The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab

Clin Cancer Res. 2016 Feb 1;22(3):575-81. doi: 10.1158/1078-0432.CCR-14-3040. Epub 2015 Oct 21.

Abstract

Purpose: The RANO criteria have not been assessed using outcome data from prospective trials. We examined the radiologic data of patients with recurrent glioblastoma from the randomized phase II trial (AVF3708g) to determine the effect of including T2/FLAIR evaluation as per RANO criteria on measurements of objective response rates (ORRs) and progression-free survival (PFS) compared with assessment based on contrast enhancement (Macdonald criteria).

Experimental design: The ORRs and median PFS were determined using the RANO criteria and compared with those obtained using the Macdonald criteria. Landmark analyses were performed at 2, 4, and 6 months, and Cox proportional hazard models were used to determine the associations between OR and progression with subsequent survival.

Results: The ORRs were 0.331 [95% confidence interval (CI), 0.260-0.409] and 0.393 (95% CI, 0.317-0.472) by RANO and Macdonald criteria, respectively (P < 0.0001). The median PFS was 4.6 months (95% CI, 4.1-5.5) using RANO criteria, compared with 6.4 months (95% CI, 5.5-7.1) as determined by Macdonald criteria (P = 0.01). At 2-, 4-, and 6-month landmarks, both OR status and PFS determined by either RANO or Macdonald criteria were predictive of overall survival [OS; hazard ratios for 4-month landmark (OR HR = 1.93, P = 0.0012; PFS HR, 4.23, P < 0.0001)].

Conclusions: The inclusion of T2/FLAIR assessment resulted in statistically significant differences in median PFS and ORRs compared with assessment of solely enhancing tumor (Macdonald criteria), although OR and PFS determined by both RANO and Macdonald criteria correlated with OS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Clinical Trials, Phase II as Topic
  • Combined Modality Therapy
  • Female
  • Glioblastoma / diagnosis*
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Observer Variation
  • Randomized Controlled Trials as Topic
  • Retreatment
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Bevacizumab