title: Early toxicity predicts long-term survival in high-grade glioma.
abstract: BACKGROUND
  Patients with high-grade gliomas are treated with surgery followed by chemoradiation. The risk factors and implications of neurological side effects are not known.
  
  
  METHODS
  Acute and late ≥ grade 3 neurological toxicities (NTs) were analysed among 2761 patients from 14 RTOG trials accrued from 1983 to 2003. The association between acute and late toxicity was analysed using a stepwise logistic regression model. The association between the occurrence of acute NT and survival was analysed as an independent variable.
  
  
  RESULTS
  There were 2610 analysable patients (86% glioblastoma, 10% anaplastic astrocytoma). All received a systemic agent during radiation (83% chemotherapy, 17% biological agents). Median radiation dose was 60 Gy. There were 182 acute and 83 late NT events. On univariate analysis, older age, poor performance status, aggressive surgery, pre-existing neurological dysfunction, poor mental status and twice-daily radiation were associated with increased acute NT. In a stepwise logistic regression model the occurrence of acute NT was significantly associated with late NT (OR=2.40; 95% CI=1.2-4.8; P=0.014). The occurrence of acute NT predicted poorer overall survival, independent of recursive partitioning analysis class (median 7.8 vs 11.8 months).
  
  
  CONCLUSIONS
  Acute NT is significantly associated with both late NT and overall survival.
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Kimmel Cancer Center, Bodine Cancer Center, 111 S. 11th Street, Philadelphia, PA 19107, USA. yaacov.lawrence@sheba.health.gov.il
authors.forename: Y R
authors.initials: YR
authors.lastname: Lawrence
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: A P
authors.initials: AP
authors.lastname: Dicker
authors.forename: D
authors.initials: D
authors.lastname: Andrews
authors.forename: W J
authors.initials: WJ
authors.lastname: Curran
authors.forename: J M
authors.initials: JM
authors.lastname: Michalski
authors.forename: L
authors.initials: L
authors.lastname: Souhami
authors.forename: W-Ka
authors.initials: WK
authors.lastname: Yung
authors.forename: M
authors.initials: M
authors.lastname: Mehta
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D015173:Supratentorial Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016019:Survival Analysis; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide