The Blood-Brain Barrier: Its Influence in the Treatment of Brain Tumors Metastases

D.      Fortin

doi:10.2174/156800912799277511

Abstract

Brain metastases represent the most common intracranial tumors in the adults. Its incidence outnumbers that of primary brain tumors by a tenfold factor. Estimated cumulative incidence is between 10 to 20% of all cancer patients, which would represent over 170 000 new cases in the US. Typically, patients with multiple brain metastases are exposed to whole brain radiation therapy, as a palliative measure. Resulting median survival improvement is modest, ranging from 3 to 5 months. This survival has not been altered despite 3 decades of clinical research aiming at improving outcome of these patients. The role of standard chemotherapy in the treatment of brain metastases has always been marginal, as the penetration of chemotherapy beyond the BBB (blood-brain barrier) is considered limited. Whereas the BBB is universally recognized as a physiological entity, its role in the treatment of brain metastases remains controversial. Metastatic lesions often depict a homogeneous intense enhancement on either CT or MRI, thus implying that the brain tumor barrier (BTB) is breached. Although there is no doubt that the BBB and BTB suffer from variable degrees of breach in integrity in the presence of malignant brain tumors, impediment to drug delivery remains, and strategy to optimize delivery must be considered if one is to really impact patient ’ s outcome in the treatment of these diseases. The intended purpose of this paper is to review current data on the role of the BBB in the treatment of CNS metastatic disease.

Keywords: Blood-brain barrier disruption, blood-brain barrier, brain metastases, chemotherapy, Convection enhanced delivery, cerebrospinal fluid, compturized tomograph, Gadolinium-DiethyleneTriamine Pentaacetic Acid, Human Epidermal growth factor Receptor 2, Magentic resonance imaging, mammalian target of rapamycin, Positron emitting tomograph, Small cell lung carcinoma, Vascular endothelial growth factor