.

Objective: To evaluate patients with advanced ovarian cancer (OC) undergoing primary debulking surgery (PDS) at a high-volume center (HVC), to determine whether socio-demographic disparities in PDS outcome and overall survival (OS) were present., Methods: All patients with stages IIIB-IV high-grade OC undergoing PDS at our institution from 1/2001-12/2013 were identified. Patients self-identified race/ethnicity as non-Hispanic White (NHW), non-Hispanic Black (NHB), Asian (A), or Hispanic (H). Income level for the entire cohort was estimated using the census-reported income level for each patient's zip code as a proxy for SES. Main outcome measures were PDS outcome and median OS. Cox proportional hazards model was used to examine differences in OS by racial/ethnic and income category, controlling for selected clinical factors., Results: 963 patients were identified for analysis: 855 NHW; 43 A, 34H, 28 NHB, and 3 unknown. PDS outcome was not significantly different among NHB and H as compared to NHW. Compared to NHW, Asians were more likely to have >1cm residual (AOR 2.32, 95%CI 1.1-4.9, p=0.03). Median income for the entire cohort was $85,814 (range $10,926-$231,667). After adjusting for significant prognostic factors, there were no significant differences in PDS outcome between income groups (p=0.7281). Median OS was 55.1mos (95%CI 51.8-58.5) with no significant differences in OS between the income (p=0.628) or racial/ethnic (p=0.615) groups., Conclusion: Statistically significant socio-demographic disparities in PDS and survival outcomes were not observed among women with advanced OC treated at this HVC. Increased efforts are needed to centralize care to and increase the diversity of pts treated at HVCs., (Copyright © 2017. Published by Elsevier Inc.)

Objectives: To assess the perioperative outcomes of minimal access surgery (MAS) in secondary surgical cytoreduction (SSCR) for recurrent epithelial ovarian cancer (ROC); to compare oncologic outcomes with laparotomy (LAP)., Methods: Using an institutional database, we identified all patients with ROC undergoing SSCR from 1/5/09-6/14/14. Selection for MAS or LAP was based on surgeon preference. To minimize selection bias, preoperative imaging was reviewed for all LAP cases. In this manner, we identified potential MAS candidates, who were used in the comparison. Intent-to-treat analyses were undertaken using statistical testing., Results: 170 cases were identified (131 LAP, 8 LSC, 31 RBT). 68/131 (52%) LAP cases were deemed potential candidates for MAS. Feasibility analyses included 68 LAP and 39 MAS cases. Six (15%) MAS cases were converted to LAP. Median age, BMI, operative time did not differ significantly between the groups. Complete gross resection was achieved in 37/39 (95%) MAS, 63/68 (93%) LAP (P=1.0). Median estimated blood loss was 50cm 3 (range, 5-500) MAS, 150cm 3 (range, 0-1500) LAP (P=0.001). Median length of stay was 1day (range, 0-23) MAS, 5days (range, 1-21) LAP (P<0.001). Complications occurred in 3/39 (8%) MAS, 15/68 (22%) LAP (P=0.06). The 2-year progression-free survival was 56.1% (SE 9%) MAS, 63.5% (SE 6%) LAP (P=1.0). The 2-year overall survival was 92.2% (SE 5.4%) MAS, 81.4% (SE 5.5%) LAP (P=0.7)., Conclusions: MAS for SSCR is feasible in properly selected cases. MAS is associated with favorable perioperative outcomes and similar oncologic outcomes, compared to LAP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Because there is no screening test for ovarian cancer, effective prevention strategies may be the best way to reduce the mortality of this most lethal gynecologic malignancy. Increasing evidence supports the hypothesis that the fallopian tube is the site of origin for the vast majority of high-grade serous carcinomas. Our growing understanding of the pathogenesis of this disease offers a rare opportunity to explore new preventive measures, such as bilateral salpingectomy, which may provide great benefit without compromising ovarian function. If the tubal paradigm is accurate, then the impact of bilateral salpingectomy could extend to BRCA1 and BRCA2 mutation carriers, high-risk noncarriers, and average-risk women. The authors present a review of the literature on the role of risk-reducing salpingectomy in all women and in high-risk groups, with a focus on morbidity, ovarian function, potential clinical applicability, and epidemiological considerations. Cancer 2017;123:1714-1720. