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Background: Isocitrate dehydrogenase-mutant astrocytoma without cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion typically follows a slow clinical course. However, some cases show early progression on magnetic resonance imaging, and these characteristics remain under-reported. This study aimed to elucidate the characteristics of isocitrate dehydrogenase-mutant astrocytoma showing early progression on magnetic resonance imaging., Methods: This retrospective study included 52 cases of primary astrocytoma, isocitrate dehydrogenase-mutant, Central Nervous System (CNS) 5 World Health Organization grade 2-3 according to the World Health Organization 2021 classification. Patients underwent surgery followed by radiation therapy and/or chemotherapy at our institution from 2006 to 2019. Progression-free survival and overall survival were analyzed., Results: There were 24 and 28 grade 2 and grade 3 astrocytomas, respectively. The median patient age was 38 years. Forty-three patients underwent radiotherapy. Progression was diagnosed by magnetic resonance imaging in 22 patients with initial radiotherapy. Thirteen of the 22 patients underwent surgery, and seven of the 13 patients received surgery within 24 months of the initial radiotherapy. Histopathologically, radiation necrosis was confirmed in four of these seven patients (57.1%). The true progression-free survival rate, excluding radiation necrosis, at 2 years after surgery was 91.3% for grade 2 astrocytoma and 88.5% for grade 3 astrocytoma. The 5-year overall survival rate was 85.7% for grade 2 tumours and 76.4% for grade 3 tumours., Conclusions: Radiation necrosis should be considered in cases showing early progression of isocitrate dehydrogenase-mutant astrocytoma, and a second surgery should be performed to confirm true recurrence or radiation necrosis. Astrocytomas with telomerase reverse-transcriptase promoter mutations may relapse relatively early and should be followed up with caution., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The goal of surgery for patients with newly diagnosed glioblastoma (GBM) is maximum safe resection of the contrast-enhancing (CE) lesion on magnetic resonance imaging. However, there is no consensus on the efficacy of FLAIRectomy, which is defined as the possible resection of fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions surrounding the CE lesion. Although retrospective analyses suggested the potential benefits of FLAIRectomy, such outcomes have not been confirmed by prospective studies. Therefore, we planned a multicenter, open-label, randomized controlled phase III trial to evaluate the efficacy of FLAIRectomy compared with gross total resection of CE lesions in patients with newly diagnosed GBM. The primary endpoint is overall survival. In total, 130 patients will be enrolled from 47 institutions over 5 years. This trial has been registered at the Japan Registry of Clinical Trials (study number jRCT1031230245)., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Boron neutron capture therapy (BNCT) is based on nuclear reactions between thermal neutron and boron-10 preferentially distributed in the cancer cells. 10 B-boronophenylalanine (BPA) is the approved drug for treatment of oral cancers for BNCT. However, the predictive biomarkers to evaluate therapeutic efficacy and side-effects have not been clarified yet. Here we performed comprehensive analysis of mRNA expression using human oral squamous carcinoma SAS cells after BPA-BNCT. The expression of particular mRNAs including inflammatory and immune-related responses and transcription factors, namely CSF2, ATF3, MAFB, PTGS2 and TNFAIP3 was increased 24 h after neutron irradiation of therapeutic dose of BPA-BNCT. NF-κB pathway genes were also activated after BNCT. The early increase of the gene product of CSF2 gene, granulocyte-macrophage colony stimulating factor (GM-CSF), in culture supernatant of SAS cells was observed by ELISA analysis after BPA-BNCT at a setting dose of 24 Gy-eq. The GM-CSF level was also increased after equivalent dose of gamma-ray and carbon beam irradiation. GM-CSF may be involved in local and systemic early responses of BNCT for particular types of cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MItsuko Masutani reports financial support was provided by Cancer Intelligence Care Systems, Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Purpose: Definitive radiotherapy for patients with scalp angiosarcoma has a poor prognosis, often resulting in severe skin adverse events. Additionally, malignant melanoma is known for its radioresistant nature. Boron neutron capture therapy (BNCT) may address these challenges due to the high uptake capacity of boron drugs in these cancer types. We aimed to determine the treatment dose for BNCT and evaluate the incidence of acute adverse events AEs following BNCT in patients with primary or recurrent angiosarcoma/malignant melanoma of the skin., Materials and Methods: This was a single-center, non-randomized clinical trial with a three-step dose escalation plan, involving maximum skin doses of 12, 15, and 18 Gy-Eq following a 3 + 3 design. The patients underwent BNCT between November 2019 and April 2022. The primary endpoint was to evaluate the incidence of acute adverse events., Results: Ten patients (scalp angiosarcomanine, forefinger malignant melanoma: one) were included. The median target lesion size was 46.5 (range: 20-145) mm. A transient asymptomatic increase in serum amylase level was the only grade 3 adverse event. The best overall response rate within 180 days was 70 % (median tumor shrinkage rate: 77.5 % [4.9-100 %])., Conclusions: BNCT with a dose of 18 Gy-Eq is a feasible treatment option, demonstrating a favorable safety profile and a high response rate in patients with primary or recurrent angiosarcoma or malignant melanoma of the skin., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Kashihara reports lecture fees from AstraZeneca and HIMEDIC, Inc. outside the submitted manuscript. Dr. Igaki reports honoraria and a research grant from Cancer Intelligence Care Systems, Inc. and HIMEDIC, Inc. outside the submitted manuscript. Dr. Nakamura received a research grant from Cancer Intelligence Care Systems, Inc. The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this study]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Boron neutron capture therapy (BNCT) is a next-generation radiotherapy, utilizing both an external neutron beam and a 10 B $^{10}{\rm B}$ -containing pharmaceutical. A compact accelerator for a high intensity neutron source was installed to conduct BNCT in a hospital. The dose administered to a patient was evaluated by measuring the proton beam current., Purpose: Neutron intensity should be monitored in real-time by measuring the neutrons emitted from the target during BNCT irradiation. This is crucial due to potential neutron target degradation. Online neutron beam monitoring systems are required for reliable measurements of the administered neutron dose. An online neutron beam monitoring system was developed to monitor neutron intensity irradiating on the patient at the National Cancer Center Hospital (NCCH)., Methods: The neutron detector comprised a back-illuminated thin Si diode of 40- μ m $\umu{\rm m}$ thickness and an ultrathin natural LiF neutron converter of 0.05- μ m $\umu{\rm m}$ thickness. The neutron detector was installed on the neutron target unit, regardless of whether a patient was present, without any additional modifications to the setup. The response functions for high photon dose rates of upto 100 Gy/h were measured. The pulse heights were measured using the neutron beam monitor during BNCT neutron irradiation. Neutron temporal response measured using the online beam monitor was acquired and compared with the proton beam current and the measurements at a patient position. From this measurement at the patient position, the neutron fluence rate irradiating on a patient was obtained., Results: The neutron events were separated from the photon events. The neutron counting rates increased rapidly with the starting of proton beam irradiation and dropped to zero upon its termination. During intermittent drops and recoveries in the proton beam, the neutron beam monitor for counting rates responded quickly, synchronizing with the beam current. A scatter plot of the neutron counting rate and proton beam current indicated a good linear correlation. A direct relationship between the online neutron beam monitor's neutron counting rates and those of the patient neutron detector showed a good correlation coefficient of 0.84. A ratio of the both neutron counting rates showed a standard deviation of 6%. The correlation coefficient and standard deviation were improved to 0.94 and 1.5%, by re-binning the neutron temporal response with longer acquisition period than 1 s. Using the online neutron beam monitor, the neutron fluence rate was obtained from the direct relationship within 1.5%. Therefore, real-time monitoring of neutron intensity was achieved within the acceptable level as per the International Commission on Radiation Units and Measurements report., Conclusions: The online neutron beam monitoring system was developed to monitor the BNCT neutron beam intensity at NCCH. The temporal response of the neutron beam monitor was synchronized with the neutron counting rate at the patient position. Using the online neutron beam monitor, the neutron fluence rate irradiating on the patient can be monitored from the direct relationship. Fluctuation of the neutron beam intensity through BNCT irradiation and the degradation of the lithium target through the lifespan of the neutron target could be monitored using the neutron beam monitor., (© 2024 American Association of Physicists in Medicine.)

