Estimation methods of blood boron concentration and error evaluation during boron neutron capture therapy for malignant brain tumor

Shibata, Yasushi*; Yamamoto, Kazuyoshi; Matsumura, Akira*; Yamamoto, Tetsuya*; Hori, Naohiko; Kishi, Toshiaki; Kumada, Hiroaki; Akutsu, Hiroyoshi*; Yasuda, Susumu*; Nakai, Kei*; et al.

JAERI-Research 2005-009, 41 Pages, 2005/03

JAERI-Research-2005-009.pdf:1.99MB

The measurement of neutron flux and boron concentration in the blood during medical irradiation is indispensable in order to evaluate the radiation in boron neutron capture therapy. It is, however, difficult to measure the blood boron concentration during neutron irradiation because access to the patient is limited. Therefore we prospectively investigated the predictability of blood boron concentrations using the data obtained at the first craniotomy after infusion of a low dosage of BSH. When the test could not be carried out, the blood boron concentration during irradiation was also predicted by using the 2-compartment model. If the final boron concentration after the end of the infusion is within 95% confidence interval of the prediction, direct prediction from biexponential fit will reduce the error of blood boron concentrations during irradiation to around 6%. If the final boron concentration at 6 or 9 hours after the end of infusion is out of 95% confidence interval of the prediction, proportional adjustment will reduce error and expected error after adjustment to around 12%.

Application of invasion mathematical model in dosimetry for boron neutron capture therapy for malignant glioma

Yamamoto, Kazuyoshi; Kumada, Hiroaki; Nakai, Kei*; Endo, Kiyoshi*; Yamamoto, Tetsuya*; Matsumura, Akira*

Proceedings of 11th World Congress on Neutron Capture Therapy (ISNCT-11) (CD-ROM), 14 Pages, 2004/10

A dose distribution considered the tumor cell density distribution is required on the radiation therapy. We propose a novel method of determining target region considering the tumor cell concentration as a new function for the next generation Boron Neutron Capture Therapy (BNCT) dosimetry system. It has not been able to sufficiently define the degree of microscopic diffuse invasion of the tumor cells peripheral to a tumor bulk in malignant glioma using current medical imaging. Referring to treatment protocol of BNCT, the target region surrounding the tumor bulk has been set as the region which expands at the optional distance with usual 2cm margin from the region enhanced on T1 weighted gadolinium Magnetic Resonance Imaging (MRI). In this research, the cell concentration of the region boundary of the target was discussed by using tumor cell diffusion model in the sphere spatio-temporal system. The survival tumor cell density distribution after the BNCT irradiation was predicted by the two regions diffusion model for a virtual brain phantom.

Reproducibility of thermal neutron flux distribution on patient's brain surface with a realistic phantom

Yamamoto, Kazuyoshi; Kumada, Hiroaki; Yamamoto, Tetsuya*; Matsumura, Akira*

Nihon Genshiryoku Gakkai Wabun Rombunshi, 3(2), p.193 - 199, 2004/06

https://doi.org/10.3327/taesj2002.3.193

To investigate the possibility of experimental approach for dose evaluation using a realistic phantom that faithfully reproduced the shape of a head, this research considered the manufacture of a patient's realistic phantom and the reappearance of actual medical irradiation conditions. We selected the rapid prototyping technology to produce the realistic phantom from the Computed Tomography (CT) imaging. This phantom was irradiated under the same clinical irradiation condition of this patient, and the thermal neutron distribution on the brain surface was measured in detail. Several subjects on material and data conversion in the production of realistic phantom were mentioned. As a result of reproducing medical irradiation using the realistic phantom, the maximum thermal neutron flux became a value about 22% lower than the surface of the actual brain. If the problems pointed out in this paper are solved, it may also be expected that it would become possible to check computational dosimetry system.

