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) Neuro-oncology, volume 26, issue 5, pp. 902 - 910
(Article)
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
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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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Keywords: Adult, Aged, Aged, 80 and over, Brain Neoplasms/genetics, Chemoradiotherapy/methods, DNA Methylation, DNA Modification Methylases/genetics, DNA Repair Enzymes/genetics, Disease Progression, Female, Follow-Up Studies, Glioblastoma/genetics, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Promoter Regions, Genetic, Snake Venoms, Tumor Suppressor Proteins/genetics, Journal Article, Research Support, Non-U.S. Gov't, Randomized Controlled Trial
ISSN: 1522-8517
Publisher: Oxford University Press
Note: Publisher Copyright: © 2024 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
(Peer reviewed)