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Background The number of brain metastases (BM) plays an important role in the decision between stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT). Methods We analyzed the survival of 5750 SRS-treated BM patients as a function of BM number. Survival analyses were performed using Kaplan-Meier analysis as well as univariate and multivariate Cox proportional hazards models. Results BM patients were first categorized as those with 1, 2–4, and 5–10 BM based on the scheme proposed by Yamamoto et al (Lancet Oncology 2014). Median overall survival for patients with 1 BM was superior to those with 2–4 BMs (7.1 mo v. 6.4 mo, p=0.009), and survival of patients with 2–4 BMs did not differ from those with 5–10 BMs (6.4 mo v. 6.3 mo, p=0.170). The median survival of patients with >10 BMs was lower than those with 2–10 BMs (6.3 mo v. 5.5 mo, p=0.025). In a multivariate model that accounted for age, Karnofsky Performance Score (KPS), systemic disease status, tumor histology, and cumulative intracranial tumor volume (CITV), we observed a ~10% increase in hazard of death when comparing patients with 1 versus 2–10 BM (p<0.001) or 10 versus >10 BM (p<0.001). When BM number was modeled as a continuous variable rather than using the Yamamoto classification, we observed a step-wise 5% increase in the hazard of death for every increment of 5–6 BM (p<0.001). Conclusions The contribution of BM number to overall survival is modest, and should be considered as one of the many variables considered in the decision between SRS and WBRT.

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