Changes in blood-brain barrier permeability induced by radiotherapy: implications for timing of chemotherapy? (Review).

The brain requires a stable internal environment, which is established by the integrity of the blood-brain barrier (BBB). The efficacy of chemotherapeutics in the treatment of brain malignancies is often hampered by the presence of the BBB. BBB disruption can be performed either by osmotic disruption, bradykinin or irradiation. Radiotherapy with doses of 20 to 30 Gy with fraction size of 2 Gy may be used to increase the permeability of the BBB. These radiation doses by themselves will not give rise to serious side effects or long-term complications. Disruption of the BBB by radiotherapy might have implications in the treatment of primary brain tumors, cerebral metastases, and prophylactic cranial irradiation in small cell lung cancer since irradiation will cause cell kill and may enhance the effect of chemotherapy. We present a review on the effects of irradiation on the BBB and subsequently discuss the potential value for therapeutic applications.