Response Assessment in Neuro-Oncology Criteria in Determining Correlation of Survival Outcomes in Glioblastoma

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In a study reported in the Journal of Clinical Oncology, Youssef et al found that the standard Response Assessment in Neuro-Oncology (RANO) and modified RANO (mRANO) criteria produced similar correlations between progression-free survival and overall survival in newly diagnosed glioblastoma and recurrent glioblastoma.

As stated by the investigators: “RANO criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (mRANO) and immunotherapy RANO [iRANO] criteria in patients with…[newly diagnosed glioblastoma] and [recurrent glioblastoma] to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update.”

Study Details

The study involved a retrospective analysis among 657 consecutive patients with IDH wild-type glioblastoma treated at Dana-Farber Cancer Institute between January 2014 and August 2020. A total of 526 patients with newly diagnosed glioblastoma and 580 cases of recurrent glioblastoma were included in the analysis.

Evaluation of tumor measurements and fluid-attenuated inversion recovery sequences were performed by blinded readers to determine disease progression using RANO, mRANO, and iRANO criteria. The mRANO criteria differ from RANO by including use of the postradiation scan as the baseline scan, omission of fluid-attenuated inversion recovery evaluation, and the requirement of a confirmation scan to identify progressive disease. Spearman’s correlations between progression-free survival and overall survival were calculated.

Key Findings

Among newly diagnosed cases, Spearman’s correlations for progression-free and overall survival were 0.69 (95% confidence interval [CI] = 0.62–0.75) with RANO and 0.67 (95% CI = 0.60–0.73) with mRANO. Among recurrent cases, Spearman’s correlations were 0.48 (95% CI = 0.40–0.55) with RANO and 0.50 (95% CI = 0.42–0.57) with mRANO.

In newly diagnosed glioblastoma, performance of a confirmation scan within 12 weeks of completion of radiotherapy to determine disease progression was associated with improved correlations. The use of postradiation magnetic resonance imaging (MRI) as a baseline scan (0.67, 95% CI = 0.60–0.73) was associated with better correlation vs preradiation MRI (0.53, 95% CI = 0.42–0.62).

The evaluation of fluid-attenuated inversion recovery sequences did not improve correlations. Among patients who received immunotherapy, Spearman’s correlations were similar with RANO (0.73, 95% CI = 0.60–0.82), mRANO (0.65, 95% CI = 0.48–0.77), and iRANO (iRANO-4; 0.70, 95% CI = 0.55–0.80) in newly diagnosed glioblastoma (n = 98). In recurrent glioblastoma (n = 175), correlations were 0.42 (95% CI = 0.27–0.55), 0.42 (95% CI = 0.27–0.56), and 0.38 (95% CI = 0.23–0.52), respectively.

The investigators concluded: “RANO and mRANO demonstrated similar correlations between [progression-free survival and overall survival]. Confirmation scans were only beneficial in [newly diagnosed glioblastoma] within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in [newly diagnosed glioblastoma]. Evaluation of [fluid-attenuated inversion recovery] can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.”

Patrick Y. Wen, MD, of the Center for Neuro-Oncology, Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

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