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Objective: We sought to examine compliance and outcomes using Memorial Sloan Kettering "(MSK) criteria" to predict complete gross resection (CGR) and compare them with the validated Tian and AGO models., Methods: Patients who underwent SCS for recurrent platinum-sensitive ovarian cancer from 5/2001-6/2014 were identified. The AGO and Tian models were applied to the study population; appropriate statistical tests were used to determine ability to predict CGR., Results: 214 SCS cases were identified. Since the implementation of MSK criteria, the CGR rate has been 86%. The AGO model had a 49% accuracy rate in predicting CGR, and predicted gross residual disease (RD) in 51%; however, CGR was achieved in 86%. The Tian model had an 88% accuracy rate. Of the 4% scored as Tian high risk for gross RD, 33% achieved a CGR. Comparing models, McNemar's p-value was 0.366 between the Tian and MSK models and <0.001 between AGO and MSK criteria. Median PFS was 21.3 (95%CI, 18.2-24.5), 22.5 (95%CI, 19.4-25.3), and 14.1months (95%CI, 9.7-22.1) for the entire cohort, for those achieving CGR, and for those left with RD, respectively (p=0.013). OS was 82.2 (95%CI, 60.2-123.3), 95.6 (95%CI, 63.6-NE), and 57.5months (95%CI, 27.5-113.9), respectively (p=0.014)., Conclusion: CGR during SCS is associated with extended PFS and OS. We report a high rate of CGR using MSK criteria. There was good concordance between the Tian and MSK models; however, the latter has fewer variables and is more user-friendly. Tian criteria may be applied to intermediate MSK cases for further stratification., (Copyright © 2017. Published by Elsevier Inc.)

Objective: To assess the ability of preoperative computed tomography scan and CA-125 to predict gross residual disease (RD) at primary cytoreduction in advanced ovarian cancer., Methods: A prospective, non-randomized, multicenter trial of patients who underwent primary debulking for stage III-IV epithelial ovarian cancer previously identified 9 criteria associated with suboptimal (>1cm residual) cytoreduction. This is a secondary post-hoc analysis looking at the ability to predict any RD. Four clinical and 18 radiologic criteria were assessed, and a multivariate model predictive of RD was developed., Results: From 7/2001-12/2012, 350 patients met eligibility criteria. The complete gross resection rate was 33%. On multivariate analysis, 3 clinical and 8 radiologic criteria were significantly associated with the presence of any RD: age≥60years (OR=1.5); CA-125≥600U/mL (OR=1.3); ASA 3-4 (OR=1.6); lesions in the root of the superior mesenteric artery (OR=4.1), splenic hilum/ligaments (OR=1.4), lesser sac >1cm (OR=2.2), gastrohepatic ligament/porta hepatis (OR=1.4), gallbladder fossa/intersegmental fissure (OR=2); suprarenal retroperitoneal lymph nodes (OR=1.3); small bowel adhesions/thickening (OR=1.1); and moderate-severe ascites (OR=2.2). All ORs were significant with p<0.01. A 'predictive score' was assigned to each criterion based on its multivariate OR, and the rate of having any RD for patients who had a total score of 0-2, 3-5, 6-8, and ≥9 was 45%, 68%, 87%, and 96%, respectively., Conclusions: We identified 11 criteria associated with RD, and developed a predictive model in which the rate of having any RD was directly proportional to a predictive score. This model may be helpful in treatment planning., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To explore the impact of primary debulking surgery (PDS) to minimal but gross residual disease (RD) in women with bulky stage IIIC ovarian, fallopian tube, or primary peritoneal cancer., Methods: We retrospectively reviewed all patients with the aforementioned diagnosis who underwent PDS at our institution from 01/2001-12/2010. Those with disease of non-epithelial histology or borderline tumors were excluded. Clinicopathologic data were abstracted, and appropriate statistical tests were used., Results: We identified 496 eligible patients. Median age