Volumetric Extension of the RANO-BM Criteria for the Assessment of Progression Following SRT

We support the efforts for standardization in the assessment of response in brain metastases put forth by the RANO-BM working group (8). While the RANO-BM guideline stresses the importance of further research on volumetric analysis in brain metastases, the proposed criteria for volumetric analysis provided in the RANO-BM guideline are incomplete due to the lack of research supporting specific recommendations for volumetric assessment (8). We therefore adopted the basic concept from the RANO-BM guideline to derive volumetric criteria from the established unidimensional recommendations using spherical geometry. In this regard, the RANO-BM guideline recommends defining volumetric partial response as ≥ 65% reduction in volume (8). Following this principle, progression was defined as ≥ 72.8% increase in volume in the present study relative to nadir/baseline, which corresponds to a ≥ 20% increase in diameter of a perfect sphere (i.e., the unidimensional RANO-BM criteria for progression). In addition, as the RANO-BM guideline recommends to consider small brain metastases between 5 and 10 mm in diameter as unchanged unless the longest diameter changes by at least 3 mm, an additional absolute increase in volume of at least 0.2 cm³ was required for the definition of progression in the present study. This corresponds to the absolute volume increase of a 5 mm sphere growing by additional 3 mm in diameter. Due to this additional requirement and because the main aim of this study was to give an adequate representation of volumetric change in brain metastases following SRT, which are frequently < 5 mm in diameter, no lower size limit for brain metastases was defined in the present study. In addition, as SRT is a localized therapy, change in distant lesions, corticosteroid use or clinical status were not considered in the definition of progression in the present study. Lesions experiencing volumetric progression as per the criteria above but that subsequently showed spontaneous regression during imaging follow-up back to baseline/nadir volume or showed volumetric partial response as per the RANO-BM recommendation (i.e., ≥ 65% reduction in volume) were classified as pseudoprogression/radionecrosis instead of progression. Similarly, in the case of resection, metastases were classified as progression, radionecrosis or both based on histology (21).