Survival benefits of hypofractionated radiotherapy combined with temozolomide or temozolomide plus bevacizumab in elderly patients with glioblastoma aged ≥ 75 years

Radiat Oncol. 2019 Nov 12;14(1):200. doi: 10.1186/s13014-019-1389-7.

Abstract

Background and purpose: The purpose of this study was to evaluate the outcomes of elderly patients (aged ≥75 years) with newly diagnosed glioblastoma (GBM), who were treated with hypofractionated radiotherapy comprising 45 Gy in 15 fractions combined with temozolomide (TMZ) or TMZ and bevacizumab (TMZ/Bev).

Materials and methods: Between October 2007 and August 2018, 30 patients with GBM aged ≥75 years were treated with hypofractionated radiotherapy consisting of 45 Gy in 15 fractions. Twenty patients received TMZ and 10 received TMZ/Bev as upfront chemotherapy. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed by pyrosequencing. The cutoff value of the mean level of methylation at the 16 CpG sites was 16%.

Results: Median overall survival (OS) and progression-free survival (PFS) were 12.9 months and 9.9 months, respectively. The 1-year OS and PFS rates were 64.7 and 34.7%, respectively. Median OS and PFS did not differ significantly between patients with MGMT promoter hypermethylation (N = 11) and those with hypomethylation (N = 16) (17.4 vs. 11.8 months, p = 0.32; and 13.1 vs. 7.3 months, p = 0.11, respectively). The median OS and PFS were not significantly different between TMZ (N = 20) and TMZ/Bev (N = 10) chemotherapy (median OS: TMZ 12.9 months vs. TMZ/Bev 14.6 months, p = 0.93, median PFS: TMZ 8.5 months vs TMZ/Bev 10.0 months, p = 0.64, respectively). The median time until Karnofsky performance status (KPS) score decreasing below 60 points was 7.9 months. The best radiological responses included 11 patients with a partial response (36.7%). Grade 3/4 toxicities included leukopenia in 15 patients (50%), anorexia in 4 (13.3%), and hyponatremia during concomitant chemotherapy in 3 (10%).

Conclusion: Our hypofractionated radiotherapy regimen combined with TMZ or TMZ/Bev showed benefits in terms of OS, PFS, and KPS maintenance with acceptable toxicities in elderly patients with GBM aged ≥75 years.

Keywords: Bevacizumab; Elderly glioblastoma; Hypofractionated radiotherapy; Temozolomide; Vulnerability.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Bevacizumab / administration & dosage*
  • Brain / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / radiotherapy*
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Methylation
  • Radiation Dose Hypofractionation
  • Retrospective Studies
  • Temozolomide / administration & dosage*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Bevacizumab
  • Temozolomide