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Purpose: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial. Patients and Methods: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan–Meier estimates. Results: Among biomarker-evaluable samples, 22% (234/1,050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1,024) had TMB ≥10 mut/Mb, and 0.3% (3/1,022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2–non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on ICs) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors. Conclusions: Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors. See related commentary by Al-Rawi et al., p. 1645

PFS by treatment arm according to TMB status (stratified by treatment approach, disease stage, and ECOG PS). A, TMB-low population. B, TMB-high population. CPB, paclitaxel, carboplatin, and bevacizumab.

Purpose:To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.Patients and Methods:Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan–Meier estimates.Results:Among biomarker-evaluable samples, 22% (234/1,050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1,024) had TMB ≥10 mut/Mb, and 0.3% (3/1,022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2–non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on ICs) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors.Conclusions:Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors.See related commentary by Al-Rawi et al., p. 1645

There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue culture and in animal tumor models of serous ovarian cancer. Cell survival, tumor growth, PI3K–AKT–mTOR pathway signaling, DNA damage and repair response (DDR) gene expression, and translational control were all investigated. We show that platinum-resistant OVCAR-3 ovarian cancer cells are resensitized to low levels of carboplatin in culture by mTOR inhibition, demonstrating reduced survival after treatment with either mTORC1 inhibitor everolimus or mTORC1/2 inhibitor PP242. Platinum resistance is shown to be associated with activating phosphorylation of AKT and CHK1, inactivating phosphorylation of 4E-BP1, the negative regulator of eIF4E, which promotes increased cap-dependent mRNA translation and increased levels of CHK1 and BRCA1 proteins. Animals with platinum-resistant OVCAR-3 tumors treated with carboplatin plus mTORC1/2 inhibition had significantly longer median survival and strikingly reduced metastasis compared with animals treated with carboplatin plus everolimus, which inhibits only mTORC1. Reduced tumor growth, metastasis, and increased survival by mTORC1/2 inhibition with carboplatin treatment was associated with reduced AKT-activating phosphorylation and increased 4E-BP1 hypophosphorylation (activation). We conclude that mTORC1/2 inhibition is superior to mTORC1 inhibition in reversing platinum resistance in tumors and strongly impairs AKT activation, DNA repair responses, and translation, promoting improved survival in the background of platinum resistance. Mol Cancer Ther; 15(7); 1557–67. ©2016 AACR.

Supplementary Figure S1: Growth inhibitory 50% (GI50) determination of single agent everolimus, PP242 and carboplatin using OVCAR-3 cells; Supplementary Figure S2: mTORC1 and mTORC1/2 inhibition sensitizes platinum resistant SKOV3 cells to carboplatin-mediated growth inhibition; Supplementary Figure S3: qRT-PCR analysis of select mRNAs in mTORC1 and mTORC1/2 inhibited cells with and without carboplatin treatment.

Supplementary Methods, Tables 1-3, Figure 1 from Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Purpose Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services. Methods We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined. Results A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27–53%] and 30% [CI 19–44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86–100%]), telemedicine (75% [CI 43–93%]), clinic-embedded genetic counselor (76% [CI 32–95%]), reflex tumor somatic genetic assessment (64% [CI 17–94%]), universal testing (57% [28–82%]), and referral forms (26% [CI 10–53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17–38%] vs. 40% [CI 25–57%]) as was being un-insured vs. insured (23% [CI 18–28%] vs. 38% [CI 26–53%]). Conclusions Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status.

The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4+ TILs were evident in 76.9% of cases, CD8+ in 92.3%, CD45RO+ in 92.3%, and FOXP3+ in 46.2%, as well as CD68+ TAMs in 100% and CD163+ in 100%. For the 15 BM cases, CD4+ TILs were evident in 60.0% of cases, CD8+ in 93.3%, CD45RO+ in 73.3%, and FOXP3+ in 35.7%, as well as CD68+ TAMs in 86.7% and CD163+ in 100%. An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.

More than 20,000 women are diagnosed with ovarian cancer each year in the United States, most with advanced stage disease.1 With five-year cause-specific survival of 47 percent, ovarian cancer is t...

BackgroundPostdischarge nausea and vomiting after ambulatory surgery is a common problem that is not adequately addressed in current practice. This prospective, randomized, double-blind, parallel-group, placebo-controlled study was designed to test the hypothesis that oral olanzapine is superior to placebo at preventing postdischarge nausea and vomiting.MethodsIn a single-center, double-blind, randomized, placebo-controlled trial, the authors compared a single preoperative dose of olanzapine 10 mg to placebo, in adult female patients 50 years old or less, undergoing ambulatory gynecologic or plastic surgery with general anesthesia. All patients received standard antiemetic prophylaxis with dexamethasone and ondansetron. The primary composite outcome was nausea and/or vomiting in the 24 h after discharge. Secondary outcomes included severe nausea, vomiting, and side effects.ResultsA total of 140 patients were randomized and evaluable. The primary outcome occurred in 26 of 69 patients (38%) in the placebo group and in 10 of 71 patients (14%) in the olanzapine group (relative risk, 0.37; 95% CI, 0.20 to 0.72; P = 0.003). Severe nausea occurred in 14 patients (20%) in the placebo group and 4 patients (6%) in the olanzapine group (relative risk, 0.28; 95% CI, 0.10 to 0.80). Vomiting occurred in eight patients (12%) in the placebo group and two patients (3%) in the olanzapine group (relative risk, 0.24; 95% CI, 0.05 to 1.10). The median score for sedation (scale 0 to 10, with 10 being highest) in the 24 h after discharge was 4 (interquartile range, 2 to 7) in the placebo group and 6 (interquartile range, 3 to 8) in the olanzapine group (P = 0.023).ConclusionsWhen combined with ondansetron and dexamethasone, the addition of olanzapine relative to placebo decreased the risk of nausea and/or vomiting in the 24 h after discharge from ambulatory surgery by about 60% with a slight increase in reported sedation.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

