title: Phase 2 study of temozolomide-based chemoradiation therapy for high-risk low-grade gliomas: preliminary results of Radiation Therapy Oncology Group 0424.
abstract: OBJECTIVE
  Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power.
  
  
  METHODS
  Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ.
  
  
  RESULTS
  From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis.
  
  
  CONCLUSIONS
  The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.
authors: London Regional Cancer Program, London, Ontario, Canada. Electronic address: barbara.fisher@lhsc.on.ca.
authors: Barbara J
authors: BJ
authors: Fisher
authors: Radiation Therapy Oncology Group-Statistical Center, Philadelphia, Pennsylvania.
authors: Chen
authors: C
authors: Hu
authors: London Regional Cancer Program, London, Ontario, Canada.
authors: David R
authors: DR
authors: Macdonald
authors: Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina.
authors: Glenn J
authors: GJ
authors: Lesser
authors: Barrow Neurological Institute, Phoenix, Arizona.
authors: Stephen W
authors: SW
authors: Coons
authors: Arizona Oncology Services Foundation, Phoenix, Arizona.
authors: David G
authors: DG
authors: Brachman
authors: Henry Ford Hospital, Detroit, Michigan.
authors: Samuel
authors: S
authors: Ryu
authors: Thomas Jefferson University Hospital Center, Philadelphia, Pennsylvania.
authors: Maria
authors: M
authors: Werner-Wasik
authors: Centre Hospitalier de l'Université de Montréal-Notre Dame, Montreal, Quebec, Canada.
authors: Jean-Paul
authors: JP
authors: Bahary
authors: GCE Solutions, Inc., Bloomington, Illinois.
authors: Junfeng
authors: J
authors: Liu
authors: The Ohio State University, The James, Columbus, Ohio.
authors: Arnab
authors: A
authors: Chakravarti
authors: University of Maryland Medical Systems, Baltimore, Maryland.
authors: Minesh
authors: M
authors: Mehta
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020266:Radiotherapy, Conformal / Q000379:methods; D012107:Research Design; D012307:Risk Factors; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide