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Uterine carcinosarcoma (UCS) is a rare but aggressive cancer. In early-stage disease data guiding treatment is sparse. The purpose of this review is to summarize the findings from the 2019 NRG oncology group summer symposium meeting as well as a review of the current literature, with a particular focus on molecular targets, ongoing clinical trials, and treatment of early and advanced/recurrent disease. A combination of expert presentations and an extensive literature search was undertaken to summarize the literature in this review. MEDLINE was queried for peer-reviewed publications on UCS. This search was not limited by year or study design, but was limited to English language publications. ClinicalTrials.gov was queried for ongoing trials in UCS. UCS is a rare cancer that is biphasic, with the carcinomatous component driving its aggressive nature. Level 3 evidence regarding early stage disease is lacking, but retrospective data suggests adjuvant therapy is warranted. The recent results of GOG 261 have contributed valuable information towards treatment strategy, including use of paclitaxel and carboplatin for UCS. Clinical trials are ongoing to investigate new targeted agents in UCS. Ongoing endometrial cancer clinical trials now include UCS patients. In combination with advances in molecular profiling, this will provide patients with UCS improved therapeutic options. Until that time, surgical resection and traditional cytotoxic chemotherapy remains standard of care. • Although UCS is a rare, biphasic tumor, the carcinomatous component drives its aggressiveness. • Early stage UCS requires adjuvant chemotherapy, radiation, or a combination of both after surgical cytoreduction. • Ongoing clinical trials are evaluating a variety of molecular targeted drugs in UCS. [ABSTRACT FROM AUTHOR]

Ovarian cancer has a high mortality to case ratio. To improve the initial response to therapy, trials of biologic agents in combination with primary chemotherapy and as maintenance after completing chemotherapy are being conducted. Multiple trials are ongoing and this strategy has great promise. However, the changing landscape of primary treatment will make designing future trials in ovarian cancer difficult as there may not be a consensus on the optimal primary therapy. We reviewed clinicaltrials.gov for recent and ongoing phase III clinical trials that are likely to impact primary therapy in ovarian cancer. We summarized the objectives and the available data from these trials. A total of 12 potentially practice-changing, randomized phase III trials in front line ovarian cancer were identified in which a biologic therapy was added to primary chemotherapy and/or was used in the maintenance setting. These trials included PARP inhibitors (PARPi), anti-angiogenic agents, immuno-oncology agents, and combinations of these agents. Of the 12 trials, 10 are ongoing, one was terminated for futility, and one has been recently reported. All of these trials emphasize the use of maintenance targeted therapy. In addition, 7 randomized phase III trials utilizing hyperthermic intraperitoneal chemotherapy (HIPEC) were identified in the setting of upfront ovarian cancer treatment. There are multiple ongoing trials in primary ovarian cancer. These trials investigate PARPi, anti-angiogenic agents, immuno-oncology agents, combinations of these agents, and HIPEC. Many of these trials will mature within the next several years and are likely to change the primary treatment of women with ovarian cancer. • There are many trials underway with biologic agents in combination and after primary chemotherapy for ovarian cancer. • SOLO 1 has changed the standard primary therapy for women with BRCA mutated ovarian cancer. • Other trials are likely to change the standard of care for the primary treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Advanced clear cell gynecologic malignancies remain among the most challenging diseases to manage. We evaluated ovarian and endometrial clear cell carcinoma (OCCC and ECCC) specimens using comprehensive sequencing technology to identify mutational targets and compared their molecular profiles to histologically similar clear cell renal cell carcinoma (ccRCC). Using next-generation sequencing (NGS), fragment analysis (FA), and in situ hybridization (ISH), 164 OCCC, 75 ECCC and 234 ccRCC specimens from 2015 to 2018 were evaluated and compared. The highest mutation rates in ECCC and OCCC were noted in: ARID1A (75.0%, 87.5%), TP53 (34.8%, 11.1%), PIK3CA (25.0%, 46.8%), PPP2R1A (8.7%, 16.7%), MSI-high (8.8%, 6.4%) and PTEN (8.3%, 7.1%). Among these mutations, there was no significant difference between OCCC and ECCC mutation prevalence except in TP53 , with higher mutation rates in ECCC versus OCCC (34.8 vs. 11.1%, respectively, p < 0.05). ccRCC demonstrated different mutation profiles with higher mutation rates in VHL (80.3%), PBRM1 (43.9%), SETD2 (31.1%), and KDM5C (29.2%). By contrast, VHL , PBRM1 , and SETD2 mutations were not found in ECCC and OCCC (0.0%). Compared to ccRCC and ECCC, OCCC was found to have a significantly higher tumor mutation burden (TMB) (19.1%). Gynecologic and renal CCC demonstrate separate and disparate somatic profiles. However, OCCC and ECCC are diseases with similar profiles. TMB and MSI analyses indicate that a subset of OCCC may benefit from immunotherapy. Prospective clinical trials are needed and are underway to examine targeted therapies in these gynecologic disease subtypes. • Ovarian and endometrial clear cell carcinomas have similar molecular profiles. • Gynecologic clear cell carcinomas have distinct molecular profiles from renal types. • Gynecologic clear cell carcinomas have high mutations rates in the PI3K/mTOR pathway. • Ovarian clear cell carcinomas had a 19.1% tumor mutation burden. [ABSTRACT FROM AUTHOR]

Low grade serous ovarian cancer (LGSOC) differs from high grade serous in terms of pathogenesis, molecular, genetic, and clinical features. Molecular studies have been hampered by small sample sizes, heterogenous histology, and lack of comprehensive testing. We sought to molecularly profile LGSOC in a homogenously tested, histologically confirmed cohort. Using hot-spot and whole exome next generation sequencing (NGS), fusion gene analysis interrogating RNA, fragment analysis, in situ hybridization and/or immunohistochemistry, 179 specimens were evaluated by Caris Life Sciences (Phoenix, AZ). A second independent histologic review confirmed histology in 153 specimens. Most frequently mutated genes (5% or greater) were members of the mitogen-activated protein kinase (MAPK) pathway: KRAS (23.7%, n = 36), NRAS (11.2%, n = 19), NF1 (7.9%, n = 5), and BRAF (6.6%, n = 10). Class III mutations were seen in 3 of 10 BRAF mutations while 7 were Class I V600E. Overall, estrogen and progesterone receptor expression was 80.2% (n = 130) and 27.8% (n = 45), respectively. Of those that were hormone negative, nearly 50% contained KRAS or NF1 mutations. None were NRAS mutated. Markers of response to immunotherapy were low to absent. BRAF mutations were seen to be lower than those traditionally reported. With increased MAPK activation resulting in ligand independent activation of ERα, a role of combination therapy with hormonal and targeted therapy should be considered as 49.2% of hormone negative specimens were KRAS or NF1 mutated. Absence of immunotherapy biomarkers suggest limited benefit to immunotherapeutic agents. • Low grade serous ovarian cancer has a unique mutational profile relative to high grade and borderline serous ovarian cancers. • BRAF mutations are rare (6.6%) and nearly a third were RAS dependent (a.k.a Class III) • Estrogen receptor expression is seen in 80% and commonly co-exist with NRAS and BRAF mutations. • Clinical biomarkers associated with response to immune checkpoint inhibitors are largely absent. [ABSTRACT FROM AUTHOR]

HER2 is an important prognostic and therapeutic target in uterine serous carcinoma (USC). Optimal HER2 testing platforms have not been defined and guidelines for testing have changed over time. Our objective is to assess the concordance of HER2 positivity based on chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) and to determine the rate of downstream mutations that may affect response to HER2 directed therapy. Utilizing the Caris tumor registry, 2192 USC tumors were identified and analyzed using NGS (NextSeq, 592 Genes and WES, NovaSEQ), IHC, and CISH. PD-L1 expression was tested by IHC. Microsatellite instability was tested by fragment analysis, IHC, and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor. HER2 positivity through IHC and CISH was determined based on 2007 and 2018 ASCO/CAP HER2 breast cancer guidelines. There was a higher rate of HER2 positivity by IHC when using the 2018 guidelines compared to the 2007 guidelines (16.3% vs 12.3%). Concordance between IHC and CISH was 98.9%. ERBB2 amplification was identified by NGS in 10.5% of tumors. Compared to CISH results, this corresponds to a concordance rate of 91.6% and a positive predictive value (PPV) of 60.3%. Single gene alterations in HER2 amplified tumors that may implicate HER2 therapy resistance included PI3K (33.1%), KRAS (2.5%), and PTEN (1.3%). There was high concordance between HER2 positivity based on CISH and IHC. Rate of HER2 positivity is the lowest by NGS. Ultimately these testing platforms need to be validated by response to targeted therapy. • IHC and CISH testing platforms have high concordance in identifying HER2+ uterine serous carcinoma. • NGS testing for ERBB2 amplification has a low sensitivity but high PPV in identifying HER2+ uterine serous carcinoma. • No major differences in gene alterations or immunotherapy biomarkers identified between HER2+ and negative tumors. [ABSTRACT FROM AUTHOR]

The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007–12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. We identified 1093 cases for analysis—715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03–149.51) and 54.98 months (range, 0.03–145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9–90.4%) and 89% (95% CI: 84.9–92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47–1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6–97.2%) and 96.6% (95% CI: 93.8–98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43–1.52; P = 0.5). This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS. • Minimally invasive (MIS) compared to open radical hysterectomy did not compromise outcomes in early-stage cervical cancer • Our findings are contrary to those of the Laparoscopic Approach to Cervical Cancer (LACC) trial favoring laparotomy • As the NCCN has changed guidelines in accordance with LACC, women may miss out on the benefits of MIS radical hysterectomy [ABSTRACT FROM AUTHOR]

Enhanced recovery after surgery (ERAS) has decreased hospital opioid use, but less attention has been directed towards its impact on clinic burden with respect to post-operative care. Our objective was to determine the impact of an ERAS protocol on post-operative opioid prescribing, and the subsequent number of pain medication refill requests and unscheduled patient-provider interactions in the 30-day post-operative period. IRB-approved retrospective study comparing post-operative opioid prescription practices 10 months before and 10 months after ERAS protocol implementation after minimally invasive gynecologic surgery. Opioid doses in morphine milligram equivalents (MMEs), number of unscheduled visits, and phone calls were compared before and after ERAS implementation. A total of 791 patients were included; 445 without and 346 with ERAS implementation. ERAS was associated with higher rates of same day discharge (49% vs 39%, p = 0.003) and lower readmission rates (2.0% vs 5.6%, p = 0.011). Post-operatively, patients who received the ERAS protocol were prescribed less opioids (197.8 vs. 223.5 MMEs, p = 0.0087). There was a trend towards less refill requests with ERAS (1.7% vs 3.6%, p = 0.11). ERAS was associated with a decreased number of post-operative phone calls (38% vs 46%, p = 0.023), including calls for pain (10% vs 16%, p = 0.021), and fewer unscheduled visits related to pain (1.5% vs 5.8%, p = 0.001). Implementation of the ERAS protocol resulted in a decrease in post-operative opioid prescribing. Despite the lower amount of prescribed post-operative opioids, the ERAS protocol translated into a decrease in the need for post-operative interactions with the clinic staff, specifically encounters associated with pain. • ERAS protocol is associated with a reduction in intra-operative opioid use and opioids prescribed for post-operative pain. • Lower doses of post-operative opioids following minimally invasive gynecologic surgery do not increase clinic staff burden. • Patients who receive ERAS protocol make less calls and visits related to pain despite lower doses of opioids prescribed. [ABSTRACT FROM AUTHOR]