Background Timely genetic testing at ovarian cancer diagnosis is essential as results impact front line treatment decisions. Our objective was to determine rates of genetic counseling and testing with an expedited genetics referral pathway wherein women with newly-diagnosed ovarian cancer are contacted by a genetics navigator to facilitate genetic counseling. Methods Patients were referred for genetic counseling by their gynecologic oncologist, contacted by a genetics navigator and offered appointments for genetic counseling. Patients completed quality of life (QoL) surveys immediately pre- and post-genetic assessment and 6 months later. The primary outcome was feasibility of this pathway defined by presentation for genetic counseling. Results From 2015 to 2018, 100 patients were enrolled. Seventy-eight had genetic counseling and 73 testing. Median time from diagnosis to genetic counseling was 34 days (range 10–189). Among patients who underwent testing, 12 (16%) had pathogenic germline mutations (BRCA1-7, BRCA2-4, MSH2-1). Sixty-five patients completed QoL assessments demonstrating stress and anxiety at time of testing, however, scores improved at 6 months. Despite the pathway leveling financial and logistical barriers, patients receiving care at a public hospital were less likely to present for genetic counseling compared to private hospital patients (56% versus 84%, P = 0.021). Conclusions Facilitated referral to genetic counselors at time of ovarian cancer diagnosis is effective, resulting in high uptake of genetic counseling and testing, and does not demonstrate a long term psychologic toll. Concern about causing additional emotional distress should not deter clinicians from early genetics referral as genetic testing can yield important prognostic and therapeutic information.

Objectives Trainee well-being is a core component of ACGME program requirements and the SGO has recognized the high incidence of burnout among gynecologic oncologists and its negative impact. To foster a culture of wellness throughout the SGO community we sought to engage current fellows along with fellowship directors in a structured didactic program designed to teach wellness. We evaluated the feasibility of and preliminary responses to a pilot curriculum designed to teach skills that promote wellness and prevent burnout. Methods The SGO Wellness Taskforce developed a curriculum with topics based on established evidence as well as specialty specific stressors such as end of life discussions. Faculty leaders from 15 pilot-sites attended a full-day training course and then taught four modules over four months. Interactive modules engaged fellows through reflective writing, guided discussion, and multimedia presentations. Fellows completed the Perceived Stress Scale pre- and post-implementation and provided feedback regarding attitudes toward wellness and the individual modules. Faculty curriculum leaders completed surveys regarding their attitudes toward the curriculum as well as their trainees' reactions. Results Among 73 participating gynecologic oncology fellows, 95% (69/73) and 52/73 (71%) completed the pre-and post-surveys, respectively. Only 34/73 (49%) respondents reported that there was wellness programming at their institution prior to the initiation of the SGO curriculum. At institutions where such programming was available, 35% (12/34) reported not utilizing them. Fifty-five (80%) fellows had PSS scores greater than 12 compared to 39 (75%) post-intervention. After the curriculum, the percentage of fellows comfortable discussing wellness topics increased from 63 to 74%. Prior to the curriculum, 75% felt they could identify symptoms of burnout or psychosocial distress. This increased to 90% post-intervention. The modules were well received by fellows, and the time spent addressing wellness was widely appreciated. Conclusions A structured curriculum to promote wellness among gynecologic oncology fellows is feasible and was associated with observed decreased reported stress among fellows at participating programs. This curriculum addresses ACGME requirements regarding trainee well-being, and showed potential for more programmatic, nationwide implementation. Fellowship culture change was not directly measured, but may have been one of the most significant positive outcomes of the wellness program. Further longitudinal studies will be necessary to understand the natural course of fellow burnout and the impact of structured wellness programming.

OBJECTIVE: Poly(ADP-Ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase 2 dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. METHODS: Veliparib and PLD were administered in a standard phase 1, 3+3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. RESULTS: 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens 4. Patients received a median of 4 cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were >200 mg BID. CONCLUSIONS: The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.

Providers who care for women at risk for hereditary gynecologic cancers must consider the impact of these conditions on reproductive and hormonal health. This document reviews potential options for cancer prevention, family building, genetic testing and management of surgical menopause in this patient population. Capsule: Women predisposed to hereditary gynecologic cancer have options for fertility preservation, preimplantation genetic testing to select embryos without pathogenic variants, pregnancy through gestational carriers after hysterectomy and hormone replacement.

The literature demonstrates that the quality of cancer family history (CFH) as currently collected in the outpatient setting is inadequate to assess disease risk. Prior to implementation of a web-based application for cancer family history collection, we aimed to review the quality of collected CFH in a gynecologic oncology outpatient clinic and determine contributing patient factors. Medical records were reviewed for 200 new patients presenting between 4/2019-7/2019. CFH was collected during the patient interview and evaluated for inclusion of eight elements based on standards set by the genetics community. Univariate and multivariable linear regression analyses were utilized to evaluate the effect of patient characteristics on the number of relatives included in the CFH. Among our cohort of 200 patients, CFH was documented for 185 patients (92.5%). On univariate analysis, patients with a family history of cancer and prior genetic testing had significantly greater median number of relatives included in the CFH. On multivariable analysis, patients with family members with cancer had significantly more relatives included. Our data are consistent with the literature, suggesting that the current collection methods may not adequately capture all measures of a high quality CFH. Patients reporting no family history of cancer and those without prior genetic testing were least likely to have CFH that included key quality elements and these patients might benefit from health information technology CFH collection tools.

Ovarian cancer (OC) is one of the leading causes of cancer mortality among women in the United States. With the approval of first-line maintenance therapies, patients with OC experienced prolonged first-line progression-free survival. While the literature addresses some costs associated with OC, further research is needed on the costs of progression that are potentially deferred or prevented by early maintenance. The objective of this study was to capture the health care resource utilization and costs of patients with advanced OC who never received poly(ADP ribose) polymerase (PARP) inhibitor maintenance.We conducted a descriptive retrospective analysis of treatment patterns and the consequences of progression through several lines of therapy (LOTs) in patients with OC, using claims from commercial and Medicare Advantage health plan members in the United States from the Optum Research Database between January 1, 2010, and April 30, 2019. Patients were required to have an index OC diagnosis (≥ 2 non-diagnostic claims). We examined up to 4 LOTs and the time between treatments.A total of 5498 women met the eligibility criteria. As the number of LOTs increased, the median duration of each line decreased from 137 days in LOT1 to 94 days in LOT4, and the time between lines also decreased from 245 to 0 days. Ambulatory care visits were a major driver of health care resource utilization, with a median of about 6 monthly visits during active treatment. The mean total monthly health care costs for patients with at least 2 LOTs were US$8588 (SD: $8533) before LOT2 and increased to $15,358 (SD: $21,460) during or after LOT2.Prolonging progression-free survival after first-line treatment in patients with OC may provide the opportunity to delay or prevent later treatment, the financial toxicity felt by patients, and the economic burden to the health care system associated with progression.Ovarian cancer is a complex disease in which 70% of patients are diagnosed with advanced disease, and one of the leading causes of cancer mortality among women in the United States. A variety of maintenance therapy options, including bevacizumab, PARP inhibitors, and PARP plus bevacizumab combination therapies, have demonstrated improvements in progression-free survival. By delaying disease progression after completion of first-line therapy, a simultaneous decrease in post-progression health care costs may be seen. The objective of this study was to capture the health care resource utilization and costs of patients with advanced ovarian cancer who did not receive a PARP inhibitor at any time in their treatmentIn patients never receiving a PARP inhibitor, this study documented substantial health care resource usage and costs associated with progression beyond the first line of treatment (surgery and/or chemotherapy) in ovarian cancer. These were largely driven by the number of ambulatory care visits. When these visits are combined with emergency department visits and inpatient stays, high costs are incurred by both patients and third-party payersProlonging progression-free survival after first-line treatment in patients with ovarian cancer may delay or prevent the need for later treatment, the financial burden felt by patients, and the economic burden to the health care system associated with subsequent disease progressions.

Previvors are becoming more aware of the option of risk-reducing salpingectomy with delayed oophorectomy (RRS-DO) to mitigate their risk of ovarian cancer. In this qualitative study, we explored the clinical and non-clinical factors that impacted previvors' decision-making to pursue RRS-DO as a risk reduction strategy.Semi-structured telephone interviews were conducted with previvors and transcribed verbatim. Using ATLAS.ti® software, two primary investigators interpreted data through thematic analysis. After coding four interviews, the investigators discussed discrepancies between codes with a moderator and resolved and refined code. The investigators applied the universal codebook to all interviews and revised the codebook using an iterative approach. Examining codes within and across interviews allowed for major themes and patterns to emerge.Interviews were conducted with seventeen previvors (ages 31-46). 6 (25%) previvors had a BRCA1 mutation, 7 (41%), a BRCA2 mutation, 3 (13%), a Lynch-related mutation, and 1 (6%), other (MUTYH mutation). At the time of interview, 12 previvors (71%) were planning (6) or had undergone (6) RRS-DO, 4 (23%) were planning (1) or had undergone (3) risk reducing salpingo-oophorectomy (RRSO), and 1 (6%) was undecided. Three major themes emerged: motivating factors for selecting surgical risk reduction option, barriers complicating surgical decision-making, and facilitating factors for surgical decision-making. RRS-DO-focused previvors prioritized avoiding menopause, and they also emphasized that self-advocacy and building rapport with providers facilitated their decision-making.By understanding previvors' priorities and experiences, physicians can better partner with previvors as they navigate their ovarian cancer risk reduction journey. This will ultimately optimize shared decision-making.

Background Strong participant recruitment practices are critical to public health research but are difficult to achieve. Traditional recruitment practices are often time consuming, costly, and fail to adequately target difficult-to-reach populations. Social media platforms such as Facebook are well-positioned to address this area of need, enabling researchers to leverage existing social networks and deliver targeted information. The MAGENTA (Making Genetic Testing Accessible) study aimed to improve the availability of genetic testing for hereditary cancer susceptibility in at-risk individuals through the use of a web-based communication system along with social media advertisements to improve reach. Objective This paper is aimed to evaluate the effectiveness of Facebook as an outreach tool for targeting women aged ≥30 years for recruitment in the MAGENTA study. Methods We designed and implemented paid and unpaid social media posts with ongoing assessment as a primary means of research participant recruitment in collaboration with patient advocates. Facebook analytics were used to assess the effectiveness of paid and unpaid outreach efforts. Results Over the course of the reported recruitment period, Facebook materials had a reach of 407,769 people and 57,248 (14.04%) instances of engagement, indicating that approximately 14.04% of people who saw information about the study on Facebook engaged with the content. Paid advertisements had a total reach of 373,682. Among those reached, just Conclusions Facebook is a useful way of enhancing clinical trial recruitment of women aged ≥30 years who have a potentially increased risk for ovarian cancer by promoting news stories over social media, collaborating with patient advocacy groups, and running paid and unpaid campaigns. Trial Registration ClinicalTrials.gov NCT02993068; https://clinicaltrials.gov/ct2/show/NCT02993068

Background Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). Methods Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. Results Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0–73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). Conclusions The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.

307 Background: In the US, more than 12,000 people die from ovarian cancer annually. Although new treatments have recently become available, ovarian cancer care delivery remains suboptimal. The Association of Community Cancer Centers (ACCC) developed a series of initiatives to improve the quality of care for patients with ovarian cancer. In Phase I, ACCC evaluated the needs of cancer programs, conducted 3 quality improvement (QI) workshops, and developed expert-driven Quality of Care recommendations to aid cancer programs in self-assessment and quality improvement. In Phase II, ACCC invited programs to self-assess their level of care using the Quality of Care recommendations. Methods: In 2022, ACCC surveyed 7 ovarian cancer programs across the US. Developed by a multidisciplinary expert steering committee, the 26-question survey assessed the patient populations served, services provided, diagnostic evaluations performed, access to molecular testing, and a self-assessment of quality care delivery and interest in conducting QI projects related to self-identified needs. The survey was administered in Qualtrics and summarized using descriptive statistics. Results: Surveys were completed by 1 community, 2 comprehensive community, 2 hospital-associated, 1 academic comprehensive, and 1 NCI-designated comprehensive cancer programs. The median annual ovarian cases was 40 [range: 2 to 68]. The 7 programs serve diverse racial/ethnic distribution of patients with ovarian cancer ranging from 55% Black to 60% Asian and 30% Pacific Islander. Five programs have a multidisciplinary team for ovarian cancer. All 5 multidisciplinary teams included gynecologic oncology and pathology; 3 teams also included medical oncology and or radiology colleague(s). Sites assessed their level of care for 7 domains of quality care from 1 (lowest) to 5 (highest). The average score was 4.0 for Care Coordination and Patient Education, Treatment Planning, and Disease Surveillance. Diagnosis and Initial Management scored on average 3.8, Equity in Care 3.25, Prevention and Screening 3.25, and Quality of Life 3.2. Sites ranked areas of interest for future QI projects (1 = area of most interest, 7 = area of least interest). The highest ranked domains were Care Coordination and Patient Education as well as Diagnosis and Initial management (average rankings 2.8). These were followed by Quality of Life (average 3.0), Prevention and Screening (Average 3.8), Treatment Planning (Average 4.4), Equity in Care (Average 5.0), and Disease Surveillance (Average 6.2). Conclusions: This assessment will be used to identify 4 additional sites for Phase II QI workshops. Findings from these projects will be combined, summarized, and disseminated to inform future education opportunities and QI initiatives. This initiative aims to help organize and standardize the care of patients with ovarian cancer and improve patient care coordination.

