LAUSR

This retrospective study evaluated the relationship between histologic subtype and treatment outcomes following SRS for the treatment of multiple brain metastases (MBM). We analyzed patients with MBM, defined here as >= 3 lesions, treated with SRS at our institution. Primary histologies examined were NSCLC, breast, and melanoma. Patients were categorized according to histology-specific subtypes (NSCLC-EGFR, ALK, KRAS, PD-L1%; breast-HER2, ER, PR; melanoma-BRAF). The primary outcome was local control (defined by RANO-BM) and secondary outcomes included intracranial progression-free survival (iPFS) and overall survival (OS). 141 patients met inclusion criteria (66 NSCLC, 61 breast, and 14 melanoma). HER2+ and BRAF V600E+ lesions had increased rates of local control following SRS (P=0.0048 and P=0.0256, respectively) compared to other breast/melanoma subtypes. EGFR mutation was not associated with increased local control with SRS (71 vs 74%), but increased iPFS (P=0.0031). On multivariable analysis, EGFR+ was independently associated with a decreased time-dependent risk of death (P=0.011). The use of progressively newer generations of EGFR-directed therapies was associated with stepwise decreasing risk of intracranial progression and death. HER2+ disease had improved iPFS and OS (P=0.0058 and P< 0.0001, respectively; it was not an independent risk factor for progression or death; however, the use of HER2-directed antibodies was associated with decreased risk of death (p=0.036). The use of tyrosine kinase inhibitors (i.e. lapatanib) was not associated with improvements, although this was a small subset. Some histologic subtypes appear to have better control with SRS, with HER2+ breast cancer and BRAF V600E+ melanoma associated with improved outcomes – this requires further validation; a volumetric analysis is pending. This the protective effect of EGFR mutation appears to be partly related to use of EGFR inhibitors, with the use of newer-generation therapies leading to improved outcomes; although local control with SRS remains excellent regardless of the mutation.