Annual Report 2022

Department of RADIATION ONCOLOGY

Tetsuo Akimoto, Sadamoto Zenda, Atsushi Motegi, Hidehiro Hojo, Masaki Nakamura, Shun-ichiro Kageyama, Hidenari Hirata, Takeshi Fujisawa, Hidekazu Ohyoshi

Introduction

 Radiotherapy (RT) plays an essential role in the management of cancer patients. It is used as (1) a curative treatment for many patients with loco-regional localized malignant disease, (2) integrated therapy combined with chemotherapy and/or surgery, and (3) palliative treatment for patients for whom curative treatment is not an option. In radiotherapeutic approaches, the radiation dose to the loco-regional tumor must be as high as possible, while the dose to the surrounding normal tissues should be kept as low as possible to maintain the severity of radiation-related complications within an acceptable level.

 The primary aim of the Department of Radiation Oncology is to develop high-precision RT such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), stereotactic body RT (SBRT), and proton beam therapy (PBT), and to establish the definitive role of RT in cancer treatment. Another important goal is to establish standard treatments for various types of cancer and optimal irradiation techniques including total dose, fractionation, and radiation fields.

The Team and What We Do

 At present, the staff of the Department of Radiation Oncology consists of seven consultant physicians (radiation oncologists), 21 radiation technologists, 5 medical physicists, 3 nurse, and 1 clerk. We have more than 1,500 new cases of conventional RT and more than 300 new patients for PBT every year. Quality assurance of conventional RT and PBT is performed by medical physicists and radiation technologists, and a conference to verify the treatment planning is held every morning in addition to a weekly work conference on research activities. RT and PBT are routinely based on three-dimensional radiation therapy planning and PBT using RT-dedicated multidetector-row helical computed tomography (CT) scanning to confirm the precise radiation dose to be administered to the targeted tumors. Respiratory gating has been employed especially in the radiotherapeutic management of patients with lung, esophagus, and liver cancers.

 The selection of treatment approaches is determined through clinical conferences between radiation oncologists, surgical oncologists, and medical oncologists. Many clinical trials involving RT as the sole treatment or in combination with other treatment modalities for various cancers are now in progress.

 Our department is responsible for conventional (photon-electron) RT that consists of four linear accelerators, a CT simulator, four treatment planning computer workstations, and other important devices. IMRT and IGRT have been routinely employed for head and neck cancer and prostate cancer. In 2021, IMRT combined with concurrent chemotherapy for locally advanced lung cancer and esophageal cancer and stereotactic irradiation for brain metastases were started. In 2022, IMRT was also applied to patients with breast and rectal cancer. Our department is also responsible for PBT, which is composed of seven operating staff members and one technician for fabricating the compensator and aperture; they are sent from manufacturing companies and work in collaboration with other staff members of our department. PBT consists of two treatment rooms, both of which are routinely used for rotational gantry treatment. In one room, line scanning and intensity modulated proton therapy (IMPT) can be used for prostate cancer, head and neck cancer, and so on. Our department ensures quality assurance and regular maintenance of the PBT machines for precise dose delivery and safe treatment.

Research Activities

 In the Department of Radiation Oncology, the following research activities are in progress:

1)  Establishment of optimal combined approaches including RT and chemotherapy for locally advanced head and neck cancer, non-small cell lung cancer, esophageal cancer, and so on

2) Establishment of the clinical utility of IMRT for head and neck cancer, localized prostate cancer, rectal cancer and cervical esophageal cancer

3) Hypofractionated IMRT for localized prostate cancer

4) Hypofractionated PBT for localized prostate cancer, head and neck cancer, and so on

5) Evaluation of long-term complications after PBT for pediatric malignancies

6) Exploration of biomarkers specific for radioresponse in various cancers

7) Radiobiological investigation of the cellular response to radiation and proton beams

8) Efficacy of liquid biopsy in patients with oligometastases

9) Exploration of molecular mechanisms for exceptional responders

Clinical Trials

1)  The Japanese Radiation Oncology Study Group (JROSG) phase II trial of IMRT with concurrent chemoradiotherapy for resectable squamous cell carcinoma of cervical esophagus.

2) JCOG1208: A non-randomized confirmatory study of intensity modulated radiation therapy (IMRT) for T1-2N0-1M0 oropharyngeal cancer.

3)  JCOG1408: Phase III study of SBRT for stage I non-small cell lung cancer.

4)  JCOG1315C: Non-randomized prospective comparative study between surgical resection and proton beam therapy for resectable hepatocellular carcinoma.

5)  JCOG1801: A phase III randomized controlled trial comparing surgery plus adjuvant chemotherapy with preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy for locally recurrent rectal cancer.

6)  JCOG1806: Avoid Mastectomy using Trastuzumab, pertuzumab and RAdiation Study for Breast Cancer (AMATERAS-BC)

7)  JCOG1912: Novel approach of prophylactic radiation to reduce toxicities comparing 2-step-40 with SIB-56 IMRT techniques for locally advanced squamous cell carcinoma of the head and neck, an intergroup phase III trial. (NEW BRIDGE)

8)  iProton study: Multi-institutional study of IMPT combined with concurrent chemotherapy for locally advanced head and neck squamous cell carcinoma.

Education

 We established an education and training system for residents and junior radiation oncologists through clinical conferences and lectures on radiation oncology, physics, and radiation biology. In addition, a training course on quality assurance of radiation therapy has been regularly held for medical physicists and radiological technologists.

Future Prospects

 We are now aiming to establish a system that can provide high-quality and safe high-precision radiation therapy, such as IMRT or SBRT. In addition, we would like to promote the research and development of innovative technologies related to RT, radiation biology, and medical physics.

List of papers published in 2022

Journal

1. Zenda S, Arai Y, Sugawara S, Inaba Y, Hashimoto K, Yamamoto K, Saigusa Y, Kawaguchi T, Shimada S, Yokoyama M, Miyaji T, Okano T, Nakamura N, Kobayashi E, Takagi T, Matsumoto Y, Uchitomi Y, Sone M. Protocol for a confirmatory trial of the effectiveness and safety of palliative arterial embolization for painful bone metastases. BMC cancer, 23:109, 2023

2. Sekiguchi K, Sumi M, Saito A, Zenda S, Arahira S, Iino K, Okumura M, Kawai F, Nozawa K. The effectiveness of moisturizer on acute radiation-induced dermatitis in breast cancer patients: a systematic review and meta-analysis. Breast cancer (Tokyo, Japan), 30:2-12, 2023

3. Sekiguchi K, Sumi M, Saito A, Zenda S, Arahira S, Iino K, Okumura M, Kawai F, Nozawa K. Correction to: The effectiveness of moisturizer on acute radiation-induced dermatitis in breast cancer patients: a systematic review and meta-analysis. Breast cancer (Tokyo, Japan), 30:13, 2023

4. Kawamura H, Nakamura K, Yoshioka Y, Itasaka S, Tomita N, Onishi M, Iwata H, Aizawa T, Kikuchi K, Nagata K, Nakamura K, Nishioka K, Ishiyama H, Ueno S, Kokubo M, Yamazaki H, Watanabe K, Toyoda T, Akimoto T. Radiotherapy for ductal carcinoma of the prostate: an analysis based on the Japanese radiation oncology study group survey. Japanese journal of clinical oncology, 53:146-152, 2023

5. Endo M, Kawahara S, Sato T, Tokunaga M, Hara T, Mawatari T, Kawano T, Zenda S, Miyaji T, Shimokawa M, Sakamoto S, Takano T, Miyake M, Aono H, Nakashima Y. Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee. BMJ open, 13:e068220, 2023

6. Nozaki M, Kagami Y, Takahashi M, Machida R, Sekino Y, Shibata T, Ito Y, Nishimura Y, Teshima T, Ushijima H, Nagata Y, Matsumoto Y, Akimoto T, Takahashi K, Murayama S, Uno T, Tsujino K, Hamamoto Y, Nakagawa K, Kodaira T, Hiraoka M. Evaluation of breast cosmetic changes with a computer-software; the breast cancer conservative treatment cosmetic results (BCCT. core) in hypofractionated whole breast irradiation after breast-conserving surgery-supplementary analysis of multicenter single-arm confirmatory trial: JCOG0906. Breast cancer (Tokyo, Japan), 29:1042-1049, 2022

