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Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail.The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system.In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived.The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p = 0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p = 0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities.This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively.

Invasive extramammary Paget's disease may cause lymph node and distant metastases. Complete lymph node dissection is generally performed for extramammary Paget's disease presenting with lymph node metastases. Patients with extramammary Paget's disease and multiple lymph node metastases typically have poor prognoses, and there is no effective postoperative treatment to prevent recurrence or further metastases in such patients to date. This study aimed to evaluate the efficacy of postoperative radiotherapy in patients with extramammary Paget's disease and multiple lymph node metastases. We enrolled 26 patients with extramammary Paget's disease with ≥3 lymph node metastases who were treated at the National Cancer Center Hospital in Japan between January 2000 and June 2021. The patients were divided into those who underwent complete lymph node dissection only or with postoperative radiotherapy. We evaluated recurrence-free survival, distant metastasis-free survival, and overall survival outcomes with Kaplan-Meier curves. Among the 26 enrolled patients, 16 underwent complete lymph node dissection only and 10 underwent complete lymph node dissection with postoperative radiotherapy. The median follow-up period was 16 months. The 5-year recurrence-free, distant metastasis-free, and overall survival values were 47.3%, 63.0%, and 90% in those with complete lymph node dissection and postoperative radiotherapy, while these outcomes were all 0% (p = 0.001, 0.004, and 0.009, respectively) in those with only complete lymph node dissection. Thus, survival was significantly prolonged with postoperative radiotherapy. Additional postoperative radiotherapy may substantially improve the prognoses of patients with extramammary Paget's disease and ≥3 lymph node metastases, and undergoing curative surgery.

To assess the accuracy of the movement of a brachytherapy source using a high-speed camera for evaluating source position, dwell time, and transit dose.A high-speed camera was used to record the source position of an Ir-192 source relative to a ruler within a custom positioning jig in a remote afterloading system. The analyzed frames can be used to assess dwell positions and times. Treatment plans had multiple dwell times equal to 0.1, 0.5, 1.0, and 2.0 s in 2.5- and 5-mm step sizes. Images were acquired at a rate of 146 frames/s. Acquired images were processed to automatically track the actual source using the correlation between a template image and each frame. The brachytherapy dose calculation formalism (AAPM TG43-U1) was applied to each frame to evaluate the transit dose contribution to the total dose.The differences in measured source positions from the nominal for dwell times equal to 0.1, 0.5, 1.0, and 2.0 s in treatment plans were approximately ≤1 mm. The corresponding differences in measured dwell times from the nominal values at 5 mm steps were -15, -9, -5, and 5 ms, respectively. The source velocities at 5 mm steps were approximately 393 mm/s. The dose differences at 5 mm from the source movement with and without the transit dose for these dwell times were 38%, 7%, 3%, and 2%, respectively.Recording a brachytherapy source using a high-speed camera allowed the evaluation of positional and dwell time accuracies as well as dosimetry assessments, such as the transit dose, based on the application of AAPM TG-43U1.

PURPOSE In this study, we report on our proposed phantom based on the new end-to-end (E2E) methodology and its results. In addition, we verify whether the proposed phantom can replace conventional phantoms. METHODS The hexagonal-shaped newly designed phantom has pockets on each side for a film dosimeter of size 80 × 90 mm2 , which is easily removable, considering the 60 Co penumbra. The new phantom comprises water, shell, and auxiliary shell phantoms. The shell and auxiliary shell materials are Solid Water HE. A mock tumor (aluminum oxide) was attached by a single prop in the water phantom and placed at the center of the new phantom. The results of a conventional E2E test were compared with those of the novel E2E test using the newly designed phantom. The irradiated film dosimeter in the novel E2E test was scanned in a flatbed scanner and analyzed using an in-house software developed with MATLAB. The irradiated field center, laser center, and mock tumor center were calculated. In the novel image-matching E2E (IM-E2E) test, image matching is performed by aligning the laser center with ruled lines. In the novel irradiation-field E2E (IF-E2E) test, the displacement of the irradiation-field center was defined as its distance from the laser center. In the composite E2E test, the overall displacement, which included the accuracy of the irradiated field and image matching, was defined as the distance between the irradiated field center and mock tumor center. In addition, using the newly designed phantom, the overall irradiation accuracy of the machine was evaluated by calculating the three-dimensional (3D) center of the irradiated field, phantom, and laser. The composite E2E test could be performed using the newly designed phantom only. RESULTS In the IM-E2E test, the results of the conventional and novel IM-E2E tests were significantly different in each direction (left-right direction: p-value

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.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.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.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.

With consideration of the ongoing developments in treatment options for cutaneous melanoma, the Japanese Skin Cancer Society published the first guidelines for cutaneous melanoma in 2007 and later revised them in 2015. Here, we report on an English version of the 2019 Japanese Melanoma Guidelines. In this latest edition, all processes were carried out according to the Grading of Recommendations, Assessment, Development and Evaluation system. A comprehensive published work search, systematic review and determination of recommendations in each clinical question were performed by a multidisciplinary expert panel consisting of dermatologists, a plastic and reconstructive surgeon, and a radiation oncologist. The advent of novel agents, such as immune checkpoint inhibitors and molecular-targeted agents, has drastically changed the nature of treatment for adjuvant and advanced-stage diseases among melanoma patients worldwide. Additionally, recent reports of clinical trials regarding surgical procedures and a better understanding of molecular biology and tumor immunology in clinical types of melanoma have had an impact on clinical practise. Based on these viewpoints, eight relevant clinical questions were raised in this report that aim to help clinicians select the appropriate therapeutic approach.

The aim of this study was to examine long‐term outcomes in patients who received salvage radiotherapy (SRT) for biochemical recurrence (BRec) of prostate cancer after radical prostatectomy (RP). One hundred and twenty patients with prostate cancer who underwent SRT for BRec after RP without evidence of clinical disease were identified in our institution from 2002 to 2014. Prescription doses to prostate beds were 64.8 Gy with a fractional dose of 1.8 Gy in 96.7% of the patients. In three‐dimensional conformal radiation therapy (3D‐CRT), the seminal vesicle bed (SVB) was not included in the radiation fields. The prognostic factors for BRec‐free survival (BRFS) and incidence of acute and late toxicities were investigated. Median follow‐up duration after SRT was 64.9 months. The 5‐year rates of BRFS, overall survival (OS), cause‐specific survival (CSS), and clinical recurrence‐free survival (CRFS) were 39.2%, 98.3%, 97.0%, and 91.9%, respectively. Only two patients experienced late grade 3 toxicity of hematuria. Multivariate analysis revealed that BRFS was significantly favorable in patients with prostate‐specific antigen (PSA) values

Background Dry mouth is a common complaint in patients undergoing radiotherapy. Here, we employed the oral moisture meter Mucus III to evaluate dry mouth in head and neck tumor patients before and after they underwent radiotherapy. Methods We recruited 17 newly diagnosed patients with pharyngeal squamous cell carcinoma or unknown primary squamous cell carcinoma, who received head and neck radiation therapy at Tokyo University Hospital in 2008–2010. The primary sites were the epipharynx (n = 1), oropharynx (n = 6), or hypopharynx (n = 5); it was unknown in five cases. Salivary function was assessed by a dry mouth questionnaire, resting saliva test, chewing gum test, and Mucus III, before (n = 17), immediately after radiotherapy (n = 10), and at 3 (n = 9) and 12 months after radiotherapy (n = 11). Results The questionnaire, resting saliva test, and chewing gum test at 3 and 12 months after radiotherapy indicated a significantly decreased resting and stimulated whole saliva flow rate than prior radiotherapy (P

Aim: This study was conducted to evaluate the effect of external radiation therapy on lymph node metastases from hepatocellular carcinoma (HCC). Methods: A total 28 patients with cytopathologically proven HCC were subjected to radiation therapy over a 5-year period, and treatment was continued in all cases. All patients underwent irradiation with a total dose ranging between 46 and 60 Gy in daily 2.0-Gy fractions, five times a week. Results: Among the metastatic lesions treated, 18 (64%) and five (18%) patients achieved partial responses and complete responses, respectively. The 1- and 2-year overall survival rates and the median survival time were 53% and 33%, respectively, and 13 months in patients given external beam radiation therapy (EBRT) for a non-palliative, near-cure intent (n = 21). Conclusions: Although lymph node metastasis from HCC is sensitive to EBRT, the intent of EBRT should be limited to palliation. For palliative purposes, it is useful in treatment with 50 Gy in 25 fractions for these patients.

The 3rd version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence-based medicine, which was published in October 2013 in Japanese. Here, we briefly describe new or changed recommendations with a special reference to the two algorithms for surveillance, diagnosis, and treatment.

Aim: We describe the clinical presentation, evaluation, management and outcome of patients experiencing small bowel perforation following radiation therapy for cervical cancer. Methods and Materials: A database consisting of 95 Japanese women with stage 0–4 A cervix cancer treated between 1991 and 2004 contained seven patients (7.4%) with small bowel perforation. Results: The median age at the time of perforation was 72.5 years (range 62–78). The median time from completion of radiotherapy to perforation was 6 months (range 2–58). Surgery (one small bowel resection and anastomosis with diversion; six small bowel resection and anastomosis) was performed immediately in all seven patients. One of seven patients died of small bowel perforation (i.e. mortality rate was 14%). Bowel adhesion was detected during the operation in only three cases (43%). Signs of peritonitis were absent in six cases (86%). Severe abdominal pain was seen in all seven patients. The perforation site was ileum in all seven cases. In all patients, pathological changes were compatible with postirradiation injury of the gastrointestinal tract. Conclusions: The presenting complaints of patients with bowel perforation following radiotherapy vary, and signs of peritonitis may be absent. Emergency physicians must be alert for these complications in patients who have been treated with radiotherapy.

BACKGROUND Treatment modalities for patients with hepatocellular carcinoma (HCC) who have portal vein tumor thrombus (PVTT) are limited and controversial; furthermore, the prognosis for these patients is extremely poor. The authors conducted a retrospective review to determine the role of proton beam therapy in the treatment of patients who had HCC with PVTT. METHODS Twelve patients with HCC who had tumor thrombus in the main trunk or major branches of the portal vein (clinical T3–T4N0M0) were treated with proton beam therapy. At the time they received proton beam irradiation, patients ranged in age from 42 years to 80 years (median, 62 years), and their tumors ranged in size from 40 mm to 110 mm (median, 60 mm) in greatest dimension. A total dose of 50–72 gray (Gy) (median, 55 Gy) in 10–22 fractions was delivered to the tumors, including PVTT. RESULTS All tumors that were treated with proton beam therapy remained controlled at a median follow-up of 2.3 years (range, 0.3–7.3 years). Among 12 patients, 10 patients had new liver tumors outside the irradiated volume 0.1–2.4 years after proton beam therapy, and 3 patients also had distant metastases; consequently, 8 patients died of disease, and 2 patients were salvaged by further therapies. The remaining two patients were alive with no evidence of disease 4.3 years and 6.4 years after proton beam therapy. The progression-free survival rates were 67% at 2 years and 24% at 5 years. The median progression-free survival was 2.3 years. According to the Acute Radiation Morbidity Scoring Criteria (Radiation Therapy Oncology Group), therapy-related toxicity ≥ Grade 3 was not observed. CONCLUSIONS Proton beam therapy for patients with HCC who had PVTT was feasible and effective. It appeared to improve survival and local control significantly for these patients. Cancer 2005. © 2005 American Cancer Society.

Budding yeast CDC45 encodes Cdc45p, an essential protein required to trigger initiation of DNA replication in late G1 phase. We cloned four and one species of the human Cdc45p homolog cDNA, resulting from different splicing patterns, from HeLa cell and human placenta cDNA libraries, respectively. A comparison of the cDNAs and the genomic sequence showed that the longest encoding a 610-amino acid protein was comprised of 20 exons. One species, which lacks exon 7 and contains the shorter of two exons 18, was identical with the previously reported CDC45L cDNA and constituted 24 out of 28 clones from HeLa cells. Splicing was different in HeLa cells and TIG-1 cells, a human diploid cell line. Human CDC45 protein was found to bind directly in vitro to human minichromosome maintenance 7 protein (hMCM7) and to the p70 subunit of DNA polymerase α. The data support a thesis that human CDC45 acts as a molecular tether to mediate loading of the DNA polymerase α on to the DNA replication complex through binding to hMCM7.

Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyo Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R2) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R2 between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R2 was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by the JSPS Core-to-Core Program(No. 23003) and Grant-in-aid from the JSPS Fellows.