Annual Report 2023

Department of Radiation Oncology

Sadamoto Zenda, Hidehiro Hojo, Masaki Nakamura, Hidenari Hirata, Takeshi Fujisawa

Introduction

 Radiotherapy (RT) plays an essential role in the management of cancer patients. It is used as a curative treatment for many patients with loco-regional localized malignant disease, integrated therapy combined with chemotherapy and/or surgery and as a 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 radiotherapy (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 5 physicians (radiation oncologists) , 27 radiation technologists, and 5 medical physicists. We have more than 1,500 new cases of RT and more than 300 new patients for PBT every year.

 Quality assurance of RT and PBT is performed by medical physicists and radiation technologists.

 The selection of treatment approach is determined through clinical conference which consists of surgeon, medical oncologists and radiation oncologists.

 As for the details of RT, we check all patients who receive RT/PBT in daily morning conference.

 Recently we have accepted not only Japanese patients but also Asian patients, and the number of Asian patients has been increasing.

Research Activities

 Head and neck cancer

1) Establishment of optimal combined approaches including proton beam therapy for skull base tumors

2) Establishment of optimal combined approaches including photon beam therapy and chemotherapy for locally advanced head and neck cancer

3) Palliative radiotherapy for elderly head and neck patients

　

 Lung cancer

1) Proton Beam Therapy (PBT) for lung cancer

2) Search for biomarkers to predict lung cancer recurrence after radiotherapy

　

 Breast cancer

1) Hypo-fractionated RT for elderly patients

2) Use of IMRT to avoid late toxicity

　

 Liver cancer

1) Proton Beam Therapy (PBT) for hepatocellular carcinoma (HCC)

2) Stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC)

3) Proton Beam Therapy (PBT) for liver metastases

　

 Prostate cancer

1) IMRT or PBT for prostate cancer

2) PBT for foreign patients with prostate cancer

Clinical Trials

1) JCOG1912

2) iProton study

3) JCOG 1315C

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 now aim to establish a system that can provide high-quality and safe high-precision radiation therapy, and 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 2023

Journal

1. Akechi T, Furukawa TA, Noma H, Iwata H, Toyama T, Higaki K, Matsuoka H, Zenda S, Iwatani T, Akahane K, Inoue A, Sagara Y, Uchida M, Imai F, Momino K, Imaizumi G, Yamaguchi T, Mashiko T, Miyaji T, Horikoshi M, Sakurai N, Onishi T, Kanemitsu Y, Murata T, Wanifuchi-Endo Y, Kuroda H, Nishikawa R, Miyashita M, Abe M, Uchitomi Y; J-SUPPORT 2001 Study group. Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study). Psychiatry Clin Neurosci. 2024 Mar; Online ahead of print. doi: 10.1111/pcn.13657.

2. Fujisawa T, Motegi A, Hirata H, Zenda S, Hojo H, Nakamura M, Oyoshi H, Tomizawa K, Zhou Y, Fukushi K, Kageyama SI, Enokida T, Okano S, Tahara M, Shinozaki T, Hayashi R, Matsuura K, Akimoto T. Long-term outcomes of patients with oral cavity cancer receiving postoperative radiotherapy after salvage neck dissection for cervical lymph node recurrence. Head Neck. 2024 Mar; 46(3):541-551. doi: 10.1002/hed.27609.

3. Mizumoto M, Ogino H, Okumura T, Terashima K, Murakami M, Ogino T, Tamamura H, Akimoto T, Waki T, Katoh N, Araya M, Onoe T, Takagi M, Iwata H, Numajiri H, Okimoto T, Uchinami Y, Maruo K, Shibuya K, Sakurai H. Proton beam therapy for hepatocellular carcinoma: Multicenter prospective registry study in Japan. Int J Radiat Oncol Biol Phys. 2024 Mar; 118(3):725-733. doi: 10.1016/j.ijrobp.2023.09.047.

4. Homma A, Ando M, Hanai N, Harada H, Honma Y, Kanda T, Kano S, Kawakita D, Kiyota N, Kizawa Y, Nakagawa M, Ogawa T, Shinomiya H, Shinozaki T, Suzuki M, Tsuji T, Yasuda K, Zenda S, Kodaira T, Kirita T, Nibu KI. Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer. Auris Nasus Larynx. 2024 Feb; 51(1):174-188. doi: 10.1016/j.anl.2023.07.003.

5. Tomizawa K, Motegi A, Oyoshi H, Fujisawa T, Zenda S, Zhou Y, Nakamura M, Hirata H, Hojo H, Kageyama SI, Hirotaki K, Matsuura K, Akimoto T. Accelerated three-dimensional conformal radiotherapy for early-stage glottic cancer in reducing dose to the internal carotid artery and pharyngeal constrictor muscles. Head Neck. 2024 Feb; 46(2):239-248. doi: 10.1002/hed.27568.

6. Jang JY, Kim K, Chen MF, Akimoto T, Wang MLC, Kim MJ, Kim K, Lee TH, Yoo GS, Park HC. A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy. Cancer Med. 2024 Feb; 13(3):e7023. doi: 10.1002/cam4.7023.

