Jeffrey S Wefel1, Terri S Armstrong2, Stephanie L Pugh3, Mark R Gilbert4, Merideth M Wendland5, David G Brachman6, Kevin S Roof7, Paul D Brown8, Ian R Crocker9, H Ian Robins10, Grant Hunter11, Minhee Won3, Minesh P Mehta12. 1. Department of Neuro-Oncology and Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 2. Neuro-Oncology Branch, University of Texas Health Science Center, Houston, Texas, USA. 3. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA. 4. Neuro-Oncology Branch, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 5. Radiation Oncology, USON-Willamette Valley Cancer Institute, Eugene, Oregon, USA. 6. Department of Radiation Oncology, Arizona Oncology Services Foundation, Phoenix, Arizona, USA. 7. Department of Radiation Oncology, Southeast Cancer Control Consortium, CCOP, Winston-Salem, North Carolina, USA. 8. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 9. Department of Radiation Oncology, Emory University, Atlanta, Georgia, USA. 10. Departments of Medicine and Human Oncology, University of Wisconsin Hospital, Madison, Wisconsin, USA. 11. Department of Radiation Oncology, Intermountain Medical Center, Murray, Utah, USA. 12. Department of Radiation Oncology, University of Maryland, Baltimore, Maryland, USA.
Abstract
BACKGROUND: Results of NRG Oncology RTOG 0825 reported adding bevacizumab to standard chemoradiation did not significantly improve survival endpoints and resulted in greater decline in neurocognitive function (NCF) and patient-reported outcomes (PRO) over time in bevacizumab-treated patients. The present report provides additional results of patient-centered outcomes over time and their prognostic association with survival endpoints. METHODS: NCF tests, MD Anderson Symptom Inventory - Brain Tumor Module (MDASI-BT), and European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) questionnaire with brain cancer module (QLQ-C30/BN20) were completed in a subset of progression-free patients at baseline and longitudinally. The prognostic value of baseline and early changes in NCF and PROs and differences between treatments from baseline to follow-up assessments were evaluated. RESULTS: A total of 508 randomized patients participated. Baseline/early changes in NCF and PROs were prognostic for OS and PFS. No between-arm differences in time to deterioration were found. At week 6, patients treated with bevacizumab evidenced greater improvement on NCF tests of executive function and the MDASI-BT Cognitive Function scale, but simultaneously reported greater decline on the EORTC Cognitive Function Scale. At later time points (weeks 22, 34, and 46), patients treated with bevacizumab had greater worsening on NCF tests as well as PRO measures of cognitive, communication, social function, motor symptoms, general symptoms, and interference. CONCLUSION: The collection of patient-centered clinical outcome assessments in this phase III trial revealed greater deterioration in NCF, symptoms, and QOL in patients treated with bevacizumab. Baseline and early change in NCF and PROs were prognostic for survival endpoints.
BACKGROUND: Results of NRG Oncology RTOG 0825 reported adding bevacizumab to standard chemoradiation did not significantly improve survival endpoints and resulted in greater decline in neurocognitive function (NCF) and patient-reported outcomes (PRO) over time in bevacizumab-treated patients. The present report provides additional results of patient-centered outcomes over time and their prognostic association with survival endpoints. METHODS: NCF tests, MD Anderson Symptom Inventory - Brain Tumor Module (MDASI-BT), and European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) questionnaire with brain cancer module (QLQ-C30/BN20) were completed in a subset of progression-free patients at baseline and longitudinally. The prognostic value of baseline and early changes in NCF and PROs and differences between treatments from baseline to follow-up assessments were evaluated. RESULTS: A total of 508 randomized patients participated. Baseline/early changes in NCF and PROs were prognostic for OS and PFS. No between-arm differences in time to deterioration were found. At week 6, patients treated with bevacizumab evidenced greater improvement on NCF tests of executive function and the MDASI-BT Cognitive Function scale, but simultaneously reported greater decline on the EORTC Cognitive Function Scale. At later time points (weeks 22, 34, and 46), patients treated with bevacizumab had greater worsening on NCF tests as well as PRO measures of cognitive, communication, social function, motor symptoms, general symptoms, and interference. CONCLUSION: The collection of patient-centered clinical outcome assessments in this phase III trial revealed greater deterioration in NCF, symptoms, and QOL in patients treated with bevacizumab. Baseline and early change in NCF and PROs were prognostic for survival endpoints.
Authors: Jeffrey S Wefel; Timothy Cloughesy; James L Zazzali; Maoxia Zheng; Michael Prados; Patrick Y Wen; Tom Mikkelsen; David Schiff; Lauren E Abrey; W K Alfred Yung; Nina Paleologos; Martin K Nicholas; Randy Jensen; James Vredenburgh; Asha Das; Henry S Friedman Journal: Neuro Oncol Date: 2011-05-09 Impact factor: 12.300
Authors: T S Armstrong; T Mendoza; I Gning; I Gring; C Coco; M Z Cohen; L Eriksen; Ming-Ann Hsu; M R Gilbert; C Cleeland Journal: J Neurooncol Date: 2006-04-06 Impact factor: 4.130
Authors: J Maringwa; C Quinten; M King; J Ringash; D Osoba; C Coens; F Martinelli; B B Reeve; C Gotay; E Greimel; H Flechtner; C S Cleeland; J Schmucker-Von Koch; J Weis; M J Van Den Bent; R Stupp; M J Taphoorn; A Bottomley Journal: Ann Oncol Date: 2011-02-15 Impact factor: 32.976
Authors: Mark R Gilbert; James J Dignam; Terri S Armstrong; Jeffrey S Wefel; Deborah T Blumenthal; Michael A Vogelbaum; Howard Colman; Arnab Chakravarti; Stephanie Pugh; Minhee Won; Robert Jeraj; Paul D Brown; Kurt A Jaeckle; David Schiff; Volker W Stieber; David G Brachman; Maria Werner-Wasik; Ivo W Tremont-Lukats; Erik P Sulman; Kenneth D Aldape; Walter J Curran; Minesh P Mehta Journal: N Engl J Med Date: 2014-02-20 Impact factor: 91.245
Authors: Teri N Kreisl; Lyndon Kim; Kraig Moore; Paul Duic; Cheryl Royce; Irene Stroud; Nancy Garren; Megan Mackey; John A Butman; Kevin Camphausen; John Park; Paul S Albert; Howard A Fine Journal: J Clin Oncol Date: 2008-12-29 Impact factor: 44.544
Authors: Henry S Friedman; Michael D Prados; Patrick Y Wen; Tom Mikkelsen; David Schiff; Lauren E Abrey; W K Alfred Yung; Nina Paleologos; Martin K Nicholas; Randy Jensen; James Vredenburgh; Jane Huang; Maoxia Zheng; Timothy Cloughesy Journal: J Clin Oncol Date: 2009-08-31 Impact factor: 44.544