Benefit From Procarbazine, Lomustine, and Vincristine in Oligodendroglial Tumors Is Associated With Mutation of IDH

• Type of Material: Article
• Authors: J. Gregory Cairncross, University of Calgary; Meihua Wang, American College of Radiology; Robert B. Jenkins, Mayo Clinic; Edward G. Shaw, Wake Forest University; Caterina Giannini, Mayo Clinic; David G. Brachman, Arizona Oncology Services Foundation; Jan C. Buckner, Mayo Clinic; Karen L. Fink, Baylor University; Luis Souhami, McGill University; Normand J. Laperriere, University of Toronto; Jason T. Huse, Memorial Sloan Kettering Cancer Center; Minesh P. Mehta, Northwestern University; Walter Curran Jr, Emory University
• Language: English
• Date: 2014-03-10
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2014 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2013.49.3726
• Title of Journal or Parent Work: Journal of Clinical Oncology
• Volume: 32
• Issue: 8
• Start Page: 783
• End Page: +
• Grant/Funding Information: Supported in part by National Cancer Institute Grants No. U10 CA21661 and U10 CA32115 to the Radiation Therapy Oncology Group, No. U10 CA25224 to the North Central Cancer Treatment Group, No. CA17145 and CA21115 to the Eastern Cooperative Oncology Group, No. CA32102 to the Southwest Oncology Group, and No. U10 CA37422 to the Community Clinical Oncology Program; by a Canadian Cancer Society grant to the National Cancer Institute of Canada Clinical Trials Group; National Institutes of Health Grants No. P50CA108961 and P30 CA15083; by National Institute of Neurological Disorders and Stroke Grant No. RC1NS068222Z; by a generous gift from Bernie and Edith Waterman; and by the Ting Tsung and Wei Fong Chao Family Foundation.
• Keywords: Oncology; Temozolomide; Follow up; Brain tumors; MGMT gene; Phase III trials; Science & Technology; Life Sciences & Biomedicine; Anaplastic oligodendroglioma; Successful chemotherapy; Adjuvant procarbazine; Survival; European organization
• Research Categories: Health Sciences, Rehabilitation and Therapy; Biology, Genetics; Health Sciences, Radiology; Health Sciences, Oncology

Abstract

Purpose: Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT. Patients and Methods: Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT. Results: IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT. Conclusion: IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.