Paul D Brown1, Caroline Chung2, Diane D Liu3, Sarah McAvoy4, David Grosshans2, Karine Al Feghali2, Anita Mahajan1,2, Jing Li2, Susan L McGovern2, Mary-Fran McAleer2, Amol J Ghia2, Erik P Sulman5, Marta Penas-Prado6, John F de Groot7, Amy B Heimberger8, Jihong Wang9, Terri S Armstrong6, Mark R Gilbert6, Nandita Guha-Thakurta10, Jeffrey S Wefel7. 1. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA. 2. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Department of Radiation Oncology, University of Maryland, Baltimore, Maryland, USA. 5. Department of Radiation Oncology, NYU Grossman School of Medicine, New York, New York, USA. 6. Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 7. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 8. Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 9. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 10. Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Abstract
BACKGROUND: To determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM). METHODS: Eligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs). RESULTS: A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02). CONCLUSIONS: In this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time.
BACKGROUND: To determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM). METHODS: Eligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs). RESULTS: A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02). CONCLUSIONS: In this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time.
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