Organ-contour-driven auto-matching algorithm in image-guided radiotherapy.

PURPOSE: This study aimed to demonstrate the potential clinical applicability of an organ-contour-driven auto-matching algorithm in image-guided radiotherapy. METHODS: This study included eleven consecutive patients with cervical cancer who underwent radiotherapy in 23 or 25 fractions. Daily and reference magnetic resonance images were converted into mesh models. A weight-based algorithm was implemented to optimize the distance between the mesh model vertices and surface of the reference model during the positioning process. Within the cost function, weight parameters were employed to prioritize specific organs for positioning. In this study, three scenarios with different weight parameters were prepared. The optimal translation and rotation values for the cervix and uterus were determined based on the calculated translations alone or in combination with rotations, with a rotation limit of ±3°. Subsequently, the coverage probabilities of the following two planning target volumes (PTV), an isotropic 5 mm and anisotropic margins derived from a previous study, were evaluated. RESULTS: The percentage of translations exceeding 10 mm varied from 9% to 18% depending on the scenario. For small PTV sizes, more than 80% of all fractions had a coverage of 80% or higher. In contrast, for large PTV sizes, more than 90% of all fractions had a coverage of 95% or higher. The difference between the median coverage with translational positioning alone and that with both translational and rotational positioning was 1% or less. CONCLUSION: This algorithm facilitates quantitative positioning by utilizing a cost function that prioritizes organs for positioning. Consequently, consistent displacement values were algorithmically generated. This study also revealed that the impact of rotational corrections, limited to ±3°, on PTV coverage was minimal.

Clinical Study of 14 Cases of Bone Augmentation with Selective Laser Melting Titanium Mesh Plates.

Additive manufacturing techniques are being used in the medical field. Orthopedic hip prostheses and denture bases are designed and fabricated based on the patient's computer-aided design (CAD) data. We attempted to incorporate this technique into dental implant bone augmentation. Surgical simulation was performed using patient data. Fourteen patients underwent bone augmentation using a selective laser melting (SLM) titanium mesh plate. The results showed no evidence of infection in any of the 14 patients. In 12 patients, only one fixation screw was used, and good results were obtained. The SLM titanium mesh plate was good adaptation in all cases, with bone occupancy greater than 90%. The average bone resorption of the marginal alveolar bone from the time of dental implant placement to the time of the superstructure placement was 0.69 ± 0.25 mm. Implant superstructures were placed in all cases, and bone augmentation with SLM titanium mesh plates was considered a useful technique.

The IGF-Independent Role of IRS-2 in the Secretion of MMP-9 Enhances the Growth of Prostate Carcinoma Cell Line PC3.

Insulin receptor substrate-2 (IRS-2), a substrate of the insulin-like growth factor (IGF)-I receptor, is highly expressed in the prostate cancer cell line, PC3. We recently demonstrated that extracellular signal-regulated kinase (Erk1/2), a kinase downstream of IGF signaling, is activated in PC3 cells under serum starvation, and this activation can be inhibited by IRS-2 knockdown. Here, we observed that adding an IGF-I-neutralizing antibody to the culture medium inhibited the activation of Erk1/2. Suppression of Erk1/2 in IRS-2 knockdown cells was restored by the addition of a PC3 serum-free conditioned medium. In contrast, the IRS-2-silenced PC3 conditioned medium could not restore Erk1/2 activation, suggesting that IRS-2 promotes the secretion of proteins that activate the IGF signaling pathway. Furthermore, gelatin zymography analysis of the conditioned medium showed that matrix metalloproteinase-9 (MMP-9) was secreted extracellularly in an IRS-2 dependent manner when PC3 was cultured under serum starvation conditions. Moreover, MMP-9 knockdown suppressed Erk1/2 activation, DNA synthesis, and migratory activity. The IRS-2 levels were positively correlated with Gleason grade in human prostate cancer tissues. These data suggest that highly expressed IRS-2 activates IGF signaling by enabling the secretion of MMP-9, which is associated with hyperproliferation and malignancy of prostate cancer cell line, PC3.