Disparate outcomes exist between Black and White patients with endometrial cancer (EC). One contributing factor is the disproportionately low representation of Black patients in clinical trials and in tumor molecular profiling studies. Our objective was to investigate molecular profiles of ECs in a cohort with a high proportion of tumors from Black patients. A total of 248 EC samples and self-reported race data were collected from 6 institutions. Comprehensive tumor profiling and analyses were performed by Caris Life Sciences. Tumors from 105 (42%) Black and 143 (58%) White patients were included. Serous histology (58% vs 36%) and carcinosarcoma (25% vs 16%), was more common among Black patients, and endometrioid was less common (17% vs 48%) (p < 0.01). Differences in gene mutations between cohorts corresponded to observed histologic differences between races. Specifically, TP53 mutations were predominant in serous tumors. In endometrioid tumors, mutations in ARID1A were the most common, and high rates of MSI-H, MMRd, and TMB-H were observed. In carcinosarcoma tumors, hormone receptor expression was high in tumors of Black patients (PR 23.4%, ER 30.8%). When stratified by histology, there were no significant differences between tumors from Black and White women. This cohort had a high proportion of tumors from Black women. Distinct molecular profiles were driven primarily by more aggressive histologic subtypes among Black women. Continued effort is needed to include Black women and other populations under-represented in EC molecular profiling studies as targeted therapies and personalized medicine become mainstream. • Black patients with endometrial cancer (EC) have worse outcomes than White patients. • The use of molecular profiling and targeted therapies in EC is increasing. • To comprehensively study molecular profiles of EC, we need adequate representation of tumors from Black patients. • This study investigates molecular profiles of tumors from a cohort with a high proportion of tumors from Black patients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the U.S. Surgeon General, the American College of Srugeons, and other surgical professional societies recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges have particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hestitate, and reintegrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, and preparations for the post-COVID-19 peak and surgical reintegration are reviewed. [ABSTRACT FROM AUTHOR]

Objectives To determine the efficacy and tolerability of sunitinib in recurrent or persistent clear cell ovarian cancer patients. Methods All patients had one or two prior regimens with measurable disease. Tumors were at least 50% clear cell histomorphology and negative for WT-1 antigen and estrogen receptor expression by immunohistochemistry. Sunitinib 50 mg per day for 4 weeks was administered in repeated 6-week cycles until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response. The study was designed to determine if the drug had a response rate of at least 20% or 6-month PFS of at least 25%. Results Of 35 patients enrolled, 30 were treated and eligible (median age: 51, range: 27–73). Twenty-five (83%) were White, 4 (13%) Asian, and 1 (3%) unknown. The majority 28 (83%) patients, underwent ≤3 but 2 (7%) had 16 courses of study therapy. Five (16.7%) patients had PFS ≥6 months (90% CI: 6.8%–31.9%). Two (6.7%) patients had a partial or complete response (90% CI: 1.2%–19.5%). The median PFS was 2.7 months. The median overall survival was 12.8 months. The most common grade 3 adverse events were fatigue (4), hypertension (4), neutropenia (4), anemia (3), abdominal pain (3), and leukopenia (3). Grade 4–5 adverse events included: thrombocytopenia (5), anemia (2), acute kidney Injury (1), stroke (1), and allergic reaction (1). Conclusion Sunitinib demonstrated minimal activity in the second- and third-line treatment of persistent or recurrent clear cell ovarian carcinoma. ClinicalTrials.gov number, NCT00979992. [ABSTRACT FROM AUTHOR]

Background: Based primarily on studies concerning early-stage tumours (treated surgically), and locally advanced disease (treated with chemoradiation), the prognosis for women with adenocarcinoma (AC) or adenosquamous (AS) carcinoma has been reported to be poorer than those with squamous cell carcinoma (SCCA) of the cervix. It is unclear whether differences in prognosis also persist in the setting of recurrent or metastatic disease treated using chemotherapy doublets with or without bevacizumab.Methods: Cases were pooled from three Gynaecologic Oncology Group randomised phase III trials of chemotherapy doublets. Pearson's test was used to evaluate response rate (RR) of AC/AS vs SCCA, Kaplan-Meier method to estimate progression-free survival (PFS) and overall survival (OS), and Cox proportional hazards model to estimate the impact of histology on PFS and OS.Results: Of 781 evaluable patients, 77% (N=599) had SCCA and 23% (N=182) AC/AS. There were no significant differences in RRs between histologic subgroups. The adjusted hazard ratio (HR) for death for SCCA vs AC/AS was 1.13 (95% CI 0.93, 1.38 P=0.23). When comparing SC/AS (N=661, 85%) to AC alone (N=120, 15%), the adjusted HR for death was 1.23 (95% CI 0.97, 1.57, P=0.09).Conclusions: AC/AS and SCCA have similar survival in recurrent or metastatic cervical carcinoma when treated with chemotherapy doublets. [ABSTRACT FROM AUTHOR]

Background Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These ovarian sex cord-stromal tumors as well as other tumors including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations. We sought to describe the clinical and genetic findings from the first 107 individuals enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Methods Medical and family history were obtained for individuals consecutively enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Pathology was centrally reviewed. DICER1 sequencing was performed on blood and tumor tissue. Results Of the 107 participants, 49 had SLCT, 25 had JGCT and 5 had GAB. Nearly all (36/37) SLCTs and 4/4 GAB tested had a DICER1 mutation in an RNase IIIb domain hotspot; approximately half of these individuals had a predisposing germline DICER1 mutation. Metachronous SLCTs were seen in 3 individuals with germline DICER1 mutations. Other DICER1 -associated conditions were seen in 19% of patients with SLCT or GAB. Three children of women with SLCT were diagnosed with PPB based on genetic testing and clinical screening during the course of this study. All were diagnosed with PPB in its earliest and most curable form (Type I), were treated with surgery alone, and are alive without evidence of disease. Conclusions Recognition of the distinct genetic basis for a group of these tumors improves precise classification in difficult cases and promotes mutation-based screening and early detection. [ABSTRACT FROM AUTHOR]

Objectives: Vulvovaginal melanomas (VVM) are considered to be a subtype of mucosal melanoma (MM) that are less immunogenic and less responsive to immuno-oncology therapy (IO) than cutaneous melanoma (CM). Due to the rarity of MM, there is a paucity of data regarding the molecular and immune profile differences between MM subtypes. Herein we compared VVM with other subtypes of mucosal melanoma and explored the significance of IO agents on survival. Methods: Tumor samples were analyzed using next-generation sequencing (TruSeq, 45 genes; NextSeq, 592 genes and NovaSeq, WES), IHC, and WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PD-L1 expression was tested by IHC using 28-8 (Agilent) and SP-142 (Spring Biosciences) (positive cut-off ≥1%). MSI was tested by FA, IHC, and NGS. TMB was measured by totaling somatic mutations per tumor (TMB-high cut-off ≥ 10 mutations per MB). Immune cell fraction was calculated by Q uantiSeq. (Finotello 2019, Genome Medicine). Survival was extracted from insurance claims data and calculated from the time of IO treatment to the last contact using Kaplan-Meier survival curves for molecularly defined cohorts. Statistical significance was determined using Chi-square and Wilcoxon rank-sum test and adjusted for multiple comparisons (q<0.05). Results: A total of 183 VVM, 84 anorectal melanomas (ARM), and 95 head and neck mucosal melanomas (HNM) tumors were evaluated. The median ages of each cohort were 66, 67, and 71, respectively. The SF3B1 RNA splicing gene was more frequently mutated among VVM and ARM compared with HNM (26.7%, 36.2%, and 1.8%, respectively, q<0.01). There was also a trend toward higher rates of TP53 and KIT mutations in VVM and ARM compared with HNM. BRCA1 and APC mutations were found exclusively in ARM tumors. KIT was the most common biomarker amplification (14.5% VVM, 10.5% ARM, and HNM). Otherwise, rates of biomarker amplification were low overall. When evaluating IO therapy-related biomarkers, VVM had the highest rate of PD-L1 positivity (34.6%) compared to ARM (18.5%) and HNM (33.3%). High TMB was present in 4.2% of ARM, 4.8% of HNM, and 0% of VVM tumors. MSI-H/dMMR tumors were absent in all three cohorts. Immune cell infiltrates were similar among all MM tumors, except for an increase in regulatory T cell infiltration in VVM tumors (q<0.01). Treatment and survival data were available for 119 VVM, 61 ARM, 42 HNM, and 4839 CM patients. Of these, 17% VVM (n =20), 31% ARM (n =19), 14% HNM (n =6) and 22% CM (n =1056) received IO therapy. Median survival was 17.5 months (mo) for VVM, 16.8 mo for ARM, and 33 mo for HNM, none of which were significantly different. There was a trend toward better survival for CM patients on IO therapy compared to MM patients (36.6 mo vs 18.8 mo, HR: 0.67, 95% CI: 0.45-1.06, p=0.087). Conclusions: MM represents a unique subset of melanoma, with worse survival and response to IO therapy than CM. VVM and ARM appear to be more similar on a molecular level than HNM. [ABSTRACT FROM AUTHOR]

Objectives: Vulvovaginal melanoma (VVM) is a rare but aggressive subtype of melanoma. VVM is considered to be less immunogenic and less responsive to immune-oncology therapy (IO) than cutaneous melanomas (CM). Vulvar and vaginal melanomas are typically grouped together due to the rare nature of the disease, though limited data suggest worse outcomes with vaginal melanomas. There is a paucity of data regarding molecular differences between these two melanoma subtypes. Our goal was to explore molecular profiles and survival between vaginal and vulvar melanomas. Methods: Samples were analyzed using next-generation sequencing (NGS) (TruSeq, 45 genes; NextSeq, 592 genes and NovaSeq, WES), IHC, and WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PD-L1 expression was tested by IHC using 28-8 (Agilent) and SP-142 (Spring Biosciences) (positive cut-off ≥1%). Microsatellite instability (MSI) was tested by fragment analysis (FA), immunohistochemistry (IHC), and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor (TMB-high cut-off ≥10 mutations/MB). Immune cell fraction was calculated by QuantiSeq (Finotello 2019, Genome Medicine). Real-world overall survival (OS) was extracted from insurance claims data and calculated from the time of IO treatment to the last contact using Kaplan-Meier survival curves for molecularly defined cohorts. Statistical significance was determined using Chi-square and Wilcoxon rank-sum test and adjusted for multiple comparisons (q<0.05). Results: A total of 183 VVM were included in this analysis: 137 (74.9%) vulvar and 46 (25.1%) vaginal. Rates of gene mutations between these tumors were similar. Vaginal tumors trended toward increased frequency of ATRX (47.1 vs 23.2%) and TP53 (29.0 vs 16.1%) mutations compared to vulvar tumors. Vulvar tumors trended toward higher rates of SF3B1 mutations (33.8 vs 4%) as well as more KIT mutations (17.7 vs 8.8%) and amplification (16.7 vs 8.0%). PD-L1 expression was similar in vaginal and vulvar tumors (40 vs 32.7%). MMR deficiency and high TMB were absent in both groups. Vulvar melanoma trended towards increased immune checkpoint gene expression compared to vaginal melanoma, most notably a 2-fold increase in both IFNG and IDO1 expression. No difference was seen in immune cell infiltrates. Treatment and survival data were available for 78 vulvar and 40 vaginal melanomas (OS: 34 vs 21 mo). In total, 15% of vulvar patients (n =12) and 18% of vaginal patients (n =7) received IO therapy. Median survival was similar between groups (vulvar 18 mo vs vaginal 19 mo, p=0.9). The survival of cutaneous melanoma (CM) patients receiving IO therapy (n =1047) was roughly twice as long (36.6 mo,p=0.038). Conclusions: This is one of the largest VVM cohorts to be studied to date. Overall, we found that these tumors were very similar in their molecular profiles and immunogenicity. Survival and response to IO therapy appeared similar between vulvar and vaginal melanomas. Our findings support continuing study of VVM as a single entity in light of the rarity of this disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective To determine the efficacy of chemotherapy after failed initial treatment in patients with high risk gestational trophoblastic neoplasia (GTN). Methods We performed a retrospective IRB-approved chart review of all patients with GTN seen at a single institution from 1985 to 2015, including all patients who failed initial treatment. We summarized clinical characteristics with descriptive statistics and estimated progression-free survival (PFS) and overall survival (OS) with the Kaplan-Meier method. Results Of 68 identified patients, 38 required > 2 chemotherapy regimens. Patients were treated for GTN ( n = 53), including choriocarcinoma, persistent GTN, and invasive mole; for placental site trophoblastic tumor (PSTT) ( n = 5); and for intermediate trophoblastic tumor (ITT) ( n = 10). Patients with GTN had a median of 2 salvage regimens, median PFS of 4.0 months, and median OS was not reached at median follow-up of 71.2 months. Active regimens included EMACO, MAC, BEP, platinum- and etoposide-based combination therapies, and ICE; 8 of 53 patients died of disease (DOD). Patients with PSTT had a median of 3 salvage regimens, median PFS of 2.8 months, and median OS of 38.8 months. Active regimens included ICE and EMA-EP; 4 of 5 patients DOD. Patients with ITT had a median of 3 salvage regimens, median PFS of 4.1 months, and median OS of 38.2 months. Active regimens included liposomal doxorubicin, platinum-containing regimens, EMA-CO, and EMA-EP; 7 of 10 patients DOD. Conclusions Several salvage chemotherapy regimens demonstrate activity in high risk GTN. Multiple regimens may be required and cure is not universal. [ABSTRACT FROM AUTHOR]

