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ImportancePlatinum-based chemotherapy has been the standard of care for ovarian cancer for the past 3 decades. Although most patients respond to platinum-based treatment, emergence of platinum resistance in recurrent ovarian cancer is inevitable during the disease course. Outcomes for patients with platinum-resistant ovarian cancer are poor, and options remain limited, highlighting a substantial unmet need for new treatment options.ObservationsThis review summarizes the current and evolving treatment landscape for platinum-resistant ovarian cancer with a focus on the development of novel compounds. Biologic and targeted therapies such as bevacizumab and poly (ADP-ribose) polymerase (PARP) inhibitors—originally approved in the platinum-resistant setting but since withdrawn—are now used in the up-front or platinum-sensitive setting, prolonging the duration of platinum sensitivity and delaying the use of nonplatinum options. The greater use of maintenance therapy and the emphasis on using platinum beyond first-line treatment has most likely been associated with a greater number of lines of platinum therapy before a patient is designated as having platinum-resistant ovarian cancer. In this contemporary setting, recent trials in platinum-resistant ovarian cancer have mostly had negative outcomes, with none having a clinically significant effect on progression-free or overall survival since the approval of bevacizumab in combination with chemotherapy. Nonetheless, a multitude of new therapies are under evaluation; preliminary results are encouraging. A focus on biomarker-directed treatment and patient selection may provide greater success in identifying novel therapies for treating platinum-resistant ovarian cancer.Conclusions and RelevanceAlthough many clinical trials in platinum-resistant ovarian cancer have had negative outcomes, these failures provide insights into how clinical trial design, biomarker-directed therapy, and patient selection could facilitate future successes in platinum-resistant ovarian cancer treatment.

PurposeTo test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer.Methods and materialsIn an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS.ResultsIn total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P=.048) and in the combined cohort (13% vs 35%, χ2P=.01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P=.216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group.ConclusionsPET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

Objective To describe the practice patterns and outcomes of patients with stage 3B endometrial cancer. Methods We queried the National Cancer Database for all surgically staged, stage 3 patients between 2012 and 2016. Patients who received any pre-operative therapy were excluded. Demographics, tumor factors, and adjuvant therapy for the stage 3 substages were compared. Logistic regression was used to identify factors associated with adjuvant therapy. Kaplan Meier curves were generated and compared using the log-rank test. Multivariable Cox Proportional Hazards Model was used to adjust for prognostic factors. Findings with p Results Of 7363 patients with stage 3 disease, 478 (6%) had stage 3B; 1732 (23%) had stage 3A, 3457 (48%) had stage 3C1, and 1696 (23%) had stage 3C2 disease. Post-surgical treatment consisted of: combined chemotherapy (CT) and radiation (RT) (49%), CT alone (28%), RT alone (9%), 14% received no postoperative therapy. Among all stage 3 substages, patients with stage 3B disease were the least likely to receive any CT, and the most likely to receive RT alone. After adjusting for known prognostic factors, patients with stage 3A (Hazard ratio (HR) of death = 0.64) and 3C1 (HR of death = 0.79) disease had significantly worse overall survival compared to stage 3B; survival was not demonstrably different from patients with stage 3C2 disease. Patients with stage 3B disease who received CT + RT had the best overall survival. Conclusion Survival of patients with stage 3B disease is similar to that of patients with para-aortic node metastases and is inferior to all others with stage 3 endometrial cancer. Less frequent CT and a higher rate of post-operative RT alone, describes a distinct practice from that seen in other stage 3 patients.

Radiomics has been applied to predict recurrence in several disease sites, but current approaches are typically restricted to analyzing tumor features, neglecting nontumor information in the rest of the body. The purpose of this work was to develop and validate a model incorporating nontumor radiomics, including whole-body features, to predict treatment outcomes in patients with previously untreated locoregionally advanced cervical cancer. Methods: We analyzed 127 cervical cancer patients treated definitively with chemoradiotherapy and intracavitary brachytherapy. All patients underwent pretreatment whole-body 18F-FDG PET/CT. To quantify effects due to the tumor itself, the gross tumor volume (GTV) was directly contoured on the PET/CT image. Meanwhile, to quantify effects arising from the rest of the body, the planning target volume (PTV) was deformably registered from each planning CT to the PET/CT scan, and a semiautomated approach combining seed-growing and manual contour review generated whole-body muscle, bone, and fat segmentations on each PET/CT image. A total of 965 radiomic features were extracted for GTV, PTV, muscle, bone, and fat. Ninety-five patients were used to train a Cox model of disease recurrence including both radiomic and clinical features (age, stage, tumor grade, histology, and baseline complete blood cell counts), using bagging and split-sample-validation for feature reduction and model selection. To further avoid overfitting, the resulting models were tested for generalization on the remaining 32 patients, by calculating a risk score based on Cox regression and evaluating the c-index (c-index > 0.5 indicates predictive power). Results: Optimal performance was seen in a Cox model including 1 clinical biomarker (whether or not a tumor was stage III-IVA), 2 GTV radiomic biomarkers (PET gray-level size-zone matrix small area low gray level emphasis and zone entropy), 1 PTV radiomic biomarker (major axis length), and 1 whole-body radiomic biomarker (CT bone root mean square). In particular, stratification into high- and low-risk groups, based on the linear risk score from this Cox model, resulted in a hazard ratio of 0.019 (95% CI, 0.004, 0.082), an improvement over stratification based on clinical stage alone, which had a hazard ratio of 0.36 (95% CI, 0.16, 0.83). Conclusion: Incorporating nontumor radiomic biomarkers can improve the performance of prognostic models compared with using only clinical and tumor radiomic biomarkers. Future work should look to further test these models in larger, multiinstitutional cohorts.