Levodopa-Carbidopa Intestinal Gel Injection for Patient with Severe Parkinson's Disease Followed by Total Hip Arthroplasty: A Case Report and Literature Review.

BACKGROUND: Patients with Parkinson's disease have a high dislocation rate after total hip arthroplasty (THA). This study describes a case with severe Parkinson's disease who developed rapidly destructive coxarthrosis (RDC) and underwent THA using a dual mobility cup after a levodopa-carbidopa intestinal gel (LCIG) infusion. CASE PRESENTATION: The patient is a 59-year-old female with a ten-year history of Parkinson's disease, which was first treated with oral levodopa. The patient developed RDC of the right hip joint. However, THA was difficult owing to Parkinson's disease and its treatment side effects, such as wearing-off, dyskinesia, and freezing of the gait, Thus, LCIG was initiated, and improvement in wearing-off and dyskinesia was observed. Two months after the LCIG therapy, the disease was controlled well. THA was subsequently performed using a dual mobility cup to prevent postoperative dislocation. Postoperatively, LCIG therapy was continuously administered to carefully manage the disease, which was controlled well with no increase in wearing-off and dyskinesia after surgery. At 1 year after surgery, the walking speed, stride length, and the Harris hip score improved compared to preoperatively. The UPDRS III motor score improved to eight without signs of wearing-off or dyskinesia. The Hoehn-Yahr scale was II in the "on" period and remained unchanged 1 year after surgery. The patient could walk without a cane and had satisfactory functional outcomes. CONCLUSION: This case proved that LCIG treatment performed preoperatively, followed by THA using a dual mobility cup, and strict management of Parkinson's disease could result in a satisfactory clinical course without recurrence of wearing-off and dyskinesia. Similar procedures may benefit other patients with Parkinson's disease who have previously been deemed unsuitable for THA.

Three-dimensional assessment of interfractional cervical and uterine motions using daily magnetic resonance images to determine margins and timing of replanning.

PURPOSE: This study was conducted to determine the margins and timing of replanning by assessing the daily interfractional cervical and uterine motions using magnetic resonance (MR) images. METHODS: Eleven patients with cervical cancer, who underwent intensity-modulated radiotherapy (IMRT) in 23-25 fractions, were considered in this study. The daily and reference MR images were converted into three-dimensional (3D) shape models. Patient-specific anisotropic margins were calculated from the proximal 95% of vertices located outside the surface of the reference model. Population-based margins were defined as the 90th percentile values of the patient-specific margins. The expanded volume of interest (expVOI) for the cervix and uterus was generated by expanding the reference model based on the population-based margin to calculate the coverage for daily deformable mesh models. For comparison, expVOIconv was generated using conventional margins: right (R), left (L), anterior (A), posterior (P), superior (S), and inferior (I) were (5, 5, 15, 15, 10, 10) and (10, 10, 20, 20, 15, 15) mm for the cervix and uterus, respectively. Subsequently, a replanning scenario was developed based on the cervical volume change. ExpVOIini and expVOIreplan were generated before and after replanning, respectively. RESULTS: Population-based margins were (R, L, A, P, S, I) of (7, 7, 11, 6, 11, 8) and (14, 13, 27, 19, 15, 21) mm for the cervix and uterus, respectively. The timing of replanning was found to be the 16th fraction, and the volume of expVOIreplan decreased by >30% compared to that of expVOIini . However, margins cannot be reduced to ensure equivalent coverage after replanning. CONCLUSION: We determined the margins and timing of replanning through detailed daily analysis. The margins of the cervix were smaller than conventional margins in some directions, while the margins of the uterus were larger in almost all directions. A margin equivalent to that at the initial planning was required for replanning.

Impact of interstitial lung abnormality on survival after adjuvant durvalumab with chemoradiotherapy for locally advanced non-small cell lung cancer.

INTRODUCTION: Concurrent chemoradiotherapy (CCRT) has been the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). BACKGROUND AND PURPOSE: The results of the PACIFIC trial established the use of consolidative durvalumab after concurrent chemoradiotherapy (CCRT) as the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). A subgroup analysis of the PACIFIC trial reported a better progression-free survival (PFS) in Asians. Although real-world data on LA-NSCLC patients who received CCRT plus durvalumab have been reported, there have been few large-scale reports on Asians. In this study, we investigated prognostic factors in the largest real-world data set in Asia of only Japanese LA-NSCLC patients treated with CCRT plus durvalumab. MATERIALS AND METHODS: One hundred and thirteen LA-NSCLC patients who received definitive CCRT and consolidative durvalumab at our institution between May 2018 and April 2021 were analyzed. Overall survival (OS), cause-specific survival (CSS), PFS, distant metastasis-free survival (DMFS), and in-field progression-free survival (IFPFS) were investigated as treatment outcomes using competing risk analyses. RESULTS: During a median follow-up of 24 months (range, 5-47) after the initiation of durvalumab therapy, 31 patients died, of whom 23 died of lung cancer. In the multivariate analysis, the pretreatment factors that correlated with OS were ILA scores, adenocarcinoma, and performance status at the initiation of durvalumab. Furthermore, ILA score and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 1 % were significantly correlated with CSS, and PD-L1 TPS ≥ 1 % was significantly correlated with PFS and IFPFS. CONCLUSION: Pretreatment ILA, adenocarcinoma, and performance status may have an impact on OS of LA-NSCLC patients receiving CCRT plus durvalumab.

Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations.

Orbital cavernous venous malformation (OCVM) is a sporadic vascular anomaly of uncertain etiology characterized by abnormally dilated vascular channels. Here, we identify a somatic missense mutation, c.121G > T (p.Gly41Cys) in GJA4, which encodes a transmembrane protein that is a component of gap junctions and hemichannels in the vascular system, in OCVM tissues from 25/26 (96.2%) individuals with OCVM. GJA4 expression was detected in OCVM tissue including endothelial cells and the stroma, through immunohistochemistry. Within OCVM tissue, the mutation allele frequency was higher in endothelial cell-enriched fractions obtained using magnetic-activated cell sorting. Whole-cell voltage clamp analysis in Xenopus oocytes revealed that GJA4 c.121G > T (p.Gly41Cys) is a gain-of-function mutation that leads to the formation of a hyperactive hemichannel. Overexpression of the mutant protein in human umbilical vein endothelial cells led to a loss of cellular integrity, which was rescued by carbenoxolone, a non-specific gap junction/hemichannel inhibitor. Our data suggest that GJA4 c.121G > T (p.Gly41Cys) is a potential driver gene mutation for OCVM. We propose that hyperactive hemichannel plays a role in the development of this vascular phenotype.

Clinical significance of local control of primary tumour in definitive radiotherapy for scalp angiosarcomas.

INTRODUCTION: Scalp angiosarcoma is a rare and aggressive cancer. Definitive radiotherapy is a treatment option for localised scalp angiosarcoma patients. Although definitive surgical resection reportedly prolongs overall survival (OS), whether initial local treatment effect affects OS when definitive radiotherapy is administered is unclear. Therefore, this study analysed whether local recurrence within 6 months of irradiation correlates with OS and cancer-specific survival (CSS). Furthermore, how local control affects patients' quality of life was investigated. MATERIALS AND METHODS: Thirty-one localised scalp angiosarcoma patients who had received definitive radiotherapy at our institution between October 2010 and July 2021 were analysed retrospectively. The most commonly used dose fractionation was 70 Gy in 35 fractions (83.9%). Local recurrence within 6 months of radiotherapy and other clinical factors were examined in univariate and subsequent multivariate analyses for correlation with OS and CSS. RESULTS: The median follow-up period was 16 months (range, 6-45 months). Local recurrence was detected in 16 patients (51.6%), 12 of whom had recurrence within 6 months. In multivariate analyses, the presence of local recurrence within 6 months of radiotherapy was significantly associated with OS and CSS (p = 0.003, 0.0001, respectively). Ten of the 16 patients with local recurrence had severe symptoms such as bleeding, pain, difficulty opening the eye and malodour. CONCLUSIONS: The initial local treatment effect was significantly associated with OS and CSS after definitive radiotherapy. Furthermore, local recurrence after radiotherapy resulted in a variety of symptoms, including bleeding and pain, which reduced the patient's quality of life.

Is it time to modify the Japanese Uterine Cervical Cancer Guidelines to recommend a higher dose for radio-resistant tumors?

Compared with the European or the United States' uterine cervical cancer management guidelines, which aim to deliver >85 Gy EQD2 (the equivalent effective dose in 2 Gy per fraction) to the high-risk clinical target volume (CTVHR) D90 (minimal dose of 90% of the CTVHR), the dose goal of the corresponding Japanese guidelines does not recommend delivering such a high dose to the CTVHR D90. Subsequently, while the rate of late radiation-induced toxicities is reported to be much lower in the Japanese schedule, the local control rate is relatively inferior to that of clinical results reported by the IntErnational study on MRI-guided BRAchytherapy in CErvical cancer study (EMBRACE-I) in which the dose goal for CTVHR D90 was >85 Gy and showed >90% local control regardless of tumor stage. In daily clinical practice, patients with residual disease supposedly due to insufficient total dose delivery are occasionally referred to our hospital for the possibility of re-irradiation, which is not usually recommended because the risk of late severe radiation-induced toxicity is high. In this report, the authors hope to raise a discussion in our community about modifying our treatment guidelines to recommend a higher dose at least for patients with poor response.

Effectiveness of mock scanners and preparation programs for successful magnetic resonance imaging: a systematic review and meta-analysis.

This review aimed to summarise the effectiveness of preparation programs for magnetic resonance imaging (MRI) in children using mock scanners and the success rates by systematically reviewing the current literature. We initially identified 67 articles using the search terms "MRI," "mock" and "child" on online databases. All studies involving a preparation programme for MRI on children ages 18 years or younger, healthy children and those with medical diagnoses were included. The authors extracted data on study design, participant data, details of the MRI protocol and the total numbers of patients who underwent preparation programs and were scanned while awake, without sedation or general anesthesia. Twenty-three studies were included in this review. Preparation programs included in-home and hospital/research facility components; these consisted of a mock scanner, explanatory booklets, recorded MRI scan sounds and other educational materials. The success rate of MRI after the preparation programme reported in each study ranged from 40% to 100%. When all participants from studies that specifically assessed the efficacy of preparation programs were combined, participants who underwent a preparation programme (n = 196) were more likely to complete a successful MRI than those who did not undergo a preparation programme (n = 263) (odds ratio [OR] = 1.98). Our results suggest that preparation programs may help reduce the risk of children failing MRI scans.

Desulfoluna limicola sp. nov., a sulfate-reducing bacterium isolated from sediment of a brackish lake.

A novel sulfate-reducing bacterium, strain ASN36T, was isolated from sediment of a brackish lake in Japan. Cells of strain ASN36T were not motile and rod-shaped, with length of 2.0-4.9 µm and width of 0.6-0.9 µm. Growth was observed at 5-35 °C with an optimum growth temperature of 25-30 °C. The pH range for growth was 6.6-8.8 with an optimum pH of 7.3. Major fatty acids were C16:1 ω7c and C16:0. Under sulfate-reducing conditions, strain ASN36T utilized lactate, malate, pyruvate, butyrate, ethanol, butanol, glycerol, yeast extract and H2/CO2 as growth substrate. Fermentative growth occurred on malate and pyruvate. The novel isolate used sulfate, sulfite and thiosulfate as electron acceptors. The genome of strain ASN36T is composed of a chromosome with length of 6.3 Mbp and G + C content of 55.1 mol%. Analyses of the 16S rRNA gene indicated that strain ASN36T is related to Desulfoluna species. Overall genome relatedness indices indicated that strain ASN36T does not belong to any existing species. In contrast to the closest relatives, strain ASN36T lacks genes for reductive dehalogenase required for organohalide respiration and does not use halogenated aromatics as electron acceptors. On the basis of its genomic and phenotypic properties, strain ASN36T (= DSM 111985 T = JCM 39257 T) is proposed as the type strain of a new species, Desulfoluna limicola sp. nov.

Desulfofustis limnaeus sp. nov., a freshwater sulfate-reducing bacterium isolated from marsh soil.

A novel sulfate-reducing bacterium, strain PPLLT, was isolated from marsh soil. Cells of strain PPLLT were rod-shaped with length of 1.5 µm and width of 0.7 µm. Growth was observed at 22-37 °C (optimum 35 °C) and pH 6.8-8.4 (optimum 7.3). Lactate, succinate, fumarate, formate and malate were utilized as electron donors for sulfate reduction. Fermentative growth was not observed on tested organic acids. Besides sulfate, sulfite, thiosulfate and elemental sulfur were utilized as electron acceptors. Hydrogen is used only in the presence acetate or yeast extract. The major fatty acid was C16:0. The complete genome of strain PPLLT was composed of a circular chromosome with length of 4.2 Mbp and G + C content of 57.7 mol%. Sequence analysis of the 16S rRNA gene showed that strain PPLLT was affiliated with the genus Desulfofustis in the family Desulfocapsaceae. On the basis of differences in the phylogenetic and phenotypic properties between the strain and the type strain of the genus Desulfofustis, strain PPLLT (DSM 110475T = JCM 39161T) is proposed as the type strain of a new species, with name of Desulfofustis limnaeus sp. nov.

Clinical impact of p16 positivity in nasopharyngeal carcinoma.

Purpose: The clinical characteristics and prognosis of HPV-related nasopharyngeal cancer (NPC) remain controversial. The relationship between p16 status and outcome was retrospectively investigated in the NPC patients. Materials and Methods: Between May 2009 and May 2019, 81 NPC patients who received definitive radiation therapy, in a hospital in Japan, were identified and the prognosis was investigated. p16, p53, and Epstein-Barr virus (EBV) status were assessed. Also, circumferential tumor extent in the nasopharyngeal cavity was assessed on a 5-point scale. Results: Nine and 72 patients were p16-positive and p16-negative, respectively. Fewer patients were EBV-encoded RNA in situ hybridization (EBER-ISH)-positive in the p16-positive group than in the p16-negative group (p < .01). Seventy-five patients were nonkeratinizing NPCs, and six patients were keratinizing NPCs. There were two p16-positive patients among the keratinizing NPCs.The mean circumferential tumor extent scores of 16-positive and p16-negative NPCs were 4.2 and 3.2, respectively with a statistically significant difference (p = .02). Two-year progression-free survival (PFS) of p16-positive and p16-negative patients undergoing chemoradiation therapy were 100% and 69%, respectively (p = .13). Conclusion: In this study conducted in Japan, p16-positive NPC patients are minor but not very low, and the proportion of keratinizing NPCs was small. p16-positive NPCs were seen both in keratinizing and nonkeratinizing NPCs. P16-positive NPC had a tendency of better PFS than p16-negative NPC. This better prognosis might be due to the higher radiosensitivity of the p16-positive cell. Additionally, p16-positive NPCs seemed to spread more extensively in circumference along the nasopharyngeal mucosa than p16-negative NPCs.

Effect of Hyaluronate Acid Injection on Dose-Volume Parameters in Brachytherapy for Cervical Cancer.

Purpose: Hyaluronate gel has been injected as a spacer into the rectovaginal fossa and vesicouterine fossa during brachytherapy for patients with cervical cancer at our institution. The effect of hyaluronate gel injection (HGI) on dose-volume parameters was investigated in this study. Methods and Materials: Between July 2008 to January 2020, a total of 104 patients (non-HGI group: 52 patients; HGI group: 52 patients) who underwent curative radiation therapy for cervical cancer were selected. The total doses of external beam radiation therapy and brachytherapy for high-risk clinical target volume (CTVHR) D90, bladder D2cc, and rectal D2cc were converted to the equivalent dose in 2 Gy fractions (EQD2) and were analyzed for association with HGI. Results: Median CTVHR D90 (EQD2) in the non-HGI group was 76.0 Gy (63.7-99.5 Gy), and in the HGI group it was 79.4 Gy (52.6-97.5 Gy) (P = .017). The median bladder D2cc and rectal D2cc (EQD2) were 62.9 Gy and 56.0 Gy in the non-HGI group and 63.7 Gy and 54.8 Gy in the HGI group, which had no significant difference. Conclusions: In cases with HGI, a significant CTVHR D90 dose increase was obtained with sufficient bladder and rectal doses suppression.

Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies.

PURPOSE: Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. METHODS AND MATERIALS: We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. RESULTS: The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs. ≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). CONCLUSIONS: Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstrated to be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

Pseudodesulfovibrio sediminis sp. nov., a mesophilic and neutrophilic sulfate-reducing bacterium isolated from sediment of a brackish lake.

A novel mesophilic and neutrophilic sulfate-reducing bacterium, strain SF6T, was isolated from sediment of a brackish lake in Japan. Cells of strain SF6T were motile and rod-shaped with length of 1.2-2.5 µm and width of 0.6-0.9 µm. Growth was observed at 10-37 °C with an optimum growth temperature of 28 °C. The pH range for growth was 5.8-8.2 with an optimum pH of 7.0. The most predominant fatty acid was anteiso-C15:0. Under sulfate-reducing conditions, strain SF6T utilized lactate, ethanol and glucose as growth substrate. Chemolithoautotrophic growth on H2 was not observed, although H2 was used as electron donor. Fermentative growth occurred on pyruvate. As electron acceptor, sulfate, sulfite, thiosulfate and nitrate supported heterotrophic growth of the strain. The complete genome of strain SF6T is composed of a circular chromosome with length of 3.8 Mbp and G+C content of 54 mol%. Analyses of the 16S rRNA gene and whole genome sequence indicated that strain SF6T belongs to the genus Pseudodesulfovibrio but distinct form all existing species in the genus. On the basis of its genomic and phenotypic properties, strain SF6T (= DSM111931T = NBRC 114895T) is proposed as the type strain of a new species, with name of Pseudodesulfovibrio sediminis sp. nov.

Non-Robustness of Ang's Risk Classification in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma in Japanese Patients.

BACKGROUND: Validity of the risk classification by Ang for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remains to be studied in the patients treated by modalities other than chemoradiotherapy and in Japanese patients. MATERIALS AND METHODS: Between 2010 and 2018, 122 patients with HPV-related OPSCC in stages III and IV by the TNM classification 7th edition (TNM-7) were treated curatively at a single institution in Japan. The median age was 62.7 years. Over 50% of the patients underwent surgery with or without adjuvant therapy. The influence of multiple factors on survival was analyzed. RESULTS: The amount of smoking dichotomized at 10 pack-year, which was used in Ang's risk classification, was not predictive of prognosis, and Ang's risk classification was not significantly influential on prognosis in multivariate analysis. In the patients treated with definitive radiation therapy, Ang's risk classification was not predictive of the prognosis in univariate analysis. The impact of smoking was significant only in the patients undergoing the definitive operation. CONCLUSIONS: Ang's risk classification was not robust in predicting the prognosis of general Japanese HPV-related OPSCC patients. The amount of smoking might have different prognostic influences depending on the therapeutic method.

Scalp angiosarcoma treated with linear accelerator-based boron neutron capture therapy: A report of two patients.

PURPOSE: This study reports the first-in-human use of a linear accelerator-based boron neutron capture therapy (BNCT) system and the first treatment of patients with scalp-angiosarcoma with accelerator-based BNCT. PATIENTS AND METHODS: A single-center open-label phase I clinical trial has been conducted using the system since November 2019. Patients with a localized node-negative scalp-angiosarcoma along with the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy were enrolled. After administration of boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose delivered to the skin being 12 Gy-Eq was performed. The safety and effectiveness of accelerator-based BNCT therapy for localized scalp angiosarcoma were evaluated. RESULTS: Scalp-angiosarcoma of the two patients did not develop the dose-limiting toxicity in the clinical trial. They reached CR within half a year and did not exhibit in-field failure 20 months after BNCT without any severe treatment-related adverse events. Although a grade 3 adverse event of an asymptomatic but increased serum amylase level was noted in both patients, it relieved without any treatment. Additionally, no severe acute dermatitis was observed for both patients, which is typically seen with conventional primary radiotherapy. CONCLUSIONS: It was suggested that BNCT would be a promising treatment modality for scalp-angiosarcoma, which is difficult to treat.