Clinical Outcomes for High-Risk WHO Grade II Glioma Patients Treated with Upfront TMZ- based Chemoradiotherapy

Abstract Purpose: RTOG 9802 demonstrated improved survival with the use of chemoradiotherapy (CRT) over radiotherapy (RT) alone for WHO grade II gliomas (LGG) using PCV chemotherapy. We analyzed our retrospective dataset of predominantly temozolomide (TMZ)-based CRT in patients with LGG who would have been eligible for RTOG 9802. Methods: We identified 67 patients (n= 38 astrocytoma (AC), 20 oligodendroglioma (OD), and 9 mixed (OA)) treated with upfront RT from 2000-2017. The CRT cohort (n=40) primarily consisted of TMZ (n=36) administered concurrently with RT. The median RT dose was 54 Gy (range 35-54 Gy). Kaplan- Meier analysis was used to assess overall survival (OS) and progression-free survival (PFS). Results: 5-year PFS was 64% vs. 44% for patients receiving CRT vs. RT alone (log-rank p=0.009). 5-year PFS for AC patients receiving CRT vs. RT alone was 57% vs. 21%, respectively (log-rank p=0.002) while 5-year PFS for OD/OA patients receiving CRT vs. RT alone was 79% vs. 72% (p=0.21). 5-year OS was 76% vs. 69% (p=0.10 ) for CRT vs. RT alone. Cox Proportional Hazards analysis revealed that patients with AC (HR=4.89, 95% CI (1.95, 12.3), p=0.0007), neurological deficits (HR=2.34, (1.12, 4.88), p=0.023), and tumors>6 cm (HR=2.69, (1.10, 6.58), p=0.03) had decreased OS. Cox analysis showed that use of upfront CRT (HR=0.40 , (0.20, 0.79), p=0.0086) was the only factor that improved PFS. Conclusion: The use of upfront, predominantly TMZ-based, CRT has a PFS benefit over RT alone in patients with LGG.