Dose-Escalated Accelerated Hypofractionation for Patients With a Newly Diagnosed Glioblastoma: A Pooled International Study.

Abstract

PURPOSE/OBJECTIVE(S)\nThe standard of care (SOC) for elderly or frail glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy. However, this regimen has a lower BED compared to the Stupp regimen, 60 Gy in 30 fractions. We hypothesize that dose escalated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to standard of care.\n\n\nMATERIALS/METHODS\nElderly GBM patients treated with 52.5 Gy in 15 fractions were pooled from 2 phase II studies, 1 phase 1 and a prospective observation study. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Univariate and multivariate analyses were performed.\n\n\nRESULTS\nSixty-two newly diagnosed patients were eligible for this analysis. Median follow-up was 10 months. The median OS and PFS was 10.3 and 6.7 months, respectively. Patients with KPS ≥ 70 and < 70 had a median OS of 15.3 and 9.5 months. No survival difference was seen between unmethylated and methylated patients with a median OS of 10.2 and 10.3 months, respectively. Univariate analysis demonstrated younger age (P\u202f=\u202f0.018) and concurrent chemo (P < 0.001) were associated with improved OS and gross total resection (P\u202f=\u202f0.010), smaller PTV volume (P\u202f=\u202f0.008) and concurrent chemo (P\u202f=\u202f0.015) associated with improved PFS. Multivariate analysis demonstrated concurrent chemo to be an independent prognostic factor. Grade 3 or higher neurologic toxicity was seen in 2 patients (3.2%).\n\n\nCONCLUSION\nThis is the first pooled, prospective analysis of elderly/frail GBM patients treated with dose-escalated hypofractionated radiation. Treatment was well tolerated and demonstrated excellent OS and PFS, exceeding that from prior elderly trials (Roa; 6.5 months [poor KPS]/Perry; 9.3 months [good KPS]). This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. Future prospective trials are needed to validate these results.