Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias　- Gap Junction and Sympathetic Neural Remodeling.

BACKGROUND: Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1-78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1-44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9-65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group. CONCLUSIONS: Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.

Interim Report of a Japanese Phase II Trial for Cardiac Stereotactic Body Radiotherapy in Refractory Ventricular Tachycardia　- Focus on Target Determination.

Background: Cardiac radiotherapy using stereotactic body radiation therapy (SBRT) has attracted attention as a minimally invasive treatment for refractory ventricular tachycardia. However, a standardized protocol and software program for determining the irradiation target have not been established. Here, we report the first preclinical stereotactic radioregulation antiarrhythmic therapy trial in Japan, focused on the target-setting process. Methods and Results: From 2019 onwards, 3 patients (age range 60-91 years) presenting with ischemic or non-ischemic cardiomyopathy were enrolled. Two patients were extremely serious and urgent, and were followed up for 6 and 30 months. To determine the irradiation targets, we aggregated electrophysiological, structural, and functional data and reflected them in an American Heart Association 17-segment model, as per the current recommendations. However, in all 3 patients, invasive electrophysiological study, phase-contrast computed tomography, and magnetic resonance imaging could not be performed; therefore, electrophysiological and structural information was limited. As alternatives, high-resolution ambulatory electrocardiography and nuclear medicine studies were useful in assessing arrhythmic substrates; however, concerns regarding test weighting and multiple scoring remain. Risks to surrounding organs were fully taken into account. Conclusions: In patients requiring cardiac SBRT, the information needed for target planning is sometimes limited to minimally invasive tests. Although there are issues to be resolved, this is a promising option for the life-saving treatment of patients in critical situations.

Effect on Heart and Lung Doses Reduction of Abdominal and Thoracic Deep Inspiratory Breath-hold Assuming Involved-field Radiation Therapy in Patients with Simulated Esophageal Cancer.

PURPOSE: The purpose of this study was to evaluate the lung and heart doses in volumetric-modulated arc therapy (VMAT) using involved-field irradiation in patients with middle-to-lower thoracic esophageal cancer during free breathing (FB), abdominal deep inspiratory breath-hold (A-DIBH), and thoracic DIBH (T-DIBH) images. METHODS: Computed tomography images of A-DIBH, T-DIBH, and FB from 25 patients with breast cancer were used to simulate patients with esophageal cancer. The irradiation field was set at an involved-field, and target and risk organs were outlined according to uniform criteria. VMAT optimization was performed, and lung and heart doses were evaluated. RESULTS: A-DIBH had a lower lung V20 Gy than FB and a lower lung V40 Gy, V30 Gy, V20 Gy than T-DIBH. The heart all dose indices were lower in T-DIBH than FB, and the heart V10 Gy was lower in A-DIBH than FB. However, the heart Dmean was comparable with A-DIBH and T-DIBH. CONCLUSIONS: A-DIBH had significant dose advantages for lungs compared to FB and T-DIBH, and the heart Dmean was comparable to T-DIBH. Therefore, when performing DIBH, A-DIBH is suggested for radiotherapy in patients with middle-to-lower thoracic esophageal cancer, excluding irradiation of the prophylactic area.

[Questionnaire Survey of Japanese Medical Physicists on Working Conditions in 2020].

The questionnaire survey was conducted in 2020 to investigate the working conditions of qualified medical physicists in Japan. We developed a web-based system for administering the questionnaire and surveyed 1,228 qualified medical physicists. The number of received responses was 405. We summarized the results of the survey by job category. The obtained results showed that most of the people working as certified medical physicists met the following conditions: (1) position of healthcare occupation, (2) direct supervisor is a medical doctor or a medical physicist, (3) licensed or passed an examination for a Class I Radiation Protection Supervisor, (4) without the license of professional radiotherapy technologist, (5) master's or doctor's degree, (6) being assigned to the section that is different from the radiological technologist section. The average annual salary was approximately 600,000 yen higher for those employed as medical physicists than for those employed as radiotherapy technologists. The percentage of work performed by a certified medical physicist in radiation therapy greatly varies depending on whether the physicist is dedicated to treatment planning and equipment quality control. Alternatively, the proportion of the true duties of medical physicists in charge of radiation therapy, as considered by qualified medical physicists in radiation therapy, was the same regardless of whether they were working full-time or not. The results of this survey updated the working status of certified medical physicists in Japan. We will continue to conduct the survey periodically and update the information to contribute to the improvement of the working conditions of medical physicists and policy recommendations.

Comparing the toxicity and disease control rate of radiotherapy for prostate cancer between salvage settings after high-intensity focused ultrasound therapy and initial settings.

