Investigating Nationwide Usage Trends and Relative Efficacy of Combined Modality Treatments for Elderly Glioblastoma Patients

Abstract

For well-functioning glioblastoma (GBM) patients under 65 years old, long-course chemoradiotherapy (LC-CRT) remains standard of care. For elderly patients, early trials established efficacy of hypofractionated radiation alone. More recent data demonstrated that short-course chemoradiation (SC-CRT) improves survival over short-course RT alone. Here, we investigated nationwide treatment patterns and relative outcomes for SC- vs. LC-CRT using the National Cancer Database (NCDB). Patients aged ≥65 with a first primary diagnosis of GBM treated from 2006-2014 who underwent surgery with or without adjuvant LCRT (58-63 Gy in 28-34 fractions) or SCRT (34-42 Gy in 10-15 fractions) were identified from the NCDB. Factors examined included facility type, location, age, sex, race, Charlson-Deyo score, median income, insurance, tumor size, extent of resection (EoR) and chemotherapy. Overall survival was assessed using Kaplan-Meier and Cox proportional hazards modeling. Multivariate logistic regression was used to characterize predictors of SC-CRT versus LC-CRT. Propensity score matching was performed for adjusted survival comparison. From 107,956 GBM cases, 12,688 elderly patients were identified that met inclusion criteria. Median age was 72 with median follow-up of 48.3 months. A total of 7358 (58%) received chemotherapy. 7187 (56.6%) and 433 (3.4%) received LCRT and SCRT, respectively. Median survivals were 11.9, 6.9 and 3.0 months for patients who received LCRT, SCRT or no RT (p<0.001), respectively, which remained significant on 1- and 3-month landmark analyses. On multivariate regression, age, Charlson-Deyo score, tumor size, EoR, receipt of RT, receipt of chemotherapy, median income, race and treatment at academic facility were significantly associated with survival. Notably, LCRT was associated with lower mortality risk than SCRT (HR: 1.261 for SCRT vs. LCRT, 95% CI: 1.135-1.402). Among 6935 patients who underwent chemoradiation, 96.2% received LC-CRT and 3.8% received SC-CRT. Factors associated with receipt of SC-CRT included treatment at academic facility (OR: 2.6), old age (OR: 3.3 for 75-84 years old, OR: 8.9 for age ≥85), insurance status (OR: 0.232 for private vs. uninsured), lower median income, EoR (OR: 0.42 for undocumented) and brainstem involvement (OR: 14.1 vs. supratentorial). On propensity score matched analysis, long-course CRT was associated with significant survival benefit over short-course CRT (11.4 months vs. 9.1 months, p < 0.005). In this registry-based study of elderly GBM patients, factors associated with receipt of long-course over short-course CRT included younger age, supratentorial location, treatment at a non-academic facility, facility location, greater median income and private insurance. Even after adjustment for covariates, LC-CRT was associated with improved survival over SC-CRT.