Opinion statement COVID-19 has transformed the care we provide to gynecologic oncology patients. In addition to directly impacting the diagnosis and treatment of women with gynecologic cancer, it has affected our patient’s ability to undergo recommended surveillance and has made an impact on every caregiver providing care during this time. Herein we review the current literature on the impact of COVID-19 on gynecologic oncology and highlight new approaches and innovations that have resulted in gynecologic cancer care as a result of the pandemic. The impact of COVID-19 on the field of gynecologic oncology has been profound. In addition to directly impacting the diagnosis and treatment of women with cancer, it has also challenged the very ethics with which we practice medicine. The equitable distribution of resources is paramount to upholding the Hippocratic Oath which we all invoke. The COVID-19 pandemic has stripped this oath down to its very core, forcing all medical practitioners to scrutinize who gets what resources and when. As the pandemic continues to unfold, the question remains — in the setting of a strained and overburdened healthcare system, how do we maximize beneficence to one group of patients, while maintaining non-maleficence to others? As gynecologic oncologists, we are responsible for advocating for our patients to ensure that the quality of their cancer care is not compromised, while also not overutilizing resources that are sorely needed for the care of COVID-19 victims, and not making them more likely to succumb to COVID-19 by the very nature of the treatment we provide. The effects of the pandemic are far-reaching and broad, and many of these are yet to be determined. Future studies are needed to analyze how the above-utilized strategies in GYN cancer care during the pandemic will impact the long-term outcomes of our patients.

Objective: With the increasing age of the population, more elderly women undergo gynecologic surgery. While multiple studies have demonstrated the advantages of minimally invasive surgery ...

Microsatellite instability-high (MSI-H) phenotype arises from defective DNA repair mechanisms and is found in many malignancies, including colorectal and endometrial cancers. Due to high neoantigen loads derived from tumor-specific mutations, evidence of tumor-infiltrating T cells and high response rates to checkpoint blockade (30-60%), MSI-H cancers can be leveraged to study the features of neoantigen-induced anti-tumor immunity in response to therapy and disease outcome. Previously we identified a set of recurrent frameshift (fs) mutations in MSI-H cancers that yielded immunogenic polyepitope neoantigens (neoAgs) eliciting CD8+ T cell responses. Here we investigate whether these shared fs-neoAgs engendered spontaneous T cell responses in MSI-H colorectal and endometrial cancer patients. Using peripheral blood mononuclear cells (PBMCs), we evaluated the frequency of the fs-neoAg-specific T cells by ex vivo IFN-γ ELISPOT upon fs-peptide stimulation. Additionally, we isolated naïve and memory T cells from MSI-H patient PBMCs and expanded fs-neoAg-specific T cells within each subset. Fs-neoAg-induced effector cytokine (IFN-γ, TNF-α) production was measured by flow cytometry and was detected only in the memory subset, supporting the hypothesis that shared fs-neoAgs prime CD8+ T cells in vivo to generate clonally-expanded memory T cells in MSI-H patients. To further evaluate the clonal expansion of fs-neoAg-specific T cells in MSI-H cancer patients, we identified fs-neoAg-specific T cell receptors (TCRs). T cell lines enriched for fs-neoAg-specific T cells were generated from patient PBMCs and sequenced for variable β chains of TCRs. These fs-neoAg-specific TCRs were monitored in the blood and tumor tissues, including those from primary and recurrent sites. Finally, to determine the spatial relationships between the infiltrating immune cells and the malignant cells at single cell resolution, we performed multiplexed immunohistochemistry using CODEX technology. A panel of 35 markers was used to evaluate the myeloid (HLA-DR, CD11c, CD14, CD68, CD206) and T (CD4, CD8, Foxp3) cell subsets, the activation (CD107a, CD69, Ki67) and exhaustion (PD-1, TIM3, LAG3) status of T cells, T cell states (TCF-1, TOX, PD-1) and the presence of tertiary lymphoid structures/antigen presenting cell niches (CD19, CD20, HLA-DR) in the tumor microenvironment of primary or recurrent MS-stable and MSI-H tumors from endometrial cancer patients. We also investigated potential immune escape mechanisms in MSI-H tumors, such as the loss of B2M and MHC-I expression. This study will provide insights into the quality and quantity of shared anti-tumor T cells within the periphery and tumor tissues and will help identify the immune correlates of response or resistance to therapy in MSI-H cancer patients. Citation Format: Cansu Cimen Bozkus, Mona Saleh, Rachel Brody, Stephanie V. Blank, Nina Bhardwaj. Analyses of tumor-specific T cell dynamics and tumor immune contexture in microsatellite instability-high cancers in response to first-line therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 253.

Mounting evidence suggests disproportionate coronavirus disease 2019 (COVID-19) hospitalizations and deaths because of racial disparities. The association of race in a cohort of gynecologic oncology patients with severe acute respiratory syndrome-coronavirus 2 infection is unknown.Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City area hospital systems. A multivariable mixed-effects logistic regression model accounting for county clustering was used to analyze COVID-19-related hospitalization and mortality.Of 193 patients who had gynecologic cancer and COVID-19, 67 (34.7%) were Black, and 126 (65.3%) were non-Black. Black patients were more likely to require hospitalization compared with non-Black patients (71.6% [48 of 67] vs 46.0% [58 of 126]; P = .001). Of 34 (17.6%) patients who died from COVID-19, 14 (41.2%) were Black. Among those who were hospitalized, compared with non-Black patients, Black patients were more likely to: have ≥3 comorbidities (81.1% [30 of 37] vs 59.2% [29 of 49]; P = .05), to reside in Brooklyn (81.0% [17 of 21] vs 44.4% [12 of 27]; P = .02), to live with family (69.4% [25 of 36] vs 41.6% [37 of 89]; P = .009), and to have public insurance (79.6% [39 of 49] vs 53.4% [39 of 73]; P = .006). In multivariable analysis, among patients aged65 years, Black patients were more likely to require hospitalization compared with non-Black patients (odds ratio, 4.87; 95% CI, 1.82-12.99; P = .002).Although Black patients represented only one-third of patients with gynecologic cancer, they accounted for disproportionate rates of hospitalization (45%) and death (40%) because of COVID-19 infection; younger Black patients had a nearly 5-fold greater risk of hospitalization. Efforts to understand and improve these disparities in COVID-19 outcomes among Black patients are critical.

