Boron Neutron Capture Therapy for Newly Diagnosed Glioblastoma

Kawabata, Shinji; Miyatake, Shin; Kuroiwa, Toshihiko; Yokoyama, Kunio; Doi, Atsushi; Iida, Kaname; Maeda, Shiro; Nonoguchi, Naosuke; Michiue, Hiroyuki; Takahashi, Masatsugu; Inomata, Taisuke; Imahori, Yoshio; Kirihata, Mitsunori; Sakurai, Yoshinori; Maruhashi, Akira; Kumada, Hiroaki; Ono, Koji

doi:10.1269/jrr.08043

Cited by 115 publications

(102 citation statements)

References 32 publications

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“…In BNCT, the presented dose is the peak point dose for normal brain. The method to estimate this dose was described in detail previously in references [4] and [10]. In SRS, the presented dose is marginal X-ray or gamma-ray dose.…”

Section: Histological and Immunohistological Analysesmentioning

confidence: 99%

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The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles

et al. 2011

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The cell type and localization of vascular endothelial growth factor (VEGF)-producing cells in human radiation necrosis (RN) are investigated from a histopathological and immunohistochemical standpoint using clinical specimens. Eighteen surgical specimens of symptomatic RN in the brain were retrospectively reviewed. These cases included different original histological tumor types and were treated with different radiation modalities. Histological analyses were performed using hematoxylin and eosin (H&E) staining, and anti-VEGF and anti-hypoxia-inducible factor (HIF)-1α immunohistochemistry. H&E staining showed marked angiogenesis and reactive astrocytosis at the perinecrotic area. The most prominent vasculature in this area was identified as telangiectasis. Immunohistochemistry indicated that HIF-1α was expressed predominantly in the perinecrotic area and that a large majority of VEGF-expressing cells were reactive astrocytes intensively distributed in this area. VEGF produced by the reactive astrocytes localized mainly in the perinecrotic area might be a major cause of both angiogenesis and the subsequent perilesional edema typically found in RN of the brain. The benefits of anti-VEGF antibody (bevacizumab) treatment in RN may be that VEGF secretion from the perinecrotic tissue is inhibited and that surgery would remove this tissue; both of these benefits result in effective reduction of edema associated with RN.

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Section: Histological and Immunohistological Analysesmentioning

confidence: 99%

“…High-dose radiation treatments may have potential for greater rates of tumor control [2][3][4][5][6], but this is typically at the expense of greater rates of RN within the treatment volume. Also, stereotactic radiosurgery (SRS) achieves good control over metastatic brain tumors with the risk of RN [7].…”

Section: Introductionmentioning

confidence: 99%

The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles

et al. 2011

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“…In Japan, Miyatake et al (15) and Kawabata et al (26,27) performed studies in which either BPA alone or in combination with BSH was administered as BNCT. They reported that patients treated with surgery and BNCT using 100 mg/kg BSH and 700 mg/kg BPA infused over 6 hours, followed by 20-30 Gy of fractionated X-rays had an MST of 23.5 months.…”

Section: Discussionmentioning

confidence: 99%

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

et al. 2014

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: The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months ; the 2-, 3-, and 5-year survival rates were 31.8% %, 22.7% %, and 9.1% %, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

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“…We have employed boron neutron capture therapy (BNCT) for the treatment of Japanese patients with either recurrent or newly diagnosed high-grade gliomas. A significant survival benefit of 23.5 months was seen in those patients with newly diagnosed GBMs who received BNCT, followed by photon boost [2, 3]. Furthermore, those patients with recurrent gliomas, especially those with poor prognosis who were classified as 3+7 by recursive partitioning analysis (RPA) [4], had a MST of 9.1 months compared to 4.4 months for those in the same RPA class [3] who had been treated by standard therapy.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

et al. 2017

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We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients’ tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

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Boron Neutron Capture Therapy for Newly Diagnosed Glioblastoma

Cited by 115 publications

References 32 publications

The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles

The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

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