title: Early post-bevacizumab progression on contrast-enhanced MRI as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 Central Reader Study.
abstract: BACKGROUND
  RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS).
  
  
  METHODS
  Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI. Two central neuroradiologists serially measured bidimensional (2D) and volumetric (3D) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity. Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria, with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing. For each MRI pulse sequence, Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression.
  
  
  RESULTS
  Radiologic progression occurred after 2 chemotherapy cycles (8 weeks) in 9 of 97 (9%), 9 of 73 (12%), and 11 of 98 (11%) 2D-T1, 3D-T1, and FLAIR cases, respectively, and 34 of 80 (43%), 21 of 58 (36%), and 37 of 79 (47%) corresponding cases after 4 cycles (16 weeks). Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors, as determined on 2D-T1 (114 vs 278 days and 214 vs 426 days, respectively; P < .0001 for both) and 3D-T1 (117 vs 306 days [P < .0001] and 223 vs 448 days [P = .0003], respectively) but not on FLAIR (201 vs 276 days [P = .38] and 303 vs 321 days [P = .13], respectively).
  
  
  CONCLUSIONS
  Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM.
authors.affiliation: Rhode Island Hospital, Department of Diagnostic Imaging, 593 Eddy St., Providence, RI 02903, USA. jboxerman@lifespan.org
authors.forename: Jerrold L
authors.initials: JL
authors.lastname: Boxerman
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yair
authors.initials: Y
authors.lastname: Safriel
authors.forename: Mykol
authors.initials: M
authors.lastname: Larvie
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Snyder
authors.forename: Rajan
authors.initials: R
authors.lastname: Jain
authors.forename: T Linda
authors.initials: TL
authors.lastname: Chi
authors.forename: A Gregory
authors.initials: AG
authors.lastname: Sorensen
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Barboriak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003287:Contrast Media; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D000077146:Irinotecan; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D003287:Contrast Media; D000068258:Bevacizumab; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide
keywords: bevacizumab and irinotecan; imaging biomarker; overall survival; progression; recurrent glioblastoma