Evaluation of RANO response criteria compared to clinician evaluation in WHO grade III anaplastic astrocytoma: implications for clinical trial reporting and patterns of failure.

The utility of current response criteria has not been established in anaplastic astrocytoma (AA). We retrospectively reviewed MR images for 20 patients with AA and compared RANO-based approaches to clinician impression described as follow: (1) standard RANO-based criteria met by growth of or development of new enhancing lesion (RANO-C), (2) RANO criteria for progression based on significant FLAIR increase (RANO-F) and (3) clinical progression usually resulting in change of treatment (Clinical). Patterns of failure (POF) were analyzed utilizing all proposed progression MRIs fused with the patients' radiotherapy treatment plan. With an overall median survival of 24.3 months, development of new enhancing lesion was the most common determinant of progression (70 % of patients). Median time to RANO-C, RANO-F and Clinical progression was 9.2, 9.2 and 11.76 months respectively. RANO-C and RANO-F preceded Clinical in 70 and 55 % of patients, respectively. In six patients (30 %) Clinical was concurrent with RANO-F; four of six also met RANO-C. POF for FLAIR component differed based on time point used to determine progression. FLAIR POF was more often marginal or distant when progression was defined clinically compared to either RANO-C or RANO-F criteria. Central POF based on FLAIR at Clinical determination of progression was associated with significantly poorer OS (9.8 vs. 34.4 months). Clinical progression occurs later than progression determined by RANO-based criteria. Evaluation of POF based on FLAIR signal abnormality at the time of clinical progression suggests central recurrences are associated with worse survival.