was 62years; 91% had disease of serous histology. Patients were grouped by RD status: no gross RD, 184 (37%); RD of 1-5mm, 127 (26%); RD of 6-10mm, 54 (11%); and RD >10mm, 131 (26%). With a median follow-up of 53months, the median progression-free survivals (PFS) were: 26.7, 20.7, 16.2, and 13.6months, respectively (p<0.001). The median overall survivals (OS) were 83.4, 54.5, 43.8, and 38.9months, respectively (p<0.001). Among patients with RD following PDS, those with RD of 1-10mm had improved PFS (p<0.001) and OS (p=0.001) compared with those with RD >10mm. Patients with RD 1-10mm who received intravenous/intraperitoneal (IV/IP) chemotherapy were younger and had prolonged OS compared with those solely exposed to IV chemotherapy (p<0.001 and p=0.002, respectively)., Conclusions: PDS to no gross RD was associated with the longest PFS and OS. However, cytoreduction to 1-10mm of RD was also associated with better survival outcomes compared with cytoreduction to >10mm of RD. We conclude that PDS remains an appropriate option for patients with a high likelihood of achieving RD 1-10mm, especially for younger patients who can receive IV/IP chemotherapy after PDS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To examine the use, as well as postoperative and long-term oncologic outcomes of diverting loop ileostomy (DI) during primary debulking surgery (PDS) for ovarian cancer., Methods: Patients with stage II-IV ovarian, fallopian tube, or primary peritoneal carcinoma who underwent colon resection during PDS from 1/2005-1/2014 were identified. Demographic and clinical data were analyzed., Results: Of 331 patients, 320 (97%) had stage III/IV disease and 278 (84%) had disease of high-grade serous histology. Forty-four (13%) underwent a DI. There were no significant differences in age, comorbidity index, smoking status, serum albumin, or attending surgeon between the DI and non-DI groups. Operative time (OR=1.21; 95% CI, 1.03-1.42; p=0.02) and length of rectosigmoid resection (OR=1.04; 95% CI, 1.01-1.08; p=0.02) were predictors of DI on multivariable analysis. The overall anastomotic leak rate was 6%. A comparison of groups (DI vs non-DI) showed no significant differences in major complications (30% vs 23%; p=0.41), anastomotic leak rate (5% vs 7%; p=0.60), hospital length of stay (10 vs 9days; p=0.25), readmission rate (23% vs 17%; p=0.33), or interval to postoperative chemotherapy (41 vs 40days; p=0.20), respectively. Ileostomy reversal was successful in 89% of patients. Median follow-up was 52.6months. There were no differences in median progression-free (17.9 vs 18.6months; p=0.88) and overall survival (48.7 vs 63.8months; p=0.25) between the groups., Conclusions: In patients undergoing PDS, those with longer operative time and greater length of rectosigmoid resection more commonly underwent DI. DI does not appear to compromise postoperative outcomes or long-term survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this article was to broadly review the most up-to-date information pertaining to the centralization of ovarian cancer care in the United States (US) and worldwide., Methods: Much of the present literature pertaining to disparities in, and centralization of, ovarian cancer care in the US and internationally was reviewed, and specifically included original research and review articles., Results: Data show improved optimal debulking rates, National Comprehensive Cancer Network (NCCN) guideline adherence, and overall survival rates in higher-volume, more specialized hospitals, and amongst higher-volume providers., Conclusions: Patients with invasive epithelial ovarian cancer, especially those with higher stages (III and IV), are better served by centralized care in high-volume hospitals and by high-volume physicians, who adhere to NCCN guidelines wherever possible. More research is needed to determine the policy changes that can increase NCCN guideline adherence in low-volume hospitals and low-provider caseload scenarios. Policy and future research should be aimed at increasing patient access, either directly or indirectly, to high-volume hospital and high-volume providers, especially amongst Medicare, lower socioeconomic status, and minority patients.

