Timing and Sequence of Chemoradiation for Low-Grade Gliomas Meeting RTOG 9802 Criteria

Abstract

RTOG 9802 has established postoperative chemoradiotherapy as the new standard of care for patients with high-risk low grade glioma (LGG) meeting trial criteria. Although all patients in the trial received sequential chemoradiation therapy (sCRT) with radiotherapy (RT) followed by chemotherapy, outcomes of chemotherapy followed by RT remain unknown. It is also unknown whether concurrent chemoradiation therapy (cCRT) may offer advantages over sCRT. The National Cancer Data Base (NCDB) was queried for newly-diagnosed WHO grade II glioma receiving CRT. Patients with unknown surgery, RT, or chemotherapy status were excluded, along with patients <40 years old that underwent gross total resection (according to RTOG 9802 exclusion criteria). Chi squared, Fisher’s exact or Wilcoxon rank-sum tests evaluated differences in characteristics between groups. Kaplan-Meier analysis was used to evaluate overall survival (OS) between groups (sCRT vs. cCRT; RT followed by chemotherapy vs. vice versa). Cox proportional hazards modeling determined variables associated with OS. In total, 509 patients were analyzed (n=327 [64.2%] cCRT, n=179 [35.1%] sCRT) with two sCRT subgroups (n=77 [43.0%] RT first, n=102 [57.0%] chemotherapy first). Groups were well balanced, with exception of a trend towards greater cCRT use in academic centers (p=0.086). Within the sCRT subgroup, patients in the Northeast were more likely to be treated with RT first and patients in the West were more likely to be treated with chemotherapy first (p=0.039). Although timing of therapy did not independently influence survival on univariable/multivariable analysis, factors associated with worse OS included advancing age (p<0.001), overlapping (p=0.019) or temporal sites (p=0.024) and Medicaid/other insurance (p=0.045). This is the only known analysis of cCRT versus sCRT, and evaluating timing of the latter, for LGG. There is no evidence that cCRT improves outcomes over sCRT, and sequencing sCRT with either chemotherapy first or RT first yields similar OS.