A prospective phase II randomized trial of proton radiotherapy vs intensity-modulated radiotherapy for patients with newly diagnosed glioblastoma.

Abstract

BACKGROUND:

To determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM).

METHODS:

Eligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs).

RESULTS:

A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02).

CONCLUSIONS:

In this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time.

• Authors: Paul D Brown, Caroline Chung, Diane D Liu, Sarah McAvoy, David Grosshans, Karine Al Feghali, Anita Mahajan, Jing Li, Susan L McGovern, Mary-Fran McAleer, Amol J Ghia, Erik P Sulman, Marta Penas-Prado, John F de Groot, Amy B Heimberger, Jihong Wang, Terri S Armstrong, Mark R Gilbert, Nandita Guha-Thakurta, Jeffrey S Wefel
• Journal: Neuro-oncology (Neuro Oncol) Vol. 23 Issue 8 Pg. 1337-1347 (08 02 2021) ISSN: 1523-5866 [Electronic] England
• PMID: 33647972 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Protons

Topics

• Brain Neoplasms (radiotherapy)
• Glioblastoma (radiotherapy)
• Humans
• Prospective Studies
• Protons
• Radiotherapy, Intensity-Modulated (adverse effects)