William A Hall1, Stephanie L Pugh2, Jeffrey S Wefel3, Terri S Armstrong4, Mark R Gilbert5, David G Brachman6, Maria Werner-Wasik7, Merideth M Wendland8, Paul D Brown9, Samuel T Chao10, Kevin S Roof11, H Ian Robins12, Minesh P Mehta13, Walter J Curran14, Benjamin Movsas15. 1. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin and Clement J. Zablocki, VA, Medical Center, Milwaukee, Wisconsin. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. 3. Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. 4. Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 5. Center for Cancer Research, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 6. Department of Radiation Oncology, University of Arizona, St. Joseph's Hospital Medical Center and Barrow Neurological Institute, Phoenix, Arizona. 7. Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. 8. Department of Radiation Oncology, Willamette Valley Cancer Institute, Eugene, Oregon. 9. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. 10. Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio. 11. Department of Radiation Oncology, Southeast Cancer Control Consortium, Inc, CCOP, Winston Salem, NC, North Carolina. 12. Departments of Medicine, Human Oncology, and Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. 13. Miami Cancer Institute, Baptist Health, Kendall, Florida. 14. Winship Cancer Institute, Emory University, Atlanta, Georgia. 15. Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan.
Abstract
BACKGROUND: The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE: To examine these uncertainties. METHODS: NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan-Meier method. RESULTS: A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings (P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test-Revised Delayed Recognition [P = .048], Trail Making Test Part A [P = .035], and Controlled Oral Word Association [P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures. CONCLUSION: STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.
BACKGROUND: The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE: To examine these uncertainties. METHODS: NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan-Meier method. RESULTS: A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings (P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test-Revised Delayed Recognition [P = .048], Trail Making Test Part A [P = .035], and Controlled Oral Word Association [P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures. CONCLUSION: STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.
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