Clinical review of the Japanese experience with boron neutron capture therapy and a proposed strategy using epithermal neutron beams

Nakagawa, Yoshinobu*; Pooh, K. H.*; Kobayashi, Toru*; Kageji, Teruyoshi*; Uyama, Shinichi*; Matsumura, Akira*; Kumada, Hiroaki

Journal of Neuro-Oncology, 62(1), p.87 - 99, 2003/04

https://doi.org/10.1023/A:1023234902479

Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles Yielded through 10B(n, alpha)7 Li reactions. In the analysis of side effects due to radiation, we included all the 159 patients treated between 1977 and 2001. With respect to the radiation dose (i.e. physical dose of boron n-alpha reaction), the new protocol prescribes a minimum tumor volume dose of 15Gy or, alternatively, a minimum target volume dose of 18Gy. The maximum vascular dose should not exceed 15Gy (physical dose of boron n-alpha reaction) and the total amount of gamma rays should remain below 10Gy, including core gamma rays from the reactor and capture gamma in brain tissue. The outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported.

User's manual of a supporting system for treatment planning in boron neutron capture therapy; JAERI computational dosimetry system

Kumada, Hiroaki; Torii, Yoshiya

JAERI-Data/Code 2002-018, 158 Pages, 2002/09

JAERI-Data-Code-2002-018.pdf:30.28MB

A boron neutron capture therapy (BNCT) with epithermal neutron beam is expected to treat effectively for malignant tumor that is located deeply in the brain. It is indispensable to estimate preliminarily the irradiation dose in the brain of a patient in order to perform the epithermal neutron beam BNCT. Thus, the JAERI Computational Dosimetry System (JCDS), which can calculate the dose distributions in the brain, has been developed. JCDS is a software that creates a 3-dimentional head model of a patient by using CT and MRI images and that generates a input data file automaticly for calculation neutron flux and gamma-ray dose distribution in the brain by the Monte Carlo code: MCNP, and that displays the dose distribution on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By treating CT data and MRI data which are medical images, a detail three-dimensional model of patinet's head is able to be made easily. The three-dimensional head image is editable to simulate the state of a head after its surgical processes such as skin flap opening and bone removal for the BNCT with craniotomy that are being performed in Japan. JCDS can provide information for the Patient Setting System to set the patient in an actual irradiation position swiftly and accurately. This report describes basic design and procedure of dosimetry, operation manual, data and library structure for JCDS (ver.1.0)

Development of the multi-leaf collimator for neutron capture therapy

Kumada, Hiroaki; Kishi, Toshiaki; Hori, Naohiko; Yamamoto, Kazuyoshi; Torii, Yoshiya

Research and Development in Neutron Capture Therapy, p.115 - 119, 2002/09

no abstracts in English

Intraoperative boron neutron capture therapy using thermal/epithermal mixed beam

Matsumura, Akira*; Yamamoto, Tetsuya*; Shibata, Yasushi*; Nakai, Kei*; Zhang, T.*; Matsushita, Akira*; Takano, Shingo*; Endo, Kiyoshi*; Akutsu, Hiroyoshi*; Yamamoto, Kazuyoshi; et al.

Research and Development in Neutron Capture Therapy, p.1073 - 1078, 2002/09

Since 1998 to 2002, a new clinical trial of an intraoperative boron neutron capture therapy (IOBNCT) at JRR-4 of Japan Atomic Energy Institute (JAERI) using BSH with mixed thermal/epithermal neutron beam has been accomplished. There have been 9 patients included in this study. The median survival time (MST) in GBM was 19.8 months and 16.8 months in AA. IOBNCT with mixed thermal/epithermal neutron beam provide better primary radiation effect than conventional therapy in selected cases. Our phase I/II clinical trial was effective in local tumor control. Further clinical trial with new design should be performed to prove the efficacy of IOBNCT.