Introduction/Background Mounting evidence suggests disproportionate COVID-19 hospitalizations and deaths due to racial disparities. The association of race in a cohort of gynecologic oncology patients with SARS-CoV-2 infection is unknown. Methodology Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City (NYC) area hospital systems. Multivariable mixed-effects logistic regression model accounting for county clustering was utilized to analyse COVID-19 related hospitalization and mortality. Results Of 193 patients with gynecologic cancer and COVID-19, 67 (34.7%) were Black and 126 (65.3%) were non-Black. Black patients were more likely to require hospitalization compared with non-Black patients (71.6% [48/67] vs. 46.0% [58/126], P=.001). Of 34 (17.6%) patients who died from COVID-19, 14 (41.2%) were Black. Among those hospitalized, Black patients compared to non-Black patients were more likely to: have ≥ 3 comorbidities (81.1% [30/37] vs 59.2% [29/49], P=.05); reside in Brooklyn (81.0% [17/21] vs 44.4% [12/27], P=.02); live with family (69.4% [25/36] vs 41.6% [37/89], P=.009); and have public insurance (79.6% [39/49] vs 53.4% [39/73], P=.006). In multivariable analysis, for patients younger than 65 years of age, Black patients were more likely to require hospitalization compared to non-Black patients (OR, 4.87; 95% CI 1.82 to 12.99, P=.002). Conclusion Although Black patients with gynecologic cancer represented only 1/3 of patients, they accounted for disproportionate rates of hospitalization (>45%) and death (>40%) due to COVID-19 infection; younger Black patients had nearly 5-fold greater risk of hospitalization. Efforts to understand and improve these disparities in COVID-19 outcomes in Black patients are critical. Disclosures B.P. reports grants, personal fees and non-financial support outside the submitted work; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genentech/Roche, and Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, Merck and Eisai. J.J. reports a patent license from MDSeq Inc. R.OC reports personal fees from Tesaro, GlaxoSmithKline, Regeneron and Genentech USA, outside the submitted work and non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies. R.OC’s institute receives funding for clinical research from Celgene/Juno, Tesaro/GSK, Ludwig Cancer Institute, Abbvie, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, Marker Therapeutics, Syndax Pharmaceuticals, Genmab Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma, Gynecologic Oncology Foundation. S.V.B. has research collaborations with Roche/Genentech, Tesaro/GK, Seattle Genetics, Merck and Asta Zeneca

Objectives: Given the multiple approvals for poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) in treatment and maintenance for first-line and recurrent ovarian cancer, most patients diagnosed with ovarian cancer will receive a PARPi at some point during their treatment continuum. Patient-reported outcomes are increasingly considered when assessing treatment effect. The purpose of this study is explore ovarian cancer survivors’ self-reported experiences with PARPi. Methods: A 26-question survey was shared via survivor networks and social media with women with a current or prior diagnosis of ovarian cancer who had received PARPi. The survey was distributed between 12/6/2019-2/15/2020. Participants completed informed consent and all collected data were anonymous. Free-text responses were analyzed by two members of the study team to identify themes using a codebook. Both manifest and latent coding were used. Results: Two hundred and three women visited the survey site and 160 (79%) completed the survey. Twenty-nine percent (47) of participants were receiving a PARPi for front-line maintenance, 58% (92) for maintenance following recurrence and 13% (21) for treatment of recurrent disease. Among the 153 patients with genetic testing, 89 (58%) had a pathogenic mutation (BRCA1 - 56, BRCA2 - 19, other - 14). When asked about their first PARPi, 55% (88) of patients were treated with olaparib, 33% (52) niraparib, 11% (18) rucaparib and 1% (2) other PARPi. Fifteen women (9%) received more than one PARPi. During first treatment with PARPi, women reported a median of two treatment side effects (range 0-9). The most commonly reported side effects included fatigue (84, 53%), nausea (72, 45%), neutropenia (35, 22%), aches/pain (22, 14%), stomach pain (21, 13%), thrombocytopenia (20, 13%) and bowel changes (20, 13%) (Figure 1). In free-text response to the question ‘What advice would you share with someone taking a PARP inhibitor for the first time?’, ovarian cancer survivors identified patience during the acclimatization phase, early proactive management of side effects, and communication with one's medical team as critical. Download : Download high-res image (77KB) Download : Download full-size image Conclusions: Women with ovarian cancer on PARPi therapy experience a multitude of side effects, and usually more than one. Proactive management of these side effects is essential to increase tolerability and compliance. The self-reported experience of survivors on PARPi, as captured in this study, provides ‘real world’ description of the PARPi treatment course, which may be valuable when setting expectations for patients and engaging in shared decision-making about PARPi. Women who have successfully managed the acclimatization phase may be especially helpful in guiding women beginning PARPi treatment.

Objectives: Social media outlets have increased in popularity within the last decade and are influencing the ways in which patients interact with the healthcare system. Daily use among adults in the US is reported as 63% for Instagram and 42% for Twitter. While social media increasingly serves as a medium for conversation between patients and their providers, the use by Gynecologic Oncology providers has not been described. The purpose of this study is to examine the presence of designated NCI-designated Cancer Centers’ Gynecology Oncology divisions on social media and to characterize the content posted by them. Methods: The 71 NCI-Designated cancer centers and their Gynecology Oncology divisions were searched on both Instagram and Twitter. Search was performed using the cancer center names independently and in gynecology oncology context. Once a social media account was identified, information about number of followers and posts was recorded, and content was reviewed and divided into categories including: marketing, patient education and awareness, patient engagement, clinical and research updates and fellowship recruitment. Results: Of 71 NCI-Designated Cancer Centers, 29 (40.8%) had Instagram accounts and 64 (90.1%) had twitter accounts with a range of 17-101,000 followers. When searched on Instagram, 4 (6%) Gynecology Oncology divisions had Instagram accounts with number of followers ranging from 60-219 and average number of posts of 32. When searched for Gynecology Oncology divisions on Twitter, 8 (12%) departments were identified with a range of 0-791 followers and average of 110 posts. When analyzing the content of Gynecology Oncology Divisions social media accounts, 5 used their account for marketing, 4 for patient education and awareness, 1 for patient engagement, 4 for clinical and research updates and 3 for fellowship recruitment (Table1). Download : Download high-res image (74KB) Download : Download full-size image Conclusions: Social media has become a powerful form of communication and engagement. While 90% of NCI-designated Cancer Centers have social media presences, Gynecology Oncology divisions are under-utilizing this medium to reach and educate patients. Greater participation by gynecology oncologists may increase patient education, raise awareness and engagement.

Objectives: Genomically unstable tumors, characterized by BRCA1/2 alterations and homologous recombination deficiency (HRD), are hypothesized to be more mutated and potentially more sensitive to immune checkpoint inhibitors. To explore this hypothesis we analyzed outcomes in the IMagyn050 trial according to BRCA1/2, HRD, and PD-L1 status [Moore, ESMO 2020]. Methods: IMagyn050 (NCT03038100) is a double-blind randomized phase III trial evaluating the efficacy and safety of adding atezolizumab/placebo to carboplatin, paclitaxel, and bevacizumab (CPB) followed by maintenance bevacizumab plus atezolizumab/placebo. PD-L1 status was determined centrally using VENTANA SP142 (PD-L1+ defined as ≥1% tumor-infiltrating immune cells expressing PD-L1). Deleterious tumor germline/somatic BRCA1/2 alterations (BRCA1/2m), genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI) were evaluated using the FoundationOne assay (Foundation Medicine, Inc., Cambridge, MA). HRD and homologous recombination proficiency (HRP) were defined as gLOH ≥16% and Results: Among 1301 randomized patients, samples from 1050 were evaluable for BRCA1/2 (22% were BRCA1/2m, 78% BRCA1/2 nonmutant) and 980 were evaluable for gLOH (46% were HRD, 54% HRP). Median TMB was similarly low in BRCA1/2m and BRCA1/2 nonmutant (3.78 vs 2.52 Mut/Mb, respectively), and HRD and HRP (3.78 vs 2.52 Mut/Mb, respectively) tumors. Only 3% (29/1024) of evaluable tumors had TMB ≥10 Mut/Mb and 0.3% (3/1022) were MSI-high (1 mixed, 1 undifferentiated, 1 other). All high-grade serous cases were MS-stable. PFS prognosis (assessed in the placebo + CPB arm) was improved in patients with BRCA1/2m (hazard ratio [HR] 0.62, 95% CI 0.46–0.84) and HRD (HR 0.63, 95% CI 0.49–0.80) tumors. There was a suggested association between PD-L1+ and HRD (HRD prevalence: 40% vs 25% in PD-L1+ vs PD-L1– subgroups, respectively; exploratory Fisher's exact test p=0.0001) but not with BRCA1/2m (BRCA1/2m prevalence: 21% vs 14%, respectively; exploratory Fisher exact test p=0.064). Adding atezolizumab to CPB did not improve PFS, irrespective of BRCA1/2 or HRD status (table). In the PD-L1+ population, HRs were similar in BRCA1/2m and BRCA1/2 nonmutant subgroups, and in HRD and HRP subgroups. In the PD-L1– population, atezolizumab did not improve PFS. Download : Download high-res image (172KB) Download : Download full-size image Conclusions: We showed that the majority of ovarian tumors have low TMB scores regardless of BRCA1/2 or HRD. Neither BRCA1/2m nor HRD was associated with greater clinical benefit from adding atezolizumab to CPB. PD-L1 status was more reliably associated with numerically longer PFS with atezolizumab + CPB. This is the first randomized double-blind trial in ovarian cancer to demonstrate that genomic instability triggered by BRCA1/2m or HRD does not improve sensitivity to immune checkpoint inhibitors.

Objectives: Despite a growing body of literature, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes in New York City (NYC) from the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). We sought to determine the hospitalization and mortality rates and their associated factors, specifically recent chemotherapy and immunotherapy use. Methods: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City (NYC) area hospital systems. Multivariable logistic regression was utilized to analyze COVID-19 related hospitalization and mortality. Results: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range, 53.0-73.0 years). A total of 106 of the 193 patients (54.9%) required hospitalization; among the hospitalized patients 13 (12.3%) required invasive mechanical ventilation and 39 (36.8%) required ICU admission. No patients requiring mechanical ventilation survived. A total of 34 of 193 (17.6%) patients died of COVID-19 complications. On multivariable analysis, hospitalization was associated with an age greater than or equal to 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status greater than or equal to 2 (OR 3.67, CI 1.25, 13.55) and greater than or equal to 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 on multivariable analysis. A total of 13 of 34 (38.23%) patients who died of COVID-19 complications received cytotoxic chemotherapy, while 4 of 34 (11.76%) patients received immunotherapy. However, recent cytotoxic chemotherapy use was not predictive of COVID-19 hospitalization or mortality on multivariable analysis. Download : Download high-res image (107KB) Download : Download full-size image Conclusions: The case fatality rate among gynecologic oncology patients with COVID-19 infection is 17.6%. Cancer-directed therapy, including immunotherapy use, is not associated with an increased risk of mortality related to COVID-19 infection in this larger cohort.

