Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology)

J Neurooncol. 2015 Nov;125(2):359-67. doi: 10.1007/s11060-015-1923-x. Epub 2015 Sep 30.

Abstract

The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.

Keywords: Chemotherapy; Elderly; Glioblastoma; Radiation therapy; Temozolomide.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy*
  • Combined Modality Therapy
  • DNA Methylation / drug effects
  • DNA Methylation / radiation effects
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / mortality
  • Glioblastoma / therapy*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Italy
  • Karnofsky Performance Status
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • Radiotherapy Dosage
  • Retrospective Studies
  • Temozolomide

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • O(6)-Methylguanine-DNA Methyltransferase
  • Temozolomide