Genomic alterations predictive of response to radiosurgery in recurrent IDH-WT glioblastoma
| Autor: | Yoshua Esquenazi, Jay-Jiguang Zhu, Magda Martir, Sigmund H. Hsu, Antonio Dono, Nitin Tandon, Mark Amsbaugh, Richard H. Smilie, Roy Riascos, Dong H. Kim, Leomar Y. Ballester, Angel I. Blanco |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Neurology Bevacizumab medicine.medical_treatment Radiosurgery Article 03 medical and health sciences 0302 clinical medicine Internal medicine parasitic diseases medicine Humans PTEN Aged Retrospective Studies Salvage Therapy biology Brain Neoplasms business.industry Recurrent glioblastoma PTEN Phosphohydrolase Middle Aged medicine.disease 030220 oncology & carcinogenesis Mutation biology.protein Biomarker (medicine) Female Neurology (clinical) Neoplasm Recurrence Local Glioblastoma business 030217 neurology & neurosurgery Chemoradiotherapy medicine.drug |
| Zdroj: | J Neurooncol |
| ISSN: | 1573-7373 0167-594X |
| Popis: | INTRODUCTION: Despite aggressive treatment, glioblastoma invariably recurs. The optimal treatment for recurrent glioblastoma (rGBM) is not well defined. Stereotactic radiosurgery (SRS) for rGBM has demonstrated favorable outcomes for selected patients; however, its efficacy in molecular GBM subtypes is unknown. We sought to identify genetic alterations that predict response/outcomes from SRS in rGBM-IDH-wild-type (IDH-WT). METHODS: rGBM-IDH-WT patients undergoing SRS at first recurrence and tested by next-generation sequencing (NGS) were reviewed (2009–2018). Demographic, clinical, and molecular characteristics were evaluated. NGS interrogating 205-genes was performed. Primary outcome was survival from GK-SRS assessed by Kaplan-Meier method and multivariable Cox proportional-hazards. RESULTS: Sixty-three lesions (43-patients) were treated at 1st recurrence. Median age was 61-years. All patients were treated with resection and chemoradiotherapy. Median time from diagnosis to 1st recurrence was 8.7-months. Median cumulative volume was 2.895 cm(3) and SRS median marginal dose was 18 Gy (median isodose-54%). Bevacizumab was administered in 81.4% patients. PFS from SRS was 12.9-months. Survival from SRS was 18.2-months. PTEN-mutant patients had a longer PFS (p = 0.049) and survival from SRS (p = 0.013) in multivariable analysis. Although no statistically significant PTEN-mutants patients had higher frequency of radiation necrosis (21.4% vs. 3.4%) and lower in-field recurrence (28.6% vs. 37.9%) compared to PTEN-WT patients. CONCLUSIONS: SRS is a safe and effective treatment option for selected rGBM-IDH-WT patients following first recurrence. rGBM-IDH-WT harboring PTEN-mutation have improved survival with salvage SRS compared to PTEN-WT patients. PTEN may be used as a molecular biomarker to identify a subset of rGBM patients who may benefit the most from SRS. |
| Databáze: | OpenAIRE |
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