Background: To analyze in a prospective study the long-term safety and efficacy of 3-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) for Japanese women with early breast cancer., Methods: Breast cancer patients with pathological tumor size ≤ 3 cm, age ≥ 20 years, lumpectomy with at least a 5 mm margin, and ≤ 3 positive axillary nodes were eligible. APBI was delivered by 3D-CRT at a dose of 38.5 Gy in 10 fractions over 10 days. The primary endpoints were the frequency and severity of acute and late radiation toxicities, and secondary endpoints were local control, survival, and cosmesis. The sample size was determined based on the incidence of ≥ grade 3 acute and late radiation toxicities, which required 71 enrollments., Results: Between 2008 and 2010, 73 patients enrolled in this trial. Twelve patients (16%) had 1-3 lymph node metastases. At a median follow-up of 12.6 years (range: 2.7-13.9 years), there were no cases of grade ≥ 3 acute or late toxicity. There were 4 ipsilateral breast tumor recurrence (IBTR) events: 12-year IBTR incidence was 4.4%. The difference in the incidence of IBTR between node-negative and node-positive patients was marginal (1.9% vs. 16.7%, p = 0.055). The majority of patients (94.4% at 2 years, 89.3% at 10 years after enrollment) had excellent/good cosmesis., Conclusions: APBI delivered with 3D-CRT is a feasible treatment option for Asian females, but it was indicated that node-positive status might increase IBTR risk., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Informed consent: Informed consent was obtained from all participants included in the study. Research involving human participants and/or animals: All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards., (© 2024. The Author(s).)

