New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient's quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

Object. To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds—sodium borocaptate (BSH) and boronophenylalanine (BPA)—with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults. Methods. Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent ¹⁸F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm³. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4–71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3–87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period. Conclusions. This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.

We evaluate the clinical results of a form of tumor selective particle radiation known as boron neutron capture therapy (BNCT) for newly-diagnosed gl