Her2-enriched breast cancer brain metastases exhibit resistance to Gamma Knife radiosurgery: findings from a single institutional series review

Abstract

Purpose/objective(s): This study aims to assess the outcomes and prognostic/predictive factors of overall survival and local control in patients with a diagnosis of brain metastasis from a breast cancer primary who underwent Gamma Knife radiosurgery (GKRS) as part of intracranial treatment. Materials/methods: A total of 69 patients were identified who were treated with GKRS for one to four brain metastases from breast cancer as a primary diagnosis. A total of 176 metastases were treated at diagnosis or as salvage treatment. Differences in overall survival time (OS) and local control time (LC) after GKRS between groups were assessed. Results: The median follow-up was 9. 2 months (range 3-90. 5 months). The median OS for this cohort was 13. 4 months (range 0. 5-90. 5 months). The median LC was 15. 8 months. For a given metastasis, univariate analysis showed that LC was significantly correlated with the dose density (DD, ratio of GKRS dose to metastasis volume, [gray per cubic centimeters]). Additionally, human epidermal growth factor receptor 2 (HER2) enrichment predicted for worse local control on univariate analysis [HR 2. 18; 95 % CI 1. 047-4. 532] (p = 0. 037). With DD as a continuous variable, the only independent and significant predictive factors were the DD [HR: 0. 99; 95%CI: 0. 984-0. 998] (p = 0. 009) and HER2-enriched subtype [HR = 2. 25; 95 % CI = 1. 074-4. 728] (p = 0. 032) after accounting for dose, metastasis volume, whole-brain radiotherapy (WBRT), and other subtypes. DD was then examined as a binary categorical variable whether or not a metastasis was treated to, at least, the median DD delivered across the cohort. With the cutoff set at this median, a DD value of 36 Gy/c3, the independent and significant predictive factor again was the DD [HR: 3. 49; 95%CI: 1. 45-8. 40] (p = 0. 005) in favor of metastases receiving at least 36 Gy/c3. Additionally, HER2 enrichment was significant when DD was examined as a binary variable, predicting for worse LC [HR 2. 20; 95 % CI: 1. 048-4. 636] (p = 0. 037). The median LC for metastasis receiving <36 Gy/c3 is 18. 7 months vs. median not reached in those receiving at least 36 Gy/c3 (p < 0. 001). For HER2-enriched metastases, a DD ≥36 Gy/c3 resulted in a 14 % failure rate (10-month actuarial), compared to that of 0 % observed in non-HER2-enriched subtypes. Conclusion: The ratio of dose delivered with GKRS to metastasis volume was significantly correlated with LC, with values ≥36 Gy/c3 improving LC. This effect was significantly diminished in HER2 subtypes, and a required higher DD for improved control, suggesting these metastases may be intrinsically resistant to radiosurgery. © 2012 Springer-Verlag.