An Application to Intraoperative BNCT using epithermal neutron of new JRR-4 mode "Epi-12"

Matsushita, Akira*; Yamamoto, Tetsuya*; Matsumura, Akira*; Nose, Tadao*; Yamamoto, Kazuyoshi; Kumada, Hiroaki; Torii, Yoshiya; Kashimura, Takanori*; Otake, Shinichi*

Research and Development in Neutron Capture Therapy, p.141 - 143, 2002/09

A thermal-epithermal mixed beam "Thermal Neutron Beam Mode I" was used in the eleven sessions of boron neutron capture therapy which have been performed at JRR-4 from 1998. We are planning to use an epithermal beam for the treatment of deeper tumors in the next trial of the intraoperative BNCT. In this study, "Epi-12" which was made by putting up a cadmium shutter of "Thermal Neutron Beam Mode I" was investigated for the clinical benefits and safety by epithermal beams. Decrease of fast neutron contamination ratio in Epi-12 mode is the advantage for BNCT, particular in the intraoperative BNCT. Because fast neutron on the brain surface is one of the critical factors in the intraoperative BNCT in which the plain beam directly interacts the normal structures. Furthermore a mixture of mode Epi-12 and Th-12 will provide various dose distribution designs. It may be used as a new method to control the best distribution for individual tumors.

In-phantom two-dimensinal thermal neutron distribution for intraoperative boron neutron capture therapy of brain tumours

Yamamoto, Tetsuya*; Matsumura, Akira*; Yamamoto, Kazuyoshi; Kumada, Hiroaki; Shibata, Yasushi*; Nose, Tadao*

Physics in Medicine & Biology, 47(14), p.2387 - 2396, 2002/07

https://doi.org/10.1088/0031-9155/47/14/302

The aim of this study was to determine the in-phantom thermal distribution derived from neutron beams for intraoperative boron neutron capture therapy (IOBNCT). Gold activation wires arranged in a cylindrical water phantom with (void-in phantom) or without (standard phantom) a cylinder styrene form placed inside were irradiated by using the epithermal beam (ENB) and the mixed thermal-epithermal beam (TNB-1) at the JRR-4. The thermal neutron distribution derived from both the ENB and TNB-1 was significantly improved in the void-in-phantom, and a double high dose area was formed lateral to the void. The flattened distribution in the circumference of the void was observed with the combination of ENB and the void-in-phantom. The measurement data suggest that the ENB may provide a clinical advantage in the form of an enhanced and flattened dose delivery to the marginal tissue in which residual and/or microscopically infiltrating tumor.

biological effectiveness of JRR-4 epithermal neutron beam; Experiment under free air beam and in water phantom (Cooperative research)

Yamamoto, Tetsuya*; Yamamoto, Kazuyoshi; Matsumura, Akira*; Kumada, Hiroaki; Kishi, Toshiaki; Hori, Naohiko; Torii, Yoshiya; Horiguchi, Yoji; Nose, Tadao*

JAERI-Research 2002-011, 56 Pages, 2002/05

JAERI-Research-2002-011.pdf:3.17MB

The surviving curve and RBE of dose components generated in boron neutron capture therapy (BNCT) were separately determined in neutron beams at JRR-4. Surviving fraction of V79 cell with or without B was obtained using an epithermal neutron beam (ENB), a mixed thermal-epithermal neutron beam (TNB-1), and a thermal neutron beam(TNB-2), which were used or planned to use for clinical trial. The cell killing effect of these beams depended highly on the neutron beam used, according to the epithermal and fast neutron content in the beam. RBE of the boron capture were 3.990.24, 3.040.19 and 1.430.08, RBE of the high-LET dose components based were 2.500.32, 2.340.30 and 2.170.28 for ENB, TNB-1 and TNB-2, respectively. The experimental determination of biological effectiveness factor outlined in this paper is applicable to the dose calculation for each dose component of the neutron beams and contribute to an accurate RBE as comparison with a neutron beam at a different facility employed in ongoing and planned BNCT clinical trials.