Clinical Outcomes in Patients with Recurrent Glioblastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry

Abstract

Purpose As a means of limiting normal tissue toxicity, proton-beam therapy (PBT) is an emerging radiation modality for glioblastoma (GBM) reirradiation. However, data for recurrent GBM treated with PBT reirradiation is limited. Therefore, we analyzed treatment patterns, toxicities, and clinical outcomes of patients with recurrent GBM treated with PBT reirradiation using the multi-institutional Proton Collaborative Group registry. Methods and Materials Prospectively collected data for patients with recurrent GBM who underwent PBT while enrolled in Proton Collaborative Group study 01-009 (NCT01255748) were analyzed. We evaluated overall survival (OS), progression-free survival (PFS), and toxicity. Toxicities were scored per the Common Terminology Criteria for Adverse Events, version 4.0. Descriptive statistics were used to report patient, tumor, and treatment characteristics. Multivariable analyses (MVA) for toxicity were conducted using logistic regression. The Kaplan-Meier method was used to calculate OS and PFS. MVA for OS and PFS was conducted using Cox proportional-hazards models. The SAS statistical software was used for the analysis. Results We identified 45 recurrent patients with GBM who underwent PBT reirradiation between 2012 and 2018. The median time between initial GBM diagnosis and recurrence was 20.2 months. The median follow-up time from PBT reirradiation was 10.7 months. Median PFS was 13.9 months (95% confidence interval [CI], 8.23-20.0 months) and median OS was 14.2 months (95% CI, 9.6-16.9 months) after PBT reirradiation. One patient experienced an acute grade 3 toxicity, 4 patients experienced late grade 3 toxicity (no grade ≥4 toxicities). MVA revealed that prior surgery was associated with a 91.3% decreased hazard of death (hazard ratio: 0.087; 95% CI, 0.02-0.42; P < .01). No explanatory variables were associated with PFS or grade 3 toxicities. Conclusions This is the largest series to date reporting outcomes for PBT reirradiation of patients with recurrent GBM. Our analysis indicates that PBT is well tolerated and offers efficacy rates comparable with previously reported photon reirradiation.

Outcomes After Proton Therapy Reirradiation for Malignant Glioma: Prospective Analysis of Over 100 Patients from the Proton Collaborative Group

“…They also reported a modest incidence of late grade 3 toxicities at 8.3%. [29] The overall incidence of grade 3 toxicity in our study was similar (5.6%) and there were notably no grade 4-5 PT-related toxicities. These outcomes are particularly encouraging given the higher reirradiation doses used in this series.…”

Current status and recent advances in reirradiation of glioblastoma

“…Results of eighteen studies including 976 patients who received stereotactic reirradiation between 2005 and 2020 are shown in Table 2 . Using total doses of 30–45 Gy delivered in 2.5–4.0 Gy per fraction, ten studies including 733 patients showed a median overall survival time ranging from 7.5 to 12.5 months [ 12 , 57 – 59 , 65 – 70 ]. A similar survival time of 7.3 to 12.5 months has been observed in eight studies including 272 patients who received high-dose hypofractionated SRT at doses of 25–35 Gy in 5–7 Gy per fraction [ 13 , 55 , 56 , 60 – 64 ].…”

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity

“…Maximizing the dose drop at the tumor margin has led to the trial of particle therapies. Currently, there is intensive research with proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) [ 67 , 68 ].…”