NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients

• Type of Material: Article
• Authors: Arif Ali, Emory University; Peixin Zhang, NRG Oncology Statistics and Data Management Center; W.K. Alfred Yung, University of Texas MD Anderson Cancer Center; Yuhchyau Chen, University of Rochester; Benjamin Movsas, Henry Ford Hospital; Raul C. Urtasun, Cross Cancer Institute; Christopher U. Jones, Sutter General Hospital; Kwang N. Choi, Suny Downstate Medical Center; Jeff M. Michalski, Washington University; A. Jennifer Fischbach, LDS Hospital; Arnold M. Markoe, University of Miami; Christopher J. Schultz, Froedtert; Marta Penas-Prado, University of Texas MD Anderson Cancer Center; Madhur K. Garg, Montefiore Medical Center; Alan C. Hartford, Dartmouth Hitchcock Medical Center; Harold E. Kim, Wayne State University; Minhee Won, NRG Oncology Statistics and Data Management Center; Walter J Curran, Emory University
• Language: English
• Date: 2018-03-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, Springer Science+Business Media, LLC.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11060-017-2558-x
• Title of Journal or Parent Work: Journal of Neuro-Oncology
• ISSN: 0167-594X
• Volume: 137
• Issue: 1
• Start Page: 39
• End Page: 47
• Grant/Funding Information: This study was supported by grants U10CA21661 (RTOG-Ops-Stat), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U10CA37422 (CCOP), from the National Cancer Institute (NCI).
• Keywords: RADIATION-THERAPY; FRACTIONATION; SURVIVAL; Oncology; GLIOBLASTOMA; Life Sciences & Biomedicine; Clinical Neurology; Science & Technology; Hyperfractionated; RECURSIVE PARTITIONING ANALYSIS; Glioma; Oligodendroglioma; Astrocytoma; GBM; Neurosciences & Neurology; CARMUSTINE
• Research Categories: Health Sciences, Oncology; Biology, Neuroscience; Biology, Radiation

Abstract

From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m 2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1–3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity. Out of the 712 patients accrued, 694 (97.5%) were analyzable cases (350 HFX, 344 standard arm). There was no significant difference between the arms on overall acute or late treatment-related toxicity. No statistically significant effect for HFX, as compared to standard therapy, was found on either OS, with a median survival time (MST) of 11.3 versus 13.1 months (p = 0.20) or PFS, with a median PFS time of 5.7 versus 6.9 months (p = 0.18). The treatment effect on OS remained insignificant based on the multivariate analysis (hazard ratio 1.16; p = 0.0682). When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme (MST: 10.3 vs. 11.2 months; p = 0.34), anaplastic astrocytoma (MST: 69.8 vs. 50.0 months; p = 0.91) or anaplastic oligodendroglioma (MST: 92.1 vs. 66.5 months; p = 0.33). Though this trial provided many invaluable secondary analyses, there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients.