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


Flies, Christina Maria; Friedrich, Michel; Lohmann, Philipp; van Garderen, Karin Alida; Smits, Marion; Tonn, Joerg-Christian; Weller, Michael; Galldiks, Norbert; Snijders, Tom Jan (2024). Treatment-associated imaging changes in newly diagnosed $MGMT$ promoter-methylated glioblastoma undergoing chemoradiation with or without cilengitide. Neuro-Oncology, 26(5):902-910.

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.

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Cancer Research, Neurology (clinical), Oncology
Language:English
Date:3 May 2024
Deposited On:21 Feb 2024 14:38
Last Modified:04 May 2024 01:06
Publisher:Oxford University Press
ISSN:1522-8517
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/neuonc/noad247
PubMed ID:38219019
Project Information:
  • : Funderthe Stophersenkanker.nu foundation
  • : Grant ID
  • : Project Title
  • : FunderFoundation Vrienden UMC Utrecht
  • : Grant ID
  • : Project Title
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)