scholarly journals ACT-3 Reactor-based boron neutron capture therapy with add-on bevacizumab for recurrent malignant glioma: The final report

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi9-vi10
Author(s):  
Motomasa Furuse ◽  
Shinji Kawabata ◽  
Masahiko Wanibuchi ◽  
Hiroyuki Shiba ◽  
Koji Takeuchi ◽  
...  

Abstract Background: Re-irradiation had a higher rate of radiation injury because recurrent MG had already irradiated in the first-line treatment. Recently, combination therapy of re-irradiation and bevacizumab showed a lower incidence of radiation injury than re-irradiation alone. Boron neutron capture therapy (BNCT), a tumor-selective particle radiation therapy, also increased radiation injury for recurrent MG, despite the greater focus on tumor cells. In this study, we evaluated the efficacy of BNCT plus bevacizumab with early induction after BNCT. Methods: Patients with recurrent MG were prospectively enrolled in this study. BNCT was performed using Kyoto University Research Reactor as a neutron source. Bevacizumab of 10 mg/kg was initiated 1–4 weeks after BNCT and was continued every 2–3 weeks until disease progression. Newly-diagnosed (de novo) glioblastoma was categorized as primary GBM (pGBM). Other MG were categorized as non-pGBM. Results: Kyoto University Research Reactor stopped irradiation for clinical use in February 2019. Twenty-five patients (14 pGBM and 11 non-pGBM) were treated with this combination therapy between June 2013 and February 2019. The median Overall survival (OS) after BNCT was 21.4 months for pGBM and 73.6 months for non-pGBM, respectively (p = 0.0428). The median progression-free survival (PFS) after BNCT was 8.3 months for pGBM and 15.6 months for non-pGBM, respectively (p = 0.0207). The objective response rate was 72 %. Alopecia occurred in all patients. Adverse events ≥ grade 3 were grade 3 proteinuria in four patients, grade 5 myocardial infarction in one patient, and grade 5 meningitis in one patient. Conclusion: BNCT plus bevacizumab showed a long OS and a long PFS, compared to our previous studies of BNCT alone for recurrent MG. Bevacizumab could provide beneficial effects not only for tumor itself, but also radiation injury. Further research with a larger sample using accelerator-based BNCT and bevacizumab is required to elucidate the efficacy and safety of this combination therapy.

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P121-P121
Author(s):  
Norimasa Morita ◽  
Aihara Teruhito ◽  
Msako Uno ◽  
Koji Ono ◽  
Tamotsu Harada

Objectives Boron neutron capture therapy (BNCT) is one of the radiation therapies known to have a selective lethal effect on tumor cells. Thermal neutrons are captured by the 10B atom, resulting in the emission of linear recoiling Alfa particles and 7Li nuclei, with traveling ranges of ∼9 and ∼5 micrometers respectively. These particles are high linear energy transfer (LET) radiation and lethally damage DNA. BNCT for cutaneous melanoma, using 10B-para-boronophe-nylalanine (BPA) as the boron delivery agent, was developed and successful BNCT treatment of 18 melanoma patients has been reported by Mishima et al. Methods Based on their treatment regimen and with the approval of the Nuclear Safety Bureau of the Japanese government and the Medical Ethics Committees of Kawasaki Medical School and Kyoto University, we have conducted BNCT clinical trials on patients with mucosal melanomas in head-and-neck at the Kyoto University Research Reactor (KUR) and the Japan Research Reactor No. 4 (JRR-4) since 2005. Results To date, we have treated 6 patients with mucosal melanomas in the nasal cavity with BNCT. 4 patients showed a complete response (CR) by 6 months and 2 patients showed a partial response (PR) 3 months after BNCT. None of the patients showed any serious damage in normal tissue surrounding tumor site. One patient from this study died due to distant metastasis. However, no local recurrence of melanoma has been observed in all CR patients and no regrowth of melanoma in all PR patients. Conclusions BNCT thus is a promising treatment for achieving local control of mucosal melanomas.


2016 ◽  
Vol 1 (1) ◽  
pp. 1
Author(s):  
Yohannes Sardjono ◽  
Susilo Widodo ◽  
Irhas Irhas ◽  
Hilmi Tantawy

Boron Neutron Capture Therapy (BNCT) is an advanced form of radiotherapy technique that is potentially superior to all conventional techniques for cancer treatment, as it is targeted at killing individual cancerous cells with minimal damage to surrounding healthy cells. After decades of development, BNCT has reached clinical-trial stages in several countries, mainly for treating challenging cancers such as malignant brain tumors. The Indonesian consortium of BNCT already developed of the design BNCT for many cases of type cancers using many neutron sources. The main objective of the Indonesian consortium BNCT are the development of BNCT technology package which consists of a non nuclear reactor neutron source based on cyclotron and compact neutron generator technique, advanced boron-carrying pharmaceutical, and user-friendly treatment platform with automatic operation and feedback system as well as commercialization of the BNCT though franchised network of BNCT clinics worldwide. The Indonesian consortium BNCT will offering to participate in Boron carrier pharmaceuticals development and testing, development of cyclotron and compact neutron generators and provision of neutrons from the 100 kW Kartini Research Reactor to guide and to validate compact neutron generator development. Studies were carried out to design a collimator which results in epithermal neutron beam for Boron Neutron Capture Therapy (BNCT) at the Kartini Research Reactor by means of Monte Carlo N-Particle 5 (MCNP5) codes. Reactor within 100 kW of output thermal power was used as the neutron source. The design criteria were based on the IAEA’s recommendation. All materials used were varied in size, according to the value of mean free path for each. Monte Carlo simulations indicated that by using 5 cm thick of Ni as collimator wall, 60 cm thick of Al as moderator, 15 cm thick of 60Ni as filter, 1,5 cm thick of Bi as "-ray shielding, 3 cm thick of 6Li2CO3-polyethylene as beam delimiter, with 3-5 cm varied aperture size, epithermal neutron beam with minimum flux of 7,8 x 108 n.cm-2.s-1, maximum fast neutron and "-ray components of, respectively, 1,9 x 10-13 Gy.cm2.n-1 and 1,8 x 10-13 Gy.cm2.n-1, maximum thermal neutron per epithermal neutron ratio of 0,009, and beam minimum directionality of 0,72, could be produced. The beam did not fully pass the IAEA’s criteria, since the epithermal neutron flux was still below the recommended value, 1,0 x 109 n.cm-2.s-1. Nonetheless, it was still usable with epithermal neutron flux exceeded 5 x 108 n.cm-2.s-1. When this collimator was surrounded by 8 cm thick of graphite, the characteristics of the beam became better that it passed all IAEA’s criteria with epithermal neutron flux up to 1,7 x 109 n.cm-2.s-1. it is still feasible for BNCT in vivo experiment and study of many cases cancer type i.e.; liver and lung curcinoma. In this case, thermal neutron produced by model of Collimated Thermal Column Kartini Research Nuclear Reactor, Yogyakarta. Sodium boroncaptate (BSH) was used as in this research. BSH had effected in liver for radiation quality factor as 0.8 in health tissue and 2.5 in cancer tissue. Modelling organ and source used liver organ who contain of cancer tissue and research reactor. Variation of boron concentration was 20, 25, 30, 35, 40, 45, and 47 $g/g cancer. Output of MCNP calculation were neutron scattering dose, gamma ray dose and neutron flux from reactor. Given the advantages of low density owned by lungs, hence BNCT is a solid option that can be utilized to eradicate the cell cancer in lungs. Modelling organ and neutron source for lung carcinoma was used Compact Neutron Generator (CNG) by deuterium-tritium which was used is boronophenylalanine (BPA). The concentration of boron-10 compound was varied in the study; i.e. the variations were 20; 25; 30; 35; 40 and 45 μg.g-1 cancer tissues. Ideally, the primary dose which is solemnly expected to contribute in the therapy is alpha dose, but the secondary dose; i.e. neutron scattering dose, proton dose and gamma dose that are caused due to the interaction of thermal neutron with the spectra of tissue can not be simply omitted. Thus, the desired output of MCNPX; i.e. tally, were thermal and epithermal neutron flux, neutron and photon dose. The liver study variation of boron concentration result dose rate to every variation were0,042; 0,050; 0,058; 0,067; 0,074; 0,082; 0,085 Gy/sec. Irradiation time who need to every concentration were 1194,687 sec (19 min 54 sec);999,645 sec (16 min 39 sec); 858,746 sec (14 min 19 sec); 743,810 sec (12 min 24 sec); 675,156 sec (11 min 15 sec); 608,480 sec (10 min 8 sec); 585,807sec (9 min 45 sec). The lung carcinoma study variations of boron-10 concentration in tissue resulted in the dose rate of each variables respectively were 0.003145, 0.003657, 0.00359, 0.00385, 0.00438 and 0.00476 Gy.sec-1 . The irradiated time needed for therapy for each variables respectively were 375.34, 357.55, 287.58, 284.95, 237.84 and 219.84 minutes.


