Accelerator based epithermal neutron source for clinical boron neutron capture therapy

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

Improvement in the neutron beam collimation for application in boron neutron capture therapy of the head and neck region

In June 2020, the Japanese government approved boron neutron capture therapy for the treatment of head and neck cancer. The treatment is usually performed in a single fraction, with the neutron irradiation time being approximately 30–60 min. As neutrons scatter in air and loses its intensity, it is preferable to bring the patient as close to the beam port as possible to shorten the irradiation time. However, this can be a challenge, especially for patients with head and neck cancer, as the shoulders are an obstacle to a clean positioning. In this study, a novel neutron collimation system for an accelerator based neutron source was designed to allow for a more comfortable treatment, without compromising the irradiation time. Experimental measurements confirmed the simulation results and showed the new collimator can reduce the irradiation time by approximately 60% (under the same condition where the distance between the source and the patient surface was kept the same). The dose delivered to the surrounding healthy tissue was reduced with the new collimator, showing a 25% decrease in the D₅₀ of the mucosal membrane. Overall, the use of the newly designed collimator will allow for a more comfortable treatment of the head and neck region, reduce the treatment time, and reduce the dose delivered to the surrounding healthy tissue

Feasibility study of chemoradiotherapy followed by amrubicin and cisplatin for limited-disease small cell lung cancer

To evaluate the feasibility of amrubicin plus cisplatin (AP) following chemoradiotherapy for limited-disease small-cell lung cancer, chemo-naïve patients aged 20–70 years with a performance status of 0 or 1 and normal organ functions were treated with etoposide 100 mg/m2 on days 1–3, cisplatin 80 mg/m2 on day 1 and concurrent thoracic radiotherapy at 45 Gy/30 fractions (EP-TRT), followed by three cycles of amrubicin 40 mg/m2 on days 1–3 and cisplatin 60 mg/m2 on day 1 every 3 weeks. The EP-TRT could be completed in 21 patients (15 male and 6 female patients with a median age of 62 years). Of these, 2, 1 and 18 (86%) patients received one, two and three cycles of AP, respectively. Sixteen (76%) patients required granulocyte-colony stimulating factor (G-CSF) support. Grade 3/4 neutropenia occurred in all patients. Grade 3 febrile neutropenia was observed in 9 patients, lasting for 1 day in 5 patients. The incidences of grade 3/4 thrombocytopenia and anemia were 43 and 24%, respectively. Grade 3 infection and anorexia occurred in 2 and 3 patients, respectively. The response rate was 95%. The median (95% confidence interval [CI]) progression-free survival (PFS) was 41.9 (0–102) months, and the 5-year PFS rate (CI) was 41.9% (20.4–63.4%). The median overall survival (OS) has not been reached yet, and the 5-year OS rate (CI) was 57.8% (35.2–80.4%). In conclusion, EP-TRT followed by AP therapy was well-tolerated, although a large number of patients required G-CSF support

Risk factors associated with fatal pulmonary hemorrhage in locally advanced non-small cell lung cancer treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify the risk factors associated with fatal pulmonary hemorrhage (PH) in patients with locally advanced non-small cell lung cancer (NSCLC), treated with chemoradiotherapy.</p> <p>Methods</p> <p>The medical records of 583 patients with locally advanced NSCLC, who were treated with chemoradiotherapy between July 1992 and December 2009 were reviewed. Fatal PH was defined as PH leading to death within 24 h of its onset. Tumor cavitation size was defined by the cavitation diameter/tumor diameter ratio and was classified as minimum (< 0.25), minor (≥ 0.25, but < 0.5), and major (≥ 0.5).</p> <p>Results</p> <p>Of the 583 patients, 2.1% suffered a fatal PH. The numbers of patients with minimum, minor, and major cavitations were 13, 11, and 14, respectively. Among the 38 patients with tumor cavitation, all 3 patients who developed fatal PH had major cavitations. On multivariate analysis, the presence of baseline major cavitation (odds ratio, 17.878), and a squamous cell histology (odds ratio, 5.491) proved to be independent significant risk factors for fatal PH. Interestingly, all patients with fatal PH and baseline major cavitation were found to have tumors with squamous cell histology, and the occurrence of fatal PH in patients having both risk factors was 33.3%.</p> <p>Conclusions</p> <p>Patients at high risk of fatal PH could be identified using a combination of independent risk factors.</p

1キ ヒショウ サイボウ ハイガン ニ タイスル コウセンリョウ ヨウシセン チリョウ

京都大学0048新制・論文博士博士(医学)乙第11872号論医博第1899号新制||医||930(附属図書館)UT51-2006-K270京都大学大学院医学研究科内科系専攻(主査)教授 小野 公二, 教授 富樫 かおり, 教授 松本 智裕学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDA

Evaluation of a treatment planning system developed for clinical boron neutron capture therapy and validation against an independent Monte Carlo dose calculation system

Boron neutron capture therapy (BNCT) for the treatment of unresectable, locally advanced, and recurrent carcinoma of the head and neck cancer has been approved by the Japanese government for reimbursement under the national health insurance as of June 2020. A new treatment planning system for clinical BNCT has been developed by Sumitomo Heavy Industries, Ltd. (Sumitomo), NeuCure® Dose Engine. To safely implement this system for clinical use, the simulated neutron flux and gamma ray dose rate inside a water phantom was compared against experimental measurements. Furthermore, to validate and verify the new planning system, the dose distribution inside an anthropomorphic head phantom was compared against a BNCT treatment planning system SERA and an in-house developed Monte Carlo dose calculation program. The simulated results closely matched the experimental results, within 5% for the thermal neutron flux and 10% for the gamma ray dose rate. The dose distribution inside the head phantom closely matched with SERA and the in-house developed dose calculation program, within 3% for the tumour and a difference of 0.3 Gyw for the brain

Evaluating dosimetric differences in spine stereotactic body radiotherapy: An international multi-institutional treatment planning study.

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

Screening for Impaired Cognitive Domains in a Large Parkinson's Disease Population and Its Application to the Diagnostic Procedure for Parkinson's Disease Dementia

Background: Dementia is a new focus of research on improved treatment for Parkinson's disease (PD). In 2007, a screening tool for PD dementia (PD-D) was developed by the Movement Disorder Society (Level I testing), which still requires verification by a large population study. Methods: We conducted a cross-sectional and multicenter study including 13 institutions administering the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to 304 PD patients (mean age: 70.6 ± 8.3 years; mean Hoehn and Yahr stage: 2.7 ± 0.7). Results: In all, 34.5% of the patients had MMSE scores Conclusions: Level I testing with administration of the MMSE and MoCA is a practical and efficient screening tool for PD-D. However, the phonemic fluency and pentagon copying tests should be replaced by more specific/sensitive ones when screening for PD-D