BackgroundThe optimal treatment strategy for women with newly diagnosed ovarian cancer has yet to be determined. Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated substantial improvement in progression-free survival as monotherapy maintenance treatment in the frontline setting versus active surveillance. Furthermore, preclinical and early clinical studies have shown that PARP inhibitors and immune checkpoint inhibitors have synergistic antitumor activity and may provide an additional therapeutic option for patients in this population.Primary ObjectivesIn women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer, we wish to assess the efficacy of frontline maintenance treatment with the PARP inhibitor rucaparib versus placebo following response to platinum-based chemotherapy (ATHENA–MONO), and to assess the combination of rucaparib plus nivolumab (a programmed death receptor 1 (PD-1)–blocking monoclonal antibody) versus rucaparib alone (ATHENA–COMBO).Study Hypothesis(1) Maintenance therapy with rucaparib monotherapy may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting. (2) The combination of nivolumab plus rucaparib may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting compared with rucaparib alone.Trial DesignATHENA is an international, randomized, double-blind, phase III trial consisting of two independent comparisons (ATHENA–MONO and ATHENA–COMBO) in patients with newly diagnosed platinum-sensitive ovarian cancer. Patients are randomized 4:4:1:1 to the following: oral rucaparib+ intravenous nivolumab (arm A); oral rucaparib + intravenous placebo (arm B); oral placebo+ intravenous nivolumab (arm C); and oral placebo + intravenous placebo (arm D). The starting dose of rucaparib is 600 mg orally twice a day and nivolumab 480 mg intravenously every 4 weeks. ATHENA–MONO compares arm B with arm D to evaluate rucaparib monotherapy versus placebo, and ATHENA–COMBO evaluates arm A versus arm B to investigate the effects of rucaparib and nivolumab in combination versus rucaparib monotherapy. ATHENA–MONO and ATHENA–COMBO share a common treatment arm (arm B) but each comparison is independently powered.Major Inclusion/Exclusion CriteriaPatients ≥18 years of age with newly diagnosed advanced, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer who have achieved a response after completion of cytoreductive surgery and initial platinum-based chemotherapy are enrolled. No other prior treatment for ovarian cancer, other than the frontline platinum regimen, is permitted.Primary EndpointThe primary endpoint is investigator-assessed progression-free survival by Response Evaluation Criteria in Solid Tumors v1.1.Sample SizeApproximately 1000 patients have been enrolled and randomized.Estimated Dates for Completing Accrual and Presenting ResultsThe trial completed accrual in 2020. While dependent on event rates, primary results of ATHENA–MONO are anticipated in early 2022 and results of ATHENA–COMBO are anticipated to mature at a later date.Trial RegistrationThis trial is registered at clinicaltrials.gov (NCT03522246).

The GOG Foundation, Inc. (GOG-F) is a non-profit 501(c)(3) organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. GOG Partners (GOG-P) is a program of the GOG-F and is positioned alongside NRG Oncology under the GOG-F organizational umbrella. GOG-P operates outside of the federally funded NCI NRG Oncology, a key distinguishing feature. By functioning as a site management organization (SMO), GOG-P provides an additional platform for clinical trial development, mentorship opportunities, patient accrual, and site infrastructure support yielding an expanded gynecologic oncology clinical trials infrastructure in the US. GOG-P has a consistent track record of conducting high quality clinical trials that lead to bringing novel FDA approved treatments for gynecologic cancer. This manuscript summarizes the history and organizational structure of the GOG-P. In addition, we outline the other key supportive programs within the GOG-F that help support the GOG-P effort to perform transformative gynecologic cancer research.

We report on a woman with aggressive estrogen receptor‐positive, KRAS‐mutated ovarian cancer who achieved a remarkable response to combination therapy with the MEK inhibitor (trametinib) and the aromatase inhibitor (letrozole), even though the disease had failed to respond to a combination of a PI3K inhibitor and different MEK inhibitor, as well as to trametinib and the estrogen modulator, tamoxifen, and to letrozole by itself. The mechanism of action for exceptional response was elucidated by in vitro experiments that demonstrated that the fact that tamoxifen can have an agonistic effect in addition to antagonist activity, whereas letrozole results only in estrogen depletion was crucial to the response achieved when letrozole was combined with an MEK inhibitor. Our current observations indicate that subtle variations in mechanisms of action of outwardly similar regimens may have a major impact on outcome and that such translational knowledge is critical for optimizing a precision medicine strategy. Key Points This report describes the remarkable response of a patient with KRAS‐mutated, estrogen receptor‐positive low‐grade serous ovarian cancer treated with trametinib (MEK inhibitor) and letrozole (aromatase inhibitor), despite prior progression on similar agents including tamoxifen (estrogen modulator).In vitro investigation revealed that tamoxifen can have agonistic in addition to antagonistic effects, which could be the reason for the patient not responding to the combination of trametinib and tamoxifen.The current observations suggest that drugs with different mechanisms of action targeting the same receptor may have markedly different anticancer activity when used in combinations., This article reports the case of a patient with aggressive estrogen receptor‐positive, KRAS‐mutated ovarian cancer who achieved a remarkable response to combination therapy with the MEK inhibitor trametinib and the aromatase inhibitor letrozole, despite earlier failures of treatment with other combination inhibitor treatment. This article focuses on the possibility that subtle variations in mechanisms of action of outwardly similar regimens may have major effects on patient outcomes.

Novel therapies combined with radiation continue to be of significant interest in the developmental treatment paradigm of gynecologic cancers. Clinical implementation of immunotherapy in oncology has rapidly changed the treatment landscape, options, paradigm, and outcomes through clinical trials. Immunotherapy has emerged as a therapeutic pillar in the treatment of solid tumors with demonstrable synergistic activity when combined with radiation therapy and chemoradiotherapy by an alteration or enhancement of the immune system. In solid tumors, radiation therapy induces migration of dendritic cells, T cell activation, and proliferation, and increases in tumor-infiltrating lymphocytes. These immunomodulatory effects in conjunction with immune checkpoint blockade are currently under active investigation in the adjuvant, definitive, and metastatic settings. Results from early phase trials demonstrate promising efficacy and overall tolerable toxicity profiles of combined modality treatment. There is significant interest in optimizing the treatment for patients with locally advanced cervical cancer beyond the standard of care-chemoradiation-which has been in place for the last 30 years. The majority of cervical cancer emerges after persistent infection with a high-risk subtype of the human papillomavirus, where viral oncoproteins lead to cellular changes and immortalization. As a result, immune tolerance can develop, resulting in cancer. Knowledge of the mechanism of human papillomavirus-related oncogenesis suggests that immune therapy or checkpoint blockade can reinvigorate an antitumor immune response. Current clinical trials are exploring the therapeutic potential of these approaches. Uterine cancers have been grouped into 4 molecular subclasses by their driver mutations, mutational burden, and copy-number alterations. Of these subgroups, the polymerase epsilon-mutated and microsatellite-unstable may represent up to 40% of endometrial cancers, and they have been shown to be immunogenic. Because of the inherent immunogenicity of these MSI-high tumors, combined immune modulation strategies, including chemotherapy, radiation, and immunotherapy and immune checkpoint inhibitor therapy, are being explored to improve treatment outcomes. In this review, we explore current immunomodulatory and multimodality therapeutic approaches in the treatment of cervical and uterine cancer through ongoing clinical trials investigating the combination of immunotherapy and radiation therapy.

ObjectiveTo evaluate the influence of marital status and other demographic factors on survival of patients with ovarian cancer.Study designData were obtained from the Surveillance, Epidemiology, and End Results database from 2010 to 2015. Analyses were performed using Kaplan–Meier and multivariate Cox proportional hazard methods.ResultsOf 19 643 patients with ovarian cancer (median age 60 years, range 18–99), 16 278 (83%), 1381 (7%), 1856 (9%), and 128 (1%) were White, Black, Asian, and Native American, respectively. The majority of patients (10 769, 55%) were married while 4155 (21%) were single, 2278 (12%) were divorced, and 2441 (12%) were widowed. Patients were more likely to be married if they were Asian (65%) or White (56%) than if they were Black (31%) or Native American (39%) (pConclusionMarried patients with ovarian cancer were more likely to undergo chemotherapy with better survival rates. Black, uninsured, or patients with Medicaid insurance had poorer outcomes.

Purpose The use of concurrent doublet chemotherapy with radiation for locoregionally advanced cervical cancer (LACC) is limited by gastrointestinal and hematologic toxicity. By reducing radiation dose to bowel and bone marrow, image guided intensity modulated radiation therapy (IG-IMRT) may improve chemotherapy tolerance. The goal of this study was to determine whether IG-IMRT could lead to improved tolerance to concurrent cisplatin and gemcitabine for LACC. Methods and Materials We conducted an open-label, nonrandomized, prospective phase 1 dose escalation trial at a tertiary academic cancer center ( ClinicalTrials.gov identifier: NCT01554410). We enrolled patients with stage IB-IVA cervical cancer, with either an intact cervix or posthysterectomy with residual/recurrent pelvic or paraortic nodal involvement, undergoing radical pelvic or extended field chemoradiation therapy. Treatment consisted of chemoradiation with IG-IMRT (45-47.6 Gy, 25-28 fractions to the pelvis ± paraortic nodes with simultaneous nodal boost to 53.2-59.4 Gy, 28 fractions) plus 5 cycles of concurrent weekly cisplatin 40 mg/m2 with escalating doses of gemcitabine (50, 75, 100, or 125 mg/m2). Cohorts were separated preregistration according to whether the patient received pelvic or extended field IG-IMRT and whether gemcitabine followed (CG) or preceded (GC) cisplatin delivery. Dose-limiting toxicity (DLT) events were monitored up to 30 days after chemoradiation therapy. The primary endpoint was maximum tolerated dose (MTD) resulting in DLT probability ≤20%. Results Between February 2011 and June 2019, 35 patients were registered. Overall, 7 patients (20.0%) experienced DLTs. For the pelvic field cohort, the estimated MTD was 100 mg/m2 with GC sequencing, which is higher than the previously reported MTD for this regimen. The extended field cohort was closed after 2 of 3 patients experienced a DLT at the first dose level. Conclusions IG-IMRT can permit higher doses of concurrent gemcitabine with cisplatin and pelvic radiation for LACC. However, acute toxicity remains a factor with this regimen, depending on radiation volume and chemotherapy sequencing.

