Benefit from procarbazine, lomustine and vincristine in oligodendroglial tumors is associated with mutation of IDH Journal Article
| Authors: | 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. Jr |
| Article Title: | Benefit from procarbazine, lomustine and vincristine in oligodendroglial tumors is associated with mutation of IDH |
| 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. © 2014 by American Society of Clinical Oncology. |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; cancer survival; controlled study; treatment outcome; disease-free survival; middle aged; cancer surgery; survival rate; gene mutation; major clinical study; overall survival; gene deletion; genetics; mutation; disease course; mortality; patient selection; cancer radiotherapy; disease free survival; brain tumor; follow up; brain neoplasms; antineoplastic agent; metabolism; allele; progression free survival; controlled clinical trial; randomized controlled trial; antineoplastic combined chemotherapy protocols; proportional hazards models; genetic association; gene frequency; odds ratio; risk factors; vincristine; enzymology; pathology; heterozygote; wild type; risk factor; lomustine; procarbazine; time; time factors; age; risk; proportional hazards model; disease progression; chi-square distribution; oligodendroglioma; therapy effect; multivariate analysis; kaplan meier method; genetic risk; astrocytoma; polymorphism, genetic; chemoradiotherapy; genetic polymorphism; personalized medicine; chi square distribution; isocitrate dehydrogenase; isocitrate dehydrogenase 1; kaplan-meier estimate; individualized medicine; long term survival; isocitrate dehydrogenase 2; humans; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 32 |
| Issue: | 8 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2014-03-01 |
| Start Page: | 783 |
| End Page: | 790 |
| Language: | English |
| DOI: | 10.1200/jco.2013.49.3726 |
| PUBMED: | 24516018 |
| PROVIDER: | scopus |
| PMCID: | PMC3940537 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):10 -- Export Date: 12 September 2014 -- CODEN: JCOND -- Source: Scopus |
