The number of prior lines of systemic therapy as a prognostic factor for patients with brain metastases treated with stereotactic radiosurgery: Results of a large single institution retrospective analysis

Abstract Objectives It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment. In this study we sought to identify whether the number of prior lines of systemic therapy are associated with clinical outcomes in patients with brain metastases who received stereotactic radiosurgery (SRS). Patients and Methods Between July 2000 and July 2017, 377 patients with brain metastases were treated with upfront SRS. We performed a large, single institution retrospective analysis of these patients. Kaplan Meier analysis was used to estimate survival times. Competing risk analysis was used to estimate times to local failure (LF) and distant brain failure (DBF). Multivariate analysis was performed to estimate the hazard ratios (HRs) for overall survival (OS), neurologic and non-neurologic death for patients with 1, 2 and 3+ lines of prior systemic therapy. Results Of the 1077 patients with brain metastases treated with SRS, 377 received prior systemic therapy with a median of 1 (range: 1–9) lines of prior therapy. Median OS was 8.70 months (95% CI, 7.9–9.5). Median OS for patients with 1 prior line of therapy, 2 prior lines of therapy and 3 or greater lines of therapy were 9.93-, 9.05-, and 6.18-months, respectively (log rank p = .04). Lines of therapy as a continuous variable was not associated with LF or DBF on competing risk analysis. The percentage of patients that died of neurological death was 36%. Greater prior lines of therapy (1 vs. 2 vs. 3 and greater) was associated with a greater likelihood of dying of non-neurologic death (gray’s p = .01), but was not associated with likelihood of dying of neurologic death (p = .57). Conclusion Lines of therapy are associated with OS and non-neurologic death but are not associated with neurologic death, LF or DBF.