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 in order to keep 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 establish the definitive role of RT in cancer treatment. Another important goal is to establish standard treatments for various cancers and optimal irradiation techniques including total dose, fractionation, and radiation fields.

Table 1. Number of patients treated with radiation therapy during 2017-2021

The Team and What We Do

At present, the staff of the Department of Radiation Oncology consists of seven consultant physicians (radiation oncologists), 19 radiation technologists, four medical physicists, one nurse, and one clerk. We have more than 1,000 new cases for conventional RT and more than 300 new patients for PBT every year. Quality assurance of both conventional RT and PBT is performed by medical physicists and radiation technologists, and a conference on verification of treatment planning is held every morning in addition to a weekly work conference regarding research activities. RT and PBT are routinely based on three-dimensional radiation therapy planning and PBT using RT-dedicated multi-detector-row helical computed tomography (CT) scanning in order to confirm the precise radiation dose to administer to the targeted tumors. Respiratory gating has been applied especially in radiotherapeutic management for patients with lung, esophagus, and liver cancers.

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 or combined 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 applied for head and neck cancer and prostate cancer. In 2020, IMRT combined with concurrent chemotherapy for locally advanced lung cancer and esophageal cancer and stereotactic irradiation for brain metastases were started. 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, and both rooms are routinely used for rotational gantry treatment. In one room, line scanning and intensity modulated proton therapy (IMPT) can be used for prostate cancer or 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. In 2021, we started high-dose and low-dose brachytherapy for uterine cervical cancer and prostate cancer.

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 and esophageal cancer, and so on

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

3) Hypofractionated IMRT for localized prostate cancer

4) Hypofractionated PBT for localized prostate cancer

5) Evaluation of feasibility of PBT combined with chemotherapy for inoperable locally advanced non-small cell lung cancer and locally advanced esophageal cancer

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

7) The role of gene polymorphism in development of acute and late radiation-related complications

8) Exploration of biomarkers for head and neck cancer

9) Radiobiological investigation of cellular response to radiation and proton beams

10) Efficacy of liquid biopsy in patients with oligometastases.

11) 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. JCOG1008: Phase II/III trial of postoperative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck

4. Dose escalation study of PBT combined with concurrent chemotherapy for locally advanced esophageal cancer

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

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

7. 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

8. JCOG1806: Avoid MAstectomy using Trastuzumab, pertuzumab and RAdiation Study for Breast Cancer (AMATERAS-BC)

9. 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 regarding quality assurance of radiation therapy has been regularly held for medical physicists and radiological technologists.

Future Prospects

We are now aiming at the establishment of 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 regarding RT, radiation biology, and medical physics.

List of papers published

Journal

1. 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

2. Matsuda Y, Yamaguchi T, Matsumoto Y, Ishiki H, Usui Y, Kako J, Suzuki K, Matsunuma R, Mori M, Watanabe H, Zenda S. Research policy in supportive care and palliative care for cancer dyspnea. Japanese journal of clinical oncology, 52:260-265, 2022

3. 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

4. Fukushima T, Tsuji T, Watanabe N, Sakurai T, St AM, St KK, Yahiro S, Oki M, Okita Y, Yokota S, Nakano J, Sugihara S, Sato H, Kawakami J, Kagaya H, Tanuma A, Sekine R, Mori K, Zenda S, Kawai A. Cancer Rehabilitation Provided by Designated Cancer Hospitals in Japan: The Current State of Outpatient Setting and Coordination after Discharge. Progress in rehabilitation medicine, 7:20220006, 2022

5. 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: official journal of the Multinational Association of Supportive Care in Cancer, 30:4327-4336, 2022

6. Yokota T, Zenda S, Ota I, Yamazaki T, Yamaguchi T, Ogawa T, Tachibana H, Toshiyasu T, Homma A, Miyaji T, Mashiko T, Hamauchi S, Tominaga K, Ishii S, Otani Y, Orito N, Uchitomi Y. Phase 3 Randomized Trial of Topical Steroid Versus Placebo for Prevention of Radiation Dermatitis in Patients With Head and Neck Cancer Receiving Chemoradiation. International journal of radiation oncology, biology, physics, 111:794-803, 2021

7. Mizumoto M, Fuji H, Miyachi M, Soejima T, Yamamoto T, Aibe N, Demizu Y, Iwata H, Hashimoto T, Motegi A, Kawamura A, Terashima K, Fukushima T, Nakao T, Takada A, Sumi M, Oshima J, Moriwaki K, Nozaki M, Ishida Y, Kosaka Y, Ae K, Hosono A, Harada H, Ogo E, Akimoto T, Saito T, Fukushima H, Suzuki R, Takahashi M, Matsuo T, Matsumura A, Masaki H, Hosoi H, Shigematsu N, Sakurai H. Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines. Cancer treatment reviews, 98:102209, 2021

