Dose-intensified chemoradiation is associated with altered patterns of failure and favorable survival in patients with newly diagnosed glioblastoma

Document Type

Article

Abstract

BACKGROUND AND PURPOSE: We evaluated whether dose-intensified chemoradiation alters patterns of failure and is associated with favorable survival in the temozolomide era. MATERIALS AND METHODS: Between 2003 and 2015, 82 patients with newly diagnosed glioblastoma were treated with 66-81 Gy in 30 fractions using conventional magnetic resonance imaging. Progression-free (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods. Factors associated with improved PFS, OS, and time to progression were assessed using multivariate Cox model and linear regression. RESULTS: Median follow-up was 23 months (95% CI 4-124 months). Sixty-one percent of patients underwent subtotal resection or biopsy, and 38% (10/26) of patients with available data had MGMT promoter methylation. Median PFS was 8.4 months (95% CI 7.3-11.0) and OS was 18.7 months (95% CI 13.1-25.3). Only 30 patients (44%) experienced central recurrence, 6 (9%) in-field, 16 (23.5%) marginal and 16 (23.5%) distant. On multivariate analysis, younger age (HR 0.95, 95% CI 0.93-0.97, p = 0.0001), higher performance status (HR 0.39, 95% CI 0.16-0.95, p = 0.04), gross total resection (GTR) versus biopsy (HR 0.37, 95% CI 0.16-0.85, p = 0.02) and MGMT methylation (HR 0.25, 95% CI 0.09-0.71, p = 0.009) were associated with improved OS. Only distant versus central recurrence (p = 0.03) and GTR (p = 0.02) were associated with longer time to progression. Late grade 3 neurologic toxicity was rare (6%) in patients experiencing long-term survival. CONCLUSION: Dose-escalated chemoRT resulted in lower rates of central recurrence and prolonged time to progression compared to historical controls, although a significant number of central recurrences were still observed. Advanced imaging and correlative molecular studies may enable targeted treatment advances that reduce rates of in- and out-of-field progression.

Medical Subject Headings

Adult; Aged; Antineoplastic Agents, Alkylating (therapeutic use); Brain Neoplasms (diagnosis, mortality, therapy); Chemoradiotherapy (mortality); Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Female; Follow-Up Studies; Glioblastoma (diagnosis, mortality, therapy); Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Salvage Therapy; Survival Rate; Temozolomide (therapeutic use); Young Adult

Publication Date

6-1-2019

Publication Title

Journal of neuro-oncology

E-ISSN

1573-7373

Volume

143

Issue

2

First Page

313

Last Page

319

PubMed ID

30977058

Digital Object Identifier (DOI)

10.1007/s11060-019-03166-3

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