Among 526 patients with newly diagnosed glioblastoma and 580 patients with recurrent glioblastoma, the correlation between progression-free survival (PFS) and overall survival (OS) was similar with the Response Assessment in Neuro-Oncology (RANO) and modified RANO criteria. The use of the postradiation magnetic resonance imaging (MRI) as baseline scan and the requirement for a confirmation scan in the first 12 weeks after completion of radiation in newly diagnosed glioblastoma were associated with a better correlation between PFS and OS. The evaluation of fluid-attenuated inversion recovery (FLAIR) sequences, however, did not improve the correlation. The immunotherapy RANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors. The findings are published by Dr. Patrick Y. Wen of the Center for Neuro-Oncology, Dana-Farber Cancer Institute in Boston, MA, US and colleagues on 7 April 2023 in the Journal of Clinical Oncology.
The authors wrote in the background that PFS and objective response rate have shown to be predictors of survival in glioblastoma, and are considered valuable endpoints in clinical studies. However, response assessment is challenging because of issues related to the irregular shape of tumours, differences in radiologic techniques, variability in tumour measurements, and treatment-related changes.
In 2010, the RANO criteria for high-grade gliomas was developed by a consensus of experts to update the original Macdonald criteria and account for challenges to response assessment such as pseudoprogression and pseudoresponse. Subsequent studies have suggested a limited benefit of incorporating T2/FLAIR evaluation on the correlation of PFS with OS. Moreover, some new therapies, particularly immunotherapies and viral therapies, are more likely to induce transient worsening of contrast enhancement that might lead to erroneous determination of radiographic disease progression. As a result, the modified RANO criteria were proposed in 2017, and differed from RANO by use of the postradiation scan as the baseline scan, omission of FLAIR evaluation, and requirement of a confirmation scan to determine progressive disease. The immunotherapy RANO criteria were established to address concerns specific to evaluating response to immunotherapies.
To evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update, the authors sought in this retrospective study to compare RANO and modified RANO criteria in a large patient population with newly diagnosed and recurrent IDH-wild-type glioblastoma. To better characterise their impact on correlation between PFS and OS, they examined specific components of the response assessment criteria, such as the identification of the appropriate baseline scan, need for a confirmation scan, and need to assess T2/FLAIR. In patients who received immunotherapy, they also evaluated whether PFS based upon immunotherapy RANO criteria correlated with OS better than RANO and modified RANO. Evaluation of tumour measurements and FLAIR sequences were performed by blinded readers to determine disease progression.
Spearman's correlations were similar between RANO and modified RANO, 0.69 (95% confidence interval [CI] 0.62 to 0.75) versus 0.67 (95% CI 0.60 to 0.73) and 0.48 (95% CI 0.40 to 0.55) versus 0.50 (95% CI 0.42 to 0.57) in newly diagnosed and recurrent glioblastoma. In newly diagnosed glioblastoma, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the post-radiation MRI as baseline scan was associated with improved correlation compared with use of the preradiation MRI, 0.67 (95% CI 0.60 to 0.73) versus 0.53 (95% CI 0.42 to 0.62). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, modified RANO, and immunotherapy RANO.
The authors concluded that their data suggest that PFS obtained by RANO and modified RANO criteria correlates similarly with OS in patients with newly diagnosed and recurrent glioblastoma. In the newly diagnosed setting, the results support the use of postradiation MRI as a baseline and a requirement for confirmation scans in the first 12 weeks after completion of radiation therapy. The evaluation of nonenhancing disease with T2/FLAIR does not increase the correlation between PFS and OS, nor does the application of immunotherapy RANO in patients who receive immune checkpoint blockade monotherapy.
The findings were previously presented in part at the Society for Neuro-Oncology RANO Virtual Webinar (28 January 2022), the National Brain Tumor Society Research Roundtable (Boston, MA, US 1 April 2022), the Alliance Neuro-Oncology Imaging Subcommittee Meeting (14 May 2022), the ASCO 2022 Annual Meeting (Chicago, IL, US, 3 June 2022), and the Society of Neuro-Oncology Annual Meeting (Tampa, FL, US, 20 November 2022).
Reference
Youssef G, Rahman R, Bay C, et al. Evaluation of Standard Response Assessment in Neuro-Oncology, Modified Response Assessment in Neuro-Oncology, and Immunotherapy Response Assessment in Neuro-Oncology in Newly Diagnosed and Recurrent Glioblastoma. JCO; Published online 7 April 2023. DOI: 10.1200/JCO.22.01579