8. Sunakawa H, Yoda Y, Takeshita N, Hasegawa H, Takashima K, Kadota T, Fujita T, Akimoto T, Fujii S, Yano T. Endoscopic resection combined with the Cryoballoon focal ablation system in the porcine normal esophagus: a preclinical study. BMC gastroenterology, 21:234, 2021

9. Okumura M, Hojo H, Nakamura M, Hiyama T, Nakamura N, Zenda S, Motegi A, Hirano Y, Kageyama SI, Parshuram RV, Fujisawa T, Kuno H, Akimoto T. Radiation pneumonitis after palliative radiotherapy in cancer patients with interstitial lung disease. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology, 161:47-54, 2021

10. 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. A questionnaire survey on evaluation for penetration and compliance of the Japanese Guideline on Febrile Neutropenia among hematology-oncology physicians and surgeons. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer, 29:6831-6839, 2021

11. Hirata H, Niida A, Kakiuchi N, Uchi R, Sugimachi K, Masuda T, Saito T, Kageyama SI, Motomura Y, Ito S, Yoshitake T, Tsurumaru D, Nishimuta Y, Yokoyama A, Hasegawa T, Chiba K, Shiraishi Y, Du J, Miura F, Morita M, Toh Y, Hirakawa M, Shioyama Y, Ito T, Akimoto T, Miyano S, Shibata T, Mori M, Suzuki Y, Ogawa S, Ishigami K, Mimori K. The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy. Cancer research, 81:4926-4938, 2021

12. Komine R, Kojima M, Ishi G, Kudo M, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Kobayashi T, Akimoto T, Murakami A, Sasaki M, Tanaka M, Matsuzaki A, Ohike N, Uchida K, Sugiyama T, Hirabayashi K, Tajiri T, Ishida K, Kai K, Omori Y, Notohara K, Yamaguchi H, Matsuda Y, Naito Y, Fukumura Y, Hamada Y, Mihara Y, Masugi Y, Gotohda N, Harada K, Fukushima N, Furukawa T. Recognition and pathological features of periampullary region adenocarcinoma with an indeterminable origin. Cancer medicine, 10:3499-3510, 2021

13. Raturi VP, Motegi A, Zenda S, Nakamura N, Hojo H, Kageyama SI, Okumura M, Rachi T, Ohyoshi H, Tachibana H, Motegi K, Ariji T, Nakamura M, Hirano Y, Hirata H, Akimoto T. Comparison of a Hybrid IMRT/VMAT technique with non-coplanar VMAT and non-coplanar IMRT for unresectable olfactory neuroblastoma using the RayStation treatment planning system-EUD, NTCP and planning study. Journal of radiation research, 62:540-548, 2021

14. Iwai K, Nambu T, Kashima Y, Yu J, Eng K, Miyamoto K, Kakoi K, Gotou M, Takeuchi T, Kogame A, Sappal J, Murai S, Haeno H, Kageyama SI, Kurasawa O, Niu H, Kannan K, Ohashi A. A CDC7 inhibitor sensitizes DNA-damaging chemotherapies by suppressing homologous recombination repair to delay DNA damage recovery. Science advances, 7:2021

15. Du J, Kageyama SI, Hirata H, Motegi A, Nakamura M, Hirano Y, Okumura M, Yamashita R, Tsuchihara K, Hojo H, Hirayama R, Akimoto T. Comparative analysis of the immune responses in cancer cells irradiated with X-ray, proton and carbon-ion beams. Biochemical and biophysical research communications, 585:55-60, 2021

16. Aibe N, Ogino H, Teramukai S, Yamazaki H, Iwata H, Matsuo Y, Okimoto T, Murakami M, Suzuki M, Arimura T, Ogino T, Murayama S, Harada H, Nakamura M, Akimoto T, Sakurai H. Multi-Institutional Retrospective Analysis of the Outcomes of Proton Beam Therapy for Patients With 1 to 3 Pulmonary Oligometastases From Various Primary Cancers. Advances in radiation oncology, 6:100690, 2021

17. Nozaki M, Kagami Y, Machida R, Nakamura K, Ito Y, Nishimura Y, Teshima T, Saito Y, Nagata Y, Matsumoto Y, Akimoto T, Hiraoka M. Final analysis of a Multicenter Single-Arm Confirmatory Trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906. Japanese journal of clinical oncology, 51:865-872, 2021

18. Nakajo K, Yoda Y, Kadota T, Murano T, Shinmura K, Ikematsu H, Akimoto T, Yano T. Radial incision and cutting for dilation before endoscopic submucosal dissection in patients with esophageal cancer on the distal side of severe benign esophageal strictures. Diseases of the esophagus: official journal of the International Society for Diseases of the Esophagus, 34:2021