Baseline T1 hyperintense and diffusion-restricted lesions are not linked to prolonged survival in bevacizumab-treated glioblastoma patients of the GLARIUS trial

J Neurooncol. 2019 Sep;144(3):501-509. doi: 10.1007/s11060-019-03246-4. Epub 2019 Jul 19.

Abstract

Purpose: The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase promoter non-methylated glioblastoma to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ). To identify subpopulations with a particularly favorable course, we assessed the prognostic potential of magnetic resonance imaging (MRI) markers before treatment onset.

Methods: MRIs at baseline (before treatment onset) were analyzed for T1-hyperintense and diffusion-restricted lesions; as well as the presence of both hyperintense and diffusion-restricted (double positive) lesions. The MRI findings were correlated with overall and progression-free survival.

Results: MRI scans were evaluable in 71% of the GLARIUS modified intention-to-treat population (n = 121 of 170; 88 patients in the BEV/IRI arm, and 33 patients in the TMZ control arm). Diffusion-restricted and T1 hyperintense lesions were present in 60% and 65% of patients in BEV/IRI arm, while 57% and 63% were found in the TMZ arm, respectively. Double positive lesions were found in 37% of BEV/IRI patients and in 39% of TMZ patients. Neither the presence of T1-hyperintense, diffusion-restricted lesions, nor double positive lesions were associated with improved survival.

Conclusions: Baseline T1-hyperintense and diffusion-restricted lesions are not suitable to predict progression-free or overall survival of patients treated with bevacizumab/irinotecan or temozolomide.

Keywords: Bevacizumab; Irinotecan; MRI; Newly diagnosed MGMT-non-methylated glioblastoma; Predictive and prognostic implications.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Camptothecin / administration & dosage
  • Dacarbazine / administration & dosage
  • Female
  • Follow-Up Studies
  • Glioblastoma / drug therapy
  • Glioblastoma / mortality*
  • Glioblastoma / pathology
  • Humans
  • Irinotecan / administration & dosage
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Prognosis
  • Survival Rate
  • Temozolomide / administration & dosage

Substances

  • Bevacizumab
  • Irinotecan
  • Dacarbazine
  • Camptothecin
  • Temozolomide

Grants and funding