7. Oyoshi H, Du J, Sakai SA, Yamashita R, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Nakamura Y, Kojima M, Suzuki A, Zenkoh J, Tsuchihara K, Akimoto T, Shibata A, Suzuki Y, Kageyama SI. Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma. Sci Adv. 2023 Dec; 9(50):eadh9069. doi: 10.1126/sciadv.adh9069.

8. Kodaira T, Kagami Y, Machida R, Shikama N, Sekino Y, Ito Y, Ishikura S, Saito Y, Matsumoto Y, Konishi K, Murakami N, Akimoto T, Fukushima Y, Toshiyasu T, Katano A, Nagata Y, Ogawa H, Uno T, Hamamoto Y, Nishimura Y, Mizowaki T; Japan Clinical Oncology Group. Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3). Int J Radiat Oncol Biol Phys. 2023 Dec; 117(5):1118-1124. doi: 10.1016/j.ijrobp.2023.06.251.

9. Uematsu M, Nakajima H, Hosono A, Kiyohara H, Hirota A, Takahashi N, Fukuda M, Kusuhara S, Nakao T, Funasaka C, Kondoh C, Harano K, Matsubara N, Naito Y, Akimoto T, Mukohara T. Safety of immune checkpoint inhibitors after proton beam therapy in head and neck mucosal melanoma: a case series. Melanoma Res. 2023 Dec; 33(6):547-552. doi: 10.1097/CMR.0000000000000924.

10. Yokota T, Zenda S, Kodaira T, Kiyota N, Fujimoto Y, Wasano K, Takahashi R, Mizowaki T, Homma A, Sasaki K, Machida R, Sekino Y, Fukuda H; Japan Clinical Oncology Group Radiation Therapy Study Group; Japan Clinical Oncology Group Head and Neck Cancer Study Group. Novel approach of prophylactic radiation to reduce toxicities comparing 2-step40 with 56-Gy simultaneous integrated boost intensity-modulated radiation therapy for locally advanced squamous cell carcinoma of the head and neck, an intergroup phase III trial (JCOG1912, NEW BRIDGE). BMC Cancer. 2023 Nov; 23(1):1068. doi: 10.1186/s12885-023-11503-z.

11. Morita TY, Yu J, Kashima Y, Kamata R, Yamamoto G, Minamide T, Mashima C, Yoshiya M, Sakae Y, Yamauchi T, Hakozaki Y, Kageyama SI, Nakamura A, Lightcap E, Tanaka K, Niu H, Kannan K, Ohashi A. CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade. Nat Commun. 2023 Nov; 14(1):7490. doi: 10.1038/s41467-023-43274-3.

12. Kawamoto T, Yasuda K, Ito Y, Zenda S, Sakanaka K, Shikama N, Nakamura N, Mizowaki T. Adjuvant treatments for locally advanced differentiated thyroid cancer: a nationwide survey in Japan. Endocr. 2023 Oct; 70(10):999-1003. doi: 10.1507/endocrj.EJ23-0330.

13. Oyoshi H, Hirata H, Hirano Y, Zenda S, Zhou Y, Tomizawa K, Fujisawa T, Nakamura M, Hojo H, Motegi A, Kageyama SI, Zenke Y, Goto K, Ishihara S, Naganawa S, Akimoto T. Prognostic impact of EGFR/ALK alterations in leptomeningeal metastasis from lung adenocarcinoma treated with whole-brain radiotherapy. Clin Exp Metastasis. 2023 Oct; 40(5):407-413. doi: 10.1007/s10585-023-10225-7.

14. Adachi T, Nakamura M, Iramina H, Matsumoto K, Ishihara Y, Tachibana H, Kurokawa S, Cho S, Tanaka K, Fukumoto K, Nishiyama T, Kito S, Mizowaki T. Identification of reproducible radiomic features from on-board volumetric images: A multi-institutional phantom study. Med Phys. 2023 Sep; 50(9):5585-5596. doi: 10.1002/mp.16376.

15. Kurokawa S, Tachibana H. A real-world assessment of the robustness of gel dosimetry. Radiation Physics and Chemistry. 2023 Sep; 210, 111009. doi: 10.1016/j.radphyschem.2023.111009

16. Sato M, Enokida T, Wada A, Okano S, Tanaka H, Fujisawa T, Ueda Y, Motegi A, Shinozaki T, Takeshita N, Tanaka N, Zenda S, Matsuura K, Akimoto T, Hayashi R, Tahara M. Potential efficacy of local therapy for progressive lesions after nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Int J Clin Oncol. 2023 Aug; 28(8):1023-1032. doi: 10.1007/s10147-023-02351-9.

17. Du J, Kageyama SI, Yamashita R, Tanaka K, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Hamaya Y, Kojima M, Nakamura Y, Suzuki A, Suzuki Y, Tsuchihara K, Akimoto T. Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways. Commun Biol. 2023 Aug; 6(1):818. doi: 10.1038/s42003-023-05080-x.