Purpose: Postoperative stereotactic radiosurgery to the resection cavity in patients with brain metastases is guideline-recommended therapy. However, Japanese Clinical Oncology Group 0504 study showed that postoperative observation could be a therapeutic option in patients with completed resected brain metastases. We hereby investigated the incidence and risk factors for local recurrence after complete resection without immediate radiotherapy and developed a scoring system for its prediction., Methods: We included 53 patients with 54 brain metastases, who underwent complete resection between January 2016 and December 2021. We identified risk factors for local recurrence and developed a scoring system to predict it using the extracted risk factors, by assigning one point to each risk factor and calculating the total scores for each patient. We evaluated the correlation between the prognostic score and time to local recurrence., Results: Local recurrence occurred in 37 of 54 tumors (68.5%), with a median follow-up duration of 21.0 months. The median time to local recurrence was 5.1 months. Univariate and multivariate analyses revealed that non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were identified as risk factors for local recurrence (non-lung adenocarcinoma, p = 0.035; infratentorial tumors, p = 0.044; and no postoperative systemic therapy, p = 0.0069). A score ≥ 2 showed a median time to local recurrence of 2.1 months, starkly contrasting with 30.8 months for a score ≤ 1 (p = 0.0002)., Conclusions: Non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were risk factors for local recurrence. Our scoring system can predict local recurrence, thus potentially aiding treatment decisions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to identify the required capabilities and workload of medical staff in accelerator-based boron neutron capture therapy (BNCT). From August to September 2022, a questionnaire related to the capabilities and workload in the accelerator-based BNCT was administered to 12 physicians, 7 medical physicists and 7 radiological technologists engaged in BNCT and 6 other medical physicists who were not engaged in BNCT to compare the results acquired by those engaged in BNCT. Only 6-21% of patients referred for BNCT received it. Furthermore, 30-75% of patients who received BNCT were treated at facilities located within their local district. The median required workload per treatment was 55 h. Considering additional workloads for ineligible patients, the required workload reached ~1.2 times longer than those for only eligible patients' treatment. With respect to capabilities, discrepancies were observed in treatment planning, quality assurance and quality control, and commissioning between medical physicists and radiological technologists. Furthermore, the specialized skills required by medical physicists are impossible to acquire from the experience of conventional radiotherapies as physicians engaged in BNCT were specialized not only in radiation oncology, but also in other fields. This study indicated the required workload and staff capabilities for conducting accelerator-based BNCT considering actual clinical conditions. The workload required for BNCT depends on the occupation. It is necessary to establish an educational program and certification system for the skills required to safely and effectively provide BNCT to patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The present study aimed to summarize and report data on errors related to treatment planning, which were collected by medical physicists. The following analyses were performed based on the 10-year error report data: (1) listing of high-risk errors that occurred and (2) the relationship between the number of treatments and error rates, (3) usefulness of the Automated Plan Checking System (APCS) with the Eclipse Scripting Application Programming Interface and (4) the relationship between human factors and error rates. Differences in error rates were observed before and after the use of APCS. APCS reduced the error rate by ~1% for high-risk errors and 3% for low-risk errors. The number of treatments was negatively correlated with error rates. Therefore, we examined the relationship between the workload of medical physicists and error occurrence and revealed that a very large workload may contribute to overlooking errors. Meanwhile, an increase in the number of medical physicists may lead to the detection of more errors. The number of errors was correlated with the number of physicians with less clinical experience; the error rates were higher when there were more physicians with less experience. This is likely due to the lack of training among clinically inexperienced physicians. An environment to provide adequate training is important, as inexperience in clinical practice can easily and directly lead to the occurrence of errors. In any environment, the need for additional plan checkers is an essential factor for eliminating errors., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: To protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥85 Gy to high-risk clinical target volume D 90 (CTV HR D 90% ). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT)., Materials and Methods: Twenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between 2017 and 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy treatment outcomes and incidence of adverse events were also examined., Results: The median cumulative CTV HR D 90% , rectum D 2cm3 , and bladder D 2cm3 were 86.6 Gy, 62.9 Gy, and 72.0 Gy, respectively. The 2-year local control rate was 95%. There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events., Conclusions: The use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to clarify the dosimetric impact of the respiratory motion of the liver on stereotactic body radiation therapy (SBRT) for spine metastasis and examine the utility of introducing beam avoidance (beam-off at specific gantry angles)., Methods: A total of 112 consecutive patients who underwent SBRT for spine metastasis between 2018 and 2024 were examined. Overall, 15 patients who had lesions near the liver dome were included in this study. Retrospective treatment plans were generated using computed tomography (CT) images acquired during inhalation and exhalation to evaluate the dosimetric impact of respiratory motion of the liver. The dose difference (DD) and relative value (DD%) were evaluated using the dose-volume histogram (DVH) metrics, planning target volume D max , D 95% , spinal cord D 0.035 cc , and esophagus D 2.5 cc . The magnitude of the liver movements was evaluated based on differences of liver size L ave at the isocentric axial plane between the inspiratory and expiratory CT images., Results: The DD in almost all DVH metrics tended to increase when the liver moved away from the target during inhalation: For example, Mean ± $ \pm $ a standard deviation (SD) DD in PTV D 95% for the treatment plan incorporating beam avoidance and those without beam avoidance was 0.5 ± $\pm$ 0.3 and 0.9 ± $ \pm $ 0.6 Gy, respectively. The spinal cord D 0.035 cc for those shows 0.4 ± $ \pm $ 0.2 and 0.7 ± $ \pm $ 0.7 Gy, respectively. The treatment plans without beam avoidance also showed moderate or strong correlations between L ave and DD for almost all DVH metrics. No correlation was seen in the beam avoidance plan. The spinal cord D 0.035 cc revealed approximately 1 Gy or +4% in DD when L ave was < -4 cm., Conclusions: Respiratory motion of the liver dome can cause substantial dosimetric discrepancies in the dose delivered to the spinal cord, although the extent depends on patient variables. Dose assessment should be performed for determining the appropriate means of respiratory management, such as breath-hold. Alternatively, beam avoidance effectively mitigates the impact., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Previous plan competitions have largely focused on dose metric assessments. However, whether the submitted plans were realistic and reasonable from a quality assurance (QA) perspective remains unclear. This study aimed to investigate the relationship between aperture-based plan complexity metrics (PCM) in volumetric modulated arc therapy (VMAT) competition plans and clinical treatment plans verified through patient-specific QA (PSQA). In addition, the association of PCMs with plan quality was examined. A head and neck (HN) plan competition was held for Japanese institutions from June 2019 to July 2019, in which 210 competition plans were submitted. Dose distribution quality was quantified based on dose-volume histogram (DVH) metrics by calculating the dose distribution plan score (DDPS). Differences in PCMs between the two VMAT treatment plan groups (HN plan competitions held in Japan and clinically accepted HN VMAT plans through PSQA) were investigated. The mean (± standard deviation) DDPS for the 98 HN competition plans was 158.5 ± 20.6 (maximum DDPS: 200). DDPS showed a weak correlation with PCMs with a maximum r of 0.45 for monitor unit (MU); its correlation with some PCMs was "very weak." Significant differences were found in some PCMs between plans with the highest 20% DDPSs and the remaining plans. The clinical VMAT and competition plans revealed similar distributions for some PCMs. Deviations in PCMs for the two groups were comparable, indicating considerable variability among planners regarding planning skills. The plan complexity for HN VMAT competition plans increased for high-quality plans, as shown by the dose distribution. Direct comparison of PCMs between competition plans and clinically accepted plans showed that the submitted HN VMAT competition plans were realistic and reasonable from the QA perspective. This evaluation may provide a set of criteria for evaluating plan quality in plan competitions., Competing Interests: Conflict of Interest There are no ethical issues concerning this manuscript. Mr. Akihisa Wakita received a research grant from the Japanese Society for Radiation Oncology (JASTRO); Dr. Hiroshi Igaki received a research grant from HekaBio K.K. honoraria for lectures from Itochu corporation and AstraZeneca, and personal fee from Hekabio., (Copyright © 2024 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Introduction: In an MRI-guided linear accelerator (MR-LINAC) system, the planned doses for organs at risk and for tumours are assessed by MR imaging and re-contouring at every treatment. This allows treatment to be safer and more precise by ensuring that it is suitable for the state of the patient's organs on that day, as well as by allowing images to be acquired during radiation therapy to prevent radiation while organs are in motion.Here, we will conduct a confirmatory study of two-fractionated stereotactic magnetic resonance-guided adaptive radiation therapy for patients with localised prostate cancer., Methods and Analysis: This will be a single-arm study to demonstrate the safety and efficacy of ultra-hypofractionated radiation (26 Gy/2 Fr) using an MR-LINAC system in patients with very low-intermediate risk prostate cancer.The primary endpoint will be the incidence of grade ≥2 acute urinary tract adverse events occurring within 90 days of the start of radiation therapy.The sample size has been determined to be 58., Ethics and Dissemination: This study is performed in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects, published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare and the modified act on the Protection of Personal Information as well as the Declaration of Helsinki. This study was approved by the institutional ethics committee of the National Cancer Center on 20 November 2021.The findings of this trial will be submitted to an international peer-reviewed journal and the key findings will be presented at an international scientific conference.Authorship will be ascribed in accordance with the International Committee of Medical Journal Editors guidance., Trial Registration Number: UMIN000049746., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon malignant neoplasm and rarely occurs in the spinal space, especially in the cauda equina. Only 8 cases of pediatric AT/RT of the cauda equina have been reported. Therefore, its clinical behavior and optimal treatment remain unclear., Observations: The authors describe the case of a 9-year-old boy who presented with progressive back and left leg pain. Initial magnetic resonance imaging showed an intradural extramedullary lesion at the L3-4 level, which progressed rapidly to the L2-5 level within a month. He underwent partial resection of the tumor with an L2-5 laminectomy. The histopathological diagnosis was AT/RT. He received adjuvant chemotherapy and radiotherapy, and his gait disturbance improved postoperatively. At 6 months' follow-up, disease recurrence was not observed., Lessons: Although extremely rare, AT/RT should be included in the differential diagnosis for prompt therapeutic intervention. Safe resection with minimal functional impairment, followed by postoperative chemoradiation, can lead to tumor control and improve neurological function. https://thejns.org/doi/10.3171/CASE24219.

