title: Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: J. Gregory Cairncross, University of Calgary, Calgary, Alberta; Luis Souhami, McGill University, Montreal, Quebec; Normand J. Laperriere, University of Toronto, Toronto, Ontario, Canada; Meihua Wang, American College of Radiology, Philadelphia, PA; Robert B. Jenkins, Caterina Giannini, and Jan C. Buckner, Mayo Clinic, Rochester, MN; Edward G. Shaw, Wake Forest School of Medicine, Winston-Salem, NC; David G. Brachman, Arizona Oncology Services Foundation/Barrow Neurological Institute, Phoenix, AZ; Karen L. Fink, Baylor University, Dallas, TX; Jason T. Huse, Memorial Sloan-Kettering Cancer Center, New York, NY; Minesh P. Mehta, Northwestern University, Chicago, IL; and Walter J. Curran Jr, Emory University, Atlanta, GA.
authors: J Gregory
authors: JG
authors: Cairncross
authors: Meihua
authors: M
authors: Wang
authors: Robert B
authors: RB
authors: Jenkins
authors: Edward G
authors: EG
authors: Shaw
authors: Caterina
authors: C
authors: Giannini
authors: David G
authors: DG
authors: Brachman
authors: Jan C
authors: JC
authors: Buckner
authors: Karen L
authors: KL
authors: Fink
authors: Luis
authors: L
authors: Souhami
authors: Normand J
authors: NJ
authors: Laperriere
authors: Jason T
authors: JT
authors: Huse
authors: Minesh P
authors: MP
authors: Mehta
authors: Walter J
authors: WJ
authors: Curran
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D016009:Chi-Square Distribution; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D009837:Oligodendroglioma / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018579:Patient Selection; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D011344:Procarbazine / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine; D007521:Isocitrate Dehydrogenase