Response assessment in recurrent glioblastoma treated with irinotecan-bevacizumab: comparative analysis of the Macdonald, RECIST, RANO, and RECIST + F criteria

Abstract

Traditionally, the most widely used criteria for response assessment in glioblastoma have been Macdonald and the Response Evaluation Criteria In Solid Tumors (RECIST). Recently, new criteria addressing contrast enhancement and fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity have been defined (the Response Assessment in Neuro-Oncology criteria) to better evaluate the effect of antiangiogenic therapy. Whether FLAIR/T2 imaging could also be helpful to refine RECIST criteria remains unresolved. This study proposed the RECIST + F criteria and compared the 4 methods (Macdonald, RECIST, RANO, and RECIST + F) to determine their agreement in identifying response and progression of recurrent glioblastomas to irinotecan-bevacizumab. Patients with recurrent glioblastoma treated with second-line irinotecan-bevacizumab were eligible. Clinical status, corticosteroid dose, and 1-dimensional and 2-dimensional measurements of tumor contrast enhancement and FLAIR hyperintensity were retrospectively assessed. Response and progression were determined according to each set of criteria. Seventy-eight patients were included. Response rates ranged from 34.2% with RECIST + F to 44.7% with Macdonald criteria. Agreement among the 4 methods in determining response and type of progression was high (kappa statistic > 0.75). One-third of patients exhibited nonenhancing progression with stable or improved contrast enhancement. Median progression-free survival was predicted by RECIST, at 13.6 weeks; RECIST + F, 12.3; Macdonald, 12.7; and RANO, 11.7 (P = .840). Intra- and interobserver correlations were high for both contrast enhancement and FLAIR hyperintensity measurements. There was a strong concordance among the different methods in determining response and progression to irinotecan-bevacizumab. Criteria integrating FLAIR hyperintensity tended, however, to reduce response rates and progression-free survival compared with criteria considering only contrast enhancement. The 1-dimensional approach appeared to be as valid as the 2-dimensional approach.

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

“…2). A prior, single-institution retrospective study by Perez-Larraya and colleagues assessing 78 patients with recurrent glioblastoma treated by bevacizumab did not observe a significant difference in PFS between the two criteria, although the use of RANO trended towards a shorter PFS (19). The value of earlier detection of nonenhancing radiographic progression needs to be evaluated in the context of residual survival benefit.…”

Clinical Impact of Bevacizumab in Patients with Relapsed Glioblastoma: Focus on a Real-Life Monocentric SurVey (SV1 Study)

“…MRI partially evaluates tumor infiltration, especially if neoangiogenesis is not widely developed. It remains important to perform MRI T2 FLAIR sequences, using both RECIST and RANO criteria, to assess as accurately as possible responses to treatment with BVZ [22]. To date, no biological marker can identify long-term responders to BVZ.…”

Imaging of the Posttherapeutic Brain

“…27 In up to 40% of cases, nonenhancing tumor progression, better appreciated with T2/fluid attenuation inversion recovery (FLAIR) images, may precede the appearance of eventual recurrent contrast-enhancing tumor. [28][29][30][31] However, it remains unclear how to incorporate quantitative assessments of these T2/FLAIR changes into determinations of disease progression. 9,13,32 Multiple studies have shown that although antiangiogenic agents seemed to demonstrate prolonged PFS in patients with recurrent GBM, there seemed to be no significant OS benefit.…”