Recurrent malignant gliomas (RMGs) are very difficult to control, and no standard treatments have been established for them. We performed boron neutron capture therapy (BNCT) for patients with RMG. BNCT enables high-dose particle radiation to be applied selectively to tumor cells. However, RMG cases generally receive nearly 60 Gy X-ray irradiation prior to re-irradiation by BNCT. Therefore, even with tumor-selective particle radiation BNCT, radiation necrosis in the brain and symptomatic pseudoprogression may develop. In four of our recent patients with RMG after BNCT, we applied the anti-VEGF antibody bevacizumab to treat two pathological entities. This approach appeared to prolong survival. Here we present the case reports of these four consecutive patients with RMG and discuss the novel use of bevacizumab in this context. Four patients with RMGs were treated with BNCT at our institutes. Upon the referral for BNCT, they were assessed as belonging to the recursive partitioning analysis (RPA) class 3 (n = 3 patients) or RPA class 4 (n = 1 patient) (the RPA classification for RMG was advocated by Carson et al. in 2007). The estimated median survival times for RPA classes 3 and 4 were 3.8 and 10.8 months, respectively, after some treatment at the recurrence. We applied BNCT for these four patients and administered bevacizumab when the lesions were considered radiation necrosis or symptomatic pseudoprogression. The class 3 patients survived after the BNCT for 14, 16.5 and > 23 months, and the class 4 patient survived > 26 months, with favorable improvements in clinical symptoms. BNCT with the addition of bevacizumab for radiation necrosis or symptomatic pseudoprogression improved the clinical symptoms and prolonged the survival in RMG patients.

We treated a 54-year-old Japanese female with a recurrent radiation-induced osteosarcoma arising from left occipital skull, by reactor-based boron neutron capture therapy (BNCT). Her tumor grew rapidly with subcutaneous and epidural extension. She eventually could not walk because of cerebellar ataxia. The tumor was inoperable and radioresistant. BNCT showed a marked initial therapeutic effect: the subcutaneous/epidural tumor reduced without radiation damage of the scalp except hair loss and the patient could walk again only 3 weeks after BNCT. BNCT seems to be a safe and very effective modality in the management of radiation-induced osteosarcomas that are not eligible for operation and other treatment modalities.

Visualization of near-infrared fluorescence through a surgical microscope can provide intraoperative information about deep-seated tissues. We studied the possibility of taking a near-infrared image through a surgical microscope after intravenous injection of indocyanine green (ICG). The surgical microscopes we used were Zeiss models OPMI MD and OPMI CS-NC. We used a halogen lamp as a light source, a band pass filter of 760 - 810 nm as an excitation filter, a laser light of 800 nm as an external light source, and a band pass filter of 820 - 920 nm as a barrier filter. Near-infrared fluorescence of vessels on the brain surface and of the dural sinus was visualized through the dura mater after intravenous injection of 25 mg ICG using a Hitachi KP-160 camera. Near-infrared fluorescence of vessels on the brain surface was observed through the dura mater. Venous images were clearer than were arterial ones. The dural sinus and the bridging veins were also clearly visualized. These results suggest that a clinical application of near-infrared fluorescence microscopy is possible. However, a stronger fluorescence emitted from ICG will be necessary for such a microscope to have practical use.

Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX) exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA) or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new approach of quantitative structure-activity relationship (QSAR) analysis to design potent ABCG2-inhibitors.

Objectives Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation that occurs when nonradioactive Boron-10 is irradiated with low-energy neutrons to produce high-energy α particles (10B [n, α] 7Li). Possible complications associated with extended surgical resection render high-grade meningioma (HGM) a challenging pathology and skull-base meningiomas (SBMs) even more challenging. Lately, we have been trying to control HGMs using BNCT. This study aims to elucidate whether the recurrence and outcome of HGMs and SBMs differ based on their location. Design Retrospective review. Setting Osaka Medical College Hospital and Kyoto University Research Reactor Institute. Participants Between 2005 and 2014, 31 patients with recurrent HGM (7 SBMs) were treated with BNCT. Main Outcome Measures Overall survival and the subgroup analysis by the anatomical tumor location. Results Positron emission tomography revealed that HGMs exhibited 3.8 times higher boron accumulation than the normal brain. Although tumors displayed transient increases in size in several cases, all lesions were found to decrease during observation. Furthermore, the median survival time of patients with SBMs post-BNCT and after being diagnosed as high-grade were 24.6 and 67.5 months, respectively (vs non-SBMs: 40.4 and 47.5 months). Conclusions BNCT could be a robust and beneficial therapeutic modality for patients with high-grade SBMs.