18. Nakamura M, Kageyama SI, Hirata H, Tochinai T, Hojo H, Motegi A, Kanai A, Suzuki Y, Tsuchihara K, Akimoto T. Detection of Pretreatment Circulating Tumor DNA Predicts Recurrence after High-Dose Proton Beam Therapy for Early-Stage Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2023 Aug; 116(5):1085-1090. doi: 10.1016/j.ijrobp.2023.02.021.

19. Funasaka C, Hanai A, Zenda S, Mori K, Fukui M, Hirano N, Shinohara R, Fuse N, Wakabayashi M, Itagaki M, Tomioka Y, Nishina M, Arai Y, Kogawa T, Ozaki Y, Nishimura M, Kobayashi T, Hara F, Takano T, Mukohara T. Mitigation of paclitaxel-induced peripheral neuropathy in breast cancer patients using limb-cooling apparatus: a study protocol for a randomized controlled trial. Front Oncol. 2023 Jul; 13:1216813. doi: 10.3389/fonc.2023.1216813.

20. Akimoto T, Aoyama H, Chua MLK, Jayamanne D, Mizowaki T, Morris L, Onishi H, Song SY, Zeidan YH, Sharma RA. Challenges and Opportunities With the Use of Hypofractionated Radiation Therapy in Cancer Care: Regional Perspectives From South Korea, Japan, Singapore, and Australia. Adv Radiat Oncol. 2023 Jun; 8(6):101291. doi: 10.1016/j.adro.2023.101291.

21. Nakajo K, Ninomiya Y, Kondo H, Takeshita N, Uchida E, Aoyama N, Inaba A, Ikematsu H, Shinozaki T, Matsuura K, Hayashi R, Akimoto T, Yano T. Anatomical classification of pharyngeal and laryngeal endoscopic images using artificial intelligence. Head Neck. 2023 Jun; 45(6):1549-1557. doi: 10.1002/hed.27370.

22. Tatebe H, Harada H, Mori K, Iwata H, Akimoto T, Murakami M, Waki T, Ogino T, Nakamura M, Taguchi H, Nakayama H, Satouchi M, Aoyama H. Clinical results of proton beam radiotherapy for inoperable stage III non-small cell lung cancer: a Japanese national registry study. J Radiat Res. 2023 Jun; 64(Supplement_1):i8-i15. doi: 10.1093/jrr/rrad017.

23. Shinozaki T, Imai T, Kobayashi K, Yoshimoto S, Zenda S, Yamaguchi T, Eguchi K, Okano T, Mashiko T, Kurosaki M, Miyaji T, Matsuura K. Preoperative steroid for enhancing patients' recovery after head and neck cancer surgery with free tissue transfer reconstruction: protocol for a phase III, placebo-controlled, randomised, double-blind study (J-SUPPORT 2022, PreSte-HN Study). BMJ Open. 2023 May; 13(5):e069303. doi: 10.1136/bmjopen-2022-069303.

24. Uchida M, Furukawa TA, Yamaguchi T, Imai F, Momino K, Katsuki F, Sakurai N, Miyaji T, Horikoshi M, Iwata H, Zenda S, Iwatani T, Ogawa A, Inoue A, Abe M, Toyama T, Uchitomi Y, Matsuoka H, Noma H, Akechi T. Optimization of smartphone psychotherapy for depression and anxiety among patients with cancer using the multiphase optimization strategy (MOST) framework and decentralized clinical trial system (SMartphone Intervention to LEssen depression/Anxiety and GAIN resilience: SMILE AGAIN project): a protocol for a randomized controlled trial. Trials. 2023 May; 24(1):344. doi: 10.1186/s13063-023-07307-y.

25. Abe M, Yamaguchi T, Fujita Y, Nishimura T, Kitagawa K, Inui N, Hirano K, Sakata Y, Iihara H, Shibuya Y, Suzuki K, Shibata K, Hori K, Daga H, Nakayama T, Sakata Y, Takahashi TY, Zenda S, Hashimoto H. Efficacy of Olanzapine in Addition to Standard Triplet Antiemetic Therapy for Cisplatin-Based Chemotherapy: A Secondary Analysis of the J-FORCE Randomized Clinical Trial. JAMA Netw Open. 2023 May; 1;6(5):e2310894. doi: 10.1001/jamanetworkopen.2023.10894.

26. Hashimoto Y, Motegi A, Akimoto T, Mitsuhashi N, Ohmatsu K, Kawanishi M, Kono S, Kuribayashi S, Iizuka J, Karasawa K. Relationship between changes in quality of life and genitourinary toxicity grade after brachytherapy with I-125 alone for localised prostate cancer. Rep Pract Oncol Radiother. 2023 Apr; 28(1):24-35. doi: 10.5603/RPOR.a2023.0015.

27. Kano Y, Kadota T, Inaba A, Sunakawa H, Takashima K, Nakajo K, Murano T, Shinmura K, Yoda Y, Ikematsu H, Akimoto T, Yano T. Efficacy and safety of repeated endoscopic radial incision and cutting procedure for benign esophageal stricture. Endosc Int Open. 2023 Mar; 11(3):E230-E236. doi: 10.1055/a-2005-7678.