Background: Dual checkpoint inhibition with anti-PD-1 and anti-CTLA4 checkpoint inhibitors have proven to be efficacious in numerous malignancies. This study presents the first results of ipilimumab and nivolumab in the clear cell gynecologic cancer cohorts of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg IV every 6wk) plus nivolumab (240mg IV every 2wk). The primary endpoint was objective response rate (ORR) (RECIST v1.1) (confirmed CR and PR); progression-free survival (PFS), overall survival (OS), stable disease (SD) >6 months, and toxicity are secondary endpoints. Results: Evaluable patients were as follows: clear cell ovarian cancer (N=19); clear cell endometrial cancer (N=8); clear cell cervical (N=5) (median ages, 53, 66, and 59 years; cohorts 46, 45, and 42, respectively) In the clear cell ovarian cancer cohort, ORR was 21.1% [CR, 15.8%, n=3; PR, 5.3%, n=1]; clinical benefit rate (CBR) (includes stable disease ≥6 months) was 31.6% (6/19 patients). Among three patients with confirmed CR, two patients showed 100% regression (with ongoing response at 36+ months and 37+ months respectively), and the other patient showed 67% regression (due to lymph node < 1.0cm), but eventually progressed after 722 days. One confirmed PR patient achieved 75% regression (ongoing response at 53+ months). Of note, three patients achieved unconfirmed PR; one showed 34% regression (5 months); another, 38% (51.5+ months); and another, 58% regression (5 months). The ORR when including unconfirmed PR is 36.8% (7/19). Median PFS was 3.7 months (95% confidence interval (CI); 1.7-∞). Median OS was 21.7 months (6.4-∞). In the clear cell endometrial cancer cohort, ORR was 0%; CBR, 25% (2/8 patients). Of note, one patient achieved unconfirmed PR with 69% regression (4 months). The ORR when including unconfirmed PR is 12.5% (1/8). Median PFS was 2.0 months (95% confidence interval; 1.8-na). Median OS was 4.3 months (4.2-na). In the clear cell cervical cancer cohort, ORR was 0%; CBR, 20.0% (1/5 patients). Median PFS was 2.2 months (95% CI; 1.9-na). Median OS was 23.6 months (95% CI; 15.3-na). The most common adverse events, in the three cohorts combined, were nausea (37.5%, n=12), fatigue (34.4%, n=11), anorexia (31.2%, n=10), hypothyroidism (31.2%, n=10), and pruritus (28.1%, n=9). Grade 3-4 adverse events were reported in 17 cases (53.1%) with no grade 5 adverse events. Conclusion: Ipilimumab plus nivolumab in 19 clear cell ovarian cancer patients resulted in an ORR of 21.1% and CBR of 31.6%, with two durable CRs ongoing at 3+ years; CBR was 25% and 20%, respectively, in clear cell endometrial and cervical cohorts, with no objective responses, albeit with only 8 and 5 patients per cohort. Correlative studies to determine response/resistance markers are ongoing. Further prospective studies in rare gynecologic malignancies are warranted. Citation Format: Young Kwang Chae, Christopher W. Ryan, Naing Aung, William R. Robinson, Megan Othus, Elad Sharon, David M. O'Malley, Floortje J. Backes, Charles D. Blanke, Ramez N. Eskander, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the clear cell ovarian, endometrial, cervical cancer cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT162.

PURPOSE Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS ( P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

Purpose:To analytically and clinically validate microsatellite instability (MSI) detection using cell-free DNA (cfDNA) sequencing.Experimental Design:Pan-cancer MSI detection using Guardant360 was analytically validated according to established guidelines and clinically validated using 1,145 cfDNA samples for which tissue MSI status based on standard-of-care tissue testing was available. The landscape of cfDNA-based MSI across solid tumor types was investigated in a cohort of 28,459 clinical plasma samples. Clinical outcomes for 16 patients with cfDNA MSI-H gastric cancer treated with immunotherapy were evaluated.Results:cfDNA MSI evaluation was shown to have high specificity, precision, and sensitivity, with a limit of detection of 0.1% tumor content. In evaluable patients, cfDNA testing accurately detected 87% (71/82) of tissue MSI-H and 99.5% of tissue microsatellite stable (863/867) for an overall accuracy of 98.4% (934/949) and a positive predictive value of 95% (71/75). Concordance of cfDNA MSI with tissue PCR and next-generation sequencing was significantly higher than IHC. Prevalence of cfDNA MSI for major cancer types was consistent with those reported for tissue. Finally, robust clinical activity of immunotherapy treatment was seen in patients with advanced gastric cancer positive for MSI by cfDNA, with 63% (10/16) of patients achieving complete or partial remission with sustained clinical benefit.Conclusions:cfDNA-based MSI detection using Guardant360 is highly concordant with tissue-based testing, enabling highly accurate detection of MSI status concurrent with comprehensive genomic profiling and expanding access to immunotherapy for patients with advanced cancer for whom current testing practices are inadequate.See related commentary by Wang and Ajani, p. 6887

Objectives This review aims to (1) describe evidence supporting the fallopian tube as a site of high-grade serous carcinoma, (2) review literature regarding salpingectomy in high- and average-risk women, and (3) discuss feasibility and safety of salpingectomy in urogynecologic surgery. Methods PubMed and university library resources were used to retrieve relevant English-language publications via keyword search, including "ovarian cancer," "salpingectomy," "risk," "safety," "hysterectomy," "trends," "technique," and "urogynecology." Each publication was reviewed in detail and references incorporated, where relevant. Results Evidence supports the fimbriated portion of the fallopian tube as a site of high-grade serous carcinoma in both hereditary and sporadic cases. Routine opportunistic salpingectomy in average-risk women may reduce ovarian cancer risk by 42% to 65% and prevent future surgery for benign tubal disease. Opportunistic salpingectomy is cost-effective for sterilization and cost-saving during hysterectomy. For genetically predisposed women, salpingo-oophorectomy remains the recommended strategy for ovarian cancer risk reduction. Despite being feasible, safe, and cost-effective, concomitant salpingectomy is least commonly performed during vaginal hysterectomy compared with other hysterectomy routes. Salpingectomy rates during vaginal hysterectomy are influenced by geographic factors, surgeon experience, and adhesive disease. Conclusions Opportunistic salpingectomy holds promise as a risk-reducing intervention for ovarian cancer. The American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncology recommend that physicians counsel average-risk women regarding opportunistic salpingectomy when planning pelvic surgery. Randomized controlled trials are needed to evaluate long-term implications of salpingectomy. Urogynecologic surgeons should discuss salpingectomy as part of surgical informed consent. Vaginal salpingectomy should be incorporated into residency and fellowship training programs.

