Impact of Biological Sex on Survival Outcomes in Low-Grade Glioma.

PURPOSE/OBJECTIVE(S) Low-grade glioma (LGG) is a heterogeneous group of brain tumors for which accurate determination of prognosis and optimal therapeutics remains challenging. Recent evidence suggests a correlation between female biological sex and favorable survival in patients with high-grade glioma. However, in patients with LGG, the impact of biological sex and other socioeconomic and treatment factors on survival is not well understood. In the present study, we aim to elucidate the relationship between biological sex and survival outcomes in LGG. We hypothesize that female sex is associated with favorable survival outcomes. MATERIALS/METHODS Using the National Cancer Database (NCDB), a retrospective analysis of patients with LGG diagnosed between 2004 and 2016 in the United States was performed. Demographic, tumor, and treatment data were abstracted; patients with missing information were excluded. Survival outcomes and factors associated with survival were assessed with the Kaplan-Meier and Cox proportional hazard methods. RESULTS 22,822 evaluable patients were identified in the NCDB. The median age was 48 years (range: 18 to 90). 44.2% of patients were female. 89% of patients were white, 5.9% were black, and 4.9% were of other or unknown race. 67% of patients had surgery, 49% of patients had radiation, and 42% had chemotherapy. The median follow-up time for the cohort was 38.8 months. Median overall survival (OS) for the cohort was 79 months. On Kaplan-Meier analysis, females had statistically significantly favorable survival outcomes: Ten-year overall survival was 44.1% for females and 38.5% for males (P < 0.001). Median OS was 7.3 years (95% confidence interval [CI] 6.9-7.8) for females and 6.1 years (95% CI 5.8-6.3) for males. On univariate analysis, age, sex, insurance status, Charlson-Deyo score, receipt of surgery, receipt of chemotherapy, and receipt of radiation were associated with survival; race was not associated with survival. On multivariable Cox regression analysis, after adjusting for patient factors (age, sex, Charlson-Deyo score, and insurance status) and treatment factors (surgery, chemotherapy, and radiation), female sex was significantly associated with decreased risk of death (hazard ratio [HR] 0.92, 95% CI 0.88-0.96, P < 0.01). Other factors associated with decreased risk of death were receipt of radiation (HR 0.67, 95% CI 0.63-0.70, P < 0.01), receipt of surgery (HR 0.58, 95% CI 0.55-0.61, P < 0.01), and receipt of chemotherapy (HR 0.94, 95% CI 0.90-0.99, P = 0.018). Factors associated with increased risk of death were higher Charlson-Deyo score (HR 1.2, 95% CI 1.18-1.25, P < 0.01) and Medicaid/uninsured/unknown insurance status (HR 1.2, 95% CI 1.11-1.26, P < 0.01). CONCLUSION In this large national cohort, female biological sex was associated with improved survival outcomes in LGG. Biological sex should be viewed as an important prognostic factor in LGG, and further study of the underlying mechanisms and clinical implications of this finding are warranted. AUTHOR DISCLOSURE S.S. Kilic: None. K. Yang: None. S. Kilic: None. A. Halima: None. J.H. Suh: Consultant; Philips, Novocure. Met to discuss current indications for TTF; Novocure. Met during 1 day retreat to discuss future of radiation oncology; Philips. Scientific advisory board; Neutron Therapeutics. T.A. Chan: None. J.S. Yu: None. S.T. Chao: Honoraria; Varian Medical Systems, Zeiss, AbbVie. Consultant; AbbVie. D. Peereboom: None. Y. Rauf: None. G. Stevens: None. D.Y. Park: None. M. Ahluwalia: Research Grant; AstraZeneca, Bristol Meyers Squibb, Bayer, Incyte, Pharmacyclics, Novocure, Mimivax, Merck. Consultant; Bayer, Novocure, Kiyatec, Insightec, GlaxoSmithKline, Nuvation, Cellularity, Apollomics. Stock; Doctible, Mimivax, Cytodyn. M.C. Tom: Research Grant; Blue Earth Diagnostics. E.S. Murphy: None.