For 1 to 3 BM, there is randomised evidence to support the use of SRS in appropriately selected patients. Although SRS for up to 10 brain metastases can be considered in some cases, randomised data is lacking.rrr Lesions up to 3-4 cm in diameter have been treated with SRS, but for lesions above 2 cm, a hypofractionated regime (3 to 5 fractions) may be preferred to improve the therapeutic ratio.r
Role of SRS + WBRT versus WBRT alone
Andrews et al. 2004 randomised 333 patients with 1 to 3 BM and demonstrated improved overall survival in those with a single brain metastasis and in recursive partitioning analysis (RPA) group 1 receiving SRS + WBRT compared to WBRT alone.r Patients in the SRS group were also more likely to have a stable or improved Karnofsky Performance Status (KPS) score and reduced steroid dependence at 6 month follow-up. There was no difference in cause of death.
Role of SRS + WBRT versus SRS alone
Kocher et al. 2011 (EORTC 22952-26001) randomised patients with 1 to 3 BM after local therapy (SRS or surgical gross total resection) to WBRT or observation.r The addition of WBRT after SRS improved radiological measures of local and distant intracranial disease, but the clinical benefit was uncertain. The probability of relapse at initial SRS sites was 31% (95%CI: 22-40%) reduced to 10% (95%CI: 11-27%) at 2 years with the addition of WBRT. WBRT did not affect overall survival, or time to deterioration in performance status. In the population overall, WBRT was associated with negative effects on quality of life and patient reported cognitive functioning at various time points.r
Aoyama et al. 2006 randomised patients with 1 to 4 BM to SRS alone vs SRS + WBRT.r They also showed the addition of WBRT to SRS did not improve median survival or 1-year actuarial survival. Brain tumour recurrence rates were significantly less after SRS + WBRT versus SRS alone (46.8% vs 76.4%; p <0.001), as was the need for salvage treatment (n = 10 vs n = 29; p <0.001). However, there was no significant difference for patient-relevant outcomes including functional preservation, toxic effects and cause of death.
Brown et al. 2016 randomised 213 patients with 1 to 3 BM to SRS alone vs SRS + WBRT.r They showed less cognitive deterioration at 3 months with SRS alone than SRS + WBRT; difference -28.2% (90%CI: -41.9 to -14.4%; p <0.001). Quality of life was higher at 3 months with SRS alone compared to SRS + WBRT, with a mean difference 9.6 points (95%CI: 3.6-15.6, p = 0.002). Median overall survival was 7.4 months with the addition of WBRT to SRS compared to 10.4 months for SRS alone (HR 1.02, 95%CI: 0.75-1.38, p = 0.92).
An individual patient data meta-analysis including the Andrews et al., Kocher et al. and Aoyama et al. studies confirmed these findings for patients with 1 to 4 BM.r They also demonstrated age was a significant modifier of outcome, and for patients aged ≤50 years, the initial omission of WBRT did not impact on distant brain relapses.