Outcomes of Stereotactic Radiosurgery in the Management of Brain Metastasis in Patients with HER2 Positive Metastatic Breast Cancer.

Abstract

Abstract Background:We present single institution experience on the effect of Her 2 status on results of Gamma knife radiosurgery (SRS) for brain metastases (BM) as to local control, pattern of relapse and survival.Material and Methods:From 2004 to 2008, 65 patients with metastatic breast cancer (MBC) were treated with GK-SRS at our center, 52 had documented Her 2 status. We performed analysis based on Her 2 status of the original tumor defined as positive by 3+ DAKO or FISH. SRS was delivered using cobalt leksell GKS to a median dose of 20Gy (range 16-20 Gy) at 50% isodose line. Responses were evaluated by gadolinium enhanced MRI. We analyzed the data as to: objective response (OR) defined as radiologic response or stable disease, and local progression –free survival (PFS) defined as freedom from progression of treated BM, appearance of new brain metastases and/or leptomeningeal progression, as well as overall survival (OS) measured from the time of SRS .ResultsTwenty-eight patients were identified as HER2 positive (Group A) and 24 patients were HER2 negative (Group B). Median time to develop BM in group A was 60 months (4 -240 months) versus 48 months (4-156) in group B. Median follow-up was 12 months (1-48) from the time of onset of BM. 66% patients in group A and 82% patients in group B have no more than 2 BM at the time of SRS.In group A, OR was 78.6% (22 pts)and 21.4%(6 pts) had progressive disease (PD) where as in group B the OR was 83% (20 pts) and 17%(4 pts) had PD. Median time to local recurrence of the treated lesion in group A was 13 months (95% CI 5.84 to 20.15) compared to 8 months (95%CI 6.75 to 9.25) in group B. Local PFS at 1 year for Group A vs. B was: control of the treated lesions 69% versus 41.2% respectively, p= 0.97 by log rank test; and development of new BM 67% compared to 86% (p=0.2).Out of all CNS relapses, almost a quarter of patients in both groups received second SRS whereas 25% patients in group A and 31% patients in group B received whole brain irradiation respectively. Interestingly, 28% (9 pts) failed as leptomeningeal disease following SRS, 7 of them with Her 2 positive tumors. Leptomeningeal relapses were seen both as only pattern of recurrence (4 pts) or associated with other types of CNS progression: local re-growth or new BM (5pts).ConclusionsSRS provides high rate of objective response and local control for BM from both Her 2 positive and Her 2 negative breast cancer. No statistically significant difference in local PFS was seen. More frequent pattern of relapse as leptomeningeal disease was seen in Her 2 positive after SRS. Evaluation of novel systemic targeted therapies in conjunction with local therapies is needed for effective management of BM from breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6152.