The purpose of this retrospective study was to compare the toxicity and disease control rate of radiotherapy for prostate cancer in salvage settings after high-intensity focused ultrasound (HIFU) therapy (HIFU cohort) with those in radical settings (non-HIFU cohort). From 2012 to 2020, 215 patients were identified for this study and 17 were treated in the salvage settings after HIFU. The median follow-up time was 34.5 months (range: 7-102 months, inter-quartile range [IQR]: 16-64 months). Genitourinary (GU) and gastrointestinal (GI) adverse events were evaluated in acute and late periods with Common Terminology Criteria for Adverse Events version 5, and the rates of biochemical-clinical failure free survival (BCFS) and overall survival (OS) were estimated. The cumulative incidence of late GU Grade 2 or greater toxicity after five years was significantly different between the non-HIFU and HIFU cohorts with rates of 7.3% and 26.2%, respectively (P = 0.03). Regarding GI Grade 2 or greater toxicity, there was no significant difference between the two cohorts. The 5y-BCFS was 84.2% in the non-HIFU cohort and 69.5% in the HIFU cohort with no significant difference (P = 0.10) and the 5y-OS was 95.9% and 92.3%, respectively (P = 0.47). We concluded that the possibility of increased late GU Grade 2 or greater should be considered when applying salvage radiotherapy for local recurrence after HIFU.

Dosimetric study of whole-brain irradiation with high-energy photon beams for dose reduction to the scalp.

OBJECTIVE: To evaluate the efficiency of high-energy photons for mitigating alopecia due to whole-brain irradiation (WBRT). METHODS: Planning CT data from 10 patients who received WBRT were collected. We prepared 4 WBRT plans that used 6 or 15 MV photon beams, with or without use of a field-in-field (FiF) technique, and compared outcomes using a treatment planning system. The primary outcome was dose parameters to the scalp, including the mean dose, maximum dose, and dose received to 50% scalp(D50%). Secondary outcomes were minimum dose to the brain surface. RESULTS: Using FiF, the mean doses were 24.4-26.0 and 22.4-24.1 Gy, and the maximum doses were 30.5-32.1 and 28.5-30.8 Gy for 6 and 15 MV photon beams, respectively. Without FiF, the mean doses were 24.6-26.9 and 22.6-24.5 Gy, and the maximum doses were 30.8-34.6 and 28.6-32.4 Gy for 6 and 15 MV photon beams. The 15 MV plan resulted in a lower scalp dose for each dose parameter (p < 0.001). Using FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.440 and 29.0 ± 0.557 Gy, respectively (p = 0.70). Without FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.456 and 29.0 ± 0.529, respectively (p = 0.66). CONCLUSION: Compared with the 6 MV plan, the 15 MV plan achieved a lower scalp dose without impairing the brain surface dose. ADVANCES IN KNOWLEDGE: High-energy photon WBRT may mitigate alopecia of patients who receiving WBRT.

[Summary of the Report of Task Group 100 of the AAPM: Application of Risk Analysis Methods to Radiation Therapy Quality Management].

In 2016, the American Association of Physicists in Medicine (AAPM) has published a report of task group (TG) 100 with a completely new concept, entitled "application of risk analysis methods to radiation therapy quality management." TG-100 proposed implementation of risk analysis in radiotherapy to prevent harmful radiotherapy accidents. In addition, it enables us to conduct efficient and effective quality management in not only advanced radiotherapy such as intensity-modulated radiotherapy and image-guided radiotherapy but also new technology in radiotherapy. It should be noted that treatment process in modern radiotherapy is absolutely more complex and it needs skillful staff and adequate resources. TG-100 methodology could identify weakness in radiotherapy procedure through assessment of failure modes that could occur in overall treatment processes. All staff in radiotherapy have to explore quality management in radiotherapy safety.

Improved proton CT imaging using a bismuth germanium oxide scintillator.

Range uncertainty is among the most formidable challenges associated with the treatment planning of proton therapy. Proton imaging, which includes proton radiography and proton computed tomography (pCT), is a useful verification tool. We have developed a pCT detection system that uses a thick bismuth germanium oxide (BGO) scintillator and a CCD camera. The current method is based on a previous detection system that used a plastic scintillator, and implements improved image processing techniques. In the new system, the scintillation light intensity is integrated along the proton beam path by the BGO scintillator, and acquired as a two-dimensional distribution with the CCD camera. The range of a penetrating proton is derived from the integrated light intensity using a light-to-range conversion table, and a pCT image can be reconstructed. The proton range in the BGO scintillator is shorter than in the plastic scintillator, so errors due to extended proton ranges can be reduced. To demonstrate the feasibility of the pCT system, an experiment was performed using a 70 MeV proton beam created by the AVF930 cyclotron at the National Institute of Radiological Sciences. The accuracy of the light-to-range conversion table, which is susceptible to errors due to its spatial dependence, was investigated, and the errors in the acquired pixel values were less than 0.5 mm. Images of various materials were acquired, and the pixel-value errors were within 3.1%, which represents an improvement over previous results. We also obtained a pCT image of an edible chicken piece, the first of its kind for a biological material, and internal structures approximately one millimeter in size were clearly observed. This pCT imaging system is fast and simple, and based on these findings, we anticipate that we can acquire 200 MeV pCT images using the BGO scintillator system.

