Tumor growth patterns of MGMT-non-methylated glioblastoma in the randomized GLARIUS trial

J Cancer Res Clin Oncol. 2018 Aug;144(8):1581-1589. doi: 10.1007/s00432-018-2671-z. Epub 2018 May 28.

Abstract

Background: We evaluated patterns of tumor growth in patients with newly diagnosed MGMT-non-methylated glioblastoma who were assigned to undergo radiotherapy in conjunction with bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ) within the randomized phase II GLARIUS trial.

Methods: In 142 patients (94 BEV/IRI, 48 TMZ), we reviewed magnetic resonance imaging scans at baseline and first tumor recurrence. Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images, we assessed tumor growth patterns and tumor invasiveness. Tumor growth patterns were classified as either multifocal or local at baseline and recurrence; at first recurrence, we additionally assessed whether distant lesions appeared. Invasiveness was determined as either diffuse or non-diffuse. Associations with treatment arms were calculated using Fisher's exact test.

Results: At baseline, 115 of 142 evaluable patients (81%) had a locally confined tumor. Between treatment arms, there was no significant difference in the fraction of tumors that changed from an initially local tumor growth pattern to a multifocal pattern (12 and 13%, p = 0.55). Distant lesions appeared in 17% (BEV/IRI) and 13% (TMZ) of patients (p = 0.69). 15% of patients in the BEV/IRI arm and 8% in the TMZ arm developed a diffuse growth pattern from an initially non-diffuse pattern (p = 0.42).

Conclusions: The tumor growth and invasiveness patterns do not differ between BEV/IRI and TMZ-treated MGMT-non-methylated glioblastoma patients in the GLARIUS trial. BEV/IRI was not associated with an increased rate of multifocal, distant, or highly invasive tumors at the time of recurrence.

Keywords: Bevacizumab; MRI tumor growth patterns; Newly diagnosed MGMT-non-methylated glioblastoma; Progression patterns.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cell Growth Processes
  • DNA Modification Methylases / metabolism*
  • DNA Repair Enzymes / metabolism*
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Female
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / enzymology
  • Glioblastoma / pathology*
  • Glioblastoma / therapy*
  • Humans
  • Irinotecan
  • Magnetic Resonance Imaging
  • Male
  • Methylation
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Radiotherapy
  • Temozolomide
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Tumor Suppressor Proteins
  • Bevacizumab
  • Irinotecan
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Camptothecin
  • Temozolomide