7. Okumura M, Du J, Kageyama SI, Yamashita R, Hakozaki Y, Motegi A, Hojo H, Nakamura M, Hirano Y, Okuma Y, Okuma HS, Tsuchihara K, Akimoto T. Comprehensive screening for drugs that modify radiation-induced immune responses. British journal of cancer, 126:1815-1823, 2022

8. Ito R, Nakamura Y, Sunakawa H, Fujiwara H, Hojo H, Nakamura N, Fujita T, Yano T, Daiko H, Akimoto T, Yoshino T, Kojima T. Tumor response and survival outcomes of salvage concurrent chemoradiotherapy with three-dimensional conformal radiotherapy and 5-fluorouracil/platinum-based chemotherapy for postoperative locoregional recurrence of esophageal squamous cell carcinoma. Esophagus, 19:645-652, 2022

9. Yokota T, Ueno T, Soga Y, Ishiki H, Uezono Y, Mori T, Zenda S, Uchitomi Y. J-SUPPORT research policy for oral mucositis associated with cancer treatment. Cancer medicine, 11:4816-4829, 2022

10. Yaguchi-Saito A, Kaji Y, Matsuoka A, Okuyama A, Fujimori M, Saito J, Odawara M, Otsuki A, Uchitomi Y, Zenda S, Shimazu T. Factors affecting the implementation of guideline-based prophylactic antiemetic therapy for chemotherapy-induced nausea and vomiting in Japan: a protocol for a hospital-based qualitative study. BMJ open, 12:e055473, 2022

11. Nakajo K, Inaba A, Aoyama N, Takashima K, Kadota T, Yoda Y, Morishita Y, Okano W, Tomioka T, Shinozaki T, Matsuura K, Hayashi R, Akimoto T, Yano T. The characteristics of missed pharyngeal and laryngeal cancers at gastrointestinal endoscopy. Japanese journal of clinical oncology, 52:575-582, 2022

12. Takeshita N, Enokida T, Okano S, Fujisawa T, Wada A, Sato M, Tanaka H, Tanaka N, Motegi A, Zenda S, Akimoto T, Tahara M. Induction chemotherapy with paclitaxel, carboplatin and cetuximab for locoregionally advanced nasopharyngeal carcinoma: A single-center, retrospective study. Frontiers in oncology, 12:951387, 2022

13. Sakai SA, Aoshima M, Sawada K, Horasawa S, Yoshikawa A, Fujisawa T, Kadowaki S, Denda T, Matsuhashi N, Yasui H, Goto M, Yamazaki K, Komatsu Y, Nakanishi R, Nakamura Y, Bando H, Hamaya Y, Kageyama SI, Yoshino T, Tsuchihara K, Yamashita R. Fecal microbiota in patients with a stoma decreases anaerobic bacteria and alters taxonomic and functional diversities. Frontiers in cellular and infection microbiology, 12:925444, 2022

14. Mizuno M, Chiba I, Mukohara T, Kondo M, Maruo K, Ohigashi T, Naruo M, Asano Y, Onishi T, Tanabe H, Muta R, Mishima S, Okano S, Yuda M, Hosono A, Ueda Y, Bando H, Itagaki H, Ferrans CE, Akimoto T. Effectiveness of an online support program to help female cancer patients manage their health and illness: Protocol for a randomized controlled trial. Contemporary clinical trials communications, 30:101035, 2022

15. Du J, Kageyama SI, Yamashita R, Hirata H, Hakozaki Y, Okumura M, Motegi A, Hojo H, Nakamura M, Hirano Y, Sunakawa H, Minamide T, Kotani D, Tanaka K, Yano T, Kojima T, Ohashi A, Tsuchihara K, Akimoto T. Impacts of the STING-IFNAR1-STAT1-IRF1 pathway on the cellular immune reaction induced by fractionated irradiation. Cancer science, 113:1352-1361, 2022

16. Nakajo K, Yoda Y, Yamashita H, Takashima K, Murano T, Kadota T, Shinmura K, Ikematsu H, Akimoto T, Yano T. Salvage endoscopic resection for cT1N0M0 local recurrence after chemoradiotherapy for esophageal squamous cell carcinoma: endoscopic submucosal dissection versus endoscopic mucosal resection. Japanese journal of clinical oncology, 52:982-991, 2022