Objectives: To investigate the representation of women as principal investigators (PI) in phase 3, gynecologic oncology clinical trials. Methods: ClinicalTrials.gov was queried for all phase 3 clinical trials with start dates between January 1, 2010 and December 31, 2020 using the search terms: ‘ovarian cancer,’ ‘endometrial cancer,’ and ‘cervical cancer.’ Trial characteristics including registration year, location, current status, results, disease site, intervention studied, primary outcome, and funding source were abstracted from the website. Gender of the PI was assessed by name and image on internet search. If this information was unavailable, the trial coordinator was queried. Trials were considered to have women's representation if women were the sole PI or among multiple co-PIs. Chi-square tests were used to compare proportions across groups; p Results: All 200 clinical trials identified were included in this analysis. Of all trials, 49% were conducted in ovarian cancer patients, 32% in cervical cancer and 20% in endometrial cancer. At the time of data collection, nearly 61% of trials were recruiting, 25% were active but not yet recruiting and 14% were completed. The majority (61%) of trials were sponsored by an academic institution, 25% by industry, and 13% by oncologic cooperative groups. Trials were registered in the United States (US) and Canada (26%), Europe (18%), Asia (31%), or multi-nationally (21%). Women were represented as a PI in 76 (38%) trials. Women were significantly more likely to be a PI of a clinical trial registered in the US/Canada compared to Asia (50% vs. 25%, p=0.01.) The proportion of women PIs was not significantly different for trials registered Europe (40%), or multi-nationally (39%), compared to those registered in the US/Canada or in Asia. Overall, women's representation as a PI increased over time (by year of registration, R2=0.61, p=0.01) (Figure 1). This increase was most pronounced in multi-national trials. The proportion of women PIs rose significantly from 19% among multinational trials registered from 2010-2015 to 52% among multinational trials registered from 2016-2020 (p=0.03.) There was no statistically significant change comparing proportion of women PIs from 2010-15 to 2016-20 in US/Canada (50% in both periods), Europe (29% vs. 48%, p=0.26), or Asia (22% vs. 29%, p=0.50.) Women were more likely to be represented in trials that are currently active/recruiting than in trials that have completed (41% vs. 21%, p=0.04). Disease site, funding source, interventions studied, and outcome measures were not associated with the representation of women as PIs in clinical trials. Download : Download high-res image (44KB) Download : Download full-size image Conclusions: Women's representation as PIs in clinical trials is increasing, most notably in multi-national trials. Reasons for observed regional variation are beyond the scope of this investigation but may be elucidated by further study.

Background New cervical cancer screening guidelines recommend primary human papillomavirus (HPV) testing for women age 30–65 years. Healthcare organizations are preparing to de-implement the previous recommended strategies of Pap testing or co-testing (Pap plus HPV test) and substitute primary HPV testing. However, there may be significant challenges to the replacement of this entrenched clinical practice, even with an evidence-based substitution. We sought to identify stakeholder-perceived barriers and facilitators to this substitution within a large healthcare system, Kaiser Permanente Southern California. Methods We conducted semi-structured qualitative interviews with clinician, administrative, and patient stakeholders regarding (a) acceptability and feasibility of the planned substitution; (b) perceptions of barriers and facilitators, with an emphasis on those related to the de-implementation/implementation cycle of substitution; and (c) perceived readiness to change. Our interview guide was informed by the Consolidated Framework for Implementation Research (CFIR). Using a team coding approach, we developed an initial coding structure refined during iterative analysis; the data were subsequently organized thematically into domains, key themes, and sub-themes using thematic analysis, followed by framework analysis informed by CFIR. Results We conducted 23 interviews: 5 patient and 18 clinical/administrative. Clinicians perceived that patients feel more tests equals better care, and clinicians and patients expressed fear of missed cancers (“…it’ll be more challenging convincing the patient that only one test is…good enough to detect cancer.”). Patients perceived practice changes resulting in “less care” are driven by the desire to cut costs. In contrast, clinicians/administrators viewed changing from two tests to one as acceptable and a workflow efficiency (“…It’s very easy and half the work.”). Stakeholder-recommended strategies included focusing on the increased efficacy of primary HPV testing and developing clinician talking points incorporating national guidelines to assuage “cost-cutting” fears. Conclusions Substitution to replace an entrenched clinical practice is complex. Leveraging available facilitators is key to ease the process for clinical and administrative stakeholders—e.g., emphasizing the efficiency of going from two tests to one. Identifying and addressing clinician and patient fears regarding cost-cutting and perceived poorer quality of care is critical for substitution. Multicomponent and multilevel strategies for engagement and education will be required. Trial registration ClinicalTrials.gov, #NCT04371887

Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).

BACKGROUND Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH

Highlights • 30.6% of responding gynecologic oncologists reported assignment of authorship that did not meet ICMJE criteria. • The majority reported that ICMJE criteria were generalizable, helpful and considered non-adherence as scientific misconduct. • Fellows and faculty in their first five year of practice were more likely not adhere to ICMJE authorship criteria., Authorship confers credit to those responsible for a publication. In 1985, the International Committee of Medical Journal Editors criteria were founded to standardize authorship assignment. We sought to investigate practices and values in authorship assignment in Society of Gynecologic Oncology (SGO) members. An anonymous online survey was distributed to SGO members from 09/2018–10/2018. Three multivariable logistic regression models were fit to predict ICJME authorship acceptance, assignment and denial. Of 1111 members surveyed, 266 responses were received (23.9%); 30.6% reported prior authorship assignment that did not meet ICMJE criteria, and 18.8% (n = 50) reported a history of accepting authorship not meeting ICJME criteria. Reasons for non-adherence included: inclusion of the author’s patients in the study (59.3%), resumé building (45.7%), and networking for career advancement (22.2%). The majority responded that ICJME criteria were generalizable (91.3%), helpful (83.8%), and considered non-adherence as scientific misconduct (66.0%). On multivariable analysis, practice duration of 5–20 years (HR 0.40, 95% CI 0.16, 0.99, p 20 years (HR 0.22, 95% CI 0.08, 0.59, p 20 years (HR 25.9, 95% CI 1.06, 3.9, p

