title: Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan.
abstract: BACKGROUND
  Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan.
  
  
  METHODS
  A total of 219 recurrent GBM patients treated with BEV plus irinotecan according to a previously published treatment protocol were included in the initial population. Prognostic models were generated by means of multivariate logistic and Cox regression analysis.
  
  
  RESULTS
  In multivariate analysis, corticosteroid use had a negative predictive impact on response at first evaluation (OR 0.45; 95% CI 0.22-0.93; p = 0.03) and at best response (OR 0.51; 95% CI 0.26-1.02; p = 0.056). Three significant (p < 0.05) prognostic factors associated with reduced progression-free survival and overall survival (OS) were identified. These factors were included in the final model for OS, namely corticosteroid use (HR 1.70; 95% CI 1.18-2.45; p = 0.004), neurocognitive deficit (HR 1.40; 95% CI 1.04-1.89; p = 0.03) and multifocal disease (HR 1.56; 95% CI 1.15-2.11; p < 0.0001). Based on these results a prognostic index able to calculate the probability for OS at 6 and 12 months for the individual patient was established. The predictive value of the model for OS was validated in a separate patient cohort of 85 patients.
  
  
  CONCLUSIONS
  A prognostic model for OS was established and validated. This model can be used by physicians to risk stratify the individual patient and together with the patient decide whether to initiate BEV relapse treatment.
authors.affiliation: a Department of Radiation Biology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;|b Department of Oncology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Thomas
authors.initials: T
authors.lastname: Urup
authors.affiliation: c Department of Oncology , Odense University Hospital , Odense , Denmark ;
authors.forename: Rikke Hedegaard
authors.initials: RH
authors.lastname: Dahlrot
authors.affiliation: a Department of Radiation Biology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;|b Department of Oncology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grunnet
authors.affiliation: d Laboratory of Gastroenterology , University of Copenhagen, Hvidovre Hospital , Copenhagen , Denmark ;
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: a Department of Radiation Biology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Signe Regner
authors.initials: SR
authors.lastname: Michaelsen
authors.affiliation: a Department of Radiation Biology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Anders
authors.initials: A
authors.lastname: Toft
authors.affiliation: e Department of Radiology , Center of Diagnostic Investigation, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Vibeke Andrée
authors.initials: VA
authors.lastname: Larsen
authors.affiliation: f Department of Neuropathology , Center of Diagnostic Investigation, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Helle
authors.initials: H
authors.lastname: Broholm
authors.affiliation: g Department of Neurosurgery , the Neurocenter, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Michael
authors.initials: M
authors.lastname: Kosteljanetz
authors.affiliation: c Department of Oncology , Odense University Hospital , Odense , Denmark ;
authors.forename: Steinbjørn
authors.initials: S
authors.lastname: Hansen
authors.affiliation: a Department of Radiation Biology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;|b Department of Oncology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;
authors.forename: Hans Skovgaard
authors.initials: HS
authors.lastname: Poulsen
authors.affiliation: a Department of Radiation Biology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;|b Department of Oncology , the Finsen Center, Rigshospitalet , Copenhagen , Denmark ;|h Phase I Unit, Finsencenter, Rigshospitalet , Copenhagen , Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lassen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin