Challenges of Applying the RANO-BM Criteria for Characterization of Brain Metastases Treatment Response

The goal of brain metastasis therapy is to reduce the risk of intracranial disease progression and to minimize treatment-related adverse effects and loss of neurologic function without compromising extracranial disease control. A response assessment system plays a critical role in the comparative evaluation of therapeutic strategies in clinical trials and in routine patient care. Since 2015, the RANO-BM criteria have become a standard schema for evaluating brain metastases treatment response, providing uniform definitions and methodology particularly practical in prospective clinical trials of systemic therapy. There have been a variety of modifications and additions to the original guidelines proposed to improve their utility for brain metastases response assessment, including lowering the measurable disease size threshold, optimizing disease progression metrics, and employing tumor volumetric analysis using automated measurement tools. However, despite these enhancements, the criteria display limitations in selected clinical scenarios. This article provides a detailed overview of these limitations and their corresponding clinical contexts and concludes with a discussion of approaches which may aid in the development of a more comprehensive brain metastases response assessment system.