Objectives: To compare the relative importance of prognostic factors, and their interactions with lymph node dissection (LND), on receipt of post-operative adjuvant radiation (RT) in patients with stage 1 EC. Methods: We queried the National Cancer Database for all EC patients with pathologic stage 1 EC who had total hysterectomy from 2012-16. Patients who received preoperative RT or any chemotherapy were excluded. Logistic regression of grade, myometrial invasion (MI), age, lymphovascular space invasion (LVSI) and LND including interaction terms of each of the prognostic factors with LND was conducted to model receipt of RT. We ranked the regression coefficients of individual prognostic factors (bfactor), and interactions with any LND (bfactorxLND) to compare the magnitude of associations with RT. Relative contribution of the interaction terms (% change=bfactorxLND/bfactor x 100%) were also compared. Findings were accepted as significant at p Results: 53,265 patients comprised the study population. The majority of patients were years old (59%), had 50% MI is independently associated with the highest probability of receiving RT, followed by poorly differentiated tumor, LVSI, moderately differentiated tumor and age 60 or greater, in that order. Although LND is independently associated with increased RT, documentation of uninvolved nodes reduces the magnitude if the association of RT with age >60, LVSI, grade 2 and >50% MI. LND was not found to modify the association of grade 3 disease with RT (Table 1). Conclusions: The positive association between any LND and increased receipt of postoperative RT has previously been reported by other investigators. Our findings suggest this finding may be due to confounding, since the interaction terms of LND with nearly all individual prognostic factors are negative, indicating that documentation of negative nodes decreases the frequency of RT associated with nearly all high risk prognostic factors. The range of bfactor's, suggests that, in practice, there is a hierarchy of concern for recurrence associated with the individual prognostic factors. Future investigations that more precisely identify the independent risk for recurrence associated with each factor, as well as confounders associated with both LND and RT, may help refine the decision making process.

Objectives: The SARS-CoV-2 pandemic forced a shift in conducting clinical research. Ensuring the safety of all stakeholders (patients, research personnel, family members), maintaining financial viability, and overcoming operational restrictions (limited access to sites, workforce restrictions, reduced data collection) are barriers to continuing clnical research. GOG Partners, the GOG Foundation industry-sponsored clinical trials group, has been proactive to implement the following: 1) immediate compliance with CDC, FDA, and NIH guidelines with regard to clinical trial management; 2) systems that allowed for remote monitoring and other remote activities (telemedicine patient visits, remote data collection, shipping of drug to patients, virtual study start-up); 3) enhance enrollment opportunites away from university-based sites towards community-based practices; 4) increased frequency of our operations meetings with industry. The objective of this report is to describe how the pandemic affected accrual to GOG Partners’ trials. Methods: Accrual data for GOG Partners trials over the past 4 years (2017- July 2020) were collected. ‘Pandemic’ months were considered March thru July 2020. Information collected included accrual numbers, institution type (university versus non-university), and region of country. Descriptive statistics were analyzed. Results: Over the past 4 years, the median monthly accrual to GOG Partners trials was 43 patients (range: 14-95). Between March and July 2020, the median accrual was 59 patients (range: 43-72). For the same 5-month period over the past 3 years (March to July 2017, 2018, 2019) the median accrual was 36 (14-95). Accrual in March 2020 was 69 patients. Accrual decreased to 43 patients in April 2020 and 47 patients in May 2020 with respective z-scores of -0.25 and -0.01. June and July 2020 showed increased accrual with 59 and 72 patients respectively. The median number of participating sites per month over the past 4 years was 32 (9-66). There was an immediate decline in the number of sites participating from April to May 2020 of 36%. The number of sites participating in June and July were 38 and 52, respectively. During the pandemic, the accrual in the New England, Mid-Atlantic, Pacific and South Atlantic regions varied from their baselines. These variations followed the trends in COVID-19 spread. Non-university institutions accrued at a near-average rate throughout the months of April and May. During that same period, universities observed a decline in accrual of 48%. Conclusions: Accrual to GOG Partners’ trials increased 37% over the median monthly accrual since the pandemic began. During the pandemic, total monthly accrual fell below or reached the median during only 1 month. Regional diversity of sites participating in GOG Partners’ studies helped in preventing a more dramatic drop in participation. While overall accrual has historically shown to be relatively balanced between institution types, non-university institutions were less negatively impacted.

Objectives: Next-generation sequencing (NGS) is being increasingly utilized in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide an N-of-One approach in order to maximize matched treatment; however, outcome data are limited. We evaluate the effect of the degree of matching patients to treatment and concordance with MTB recommendations on oncologic outcomes, including overall response rate (ORR), clinical benefit rate (CBR) (stable disease ≥6 months/partial or complete remission), progression-free survival (PFS), and overall survival (OS). Methods: 164 consecutive gynecologic and breast cancer patients presented at MTB from December 2012-September 2018 were assessed for clinicopathologic data, NGS results, MTB recommendations, therapy received, and oncologic outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment out of total number of pathogenic alterations, and concordance with MTB recommendations were analyzed in context of oncologic outcomes. Disease site, age, and number of prior lines of therapy were considered as covariates in univariate analysis and included in multivariate analysis if p Results: 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS > 40% had higher ORR (30.8% vs. 7.1%; p=0.001) and CBR (73.1% vs. 31.2%; p Download : Download high-res image (138KB) Download : Download full-size image Conclusions: Concordance with MTB recommendations resulted in higher degrees of matched therapy and was associated with improved oncologic outcomes in gynecologic and breast cancer patients.