Purpose: Patients with head and neck cancer (HNC) who undergo dental procedures during radiotherapy (RT) face an increased risk of developing osteoradionecrosis (ORN). Accordingly, new tools must be developed to extract critical information regarding the dose delivered to the teeth and mandible. This article proposes a novel approach for visualizing 3-dimensional planned dose distributions on panoramic reconstruction computed tomography (pCT) images., Materials and Methods: Four patients with HNC who underwent volumetric modulated arc therapy were included. One patient experienced ORN and required the extraction of teeth after RT. In the study approach, the dental arch curve (DAC) was defined using an open-source platform. Subsequently, pCT images and dose distributions were generated based on the new coordinate system. All teeth and mandibles were delineated on both the original CT and pCT images. To evaluate the consistency of dose metrics, the Mann-Whitney U test and Student t -test were employed., Results: A total of 61 teeth and 4 mandibles were evaluated. The correlation coefficient between the 2 methods was 0.999, and no statistically significant difference was observed ( P >0.05). This method facilitated a straightforward and intuitive understanding of the delivered dose. In 1 patient, ORN corresponded to the region of the root and the gum receiving a high dosage (approximately 70 Gy)., Conclusion: The proposed method particularly benefits dentists involved in the management of patients with HNC. It enables the visualization of a 3-dimensional dose distribution in the teeth and mandible on pCT, enhancing the understanding of the dose delivered during RT., Competing Interests: Conflicts of Interest: None, (Copyright © 2024 by Korean Academy of Oral and Maxillofacial Radiology.)

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction., (© 2024. The Author(s).)

A combination of BRAF and MEK inhibitors is reported to be effective for gliomas with the BRAF V600E mutation; however, its efficacy in gliomas with leptomeningeal metastases (LMM) is still unknown. In this report, we describe two pediatric patients with high-grade glioma featuring the BRAF V600E mutation who were treated with dabrafenib and trametinib for LMM. Both 2 cases underwent craniotomy for primary intracranial lesions and were diagnosed as a high-grade glioma with BRAF V600E mutation; one case was consistent with anaplastic pleomorphic xanthoastorocytoma, the other was epithelioid glioblastoma. They received standard treatment for the lesions but subsequently were found to have new lesions including multiple spinal dissemination. We started administering dabrafenib and trametinib. Within a few days of starting treatment, the symptoms improved dramatically and MRI performed one month after the prescription of the two drugs demonstrated remission of both brain and spinal lesions. This report shows that dabrafenib and trametinib are effective not only for recurrent lesions but also for LMM in pediatric patients., Competing Interests: Conflict of interestNarita Y. has a grant from MBL which developed a commercially available kit detecting BRAF V600E., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: Hydrogel spacer (HS) was developed to reduce rectal toxicities caused by radiotherapy, but has been reported to cause major adverse events. Our institute has attempted to introduce a hyaluronic acid (HA) as an alternative spacer. This study aimed to compare rectal doses and geometric distributions between the HS and HA implantation in prostate cancer., Methods: HS and HA were inserted in 20 and 18 patients undergoing high-dose brachytherapy, respectively. The rectum spacer volumes injected were 10 mL and 22 mL, respectively. In the treatment planning system, 13.5 Gy was administered with common catheter positions. The rectal dose indices were assessed between the spacer groups for dosimetry evaluation. Distances between the prostate and rectum and configurations of the spacers were compared., Results: The mean doses irradiated to 0.1 and 2 mL of the rectum were 10.45 Gy and 6.71 Gy for HS, and 6.73 Gy and 4.90 Gy for HA ( p <0.001). The mean minimum distances between the prostate and rectum were 1.23 cm and 1.79 cm for HS and HA, respectively ( p <0.05). Geometrical configuration comparisons revealed that HA has a higher ability to expand the space than HS., Conclusion: The rectal dose reduction ability of HA is significantly greater than that of HS, suggesting its potential as a new spacer., Competing Interests: Dr. Kashihara T reports lecture fees from 10.13039/100004325AstraZeneca (Cambridge, UK), outside the submitted work. Dr. Igaki reports personal fees from Itochu (Tokyo, Japan), personal fees from ViewRay Inc., grants from HekaBio (Tokyo, Japan), outside the submitted work. The others declare no conflict of interest., (© 2024 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Background: Despite its efficacy, if adherence to dose constraints for surrounding normal tissues proves unattainable, the risk of late radiation-related adverse events after primary radiotherapy involving brachytherapy remains a noteworthy concern. Some studies suggest that similar to prostate radiotherapy, spacers may potentially reduce doses to surrounding healthy rectal or bladder tissues. However, guidance on spacer injections for gynecologic brachytherapy is scarce, and the optimal anatomical location for spacer placement remains undefined. We discuss maximizing the effects of spacers from an anatomical perspective., Findings: As vesicovaginal and rectovaginal septa form part of the endopelvic fascia and are not uniform tissues, spacer injection resistance varies. In pelvic organ prolapse surgery, saline is injected into the anterior and posterior vaginal walls as a spacer, and the vagina, vesicovaginal septum, and bladder can be fluidly dissected. Relatively firm vesicovaginal septum tissue is used as a reconstructive organ, whereas rectovaginal septum tissue is less dense. Cervical cancer is invasive, involving surrounding fascia and ligaments. Ideally, the vesicovaginal and rectovaginal septa should be resected in radical hysterectomy. Here, spacer adaptation and the technical details of injection are described. When using ultrasound guidance for spacer injection, the target site should be adequately magnified, and the spacer ideally injected into the incision layer during radical hysterectomy. Finally, posthysterectomy, the intestinal tract may adhere to the vaginal cuffs. Therefore, artificial ascites may be useful; however, the spread depends on perioperative manipulation., Conclusions: Anatomical and surgical viewpoints are advantageous for safe, therapeutic, and replicable spacer injection administration., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

This study incorporated topology Betti number (BN) features into the prediction of primary sites of brain metastases and the construction of magnetic resonance-based imaging biopsy (MRB) models. The significant features of the MRB model were selected from those obtained from gray-scale and three-dimensional wavelet-filtered images, BN and inverted BN (iBN) maps, and clinical variables (age and gender). The primary sites were predicted as either lung cancer or other cancers using MRB models, which were built using seven machine learning methods with significant features chosen by three feature selection methods followed by a combination strategy. Our study dealt with a dataset with relatively smaller brain metastases, which included effective diameters greater than 2 mm, with metastases ranging from 2 to 9 mm accounting for 17% of the dataset. The MRB models were trained by T1-weighted contrast-enhanced images of 494 metastases chosen from 247 patients and applied to 115 metastases from 62 test patients. The most feasible model attained an area under the receiver operating characteristic curve (AUC) of 0.763 for the test patients when using a signature including features of BN and iBN maps, gray-scale and wavelet-filtered images, and clinical variables. The AUCs of the model were 0.744 for non-small cell lung cancer and 0.861 for small cell lung cancer. The results suggest that the BN signature boosted the performance of MRB for the identification of primary sites of brain metastases including small tumors., (© 2023. Australasian College of Physical Scientists and Engineers in Medicine.)

Purpose: The use of a hydrogel spacer inserted into recto-vaginal fossa is a valuable strategy to mitigate radiation exposure to the rectum during radiation therapy for female pelvic malignancies. However, when the sigmoid colon is in proximity to the cervix, radiation exposure to the sigmoid colon cannot be adequately mitigated with a hydrogel spacer injected into the recto-vaginal fossa. Here, we presented a case, in which a hydrogel spacer was injected into the meso-sigmoid to protect the sigmoid colon., Material and Methods: A 73-year-old female diagnosed with T3b stage IIIC2r uterine cervical cancer (FIGO 2018) underwent high-dose-rate interstitial brachytherapy consisting of 24 Gy in 4 fractions, following concurrent chemoradiotherapy with external beam radiation therapy of 50 Gy in 25 fractions of whole pelvic radiation therapy. In the initial brachytherapy, the sigmoid colon was in close contact with the uterine cervix. In the second brachytherapy, attempts to create a space between the sigmoid colon and uterine cervix using injected artificial ascites were unsuccessful due to rapid absorption of fluid. In the third and fourth brachytherapy fractions, 5 mL of hydrogel was injected into the meso-sigmoid through a pouch of Douglas under trans-rectal ultrasonography guidance. Dose ratio of sigmoid colon D 2cc and high-risk clinical target volume (HR-CTV) D 90 of each brachytherapy were evaluated., Results: Dose ratio of the sigmoid colon D 2cc to HR-CTV D 90 was 1.03, 0.43, 0.56, and 0.47 in each respective brachytherapy session, indicating dose escalation to HR-CTV whilst achieving acceptable sigmoid dose with hydrogel spacer injected into the meso-sigmoid., Conclusions: The dose ratio of the sigmoid colon to HR-CTV D 90 was decreased by introducing a hydrogel spacer into the meso-sigmoid. In cases where the sigmoid colon is in proximity to the cervical tumor, this novel technique can be considered to achieve better clinical outcomes., Competing Interests: There is no conflict of interest to declare, except for the following: Dr. Murakami reports grants from Chiyoda Technol Corporation and Boston Scientific outside the submitted work. Dr. Kashihara reports grants from the Foundation for Promotion of Cancer Research in Japan outside the submitted work. Dr. Okamoto reports grants from Accuray and Item Corporation outside the submitted work. Dr. Igaki reports grants from Elekta KK and personal fees from VARIAN outside the submitted work., (Copyright © 2023 Termedia.)