Regulators increasingly use patient-reported outcomes (PROs) to inform the risks and benefits of new drug therapies. Dostarlimab is a programmed death receptor 1 (PD-1)-blocking antibody that is approved in the US as a monotherapy in adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC) that has progressed on or following prior treatment with a platinum-containing regimen or with dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. Here, PROs from the GARNET trial in patients with dMMR solid tumors treated with dostarlimab are reported. GARNET is a phase 1, multicenter, open-label, single-arm study conducted in 2 parts: dose escalation and expansion. Expansion cohort A1 enrolled patients with EC, and cohort F enrolled patients with non-EC solid tumors. Patients received dostarlimab 500 mg IV Q3W for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. PRO assessment, an exploratory endpoint, was measured using the EORTC-QLQ-C30. PROs were collected at baseline, each dose cycle, and after discontinuation. Multiitem and item-level analyses were collected to understand response distribution and change from baseline. PRO data were available for 94/126 patients in cohort A1 and 138/144 patients in cohort F who received ≥1 dose of dostarlimab. Questionnaire completion rates were consistent across domains in both cohorts. Improvements from baseline for pain and fatigue were observed for both cohorts A1 and F starting at cycles 2 and 3, respectively. Improvements in physical functioning were maintained above baseline from cycle 4 for cohort A1 and from cycle 3 for cohort F. Symptomatic AEs were experienced by a minority of patients; <25% of patients in cohort A1 and <26% of patients in cohort F experienced 1 category or greater worsening. Improved scores were reported in 5%-33% of patients in cohort A1 and 9%-39% of patients in cohort F. PROs from the GARNET trial show dostarlimab was generally well tolerated and that disease-related symptoms were improved or maintained while on treatment. PRO results were consistent between patients with dMMR EC and those with dMMR non-EC tumors. These data, with previously reported efficacy and safety profile of dostarlimab, support the use of dostarlimab in patients with dMMR solid tumors. [ABSTRACT FROM AUTHOR]

Objectives Small cell cervical cancer is a rare malignancy with limited treatment options for recurrent disease. We sought to determine if tumor specimens of small cell cervical cancer harbor common somatic mutations and if any of these are actionable. Methods Using a registry of patients with neuroendocrine cervical cancer, we identified 44 patients with pure or mixed small cell cervical cancer who had undergone mutational analysis. Mutations had been detected using next generation sequencing of mutational hotspots in 50 cancer-related genes. Results Thirty-five mutations were identified in 24 patients (55%). Fifteen of these 24 patients (63%) had 1 mutation, 7 patients (29%) had 2 mutations, and 2 patients (8%) had 3 mutations. In all 44 patients, the most commonly seen mutations were mutations in PIK3CA (8 patients; 18%), KRAS (6 patients; 14%), and TP53 (5 patients; 11%). No other mutation was found in > 7% of specimens. Of the 24 patients who had a mutation, 21 (88%) had at least 1 alteration for which there currently exists a class of biological agents targeting that mutation. In the entire cohort of 44 patients, 48% had at least 1 actionable mutation. Conclusion Although no single mutation was found in the majority of patients with small cell cervical cancer, almost half had at least 1 actionable mutation. As treatment options for patients with recurrent small cell cervical cancer are currently very limited, molecular testing for targetable mutations, which may suggest potential therapeutic strategies, may be useful for clinicians and patients. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to evaluate the impact of premedications given as an adjunct to carboplatin on the incidence of hypersensitivity reactions in women with ovarian cancer. Medications of interest include a histamine1 (H1) and histamine2 (H2) blocker in addition to dexamethasone. Methods This was a retrospective chart review evaluating the addition of an H1 and H2 blocker in addition to dexamethasone as standard premedications on the incidence of carboplatin hypersensitivity reactions ( CHRs) in women with ovarian cancer. Main Results The odds ratio for premedication use was 0.46 with a 95% confidence interval (0.17-1.27), suggesting that patients with premedication use had approximately half the risk of CHR compared with patients without premedication. The overall incidence of CHRs decreased from 7.9% at baseline to 3.2% after the addition of premedications. The incidence of CHRs was 5.2% in 58 patients with recurrent or progressive disease compared with 2.1% in 96 newly diagnosed patients. Lifetime dose greater than 3377 mg, number of cycles more than six, and progressive or recurrent disease were predictive factors of CHR in women with ovarian cancer. Principal Conclusions Total lifetime exposure to carboplatin remains the greatest predictive factor of CHR in women with ovarian cancer. Although data analysis indicates the addition of premedications for all ovarian cancer patients receiving carboplatin did not result in a statistically significant reduction in CHRs, a patient benefit in CHR reduction was observed. A prospective study is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: Patients receiving postoperative opioids have a dosedependent risk of misuse and addiction. While the introduction of the enhanced recovery after surgery (ERAS) protocol has been shown to decrease hospital narcotic use, less attention has been directed towards the impact of ERAS on the clinic burden with respect to postoperative care. The objective of our study was to determine the impact of an ERAS protocol on narcotic prescription patterns after laparoscopic gynecologic surgery measured as the number of prescription pain medication refill requests, clinic phone calls, and unscheduled visits in the 30-day postoperative period. Methods: This retrospective study compared postoperative narcotic prescriptions and clinic burden ten months prior to and ten months following the implementation of a standard ERAS protocol after laparoscopic gynecologic surgery. The study included patients who underwent surgeries between January 2018, and July 2019, with the ERAS implementation in November 2018. The total oral morphine milligram equivalents (MMEs) prescribed postoperatively, and the number of unscheduled clinic visits and phone calls were compared before and after the implementation of the ERAS protocol. Postoperative prescribing practices were not standardized during the study period. Results: A total of 791 patients were identified with clinic follow-up; 445 before and 346 after ERAS implementation. All patients underwent laparoscopic or robotic-assisted surgery alone or in combination with mini-laparotomy. Baseline characteristics, including procedure, diagnosis, smoking, and alcohol use did not differ between groups. Use of ERAS was associated with higher rates of same-day discharge (49% vs 39%, p=0.003) and lower readmission rates (2.0% vs 5.6%, p=0.011). Postoperatively, patients who received the ERAS protocol were prescribed significantly less narcotics (197.8 vs 223.5 MMEs, p=0.0087) even though the postop narcotic doses were not specified. The number of refill requests was lower with ERAS (1.7% vs 3.6%, p=0.11). ERAS was associated with a lower chance of postoperative clinic phone calls (38% vs 46%, p=0.023), including calls for pain (10% vs 16%, p=0.021). There was a decrease in unscheduled visits related to pain (1.5% vs 5.8%, p=0.001), and a trend towards a decrease in the number of overall unscheduled visits (14% vs 18%; p=0.08) after ERAS implementation. Conclusions: Implementation of the ERAS protocol after laparoscopic gynecologic surgery resulted in a decrease in postoperative opioid prescribing and a lower incidence of unplanned interactions with the clinic staff, despite the lower amount of prescribed postoperative narcotics. [ABSTRACT FROM AUTHOR]

Objectives: Although the median age of diagnosis of endometrial cancer (EC) is 62 years (y), most deaths from EC occur in patients (pts) older than 65 y (median age at death is 70 y). The current standard of care in EC does not address the unmet need for care in older pts. Dostarlimab is a programmed death receptor 1 (PD-1)-blocking antibody approved in the US for (1) the treatment of adults with mismatch repair deficient (dMMR) recurrent/advanced EC that has progressed on or after prior treatment with a platinum-containing regimen or (2) dMMR recurrent/advanced solid tumors that have progressed on or after prior treatment and who have no satisfactory alternative treatment option. Here, we present a post-hoc analysis of the antitumor activity and safety of dostarlimab by age subgroup in pts with dMMR/microsatellite instability-high (MSI-H) EC and mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC. Methods: GARNET is a phase I, multi-center, open-label, single-arm study of dostarlimab monotherapy in pts with advanced/recurrent solid tumors. Within GARNET, two expansion cohorts enrolled pts with advanced/recurrent EC: cohort A1 enrolled pts with dMMR/ MSI-H EC, and cohort A2 enrolled pts with MMRp/MSS EC. Based on age at baseline, pts were stratified into three age groups: <65 y, ≥65 to <75 y, and ≥75 y. Antitumor activity and safety were assessed in each subgroup by using data from the March 1, 2020, interim analysis. Results: Of 129 pts with dMMR/MSI-H EC enrolled in cohort A1, 51.2% (n =66) were <65 y, 39.5% (n =51) were ≥65 to <75 y, and 9.3% (n =12) were ≥75 y. Of 161 pts with MMRp/MSS EC enrolled in cohort A2, 43.5% (n =70) were <65 y, 44.7% (n =72) were ≥65 to <75 y, and 11.8% (n =19) were ≥75 y. For this interim analysis, pts with measurable disease at baseline and sufficient follow-up time (≥24 weeks) were included in the efficacy-evaluable population. The confirmed objective response rates (ORRs) per RECIST v1.1 assessed by blinded independent central review were similar across age groups for dMMR/MSI-H EC (<65 y: 45.3%; 95% CI: 31.6%-59.6%; ≥65 to <75 y: 43.9%; 95% CI: 28.5%-60.3%; ≥75 y: 45.5%; 95% CI: 16.7%-76.6%). The confirmed ORRs for pts with MMRp/MSS EC were not dissimilar across age groups (<65 y: 9.1%; 95% CI: 3.4%-18.7%; ≥65 to <75 y: 16.9%; 95% CI: 9.0%-27.7%; ≥75 y: 21.1%; 95% CI: 6.1%-45.6%). There were few grade ≥3 treatment-related adverse events (TRAEs) and these were generally similar between age groups. Pts aged ≥75 y did not have increased incidence of grade ≥3 TRAEs compared with younger age groups (Table). Conclusions: Dostarlimab's antitumor activity and safety for pts with dMMR/MSI-H EC and MMRp/MSS EC were generally comparable across age groups, with low incidence of grade ≥3 TRAEs across all subgroups. Older pts with advanced/recurrent dMMR/MSI-H EC experienced broadly similar treatment benefits as younger pts. [ABSTRACT FROM AUTHOR]

Objectives: To determine the impact of race, insurance status, and median income on the uptake of maintenance therapy after primary or secondary chemotherapy in platinum responsive platinum-sensitive ovarian cancer (OC). Methods: This IRB-approved study evaluated the association of race, income, and insurance status with the use of maintenance therapy in the primary or platinum-sensitive recurrent setting. All patients were identified who were eligible for maintenance therapy from January 1, 2015, to December 31, 2019. Logistic regression models were used to investigate the association between the use of maintenance therapy and race, insurance status, and census tract median household income as determined by linking geocoded addresses to census data. Results: A total of 180 patients were identified who met the study criteria. Of these patients, 71 were treated with maintenance therapy (19% primary, 41% either). The most common treatments included PARPi in 46%, Bev in 41%, and both in 13%. Insurance status was commercial in 28%, public in 63%, and self-pay in 9%. The use of maintenance therapy was higher with commercial insurance than public or no insurance (26% vs 17% vs 12%), but this was not statistically significant (p=0.44). Patients receiving maintenance therapy lived in areas with slightly higher median household income, but this was not statistically significant ($71,828 vs $64,881; p=0.077). However, fewer black patients received maintenance therapy in either setting (20% vs 41%; p=0.034). Similarly, fewer Black patients received maintenance therapy in the primary setting (4% vs 21%: p = 0.040). In a multivariable regression model, race, census tract median income, and insurance status were not significantly associated with receiving maintenance therapy. Black patients were less likely to receive maintenance therapy in the multivariable model, although this did not reach significance (OR: 0.33; 95% CI: 0.10-1.08, p=0.08). Black patients are less likely to be treated with maintenance therapy after responding to platinum-based chemotherapy. This difference is not explained by insurance status or household income. It is important to understand why racial differences persist in healthcare delivery to optimize outcomes for all patients. [ABSTRACT FROM AUTHOR]