Objectives: Poly(ADP-ribose) polymerase inhibitor maintenance (PARPm) therapy is now available to all women with advanced ovarian cancer following response to initial chemotherapy. As the COVID-19 pandemic has resulted in unprecedented challenges for cancer patients, we aimed to evaluate the unique experience for women on maintenance PARP inhibitors. Methods: Women with a current or prior diagnosis of ovarian cancer completed an online survey focusing on treatment interruptions and quality of life (QOL). QOL was measured with the Cancer Worry Scale and Hospital Anxiety and Depression Scale. The survey was distributed through survivor networks and social media. The chi-square and ANOVA test were used with a Bonferroni correction to account for multiple comparison testing. Results: Six hundred and three women, from 41 states, visited the survey website between March 30 and April 13, 2020 and 525 (87%) completed the survey and provided information on current treatment status. Sixty-four women (12%) were on PARPm, 153 (29%) on other anti-cancer therapy and 308 (59%) on no treatment. Other anticancer therapies included intravenous chemotherapy (61, 40%), anti-angiogenic (29, 19%), hormonal (25, 16%), oral chemotherapy (12, 8%), immunotherapy (10, 6.5%) and other (16, 10%). There were no differences among women on PARPm, no treatment or other treatment for disease stage, medical comorbidities, COVID-19 symptoms or treatment delays. Women on PARPm were more likely to be self-described as immunocompromised versus women not on treatment (79% vs. 34%, P Download : Download high-res image (96KB) Download : Download full-size image Conclusions: The COVID-19 crisis is impacting cancer care and it is critical that providers consider and address the unique stressors facing women with ovarian cancer during this challenging time. Women on PARPm, in particular, perceive themselves as immunocompromised, perhaps making them more open to alternative means of care delivery, as demonstrated by their willingness to adopt telemedicine. Women with ovarian cancer on PARPm report similar cancer worry, anxiety and depression to women not on treatment and those on other anti-cancer treatment.

Summary Microsatellite instability-high (MSI-H) tumors are characterized by high tumor mutation burden and responsiveness to checkpoint blockade. We identified tumor-specific frameshifts encoding multiple epitopes that originated from indel mutations shared among patients with MSI-H endometrial, colorectal, and stomach cancers. Epitopes derived from these shared frameshifts have high population occurrence rates, wide presence in many tumor subclones, and are predicted to bind to the most frequent MHC alleles in MSI-H patient cohorts. Neoantigens arising from these mutations are distinctly unlike self and viral antigens, signifying novel groups of potentially highly immunogenic tumor antigens. We further confirmed the immunogenicity of frameshift peptides in T cell stimulation experiments using blood mononuclear cells isolated from both healthy donors and MSI-H cancer patients. Our study uncovers the widespread occurrence and strong immunogenicity of tumor-specific antigens derived from shared frameshift mutations in MSI-H cancer and Lynch syndrome patients, suitable for the design of common “off-the-shelf” cancer vaccines.

Background: The COVID-19 pandemic has resulted in unprecedented challenges for people living with cancer, impacting not only physical health but psychological well-being. The psychological response affects the individual as well as the community and can persist long after the outbreak. We aim to assess coping strategies employed by women with ovarian cancer during the COVID-19 pandemic. Methods: Women with a current or prior diagnosis of ovarian cancer completed an online survey which included a query about coping strategies during the COVID-19 pandemic. The survey was distributed from March 30th through April 13, 2020 through survivor networks and social media. Results: Six hundred and three women visited the survey website during the study period and 555 (92.0%) completed the survey. Four hundred and eight (73.5%) provided information on coping strategies utilized during COVID-19. Among those who responded, the median age was 58 years (range 20–85) and 150 participants (40.8%) were undergoing active cancer treatment. Commonly utilized adaptive coping strategies included emotional support (159, 39.0%), self care (148, 36.3%), hobbies (139, 34.1%), planning (87, 21.3%), positive reframing (54, 13.2%), religion (50, 12.3%) and instrumental support (38, 9.3%). Many participants also relied on avoidance coping strategies including self distraction (111, 27.2%) and substance use (19, 4.7%). Conclusions: Most ovarian cancer survivors are using adaptive, problem-focused coping strategies during the COVID-19 pandemic, however many are practicing avoidance strategies as well. As coping mechanisms profoundly impact quality of life, oncology providers must assist patients in identifying coping strategies that optimize physical and psychological well-being., Highlights • 408 ovarian cancer survivors provided information on coping strategies utilized during the COVID-19 pandemic. • 371 participants (90.9%) reported using at least one adaptive coping strategy. • 146 participants (35.8%) reported using at least one dysfunctional coping strategy. • Commonly used adaptive strategies included emotional support (159, 39.0%), self-care (148, 36.3%) and hobbies (139, 34.1%). • Commonly used dysfunctional coping strategies included self-distraction (111, 27.2%) and substance use (19, 4.7%).

Background The coronavirus disease 2019 pandemic has resulted in unprecedented challenges for the oncology community. For people living with cancer, treatments are interrupted, surgeries cancelled, and regular oncology evaluations rescheduled. People with cancer and their physicians must balance plausible fears of coronavirus disease 2019 and cancer treatment with the consequences of delaying cancer care. Objective We aim to evaluate the experience of women with ovarian cancer during the coronavirus disease 2019 pandemic. Study Design Women with a current or previous diagnosis of ovarian cancer completed an online survey focusing on treatment interruptions and quality of life. The quality of life was measured with the Cancer Worry Scale and Hospital Anxiety and Depression Scale. The survey was distributed through survivor networks and social media. Univariate and multivariable linear regression analysis were used to evaluate the effect of participant characteristics on quality of life survey scores. Results A total of 603 women, from 41 states, visited the survey website between March 30, 2020, and April 13, 2020, and 555 (92.0%) completed the survey. The median age was 58 years (range, 20–85). At the time of survey completion, 217 participants (43.3%) were in active treatment. A total of 175 participants (33%) experienced a delay in some component of their cancer care. Ten (26.3%) of the 38 participants scheduled for surgery experienced a delay, as did 18 (8.3%) of the 217 participants scheduled for nonsurgical cancer treatment. A total of 133 participants (24.0%) had a delayed physician appointment, 84 (15.1%) laboratory tests, and 53 (9.6%) cancer-related imaging. Among the cohort, 88.6% (489) reported significant cancer worry, 51.4% (285) borderline or abnormal anxiety, and 26.5% (147) borderline or abnormal depression. On univariate analysis, age less than 65 years, being scheduled for cancer treatment or cancer surgery, delay in oncology care, being self-described as immunocompromised, and use of telemedicine were all associated with higher levels of cancer worry. Higher anxiety scores were associated with age less than 65 years and being self-described as immunocompromised. Higher depression scores were associated with age less than 65 years, being scheduled for cancer surgery, delay in oncology care, being self-described as immunocompromised, and use of telemedicine. On multivariable linear regression analysis, age less than 65 and being self-described as immunocompromised were independently predictive of greater cancer worry, anxiety, and depression, and delay in cancer care was predictive of anxiety and depression. Conclusion The coronavirus disease 2019 crisis is affecting care of patients with ovarian cancer; surgeries, treatments, scheduled physician appointments, laboratory tests, and imaging are cancelled or delayed. Younger age, presumed immunocompromise, and delay in cancer care were associated with significantly higher levels of cancer worry, anxiety, and depression. Providers must work with patients to balance competing risks of coronavirus disease 2019 and cancer, recognizing that communication is a critical clinical tool to improve quality of life in these times.