Objective: The aim of this study was to evaluate the use of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) before and after results from a randomized trial were published and showed non-inferiority between NACT and PDS in the management of advanced-stage ovarian carcinoma., Methods: We evaluated consecutive patients with advanced-stage ovarian cancer treated at our institution from 1/1/08-5/1/13, which encompassed 32 months before and 32 months after the randomized trial results were published. We included all newly diagnosed patients with high-grade histology and stage III/IV disease. Associations between the use of NACT and clinical variables over time were evaluated., Results: Our study included 586 patients. Median age was 62 years (range, 30-90); 406 patients (69%) had stage III disease, and 570 (97%) had disease of serous histology. Twenty-six percent (154/586) were treated with NACT and 74% (432/586) with PDS. NACT use increased significantly from 22% (56/256) before 2010 (at which point the results of the randomized trial were published) to 30% (98/330) after 2010 (p=0.037). Although patients who underwent PDS were more likely to experience grade 3/4 surgical complications than those who underwent NACT, those selected for PDS had a median OS of 71.7 months (CI, 59.8-not reached) compared with 42.9 months (CI 37.1-56.3) for those selected for NACT., Conclusions: In this single-institution analysis, the best survival outcomes were observed in patients who were deemed eligible for PDS followed by platinum-based chemotherapy. Selection criteria for NACT require further definition and should take institutional surgical strategy into account., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict perioperative complications and survival in patients undergoing primary debulking for advanced epithelial ovarian cancer (EOC)., Methods: Data were analyzed for all patients with stage IIIB-IV EOC who underwent primary cytoreduction from 1/2001-1/2010 at our institution. Patients were divided into 3 groups based on an ACCI of 0-1, 2-3, and ≥4. Clinical and survival outcomes were assessed and compared., Results: We identified 567 patients; 199 (35%) had an ACCI of 0-1, 271 (48%) had an ACCI of 2-3, and 97 (17%) had an ACCI of ≥4. The ACCI was significantly associated with the rate of complete gross resection (0-1=44%, 2-3=32%, and ≥4=32%; p=0.02), but was not associated with the rate of minor (47% vs 47% vs 43%, p=0.84) or major (18% vs 19% vs 16%, p=0.8) complications. The ACCI was also significantly associated with progression-free (PFS) and overall survival (OS). Median PFS for patients with an ACCI of 0-1, 2-3, and ≥4 was 20.3, 16, and 15.4 months, respectively (p=0.02). Median OS for patients with an ACCI of 0-1, 2-3, and ≥4 was 65.3, 49.9, and 42.3 months, respectively (p<0.001). On multivariate analysis, the ACCI remained a significant prognostic factor for both PFS (p=0.02) and OS (p<0.001)., Conclusions: The ACCI was not associated with perioperative complications in patients undergoing primary cytoreduction for advanced EOC, but was a significant predictor of PFS and OS. Prospective clinical trials in ovarian cancer should consider stratifying for an age-comorbidity covariate., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Granulosa cell tumors (GCTs) are rare, and the role of chemotherapy in their management is not clearly defined., Methods: We performed a retrospective cohort study of GCT patients diagnosed from January 1996 through June 2013 at the Memorial Sloan Kettering Cancer Center, comparing those who received adjuvant chemotherapy to those who did not. Differences between groups were assessed using the log-rank test. Statistical significance was set at p<0.05., Results: Of 118 patients, 10 (8%) received adjuvant chemotherapy (1 [1%] of 103 stage I and 9 [60%] of 15 stage II-IV patients). Thirty-two patients (27%) experienced disease recurrence. Four patients had residual disease after initial surgery, and all received adjuvant chemotherapy; each recurred within 24.3 months (median PFS, 8.2 months). The time to first recurrence was longer in patients who did not receive adjuvant chemotherapy. For patients with recurrent disease, receiving chemotherapy after surgery for first recurrence did not