Background: Melanoma brain metastasis (MBM) has a poor prognosis, although recent treatments, including immune checkpoint inhibitors and targeted therapy, have improved the prognosis. However, these systemic therapies have been reported to be less efficient for Asian patients. We investigated the survival of Asian patients with MBM and the effectiveness of systemic therapies., Methods: We retrospectively reviewed the survival rates of patients diagnosed with MBM between January 2011 and December 2021 at the National Cancer Center Hospital in Tokyo, Japan. In addition, we identified factors associated with survival using Cox regression analysis., Results: A total of 135 patients were included. The median overall survival (OS) after an MBM diagnosis was 7.8 months (95% confidence interval [CI] 6.1-9.6). The 6-month and 1-year survival rates were 60.7% and 34.8%, respectively. We identified the prognostic factors of MBM, including non-acral primary location, low serum LDH levels, systemic therapy of single-agent immune checkpoint inhibitors (ICIs) or targeted therapies (TTs), and radiotherapy of stereotactic irradiation (STI). We found no significant difference in effectiveness between single-agent ICIs, the combination of Nivolumab and Ipilimumab (COMBI-ICI), and TTs (COMBI-ICI vs. single-agent ICI, hazard ratio 0.71, 95% confidence interval 0.27-1.88, p = 0.49; COMBI-ICI vs. TT: hazard ratio 0.46, 95% confidence interval 0.14-1.55, p = 0.21)., Conclusions: Systemic therapy and radiotherapy have improved the survival of MBM patients, but the survival of Asian patients remains poor. Our findings suggest that COMBI-ICIs are not significantly more effective than single-agent ICI or TT in treating MBM., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The uterus is known as one of the moving organs. We evaluated the movement of the uterus during irradiation and the effects of changes in the surrounding organs using a magnetic resonance (MR)-guided radiotherapy system. Seven patients with cervical cancer underwent pre- and posttreatment MR imaging to assess changes in the positioning of the uterus and cervix as well as the alterations in bladder and rectal volume. The study revealed that the movements of the uterus were greater than that of the cervix and showed a tendency to correlate with the bladder rather than the rectum. We also examined whether intrafractional motion could lead to insufficient dose coverage of the clinical target volume (CTV), specifically focusing on the D98% of the CTV in the uterine body and cervix. The impact of intrafractional motion on the D98% varied among patients, with one out of the seven patients experiencing an average dosimetric change of -2.6 Gy in the uterus, although larger planning target volume margins of 1.5 cm were applied, therefore, indicating the need for individualized optimal margins in each case. Online adaptive radiotherapy offers the advantage of modifying the treatment plan when irradiating moving organs, such as the uterus. However, it should be noted that this approach may result in longer overall treatment times compared with the traditional methods. Therefore, we must carefully consider the influence of intrafractional organ motions when opting for such a treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: The neurological status of glioblastoma patients rapidly deteriorates. We recently demonstrated that early diagnosis and surgery within 3 weeks from the initial symptoms are associated with improved survival. While glioblastoma is a semi-urgent disease, the prehospital behaviors and clinical outcomes of glioblastoma patients are poorly understood. We aimed to disclose how prehospital patient behavior influences the clinical outcomes of glioblastoma patients., Methods: Isocitrate dehydrogenase-wildtype glioblastoma patients treated at our institution between January 2010 and December 2019 were reviewed. Patients were divided into two groups, neurosurgeon and non-neurosurgeon groups, based on the primary doctor whom patients sought for an initial evaluation. Patient demographics and prognoses were examined., Results: Of 170 patients, 109 and 61 were classified into the neurosurgeon and non-neurosurgeon groups, respectively. The median age of neurosurgeon group was significantly younger than the non-neurosurgeon group (61 vs. 69 years old, P = 0.019) and in better performance status (preoperative Karnofsky performance status scores $\ge$80: 72.5 vs. 55.7%, P = 0.027). The neurosurgeon group exhibited a significantly shorter duration from the first hospital visit to the first surgery than the non-neurosurgeon group (18 vs. 29 days, P < 0.0001). Furthermore, the overall survival of the neurosurgeon group was significantly more prolonged than that of the non-neurosurgeon group (22.9 vs. 14.0 months, P = 0.038)., Conclusion: Seeking an initial evaluation by a neurosurgeon was potentially associated with prolonged survival in glioblastoma patients. A short duration from the first hospital visit to the first surgery is essential in enhancing glioblastoma patient prognosis., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

It has been shown that a group of rectal cancer patients will achieve a pathological complete response following preoperative chemoradiotherapy, and non-operative management has recently gained attention. To escalate the tumour dose and increase the likelihood of pathological complete response, brachytherapy can play an important role in safely increasing the total dose. However, at the time this report was published, an applicator dedicated to rectal brachytherapy was unaffordable in Japan. Here, we report two T3 rectal cancer patients who were inoperable or refused surgery and treated by chemoradiotherapy following intracavitary brachytherapy involving a vaginal cylinder applicator with lead shielding., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The correlation between L-type amino acid transporter 1 (LAT1) expression and 4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18 F-FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA positron emission tomography (PET)., Methods: Altogether, 28 patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA PET at our institution between March 2012 and January 2018 were included. Correlations between standardized uptake values (SUVs); the maximum SUV (SUV max ), the mean SUV within a 1 cm 3 sphere centered at a single point, that is, the SUV max (SUV peak ), the minimum SUV (SUV min ), and the intensity of LAT1 expression (maximum and minimum LAT1 expressions) were investigated., Results: Weak correlations were identified between SUV max and LAT1 maximum score, SUV min and LAT1 maximum score, and SUV min and LAT1 minimum score (ρ = 0.427, 0.362, and 0.330, respectively). SUV max and LAT1 minimum score, SUV peak and LAT1 maximum score, and SUV peak and LAT1 minimum score demonstrated moderate correlations (ρ = 0.535, 0.556, and 0.661, respectively). Boron neutron capture therapy (BNCT) was performed in 2 of the 4 patients with discrepancies between 18 F-FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response., Conclusion: 18 F-FBPA accumulation and the intensity of LAT1 expression demonstrated a moderate correlation; however, LAT1 expression may be a better predictor of treatment response of BNCT in patients with discrepancies., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