Objectives: To compare recurrence rates between patients with mismatch repair proficient (pMMR) and MMR deficient (dMMR) high intermediate risk (HIR) endometrial cancer Methods: Adult women with HIR endometrial cancer diagnosed between January 1, 2016, and December 31, 2018, were identified from UC San Diego and Kaiser Southern California. Patient and disease characteristics were collected by chart review. Cases were limited to those who underwent hysterectomy with endometrioid histology and stage 1 disease. HIR disease was defined as the presence of three risk factors if age Results: Two hundred forty-four patients with HIR endometrial cancer were identified during the study period. One hundred fifty-eight patients (65%) were pMMR by immunohistochemical staining, and 86 patients (35%) were dMMR. There were no differences in mean age, mean body mass index (BMI), race, grade, mean follow-up time, or type of adjuvant treatment received between the pMMR versus dMMR cohorts. In total, 40 (16%) patients experienced cancer recurrence, and there were 11 (4.5%) cancer-related deaths during the study period. There was no statistically significant difference in recurrence rates between the pMMR and dMMR cohorts (15% versus 19%, p=0.49). The lack of association between MMR status and recurrence persisted after controlling for depth of myometrial invasion and LVSI in logistic regression multivariable analysis. pMMR tumors were more likely to exhibit ≥50% myometrial invasion than patients with dMMR tumors (p=0.03). dMMR tumors were significantly more likely to exhibit LVSI than pMMR tumors (p Download : Download high-res image (225KB) Download : Download full-size image Conclusions: Our analysis represents one of the largest recurrence rate analyses of HIR endometrial cancer as stratified by MMR status. Although our pMMR and dMMR patient cohorts with HIR did not differ with respect to patient characteristics, dMMR tumors were significantly more likely to have

In gynecologic cancer patients, therapy matched to ctDNA alterations (N = 33 patients) was independently associated with improved overall survival (hazard ratio: 0.34, P = 0.007) compared to unmatched therapy (N = 28 patients) in multivariate analysis. Tissue and ctDNA genomic results showed high concordance unaffected by temporal or spatial factors. ctDNA may be an important tool to individualize cancer therapy in patients with gynecologic cancer., Molecular characterization of cancers is important in dictating prognostic factors and directing therapy. Next‐generation sequencing of plasma circulating tumor DNA (ctDNA) offers less invasive, more convenient collection, and a more real‐time representation of a tumor and its molecular heterogeneity than tissue. However, little is known about the clinical implications of ctDNA assessment in gynecologic cancer. We describe the molecular landscape identified on ctDNA, ctDNA concordance with tissue‐based analysis, and factors associated with overall survival (OS) in gynecologic cancer patients with ctDNA analysis. We reviewed clinicopathologic and genomic information for 105 consecutive gynecologic cancer patients with ctDNA analysis, including 78 with tissue‐based sequencing, enrolled in the Profile‐Related Evidence Determining Individualized Cancer Therapy (NCT02478931) trial at the University of California San Diego Moores Cancer Center starting July 2014. Tumors included ovarian (47.6%), uterine (35.2%), cervical (12.4%), vulvovaginal (2.9%), and unknown gynecologic primary (1.9%). Most ovarian and uterine cancers (86%) were high grade. 34% (N = 17) of ovarian cancers had BRCA alterations, and 22% (N = 11) were platinum sensitive. Patients received median 2 (range 0–13) lines of therapy prior to ctDNA collection. Most (75.2%) had at least one characterized alteration on ctDNA analysis, and the majority had unique genomic profiles on ctDNA. Most common alterations were TP53 (N = 59, 56.2% of patients), PIK3CA (N = 26, 24.8%), KRAS (N = 14, 13.3%), BRAF (N = 10, 9.5%), ERBB2 (N = 8, 7.6%), and MYC (N = 8, 7.6%). Higher ctDNA maximum mutation allele frequency was associated with worse OS [hazard ratio (HR): 1.91, P = 0.03], while therapy matched to ctDNA alterations (N = 33 patients) was independently associated with improved OS (HR: 0.34, P = 0.007) compared to unmatched therapy (N = 28 patients) in multivariate analysis. Tissue and ctDNA genomic results showed high concordance unaffected by temporal or spatial factors. This study provides evidence for the utility of ctDNA in determining outcome and individualizing cancer therapy in patients with gynecologic cancer.

The objective of this study was to examine the rate of and indications for readmission in patients with advanced staged ovarian cancer undergoing rectosigmoid resection and primary anastomosis, an important quality metric. A retrospective review was conducted of patients with primary ovarian cancer who underwent rectosigmoid resection as part of cytoreductive surgery between July 2003 and July 2014. Univariate analysis identified rates and predictors of readmission. Fifty patients were eligible for analysis. The unanticipated 30-day readmission rate was 18% (

To assess the use of Multivariate Index Assay (MIA OVA1) by gynecologists and determine referral practices and surgical decision making for women with adnexal masses and low-risk MIA OVA1 scores.Information on patients who received an OVA1 test was collected retrospectively from 22 gynecologic practices through a chart review. Referral patterns were examined for patients with low-risk OVA1 results prior to first surgical intervention. Chart reviews were from a variety of practice and hospital settings representing major geographic regions within the United States.A total of 282 independent patient charts were reviewed. Low-risk results were found for 146 patients (52%). Surgery was performed on 82 (56%) patients with low-risk scores. The referral rate to specialty care was 21% (17/82) for low-risk OVA1 patients. Three low-malignant potential tumors were identified in the low-risk patients, with no cases of invasive malignancy. Eighty-six percent of the surgeries performed on low-risk OVA1 patients were minimally invasive. In 44% of the low-risk OVA1 patients, no surgical intervention was performed.A high proportion of low-risk OVA1 patients were not referred to a gynecologic oncologist prior to surgery, indicating gynecologists may use MIA OVA1 along with clinical and radiographic findings to appropriately retain patients for their care. This practice is safe and may be cost-saving, with patient satisfaction implications.