seem to improve time to second recurrence versus surgery alone (HR 0.98; p=0.965). Additionally, 12 patients (10%) had a previous diagnosis of breast cancer-an incidence rate 3.22 times higher than Surveillance, Epidemiology, and End Results (SEER) data predicts (p<0.001)., Conclusions: Although the numbers were small, in this analysis chemotherapy was not found to improve the recurrence-free interval of patients with GCTs, a finding that requires prospective validation. Residual disease after surgery was associated with poor prognosis. Finally, there was a significantly higher than expected incidence of antecedent breast cancer in this population, an association that deserves further exploration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess the ability of preoperative computed tomography (CT) scan of the abdomen/pelvis and serum CA-125 to predict suboptimal (>1cm residual disease) primary cytoreduction in advanced ovarian, fallopian tube, and peritoneal cancer., Methods: This was a prospective, non-randomized, multicenter trial of patients who underwent primary cytoreduction for stage III-IV ovarian, fallopian tube, and peritoneal cancer. A CT scan of the abdomen/pelvis and serum CA-125 were obtained within 35 and 14 days before surgery, respectively. Four clinical and 20 radiologic criteria were assessed., Results: From 7/2001 to 12/2012, 669 patients were enrolled; 350 met eligibility criteria. The optimal debulking rate was 75%. On multivariate analysis, three clinical and six radiologic criteria were significantly associated with suboptimal debulking: age ≥ 60 years (p=0.01); CA-125 ≥ 500 U/mL (p<0.001); ASA 3-4 (p<0.001); suprarenal retroperitoneal lymph nodes >1cm (p<0.001); diffuse small bowel adhesions/thickening (p<0.001); and lesions >1cm in the small bowel mesentery (p=0.03), root of the superior mesenteric artery (p=0.003), perisplenic area (p<0.001), and lesser sac (p<0.001). A 'predictive value score' was assigned for each criterion, and the suboptimal debulking rates of patients who had a total score of 0, 1-2, 3-4, 5-6, 7-8, and ≥ 9 were 5%, 10%, 17%, 34%, 52%, and 74%, respectively. A prognostic model combining these nine factors had a predictive accuracy of 0.758., Conclusions: We identified nine criteria associated with suboptimal cytoreduction, and developed a predictive model in which the suboptimal rate was directly proportional to a predictive value score. These results may be helpful in pretreatment patient assessment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate the risk factors and potential morbidity associated with intraoperative hypothermia (IH) during cytoreductive surgery (CRS) for advanced ovarian cancer., Methods: Demographic and perioperative data were collected for all patients with stage IIIC-IV ovarian, fallopian tube, and primary peritoneal carcinoma who underwent primary CRS at our institution from 2001 to 2010. Only patients with carcinomatosis and/or bulky upper abdominal disease and residual disease of <1cm were included. Intraoperative hypothermia was defined as temperature of <36.0 degrees Celsius (°C). Associations with 21 perioperative factors, 12 systems-based complications, and specific complications including but not limited to venous thromboembolism and surgical site infection were evaluated., Results: Two hundred ninety-seven patients met the inclusion criteria. An intraoperative temperature <36°C was noted in 72.1% of patients, and a temperature <36°C at the time of abdominal closure was noted in 45.5%. Intraoperative vasopressors (P=0.02), epidural anesthesia (P=0.01), transfusion of fresh frozen plasma (P<0.05), and blood loss (P=0.01) were associated with IH. There was no association between IH and postoperative complications in general (P=0.48) or specifically grade 3-5 complications (P=0.34). Univariate analysis did show an association between hematologic complications and IH; however, this did not persist on multivariate analysis (P=0.14)., Conclusions: In patients who underwent optimal primary CRS for advanced ovarian cancer, IH alone was not associated with the development of postoperative complications. Postoperative morbidity in these patients is multifactorial and further investigation into modifiable risk factors is warranted., (© 2013.)