Adult granulosa cell tumors (AGCT) of the ovary represent less than 5% of all ovarian tumors. Despite having a favorable prognosis, nearly one-third of women with this diagnosis will recur, and therapeutic options are limited. We aim to describe a molecular profile of AGCT to improve prognostication and elucidate actionable molecular targets. AGCT samples were analyzed using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and whole transcriptome sequencing (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PD-L1 expression was tested by SP-142 (Ventana; positive cut-off ≥1%). Microsatellite instability (MSI) was tested by fragment analysis, IHC and NGS. Tumor mutational burden (TMB) was measured by counting all somatic mutations per tumor (TMB-high cut-off ≥10 mutations per MB). Immune cell fraction was calculated by QuantiSeq (Finotello 2019, Genome Medicine). Gene Set Enrichment Analysis (GSEA) was used to determine enrichment of cancer hallmark pathways (Broad Institute). Survival analyses were performed using the Kaplan-Meier estimate. Of the 319 patients, the median age was 55, and most patients had metastatic disease (82.4 %). A majority of the tumors carried FOXL2 mutations (83.6%), of which 90% demonstrated a C134W missense mutation. Patients with FOXL2 mutations were significantly older (56 versus 47 years, p=0.003) and more likely to have metastatic disease than patients with wild-type FOXL2 (p=0.045). Other frequent mutations included KMT2D (14%) and PIK3CA (8%) mutations. There were no pathogenic BRCA1 or BRCA2 mutations identified in this cohort; however, a BRCA2 mutation variant of unknown significance was noted in three tumors. Pathway analyses demonstrated that alterations in chromatin remodeling were significantly more common in tumors with FOXL2 mutations compared to wild-type status (16.1% versus 9.7%, p<0.05), as were alterations in the PI3K pathway (13.9% versus 0%, p<0.05). There was a low frequency of PD-L1 high expression (2.7%), and there were no tumors with high TMB or MSI. Patients with tumors with FOXL2 mutations had improved overall survival compared to patients with wild-type FOXL2 tumors (HR 2.07, CI 1.01-4.25, p=0.043). KMT2D and PI3KCA mutations were not associated with differences in overall survival when compared to wild-type tumors. Copy number alterations in the genes GPHN, HOOK3, SPEN, CAMTA1 and BCL2L11 were associated with survival differences in patients treated with bevacizumab. A majority of AGCT carry FOXL2 mutations. The next most common mutations were KMT2D, PIK3CA, and alterations in chromatin remodeling. In this cohort of patients, the FOXL2 mutation was associated with improved overall survival. Copy number alterations in specific genes were associated with differences in survival in patients treated with bevacizumab. These results support molecular profiling of AGCT to improve prognostication for these patients. These findings provide groundwork to direct further investigation into novel treatment strategies and targeted agents in AGCT. [ABSTRACT FROM AUTHOR]

Due to the rarity of vulvar/vaginal melanoma (VVM), current therapeutic strategies mimics that of cutaneous melanoma (CM) without scientific rationale. Currently, immuno-oncology (IO) is a front-line treatment option for advanced melanoma, however data are limited for IO outcomes in advanced VVM. Considering 5-year survival for vulvar (58%) and vaginal (27%) melanoma is significantly inferior to cutaneous melanoma (81%), this calls into question the assumed similarity of these malignancies. As such, our goal is to compare molecular profiles of VVM with CM and explore the significance of IO agents on survival. Samples were analyzed using next-generation sequencing (NextSeq, 592 Genes and WES, NovaSEQ), IHC and WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PD-L1 expression was tested by IHC using 28-8 (Agilent) and SP-142 (Spring Biosciences) (positive cut-off ≥1%). MSI was tested by FA, IHC and NGS. TMB was measured by totaling somatic mutations per tumor (TMB-high cut-off ≥10 mutations per MB). Immune cell fraction was calculated by QuantiSeq (Finotello 2019, Genome Medicine). Survival was extracted from insurance claims data and calculated from time of IO treatment to last contact using Kaplan-Meier survival curves. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons. Molecular analysis was performed on 171 VVM and 5255 CM between 1998 and 2020. Median age for VVM and CM was 65 and 63, respectively. A total of 114 (66.7%) VVM and 3538 (67.3%) CM were metastatic at time of diagnosis. Immunogenicity of VVM was significantly lower than CM, demonstrated by an absence of high tumor mutation burden (0% vs 48%) and a decrease in PD-L1 expression (34.1% vs 45.2%) (Fig 1A). Adaptive immune gene expression was lower in VVM compared to CM (Fig 1B). By QuantiSeq, the cell fractions for type I macrophages and C8+ T-cells were significantly lower in VVM compared to CM (Fig 1C). Median survival was shorter for VVM than for CM (19 vs 37 months, p=.058; Fig 1D). VVM also demonstrated significantly (p<.01) less frequent BRAF mutations (8.4% vs 35.8%), more frequent KIT mutations (13.2% vs 2.8%), KIT amplifications (14.7% vs 1.5%), ATRX mutations (28.4% vs 3.8%), and SF3B1 mutations (27.8% vs 1.6%). NRAS mutations were similar (14.6% vs 19.5%). Alteration in pathways involving DNA damage (16.4% vs 5.2%) and mRNA splicing (28.9% vs 2.8%) were more common in VVM, while alterations in cell cycle (7.2% vs 18.8%) and chromatin remodeling (6.3% vs 21.4%) were less common (Fig 1E). [Display omitted] VVM represents a distinct molecular profile from CM with a less favorable immune phenotype demonstrated by absence of TMB-high, lower rates of PD-L1 positivity, and lower adaptive immune gene expression and cell fractions of effector T-cells and immune promoting macrophages. Compared with CM, patients with VVM were found to have significantly worse survival when treated with IO therapy. Though IO has been a mainstay of treatment in recent years, these findings suggest that new therapeutic strategies are needed. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the feasibility of using social media to perform cross-sectional epidemiologic and quality-of-life research on patients with rare gynecologic tumors, we performed a survey of patients with neuroendocrine tumors of the cervix using Facebook. Methods: After approval from our Institutional Review Board, a support group of patients with neuroendocrine tumors of the cervix was identified on Facebook. Group members were asked to complete a survey comprising 84 questions evaluating clinical presentation; treatment; recurrence; quality of life; and sexual function. Results: The survey was posted for 30days, during which 57 women responded from 8 countries across 4 continents treated at 51 centers. All respondents provided a detailed clinical and tumor history. The mean age was 38.5years. The stage distribution was stage I, 36 patients (63%); II, 13 (23%); III, 2 (4%); and IV, 6 (11%). Forty-nine patients (86%) had small cell and 8 (14%) had large cell tumors. Forty-five of the respondents (79%) had completed primary therapy and were without evidence of disease. Five (9%) had recurrence, 3 (5%) had persistent disease after therapy, and 4 (7%) were still under treatment. Forty-one patients (72%) reported symptoms at time of presentation. Thirty-seven patients (65%) received multimodality primary therapy. Quality of life instruments demonstrated high scores for anxiety and a negative impact of anxiety and cancer on functional and emotional well-being. Sexual function scores did not differ significantly between respondents and the PROMIS reference population. Conclusions: Use of a social media network to perform epidemiologic and quality of life research on patients with rare gynecologic tumors is feasible and permits such research to be conducted efficiently and rapidly. [Copyright &y& Elsevier]

Abstract: Objective: Cervical adenocarcinoma in situ (AIS) is increasing in incidence among reproductive-age women. Cervical conization is an alternative to hysterectomy that allows future fertility, however reports regarding the risk of residual AIS and underlying adenocarcinoma are conflicting. The purpose of this study was to determine the outcomes of a large cohort of women treated for AIS. Methods: The medical records of 180 women with cervical AIS evaluated at the University of Texas MD Anderson Cancer Center and its outlying clinics between 1983 and 2011 were reviewed for demographic information, treatment history, pathologic findings and outcomes. Results: The mean age at diagnosis was 33.8years (range 17.6–76.1years). 172 of the 180 women had at least one cone biopsy performed, with 110 (64.0%) undergoing a cold knife cone (CKC), and 62 (36.0%) undergoing a loop electrosurgical excision procedure (LEEP) as their initial method of treatment. Positive margins were noted in 35.0% of patients undergoing CKC compared with 55.6% undergoing LEEP (p=0.017). 71 patients ultimately underwent hysterectomy with residual disease noted in 10 patients (14.1%), 8 patients (11.3%) with residual AIS and 2 patients (2.8%) with invasive carcinoma. Of the 101 patients who did not undergo hysterectomy, 2 patients (2.0%) developed recurrent AIS at a median of 27.5months (range 18–37months) from the last cone, and none developed invasive carcinoma. Conclusion: Patients undergoing conservative management for AIS with cervical conization alone should be monitored closely and counseled regarding the potential risks of residual and recurrent disease, even when negative cone margins are obtained. [Copyright &y& Elsevier]

Abstract: Objective: To prospectively evaluate tumor control, survival, and toxic effects in patients with International Federation of Gynecology and Obstetrics (1988) stage I–IIIA papillary serous carcinoma of the endometrium treated with concurrent chemoradiation and adjuvant chemotherapy. Methods: Thirty-two patients were enrolled from October 2001 through July 2009. Patients underwent full surgical disease staging and postoperative concurrent weekly paclitaxel (50mg/m2) and pelvic RT to 45Gy plus a vaginal cuff boost followed by 4cycles of adjuvant paclitaxel (135mg/m2). Results: Thirty patients (94%) were evaluable (3 with stage IA disease, 11 IB, 3 IC, 1 IIB, and 12 IIIA). Eighteen patients (60%) received all 5 planned courses of concurrent chemotherapy, 10 (33%) received 4 courses, and 2 (7%) received 3 courses. All 30 patients received RT; 27 (90%) received the full dose, 2 received 43.2Gy, and 1 received 39.6Gy owing to toxic effects. Twenty-three patients (77%) completed all 4cycles of adjuvant paclitaxel, 3 (10%) completed 3cycles, 2 (7%) completed 2cycles, and 2 received no adjuvant therapy. Overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 93%, 87%, and 87%, respectively, at 2years and 85%, 83%, and 87%, respectively, at 5years. Six patients developed (20%) grade 3/4 toxicities from the treatment. Four patients (13%) had grade 3 or more severe bowel complications and two patients developed symptomatic pelvic fractures. Conclusions: Treatment with concurrent paclitaxel and pelvic RT followed by 4 courses of systemic paclitaxel produced favorable results in patients with surgically staged I–III UPSC. [Copyright &y& Elsevier]

Abstract: Objective: Few studies have examined the dietary habits of ovarian cancer survivors. Therefore, we conducted a study to assess the feasibility and impact of two dietary interventions for ovarian cancer survivors. Methods: In this randomized, parallel-group study, 51 women (mean age, 53years) diagnosed with stages II–IV ovarian cancer were recruited and randomly assigned to a low fat, high fiber (LFHF) diet or a modified National Cancer Institute diet supplemented with a soy-based beverage and encapsulated fruit and vegetable juice concentrates (FVJCs). Changes in clinical measures, serum carotenoid and tocopherol levels, dietary intake, anthropometry, and health-related quality of life (HRQOL) were assessed with paired t-tests. Results: The recruitment rate was 25%, and the retention rate was 75% at 6months. At baseline, 28% and 45% of women met guidelines for intake of fiber and of fruits and vegetables, respectively. After 6months, total serum carotenoid levels and α- and β-carotene concentrations were significantly increased in both groups (P <0.01); however, β-carotene concentrations were increased more in the FVJC group. Serum β-cryptoxanthin levels, fiber intake (+5.2g/day), and daily servings of juice (+0.9servings/day) and vegetables (+1.3servings/day) were all significantly increased in the LFHF group (all P <0.05). Serum levels of albumin, lutein and zeaxanthin, retinol, and retinyl palmitate were significantly increased in the FVJC group (all P <0.05). No changes in cancer antigen-125, anthropometry, or HRQOL were observed. Conclusion: Overall, this study supports the feasibility of designing dietary interventions for stages II–IV ovarian cancer survivors and provides preliminary evidence that a low fat high fiber diet and a diet supplemented with encapsulated FVJC may increase phytonutrients in ovarian cancer survivors. [Copyright &y& Elsevier]

Abstract: Objective: To compare intra-operative, postoperative and pathologic outcomes of three surgical approaches to radical hysterectomy and bilateral pelvic lymph node dissection over a three year time period during which all three approaches were used. Methods: We reviewed all patients who underwent radical hysterectomy with pelvic lymph node dissection between 1/2007 and 11/2010. Comparison was made between robotic, laparoscopic and open procedures in regard to surgical times, complication rates, and pathologic findings. Results: A total of 95 radical hysterectomy procedures were performed during the study period: 30 open (RAH), 31 laparoscopic (LRH) and 34 robotic (RRH). There were no differences in age, body mass index or other demographic factors between the groups. Operative time was significantly shorter in the RAH compared to LRH and RRH (265 vs 338 vs 328min, p=0.002). Estimated blood loss was significantly lower in LRH and RRH compared with RAH (100 vs 100 vs 350mL, p<0.001). Thirteen (24%) of RAH required blood transfusion. Conversion rates were higher in the LRH (16%) compared to RRH (3%) although not significant (p=0.10). Median length of stay was significantly shorter in RRH (1day) vs LRH or RAH (2 vs 4days, p<0.01). Pathologic findings were similar among all groups. Conclusion: Minimally invasive surgery has made a significant impact on patients undergoing radical hysterectomy including decrease in blood loss and transfusion rates however; operative times were significantly longer compared to open radical hysterectomy. Our findings suggest that the robotic approach may have the added benefit of even shorter length of stay compared to traditional laparoscopy. [Copyright &y& Elsevier]

Abstract: Purpose: The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of the anti-EGFR antibody cetuximab, in persistent or recurrent carcinoma of the cervix. Patients and methods: Eligible patients had cervical cancer, measurable disease, and GOG performance status ≤2. Treatment consisted of cetuximab 400mg/m2 initial dose followed by 250mg/m2 weekly until disease progression or prohibitive toxicity. The primary endpoints were progression-free survival (PFS) at 6months and response. The study used a 2-stage group sequential design. Results: Thirty-eight patients were entered with 3 exclusions, leaving 35 evaluable for analysis. Thirty-one patients (88.6%) received prior radiation as well as either 1 (n=25, 71.4%) or 2 (n=10) prior cytotoxic regimens. Twenty-four patients (68.6%) had a squamous cell carcinoma. Grade 3 adverse events possibly related to cetuximab included dermatologic (n=5), GI (n=4), anemia (n=2), constitutional (n=3), infection (n=2), vascular (n=2), pain (n=2), and pulmonary, neurological, vomiting and metabolic (n=1 each). No clinical responses were detected. Five patients (14.3%; two-sided 90% CI, 5.8% to 30%) survived without progression for at least 6months. The median PFS and overall survival (OS) times were 1.97 and 6.7months, respectively. In this study, all patients with PFS at 6months harbored tumors with squamous cell histology. Conclusion: Cetuximab is well tolerated but has limited activity in this population. Cetuximab activity may be limited to patients with squamous cell histology. [Copyright &y& Elsevier]

Immunotherapy has emerged as a promising intervention in metastatic or recurrent cervical cancer, but response rates have been modest, albeit with some durable responses. To date, immune profiling and pathway characterization via whole transcriptome sequencing (WTS) has been limited to sampled tumors from newly diagnosed, mostly early stage disease. In the current study, we sought to use WTS-based immune profiling to develop a more representative analysis of the cervical cancer population receiving immunotherapy. Cervical cancer tumor samples were analyzed using next-generation sequencing and whole exome sequencing (NGS: NextSeq, 592 Genes and NovaSEQ, WES), immune-histochemistry (IHC), and WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PD-L1 expression was tested by IHC using standard protocol (PD-L1+ threshold: CPS ≥1). Microsatellite instability (MSI) was tested by fragment analysis, IHC and NGS. Tumor mutational burden (TMB) was measured by counting all somatic mutations found per tumor (TMB-high: ≥10 mutations per MB). Immune cell infiltration was calculated by QuantiSeq. TP53 mutations were used as a proxy indicator for non-HPV tumors. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons using Benjamini & Hochberg and Bonferroni, respectively (significance threshold: adjusted p-value < 0.01). 930 patients with cervical cancer underwent profiling from 2008-2020. Median age was 52 years. 449 (48.3%) patients had metastatic disease. Among FDA-approved companion markers of response to immunotherapy, the most commonly present was PD-L1+ (83.5%). Compared to adenocarcinoma, squamous cell carcinoma (SCC) had a more robust immune signal, with increased: PD-L1+, TMB-high status, infiltration of multiple types of immune cells (neutrophils, CD8+ T cells, regulatory T cells), as well as increased expression of multiple immune checkpoint genes (see Table 1). PD-L1+ status was significantly associated with increased macrophage M1 (3.51% vs 2.04%), CD8+ T (0.7% vs. 0%) and regulatory T (2.4% vs 1.3%) cell infiltration, yet decreased NK (2.6% vs 3.2%) cell infiltration. TMB-high was associated with significantly increased infiltration of neutrophils and CD8+ T cells. Older (≥63 yrs;) patients had significantly more somatic TP53 mutations (25.2% vs 10.1%, indicating more non-HPV tumors with increasing age) and dendritic cell infiltration compared to younger patients (Table 1). [Display omitted] Cervical SCC had a higher immune signal than adenocarcinoma: increased immunotherapy biomarkers (PD-L1 and TMB), immune cell infiltration, and upregulation of immune checkpoint genes. Non-HPV status and dendritic cell infiltration increased with advanced age. The variety of signals noted in this analysis suggests that transcriptomic immune profiling should be further investigated in the push to better predict which patients with cervical cancer might benefit most from immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST)., Methods: This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov, NCT01042522., Results: At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4-52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%)., Conclusions: The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST., Competing Interests: Declaration of competing interest Dr. Brown has participated in the Speakers' Bureau for Clovis and for Eisai and has received funding for this. Dr. Brown has participated in Advisory Boards or as a consultant with AstraZeneca, Caris, Biodesix, Janssen, Tempus, Olympus, Clovis, Invitae, Verastem, and GSK/Tesaro. Dr. Brown has participated in research with GSK/Tesaro and Genentech. Dr. Austin Miller reports that his institution received payments for serving on a Data Safety Monitoring Board or Advisory Board for Agenus, AstraZeneca, VBL Therapeutics. Dr. Floor Backes reports research grants to Institution from Merck, Eisai, ImmunoGen, Clovis, Beigene, Natera, Tempus, AstraZeneca. Dr. Backes reports receiving personal fees from UptoDate. Dr. Backes reports receiving personal fees for serving on Advisory boards for Agenus, Merck, Clovis, Immunogen, Eisai, AstraZeneca, GlaxoSmithKline, Myriad, BioNTech and Daiichi Sankyo. Dr. Backes received honoraria for CME lectures from Clinical Educational Concepts, Clinical Care Options, Medscape/WebMD, Med Learning 13Health, CMR Institute, Global Learning Initiative/Prova, OncLive, Targeted Oncology and Research to Practice. GlaxoSmithKline provided Dr. Backes with support for travel. Dr. Backes served as a Board member for the Society of Gynecology Oncology (unpaid), Dr. Backes served as Co-Chair for NRG Oncology Developmental Therapeutics Committee as well as Co-Chair for IGCS Education 360. Dr. David Bender reports receiving grant support from Merck, Sharp & Dohme Company, Clovis Oncology, Inc. and Genentech. Dr. David Miller reports Grants to Institution from Advenchen, Forty Seven, Merck, Syros, US BIOTEST and Regeneron. He also reports receiving royalties from Karyopharm. Dr. Miller received consulting fees from Karyopharm, Incyte, Eisai, Merck, GlaxoSmithKline and Immunogen. Dr. Matthew Powell reports personally receiving consulting fees from GSK, Merck, Eisai, Seagen, Jazz, Clovis Oncology, AstraZeneca, Asdi Bioscience and AbbVie. He also reports participating on an Advisory Board for GSK and receiving compensation for the same. Additionally, Dr. Powell served in Leadership roles for SGO, NRG and GCSC and receiving compensation for the same. Dr. Westin has received research support to institution from AstraZeneca, Avenge Bio, Inc., Bayer, Bio-Path, Clovis Oncology, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, Roche/Genentech, Zentalis. Dr. Westin has received consulting fees from AstraZeneca, Caris, Clovis Oncology, Eisai, EQRX, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mereo, Mersana, NGM Bio, Nuvectis, Roche/Genentech, SeaGen, Verastem, Vincerx, Zentalis and ZielBio. Dr. Bonebrake reports providing patients with diagnosis of stromal ovarian tumors. Additionally, Dr. Bonebrake reports participating on Advisory Board for Blueprint Medicine (no consulting fee received), Merck – Global Cervical and Ovarian Cancer Virtual Advisory Board (no consulting fee) and AstraZeneca – AZ eVOLVE DMC (ongoing). Dr. Bonebrake served on the Board of Directors for the GOG Foundation (unpaid) and reports receiving occasional travel reimbursement to attend meetings and NRG Oncology Board of Directors (unpaid). Dr. Muller reports grants to her Institution, New Mexico Minority Underserved NCORP) to support enrollment to all NCI NCTN trials. Dr. Muller also reports contracts to institution to enroll to GOG Partner trials from GOG Partners Foundation (Seagen, GSK, Mersana, Alkermes Inc., Merck, Verastem, Immunogen, etc.) as well as contracts to her Institution for enrollment to specific clinical trials, Linnaeus Therapeutics. Dr. Muller also reports serving as advisory on disparity advisory councils for GSK and Seagen to advise on ways to increase minority enrollment to clinical trials. Dr. Secord reports grants received to Institution from AbbVie, Aravive Inc., AstraZeneca, Clovis, Eisai, Ellipses, I-MAB Biopharma, GSK, Immunogen, Merck, Mersana OncoQuest/CanariaBio, Roche/Genentech, Seagen Inc., TapImmune, Tesaro/GSK, VBL Therapeutics. Dr. Secord reports personally receiving honoraria from @Point of Care, Clinical Care Options, Curio Science, PeerView, Bio ASCENT, RTP, GOG Foundation (Highlight reel) and GOG Foundation Symposium. Also, patents planned, issued or pending on “Blood based biomarkers in ovarian cancer” without compensation, She reports serving on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Clovis, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova and OncoQuest/Canariabio without compensation. Dr. Secord reports serving in leadership role for SGO (uncompensated), GOG (personal fee received), AAOGF (uncompensated) and NRG who provided grant to her institution. Finally, Dr. Secord receiving medical writing from AstraZeneca. Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio), all without compensation. Dr. Crane reports serving on the Speakers Bureau for Merck and GlaxoSmithKline but the relationship for each of these has been terminated. Dr. Crane served on the Advisor Board for both AstraZeneca and GlaxoSmithKline. Dr. Schorge reports receiving Williams Gynecology royalties from McGraw-Hill and royalties for 2 articles from UpToDate. Dr. Schorge also reports receiving Consulting fees from Best Doctors. Dr. Tew reports receiving consulting fees from UpToDate and honoraria for the Chemotherapy Foundation Symposium 2022. Dr. Sood reports NCI grant received relative to this study as well as receiving the American Cancer Society Research Professor Award. Dr. Sood reports consulting fees received from KIYATEC, ImmunoGen, Merck & Co, Lyon, GSK, AstraZeneca and Onxeo. He also reports patents planned issued or pending for the EGFL6 antibody. Dr. Sood participated on an Advisory Board for Advenchen and has stock in Bio-Path Holdings. Dr. Bookman reports serving on a DMC for Immunogen as well as an Advisory Board for Clovis, and his institution received payment for both. Dr. Aghajanian reports Clinical trial funding to Institution (MSK) from AbbVie – MSK PI, GOG3005; AstraZeneca – MSK PI, SOLO1/GOG 3004; National Coordinating Investigator & MSK PI, D081RC00001; ENGOT-ov6; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, Ariel 2 & 3 and Genentech/Roche-MSK PI, GOG3015 (1Magyn050). Dr. Gershenson reports grants received from Novartis to his Institution. He also reports royalties personally received from Elsevier and UpToDate. Dr. Gershenson also received consulting fees from Verastem and Genentech. Dr. Gershenson also reports personal fees received for serving on the Advisory Boards for Aadi, Verastem and Beigene/Springworks. He received no compensation for serving as Chair, International Consortium for Low-Grade Serous Ovarian Cancer and reports stock ownership for Bristol Myers Squib, Johnson & Johnson and Procter and Gamble. The following Coauthors have no conflicts of Interest to disclose: Dr. Holman and Dr. Nagel., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Unlike other surgical specialties, obstetrics and gynecology (OB-GYN) has been predominantly female for the last decade. The association of this with gender bias and sexual harassment is not known., Objective: To systematically review the prevalence of sexual harassment, bullying, abuse, and discrimination among OB-GYN clinicians and trainees and interventions aimed at reducing harassment in OB-GYN and other surgical specialties., Evidence Review: A systematic search of PubMed, Embase, and ClinicalTrials.gov was conducted to identify studies published from inception through June 13, 2023.: For the prevalence of harassment, OB-GYN clinicians and trainees on OB-GYN rotations in all subspecialties in the US or Canada were included. Personal experiences of harassment (sexual harassment, bullying, abuse, and discrimination) by other health care personnel, event reporting, burnout and exit from medicine, fear of retaliation, and related outcomes were included. Interventions across all surgical specialties in any country to decrease incidence of harassment were also evaluated. Abstracts and potentially relevant full-text articles were double screened.: Eligible studies were extracted into standard forms. Risk of bias and certainty of evidence of included research were assessed. A meta-analysis was not performed owing to heterogeneity of outcomes., Findings: A total of 10 eligible studies among 5852 participants addressed prevalence and 12 eligible studies among 2906 participants addressed interventions. The prevalence of sexual harassment (range, 250 of 907 physicians [27.6%] to 181 of 255 female gynecologic oncologists [70.9%]), workplace discrimination (range, 142 of 249 gynecologic oncologists [57.0%] to 354 of 527 gynecologic oncologists [67.2%] among women; 138 of 358 gynecologic oncologists among males [38.5%]), and bullying (131 of 248 female gynecologic oncologists [52.8%]) was frequent among OB-GYN respondents. OB-GYN trainees commonly experienced sexual harassment (253 of 366 respondents [69.1%]), which included gender harassment, unwanted sexual attention, and sexual coercion. The proportion of OB-GYN clinicians who reported their sexual harassment to anyone ranged from 21 of 250 AAGL (formerly, the American Association of Gynecologic Laparoscopists) members (8.4%) to 32 of 256 gynecologic oncologists (12.5%) compared with 32.6% of OB-GYN trainees. Mistreatment during their OB-GYN rotation was indicated by 168 of 668 medical students surveyed (25.1%). Perpetrators of harassment included physicians (30.1%), other trainees (13.1%), and operating room staff (7.7%). Various interventions were used and studied, which were associated with improved recognition of bias and reporting (eg, implementation of a video- and discussion-based mistreatment program during a surgery clerkship was associated with a decrease in medical student mistreatment reports from 14 reports in previous year to 9 reports in the first year and 4 in the second year after implementation). However, no significant decrease in the frequency of sexual harassment was found with any intervention., Conclusions and Relevance: This study found high rates of harassment behaviors within OB-GYN. Interventions to limit these behaviors were not adequately studied, were limited mostly to medical students, and typically did not specifically address sexual or other forms of harassment.

