title: Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study.
abstract: OBJECTIVE
  Evaluation of treatment effects in malignant brain tumors is challenging because of the lack of reliable response predictors of tumor response. This study examines the predictive value of positron emission tomography (PET) using [18F] fluorothymidine (FLT), an imaging biomarker of cell proliferation, in patients with recurrent malignant gliomas treated with bevacizumab in combination with irinotecan.
  
  
  METHODS
  Patients with recurrent malignant gliomas treated with biweekly cycles of bevacizumab and irinotecan were prospectively studied with FLT-PET at baseline, after 1 to 2 weeks, and after 6 weeks from start of treatment. A more than 25% reduction in tumor FLT uptake as measured by standardized uptake value was defined as a metabolic response. FLT responses were compared with response as shown by magnetic resonance imaging (MRI) and patient survival.
  
  
  RESULTS
  Twenty-one patients were included, and 19 were assessable for metabolic response evaluation with FLT-PET. There were nine responders (47%) and 10 nonresponders (53%). Metabolic responders survived three times as long as nonresponders (10.8 v 3.4 months; P = .003), and tended to have a prolonged progression-free survival (P = .061). Both early and later FLT-PET responses were more significant predictors of overall survival (1 to 2 weeks, P = .006; 6 weeks, P = .002), compared with the MRI responses (P = .060 for both 6-week and best responses).
  
  
  CONCLUSIONS
  FLT-PET as an imaging biomarker seems to be predictive of overall survival in bevacizumab and irinotecan treatment of recurrent gliomas. Whether FLT-PET performed as early as 1 to 2 week after starting treatment is as predictive as the study indicates at 6 weeks warrants further investigation.
authors.affiliation: Ahmanson Biological Imaging Division and the Department of Molecular and Medical Pharmacology, Biostatistics, Radiology,University of California, Los Angeles, Los Angeles, CA 90005-6942, USA. weichen@mednet.ucla.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Sibylle
authors.initials: S
authors.lastname: Delaloye
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Silverman
authors.forename: Cheri
authors.initials: C
authors.lastname: Geist
authors.forename: Johannes
authors.initials: J
authors.lastname: Czernin
authors.forename: James
authors.initials: J
authors.lastname: Sayre
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Whitney
authors.initials: W
authors.lastname: Pope
authors.forename: Albert
authors.initials: A
authors.lastname: Lai
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D049109:Cell Proliferation; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005910:Glioma / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009367:Neoplasm Staging; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015996:Survival Rate; D013936:Thymidine / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D000068258:Bevacizumab; D000077146:Irinotecan; D013936:Thymidine; D002166:Camptothecin