悪性神経膠腫に対する中性子捕捉療法 : 混合ビーム（熱中性子と熱外中性子ビーム）を用いた新しい治療戦略

The purpose of this study was to clarify the clinical interim results of boron neutron capture therapy (BNCT) using mixed epithermal-and thermal neutron beams in patients with malignant glioma. The mixed neutron beam for BNCT has been used clinically since 1998. Its great advantage consists of its greater ability than the pure thermal neutron beam to reach sites deep from the brain surface.
Sixteen patients with malignant glioma (glioblastoma n=14, anaplastic ependymoma n=1, PNET n=1) underwent mixed epithermal-and thermal neutron beam treatment between 1998 and 2003. They included 2 children younger than 3 years. Sodium borocaptate (Na2B12H11SH, BSH ; 80-100 mg/kg) was administered intravenously at 12-15 hr before neutron irradiation. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the he protocol used between 1997 and 2000 (Protocol A) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B) ; it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. In both protocols, the maximum vascular radiation dose to the brain surface is not to exceed 15 Gy. Of the 12 patients, 8 were treated according to Protocols A and 4 according to Protocol B. 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 four glioblastoma patients (Protocol C).
Of the 8 patients treated under Protocol A, 7 died (dissemination n=4, local recurrence, infection, unknown causes, n=1 each). Of the 4 patients treated under Protocol B, 2 died. Concerning the adverse effects of BNCT, Protocol B resulted in higher complication rates with respect to both acute and delayed radiation injury. The estimated median survival time after diagnosis and after BNCT in all patients were 16.7 and 14.6 months, respectively. In 8 patients of Protocol A, the estimated median survival time after diagnosis was 16.0 months ; 1-year and 2-year survival rate were 75.0% and 12.5%, respectively. On the other hand, in 8 patients in Protocol B and C, the estimated median survival time after diagnosis was 15.5 months ; 1-year and 2-year survival rate were 80.0% and 53.3%, respectively.
Our limited clinical evaluation suggests that BNCT could achieve local control of glioblastomas at the primary site and that possible dose escalation is limited. While the dose escalation can contribute to the improvement of survival rate, it results in the radiation injury. We conclude that not only the radiation dose at the target point, but also the distribution of neutron flux in the radiation field may contribute to the cure of glioblastoma by BNCT. Computation-assisted dose planning can contribute to improved clinical results following BNCT and to the prevention of cerebrospinal fluid dissemination. We will introduce pure epithermal neutron beam instead of mixed neutron beam in the near future. It has greater advantage than mixed neutron beam to deep-seated glioma because it has a peak in neutron flux at 2-3 cm depth from the brain surface. The dose-planning system and pure epithermal neutron beam can lead to further improvements in the clinical outcomes and the avoidance of adverse effects in brain tumor patients subjected to BNCT.

四国医学雑誌 : http://www.tokushima-u.ac.jp/med/research/shikoku_acta_medica.html