Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide

Int J Radiat Oncol Biol Phys. 2014 Nov 15;90(4):877-85. doi: 10.1016/j.ijrobp.2014.07.014. Epub 2014 Sep 23.

Abstract

Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT).

Methods and materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM.

Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR.

Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Combined Modality Therapy / methods
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Follow-Up Studies
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / radiotherapy*
  • Humans
  • Maintenance Chemotherapy / methods
  • Male
  • Middle Aged
  • Radiotherapy Planning, Computer-Assisted / methods
  • Temozolomide
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide