Radiation injury of boron neutron capture therapy using mixed epithermal- and thermal neutron beams in patients with malignant glioma.

The purpose of this study was to clarify the radiation injury in acute or delayed stage after boron neutron capture therapy (BNCT) using mixed epithermal- and thermal neutron beams in patients with malignant glioma. Eighteen patients with malignant glioma underwent mixed epithermal- and thermal neutron beam and sodium borocaptate between 1998 and 2004. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the protocol used between 1998 and 2000 (Protocol A, n = 8) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B, n = 4); it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to 6 glioblastoma patients (Protocol C, n = 6). The average values of the maximum vascular dose of brain surface in Protocol A, B and C were 11.4+/-4.2 Gy, 15.7+/-1.2 and 13.9+/-3.6 Gy, respectively. Acute radiation injury such as a generalized convulsion within 1 week after BNCT was recognized in three patients of Protocol B. Delayed radiation injury such as a neurological deterioration appeared 3-6 months after BNCT, and it was recognized in 1 patient in Protocol A, 5 patients in Protocol B. According to acute radiation injury, the maximum vascular dose was 15.8+/-1.3 Gy in positive and was 12.6+/-4.3 Gy in negative. There was no significant difference between them. According to the delayed radiation injury, the maximum vascular dose was 13.8+/-3.8 Gy in positive and was 13.6+/-4.9 Gy in negative. There was no significant difference between them. The dose escalation is limited because most patients in Protocol B suffered from acute radiation injury. We conclude that the maximum vascular dose does not exceed over 12 Gy to avoid the delayed radiation injury, especially, it should be limited under 10 Gy in the case that tumor exists in speech center.