Evaluation of Sex-Based Differences in Patient Characteristics, Tumor-Related Factors, and Clinical Outcomes in Patients With Newly Diagnosed IDH-Wildtype Glioblastoma Receiving Chemoradiation

Abstract

While glioblastoma (GBM) is known to have increased incidence in males, recent work has identified possible sex-specific molecular differences that could be associated with improved clinical outcomes for female GBM patients. We evaluated sex-based differences in patient and tumor characteristics, and clinical outcomes in newly diagnosed GBM patients.We reviewed 665 newly diagnosed adult IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 who were treated at our institution from January 1, 2010 to May 30, 2019. Patient, tumor and treatment details were obtained from the electronic medical record. An unpaired t-test, Fisher's exact test and univariable/multivariable Cox proportional hazards modeling were used to evaluate associations, including progression free survival (PFS) and overall survival (OS).In our GBM cohort, 384 (57.7%) were male and 281 (42.3%) were female. There were no significant differences in age (60.6 years in males vs. 60.0 years in females, P = 0.16), KPS (KPS ≥90 in 46.1% in males vs. 43.4% in females, P = 0.53), extent of resection (gross total resection in 44.8% in males vs. 47.7% in females, P = 0.48), or prevalence of MGMT methylation (37.8% in males vs. 43.4% in females, P = 0.11). There were also no differences in receipt of temozolomide (95.1% of males vs. 95.7% of females, P = 0.71), radiation dose (≥59.4 Gy in 85.2% in males vs. 87.5% in females, P = 0.43), or clinical trial enrollment (24.7% males vs. 21.0% females, P = 0.27). Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, P = 0.02). On multivariable analysis adjusted for age (adjusted hazard ratio [AHR] 1.04, 95% CI [1.03-1.05], P < 0.001), KPS ≥90 (AHR 0.73, 95% CI [0.60-0.89], P = 0.002), extent of resection (AHR 1.12, 95% CI 0.92-1.37, P = 0.26), and MGMT methylation status (AHR 0.38, 95% CI [0.31-0.47], P < 0.001), female sex (AHR 0.78, 95% CI [0.64-0.95], P = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT unmethylated patients (HR 0.69, 95% CI [0.54-0.90], P = 0.005) but not in MGMT methylated patients (HR 0.85, 95% CI [0.64-1.14], P = 0.28). While age (AHR 1.02, 95% CI [1.02-1.03], P < 0.001), KPS ≥90 (AHR 0.79, 95% CI [0.66-0.95], P = 0.01), and MGMT methylation (AHR 0.40, 95% CI [0.33-0.49], P < 0.001) were associated with PFS, biologic sex was not associated with PFS (AHR 0.94, 95% CI [0.78-1.12], P = 0.49).Female sex was associated with improved survival after adjustment of known clinical covariates in newly diagnosed GBM patients. Further study is necessary to understand biologic mechanism for sex-based differences in clinical outcome given implications for therapy development and clinical trial design.D.D. Shi: None. M. Lim-Fat: None. G.C. Youssef: None. S. Whorral: None. M. Allen: None. D.N. Cagney: None. S. Tanguturi: None. D. Haas-Kogan: Research Grant; Novartis; Cellworks. A.A. Aizer: Research Grant; Varian. Consultant; Novartis. Advisory Board; Seattle Genetics. J. McFaline-Figueroa: None. U.N. Chukwueke: None. E.Q. Lee: None. D.A. Reardon: Research Grant; Celldex, Inovio, Midatech. Consultant; Amgen. Speaker's Bureau; Merck/Schering, Roche/Genentech. Advisory Board; AbbVie, Bristol Myers Squibb, Cavion, Celldex, EMD Serono, Juno Pharmaceuticals, Momenta Pharmaceuticals, Novartis, Novocure, Oxigene, Regeneron, Roche/Genentech, Stemline. L. Nayak: None. W.L. Bi: Research Grant; The Leukemia and Lymphoma Society, NIH/NCI.R. Beroukhim: Independent Contractor; Scorpion Therapeutics. Stock; Scorpion Therapeutics. K.L. Ligon: None. B.M. Alexander: Research Grant; Puma Biotechnology, Eli Lily, Celgene. Stock; Hoffman-La Roche. P.Y. Wen: None. R. Rahman: Research Grant; Project Data Sphere, LLC.