Benefit from procarbazine, lomustine and vincristine in oligodendroglial tumors is associated with mutation of IDH

J. Gregory Cairncross, Meihua Wang, Robert B. Jenkins, Edward G. Shaw, Caterina Giannini, David G. Brachman, Jan C. Buckner, Karen L. Fink, Luis Souhami, Normand J. Laperriere, Jason T. Huse, Minesh P. Mehta, Walter J. Curran

Research output: Contribution to journalArticle

245 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)783-790
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number8
DOIs
StatePublished - Mar 10 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cairncross, J. G., Wang, M., Jenkins, R. B., Shaw, E. G., Giannini, C., Brachman, D. G., Buckner, J. C., Fink, K. L., Souhami, L., Laperriere, N. J., Huse, J. T., Mehta, M. P., & Curran, W. J. (2014). Benefit from procarbazine, lomustine and vincristine in oligodendroglial tumors is associated with mutation of IDH. Journal of Clinical Oncology, 32(8), 783-790. https://doi.org/10.1200/JCO.2013.49.3726