Objective Elevated inflammatory markers are predictive of COVID-19 infection severity and mortality. It is unclear if these markers are associated with severe infection in patients with cancer due to underlying tumor related inflammation. We sought to further understand the inflammatory response related to COVID-19 infection in patients with gynecologic cancer. Methods Patients with a history of gynecologic cancer hospitalized for COVID-19 infection with available laboratory data were identified. Admission laboratory values and clinical outcomes were abstracted from electronic medical records. Severe infection was defined as infection requiring ICU admission, mechanical ventilation, or resulting in death. Results 86 patients with gynecologic cancer were hospitalized with COVID-19 infection with a median age of 68.5 years (interquartile range (IQR), 59.0–74.8). Of the 86 patients, 29 (33.7%) patients required ICU admission and 25 (29.1%) patients died of COVID-19 complications. Fifty (58.1%) patients had active cancer and 36 (41.9%) were in remission. Patients with severe infection had significantly higher ferritin (median 1163.0 vs 624.0 ng/mL, p, Highlights • Ferritin, procalcitonin, and CRP may have prognostic value for severe COVID-19 infection in gynecologic cancer patients. • Elevated admission white blood cell count, lactate, and creatinine may also be prognostic of severe COVID-19 disease. • D-dimer levels do not appear to be predictive of severe COVID-19 infection in patients with gynecologic cancer.

The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens.We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection.A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.

The COVID-19 pandemic has challenged our abilities to provide timely surgical care for patients, including women with gynecologic cancer In March 2020, the American College of Surgeons, The US Surgeon General, and many medical and surgical academic societies recommended postponing elective surgical interventions Recognizing that the pandemic may occur in waves, special considerations should be made for appropriate indications for surgical intervention in the setting of strained resources and personnel to meet surgical demand and prioritize excellent patient care 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 hesitate, and reintegrate surgery Regarding prioritization, patients should be counseled on risks of surgical delay versus in-hospital or community-acquired COVID-19 exposure in the perioperative setting Patients should be informed that surgical prioritization is based on (1) local projected resources, (2) disease prevalence, (3) patient and tumor characteristics, and (4) expected outcomes from delays Several prioritization algorithms have been developed that take into account disease characteristics, patient comorbidities, available personal protective equipment, length of hospital stay, local COVID-10 prevalence, and more Most oncological procedures have been classified as semiurgent, with a high priority tier 3 designation (second to emergent cases and trauma) Published literature demonstrates that most women with newly diagnosed gynecologic cancer are unlikely to be impacted by a few weeks surgical delay Those with malignancies with a propensity for metastasis or advanced stage ovarian and uterine malignancies that require interval cytoreduction should be prioritized when possible For mitigation of complications before, during, and after surgery, patients should be educated on recommendations for social distancing, hand hygiene, and personal protective equipment such as face masks Providers should abide by similar recommendations and use eye protection in the ambulatory and inpatient settings N95 respirators or powered air-purifying respirators are recommended in the care of suspected or known COVID-19 patients Clinical screening should be done at multiple points, COVID-19 testing should be done preoperatively, and a positive test result should delay surgery until asymptomatic formore than 14 days Safety protocols are critical during procedural intubation and extubation, as this is themost hazardous aspect of surgery in a COVID-19-positive/unknown patient Open surgery should not be considered safer than minimally invasive surgery Practitioners for whom the risk of severe disease and death is highest should avoid participating in the surgical care of known COVID-19-positive patients, if possible Telemedicine should be incorporated to limit provider and patient exposure in the postoperative setting Virtual platforms have also demonstrated efficacy in virtual rounding as well as patient care settings to involve family members in treatment planning and discussions around diagnosis Platforms emphasizing enhanced recovery time and same-day discharge should be prioritized, and measures should be taken to reduce delirium risk given lack of patient visitors Reintegration efforts should focus on systematically prioritizing the nonurgent cases that were initially delayed Surgical restrictions are likely to continue for some time, and institutional and departmental leadership will be paramount to optimize surgical manpower, support operative personnel, and use hospital resources equitably and responsibly

• COVID-19 is likely uniquely unsettling to gynecologic oncology patients. • Resources addressing the questions of patients with cancer during the COVID-19 crises remain scarce. • Women with gynecologic cancer were invited to participate in a webinar on COVID-19 and cancer concerns. • We share participant questions to understand concerns and utilize this knowledge to improve patient education and support.

PURPOSE A powerful consequence of detecting cancer-associated pathogenic variants is the ability to test at-risk relatives (ARRs), termed cascade testing. However, historical studies suggest cascade testing uptake of 30% or less. Here, we tested the feasibility of a novel, streamlined method of cascade testing using telephone genetic counseling and mailed saliva-based genetic testing. PATIENTS AND METHODS Probands with newly diagnosed cancer-associated pathogenic variants were offered facilitated cascade testing whereby the genetics team identified and contacted ARRs by telephone to disclose the familial pathogenic variant and offer telephone counseling and mailed saliva testing. Results and guideline-based recommendations were reviewed by telephone and shared with the primary care physician. RESULTS Thirty probands were enrolled, and 114 ARRs were identified. Twelve ARRs were excluded (lived outside of the United States, n = 5; proband did not approve of contact, n = 7). Among 102 ARRs telephoned, contact was established with 95 (93%). Among 114 identified ARRs, 66 (58%) completed genetic testing. Among those completing testing, 27 (41%) carried the familial pathogenic variant. Surveys of ARRs at the time of genetic testing and 6 months later demonstrated low levels of anxiety, depression, distress, and uncertainty and high levels of satisfaction with testing. At 6 months, 7 ARRs with pathogenic variants had undergone cancer surveillance interventions and 4 had undergone cancer risk-reducing surgery. CONCLUSION Facilitated cascade testing with telephone genetic counseling and mailed saliva kits resulted in high testing uptake among ARRs. Positive genetic testing resulted in utilization of genetically targeted primary disease prevention at short-term follow-up. Facilitated cascade testing is a straightforward, low-cost, easily implemented strategy with significant potential to promote early detection for affected ARRs and reduce cancer mortality and should be evaluated in larger scale clinical trials.