Purpose: This interim report of the GARNET phase I trial presents efficacy and safety of dostarlimab in patients with advanced or recurrent endometrial cancer (EC), with an analysis of tumor biomarkers as prognostic indicators., Patients and Methods: A total of 153 patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and 161 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC were enrolled and dosed. Patients received 500 mg dostarlimab every 3 weeks for four cycles, then 1,000 mg every 6 weeks until progression. Primary endpoints were objective response rate (ORR) and duration of response (DOR)., Results: A total of 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS EC were evaluated for efficacy. ORR was 45.5% (n = 65) and 15.4% (n = 24) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. Median DOR for dMMR/MSI-H EC was not met (median follow-up, 27.6 months); median DOR for MMRp/MSS EC was 19.4 months. The ORRs by combined positive score (CPS) ≥1 status were 54.9% and 21.7% for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORRs by high tumor mutational burden (≥10 mutations/Mb) were 47.8% (43/90) and 45.5% (5/11) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORR in TP53mut or POLεmut molecular subgroups was 18.1% (17/94) and 40.0% (2/5), respectively. The safety profile of dostarlimab was consistent with previous reports., Conclusions: Dostarlimab demonstrated durable antitumor activity and safety in patients with dMMR/MSI-H EC. Biomarkers associated with EC may identify patients likely to respond to dostarlimab. See related commentary by Jangra and Dhani, p. 4521., (©2023 The Authors; Published by the American Association for Cancer Research.)

Importance: Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti-programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor., Objective: To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors., Design, Setting, and Participants: The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017. Participants had advanced or recurrent dMMR and microsatellite instability-high (MSI-H) or polymerase epsilon (POLE)-altered solid tumors. The data cut for this interim analysis was from November 1, 2021, with median follow-up of 27.7 months., Interventions: Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal., Main Outcomes and Measures: The primary objective was to evaluate objective response rate and duration of response in patients with dMMR solid tumors by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1., Results: The efficacy population included 327 patients (median [range] age, 63 [24-85] years; 235 [71.9%] female; 7 [2.1%] Asian, 6 [1.8%] Black, and 206 [63.0%] White patients), with 141 patients (43.1%) with dMMR endometrial cancer, 105 patients (32.1%) with dMMR colorectal cancer, and 81 patients (24.8%) with other dMMR tumor types. All patients had at least 1 previous line of therapy. Objective response rate assessed per blinded independent central review for dMMR solid tumors was 44.0% (95% CI, 38.6% to 49.6%). Median duration of response was not reached (range, ≥1.18 to ≥47.21 months); 72.2% of responders (104 of 144) had a response lasting 12 or more months. Median progression-free survival was 6.9 months (95% CI, 4.2 to 13.6 months); probability of progression-free survival at 24 months was 40.6% (95% CI, 35.0% to 46.1%). Median overall survival was not reached (95% CI, 31.6 months to not reached). The most frequent immune-related adverse events were hypothyroidism (25 [6.9%]), alanine aminotransferase increase (21 [5.8%]), and arthralgia (17 [4.7%]). No new safety concerns were identified., Conclusions and Relevance: In this nonrandomized controlled trial, dostarlimab was a well-tolerated treatment option with rapid, robust, and durable antitumor activity in patients with diverse dMMR solid tumors. These findings suggest that dostarlimab provides meaningful long-term benefit in a population with high unmet need., Trial Registration: ClinicalTrials.gov Identifier: NCT02715284.

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care., Competing Interests: Competing interests: RG reports fees for grants/contracts from Context Therapeutics, Versatem, SpringWorks, Bayer, Novartis; fees for consulting for GSK, AstraZeneca, Natera, Corcept, Intellisphere, SpringWorks, Verastem, Myriad; fees for payment/honoraria from Prime Oncology, MCM Education, OncLive, Aptitude Health, Cardinal Health; fees for leadership/ fiduciary role with NCCN Ovarian Cancer Guidelines Committee Member, and ICLC Precision Therapeutics. BS reports consulting fees for AstraZeneca, Clovis, GSK, Genentech, Onconova, Nuvation, Lilly, EQRx, Myriad, Immunogen, Novocure, and Merck. NA has no conflicts to disclose. SB reports fees for grants/contracts from AstraZeneca, GSK; fees for consulting for AstraZeneca, GSK, Immunogen, Merck Sharpe Dohme, EMD/Merck Serono, Mersana, Novartis, Oncxerna, Seagen, Shattuck Labs, Regeneron, Epsilogen; fees for payment/honoraria from Amgen, AstraZeneca, Clovis, GSK, Immunogen, Merck Sharpe Dohme, Mersana, Pfizer, Roche, Takeda, Novacure; fees for support for attending meetings/travel from AstraZeneca, GSK, Verastem; fees for leadership/fiduciary role from ESMO Director of Membership (2020-2022); and fees for other financial or non-financial interests from Global PI ENGOTov60/GOG3052/RAMP201. JB reports fees for consulting for Caris Life Sciences, AstraZeneca, Verastem, Genentech, GSK Tesaro; fees for participation on a Data Safety Monitoring Board/Advisory Board from Caris, AstraZeneca, GSK Tesaro, Verastem; fees for a leadership/fiduciary role from American Association of Gynecologic Laparoscopy, and Society of Gynecologic Oncology. MSC reports fees for grants/contracts from Canada Research Society, Canadian Institute for Health Research, Ovarian Cancer Canada, BC Cancer Foundation, Department of Defense US Army, Australian Medical Research Fund; fees for payment/honoraria from Verastem; fees for leadership/fiduciary role from Canadian Cancer Trials Group; and fees for stock or stock option from Bausch Health Companies, Illumina, aiGENE, DentalToday, Hexamer Therapeutics. HC reports fees for payment/honoraria from Verastem Oncology. RLC reports fees for grants/contracts from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Roche/Genentech; consulting fees from Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, OncoQuest, Onxerna, Regeneron, Roche/Genentech, Novocure, Merck, Abbvie; fees for payment/honoraria from AstraZeneca, Clovis, Roche/Genentech, Merck; fees for participation on a Data Safety Monitoring Board/Advisory Board from VBL Therapeutics, and Eisai/BMS. ANF reports fees for advisory board support from Versatem and PI of the NCI NRG GY019. SG reports fees for patents for United States Patent Nos 10,258,604 & 10,905,659; and fees for participation on a Data Safety Monitoring Board/Advisory Board from Verastem. CG reports fees for grants from AstraZeneca, GSK, Tesaro, Clovis, MSD, BergenBio, Novartis, Aprea, Nucana, Versatem, Roche, Medannexin; fees for consulting from AstraZeneca, MSD, GSK, Tesaro; fees for payment/honoraria from AstraZeneca, MSD, GSK, Tesaro, Clovis, Roche, Nucana, Chugai, Takeda, Cor2Ed, Peervoice; fees for participation on a Data Safety Monitoring Board/Advisory Board from AstraZeneca, MSD, GSK, Tesaro, Roche, Nucana, Chugai; and fees for a leadership/fiduciary role from Scottish Medicines Consortium. AKS reports fees for grants from American Cancer Society Research Professor Award; fees for royalties from EGFL6 antibody; fees for consulting for Merck, GSK, Iylon, ImmunoGen, Onxeo, Kiyatec; fees for leadership/fiduciary role from SGO Board of Directors; and fees from stock/stock options for BioPath. BJM reports fees for consulting for Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Tesaro/GSK, US Oncology Research, VBL, Verastem, Zentalis; fees for payment/honoraria from AstraZeneca, Clovis, Easai, Merck, Myriad, Roche/Genentech, and Tesaro/GSK. KNM reports fees for grants/contracts and participation on a data safety monitoring board from PTC Therapeutics, Lilly, Clovis, Genentech, GSK, Verastem; fees for consulting for AstraZeneca, Aravive, Alkemeres, Addi, Blueprint pharma, Clovis, Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Mereo, Mersana, Merck, Myriad, Norvartis, Novocur, OncXerna, Onconova, Tarveda, VBL Therapeutics, Verastem; fees for payment/honoraria from AstraZeneca, GSK, Immunogen, PRIME, RTP, Medscape, Great Debates and Updates; fees for support for attending meetings/travel from AstraZeneca; and a leadership/fiduciary role with GOG P Associate Director. IRC reports fees for grants/contracts from MSH, Roche, BMS, Novartis, AstraZeneca, Merck, Sereno; fees for consulting for Agenus, Amgen, BMS, AstraZeneca, Roche, GSK, Deciphera, Mersena, Novartis, Clovis, Adaptimmun, DAICHI Sankyo, Immunogen, Blueprint; fees for support for attending meetings/travel from OSE Company (ASCO 2022); fees for participation on a Data Safety Monitoring Board or Advisory Board from Athena trial, Attend trial and AGO-OVAR57 trial. IMS has no conflicts of interest. SNW reports fees for grants/contracts from AstraZeneca, Bayer, Clovis Oncology, AvengeBio, GSK, Mereo, Novartis, Bio-Path, Roche/Genentech, Zentalis; fees for consulting for ZielBio, AstraZeneca, Clovis Oncology, Eisai, Merck, Mereo, Mersana, Seagen, Nuvectis, Verastem, EQRx, GSK, Immunogen, Lilly, Zentalis, Roche/Genentech, Caris, Vincerx, and NGM Bio. KKW reports fees for support for the present manuscript from MD Anderson Ovarian Cancer Moon Shot Program, STAAR Ovarian Cancer Foundation, The Ludemann Family, and Department of Defense Grant (W81XWH-19-1-0169). DG reports fees for support for the present manuscript from Verastem; fees for grants/contracts from National Cancer Institute, Novartis; fees for royalties/licenses from Elsevier, UpToDate; fees for consulting for Genentech, Verastem; fees for payment/honoraria from University of Washington Grand Rounds, Yale University School of Medicine Grand Rounds; fees for support for attending meetings/travel from Society of Gynecologic Oncology Bridges Program, Verastem; fees for participation on a Data Safety Monitoring Board or Advisory Board from Verastem, Aadi, Onconova; fees for leadership/fiduciary role from Chair, International Consortium of Low-Grade Serious Ovarian Cancer; and fees for stock/stock options from J&J, BMS, and Procter and Gamble., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

