Particle radiation therapy in the management of malignant glioma: Early experience at the Shanghai Proton and Heavy Ion Center

Cancer. 2020 Jun 15;126(12):2802-2810. doi: 10.1002/cncr.32828. Epub 2020 Mar 13.

Abstract

Background: The objective of this study was to evaluate the outcomes of patients with high-grade glioma who received treatment with particle radiotherapy.

Methods: Between June 2015 and October 2018, 50 consecutive and nonselected patients with glioblastoma multiforme (n = 34) or anaplastic glioma (n = 16) were treated at the Shanghai Proton and Heavy Ion Center. Twenty-four patients received proton radiotherapy (at a dose of 60 gray-equivalents in 30 daily fractions), and 26 patients received proton radiotherapy plus a carbon-ion radiotherapy (CIRT) boost in various dose-escalating schemes. All patients received temozolomide because of their age or their O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Progression-free survival (PFS) and overall survival (OS) rates, as well as treatment-induced toxicities, were analyzed.

Results: At a median follow-up of 14.3 months (range, 4.8-39.6 months), the 12-month and 18-month OS rates were 87.8% (95% CI, 77.6%-98.0%) and 72.8% (95% CI, 56.7%-88.9%), respectively, and the 12-month and 18-month PFS rates were 74.2% (95% CI, 60.9%-87.5%) and 59.8% (95% CI, 43.1%-76.5%), respectively. Univariate analyses revealed that age (>50 vs ≤50 years), World Health Organization grade (3 vs 4), and Karnofsky performance status (>80 vs ≤80) were significant prognosticators for OS, and IDH mutation and World Health Organization grade were significant for predicting PFS. Furthermore, MGMT promoter methylation, performance status, and age showed a trend toward predicting PFS. No significant predictive factors for PFS or OS were identified in multivariate analyses. Twenty-nine patients experienced grade 1 treatment-related acute adverse effects, and 11 developed grade 1 (n = 6) or grade 2 (n = 5) late adverse effect of radiation-induced brain necrosis. No grade 3, 4, or 5 toxicities were observed.

Conclusions: Particle radiotherapy produced 18-month OS and PFS rates of 72.8% and 59.8%, respectively, with acceptable adverse effects in patients with high-grade glioma. Particle radiotherapy at a dose ≥60 gray-equivalents appears to be safe and potentially effective.

Keywords: glioblastoma; high-grade glioma; particle radiotherapy; survival; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / metabolism
  • Dose Fractionation, Radiation
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy
  • Glioma / drug therapy
  • Glioma / mortality*
  • Glioma / pathology
  • Glioma / radiotherapy*
  • Heavy Ion Radiotherapy / adverse effects
  • Heavy Ion Radiotherapy / methods*
  • Humans
  • Male
  • Middle Aged
  • Proton Therapy / adverse effects
  • Proton Therapy / methods*
  • Temozolomide / therapeutic use
  • Treatment Outcome
  • Tumor Suppressor Proteins / metabolism
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide