Description of Technology/Procedure

The blood brain barrier (BBB) of the central nervous system (CNS) prevents toxic substances (including chemotherapeutic drugs) from entering the brain. The blood-tumor barrier is more permeable to circulating drugs so its importance in limiting drug delivery is unclear. Blood brain barrier disruption (BBBD) using hyperosmolar agents to temporarily shrink the endothelial cells that form the barrier theoretically increases the concentration of chemotherapy drugs delivered to the tumor and prolongs the drug-tumor contact time.

Committee Summary

With regard to blood brain barrier disruption chemotherapy, the ICSI Technology Assessment Committee finds:

1. The long term effects of repeated BBBD procedures are unknown. The exact roles of standard chemotherapy and radiation therapy in the treatment of many brain tumors remains controversial. At present, there are no randomized, controlled trial data to establish the superiority of BBBD with chemotherapy over conventional chemotherapy; the available evidence is predominantly from case series. Logistical problems and the labor-intensive, highly technical nature of the procedure are barriers to conducting randomized trials. A non-randomized comparison study is in progress.
   
2. BBBD with chemotherapy is an acceptably safe procedure when performed by experienced physicians in large, regional centers. The incidence of serious side effects has been acceptable and treatment related mortality is uncommon. Proponents of BBBD agree that there is a steep learning curve required to master the procedure.
   
3. PCNSL: protocols using high-dose methotrexate with or without BBBD consistently produced response rates of >75% and prolonged survival with positive cognitive outcomes compared with historical experience. The use of BBBD may preclude the need for whole brain radiation therapy. (Conclusion Grade II)
   
4. Anaplastic astrocytoma or glioblastoma multiforme: Some patients (typically <50%) experienced tumor shrinkage.
   
5. CNS germ cell tumors: Response rates of approximately 75% were observed (based on a limited number of evaluable cases). The relative efficacy compared with conventional chemotherapy is unknown. (Conclusion Grade III)
   
6. PNET/medulloblastoma: Response rates >69% were observed (based on few evaluable cases). (Conclusion Grade III)
   
7. Metastatic brain disease: few patients are eligible for BBBD since the systemic disease must be well-controlled or in remission. There are insufficient data to make comparisons with conventional chemotherapy.