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Purpose: Since June 2020, boron neutron capture therapy (BNCT) has been a health care service covered by health insurance in Japan to treat locally advanced or recurrent unresectable head and neck cancers. Therefore, we aimed to assess the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers. Materials and Methods: We retrospectively analyzed data from patients who were treated using BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. We assessed objective response rates based on the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events based on the Common Terminology Criteria for Adverse Events, version 5.0. Additionally, we conducted a survival analysis and explored the factors that contributed to the treatment results. Results: Sixty‐nine patients (72 treatments) were included in the study, with a median observation period of 15 months. The objective response rate was 80.5%, and the 1‐year locoregional control, progression‐free survival, and overall survival rates were 57.1% (95% confidence interval [CI]: 43.9%–68.3%), 42.2% (95% CI: 30.1%–53.8%), and 75.4% (95% CI: 62.5%–84.5%), respectively. Locoregional control was significantly longer in patients with earlier TNM staging and no history of chemotherapy. Conclusions: BNCT may be an effective treatment option for locally advanced or recurrent unresectable head and neck cancers with no other definitive therapies. If definitive surgery or radiation therapy are not feasible, BNCT should be considered at early disease stages. [ABSTRACT FROM AUTHOR]

Simple Summary: In post-irradiated recurrent head and neck cancer (R-HNC), the treatment safety margin is limited by accumulated toxicity. Despite the development of aggressive curative treatment methods, such as reirradiation with photon or particle beam therapy with or without chemotherapy, sufficient clinical outcomes have not been achieved in various prospective trials due to the limitations imposed by toxicity. Boron neutron capture therapy (BNCT), with its selective cell-by-cell dose delivery, may be an effective and safe treatment option for patients with a prior radiotherapy history, as the previous Phase II trial of BNCT in unresectable locally recurrent or locally R-HNC has shown encouraging results. In this study, we analyzed the results of a Japanese nationwide post-marketing surveillance of BNCT for R-HNC conducted under the national health insurance system and found that toxicity was well-tolerated with preferable efficacy. BNCT is suggested to be a promising treatment option in post-irradiated R-HNC. Background: This study was conducted to evaluate the real-world safety and efficacy of boron neutron capture therapy (BNCT) with borofalan(10B) in Japanese patients with locally advanced or locally recurrent head and neck cancer (LA/LR-HNC). Methods: This prospective, multicenter observational study was initiated in Japan in May 2020 and enrolled all patients who received borofalan(10B) as directed by regulatory authorities. Patient enrollment continued until at least 150 patients were enrolled, and adverse events attributable to drugs, treatment devices, and BNCT were evaluated. The patients with LA/LR-HNC were systematically evaluated to determine efficacy. Results: The 162 patients enrolled included 144 patients with squamous cell carcinoma of the head and neck (SCCHN), 17 patients with non-SCCHN (NSCCHN), and one patient with glioblastoma. Treatment-related adverse events (TRAEs) were hyperamylasemia (84.0%), stomatitis (51.2%), sialoadenitis (50.6%), and alopecia (49.4%) as acute TRAEs, and dysphagia (4.5%), thirst (2.6%), and skin disorder (1.9%) as more common late TRAEs. In patients with LA/LR-HNC, the overall response rate (ORR) was 72.3%, with a complete response (CR) in 63 (46.0%) of 137 patients with SCCHN. Among 17 NSCCHN patients, the ORR was 64.7%, with eight cases (47.1%) of CR. One- and two-year OS rates in patients with recurrent SCCHN were 78.8% and 60.7%, respectively. Conclusions: This post-marketing surveillance confirmed the safety and efficacy of BNCT with borofalan(10B) in patients with LA/LR-HNC in a real-world setting. [ABSTRACT FROM AUTHOR]

