Relationship between HER2 status and prognosis in women with brain metastases from breast cancer.

PURPOSE: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. METHODS AND MATERIALS: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. RESULTS: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2- breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. CONCLUSIONS: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2- lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2- and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

Gamma knife stereotactic radiosurgery for the management of incidentally-identified brain metastasis from non-small cell lung cancer.

Initial staging workup of non-small cell lung cancer (NSCLC) patients has led to increased identification of incidental brain metastases in patients who otherwise have minimal or no neurologic symptoms. We present our experience treating these metastases with stereotactic radiosurgery (SRS) alone and compare outcomes to those of patients with brain metastases treated with other strategies. We queried our neuro-oncology and radiation oncology databases for patients with incidentally-identified NSCLC brain metastases treated with upfront SRS alone between 1997 and 2006. We performed a retrospective analysis to evaluate outcomes in these patients. We found 26 patients with incidentally-identified NSCLC brain metastases (KPS 90-100) treated with SRS alone within 60 days of diagnosis of the metastases. These patients underwent SRS at a median 15 days from diagnosis to an average of 1.6 lesions (range: 1-7), with a mean lesion volume of 1.86 cm(3). The median prescription was 24 Gy delivered to the median 53% isodose line. The median survival for these patients was 8.2 months (mean 12.3 months) from diagnosis of brain metastases. Local CNS progression occurred in 2 patients (7.7%, mean 229.7 days). Survival was not statistically different from similar patients treated with whole brain radiotherapy (WBRT) (P = 0.98), WBRT + Surgery (P = 0.07) or WBRT + SRS (P = 0.62). Patients with incidentally-identified NSCLC brain metastases treated with SRS alone may achieve a survival rate comparable to patients managed with other standard therapeutic modalities. Our findings suggest that SRS alone may be a viable therapeutic option for patients with incidentally-discovered NSCLC brain metastases.

Role of stereotactic radiosurgery for multiple (>4) brain metastases.

Stereotactic radiosurgery (SRS) is a very important treatment option for patients with brain metastases. Prospective data supports the use of SRS for patients with 1-4 brain metastases. Although whole brain radiation therapy (WBRT) has been an effective adjunct to SRS and surgery and has also provided effective palliation for many patients with brain metastases, the potential side effects especially neurocognitive function decline has increased the use of SRS alone even for patients with multiple (>4) brain metastases despite data that suggests that tumor progression is worse than the potential neurocognitive effects of WBRT. In addition, current stereotactic radiosurgery machines and techniques allow the delivery of SRS to multiple lesions in an efficient manner. As a result, the optimal management of multiple brain metastases (>4) is becoming more contentious given the lack of prospective data. Until further data is available, a multidisciplinary team of neurosurgeons, radiation oncologists, medical oncologists and medical physicists should work closely together to implement individualized treatment for patients with multiple brain metastases. This paper will review some of the institutional, multi-institutional and randomized trials of SRS for patients with brain metastases, and review the outcomes for patients with multiple (>4) brain metastases treated by SRS and the associated costs.

Stereotactic radiosurgery as single-modality treatment of incidentally identified renal cell carcinoma brain metastases.

BACKGROUND: Initial staging evaluation of patients with renal cell carcinoma (RCC) has led increasingly to the diagnosis of brain metastases in patients who are otherwise neurologically asymptomatic. We present our experience treating patients with incidentally identified brain metastases with initial stereotactic radiosurgery (SRS) monotherapy and compare outcomes with those of patients treated at our institution with other strategies and with those reported in the literature. METHODS: We conducted a retrospective outcomes analysis in patients with incidentally identified RCC brain metastasis treated with initial SRS monotherapy. Our radiation oncology and tumor databases were reviewed, identifying 80 patients treated between 1990 and 2006. RESULTS: We found 19 patients with asymptomatic, incidentally identified brain metastasis (KPS, 90-100) treated with SRS monotherapy within 60 days of diagnosis. Stereotactic radiosurgery was performed at a mean of 17.8 days from diagnosis to an average of 3.1 lesions (range, 3-11; mean lesion volume, 1.72 cm(3); mean total volume, 4.53 cm(3)). The mean prescription was 21.3 Gy delivered to the mean 59.97% isodose line. The mean survival for these patients was 21.5 months (median, 12.6 months) and was not statistically different from survival in similar patients treated with other therapeutic modalities. Local control was achieved in 95% of patients; distant central nervous system progression occurred in 79% of patients at a mean of 450 days. CONCLUSIONS: We demonstrate that patients with incidentally identified RCC brain metastases treated with initial SRS monotherapy achieved a survival rate comparable with that of patients managed with standard therapeutic modalities. Our findings suggest that SRS alone is an attractive therapeutic option for patients with incidentally identified brain metastases from RCC.

Design and synthesis of a G-protein-coupled receptor antagonist library of aryloxyalkanolamines using a polymer-supported acyclic acetal linker.

A G-Protein-coupled receptor-targeted library of aryloxypropanolamines and aryloxybutanolamines was efficiently executed using a novel, polymer-supported acyclic acetal linker, producing compounds in good yields and purities.

Discovery of a tetrazole-based growth hormone secretagogue: 4-(hydroxybutyl)carbamic acid 2-{5-[1-(2-amino-2-methylpropionylamino)-2- benzyloxyethyl]tetrazol-1-yl}ethyl ester (BMS-317180).

A tetrazole-based peptidomimetic 2 (BMS-317180) was discovered as a human growth hormone secretagogue (GHS). Compound 2 is a potent, novel, orally effective GHS that shows an excellent safety profile in preclinical studies. The compound was advanced into clinical development.