Annual Report 2022

Section of Radiation Safety and Quality Assurance

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), Yasunori Shuto, BS (radiation technologist), Tetsu Nakaichi, PhD (medical physicist resident), Shohei Mikasa, Msc (medical physicist resident), Mihiro Takemori, Msc, Yuka Urago, Msc, Masato Nishitani, Msc

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 conducted 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 the 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-the-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 conducted using CyberKnife for treating 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 primarily used 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 employed: an Ir-192 high-dose-rate (HDR) afterloading system including a 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 increase. 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 make efforts 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, development of quality control methods, and basic research on medical safety in cooperation with the radiotherapy department from medical physics aspects. In 2022, the National Cancer Center Research and Development Fund (20220-A-18, Chief Hiroyuki Okamoto, researchers our staff) started to launch several projects, e.g., the establishment of a medical care team involving radiotherapy, introduction of a Quality Indicator (QI) for medical safety in radiotherapy, clinically 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. These projects must be promoted by corporation with other organizations.

 In addition, we have continued research and development (R&D) for the accelerator-based BNCT system employing the Li target to expand indications in BNCT. We also participated in a Phase I trial on the accelerator-based BNCT system to perform BNCT effectively and safely. As a result, the trial was completed without any problems. Furthermore, based on the excellent results of the Phase I trial, a Phase II trial for angiosarcoma was initiated.

  The accelerator-based BNCT system is still in the development phase worldwide. We documented the requirement specifications for an accelerator-based BNCT system at the request of the International Atomic Energy Agency (IAEA). The document will be published as “Advances in Boron Neutron Capture Therapy” in June 2023. We also initiated activities to establish international standards for the accelerator-based BNCT system. As a result, the international standard (International Electrotechnical Commission standard) for the accelerator-based BNCT system was proposed by the Japan team in which we were participating. It was the first time for the Japan team to propose the international standard for the equipment of radiation therapy. In addition, we have been conducting basic researches for the establishing international standards.

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 through the development of an independent dose assessment system.

List of papers published in 2022

Journal

1. Kashihara T, Nakayama Y, Okuma K, Takahashi A, Kaneda T, Katagiri M, Nakayama H, Kubo Y, Ito K, Nakamura S, Takahashi K, Inaba K, Murakami N, Saito T, Okamoto H, Itami J, Kusumoto M, Ohe Y, Igaki H. Impact of interstitial lung abnormality on survival after adjuvant durvalumab with chemoradiotherapy for locally advanced non-small cell lung cancer. Radiotherapy and oncology, 180:109454, 2023

2. Kashihara T, Ogata D, Okuma K, Nakamura S, Nakayama H, Mori T, Takahashi A, Namikawa K, Takahashi A, Takahashi K, Kaneda T, Inaba K, Murakami N, Okamoto H, Nakayama Y, Yamazaki N, Igaki H. Clinical significance of local control of primary tumour in definitive radiotherapy for scalp angiosarcomas. Skin research and technology, 29:e13243, 2023

3. Kon M, Okamoto H, Nakamura S, Iijima K, Chiba T, Takemori M, Nakayama H, Nakaichi T, Mikasa S, Fujii K, Urago Y, Ishikawa M, Sofue T, Katsuta S, Inaba K, Igaki H, Aso T. Planning study: prone versus supine position for stereotactic body radiotherapy in prostate by CyberKnife. Journal of radiation research, 64:186-194, 2023

4. Matsumura A, Asano T, Hirose K, Igaki H, Kawabata S, Kumada H. Initiatives Toward Clinical Boron Neutron Capture Therapy in Japan. Cancer biotherapy & radiopharmaceuticals, 38:201-207, 2023

5. Takemori M, Nakamura S, Sofue T, Ito M, Goka T, Miura Y, Iijima K, Chiba T, Nakayama H, Nakaichi T, Mikasa S, Takano Y, Kon M, Shuto Y, Urago Y, Nishitani M, Kashihara T, Takahashi K, Murakami N, Nishio T, Okamoto H, Chang W, Igaki H. Failure modes and effects analysis study for accelerator-based Boron Neutron Capture Therapy. Medical physics, 50:424-439, 2023

