A scoping review of proton radiation therapy and mutant-isocitrate dehydrogenase-inhibitors in IDH mutated lower-grade gliomas: pushing beyond surrogate end-points.
Dima Harba, Alba Corell, Alireza Mansouri, Petter Brandal, Malin Blomstrand, Asgeir Store Jakola
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引用次数: 0
Abstract
Background: Proton radiation therapy (PRT) and mutant isocitrate dehydrogenase inhibitors (mIDH-inhibitors) are emerging therapies for mIDH lower grade gliomas (LGGs). Despite their substantial theoretical benefits, comparisons with current standards - particularly pertaining to patient-centred outcomes - are limited.
Methods: Through PubMed and Scopus, a search strategy based on keywords focusing on PRT and mIDH-inhibitors was applied on December 3, 2024. Studies in English on at least 20 adult patients (≥ 18 years) with mIDH-LGG grade 2 or 3 and published between January 1, 2011 and August 31, 2024 were included. Review articles were excluded.
Results: Of 6383 identified articles, seven per treatment strategy were included. Overall survival was not reported for mIDH-inhibitors. The lack of high-quality studies comparing PRT to photon radiation therapy precludes conclusions regarding efficacy, effectiveness or even post-PRT radiological manifestations. For the mIDH-inhibitor Vorasidenib (AG-881), the radiological objective response rate was 10.0-42.9%, although lower for contrast-enhancing tumors. Vorasidenib significantly delayed tumor progression (27.7 versus 11.1 months, p < 0.001) and time to next intervention (not reached versus 17.8 months, p < 0.001) when compared to placebo. Adverse events were mostly mild, including elevated liver enzymes (15.6-44.2%) and headache (26.9-46.2%). Only 1/14 studies included assessments related to quality of life (QoL)-domains with inconclusive research on cognitive outcomes.
Conclusion: Studies reporting on patient-centred data including survival, cognition and QoL remain scarce. Larger, comparative prospective studies, preferably randomized controlled trials, with such outcomes are needed to inform clinicians whether the theoretical and radiological benefits can be translated to improved outcomes that matter to patients, i.e. living better and/or longer.
期刊介绍：
The journal "Acta Neurochirurgica" publishes only original papers useful both to research and clinical work. Papers should deal with clinical neurosurgery - diagnosis and diagnostic techniques, operative surgery and results, postoperative treatment - or with research work in neuroscience if the underlying questions or the results are of neurosurgical interest. Reports on congresses are given in brief accounts. As official organ of the European Association of Neurosurgical Societies the journal publishes all announcements of the E.A.N.S. and reports on the activities of its member societies. Only contributions written in English will be accepted.
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