Annual Report 2021

Division of Radiation Oncology and Particle Therapy

Tetsuo Akimoto, Sadatomo Zenda, Atsushi Motegi, Hidenobu Tachibana, Kenji Hotta, Hiromi Baba, Kana Motegi, Masaki Nakamura, Hidehiro Hojo, Ryo Takahashi, Shunichiro Kageyama, Hidenari Hirata

Introduction

 The aim of research in the Division of Radiation Oncology and Particle Therapy at the National Cancer Center Hospital East (NCCHE) is to study and develop innovative treatment techniques and pilot a clinical trial for proton beam therapy (PBT). Medical physicists mainly perform the development and verification of the systems for beam irradiation, dose calculation, dose measurement, and imaging of PBT. Radiation oncologists mainly perform studies on the clinical trials, efficacy, and side-effects of PBT.

The Team and What We Do

 At present, the staff of the Division of Radiation Oncology and Particle Therapy consists of seven consultant physicians (radiation oncologists), six radiation technologists, four medical physicists, one nurse, and one clerk. We have more than 300 new patients for PBT every year. Quality assurance of 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. PBT is 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.

 Our division is 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 division. PBT consists of two treatment rooms, both of which are routinely used for rotational gantry treatment. Our division ensures quality assurance and regular maintenance of the PBT machines for precise dose delivery and safe treatment.

Research activities

1. Phase II study of PBT combined with chemotherapy for inoperable non-small cell lung cancer.

2. Phase I/II study of dose escalated PBT combined with chemotherapy for esophageal cancer.

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

4. Establishment of feasibility and effectiveness of line scanning for localized prostate cancer.

5. Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

6. Radiobiological evaluation of cellular response to PBT.

7. Radiobiological evaluation of combined effect of chemotherapeutic agents on enhancement of PBT.

8. Standardization of methods of PBT and quality assurance of PBT among Japanese proton beam facilities.

9. Establishment of infrastructure for multi-institutional study of PBT for various cancers. Technical development of intensity modulated proton beam therapy (IMPT).

10.  In silico comparison of dose distribution between IMRT and IMPT for locally advanced head and neck squamous cell carcinoma.

Clinical trials

 The following in-house and multi-institutional clinical trials are under way.

1) Phase I/II study of dose escalated PBT combined with chemotherapy for esophageal cancer.

2) Phase I/II study of line scanning for localized prostate cancer.

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

4) Pilot study of IMPT for locally advanced head and neck squamous cell carcinoma.

5) iProron 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 including PBT 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 PBT. In addition, we would like to promote the research and development of innovative technologies regarding PBT, radiation biology, and medical physics.

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

List of papers published in 2021

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