6. Murakami N, Takano A, Niizeki I, Sakuramachi M, Kashihara T, Okamoto H, Ito M, Ueno T, Igaki H. Nursing management of patients receiving interstitial brachytherapy for head and neck malignancies. Brachytherapy, 22:214-220, 2023

7. Mizuno N, Okamoto H, Minemura T, Kawamura S, Tohyama N, Kurooka M, Kawamorita R, Nakamura M, Ito Y, Shioyama Y, Aoyama H, Igaki H. Establishing quality indicators to comprehensively assess quality assurance and patient safety in radiotherapy and their relationship with an institution’s background. Radiotherapy and oncology, 179:109452, 2023

8. Nakaichi T, Okamoto H, Kon M, Takaso K, Aikawa A, Nakamura S, Ijima K, Chiba T, Nakayama H, Takemori M, Mikasa S, Fujii K, Urago Y, Goka T, Shimizu Y, Igaki H. Commissioning and performance evaluation of commercially available mobile imager for image guided total body irradiation. Journal of applied clinical medical physics, 24:e13865, 2023

9. 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 AI, Ichikawa M, Okuda T, Tsuchida K, Sakurai H, Yoshimura R, Yoshioka Y, Yorozu A, Kunitake N, Okamoto H, Inaba K, Kato T, Igaki H, Itami J. Phase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer. Journal of gynecologic oncology, 34:e24, 2023

10. Murakami N, Masui K, Yoshida K, Noda SE, Watanabe M, Takenaka T, Ii N, Atsumi K, Umezawa R, Inaba K, Iijima K, Kubo A, Igaki H, Shikama N, Ikushima H. Hands-on seminar for image-guided adaptive brachytherapy and intracavitary/interstitial brachytherapy for uterine cervical cancer. Japanese journal of clinical oncology, 53:508-513, 2023

11. Nakayama H, Okamoto H, Nakamura S, Iijima K, Chiba T, Takemori M, Nakaichi T, Mikasa S, Fujii K, Sakasai T, Kuwahara J, Miura Y, Fujiyama D, Tsunoda Y, Hanzawa T, Igaki H, Chang W. Film measurement and analytical approach for assessing treatment accuracy and latency in a magnetic resonance-guided radiotherapy system. Journal of applied clinical medical physics, 24:e13915, 2023

12. Okamoto H, Murakami N, Isohashi F, Kasamatsu T, Hasumi Y, Kobayashi H, Ishikawa M, Nakamura M, Nishio T, Igaki H, Ishikura S, Yaegashi N, Mizowaki T, Nishimura Y, Toita T. Plan quality association between dummy run and individual case review in a prospective multi-institutional clinical trial of postoperative cervical cancer patients treated with intensity-modulated radiotherapy: Japan clinical Oncology Group study (JCOG1402). Radiotherapy and oncology, 183:109630, 2023

13. Kashihara T, Urago Y, Okamoto H, Takemori M, Nakayama H, Mikasa S, Nakaichi T, Iijima K, Chiba T, Kuwahara J, Nakamura S, Chang W, Matsui Y, Igaki H. A preliminary study on rectal dose reduction associated with hyaluronic acid implantation in brachytherapy for prostate cancer. Asian Journal of Urology, 2023

14. Shimizu Y, Murakami N, Mori T, Takahashi K, Kubo Y, Yoshimoto S, Honma Y, Nakamura S, Okamoto H, Iijima K, Takahashi A, Kaneda T, Kashihara T, Inaba K, Okuma K, Nakayama Y, Igaki H, Itami J. Clinical impact of p16 positivity in nasopharyngeal carcinoma. Laryngoscope investigative otolaryngology, 7:994-1001, 2022