Background: The out‐of‐field radiation dose for boron neutron capture therapy (BNCT), which results from both neutrons and γ‐rays, has not been extensively evaluated. To safely perform BNCT, the neutron and γ‐ray distributions inside the treatment room and the whole‐body dose should be evaluated during commissioning. Although, certain previous studies have evaluated the whole‐body dose in the clinical research phase, no institution providing BNCT covered by health insurance has yet validated the neutron distribution inside the room and the whole‐body dose. Purpose: To validate the Monte Carlo model of the BNCT irradiation room extended for the whole‐body region and evaluate organ‐at‐risk (OAR) doses using the validated model with a human‐body phantom. Methods: First, thermal neutron distribution inside the entire treatment room was measured by placing Au samples on the walls of the treatment room. Second, neutron and gamma‐ray dose‐rate distributions inside a human‐body water phantom were measured. Both lying and sitting positions were considered. Bare Au, Au covered by Cd (Au+Cd), In, Al, and thermoluminescent dosimeters were arranged at 11 points corresponding to locations of the OARs inside the phantom. After the irradiation, γ‐ray peaks emitted from the samples were measured by a high‐purity germanium detector. The measured counts were converted to the reaction rate per unit charge of the sample. These measurements were compared with results of simulations performed with the Particle and Heavy Ion Transport code System (PHITS). A male adult mesh‐type reference computational phantom was used to evaluate OAR doses in the whole‐body region. The relative biological effectiveness (RBE)‐weighted doses and dose‐volume histograms (DVHs) for each OAR were evaluated. The median dose (D50%) and near‐maximum dose (D2%) were evaluated for 14 OARs in a 1‐h‐irradiation process. The evaluated RBE‐weighted doses were converted to equivalent doses in 2 Gy fractions. Results: Experimental results within 60 cm from the irradiation center agreed with simulation results within the error bars except at ±20, 30 cm, and those over 70 cm corresponded within one digit. The experimental results of reaction rates or γ‐ray dose rate for lying and sitting positions agreed well with the simulation results within the error bars at 8, 4, 11, 7 and 7, 4, 7, 6, 5, 6 out of 11 points, respectively, for Au, Au+Cd, In, Al, and TLD. Among the detectors, the discrepancies in reaction rates between experiment and simulation were most common for Au+Cd, but were observed randomly for measurement points (brain, lung, etc.). The experimental results of γ‐ray dose rates were systematically lower than simulation results at abdomen and waist regions for both positions. Extending the PHITS model to the whole‐body region resulted in higher doses for all OARs, especially 0.13 Gy‐eq increase for D50% of the left salivary gland. Conclusion: The PHITS model for clinical BNCT for the whole‐body region was validated, and the OAR doses were then evaluated. Clinicians and medical physicists should know that the out‐of‐field radiation increases the OAR dose in the whole‐body region. [ABSTRACT FROM AUTHOR]

Background: Evaluation of the boron dose is essential for boron neutron capture therapy (BNCT). Nevertheless, a direct evaluation method for the boron‐dose distribution has not yet been established in the clinical BNCT field. To date, even in quality assurance (QA) measurements, the boron dose has been indirectly evaluated from the thermal neutron flux measured using the activation method with gold foil or wire and an assumed boron concentration in the QA procedure. Recently, we successfully conducted optical imaging of the boron‐dose distribution using a cooled charge‐coupled device (CCD) camera and a boron‐added liquid scintillator at the E‐3 port facility of the Kyoto University Research Reactor (KUR), which supplies an almost pure thermal neutron beam with very low gamma‐ray contamination. However, in a clinical accelerator‐based BNCT facility, there is a concern that the boron‐dose distribution may not be accurately extracted because the unwanted luminescence intensity, which is irrelevant to the boron dose is expected to increase owing to the contamination of fast neutrons and gamma rays. Purpose: The purpose of this research was to study the validity of a newly proposed method using a boron‐added liquid scintillator and a cooled CCD camera to directly observe the boron‐dose distribution in a clinical accelerator‐based BNCT field. Method: A liquid scintillator phantom with 10B was prepared by filling a small quartz glass container with a commercial liquid scintillator and boron‐containing material (trimethyl borate); its natural boron concentration was 1 wt%. Luminescence images of the boron‐neutron capture reaction were obtained in a water tank at several different depths using a CCD camera. The contribution of background luminescence, mainly due to gamma rays, was removed by subtracting the luminescence images obtained using another sole liquid scintillator phantom (natural boron concentration of 0 wt%) at each corresponding depth, and a depth profile of the boron dose with several discrete points was obtained. The obtained depth profile was compared with that of calculated boron dose, and those of thermal neutron flux which were experimentally measured or calculated using a Monte Carlo code. Results: The depth profile evaluated from the subtracted images indicated reasonable agreement with the calculated boron‐dose profile and thermal neutron flux profiles, except for the shallow region. This discrepancy is thought to be due to the contribution of light reflected from the tank wall. The simulation results also demonstrated that the thermal neutron flux would be severely perturbed by the 10B‐containing phantom if a relatively larger container was used to evaluate a wide range of boron‐dose distributions in a single shot. This indicates a trade‐off between the luminescence intensity of the 10B‐added phantom and its perturbation effect on the thermal neutron flux. Conclusions: Although a partial discrepancy was observed, the validity of the newly proposed boron‐dose evaluation method using liquid‐scintillator phantoms with and without 10B was experimentally confirmed in the neutron field of an accelerator‐based clinical BNCT facility. However, this study has some limitations, including the trade‐off problem stated above. Therefore, further studies are required to address these limitations. [ABSTRACT FROM AUTHOR]