Association between radiographic response and subsequent recurrence in brain metastases treated with radiation: implications for response assessment criteria

BACKGROUND: The Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM) criteria comprise the foundation for assessment of investigational approaches in brain metastases, including novel radiation-based techniques. We characterized the relationship between RANO-BM response and long-term tumor control, the primary objective of radiation, in patients with brain metastases. METHODS: We identified 1454 patients with 4166 newly-diagnosed brain metastases managed with radiation therapy between 2008-2022. Initial response (progressive disease, stable disease, partial response, or complete response) was assessed per-metastasis by RANO-BM criteria. Multivariable Fine and Gray's competing risk regression identified patient and metastasis-level characteristics, including response, associated with local recurrence. RESULTS: The study population had a median (IQR) of 3 (1-6) brain metastases. Per-metastasis, partial response was most common (n = 1662, 40%), followed by stable disease (n = 1304, 31%), complete response (n = 1023, 25%), and progressive disease (n = 177, 4%). Compared to partial response, complete response was associated with a lower likelihood of local recurrence (HR = 0.44, 95% CI: 0.31, 0.63, p < 0.001) whereas stable disease was not (HR = 1.15, 95% CI: 0.91, 1.45, p = 0.25). On subgroup analysis, the association between stable disease versus partial response and local recurrence was modality-dependent, with no difference after whole brain radiation noted but higher recurrence with stable disease after stereotactic radiation observed. CONCLUSIONS: In radiotherapeutically-managed brain metastases, particularly those treated with whole brain radiation, the association between response and local control is weak, especially among the most common response categories of partial response and stable disease. If validated, trials and guidelines assessing novel radiotherapeutic approaches should focus on long-term local control.