15. Miyata Y, Murakami N, Honma Y, Mori T, Yoshimoto S, Kashihara T, Takemori M, Nakayama Y, Itami J, Ogo E, Igaki H. Technical report: a high-dose-rate interstitial brachytherapy boost for residual sinonasal undifferentiated carcinoma. Journal of radiation research, 63:879-883, 2022

16. 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

17. Nakaichi T, Nakamura S, Ito K, Takahashi K, Takemori M, Kashihara T, Kunito K, Murakami N, Iijima K, Chiba T, Nakayama H, Mikasa S, Nishio T, Okamoto H, Itami J, Kurihara H, Igaki H. Analyzing spatial distribution between (18)F-fluorodeoxyglucose and (18)F-boronophenylalanine positron emission tomography to investigate selection indicators for boron neutron capture therapy. EJNMMI physics, 9:89, 2022

18. Kawahara D, Tsuneda M, Ozawa S, Okamoto H, Nakamura M, Nishio T, Nagata Y. Deep learning-based auto segmentation using generative adversarial network on magnetic resonance images obtained for head and neck cancer patients. Journal of applied clinical medical physics, 23:e13579, 2022

19. 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, 49:4804-4811, 2022

20. 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

21. 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, 52:859-868, 2022

22. Takagawa Y, Murakami N, Igaki H, Okamoto H, Itami J. High-dose-rate interstitial brachytherapy as a suitable option for metastatic extraskeletal myxoid chondrosarcoma - a case report. Journal of contemporary brachytherapy, 14:198-204, 2022

23. 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

24. Nishioka S, Okamoto H, Chiba T, Sakasai T, Okuma K, Kuwahara J, Fujiyama D, Nakamura S, Iijima K, Nakayama H, Takemori M, Tsunoda Y, Kaga K, Igaki H. Identifying risk characteristics using failure mode and effect analysis for risk management in online magnetic resonance-guided adaptive radiation therapy. Physics and imaging in radiation oncology, 23:1-7, 2022

25. Miyata Y, Murakami N, Okuma K, Shimizu Y, Takahashi A, Kashihara T, Kaneda T, Takahashi K, Inaba K, Sakuramachi M, Kojima K, Aoshika T, Morishima K, Nakayama Y, Itami J, Kato T, Ogo E, Igaki H. Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies. Brachytherapy, 21:647-657, 2022

26. Okamoto H, Igaki H, Chiba T, Shibuya K, Sakasai T, Jingu K, Inaba K, Kuroda K, Aoki S, Tatsumi D, Nakamura M, Kadoya N, Furuyama Y, Kumazaki Y, Tohyama N, Tsuneda M, Nishioka S, Itami J, Onishi H, Shigematsu N, Uno T. Practical guidelines of online MR-guided adaptive radiotherapy. Journal of radiation research, 63:730-740, 2022

27. Kawahara D, Tsuneda M, Ozawa S, Okamoto H, Nakamura M, Nishio T, Saito A, Nagata Y. Stepwise deep neural network (stepwise-net) for head and neck auto-segmentation on CT images. Computers in biology and medicine, 143:105295, 2022

28. 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

29. Kashihara T, Igaki H, Ogata D, Nakayama H, Nakamura S, Okuma K, Mori T, Yamakawa K, Takahashi A, Namikawa K, Takahashi A, Takahashi K, Kaneda T, Inaba K, Murakami N, Nakayama Y, Okamoto H, Yamazaki N, Itami J. Prognostic factor analysis of definitive radiotherapy using intensity-modulated radiation therapy and volumetric modulated arc therapy with boluses for scalp angiosarcomas. Scientific reports, 12:4355, 2022

30. 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

31. Shimizu Y, Murakami N, Chiba T, Kaneda T, Okamoto H, Nakamura S, Takahashi A, Kashihara T, Takahashi K, Inaba K, Okuma K, Nakayama Y, Itami J, Igaki H. High-Dose-Rate Interstitial Brachytherapy for Deeply Situated Gynecologic Tumors Guided by Combination of Transrectal and Transabdominal Ultrasonography: A Technical Note. Frontiers in oncology, 11:808721, 2021