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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]

IntroductionStereotactic body radiotherapy (SBRT) planning for spinal metastases is a challenging task that involves complex target shapes and steep dose gradients proximal to the spinal cord. The aim of the present study is to investigate dosimetric variability among delivery systems and institutions doing spine SBRT.Materials and Methods: Three institutions (in Japan, Canada, and the USA) participated in this retrospective treatment planning study. Computed tomography (CT) datasets for three patients including fully delineated targets and organs-at-risk (OAR) were distributed to all three institutions for planning. Delivery systems included the Clinac 21EX, Vero4DRT, Synergy S, and CyberKnife. All treatment plans were generated using a prescribed dose of 24 Gy in 2 fractions and met the following objectives: the evaluated planning target volume (PTVevl, defined as the PTV minus spinal cord) should receive greater than 16.8 Gy in at least 95% of the volume (D95 > 16.8 Gy) and a maximum dose to the less than 140% of the prescribed dose (Dmax < 33.6 Gy). The maximum dose of planning risk volume (PRV) cord or thecal sac was limited to 0.035 cm3 receiving less than 17 Gy. Aside from minimum and maximum dose objectives for the PTVevl, there were no criteria regarding the shape of the PTVevl dose-volume histogram (DVH). For each completed treatment plan, the following DVH parameters were evaluated for the PTVevl: D95, D80, D50, D2 and sigma-index (S-index, standard deviation of the differential DVH).ResultsThe PTVevl and OAR dose volume constraints were satisfied in all treatment plans. For Case 1, the mean PTVevl D50 was 25.4 ± 1.5 Gy (range: 23.7 - 27.8 Gy), for Case 2 it was 26.7 ± 2.0 Gy (23.6 - 28.6 Gy), and for Case 3 it was 26.0 ± 1.3 Gy (24.1 - 27.3 Gy). The mean PTVevl D2 was 27.3 ± 2.2 Gy (24.4 - 30.2 Gy), 28.9 ± 3.0 Gy (24.5 - 31.4 Gy) and 28.7 ± 2.7 Gy (25.2 - 31.6 Gy) for Cases 1, 2, and 3, respectively. However, there were statistically significant variations in the DVH parameters of PTVevl between apparatuses (CyberKnife versus non-CyberKnife) and among institutions (between 2 CyberKnife sites or between 2 conventional accelerator sites).ConclusionsAlthough all institutions met the minimum prescribed objectives, inter-institutional and inter-apparatus target dose variations were observed. Further study is necessary to determine target dose constraints that may minimize inter-institutional variations and lead to plan standardization.

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: The goal of the study was to evaluate the diagnostic ability of 18F-FBPA PET/CT for malignant tumors. Findings from 18F-FBPA and 18F-FDG PET/CT were compared with pathological diagnoses in patients with malignant tumors or benign lesions. Methods: A total of 82 patients (45 males, 37 females; median age, 63 years; age range, 20–89 years) with various types of malignant tumors or benign lesions, such as inflammation and granulomas, were examined by 18F-FDG and 18F-FBPA PET/CT. Tumor uptake of FDG or FBPA was quantified using the maximum standardized uptake value (SUVmax). The final diagnosis was confirmed by cytopathology or histopathological findings of the specimen after biopsy or surgery. A ROC curve was constructed from the SUVmax values of each PET image, and the area under the curve (AUC) and cutoff values were calculated. Results: The SUVmax for 18F-FDG PET/CT did not differ significantly for malignant tumors and benign lesions (10.9 ± 6.3 vs. 9.1 ± 2.7 P = 0.62), whereas SUVmax for 18F-FBPA PET/CT was significantly higher for malignant tumors (5.1 ± 3.0 vs. 2.9 ± 0.6, P < 0.001). The best SUVmax cutoffs for distinguishing malignant tumors from benign lesions were 11.16 for 18F-FDG PET/CT (sensitivity 0.909, specificity 0.390) and 3.24 for 18F-FBPA PET/CT (sensitivity 0.818, specificity 0.753). ROC analysis showed significantly different AUC values for 18F-FDG and 18F-FBPA PET/CT (0.547 vs. 0.834, p < 0.001). Conclusion: 18F-FBPA PET/CT showed superior diagnostic ability over 18F-FDG PET/CT in differential diagnosis of malignant tumors and benign lesions. The results of this study suggest that 18F-FBPA PET/CT diagnosis may reduce false-positive 18F-FDG PET/CT diagnoses. [ABSTRACT FROM AUTHOR]

The world's first accelerator based epithermal neutron source for clinical boron neutron capture therapy (BNCT) was designed, developed, and commissioned between 2008 and 2010 by Sumitomo Heavy Industries in collaboration with Kyoto University at the Kyoto University Institute for Integrated Radiation and Nuclear Science. The accelerator system is cyclotron-based and accelerates a proton up to an energy of approximately 30 MeV. The proton strikes a beryllium target, which produces fast neutrons that traverse a beam shaping assembly composed of a combination of lead, iron, aluminum, and calcium fluoride to reduce the neutron energy down to the epithermal range (∼10 keV) suitable for BNCT. The system is designed to produce an epithermal neutron flux of up to 1.4 × 10 9 n · cm − 2 · s − 1 (exiting from the moderator of a 12 cm diameter collimator) with a proton current of 1 mA. In 2017, the same type of accelerator was installed at the Kansai BNCT Medical Center and in March 2020 the system received medical device approval in Japan (Sumitomo Heavy Industries, NeuCure® BNCT system). Soon after, BNCT for unresectable, locally advanced, and recurrent carcinoma of the head and neck region was approved by the Japanese government for reimbursement covered by the national health insurance system. [ABSTRACT FROM AUTHOR]