title: 3'-deoxy-3'-18F-fluorothymidine PET and MRI for early survival predictions in patients with recurrent malignant glioma treated with bevacizumab.
abstract: With the dismal prognosis for malignant glioma patients, survival predictions become key elements in patient management. This study compares the value of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and MRI for early outcome predictions in patients with recurrent malignant glioma on bevacizumab therapy.
  
  
  METHODS
  Thirty patients treated with bevacizumab combination therapy underwent (18)F-FLT PET immediately before and at 2 and 6 wk after the start of treatment. A metabolic treatment response was defined as a decrease of equal to or greater than 25% in tumor (18)F-FLT uptake (standardized uptake values) from baseline using receiver-operating-characteristic analysis. MRI treatment response was assessed at 6 wk according to the Response Assessment in Neurooncology criteria. (18)F-FLT responses at different times were compared with MRI response and correlated with progression-free survival and overall survival using Kaplan-Meier analysis. Metabolic response based on (18)F-FLT was further compared with other outcome predictors using Cox regression analysis.
  
  
  RESULTS
  Early and late changes in tumor (18)F-FLT uptake were more predictive of overall survival than MRI criteria (P < 0.001 and P = 0.01, respectively). (18)F-FLT uptake changes were also predictive of progression-free survival (P < 0.001). The median overall survival for responders was 3.3 times longer than for nonresponders based on (18)F-FLT PET criteria (12.5 vs. 3.8 mo, P < 0.001) but only 1.4 times longer using MRI assessment (12.9 vs. 9.0 mo, P = 0.05). On the basis of the 6-wk (18)F-FLT PET response, there were 16 responders (53%) and 14 nonresponders (47%), whereas MRI identified 9 responders (7 partial response, 2 complete response, 31%) and 20 nonresponders (13 stable disease, 7 progressive disease, 69%). In 7 of the 8 discrepant cases between MRI and PET, (18)F-FLT PET was able to demonstrate response earlier than MRI. Among various outcome predictors, multivariate analysis identified (18)F-FLT PET changes at 6 wk as the strongest independent survival predictor (P < 0.001; hazard ratio, 10.051).
  
  
  CONCLUSIONS
  Changes in tumor (18)F-FLT uptake were highly predictive of progression-free and overall survival in patients with recurrent malignant glioma on bevacizumab therapy. (18)F-FLT PET seems to be more predictive than MRI for early treatment response.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90005-6942, USA.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwarzenberg
authors.forename: Johannes
authors.initials: J
authors.lastname: Czernin
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
authors.forename: Whitney B
authors.initials: WB
authors.lastname: Pope
authors.forename: Cheri
authors.initials: C
authors.lastname: Geist
authors.forename: Magnus
authors.initials: M
authors.lastname: Dahlbom
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Silverman
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001692:Biological Transport; D015224:Dideoxynucleosides / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015224:Dideoxynucleosides; D000068258:Bevacizumab; C002854:alovudine