Antonio Dono1,2, Mark Amsbaugh1,3, Magda Martir1,3, Richard H Smilie1, Roy F Riascos3,4, Jay-Jiguang Zhu1,3, Sigmund Hsu1,3, Dong H Kim1,3, Nitin Tandon1,3, Leomar Y Ballester5,6,7, Angel I Blanco1,3, Yoshua Esquenazi8,9,10. 1. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. 2. Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. 3. Memorial Hermann Hospital-TMC, Houston, TX, USA. 4. Department of Diagnostic and Interventional Imaging, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. 5. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Leomar.Y.Ballester@uth.tmc.edu. 6. Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Leomar.Y.Ballester@uth.tmc.edu. 7. Memorial Hermann Hospital-TMC, Houston, TX, USA. Leomar.Y.Ballester@uth.tmc.edu. 8. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Yoshua.EsquenaziLevy@uth.tmc.edu. 9. Memorial Hermann Hospital-TMC, Houston, TX, USA. Yoshua.EsquenaziLevy@uth.tmc.edu. 10. Center for Precision Health, School of Biomedical Informatics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Yoshua.EsquenaziLevy@uth.tmc.edu.
Abstract
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 cm3 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.
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 cm3 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.
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