Antonio Dono1,2, Sonali Mitra2,3, Mauli Shah2, Takeshi Takayasu2, Jay-Jiguang Zhu1,4, Nitin Tandon1,4, Chirag B Patel5,6, Yoshua Esquenazi7,8,9, Leomar Y Ballester10,11,12. 1. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center At Houston, Houston, TX, 77030, USA. 2. Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center At Houston, Houston, TX, 77030, USA. 3. Rice University, Houston, TX, 77030, USA. 4. Memorial Hermann Hospital-TMC, Houston, TX, 77030, USA. 5. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA. 6. Department of Radiology, Stanford University School of Medicine, Stanford, CA, 94305, USA. 7. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center At Houston, Houston, TX, 77030, USA. Yoshua.EsquenaziLevy@uth.tmc.edu. 8. Memorial Hermann Hospital-TMC, Houston, TX, 77030, USA. Yoshua.EsquenaziLevy@uth.tmc.edu. 9. Center for Precision Health, The University of Texas Health Science Center at Houston - McGovern Medical School, 6400 Fannin Street, Suite # 2800, Houston, TX, 77030, USA. Yoshua.EsquenaziLevy@uth.tmc.edu. 10. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center At Houston, Houston, TX, 77030, USA. Leomar.Y.Ballester@uth.tmc.edu. 11. Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center At Houston, Houston, TX, 77030, USA. Leomar.Y.Ballester@uth.tmc.edu. 12. Memorial Hermann Hospital-TMC, Houston, TX, 77030, USA. Leomar.Y.Ballester@uth.tmc.edu.
Abstract
INTRODUCTION: Optimal treatment for recurrent glioblastoma isocitrate dehydrogenase 1 and 2 wild-type (rGBM IDH-WT) is not standardized, resulting in multiple therapeutic approaches. A phase III clinical trial showed that tumor treating fields (TTFields) monotherapy provided comparable survival benefits to physician's chemotherapy choice in rGBM. However, patients did not equally benefit from TTFields, highlighting the importance of identifying predictive biomarkers of TTFields efficacy. METHODS: A retrospective review of an institutional database with 530 patients with infiltrating gliomas was performed. Patients with IDH-WT rGBM receiving TTFields at first recurrence were included. Tumors were evaluated by next-generation sequencing for mutations in 205 cancer-related genes. Post-progression survival (PPS) was examined using the log-rank test and multivariate Cox-regression analysis. RESULTS: 149 rGBM patients were identified of which 29 (19%) were treated with TTFields. No significant difference in median PPS was observed between rGBM patients who received versus did not receive TTFields (13.9 versus 10.9 months, p = 0.068). However, within the TTFields-treated group (n = 29), PPS was improved in PTEN-mutant (n = 14) versus PTEN-WT (n = 15) rGBM, (22.2 versus 11.6 months, p = 0.017). Within the PTEN-mutant group (n = 70, 47%), patients treated with TTFields (n = 14) had longer median PPS (22.2 versus 9.3 months, p = 0.005). No PPS benefit was observed in PTEN-WT patients receiving TTFields (n = 79, 53%). CONCLUSIONS: TTFields therapy conferred a significant PPS benefit in PTEN-mutant rGBM. Understanding the molecular mechanisms underpinning the differences in response to TTFields therapy could help elucidate the mechanism of action of TTFields and identify the rGBM patients most likely to benefit from this therapeutic option.
INTRODUCTION: Optimal treatment for recurrent glioblastoma isocitrate dehydrogenase 1 and 2 wild-type (rGBM IDH-WT) is not standardized, resulting in multiple therapeutic approaches. A phase III clinical trial showed that tumor treating fields (TTFields) monotherapy provided comparable survival benefits to physician's chemotherapy choice in rGBM. However, patients did not equally benefit from TTFields, highlighting the importance of identifying predictive biomarkers of TTFields efficacy. METHODS: A retrospective review of an institutional database with 530 patients with infiltrating gliomas was performed. Patients with IDH-WT rGBM receiving TTFields at first recurrence were included. Tumors were evaluated by next-generation sequencing for mutations in 205 cancer-related genes. Post-progression survival (PPS) was examined using the log-rank test and multivariate Cox-regression analysis. RESULTS: 149 rGBM patients were identified of which 29 (19%) were treated with TTFields. No significant difference in median PPS was observed between rGBM patients who received versus did not receive TTFields (13.9 versus 10.9 months, p = 0.068). However, within the TTFields-treated group (n = 29), PPS was improved in PTEN-mutant (n = 14) versus PTEN-WT (n = 15) rGBM, (22.2 versus 11.6 months, p = 0.017). Within the PTEN-mutant group (n = 70, 47%), patients treated with TTFields (n = 14) had longer median PPS (22.2 versus 9.3 months, p = 0.005). No PPS benefit was observed in PTEN-WT patients receiving TTFields (n = 79, 53%). CONCLUSIONS: TTFields therapy conferred a significant PPS benefit in PTEN-mutant rGBM. Understanding the molecular mechanisms underpinning the differences in response to TTFields therapy could help elucidate the mechanism of action of TTFields and identify the rGBM patients most likely to benefit from this therapeutic option.
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