2021 ◽  
Author(s):  
Motomasa Furuse ◽  
Shinji Kawabata ◽  
Masahiko Wanibuchi ◽  
Hiroyuki Shiba ◽  
Koji Takeuchi ◽  
...  

Abstract Introduction: Boron neutron capture therapy (BNCT) has shown excellent survival data but increases in radiation necrosis against recurrent malignant glioma (MG) in previous studies. We proposed that bevacizumab may reduce radiation injury from BNCT by re-irradiation. We evaluated the efficacy and safety of a combination therapy of BNCT and add-on bevacizumab in patients with recurrent MG.Methods: Patients with recurrent MG were treated with reactor-based BNCT. Treatment with bevacizumab (10 mg/kg) was initiated 1–4 weeks after BNCT irradiation and was re-administered every 2–3 weeks until disease progression. Initially diagnosed glioblastomas were categorized as primary glioblastoma (pGBM) and other forms of MG were categorized as non-pGBM. Results: Twenty-five patients (14 with pGBM and 11 with non-pGBM) were treated with BNCT and add-on bevacizumab. The 1-year survival rate for pGBM and non-pGBM was 63.5% (95% CI, 33.1–83.0) and 81.8% (95%CI, 44.7–95.1), respectively. The median OS was 21.4 months (95% CI, 7.0–36.7) and 73.6 months (95% CI, 11.4–77.2) for pGBM and non-pGBM, respectively (p = 0.0428). The median PFS was 8.3 months (95%CI, 4.2–12.1) and 15.6 months (95% CI, 3.1–29.8) for pGBM and non-pGBM, respectively (p = 0.0207). Alopecia occurred in all patients. Six patients experienced adverse events ≥ grade 3.Conclusions: BNCT and add-on bevacizumab were found to provide both a long OS and a long PFS, compared to the previous studies of BNCT alone for recurrent MG. The add-on bevacizumab may reduce the detrimental effects of BNCT radiation, including pseudoprogression and radiation necrosis.


2016 ◽  
Vol 1 (2) ◽  
pp. 108
Author(s):  
Widarto Widarto ◽  
Isman Mulyadi Tri Atmoko ◽  
Gede Sutresna Wijaya

The quality manajement system program of in vitro / in vivo test facility of  Boron Neutron Capture Therapy (BNCT) methode as quality assurance requirement for utilization of radial pearcing beamport of Kartini research have been done.  Identification and management of technical specification and parameters meassurement of to the radial piercing beamport have been determined for preparing in vitro / in vivo test facility. The parameters are epithermal neutron flux is  9,8243E+05  n cm<sup>-2</sup> s<sup>-1</sup>and  thermal neutron flux is 3,0691E+06 n cm<sup>-2</sup> s<sup>-1</sup>, radiation shielding of parafin,  dimension and size  of piercing radial and instrumentatin and control system for automatic transfer of in vitro / in vivo samplels have been documented. Management system of the documents for fullfil  basic guidance to perform working job of in vitro / in vivo at the piercing radial beamport of Kartini Research Reactor in order purpose utilization of the reactor  for safety worker of the radiation area, society  and invironment beeing safely


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