Clinical actionability in gliomas revealed by real-world next-generation sequencing: a multicentric study

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 the integration of NGS into standard care for glioma, facilitating precise molecular classification, expanding therapeutic options, and improving access to matched clinical trials.