What Is This Summary About?: Dostarlimab, also known by the brand name JEMPERLI, is a medicine that can be used to treat certain types of endometrial cancer. GARNET is an ongoing phase 1 clinical study that is testing the safety and side effects of dostarlimab and the best way to administer it to patients. The results presented in this summary are from a time point in the middle of the study., What Were the Results?: The results from the GARNET study published in 2022 showed how well dostarlimab worked for people participating in the study. Dostarlimab was found to reduce the size of tumors in patients with certain types of endometrial cancer. The patients treated with dostarlimab had side effects that could be managed and few severe side effects., What Do the Results Mean?: The results of the GARNET study led to dostarlimab being approved to treat patients with certain types of endometrial cancer. For patients with advanced-stage endometrial cancer, or endometrial cancer that has come back after chemotherapy (recurrent), there are few treatment options. The results suggest that dostarlimab may provide long-term benefits for these patients.

Objective: The goals of this study were to describe opioid and benzodiazepine prescribing practices in the gynecologic oncology patient population and determine risks for opioid misuse in these patients., Methods: Retrospective study of opioid and benzodiazepine prescriptions for patients treated for cervical, ovarian (including fallopian tube/primary peritoneal), and uterine cancers within a single healthcare system from January 2016 to August 2018., Results: A total of 7643 prescriptions for opioids and/or benzodiazepines were dispensed to 3252 patients over 5754 prescribing encounters for cervical (n=2602, 34.1%), ovarian (n=2468, 32.3%), and uterine (n=2572, 33.7%) cancer. Prescriptions were most often written in an outpatient setting (51.0%) compared with inpatient discharge (25.8%). Cervical cancer patients were more likely to have received a prescription in an emergency department or from a pain/palliative care specialist (p=0.0001). Cervical cancer patients were least likely to have prescriptions associated with surgery (6.1%) compared with ovarian cancer (15.1%) or uterine cancer (22.9%) patients. The morphine milligram equivalents prescribed were higher for patients with cervical cancer (62.6) compared with patients with ovarian and uterine cancer (46.0 and 45.7, respectively) (p=0.0001). Risk factors for opioid misuse were present in 25% of patients studied; cervical cancer patients were more likely to have at least one risk factor present during a prescribing encounter (p=0.0001). Cervical cancer was associated with a higher number of risk factors (p<0.001)., Conclusions: Opioid and benzodiazepine prescribing patterns differ for cervical, ovarian, and uterine cancer patients. Gynecologic oncology patients are overall at low risk for opioid misuse; however, patients with cervical cancer are more likely to have risk factors present for opioid misuse., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objective: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer., Design: Retrospective cohort., Setting: Teaching hospital., Patients: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after., Interventions: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020., Measurements and Main Results: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66)., Conclusion: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: There is an increase in patient-reported outcome assessments to gain information on new drug candidates from the patient's perspective. A data gap remains in patient-reported outcome measurements for anti-programmed death 1 (anti-PD-1) therapies in endometrial cancer. We present patient-reported outcome measures collected from patients with mismatch repair-deficient/microsatellite instability-high advanced or recurrent endometrial cancer treated with dostarlimab, an anti-PD-1 monoclonal antibody, in an expansion cohort of the GARNET trial., Methods: GARNET (NCT02715284) is a phase I single-arm study of dostarlimab monotherapy in multiple tumor types. Patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer were treated with 500 mg of intravenous dostarlimab once every 3 weeks for four cycles, then 1000 mg of intravenous dostarlimab every 6 weeks. Patient-reported outcome assessments were an exploratory endpoint, measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)., Results: At data cut-off, 88 patients with mismatch repair-deficient endometrial cancer were included in the analysis. Patient-reported outcome assessment completion was >95.5% throughout cycle 7 of the trial, with no individual domain completion <90.9%. Quality of life, emotional functioning, and social functioning showed improvement compared with baseline. All symptom scores showed either improvement or stability from baseline through cycle 7. Categorical change in response across all symptom scales and single-item response scores showed stability or improvement for most patients. For patients who saw a worsening of their categorical change in response, ≤7.4% experienced a 2-category worsening and ≤2.5% experienced a 3-category worsening., Conclusions: Most patients remained stable or had improved quality of life while receiving dostarlimab for the treatment of recurrent or advanced mismatch repair-deficient endometrial cancer., Trial Registration Number: NCT02715284., Competing Interests: Competing interests: RK reports grants from Clovis and MSD; honoraria and consultancy fees from AstraZeneca, Basilea Pharmaceutica, Clovis, Eisai, Incyte, MSD, and PharmaMar; and personal fees from GSK. CM reports institutional grants from GSK. AR reports institutional grants from Eisai, PharmaMar, and Roche; and advisory roles at AstraZeneca, GSK, PharmaMar, and Roche. SB is an employee of GSK. JH and EI are former employees of GSK. JB reports honoraria from Olympus; consulting or advisory role at AstraZeneca, Caris, Clovis, Genentech, and GSK; and speakers’ bureau at Clovis., (© IGCS and ESGO 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Dostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab., Methods: GARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500 mg every 3 weeks for 4 cycles, then dostarlimab 1000 mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review., Results: Screening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5-22.1) for cohort A1 and 11.5 months (IQR 11.0-25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1-2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Grade≥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab., Conclusion: Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile., Trial Registration Number: NCT02715284., Competing Interests: Competing interests: AO reports consulting fees from AstraZeneca, Bristol Meyers Squibb, Deciphera Pharmaceutical, Genmab, GlaxoSmithKline, ImmunoGen, Mersana Therapeutics, SUTRA, and Roche; institutional grants from Abbie Deutschland, Ability Pharmaceuticals, Advaxis Inc, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Clovis Oncology Inc, Eisai Ltd, F. Hoffmann-La Roche Ltd, GlaxoSmithKline, ImmunoGen Inc, and Merck Sharp & Dohme de Espana SA, Millennium Pharmaceuticals Inc, PharmaMar, and Regeneron Pharmaceuticals, and travel support from AstraZeneca, Clovis Oncology, PharmaMar, and Roche. LG reports institutional grants from AstraZeneca, Pfizer, and Merck Sharp & Dohme, Karyopharm, Tesaro, IMV, Alkermes, Clovis, ImmunoGen Inc, Roche, Mersana, Esperas, Novocure GmbH, OncoQuest Pharmaceuticals; consulting fees from Merck; honoraria from AstraZeneca, GlaxoSmithKline, Eisai, Eisai-Merck, and Alkermes. AVT reports institutional grants from AstraZeneca and personal fees from AstraZeneca and Eisai. JB reports honoraria from Olympus; consulting or advisory role at Caris, GlaxoSmithKline, Clovis, AstraZeneca, and Genentech; and speakers’ bureau at Clovis. CM reports institutional grants from GlaxoSmithKline. JP has nothing to disclose. RS reports institutional grants from AstraZeneca and Eisai; personal fees from AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, and Roche; and nonfinancial support from Amgen, AstraZeneca, Pfizer, and Roche. DMO'M reports personal fees from Agenus, Array Biopharma, Eisai, GlaxoSmithKline, and ImmunoGen; consultant/advisory board for Abbvie, Ambry, Amgen, Clovis, EMD Serono, Ergomed, Janssen/J&J, Myriad Genetics, Novacure, Regeneron, Tarveda, and VentiRx; steering committee for Genentech/Roche and Merck; institutional funding from Ajinomoto Inc, Bristol Myers Squibb, Cerulean Pharma, GOG Foundation, INC Research Inc, Inventiv Health Clinical, Iovance Biotherapeutics Inc, Ludwig Cancer Research, New Mexico Cancer Care Alliance, PRA International, Serono Inc, Stemcentrx Inc, Tracon Pharmaceuticals, and Yale University. VS has nothing to disclose. VB reports consulting or advisory roles at Guidepoint Global and OncoArt; speakers’ bureau fees from Solti; travel support from START; honoraria from Loxo and IDEAYA Biosciences; and institutional grants from Abbvie, Adaptimmune, Alkermes, Amgen, Array BioPharma, AstraZeneca, Bayer, BioNTech AG, Boehringer Ingelheim, Boston Biomedical, Bristol Myers Squibb, CytomX Therapeutics, Genmab, GlaxoSmithKline, Incyte, Janssen Oncology, Kura Oncology, Lilly, Loxo, Menarini, Merck, Merus, Novartis, Pfizer, Pumo Biotechnology, Roche/Genentech, Sanofi, Seattle Genetics, Synthon, and Zenith Epigenetics. LD reports personal fees from Advance Medical, ASCO, AstraZeneca, British Journal of OB/GYN, ClearView Health Care, Cue Biopharma, Elsevier, Genentech/Roche, Innovio, JB Learning, Merck, MorphoTek, National Cancer Institute, Parexel, State of California, and UpToDate; and institutional grants from Abbvie, Advaxis, Aduro BioTech, Cerulean/NextGen, Eisai, Genentech/Roche, GlaxoSmithKline, Inovio, LEAP Therapeutics, Ludwig, Lycera, Morab, Morphotek, Merck, Novartis, Pfizer, and Syndax. SG reports consulting or advisory role from Seattle Genetics; speakers’ bureau fees from GlaxoSmithKline; and institutional research funding from Abbvie, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, and Takeda. PG has nothing to disclose. RK reports personal fees from GlaxoSmithKline. CL reports contracted research for GlaxoSmithKline and scientific advisory board fees from GlaxoSmithKline, Eisai, Clovis Oncology, Seattle Genetics, and AbbVie. WG is a former employee of GlaxoSmithKline. EI is a former employee of GlaxoSmithKline. SZ, XH, TD, and JV are employees of GlaxoSmithKline. BP reports institutional grants support from Tesaro/GSK, AstraZeneca, Merck, Genentech/Roche, Celsion, Mersana, Karyopharm, and Clovis Oncology; and advisory board fees from Tesaro/GSK, AstraZeneca, Merck, Eisai, Toray, Mersana, Elevar Therapeutics, Arquer Diagnostics, Sutro Biopharma, and Clovis Oncology., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objective: To identify factors associated with same day discharge (SDD) after laparoscopic surgery in gynecologic oncology., Design: Retrospective cohort., Setting: Teaching hospital., Patients: Total of 800 patients having minimally invasive surgery in the division of gynecologic oncology during a 20-month period., Intervention: Minimally invasive surgery cases were reviewed for determinants of SDD to identify factors that could improve the SDD rate., Measurements and Main Results: During the study period, 800 minimally invasive procedures were performed with a 43.0% SDD rate. Patients who had SDD were younger (52.3 years vs 58.0 years; p <.001), had a lower body mass index (31.1 kg/m 2 vs 33.7 kg/m 2 ; p <.001), were less likely to have a malignancy (28.2% vs 55.5%; p <.001), had a lower estimated blood loss (36 vs 72 mL; p <.001), and were more likely to have received an enhanced recovery after surgery protocol (49.8% vs 39.3%; p <.003). Total surgical time was shorter in women with SDD (156 minutes vs 208 minutes) as was total narcotic use in morphine equivalents (MEq) (milligram intravenous MEq, 23.1 mg MEq vs 28.8 mg MEq). SDD was also associated with earlier start time (p <.001). Laparoscopic cases were most likely to have SDD (51.4%) as compared with robotic assisted surgery (16.1%) or minilaparotomy (10.5%). There was a wide range of SDD among surgeons ranging from 19.8% to 56.2% (p <.001). In a multivariate analysis, the factors predicting SDD in order of predictive factors were surgical time (p <.001), recovery time (p <.001), start time (p <.001), surgeon (p <.001), age (p <.001), estimated blood loss (p <.001), and type of surgery (p = .005)., Conclusion: Multiple factors affect SDD. Modifiable factors for SDD include the start time, surgeon preference, and patient expectations for SDD. Given these data, centers should prioritize surgical order by which patients are more likely to go home, and surgeons should analyze their own data with respect to achieving higher SDD rates., (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To compare intraoperative and perioperative narcotic use, recovery room time, and total hospital stay for patients treated with robotic vs laparoscopic surgery for endometrial cancer., Design: Retrospective cohort., Setting: Teaching hospital., Patients: All patients having minimally invasive surgery in the division of gynecologic oncology during a 20-month period., Intervention: Laparoscopic cases were compared with robot-assisted cases with respect to perioperative outcome., Measurement and Main Results: Hospital billing records were used to identify all patients with endometrial cancer treated from January 1, 2018 through July 31, 2019 undergoing either laparoscopic or robotic surgery. Data were collected including total narcotic use converted to intravenous morphine milligram equivalent (MME), total amount of time in recovery, and length of hospital stay. A total of 139 laparoscopic and 101 robotic surgeries were eligible for analysis. There was no difference between the groups with respect to blood loss, alcohol use, or smoking. Patients undergoing laparoscopy had a significantly lower body mass index compared with patients undergoing robotic surgery (32.9 vs 38.0 kg/m 2 ; p <.001). Univariate analysis showed no difference between the 2 groups with respect to narcotic use in surgery (21.7 vs 21.1 MME; p = .64), recovery (4.3 vs 4.5 MME; p = .70), or total dose (26.0 vs 25.6 MME; p = .78). However, patients who underwent a robotic approach had a longer recovery room time (128 minutes vs 163 minutes; p <.001 and a longer surgical time (288 minutes vs 204 minutes; p = .001). Patients in the robotic group were also more likely to undergo full lymphadenectomy than patients in the laparoscopy group (38.0% vs 20.8% p <.001). In a multivariate analysis, the only significant factors for predicting total narcotic dose were age, use of a preoperative enhanced recovery after surgery program, and surgical time. Patients who had laparoscopy were more likely to achieve same-day discharge (39.3% vs 17.8%; p <.001), but in the multivariate analysis, the type of surgery did not predict same-day discharge., Conclusion: There was no difference in narcotic use in the perioperative period with robotic surgery compared with laparoscopy. Recovery time was longer for robotic surgery, but this was not significant in multivariate analysis. Same-day discharges were less frequent with robotics, which may be more related to the physician's choice rather than the procedure., (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

