Financial toxicity in gynecologic oncology: a multi-practice survey.

BACKGROUND: Financial toxicity is associated with worse cancer outcomes, including lower survival. OBJECTIVE: To characterize the prevalence of, and patient risk factors for, financial toxicity among gynecologic oncology patients in a multi-site health system. METHODS: We identified patients seen in University of Pennsylvania gynecologic oncology practices between January 2020 and February 2022 with a patient portal account. We sent a survey to all alive patients twice between March and April 2022, including the 11-item Comprehensive Score for Financial Toxicity (COST) tool. We compared differences between patients reporting high (COST score <26) and low financial toxicity (COST score ≥26) in Χ2 and regression analyses. RESULTS: Of 8239 patients, 6925 had a portal account, and 498 completed the survey for 7.2% response rate. 44% had a COST score <26, indicating financial toxicity. Patients with high financial toxicity were more likely to be younger (mean age 54 vs 60), have cervical cancer (10% vs 4%; p=0.008), be privately insured (71% vs 57%; p=0.003) or have Medicaid (7% vs 3%; p=0.03), or be unemployed (18% vs 3%; p=<0.001), and less likely to be white (79% vs 90%, p=0.003) than those with low financial toxicity. Patients with Medicare were less likely to experience financial toxicity than privately insured patients (RR=0.59, 95% CI 0.37 to 0.95). CONCLUSION: In this study of patients with gynecologic cancer or pre-cancer, 44% had financial toxicity. Financial toxicity was higher in patients who were younger, did not identify as White, and had private insurance. Targeted measures to address financial toxicity are needed to minimize disparities in patient burden of cancer treatment.

TP53 mutation and abnormal p53 expression in endometrial cancer: Associations with race and outcomes.

OBJECTIVE: This multi-center cohort study assessed associations between race, TP53 mutations, p53 expression, and histology to investigate racial survival disparities in endometrial cancer (EC). METHODS: Black and White patients with advanced or recurrent EC with Next Generation Sequencing data in the Endometrial Cancer Molecularly Targeted Therapy Consortium database were identified. Clinicopathologic and treatment variables were summarized by race and compared. Overall survival (OS) and progression-free survival (PFS) among all patients were estimated by the Kaplan-Meier method. Cox proportional hazards models estimated the association between race, TP53 status, p53 expression, histology, and survival outcomes. RESULTS: Black patients were more likely than White patients to have TP53-mutated (N = 727, 71.7% vs 49.7%, p < 0.001) and p53-abnormal (N = 362, 71.1% vs 53.2%, p = 0.003) EC. Patients with TP53-mutated EC had worse PFS (HR 2.73 (95% CI 1.88-3.97)) and OS (HR 2.20 (95% CI 1.77-2.74)) compared to those with TP53-wildtype EC. Patients with p53-abnormal EC had worse PFS (HR 2.01 (95% CI 1.22-3.32)) and OS (HR 1.61 (95% CI 1.18-2.19)) compared to those with p53-wildtype EC. After adjusting for TP53 mutation and p53 expression, race was not associated with survival outcomes. The most frequent TP53 variants were at nucleotide positions R273 (n = 54), R248 (n = 38), and R175 (n = 23), rates of which did not differ by race. CONCLUSIONS: Black patients are more likely to have TP53-mutated and p53-abnormal EC, which are associated with worse survival outcomes than TP53- and p53-wildtype EC. The higher frequency of these subtypes among Black patients may contribute to survival disparities.

Therapeutic approaches to repair defects in deltaF508 CFTR folding and cellular targeting.

The deltaF508 mutation in the cystic fibrosis transmembrane regulator (CFTR) gene is the most common mutation in CF. The mutant CFTR protein is defective with respect to multiple functions including cAMP-regulated chloride conductance, nucleotide transport, and regulatory actions on other ion channels. Since the deltaF508 protein is also temperature-sensitive and unstable during translation and folding in the endoplasmic reticulum (ER), most of the nascent chains are targeted for premature proteolysis from the ER. This paper focuses on the events that occur in the ER during folding and reviews potential targets for therapeutic intervention.