Abstract
Treatment options for patients with gliomas remain limited, and prognosis is generally poor. While next-generation sequencing (NGS) is increasingly used to stratify glioma patients and guide therapy, its implementation in routine clinical practice remains variable. We conducted a multicenter retrospective study across seven Spanish hospitals to evaluate the clinical utility of NGS in glioma management, focusing on its impact on diagnosis and treatment selection based on the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). A total of 541 glioma patients diagnosed between 2018 and 2022 were included; 76% had glioblastomas and 24% other glioma subtypes. Among glioblastoma patients, 9% harbored ESCAT tier 1/2 alterations and 74% tier 3/4. Molecularly matched therapy was administered in 10.2% of glioblastoma cases. Objective responses were observed in 17.6% of glioblastoma and 33% of non-glioblastoma patients with ESCAT tier 1/2 alterations. Patients with tier 1/2 alterations experienced significantly longer progression-free survival compared to those with tier 3/4. These findings support genomic profiling of gliomas in research centers to expand therapeutic options in molecularly guided clinical trials.
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Deidentified patient data from this study can be made available to qualified investigators who provide a methodologically sound research proposal and sign a data access agreement. Please email oriolmirallas@vhio.net for information. The study protocol, statistical analysis plan, and informed consent form will also be made available upon request. Data will be shared via a secure online platform; REDcap and public repository on the VHIO website.
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Acknowledgements
The authors would like to thank all the patients and families who agreed to participate in this study; progress in oncology care would be impossible without them. The first author would like to thank all the health staff at the different centers for working together to make this study possible. The first author wishes to express his sincere gratitude to Javier Carmona Cortés, PhD, for his input to this manuscript. The development of this publication was supported by Hoffman-La Roche & Co, Spain, through a grant for the publishing fees. The views and opinions contained in this publication do not necessarily reflect the ideas of the awarding entity of the scholarship. The founder of the study had no role in the study design, data collection, analysis, interpretation of the data, and writing of the report.
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Conception and design: Oriol Mirallas, Rodrigo Dienstmann, and Maria Vieito. Provision of study materials or patients: Gabriel Velilla, Diego Gomez-Puerto, Teresa Gorria, Jesus Yaringaño, Alvaro Martinez-Monino, Antonio Di Muzio, Daniel López-Valbuena, Maria Angeles Vaz, Ainhoa Hernandez, Elena Martínez-Saez, Maria Aguado Sorolla, Maria Castro Henriques, María Martínez-García, Marta Domenech, Carmen Balaña, Estela Pineda, and Juan Manuel Sepúlveda. Collection and assembly of data: Fiorella Ruiz, Oriol Mirallas, Gabriel Velilla, Diego Gomez-Puerto, Teresa Gorria, Jesus Yaringaño, Antonio Di Muzio, Alvaro Martinez-Monino, Daniel López-Valbuena, Maria Angeles Vaz, Ainhoa Hernandez, Elena Martínez-Saez, Maria Aguado Sorolla, Maria Castro Henriques, María Martínez-García, Marta Domenech, and Estela Pineda. Data analysis and interpretation: Fiorella Ruiz, Oriol Mirallas, Rodrigo Dientsmann, and Maria Vieito. Manuscript writing: all authors.Final approval of manuscript: all authors. Accountable for all aspects of the work: all authors.
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O.M. reports writing aid from Merck and Roche, and travel aid from Almirall, Kyowa Kirin, and Recordati. D.G. reports honoraria for lectures from LEO Pharma. T.G. reports disclose lectures/educational activities G.S.K., and travel expenses Pfizer, Reddy’s, BMS, MSD. M.A.V.S. reports grants from Pfizer, honoraria for lectures from Novocure and Servier, and advisory board from Servier. M.C.H. reports consulting fees from Genomic Health, payments for expert testimony from Novartis, Daichii-Sankyo, Pfizer, Gilead, Astra-Zeneca, travel expenses from Lilly, fizer, Daichii-Sankyo, Novartis, Astra-Zeneca, Roche. M.G. reports writing aid Merck Sharp & Dohme, Bayer, Pfizer, Ipsen Pharma and travel aid from Roche, Sanofi Aventis, Astellas, Pfizer, Janssen, Merck Sharp & Dohme, Bayer, and Lilly. M.M.G. reports consulting fees from Gilead, Novocure, Seagen, Boehringer Ingelheim, Roche, Celgene, and Lilly, travel aid from Pfizer, Roche, Gilead, Astra Zeneca-Daiichi Sankyo, and participation on the Advisory Board of Gilead, Novocure, Seagen, Boehringer Ingelheim, Roche, Celgene, and Lilly. M.D. reports grants from Roche, honoraria for lectures from BMS, and travel aid from Takeda and Lilly. J.C. reports consulting fees from Astellas Pharma; AstraZeneca; Bayer; Bristol-Myers Squibb; Exelixis; Ipsen; Johnson & Johnson; MSD Oncology; Novartis (AAA); Pfizer; Sanofi, payment or honoraria for lectures from Astellas Pharma; Bayer; Johnson & Johnson; Sanofi, and support for attending meetings from BMS, Ipsen, Roche, AstraZéneca, Bayer. R.D. reports grants from Merck, Novartis, Daiichi-Sankyo, GlaxoSmithKline, and AstraZeneca; consulting fees from Roche, Foundation Medicine, and AstraZeneca; payment or honoraria for lectures from Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp & Dohme, Lilly, AstraZeneca, Janssen, Takeda, Bristol-Myers Squibb, GlaxoSmithKline, and Gilead; and holds stocks in Trialing Health. J.M. reports grants from Cantex and IDP Pharma, consulting fees from Cantex, GSK, Servier, and Novocure, payment or honoraria for lectures from GSK and Novocure, travel aid from Pfizer, and participation on Advisory Board of Cantex and G.S.K. M.V. reports. C.B. reports support for attending meeting from Servier and payment or honoraria as for DSMB member by Laminar Pharmaceuticals. The rest of the authors declare no conflicts of interest.
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Mirallas, O., Ruiz-Pace, F., Velilla, G. et al. Clinical actionability in gliomas revealed by real-world next-generation sequencing: a multicentric study. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-025-01247-3
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DOI: https://doi.org/10.1038/s41698-025-01247-3