Objective To describe our single-institution oncologic outcomes of patients who received neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Methods We compared clinicopathologic information and outcomes for all patients with advanced stage, high-grade serous ovarian cancer who received NACT and IDS with (N = 20) or without (N = 48) HIPEC at our institution from 2010 to 2019 Results Mean age (62 years with HIPEC and 60 years without HIPEC) and proportion of stage 4 disease (40% for both) did not differ between cohorts. HIPEC patients had higher rates of complete cytoreduction (95% vs 50%), longer mean duration of surgery (530 vs. 216 min), more grade 3 or 4 postoperative complications (65% vs. 4%), and longer mean length of hospital stay (8 vs. 5 days). HIPEC patients had significantly higher risk for platinum-refractory progression or platinum-resistance recurrence (50% vs 23%; RR = 2.18; 95% CI 1.11, 4.30, p = 0.024). Median progression free survival (11.5 vs. 12 months) and all-cause mortality (19.1 vs. 30.5 months) in the HIPEC and non-HIPEC cohorts, respectively, did not differ Conclusions HIPEC was associated with increased risk for platinum refractory or resistant disease. Higher surgical complexity may contribute to higher complication rates without improving oncologic outcomes in our patients. Further investigations and long-term follow-up are needed to assess the utility of HIPEC in primary treatment of advanced stage ovarian cancer

Objectives To describe the transition from a mentee to mentor role in a cohort of academic gynecologic oncologists by studying the evolution of authorship placement in peer reviewed publications by current gynecologic oncology (GO) fellowship directors. Methods Current GO fellowship directors were identified from the ACGME website. A Pubmed search identified all publications by all listed fellowship directors. Number of publications, and order of authorship were counted by years since medical school graduation. Milestones representing likely career transition points were developed and tracked. Descriptive statistics were used to characterize the individuals and associated institutions. Time to event curves were compared using the Kaplan Meier method. Results The study cohort comprised 58 GO fellowship program directors. The median time since medical school graduation was 22 years. Eight unique milestones reflecting the relative frequencies of authorship placement were studied. The median time to accomplishing these milestones ranged from 6 to 18 years. The timing of milestone attainment suggests a stepwise progression of events and was associated with both individual and institutional factors. Conclusions In this cohort of 58 fellowship directors, a roadmap to mentorship was identified, that includes several measurable milestones, and representative times to attain each. Further analyses identified a set of factors associated with the rate of progression. We hope these findings can inform the evolution of mentorship in gynecologic oncology. It is possible that initiatives focused on mentorship training might include milestone tracking to facilitate development.

1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC.We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively.152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC.Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.

PARP inhibitors (PARPi) have shown have activity in the treatment of ovarian cancer. Previous studies documented activity in patients with germline (gBRCA) and tumor (tBRCA) BRCA mutations (BRCAm) for treatment in lieu of chemotherapy as well as in recurrent ovarian cancer as maintenance therapy. The recent data from four randomized phase 3 trials have established an important role for frontline PARPi maintenance therapy in ovarian cancer. While SOLO-1 only included BRCAm patients, PRIMA, VELIA, and PAOLA-1 enrolled broader patient populations. The magnitude of benefit of PARPi in these studies was consistently greatest in the BRCAm patients (germline or tumor). PARPi treatment also improved PFS in the HRD cohort but to a lesser degree than in patients with BRCAm. In secondary analyses, the overall impact of PARPi treatment in HR proficient patients, which comprise about 50% of ovarian cancers, was more limited than in the other subgroups. Data for overall survival, also a secondary endpoint, is currently immature for these four trials. Fatigue, hematologic, and GI toxicities are the most commonly noted adverse events with PARPi therapy. The recent FDA approvals of PARPi in the maintenance setting will enable clinicians to incorporate these into frontline armamentarium of ovarian cancer treatment.

Morcellation of benign uterine tumors allows for removal of the tumors via minimally invasive laparoscopic procedures. However, in rare cases, morcellation has been associated with upstaging of unexpected malignancies. Morcellation has also been associated with dissemination of benign pathologic processes such as endometriosis and leiomyomas. Endometrial stromal sarcoma typically arises in the uterine cavity, although cases of extrauterine endometrioid stromal sarcoma arising out of foci of endometriosis have been reported. Dissemination of endometrial stromal sarcomas can be an unintended consequence of morcellation procedures, as can dissemination of endometriosis, from which endometrioid stromal sarcomas can arise. Herein, we report a case of a 55-year-old woman who was found to have disseminated endometriosis and low-grade endometrioid stromal sarcoma, with bowel and liver parenchymal metastasis, 7 years after undergoing supracervical hysterectomy with unconfined uterine morcellation for adenomyosis. Our case highlights the potential for malignant transformation of disseminated adenomyosis/endometriosis and the importance of patient counseling and shared decision-making prior to morcellation procedures.

PURPOSE: We sought to determine the level of concordance among surgeons’ assessment of residual disease (RD) and pre-treatment computed tomography (CT) findings among women who underwent optimal surgical cytoreduction for advanced stage ovarian cancer. METHODS: This is a post-trial ad hoc analysis of a phase 3 randomized clinical trial evaluating the impact of bevacizumab in primary and maintenance therapy for patients with advanced stage ovarian cancer following surgical cytoreduction. All subjects underwent imaging of the chest/abdomen/pelvis to establish a post-surgical baseline prior to the initiation of chemotherapy. Information collected on trial was utilized to compare surgeon’s operative assessment of RD, to pre-treatment imaging. RESULTS: Of 1,873 enrolled patients, surgical outcome was described as optimal (RD ≤ 1 cm) in 639 subjects. Twelve patients were excluded as they did not have a baseline, pretreatment imaging, leaving 627 participants for analysis. The average interval from surgery to baseline scan was 26 days (range: 1–109). In 251 cases (40%), the post-operative scan was discordant with surgeon assessment, demonstrating RD > 1 cm in size. RD > 1 cm was most commonly identified in the right upper quadrant (28.4%), retroperitoneal para-aortic lymph nodes (RD > 1.5 cm; 28.2%) and the left upper quadrant (10.7%). Patients with RD > 1 cm on pre-treatment CT (discordant) exhibited a significantly greater risk of disease progression (HR 1.30; 95% CI 1.08–1.56; p=0.0059). CONCLUSIONS: Among patients reported to have undergone optimal cytoreduction, 40% were found to have lesions > 1 cm on postoperative, pretreatment imaging. Although inflammatory changes and/or rapid tumor regrowth could account for the discordance, the impact on PFS and distribution of RD may suggest underestimation by the operating surgeon.