This study reports the first patient treatment for cutaneous malignant melanoma using a linear accelerator-based boron neutron capture therapy (BNCT) system. A single-center open-label phase I clinical trial had been conducted using the system since November 2019. A patient with a localized node-negative acral malignant melanoma and the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy was enrolled. After administering boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose of 18 Gy-Eq delivered to the skin was performed. The safety and efficacy of the accelerator-based BNCT system for treating localized cutaneous malignant melanoma were evaluated. The first patient with cutaneous malignant melanoma in situ on the second finger of the left hand did not develop dose-limiting toxicity in the clinical trial. After BNCT, the treatment efficacy was gradually observed, and the patient achieved PR within 6 months and CR within 12 months. Moreover, during the follow-up period of 12 months after BNCT, the patient did not exhibit a recurrence without any treatment-related grade 2 or higher adverse events. Although grade 1 adverse events of dermatitis, dry skin, skin hyperpigmentation, edema, nausea, and aching pain were noted in the patient, those adverse events were relieved without any treatment. This case report shows that the accelerator-based BNCT may become a promising treatment modality for cutaneous malignant melanoma. We expect further clinical trials to reveal the efficacy and safety of the accelerator-based BNCT for cutaneous malignant melanoma., Competing Interests: This study was supported by research funds Cancer Intelligence Care Systems, Inc. SN. This study was also supported by a commissioned study from Stella Pharma Corporation and Cancer Intelligence Care Systems, Inc. Hiroshi Igaki and Jun Itami. These sponsors were involved in the management of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Igaki, Nakamura, Yamazaki, Kaneda, Takemori, Kashihara, Murakami, Namikawa, Nakaichi, Okamoto, Iijima, Chiba, Nakayama, Nagao, Sakuramachi, Takahashi, Inaba, Okuma, Nakayama, Shimada, Nakagama and Itami.)

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, expVOI conv 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. ExpVOI ini and expVOI replan 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 16 th fraction, and the volume of expVOI replan decreased by >30% compared to that of expVOI ini . 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., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies., Methods: This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted., Results: Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models., Conclusion: Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC., (© 2023. Society of Surgical Oncology.)

Background: The use of endobronchial Watanabe spigots for intractable secondary pneumothorax in patients with cancer has not been adequate. This study aimed to investigate the use of endobronchial Watanabe spigots for intractable pneumothorax in patients with malignant tumors., Methods: Consecutive patients with malignant tumors who underwent occlusion with an endobronchial Watanabe spigot for intractable pneumothorax associated with perioperative treatment or drug therapy at our institution between January 2014 and February 2022 were reviewed., Results: Of the 32 cases in which an endobronchial Watanabe spigot was used, six were excluded; we thus evaluated 26 cases in which the chest tube was removed. Chest tubes were removed in 19 cases (73.1%) and could not be removed and required surgical treatment under general anesthesia in seven patients (26.9%), of which four (14.8%) underwent open-window thoracostomy. Half of the patients were treated with both an endobronchial Watanabe spigot and pleurodesis. Although thin-slice chest computed tomography revealed a fistula in 15 patients, the chest tube was removed in 11 (57.9%) patients. A significant difference was only observed in patients with a history of heavy smoking., Conclusions: The chest tube removal rate was comparable to those reported in previous studies. An endobronchial Watanabe spigot may be a useful treatment option for intractable cancer-related pneumothorax., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Reports on BCOR-CCNB3 sarcoma in the head and neck region are scarce, given their unknown etiology. An 18-year-old male patient presented a rapidly enlarging tumor extending from the right nasopharynx to the oropharynx. Histological examination showed a spindle cell sarcoma with BCOR-CCNB3 fusion detected by fluorescence in situ hybridization, and BCOR-CCNB3 was diagnosed. After three courses of alternating VDC-IE therapy, the patient underwent tumor resection based on the original tumor range with a minimal margin, using the mandibular swing technique. Radiation therapy (50.4 Gy) was administered postoperatively, followed by three additional courses of alternating VDC-IE therapy. The patient survived and showed no evidence of disease at 12 months postoperatively. BCOR-CCNB3 sarcoma is a chemotherapy-sensitive sarcoma, and conservative resection with a minimal margin that does not interfere with the treatment flow is preferable., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier B.V.)

Aim: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study., Methods: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT., Results: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed., Conclusion: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment., (© 2023 Japan Society of Hepatology.)

Background: Treatment of brain metastases (BMs) from colorectal cancer (CRC) has transitioned with the expansion of indications for stereotactic radiotherapy. Our study aimed to assess changes in prognosis and prognostic factors associated with changes in treatment for BMs from CRC., Methods: We retrospectively surveyed treatments for and outcomes of BMs from CRC in 208 patients treated during 1997-2018. Patients were divided into two groups according to time of BM diagnosis, i.e., 1997-2013 ("first period") and 2014-2018 ("second period"). We compared overall survival between the periods and assessed how the transition impacted prognostic factors affecting overall survival, including the following prognostic factors such as Karnofsky performance status (KPS), volume-related factors (BM number and diameter), and BM treatment modalities as covariates., Results: Of the 208 patients, 147 were treated in the first period and 61 in the second period. Whole-brain radiotherapy use decreased from 67 to 39% in the second period, and stereotactic radiotherapy use increased from 30 to 62%. Median survival after BM diagnosis improved from 6.1 to 8.5 months (p = 0.0272). Multivariate analysis revealed KPS, control of primary tumor, stereotactic radiotherapy use, and chemotherapy history as independent prognostic factors during the entire observation period. Hazard ratios of KPS, primary tumor control, and stereotactic radiotherapy were higher in the second period, whereas prognostic impact of chemotherapy history before BM diagnosis was similar in both periods., Conclusion: Overall survival of patients with BMs from CRC improved since 2014, which can be attributed to advances in chemotherapy and the more widespread use of stereotactic radiotherapy., (© 2023. The Author(s).)

An 80-year-old male presented with T1N0M0 myxofibrosarcoma in or next to the humeral canal, which is located between the biceps and triceps of the right upper arm. Because the tumor was close to critical anatomical structures such as the brachial artery, median nerve and ulnar nerve, it was deemed impossible to perform limb-sparing surgery with an adequate resection margin. Therefore, preoperative external beam radiation therapy (EBRT) followed by limb-sparing surgery was offered. Magnetic resonance imaging taken after 40 Gy/20 fractions of EBRT showed an inadequate response, and limb-sparing surgery was not deemed possible at this point. Amputation of the right arm was offered, but the patient refused. Therefore, salvage high-dose-rate interstitial brachytherapy (HDR-ISBT) was offered. Under local anesthesia and sedation, 14 plastic needles were inserted, and 36 Gy in 6 fractions of HDR-ISBT was performed. Although radiation-induced incomplete paralysis of the median nerve was noted, no local progression or distant metastasis was found on the CT that was taken 2 years after the treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

This study aimed to quantify the relative biological effectiveness (RBE) for epithermal neutron beam contaminated with fast neutrons in the accelerator-based boron neutron capture therapy (BNCT) system coupled to a solid-state lithium target. The experiments were performed in National Cancer Center Hospital (NCCH), Tokyo, Japan. Neutron irradiation with the system provided by Cancer Intelligence Care Systems (CICS), Inc. was performed. X-ray irradiation, which was assigned as the reference group, was also performed using a medical linear accelerator (LINAC) equipped in NCCH. The four cell lines (SAS, SCCVII, U87-MG and NB1RGB) were utilized to quantify RBE value for the neutron beam. Before both of those irradiations, all cells were collected and dispensed into vials. The doses of 10% cell surviving fraction (SF) (D10) were calculated by LQ model fitting. All cell experiments were conducted in triplicate at least. Because the system provides not only neutrons, but gamma-rays, the contribution from the gamma-rays to the survival fraction were subtracted in this study. D10 value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was 4.26, 4.08, 5.81 and 2.72 Gy, respectively, while that acquired by the X-ray irradiation was 6.34, 7.21, 7.12 and 5.49 Gy, respectively. Comparison of both of the D10 values, RBE value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was calculated as 1.7, 2.2, 1.3 and 2.5, respectively, and the average RBE value was 1.9. This study investigated RBE of the epithermal neutron beam contaminated with fast neutrons in the accelerator-based BNCT system coupled to a solid-state lithium target., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar., Methods: The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence)., Results: A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001)., Conclusion: It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated., (© Crown copyright 2023.)

Background and Purpose: The Japan Clinical Oncology Group (JCOG) 1402 conducted a multicenter clinical trial of postoperative intensity-modulated radiotherapy (IMRT) for high-risk uterine cervical cancer patients. We assess effectiveness of the quality assurance (QA) program in central review through dummy runs (DRs) performed before patient enrollment and post-treatment individual case review (ICR), and clarify the pitfalls in treatment planning., Material and Methods: The ICRs were conducted using the same QA program as the DR for 214 plans. The deviations were compared with those demonstrated in the DRs, and the pitfalls were clarified. Fifteen face-to-face meetings were held with physicians at participating institutions to provide feedback., Results: Two-hundred and eighty-eight deviations and nine violations were detected in the 214 plans. The patterns of the deviations observed in the ICRs were similar to that in the DR. Frequent deviations were observed in clinical target volume (CTV) delineations, 50% in the DRs and 37% in the ICRs, respectively. In the ICRs, approximately 1.4 deviations/violations were observed per plan, which was lower than DR. Nine violations included inaccurate CTV delineation and improper PTV (planning target volume) margin, which had risks in loco-regional failures by inadequate dose coverage., Conclusions: Our developed QA program commonly used in DR and ICR clarified the pitfalls in treatment plans. Although the frequent deviations in CTV delineations were observed in the ICR, the deviations decreased compared to that in the DR. More specified face-to-face meetings with participating institutions will be necessary to maintain the quality of IMRT in the clinical protocol., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT., Materials and Methods: Calculated dose-volume indices between HDR-BT without a perirectal spacer (n = 20), robotic SBRT without a spacer (n = 40), and conventional (non-robotic) SBRT with a spacer (n = 40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared., Results: The D50% of the PTV with HDR-BT (140.5% ± 4.9%) was significantly higher than that with robotic or conventional SBRT (116.2% ± 1.6%, 101.0% ± 0.4%, p < 0.01). The D2cm 3 of the bladder with HDR-BT (65.6% ± 6.4%) was significantly lower than those with SBRT (105.3% ± 2.9%, 98.0% ± 1.3%, p < 0.01). The D2cm 3 of the rectum with HDR-BT (60.6% ± 6.2%) was also significantly lower than those with SBRT (85.1% ± 8.8%, 70.4% ± 9.6%, p < 0.01). By contrast, the D0.1cm 3 of the urethra with HDR-BT (117.1% ± 3.6%) was significantly higher than those with SBRT (100.2% ± 0.7%, 104.5% ± 0.6%, p < 0.01)., Conclusions: HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial., Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%., Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met., Conclusion: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses., Competing Interests: Dr. Itami reports personal fees from HekaBio, grants and personal fees from Itochu, grants from Elekta, personal fees from AlphaTAU, personal fees from ViewRay, personal fees from Palette Science, outside the submitted work., (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Purpose: We measure the dose distribution of gated delivery for different target motions and estimate the gating latency in a magnetic resonance-guided radiotherapy (MRgRT) system., Method: The dose distribution accuracy of the gated MRgRT system (MRIdian, Viewray) was investigated using an in-house-developed phantom that was compatible with the magnetic field and gating method. This phantom contains a simulated tumor and a radiochromic film (EBT3, Ashland, Inc.). To investigate the effect of the number of beam switching and target velocity on the dose distribution, two types of target motions were applied. One is that the target was periodically moved at a constant velocity of 5 mm/s with different pause times (0, 1, 3, 10, and 20 s) between the motions. During different pause times, different numbers of beams were switched on/off. The other one is that the target was moved at velocities of 3, 5, 8, and 10 mm/s without any pause (i.e., continuous motion). The gated method was applied to these motions at MRIdian, and the dose distributions in each condition were measured using films. To investigate the relation between target motion and dose distribution in the gating method, we compared the results of the gamma analysis of the calculated and measured dose distributions. Moreover, we analytically estimated the gating latencies from the dose distributions measured using films and the gamma analysis results., Results: The gamma pass rate linearly decreased with increasing beam switching and target velocity. The overall gating latencies of beam-hold and beam-on were 0.51 ± 0.17 and 0.35 ± 0.05 s, respectively., Conclusions: Film measurements highlighted the factors affecting the treatment accuracy of the gated MRgRT system. Our analytical approach, employing gamma analysis on films, can be used to estimate the overall latency of the gated MRgRT system., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)