17. Takahashi S, Ohno I, Ikeda M, Konishi M, Kobayashi T, Akimoto T, Kojima M, Morinaga S, Toyama H, Shimizu Y, Miyamoto A, Tomikawa M, Takakura N, Takayama W, Hirano S, Otsubo T, Nagino M, Kimura W, Sugimachi K, Uesaka K. Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-label Multicenter Prospective Trial (JASPAC05). Annals of surgery, 276:e510-e517, 2022

18. Akiyama N, Okamura T, Yoshida M, Kimura SI, Yano S, Yoshida I, Kusaba H, Takahashi K, Fujita H, Fukushima K, Iwasaki H, Tamura K, Saeki T, Takamatsu Y, Zenda S. Difference of compliance rates for the recommendations in Japanese Guideline on Febrile Neutropenia according to respondents’ attributes: the second report on a questionnaire survey among hematology-oncology physicians and surgeons. Supportive care in cancer, 30:4327-4336, 2022

19. Okumura M, Hojo H, Akimoto T. Response to palliative radiotherapy for cancer patients with interstitial lung disease: A physician’s perspective. Radiotherapy and oncology, 169:157-158, 2022

20. Tamaki Y, Aibe N, Komiyama T, Nagasaka S, Imagumbai T, Itazawa T, Onishi H, Akimoto T, Nagata Y, Nakayama Y. Optimal Clinical Target Volume of Radiotherapy Based on Microscopic Extension around the Primary Gross Tumor in Non-Small-Cell Lung Cancer: A Systematic Review. Cancers, 14:2318, 2022

21. Yamaguchi T, Sugiyama Y, Tanaka T, Kimura T, Yumura Y, Nakano M, Sugiyama T, Miura N, Goya M, Yamamoto A, Takahashi S, Miura Y, Tsuzuki T, Masumori N, Nishiyama H, Yao M, Koie T, Miyake H, Saika T, Saito S, Akimoto T, Tamada T, Ando Y, Takahashi S, Suzuki T, Hinotsu S, Kamba T. Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association. International journal of urology, 29:780-792, 2022

22. Tachibana H, Takahashi R, Kogure T, Nishiyama S, Kurosawa T. Practical dosimetry procedure of air kerma for kilovoltage X-ray imaging in radiation oncology using a 0.6-cc cylindrical ionization chamber with a cobalt absorbed dose-to-water calibration coefficient. Radiological physics and technology, 15:264-270, 2022

23. Tachibana H, Watanabe Y, Kurokawa S, Maeyama T, Hiroki T, Ikoma H, Hirashima H, Kojima H, Shiinoki T, Tanimoto Y, Shimizu H, Shishido H, Oka Y, Hirose TA, Kinjo M, Morozumi T, Kurooka M, Suzuki H, Saito T, Fujita K, Shirata R, Inada R, Yada R, Yamashita M, Kondo K, Hanada T, Takenaka T, Usui K, Okamoto H, Asakura H, Notake R, Kojima T, Kumazaki Y, Hatanaka S, Kikumura R, Nakajima M, Nakada R, Suzuki R, Mizuno H, Kawamura S, Nakamura M, Akimoto T. Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter. Brachytherapy, 21:956-967, 2022

24. Ota Y, Kodaira T, Fujii H, Shimokawa M, Yokota T, Nakashima T, Monden N, Homma A, Ueda S, Akimoto T. Real-world clinical outcomes in Japanese patients with locally advanced squamous cell carcinoma of the head and neck treated with radiotherapy plus cetuximab: a prospective observational study (JROSG12-2). International journal of clinical oncology, 27:1675-1683, 2022

25. Watanabe Y, Maeyama T, Mizukami S, Tachibana H, Terazaki T, Takei H, Muraishi H, Gomi T, Hayashi SI. Verification of dose distribution in high dose-rate brachytherapy for cervical cancer using a normoxic N-vinylpyrrolidone polymer gel dosimeter. Journal of radiation research, 63:838-848, 2022

26. Matsumura H, Yoshida G, Toyoda A,  Masumoto K, Nakamura H, Miura T, Nishikawa K, Bessho K, Akita T, Katsuta S, Akimoto T, Sugama Y, Nobuhara F, Nagashima Y. Investigation of Concrete Radioactivation in Cyclotron Type Proton Therapy Facilities using in situ 24Na Measurement Method. Radiation Safety Management, 21:13-25, 2022