A case-matched study of stereotactic radiosurgery for patients with multiple brain metastases: comparing treatment results for 1-4 vs ≥ 5 tumors: clinical article.

Object: Although stereotactic radiosurgery (SRS) alone for patients with 4-5 or more tumors is not a standard treatment, a trend for patients with 5 or more tumors to undergo SRS alone is already apparent. The authors' aim in the present study was to reappraise whether SRS results for ≥ 5 tumors differ from those for 1-4 tumors.

Methods: This institutional review board-approved retrospective cohort study used the authors' database of prospectively accumulated data that included 2553 consecutive patients who underwent SRS, not in combination with concurrent whole-brain radiotherapy, for brain metastases (METs) between 1998 and 2011. These 2553 patients were divided into 2 groups: 1553 with tumor numbers of 1-4 (Group A) and 1000 with ≥ 5 tumors (Group B). Because there was considerable bias in pre-SRS clinical factors between Groups A and B, a case-matched study was conducted. Ultimately, 1096 patients (548 each in Groups A and B) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival and the post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.

Results: The post-SRS median survival time was significantly longer in the 548 Group A patients (7.9 months, 95% CI 7.0-8.9 months) than in the 548 Group B patients (7.0 months 95% [CI 6.2-7.8 months], HR 1.176 [95% CI 1.039-1.331], p = 0.01). However, incidences of neurological death were very similar: 10.6% in Group A and 8.2% in Group B (p = 0.21). There was no significant difference between the groups in neurological death-free survival intervals (HR 0.945, 95% CI 0.636-1.394, p = 0.77). Furthermore, competing risk analyses showed that there were no significant differences between the groups in cumulative incidences of local recurrence (HR 0.577, 95% CI 0.312-1.069, p = 0.08), repeat SRS (HR 1.133, 95% CI 0.910-1.409, p = 0.26), neurological deterioration (HR 1.868, 95% CI 0.608-1.240, p = 0.44), and major SRS-related complications (HR 1.105, 95% CI 0.490-2.496, p = 0.81). In the authors' cohort, age ≤ 65 years, female sex, a Karnofsky Performance Scale score ≥ 80%, cumulative tumor volume ≤ 10 cm(3), controlled primary cancer, no extracerebral METs, and neurologically asymptomatic status were significant factors favoring longer survival equally in both groups.

Conclusions: This retrospective study suggests that increased tumor number is an unfavorable factor for longer survival. However, the post-SRS median survival time difference, 0.9 months, between the two groups is not clinically meaningful. Furthermore, patients with 5 or more METs have noninferior results compared to patients with 1-4 tumors, in terms of neurological death, local recurrence, repeat SRS, maintenance of good neurological state, and SRS-related complications. A randomized controlled trial should be conducted to test this hypothesis.