However, our findings are consistent with other reports. In the sunitinib extended access program, the median progression free survival and overall survival for the entire population were 10. 9 and 18. 4 months, respectively, whereas the subgroup of patients with BM was shown to achieve a median PFS and OS of 5. 6 and 9. 2 months, only. Although surgery was shown to provide excel lent local selleck chemicals llc control in up to 96% of the patients, it would be expected that reduced overall survival of BM patients is related to the tenuous site of metastases. This is supported by the Inhibitors,Modulators,Libraries report of Sperduto and colleagues who found that the number of cerebral lesions is an independent prognostic factor in patients with RCC. Brain metastases Inhibitors,Modulators,Libraries may dramatically endanger the patient by leading to local edema, increased intracranial pressure and fatal bleeding.

However, in our series, brain metastases per se were not responsible for shorter survival of these patients. All patients with BMs were neurologically Inhibitors,Modulators,Libraries unsuspicious in the last 24 hours before death and died obviously from disease progression of extracerebral metastatic sites, leading most commonly to respiratory or hepatic failure. Among those who are alive, none is endangered by intracerebral disease pro gression. Hence, the presence of BM was not Inhibitors,Modulators,Libraries a risk fac tor for shorter overall survival. In the multivariate analysis, only ECOG Performance status and the time from primary tumor to development of metastases were independent risk factors for short survival. Our results are consistent with the findings of Hara et al.

who reported that a poor performance status accounts for shorter survival of BM patients rather than the presence of Inhibitors,Modulators,Libraries brain metastases per se. Consequently the authors suggested that effective therapeutic strategies for systemic disease may prolong survival in patients with locally treated brain metastases. Although all patients of the present analysis had access to at least one type of effective RCC treatment leading to stable disease or objective remission in the majority and while no patient died from BM related progression, the outcome is still different between BM and non BM patients. Several reasons may account for these differences. First, brain metastases were shown to occur late in the progression of mRCC. Conse quently, the overall survival of these patients may often reflect only the length of the very last life span within the course of metastatic disease.

Second, the occurrence of brain metastases may represent an epiphenomenon of an altered, meanwhile highly aggressive behaviour of the tumor. Hence, it could be speculated that patients with Verdinexor (KPT-335)? BM require far more aggressive treatment strategies than patients without and that alternative therapeutic targets may become more relevant. In this context, the signal transducer and activator of transcription 3 might be an interesting target. Activation of Stat3 was shown to be increased in brain metastases.