title: Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival.
abstract: OBJECTIVE
  To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases.
  
  
  METHODS
  Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months.
  
  
  RESULTS
  Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival.
  
  
  CONCLUSIONS
  The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.
authors.affiliation: Department of Radiation Oncology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA. bstea@azcc.arizona.edu
authors.forename: Baldassarre
authors.initials: B
authors.lastname: Stea
authors.forename: John H
authors.initials: JH
authors.lastname: Suh
authors.forename: Adam P
authors.initials: AP
authors.lastname: Boyd
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Cagnoni
authors.forename: Edward
authors.initials: E
authors.lastname: Shaw
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary*; D016371:Cranial Irradiation / Q000379:methods*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010100:Oxygen / Q000008:administration & dosage; D011422:Propionates / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000814:Aniline Compounds; D011422:Propionates; D011838:Radiation-Sensitizing Agents; C067396:efaproxiral; D010100:Oxygen