Barriers to early detection: Insurance denials for breast MRI screening in women with germline BRCA1/2 mutations.

Objectives: Women with germline BRCA1/2 pathogenic variants (gBRCA1/2) are recommended to undergo annual breast MRI and mammography. Our objective was to describe the frequency of insurance denials for annual breast MRIs in women with gBRCA1/2 and determine denial trends.

Methods: Women with gBRCA1/2 following in a high-risk breast cancer clinic with breast MRIs ordered from 2020 to 2021 were identified and cross-referenced with a database of insurance denials.

A pre-operative scoring model to estimate the risk of blood transfusion over an ovarian cancer debulking surgery (BLOODS score): a Memorial Sloan Kettering Cancer Center Team Ovary study.

Objectives: To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery.

Methods: We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated.

Molecular profiling of primary endometrioid endometrial cancer and matched lung metastases: mutation as a potential driver.

•Both primary endometrial cancers (ECs) and matched lung metastases shared a common ancestor with independent evolution at each site.•The two endometrioid ECs studied acquired additional mutations during the distant metastatic process.•Subclonal hotspot mutations in the two primary ECs studied became clonal in the distant metastases.

Regionalizing ovarian cancer cytoreduction to high-volume centers and the impact on patient travel in New York State.

Objective: To evaluate the theoretical impact of regionalizing cytoreductive surgery for ovarian cancer (OC) to high-volume facilities on patient travel.

Methods: We retrospectively identified patients with OC who underwent cytoreduction between 1/1/2004-12/31/2018 from the New York State Cancer Registry and Statewide Planning and Research Cooperative System. Hospitals were stratified by low-volume (<21 cytoreductive surgical procedures for OC annually) and high-volume centers (≥21 procedures annually).

Pathogenic germline variants in patients with endometrial cancer of diverse ancestry.

Background: Racial disparities in outcomes exist in endometrial cancer (EC). The contribution of ancestry-based variations in germline pathogenic variants (gPVs) is unknown.

Methods: Germline assessment of ≥76 cancer predisposition genes was performed in patients with EC undergoing tumor-normal Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets sequencing from January 1, 2015 through June 30, 2021.

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer.

Objective: To evaluate adverse events (AEs) of combination lenvatinib plus pembrolizumab for the treatment of recurrent endometrial cancer (EC) and to assess outcomes by lenvatinib starting dose.

Methods: We retrospectively reviewed patients with recurrent EC treated with lenvatinib plus pembrolizumab at our institution between 10/1/2019-11/30/2021. Starting dose of lenvatinib was defined as standard (20 mg) or reduced (10 mg/14 mg).

Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer.

Purpose: To evaluate rates of germline pathogenic/likely pathogenic variants (PVs) and genetic counseling by ancestry in patients with epithelial ovarian cancer (EOC).

Methods: Patients with pathologically confirmed EOC who underwent clinical tumor-normal sequencing from January 1, 2015, to December 31, 2020, inclusive of germline analysis of ≥76 genes were included. Patients with newly identified PVs were referred for Clinical Genetics Service (CGS) counseling.

Salpingectomy for the Primary Prevention of Ovarian Cancer: A Systematic Review.

Importance: Most ovarian cancers originate in the fimbriated end of the fallopian tube. This has led to the hypothesis that surgical resection of the fallopian tubes at the time of gynecologic and nongynecologic surgical procedures-referred to as an opportunistic salpingectomy-may prevent the development of epithelial ovarian cancer for women at an average risk of developing the disease.

Objective: To compile a comprehensive, state-of-the-science review examining the current landscape of performing bilateral salpingectomy for ovarian cancer prevention.

Germline drivers of gynecologic carcinosarcomas.

Objectives: To describe the prevalence of germline pathogenic variants (gPVs) in endometrial and ovarian carcinosarcomas and determine if gPVs are drivers of carcinosarcoma.

Methods: Patients with endometrial or ovarian carcinosarcomas who underwent clinical tumor-normal sequencing from 1/1/2015 to 6/1/2021 and consented to germline assessment of ≥76 cancer predisposition genes were included. In patients with gPVs, biallelic inactivation was identified through analysis of loss of heterozygosity and somatic pathogenic alterations.

Chemotherapy response in low-grade serous ovarian carcinoma at a comprehensive cancer center: Readdressing the roles of platinum and cytotoxic therapies.

Background: Data on platinum sensitivity of low-grade serous ovarian carcinoma (LGSOC) in the upfront setting is lacking, and there is limited and contradictory information on chemotherapy responses in recurrent disease.

Methods: Patients with LGSOC seen at a comprehensive cancer center from January 1, 1998 to September 30, 2021 were identified from institutional databases. Response to neoadjuvant chemotherapy (NACT) or adjuvant platinum-based chemotherapy and to second- to fifth-line regimens was retrospectively characterized by Response Evaluation Criteria in Solid Tumors (RECIST) v1.

Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival.

Comprehensive analysis of germline drivers in endometrial cancer.

Background: We sought to determine the prevalence of germline pathogenic variants (gPVs) in unselected patients with endometrial cancer (EC), define biallelic gPVs within tumors, and describe their associations with clinicopathologic features.

Methods: Germline assessment of at least 76 cancer predisposition genes was performed in patients with EC undergoing clinical tumor-normal Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing from January 1, 2015, to June 30, 2021. In patients with gPVs, biallelic alterations in ECs were identified through analysis of loss of heterozygosity and somatic PVs.

Ten-year conditional probability of survival for patients with ovarian cancer: A new metric tailored to Long-term survivors.

Objectives: We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years.

Methods: We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001-12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded.

Management of patients with early-stage ovarian clear cell carcinoma: risk stratification and fertility conservation.

Objective: We sought to describe clinicopathologic and treatment factors associated with oncologic outcomes in patients with early-stage ovarian clear cell carcinoma undergoing complete staging and in a sub-set of these patients undergoing fertility-conserving surgery.

Methods: We retrospectively identified patients with ovarian clear cell carcinoma initially treated at our institution from January 1, 1996 to March 31, 2020. Survival was estimated using Kaplan-Meier curves and compared by log-rank test.

Small cell neuroendocrine carcinoma of the cervix: Analysis of prognostic factors and patterns of metastasis.

Objectives: To describe characteristics and outcomes of patients with small cell neuroendocrine carcinoma of the cervix (SCNCC) and determine the staging system most predictive of outcome-the two-tier (limited-stage [LS] vs. extensive-stage [ES]) or International Federation of Gynecology and Obstetrics (FIGO) staging system.

Methods: Patients with SCNCC evaluated at our institution from 1/1/1990-6/30/2021 were included.

Microsatellite Instability-High Endometrial Cancers with MLH1 Promoter Hypermethylation Have Distinct Molecular and Clinical Profiles.

Purpose: Microsatellite instability-high (MSI-H) endometrial carcinomas are underpinned by distinct mechanisms of DNA mismatch repair deficiency (MMR-D). We sought to characterize the clinical and genetic features of MSI-H endometrial cancers harboring germline or somatic mutations in MMR genes or MLH1 promoter hypermethylation (MLH1ph).

Experimental Design: Of > 1,100 patients with endometrial cancer that underwent clinical tumor-normal sequencing, 184 had MSI-H endometrial cancers due to somatic MMR mutations or MLH1ph, or harbored pathogenic germline MMR mutations.

Treatment of ovarian clear cell carcinoma with immune checkpoint blockade: a case series.

Background: Although immune checkpoint blockade has demonstrated limited effectiveness against ovarian cancer, subset analyses from completed trials suggest possible superior efficacy in the clear cell carcinoma subtype.

Objective: To describe the outcomes of patients with ovarian clear cell carcinoma treated with immune checkpoint blockade.

Methods: This was a single-institution, retrospective case series of patients with ovarian clear cell carcinoma treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor with or without concomitant cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition between January 2016 and June 2021.

MAPK Pathway Genetic Alterations Are Associated with Prolonged Overall Survival in Low-Grade Serous Ovarian Carcinoma.

Purpose: To characterize the somatic mutational landscape, investigate associations between genetic alterations and clinical outcomes, and determine the prevalence of pathogenic germline mutations in low-grade serous ovarian carcinomas (LGSC).

Experimental Design: Patients with LGSC tumors who underwent panel-based sequencing of up to 505 genes were identified. Data on somatic and germline mutations; copy-number alterations; and clinicopathologic features, including age at diagnosis, platinum sensitivity, and overall survival (OS), were collected.

An assessment of oncofertility content on reproductive endocrinology and infertility clinic websites.

Purpose: To assess oncofertility content on fertility clinic websites as indicated by eight relevant keywords. Additionally, we sought to describe the relationship between oncofertility content and five predetermined clinic characteristics.

Methods: We examined 381 fertility clinic websites that are members of the Society for Associated Reproductive Technology (SART).

Pre-clinical activity of the oral DNA-PK inhibitor, peposertib (M3814), combined with radiation in xenograft models of cervical cancer.

DNA-dependent protein kinase (DNA-PK) plays a crucial role in repair of DNA double-strand breaks by facilitating non-homologous end-joining. Inhibitors of DNA-PK have the potential to block DNA repair and enhance DNA-damaging agents. Peposertib (M3814) is a DNA-PK inhibitor that has shown preclinical activity in combination with DNA-damaging agents, including ionizing radiation (IR) and topoisomerase II inhibitors.

Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines.

Objectives: To perform a systematic review of gastric-type adenocarcinoma of the cervix and lobular endocervical glandular hyperplasia (a possible precursor lesion) in Peutz-Jeghers syndrome, and to analyze data from the literature, along with our institutional experience, to determine recommendations for screening and detection.

Methods: A comprehensive literature searc and retrospective search of pathology records at our institutio were conducted. Articles were screened by two independent reviewers.

Risk factors for financial toxicity in patients with gynecologic cancer.

Background: The cost of cancer care is high and rising. Evidence of increased patient cost burden is prevalent in the medical literature and has been defined as "financial toxicity," the financial hardship and financial concerns experienced by patients because of a disease and its related treatments. With targeted therapies and growing out-of-pocket costs, patient financial toxicity is a growing concern among patients with gynecologic cancer.