Boron neutron capture therapy combined with fractionated photon irradiation for glioblastoma: a recursive partitioning analysis of BNCT patients.

Eight patients to received Boron Neuron Capture Therapy (BNCT) were selected from 33 newly diagnosed glioblastoma patients (NCT(+) group). Serial 42 glioblastoma patients (NCT(-) group) were treated without BNCT. The median OS of the NCT(+) group and NCT (-) group were 24.4 months and 14.9 months. In the high risk patients (RPA class V), the median OS of the NCT(+) group tended to be better than that of NCT(-) group. 50% of BNCT patients were RPA class V.

Intracellular uptake of a new boronated porphyrin EC032.

We measured the toxicity and intracellular uptake of a newly developed boronated porphyrin EC032, and verified the fluorescence-based boron concentration measuring methods. Toxicity study showed that concentration required to produce a 50% reduction in viability (IC(50)) of EC032 was more than 0.25 mM. Fluorescence study showed the intracellular uptake of EC032 increased up until 24 h after its exposure to C6, 9L, U87, and U251 cells. There was also a linear correlation between ICP-AES and fluorescence intensity as an arbitrary unit about measurement of boron concentration. Fluorescence-based boron concentration measuring methods are very simple and useful methods, especially for screening of slight test dose of porphyrin compounds.

Boron neutron capture therapy for newly diagnosed glioblastoma: a pilot study in Tsukuba.

Neutron capture therapy (NCT) theoretically allows an unique tumor-cell-selective high-LET particle radiotherapy. The survival benefits and safety of NCT were evaluated in 15 patients with newly diagnosed glioblastoma multiforme (GBM). Seven patients received intra-operative (IO-) NCT and eight patients received external beam (EB-) NCT. Sulfhydryl borane (BSH, 5 g/body) was administered intravenously 12 h before neutron irradiation. Additionally, p-dihydroxyboryl-phenylalanine (BPA, 250 mg/kg) was given 1 h before irradiation to the eight patients who underwent EB-NCT. EB-NCT was combined with fractionated photon irradiation. Five of 15 patients were alive at analysis for a mean follow-up time of 20.3 M. In 11 of 15 patients followed up for more than 1-year, eight (72.7%) maintained their Karnofsky performance status (KPS; 90 in 6 and 100 in 2). The median overall survival (OS) and time to magnetic resonance (MR) change (TTM) for all patients were 25.7 and 11.9 M, respectively. There was no difference in TTM between the IO-NCT (12.0 M) and EB-NCT (11.9 M) groups. The 1- and 2-year survival rates were 85.7% and 45.5%, respectively. This NCT pilot study in 15 patients with newly diagnosed GBM showed survival benefits, suggesting that the neutron capture reaction may function sufficiently to control tumors locally, and that further optimized studies in large series of patients are warranted.

Dose distribution and clinical response of glioblastoma treated with boron neutron capture therapy.

The dose distribution and failure pattern after treatment with the external beam boron neutron capture therapy (BNCT) protocol were retrospectively analyzed. BSH (5 g/body) and BPA (250 mg/kg) based BNCT was performed in eight patients with newly diagnosed glioblastoma. The gross tumor volume (GTV) and clinical target volume (CTV)-1 were defined as the residual gadolinium-enhancing volume. CTV-2 and CTV-3 were defined as GTV plus a margin of 2 and 3 cm, respectively. As additional photon irradiation, a total X-ray dose of 30 Gy was given to the T2 high intensity area on MRI. Five of the eight patients were alive at analysis for a mean follow-up time of 20.3 months. The post-operative median survival time of the eight patients was 27.9 months (95% CI=21.0-34.8). The minimum tumor dose of GTV, CTV-2, and CTV-3 averaged 29.8+/-9.9, 15.1+/-5.4, and 12.4+/-2.9 Gy, respectively. The minimum tumor non-boron dose of GTV, CTV-2, and CTV-3 averaged 2.0+/-0.5, 1.3+/-0.3, and 1.1+/-0.2 Gy, respectively. The maximum normal brain dose, skin dose, and average brain dose were 11.4+/-1.5, 9.6+/-1.4, and 3.1+/-0.4 Gy, respectively. The mean minimum dose at the failure site in cases of in-field recurrence (IR) and out-field recurrence (OR) was 26.3+/-16.7 and 14.9 GyEq, respectively. The calculated doses at the failure site were at least equal to the tumor control doses which were previously reported. We speculate that the failure pattern was related to an inadequate distribution of boron-10. Further improvement of the microdistribution of boron compounds is expected, and may improve the tumor control by BNCT.

Ectopic fingerlike structure in the thoracic region. Case report.

The authors present a case of a rare cutaneous lesion resembling a human finger that protruded from the posterior thoracic region of a 7-month-old girl who was examined after the fingerlike protrusion was noted at birth. The protrusion measured 3 cm in length and 1 cm in diameter. It was located at the level of T-12 and was surrounded by angiomatous and lipomatous tissue. A computerized tomography scan demonstrated three bones in the protrusion. including deformities of the T-9 and T-10 and T-11 dysraphism. Magnetic resonance imaging revealed a hyperintense signal on the T1-weighted sequence and a hypointense signal on the T2-weighted sequence, which was visualized at the attachment to the spinal cord from T9-11. After removal of the fingerlike structure and subcutaneous mass, a T10-11 laminectomy and removal of the intradural mass were performed. Histological examination showed that the appendage was composed of nail, three bones, cartilage, and normal skin. This appendage can be recognized not only as a variant type of caudal appendage but as an ectopic finger and fingernail. The authors discuss the developmental differences among the protrusion in the present case and ordinary caudal appendages.

Retardation of early-onset PMA-induced apoptosis in mouse neutrophils deficient in myeloperoxidase.

Neutrophil apoptosis is a mechanism involved in the resolution of inflammation. To explore the role of hypochlorous acid (HOCl) produced by neutrophils while they are undergoing apoptosis, we compared the rates of apoptosis in neutrophils isolated from normal mice and from myeloperoxidase (MPO)-deficient mice, which are unable to generate HOCl. Apoptosis in MPO-deficient neutrophils stimulated by phorbol myristate acetate (PMA) was significantly slower than in normal neutrophils during 3 h of incubation. Exposure of normal neutrophils to H(2)O(2) together with PMA resulted in a dramatic acceleration of apoptosis, and almost all of the cells revealed apoptotic morphology at 1 h. This acceleration was inhibited by cytochrome c, a superoxide scavenger. Conversely, in MPO-deficient neutrophils activated with PMA and H(2)O(2), little acceleration was observed before 1 h, although it gradually increased thereafter. This retardation was almost completely reversed when MPO or HOCl was exogenously added. These results suggest that coexistence of HOCl and superoxide accelerates the early onset of neutrophil apoptosis.