BIOM-36. A STUDY OF CLINICAL AND MOLECULAR PROGNOSTIC FACTORS FOR RESPONSE TO REGORAFENIB IN RECURRENT GLIOBLASTOMAстатья из журнала
Аннотация: Abstract Introduction Following the results from the REGOMA study, regorafenib has become the first chemotherapeutic option for recurrent glioblastoma, IDH-wildtype, in many countries. However, predictive factors for response to regorafenib are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. METHODS We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a rapid, cheap, and clinically validated platform. MGMT methylation was assessed using methylation-specific PCR, and EGFRvIII expression was assessed using RT-PCR. RESULTS In our series, six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months: these data are consistent with current literature. Among clinical variables, gross-total resection was endowed with a positive prognostic value for PFS (p=0.0296, log-rank test). NGS analysis revealed a mutation in the EGFR pathway (EGFR and/or PIK3CA) in 18% of cases; a mutation in the mitogen-activated protein-kinase (MAPK) pathway (RAS and/or RET) in 18% of cases; no mutations in the remaining cases. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p=0.0061; for OS, 7 vs 9 months, p=0.1076). By combining NGS analysis with RT-PCR for EGFRvIII, we identified 14 patients with EGFR pathway activation, who had a significantly longer PFS and OS after regorafenib treatment. Multivariate analysis confirmed that MAPK pathway mutations predicted a scarce response to regorafenib treatment. Conclusions Through an easy-to-use and cheap platform, we identified a mesenchymal, MAPK-altered signature in IDH-wildtype glioblastoma, predictive of scarce response to regorafenib at recurrence. We thus provide a molecular selection criterion to implement in the clinical practice.
Год издания: 2022
Авторы: S. Chiesa, Antonella Mangraviti, Maurizio Martini, Tonia Cenci, Ciro Mazzarella, Simona Gaudino, Serena Bracci, Antonella Martino, Giuseppe Maria Della Pepa, Martina Offi, Marco Gessi, Rosellina Russo, Matia Martucci, Francesco Beghella Bartoli, Rina Di Bonaventura, Luigi Maria Larocca, Liverana Lauretti, Alessandro Olivi, Roberto Pallini, M. Balducci, Quintino Giorgio D’Alessandris
Издательство: Oxford University Press
Источник: Neuro-Oncology
Ключевые слова: Glioma Diagnosis and Treatment, Radiomics and Machine Learning in Medical Imaging, Cancer Genomics and Diagnostics
Другие ссылки: Neuro-Oncology (PDF)
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PubMed Central (HTML)
Neuro-Oncology (HTML)
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Открытый доступ: bronze
Том: 24
Выпуск: Supplement_7
Страницы: vii12–vii12