Volumetric analysis: Rethinking brain metastases response assessment

Abstract

Background: The Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) criteria are the gold standard for assessing brain metastases (BMs) treatment response. However, they are limited by their reliance on 1D, despite the routine use of high-resolution T1-weighted MRI scans for BMs, which allows for 3D measurements. Our study aimed to investigate whether volumetric measurements could improve the response assessment in patients with BMs.

Methods: We retrospectively evaluated a dataset comprising 783 BMs and analyzed the response of 185 of them from 132 patients who underwent stereotactic radiotherapy between 2007 and 2021 at 5 hospitals. We used T1-weighted MRIs to compute the volume of the lesions. For the volumetric criteria, progressive disease was defined as at least a 30% increase in volume, and partial response was characterized by a 20% volume reduction.

Results: Our study showed that the proposed volumetric criteria outperformed the RANO-BM criteria in several aspects: (1) Evaluating every lesion, while RANO-BM failed to evaluate 9.2% of them. (2) Classifying response effectively in 140 lesions, compared to only 72 lesions classified by RANO-BM. (3) Identifying BM recurrences a median of 3.3 months earlier than RANO-BM criteria.

Conclusions: Our study demonstrates the superiority of volumetric criteria in improving the response assessment of BMs compared to the RANO-BM criteria. Our proposed criteria allow for evaluation of every lesion, regardless of its size or shape, better classification, and enable earlier identification of progressive disease. Volumetric criteria provide a standardized, reliable, and objective tool for assessing treatment response.

Keywords: MRI; brain metastases; progressive disease; stereotactic radiosurgery; volumetric analysis.

Figure 1.

Percentage changes in total volume (blue) and RANO diameter (red) at the first instance of progressive disease or response as defined by any of the criteria. On the x-axis are all the lesions ordered by total volume change, from the one that increased the most (1) to the one that decreased the most (185). When no progressive disease or response was detected, the latest available time point was used. The RANO diameter axes have been adjusted to match the definitions of the volumetric criteria.

Figure 2.

Comparison of criteria for progressive disease lesions. (a) Times to progression according to each criterion. Points over the line correspond to the lesions with the same time to progression and blue points on the vertical axis indicate BMs identified as progressive disease by total volume but not by RANO-BM. P-values correspond to the Wilcoxon signed-rank test for the points outside the axes. (b) Kaplan–Meier curves per lesion comparing time to progression for the 2 study criteria: total volume (30% increase) and RANO-BM criteria (n = 80 lesions). (c) Illustration of a progressive BM from a non–small cell lung cancer (NSCLC) where the RANO-BM criteria identified progressive disease 4.6 months later than the total volume criteria. (d) A progressive lesion from a small cell lung cancer (SCLC) was identified by the volumetric criteria but not by the RANO-BM criteria. Yellow squares represent measured volumes, dashed gray lines with flash symbols indicate the time of stereotactic radiotherapy treatment, and purple lines represent interpolated longitudinal volumetric data (provided for reference). Axial slices from contrast-enhanced (CE) T1-weighted MRI sequences are shown.

Figure 3.

Comparison of criteria for responding lesions. (a) Times to progression according to each criterion. Points over the line correspond to the lesions with the same time to progression, blue points on the vertical axis indicate BMs identified as progression by total volume but not by RANO-BM, while red points on the horizontal axis signify response according to RANO-BM but not total volume. P-values correspond to the Wilcoxon signed-rank test for the points outside the axes. (b) Kaplan–Meier curves per lesion comparing time to response for the 2 criteria considered in this study: Total volume (20% decrease) and RANO-BM criteria for BMs labeled as responding by any of the criteria (n = 64 lesions).