Electron-tracking Compton camera imaging of technetium-95m.

Imaging was conducted using an electron tracking-Compton camera (ETCC), which measures γ-rays with energies in the range of 200-900 keV from 95mTc. 95mTc was produced by the 95Mo(p, n)95mTc reaction on a 95Mo-enriched target. A method for recycling 95Mo-enriched molybdenum trioxide was employed, and the recycled yield of 95Mo was 70%-90%. Images were obtained with the gate of three energies. The results showed that the spatial resolution increases with increasing γ-ray energy, and suggested that the ETCC with high-energy γ-ray emitters such as 95mTc is useful for the medical imaging of deep tissue and organs in the human body.

Educational outcomes of a medical physicist program over the past 10 years in Japan.

The promotion plan for the Platform of Human Resource Development for Cancer (Ganpro) was initiated by the Ministry of Education, Culture, Sports, Science and Technology of Japan in 2007, establishing a curriculum for medical physicists. In this study, we surveyed the educational outcomes of the medical physicist program over the past 10 years since the initiation of Ganpro. The Japan Society of Medical Physics mailing list was used to announce this survey. The questionnaire was created by members of the Japanese Board for Medical Physicist Qualification, and was intended for the collection of information regarding the characteristics and career paths of medical physics students. Students who participated in the medical physics program from 2007 to 2016 were enrolled. Thirty-one universities (17 accredited and 14 non-accredited) were represented in the survey. In total, 491, 105 and 6 students were enrolled in the Master's, Doctorate and Residency programs, respectively. Most students held a Bachelor's degree in radiological technology (Master's program, 87%; Doctorate program, 72%). A large number of students with a Master's degree worked as radiological technologists (67%), whereas only 9% (n = 32) worked as medical physicists. In contrast, 53% (n = 28) of the students with a Doctorate degree worked as medical physicists. In total, 602 students (from 31 universities) completed the survey. Overall, although the number of the graduates who worked as medical physicists was small, this number increased annually. It thus seems that medical institutions in Japan are recognizing the necessity of licensed medical physicists in the radiotherapy community.

Development of proton CT imaging system using plastic scintillator and CCD camera.

A proton computed tomography (pCT) imaging system was constructed for evaluation of the error of an x-ray CT (xCT)-to-WEL (water-equivalent length) conversion in treatment planning for proton therapy. In this system, the scintillation light integrated along the beam direction is obtained by photography using the CCD camera, which enables fast and easy data acquisition. The light intensity is converted to the range of the proton beam using a light-to-range conversion table made beforehand, and a pCT image is reconstructed. An experiment for demonstration of the pCT system was performed using a 70 MeV proton beam provided by the AVF930 cyclotron at the National Institute of Radiological Sciences. Three-dimensional pCT images were reconstructed from the experimental data. A thin structure of approximately 1 mm was clearly observed, with spatial resolution of pCT images at the same level as that of xCT images. The pCT images of various substances were reconstructed to evaluate the pixel value of pCT images. The image quality was investigated with regard to deterioration including multiple Coulomb scattering.

[New medical imaging based on electron tracking Compton camera (ETCC)].

We have developed an Electron-Tracking Compton Camera (ETCC) for medical imaging due to its wide energy dynamic range (200-1,500keV) and wide field of view (FOV, 3 str). This camera has a potential of developing the new reagents. We have carried out several imaging reagent studies as examples; (1) 18F-FDG and 131I-MIBG simultaneous imaging for double clinical tracer imaging, (2) imaging of some minerals (Mn-54, Zn-65, Fe-59) in mouse and plants. In addition, ETCC has a potential of real-time monitoring of the Bragg peak location by imaging prompt gamma rays for the beam therapy. We carried out the water phantom experiment using 140MeV proton beam, and obtained the images of both 511 keV and high energy gamma rays (800-2,000keV). Here better correlation of the latter image to the Bragg peak has been observed. Another potential of ETCC is to reconstruct the 3D image using only one-head camera without rotations of both the target and camera. Good 3D images of the thyroid grant phantom and the mouse with tumor were observed. In order to advance those features to the practical use, we are improving the all components and then construct the multi-head ETCC system.