This document provides a short summary of the GARNET trial which was published in JAMA Oncology in October 2020. At the end of this document, there are links to websites where you can find more information about this study. The trial enrolled adult participants with advanced solid tumors. This report is restricted to patients with a particular type of endometrial cancer that has a deficient mismatch repair (dMMR) status. Patients received a trial treatment called dostarlimab (also known by the brand name Jemperli). In the US, dostarlimab is approved as a single therapy in adult patients with dMMR recurrent or advanced endometrial cancer that has progressed on or after platinum-based chemotherapy. In the EU, dostarlimab is approved as a single therapy in adult patients with recurrent or advanced dMMR/microsatellite instability-high (MSI-H) endometrial cancer that has progressed on or after treatment with a platinum-containing regimen. The GARNET trial looked at dostarlimab given intravenously to patients with dMMR endometrial cancer from 7 countries. The trial showed that dostarlimab was successful in shrinking the tumor in 42% of these patients. In general, the percentage of participants who experienced medical problems (referred to as side effects) was low and within expectations for this type of treatment. ClinicalTrials.gov NCT number: NCT02715284. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Link to original article here .

Study Objective: To review the perioperative differences between patients undergoing a minimally invasive sentinel lymph node dissection and those undergoing a full lymphadenectomy., Design: Retrospective review., Setting: Teaching hospital., Patients: All patients undergoing a minimally invasive procedure for endometrial cancer that included nodal evaluation., Interventions: Patients who underwent a sentinel lymph node biopsy were compared with those who underwent a full lymphadenectomy at the time of minimally invasive surgery by either laparoscopic or robot-assisted surgery., Measurements and Main Results: A total of 241 minimally invasive surgery procedures for endometrial cancer were performed during the 20-month study period. Nodal dissection was indicated and performed in 156 (65%) of these patients, with 93 undergoing a sentinel lymph node biopsy and 63 a full lymphadenectomy. There was no difference between the sentinel group and the lymphadenectomy group with respect to age, estimated blood loss (p = .23), use of a preoperative enhanced recovery after surgery program (p = .82), or body mass index (34.0 kg/m 2 vs 33.7 kg/m 2 ; p = .87). The use of full lymphadenectomy was very dependent on the surgeon (p <.001). There was no difference in narcotic use in milligram intravenous equivalents of morphine in surgery (20.9 vs 22.2; p = .37), recovery (4.6 vs 4.9; p = .73), or total dose (25.4 vs 27.0; p = .33). The surgical procedure was longer with lymphadenectomy (185.2 minutes vs 214.2 minutes; p <.001) and the relative risk of discharge from recovery was lower (0.71; 95% confidence interval, 0.51-0.97; p = .03). The hospital stay was longer with lymphadenectomy (16.3 hours vs 25.5 hours; p <.001) and same-day discharge less frequent (48.5% vs 13.8%; p <.001). A multivariate analysis confirmed that sentinel node biopsy was associated with an increased relative risk of discharge of 1.68 (95% confidence interval 1.11-2.53; p = .01) CONCLUSION: Total narcotic requirements are similar between sentinel node biopsy and lymphadenectomy. However, sentinel node biopsy is associated with a shorter surgical time, recovery time, and hospital stay., (Copyright © 2021. Published by Elsevier Inc.)

Study Objective: To review the impact of enhanced recovery after surgery (ERAS) after minimally invasive surgery (MIS) with respect to perioperative narcotics, time in the recovery room, and total time in hospital., Design: Retrospective cohort., Setting: Teaching hospital., Patients: All patients having MIS in the division of gynecologic oncology during a 20-month period., Intervention: MIS cases were compared before and after the implementation of an ERAS protocol that incorporated orally administered acetaminophen, gabapentin, and celecoxib., Measurement and Main Results: A total of 800 MIS cases were performed during the period (77% laparoscopy, 18% robotic, 5% mini-lap). Of these, 449 cases were treated without and 351 with the ERAS protocol. There were no significant differences between the groups with respect to age, BMI, surgery type, smoking, surgical indication, blood loss, or diagnosis. Total narcotic use in milligram intravenous equivalents of morphine (mg IV Eq) was significantly less in the ERAS patients (28.5-mg IV Eq vs 23.6-mg IV Eq; p <.001). There was a trend toward less narcotics in recovery (4.8-mg IV Eq vs 4.1-mg IV Eq; p = .08). Postoperative recovery room time was not different between the groups (129 minutes vs 131 minutes; p = .66). ERAS was associated with a higher rate of same day discharge (38.5% vs 49.0%; p = .003) and a shorter length of hospital stay (22.9 hours vs 18.5 hours; p = .008), with a hazard ratio for discharge of 0.82 (0.71-0.94). However, the same day discharge rate varied widely between treating physicians (20% to 56%)., Conclusions: Implementation of an ERAS protocol for MIS appears to reduce total perioperative narcotic use but does not reduce recovery room time. There was a reduction in total hospital time, but this may be dependent on practice patterns of individual physicians., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To compare outcomes after minimally invasive surgery (MIS) vs open radical hysterectomy for early stage cervical cancer incorporating 2018 Federation of Gynecology and Obstetrics (FIGO) staging., Design: A retrospective analysis., Setting: A single teaching hospital., Patients: Patients after radical hysterectomy for stage IA1 with lymphovascular invasion, IA2, or IB1 squamous, adenosquamous, or adenocarcinoma of the cervix between 2007 and 2018, mirroring the Laparoscopic Approach to Cervical Cancer trial criteria., Interventions: The use of MIS surgery for performing radical hysterectomy., Measurements and Main Results: The outcomes were compared between patients undergoing MIS vs open approaches. A total of 126 patients met the inclusion criteria. The approach was open in 44 patients (35%) and MIS in 82 patients (65%); 49% were laparoscopic and 51% were robotic. Distribution based on the 2009 FIGO staging showed 1 stage IA1 with lymphovascular invasion, 15 stage IA2, and 110 stage IB1 patients. Although not statistically significant, the 3-year disease-free survival (DFS) was higher in the open compared to the MIS group (95% vs 87%; p = .17), and the overall survival was higher in the open compared to the MIS group (97% vs 92%; p = .25). Fourteen patients whose disease recurred were Stage IB1 by FIGO 2009 staging; 11/14 were reclassified to a higher stage by 2018 FIGO staging (5/5 open, 6/9 MIS). Adjuvant therapy was recommended for all these patients based on the Sedlis criteria (10/14) or other risk factors (4/14). Despite this, only 1/9 of MIS patients whose disease recurred received adjuvant therapy compared with 3/5 patients whose disease recurred in the open group (p = .05)., Conclusion: In a cohort of patients similar to that of the Laparoscopic Approach to Cervical Cancer trial, 2018 FIGO staging may be useful to refine indications for MIS radical hysterectomy in early stage cervical cancer. However, disparate outcomes between MIS and open approaches may be explained by differences in compliance with National Comprehensive Cancer Network guidelines for adjuvant therapy., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Importance: Deficient mismatch mutation repair mechanisms may sensitize endometrial cancers to anti-programmed death 1 (PD-1) therapies. Dostarlimab (TSR-042) is an investigational anti-PD-1 antibody that binds with high affinity to the PD-1 receptor., Objective: To assess the antitumor activity and safety of dostarlimab for patients with deficient mismatch repair endometrial cancer., Design, Setting, and Participants: This ongoing, open-label, single-group, multicenter study began part 1 on March 7, 2016, and began enrolling patients with deficient mismatch mutation repair endometrial cancer on May 8, 2017. Median follow-up was 11.2 months (range, 0.03 [ongoing] to 22.11 [ongoing] months; based on radiological assessments). Statistical analysis was performed July 8 to August 9, 2019., Interventions: Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, treatment discontinuation, or withdrawal., Main Outcomes and Measures: The primary end point was objective response rate and duration of response by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1., Results: As of the data cutoff, 104 women (median age, 64.0 years [range, 38-80 years]) with deficient mismatch mutation repair endometrial cancers were enrolled and treated with dostarlimab. Of these, 71 had measurable disease at baseline and at 6 months or more of follow-up and were included in the analysis. There was a confirmed response in 30 patients (objective response rate, 42.3%; 95% CI, 30.6%-54.6%); 9 patients (12.7%) had a confirmed complete response, and 21 patients (29.6%) had a confirmed partial response. Responses were durable; the median duration of response was not reached (median follow-up was 11.2 months). The estimated likelihood of maintaining a response was 96.4% at 6 months and 76.8% at 12 months. Anemia (3 of 104 [2.9%]), colitis (2 of 104 [1.9%]), and diarrhea (2 of 104 [1.9%]) were the most common grade 3 or higher treatment-related adverse events., Conclusions and Relevance: In this nonrandomized trial, dostarlimab was associated with clinically meaningful and durable antitumor activity with an acceptable safety profile for patients with deficient mismatch mutation repair endometrial cancers after prior platinum-based chemotherapy., Trial Registration: ClinicalTrials.gov identifier: NCT02715284.