Highlights d High rate of NF1 loss in the R0 compared to neoadjuvant chemotherapy (NACT) group d Lower chromothripsis-like pattern and higher neoantigens in the R0 versus NACT group d Increased number of infiltrated T cells and decreased macrophages in the R0 group d Significant transcriptomic and proteomic variations between HGSC subgroups

Background New York City (NYC) is the epicenter of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID‐19]) in the United States. Clinical characteristics and outcomes of vulnerable populations, such as those with gynecologic cancer who develop COVID‐19 infections, is limited. Methods Patients from 6 NYC‐area hospital systems with known gynecologic cancer and a COVID‐19 diagnosis were identified. Demographic and clinical outcome data were abstracted through a review of electronic medical records. Results Records for 121 patients with gynecologic cancer and COVID‐19 were abstracted; the median age at the COVID‐19 diagnosis was 64.0 years (interquartile range, 51.0‐73.0 years). Sixty‐six of the 121 patients (54.5%) required hospitalization; among the hospitalized patients, 45 (68.2%) required respiratory intervention, 20 (30.3%) were admitted to the intensive care unit, and 9 (13.6%) underwent invasive mechanical ventilation. Seventeen patients (14.0%) died of COVID‐19 complications. No patient requiring mechanical ventilation survived. On multivariable analysis, hospitalization was associated with an age ≥64 years (risk ratio [RR], 1.73; 95% confidence interval [CI], 1.18‐2.51), African American race (RR, 1.56; 95% CI, 1.13‐2.15), and 3 or more comorbidities (RR, 1.43; 95% CI, 1.03‐1.98). Only recent immunotherapy use (RR, 3.49; 95% CI, 1.08‐11.27) was associated with death due to COVID‐19 on multivariable analysis; chemotherapy treatment and recent major surgery were not predictive of COVID‐19 severity or mortality. Conclusions The case fatality rate among gynecologic oncology patients with a COVID‐19 infection is 14.0%. Recent immunotherapy use is associated with an increased risk of mortality related to COVID‐19 infection. Lay Summary The case fatality rate among gynecologic oncology patients with a coronavirus disease 2019 (COVID‐19) infection is 14.0%; there is no association between cytotoxic chemotherapy and cancer‐directed surgery and COVID‐19 severity or death. As such, patients can be counseled regarding the safety of continued anticancer treatments during the pandemic. This is important because the ability to continue cancer therapies for cancer control and cure is critical.

Primary debulking surgery followed by adjuvant chemotherapy is the standard treatment for ovarian cancer. Residual disease after primary surgery is associated with poor patient outcome. Previously, we discovered ADH1B to be a molecular biomarker of residual disease. In the current study, we investigated the functional role of ADH1B in promoting ovarian cancer cell invasiveness and contributing to residual disease. We discovered that ADH1B overexpression leads to a more infiltrative cancer cell phenotype, promotes metastasis, increases the adhesion of cancer cells to mesothelial cells, and increases extracellular matrix degradation. Live cell imaging revealed that ADH1B-overexpressing cancer cells efficiently cleared the mesothelial cell layer compared to control cells. Moreover, gene array analysis revealed that ADH1B affects several pathways related to the migration and invasion of cancer cells. We also discovered that hypoxia increases ADH1B expression in ovarian cancer cells. Collectively, these findings indicate that ADH1B plays an important role in the pathways that promote ovarian cancer cell infiltration and may increase the likelihood of residual disease following surgery.

Background Racial disparities in cancer outcomes are increasingly recognized, but comprehensive analyses, including molecular studies, are limited. The objective of the current study was to perform a pan‐cancer clinical and epigenetic molecular analysis of outcomes in African American (AA) and European American (EA) patients. Methods Cross‐platform analyses using cancer databases (the Surveillance, Epidemiology, and End Results program database and the National Cancer Data Base) and a molecular database (The Cancer Genome Ancestry Atlas) were performed to evaluate clinical and epigenetic molecular differences between AA and EA patients based on genetic ancestry. Results In the primary pan‐cancer survival analysis using the Surveillance, Epidemiology, and End Results database (2,045,839 patients; 87.5% EA and 12.5% AA), AA patients had higher mortality rates for 28 of 42 cancer types analyzed (hazard ratio, >1.0). AAs continued to have higher mortality in 13 cancer types after adjustment for socioeconomic variables using the National Cancer Database (5,150,023 patients; 11.6% AA and 88.4% EA). Then, molecular features of 5,283 tumors were analyzed in patients who had genetic ancestry data available (87.2% EA and 12.8% AA). Genes were identified with altered DNA methylation along with increased microRNA expression levels unique to AA patients that are associated with cancer drug resistance. Increased miRNAs (miR‐15a, miR‐17, miR‐130‐3p, miR‐181a) were noted in common among AAs with breast, kidney, thyroid, or prostate carcinomas. Conclusions The current results identified epigenetic features in AA patients who have cancer that may contribute to higher mortality rates compared with EA patients who have cancer. Therefore, a focus on molecular signatures unique to AAs may identify actionable molecular abnormalities.

No abstract