Treatment-associated imaging changes in newly diagnosed MGMT promoter-methylated glioblastoma undergoing chemoradiation with or without cilengitide

Neuro Oncol. 2024 May 3;26(5):902-910. doi: 10.1093/neuonc/noad247.

Abstract

Background: Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017.

Methods: Patients with ≥ 3 follow-up MRIs were included. Preliminary PD was defined as a ≥ 25% increase of the sum of products of perpendicular diameters (SPD) of a new or increasing lesion compared to baseline. PD required a second ≥25% increase of the SPD. Treatment-associated changes require stable or regressing disease after preliminary PD.

Results: Of the 424 evaluable patients, 221 patients (52%) were randomized into the cilengitide and 203 patients (48%) into the control arm. After chemoradiation with or without cilengitide, preliminary PD occurred in 274 patients (65%) during available follow-up, and 88 of these patients (32%) had treatment-associated changes, whereas 67 patients (25%) had PD. The remaining 119 patients (43%) had no further follow-up after preliminary PD. Treatment-associated changes were more common in the cilengitide arm than in the standard-of-care arm (24% vs. 17%; relative risk, 1.3; 95% CI, 1.004-1.795; P = .047). Treatment-associated changes occurred mainly during the first 6 months after RT (54% after 3 months vs. 13% after 6 months).

Conclusions: With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.

Keywords: glioma; modified RANO criteria; pseudoprogression; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / therapy
  • Chemoradiotherapy* / methods
  • DNA Methylation*
  • DNA Modification Methylases* / genetics
  • DNA Repair Enzymes* / genetics
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glioblastoma* / diagnostic imaging
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Glioblastoma* / pathology
  • Glioblastoma* / therapy
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic*
  • Snake Venoms*
  • Tumor Suppressor Proteins* / genetics

Substances

  • Cilengitide
  • Snake Venoms
  • DNA Modification Methylases
  • DNA Repair Enzymes
  • MGMT protein, human
  • Tumor Suppressor Proteins