Annual Report 2021

Radiation Safety and Quality Assurance Office

Hiroyuki Okamoto, PhD (chief medical physicist), Satoshi Nakamura, PhD (medical physicist), Kotaro Iijima, PhD (medical physicist), Takahito Chiba, Msc (medical physicist), Hiroki Nakayama, Msc (medical physicist), Mitsuhiro Kon, BS (radiation technologist), Yasunori Shuto, BS (radiation technologist), Tetsu Nakaichi, PhD (medical physicist resident), Shohei Mikasa, Msc (medical physicist resident), Mihiro Takemori, Msc, Yuka Urago, MS, Masato Nishitani, Bsc

Introduction

 The role of our department is to conduct quality management for safety in radiotherapy and to establish standard procedures by implementing state-of-the-art radiation therapy in Japan. All our activities are dedicated to cancer patients; thus, we educate and develop the expertise of radiation oncologists, radiation technologists, and medical physicists. An accelerator-based boron neutron capture therapy (BNCT) system with a Li target was installed in the new facility and an epithermal neutron beam was obtained in August of 2015; the neutron facility passed the governmental inspection for radiation leakage. Non-clinical tests, such as physical and biological experiments, have been performed and a clinical trial using the system and a boron-10 compound, which is provided by STELLA PHARMA CORPORATION, has been underway since November, 2019. The first patient was treated in November, 2019, and it was the first treatment in the world for humans using an accelerator-based BNCT system with a Li target. Additionally, an MRI-guided radiation therapy machine (MRIdian) was introduced for the first time in Japan. After strict acceptance and commissioning procedures, the MRIdian is used mainly for online adaptive radiotherapy in abdominal tumors.

The Team and What We Do

 Our department is collaborating with the Department of Radiation Oncology and Department of Radiological Technology, which is one of the largest radiation oncology departments in Japan. Four linear accelerators, as well as CyberKnife, MRIdian, four CT-simulators, and 15 treatment planning computers are working together via online networks to provide state-of-art precision external beam radiation therapy. In addition to the conventional X-ray and electron therapies, stereotactic irradiations of brain and body tumors and intensity-modulated radiation therapy (IMRT) are routinely performed. Stereotactic brain irradiation is performed with CyberKnife in the treatment of metastatic as well as primary brain tumors. Stereotactic body tumor irradiation is performed in lung and liver tumors by respiratory gating in linear accelerators or CyberKnife. All linear accelerators have on-board kilovoltage CT imagers, allowing us to precisely align patient and tumor coordinates. These image guided radiation therapy (IGRT) facilities enable the precise delivery of IMRT in head and neck cancers, brain tumors, prostate cancers, and postoperative cervical cancers. Fiducial markers have been implanted to improve geometric precision of radiation field reproducibility. MRIdian is used mainly for pancreatic cancer and other upper abdominal cancers in MRI-guided radiotherapy. Brachytherapy is also performed intensively to improve local control, and many patients are referred to us from all over Japan. For brachytherapy, the following modalities are being employed: an Ir-192 high-dose-rate (HDR) afterloading system including dedicated CT simulator and fluoroscopy, an I-125 seed implantation system, and other low-dose rate (LDR) brachytherapy systems using Au grains and ruthenium eye plaques. The number of patients undergoing HDR brachytherapy has continued to rise. This department is the only institution in Tokyo where HDR interstitial as well as intracavitary irradiations can be performed. HDR interstitial radiation is performed mainly on gynecological, genitourinary, and head and neck tumors. Ruthenium mold therapy is performed by ophthalmologists to treat retinoblastomas and choroidal melanomas. BNCT is also performed to treat patients with angiosarcoma or melanoma as a clinical trial. Although these tumors are rare, the efficacy of treatments are not generally excellent. We also endeavor to apply BNCT to other tumors that are resistant to conventional therapies.

Research activities

 The main research activities of our division are the development of highly advanced radiotherapy techniques, the development of quality control methods, and basic research on medical safety in cooperation with the radiotherapy department from medical physics perspectives. In 2021, we reviewed the research findings in the National Cancer Center Research and Development Fund (30-A-14) activities, which had been performed for three years until last year, and discussed current issues. Current issues include the establishment of a medical care team involving radiotherapy, introduction of a Quality Indicator (QI) for medical safety in radiotherapy, clinical implementation of risk analysis in radiotherapy, and establishment of an implementation system and guidelines for advanced radiation therapy such as BNCT and MR-guided radiation therapy. The project will be promoted by the National Cancer Center Research and Development Fund (2022-A-18) starting in 2022.

 Additionally, research and development (R&D) were performed for the accelerator-based BNCT system employing a Li target. As a result, development and improvement of the accelerator-based BNCT system was begun in order to expand indications for cancer in BNCT. Given the accelerator-based BNCT system is still in the development phase all around the world, the requirement specifications for an accelerator-based BNCT system were summarized at the request of the International Atomic Energy Agency (IAEA), and submission of the revised draft was then completed. These will be published as a technical document for the IAEA in the next year. Activities for establishing the international standards for the accelerator-based BNCT system were also conducted. In this year, we proposed the device requirements for establishing a standard neutron measurement method in BNCT to BIPM (the international organization established by the Metre Convention). The aim of this basic research is to ensure traceability to international standards for BNCT dosimetry as well as for conventional radiotherapy.

Clinical trials

 One of our activities is to help radiation oncologists to conduct clinical trials without any problems. In addition, the credentialing process has been established in certain clinical trials by development of an independent dose assessment system.

List of papers published in 2021

Journal

1. Nakamura S, Murakami N, Suzuki S, Ito K, Takemori M, Nakayama H, Kaga K, Chiba T, Iijima K, Takahashi K, Goka T, Itami J, Okamoto H, Igaki H. Monte Carlo simulation of tilted contact plaque brachytherapy placement for juxtapapillary retinoblastoma. Radiation oncology (London, England), 17:16, 2022

2. Imamichi S, Chen L, Ito T, Tong Y, Onodera T, Sasaki Y, Nakamura S, Mauri P, Sanada Y, Igaki H, Murakami Y, Suzuki M, Itami J, Masunaga S, Masutani M. Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy. Biology, 11:2022

3. Igaki H, Murakami N, Nakamura S, Yamazaki N, Kashihara T, Takahashi A, Namikawa K, Takemori M, Okamoto H, Iijima K, Chiba T, Nakayama H, Takahashi A, Kaneda T, Takahashi K, Inaba K, Okuma K, Nakayama Y, Shimada K, Nakagama H, Itami J. Scalp angiosarcoma treated with linear accelerator-based boron neutron capture therapy: A report of two patients. Clinical and translational radiation oncology, 33:128-133, 2022

4. Murakami N, Okuma K, Okamoto H, Nakamura S, Kashihara T, Kaneda T, Takahashi K, Inaba K, Igaki H, Masui K, Yoshida K, Kato T, Itami J. Bevacizumab increases late toxicity in re-irradiation with image-guided high-dose-rate brachytherapy for gynecologic malignancies. Journal of contemporary brachytherapy, 14:52-59, 2022

5. Murakami N, Ohno T, Toita T, Ando K, Ii N, Okamoto H, Kojima T, Tsujino K, Masui K, Yoshida K, Ikushima H. Japanese Society for Radiation Oncology Consensus Guidelines of combined intracavitary and interstitial brachytherapy for gynecological cancers. Journal of radiation research, 63:402-411, 2022

6. Murakami N, Watanabe M, Uno T, Sekii S, Tsujino K, Kasamatsu T, Machitori Y, Aoshika T, Kato S, Hirowatari H, Kaneyasu Y, Nakagawa T, Ikushima H, Ando K, Murata M, Yoshida K, Yoshioka H, Murata K, Ohno T, Okonogi N, Saito A, Ichikawa M, Okuda T, Tsuchida K, Sakurai H, Yoshimura R, Yoshioka Y, Yorozu A, Okamoto H, Inaba K, Kato T, Igaki H, Itami J. Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial. Japanese journal of clinical oncology, 2022

7. Okamoto H, Okuma K, Nakayama H, Nakamura S, Iijima K, Chiba T, Takemori M, Fujii K, Mikasa S, Nakaichi T, Aikawa A, Katsuta S, Igaki H. In vivo dosimetry for testicular and scalp shielding in total skin electron therapy using a radiophotoluminescence glass dosimeter. Journal of radiation research, 63:51-54, 2022

8. Okamoto H, Iijima K, Chiba T, Takemori M, Nakayama H, Fujii K, Kon M, Mikasa S, Nakaichi T, Urago Y, Aikawa A, Katsuta S, Nakamura S, Igaki H. Technical note: Analysis of brachytherapy source movement by high-speed camera. Medical physics, 2022

9. Tamura Y, Demachi K, Igaki H, Okamoto H, Nakano M. A Real-Time Four-Dimensional Reconstruction Algorithm of Cine-Magnetic Resonance Imaging (Cine-MRI) Using Deep Learning. Cureus, 14:e22826, 2022

10. Kobayashi R, Murakami N, Chiba T, Okuma K, Inaba K, Takahashi K, Kaneda T, Kashihara T, Takahashi A, Shimizu Y, Nakayama Y, Kato T, Ito Y, Igaki H . Effect of Hyaluronate Acid Injection on Dose-Volume Parameters in Brachytherapy for Cervical Cancer. Advances in radiation oncology, 7:100918, 2022

11. Chen L, Imamichi S, Tong Y, Sasaki Y, Onodera T, Nakamura S, Igaki H, Itami J, Masutani M. A Combination of GM-CSF and Released Factors from Gamma-Irradiated Tumor Cells Enhances the Differentiation of Macrophages from Bone Marrow Cells and Their Antigen-Presenting Function and Polarization to Type 1. Medicines (Basel, Switzerland), 8:2021

12. Itami J, Murakami N, Watanabe M, Sekii S, Kasamatsu T, Kato S, Hirowatari H, Ikushima H, Ando K, Ohno T, Okamoto H, Okuma K, Igaki H. Combined Interstitial and Intracavitary High-Dose Rate Brachytherapy of Cervical Cancer. Frontiers in oncology, 11:809825, 2021

13. Murakami N, Nakamura S, Kashihara T, Inaba K, Kaneda T, Takahashi K, Okuma K, Igaki H, Itami J. Increased number of prostate cancer patients selecting high dose-rate interstitial brachytherapy during the COVID-19 pandemic. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology, 154:274-275, 2021

14. Murakami N, Omura G, Yatsuoka W, Okamoto H, Yoshimoto S, Ueno T, Itami J. Hybrid Intracavitary-Interstitial brachytherapy in a case of nasal vestibule cancer penetrating the hard palate. BJR case reports, 7:20200178, 2021

15. Umezawa R, Wakita A, Katsuta Y, Ito Y, Nakamura S, Okamoto H, Kadoya N, Takahashi K, Inaba K, Murakami N, Igaki H, Jingu K, Itami J. A Pilot Study of Synchronization of Respiration-Induced Motions in the Duodenum and Stomach for the Primary Tumor in Radiation Therapy for Pancreatic Cancer Using 4-Dimensional Computed Tomography. Advances in radiation oncology, 6:100730, 2021

16. Nakamura S, Igaki H, Ito M, Imamichi S, Kashihara T, Okamoto H, Nishioka S, Iijima K, Chiba T, Nakayama H, Takemori M, Abe Y, Kaneda T, Takahashi K, Inaba K, Okuma K, Murakami N, Nakayama Y, Masutani M, Nishio T, Itami J. Neutron flux evaluation model provided in the accelerator-based boron neutron capture therapy system employing a solid-state lithium target. Scientific reports, 11:8090, 2021

17. Takada M, Nunomiya T, Masuda A, Matsumoto T, Tanaka H, Nakamura S, Endo S, Nakamura M, Aoyama K, Ueda O, Narita M, Nakamura T. Development of a real-time neutron beam detector for boron neutron capture therapy using a thin silicon sensor. Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine, 176:109856, 2021

18. Urago Y, Okamoto H, Kaneda T, Murakami N, Kashihara T, Takemori M, Nakayama H, Iijima K, Chiba T, Kuwahara J, Katsuta S, Nakamura S, Chang W, Saitoh H, Igaki H. Evaluation of auto-segmentation accuracy of cloud-based artificial intelligence and atlas-based models. Radiation oncology (London, England), 16:175, 2021

19. Nakayama H, Nakamura S, Iijima K, Chiba T, Takemori M, Kashihara T, Okuma K, Igaki H, Saitoh H, Chang W, Okamoto H. Efficacy of tangential irradiation with volumetric modulated arc therapy on scalp angiosarcoma using medical linac. Physica medica: PM: an international journal devoted to the applications of physics to medicine and biology: official journal of the Italian Association of Biomedical Physics (AIFB), 91:105-116, 2021

20. Iijima K, Okamoto H, Nishioka S, Sakasai T, Nakamura S, Chiba T, Kaga K, Takemori M, Nakayama H, Miura Y, Fujiyama D, Tsunoda Y, Igaki H, Katsuta S, Itami J. Performance of a newly designed end-to-end phantom compatible with magnetic resonance-guided radiotherapy systems. Medical physics, 48:7541-7551, 2021