Impact of brain metastasis size at the time of radiotherapy on local control and radiation necrosis.

Purpose: No consensus has been reached regarding whether upfront versus deferred radiation to small, asymptomatic brain metastases is most optimal. We sought to assess the relationship between tumor size at radiation and subsequent development of local recurrence and radiation necrosis to make data-driven recommendations regarding timing of radiation utilization.

Methods: We identified 2268 patients with 6308 newly diagnosed brain metastases between 2010 and 2022 managed with brain-directed radiotherapy at Brigham and Women's Hospital/Dana-Farber Cancer Institute (Boston, MA). Tumors were grouped by maximal unidimensional size: <0.5 cm, 0.5 to < 1 cm, 1 cm to < 2 cm, and ≥ 2 cm; local recurrence and radiation necrosis by tumor size were assessed using competing risks regression.

Results: Among metastases initially treated with stereotactic radiation or whole brain radiotherapy, lesions 1 to < 2 cm (HR 2.30 [95% CI, 1.38-3.81], p = 0.001 and HR 2.61 [95% CI 1.76-3.89], p < 0.001, respectively) and ≥ 2 cm (HR 3.10 [95% CI, 1.62-5.94], p < 0.001 and HR 3.03 [95% CI 1.92-4.79], p < 0.001, respectively) displayed greater local recurrence compared to tumors < 0.5 cm. In addition, among patients treated with stereotactic radiation, significantly higher risk of radiographic and symptomatic necrosis was observed in tumors ≥ 0.5 cm versus < 0.5 cm at radiotherapy, with hazard ratios ranging from 3.27 to 18.90.

Conclusion: Larger metastasis size is associated with markedly poorer local control and increased necrosis following brain-directed radiation, suggesting a role for earlier utilization of radiation therapy in patients with small, asymptomatic metastases and a favorable prognosis.