Annual Report 2017

Jun Itami, Yoshinori Ito (till August 2017), Yuko Nakayama (since September 2017), Hiroshi Igaki, Naoya Murakami, Koichi Inaba, Kana Takahashi, Kazuma Kobayashi, Yoshiaki Takagawa, Hiroyuki Okamoto, Akihisa Wakita, Satoshi Nakamura, Shie Nishioka

Introduction

 The roles of the Department of Radiation Oncology are to provide state-of-the-art radiation therapy for all relevant patients, to educate and develop the expertise of radiation oncologists, radiation technologists, and medical physicists, and to lead new developments in radiation oncology in Japan as well as worldwide. All departmental activities are dedicated to cancer patients. A linear accelerator for hospital-based boron neutron capture therapy (BNCT) was installed in the new facility and an epithermal neutron beam was obtained already in August 2015 and presently stable output of epithermal neutrons is attained and preclinical experiments were commenced. Additionally, in this year a brand-new MRI-guided radiation therapy system, MRIdian of ViewRay was installed as a first machine in Japan.

Our team and what we do

 The Department of Radiation Oncology of the National Cancer Center Hospital (NCCH) is the greatest radiation oncology department in Japan. Four linear accelerators, CyberKnife, MRIdian, one X-ray simulator, three XCT-simulators, and 15 treatment planning computers are working together through on-line networks to provide the 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 performed routinely. Stereotactic brain irradiation is performed with CyberKnife in the treatment of metastatic as well as primary brain tumors. Stereotactic body tumor irradiation is performed in lung and liver tumors under respiratory gating in linear accelerators or CyberKnife. All linear accelerators have on-board kilovoltage CT imagers, which help to align patient and tumor coordinates precisely. 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. Gold marker fiducials have been implanted to improve geometric precision of radiation field reproducibility. In this year, MRIdian of ViewRay was installed as a first machine in Japan, which enables MRI-guided adaptive radiation therapy.

 Brachytherapy is also performed very intensively to improve local control and many patients are referred to from all over Japan. For brachytherapy, the following modalities are being employed: an Ir-192 high dose rate (HDR) afterloading system including dedicated CT simulator and fluoroscopy, an I-125 seed implantation system, and other low dose rate (LDR) brachytherapy systems using Au grains, Ir-thin wires, and ruthenium eye plaques. The number of patients undergoing HDR brachytherapy continued to rise constantly. Our department is the only institution in Tokyo, where HDR interstitial as well as intracavitary irradiations can be performed. HDR interstitial radiation is performed mainly in gynecological, genitourinary, and head and neck tumors. Additionally, there are two beds in the shielded ward in Floor 13B. Ruthenium mold therapy is performed by ophthalmologists to treat retinoblastomas and choroidal melanomas. LDR interstitial implants are carried out by

radiation oncologists using Au-198 grains and

Ir-192 thin wires for the management of head and neck tumors and gynecological malignancies.

 Additionally, basic physical and biological experiments concerning accelerator-based BNCT system is being performed intensively toward clinical application.

Research activities

 Clinical research is an indispensable part of daily activities of our department. The primary interests of research activities of our department are: 1) an optimal fractionation regimen for the pain palliation of bone metastasis; 2) the safety and feasibility of shortened fractionation regimen for various malignancies, especially for breast cancer and vocal cord cancer; 3) Image-guided HDR and LDR brachytherapy for genitourinary and gynecologic cancers; 4) hypofractionated stereotactic irradiation of brain and body tumors; 5) adaptive radiation therapy in accordance with the intratherapeutic tumor and normal tissue change; and 6) development of accelerator-based BNCT system.

Clinical trials

*Metastatic brain tumor: Phase II trial of hippocampal sparing IMRT

*Lung cancer: Various JCOG studies

*Lung cancer: Stereotactic radiation therapy for histologically non-verified lung tumors

*Pediatrics: Phase II clinical trial on multimodality therapy in localized Ewing sarcomas and related tumors (JESS 04)

*Head and Neck cancers: Various JCOG studies including IMRT for nasopharyngeal and oropharyngeal cancers

*Breast cancer: Phase II trial of SAVI applicator HDR brachytherapy after partial mastectomy

*Liver cancer: Phase I trial on stereotactic hypofractionated radiation to hepatocellular carcinoma

*Cervical cancer: Phase I/II trial of hybrid brachytherapy of cervical cancer

*F-BPA PET/CT: Feasibility study of F-BPA PET/CT in detecting malignancies with comparison to FDG PET/CT

*Development of an Adaptive Radiation Therapy System

Education

 Five residents were trained in all fields of radiation oncology except particle beam therapy. Seminars about biology, physics, and clinical radiation oncology are regularly held in the evening time. This year, trainees from Chile and

China studied and researched in our department.

Future prospects

 With the expanding indications of radiation therapy, further manpower will be required and research perspectives will be very widened. Radiation oncology is one of the most promising disciplines in oncology.

List of papers published in January 2017 - March 2018

Journal

 1. Igaki H, Harada K, Umezawa R, Miyakita Y, Ohno M, Takahashi M, Sumi M, Inaba K, Murakami N, Ito Y, Narita Y, Itami J. Outcomes of surgery followed by local brain radiotherapy compared with surgery followed by whole brain radiotherapy for single brain metastasis. Tumori, 103:367-373, 2017

 2. Honma Y, Hokamura N, Nagashima K, Sudo K, Shoji H, Iwasa S, Takashima A, Kato K, Hamaguchi T, Boku N, Umezawa R, Ito Y, Itami J, Koyanagi K, Igaki H, Tachimori Y. Clinical Outcomes of Resectable Esophageal Cancer with Supraclavicular Lymph Node Metastases Treated with Curative Intent. Anticancer Res, 37:3741-3749, 2017

 3. Yoshioka Y, Kotsuma T, Komiya A, Kariya S, Konishi K, Nonomura N, Ogawa K, Tanaka E, Nishimura K, Fujiuchi Y, Kitamura H, Yamagami T, Yamasaki I, Teshima T, Nakamura K, Itami J. Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer. Int J Radiat Oncol Biol Phys, 97:952-961, 2017

 4. Sekii S, Murakami N, Kato T, Harada K, Kitaguchi M, Takahashi K, Inaba K, Igaki H, Ito Y, Sasaki R, Itami J. Outcomes of salvage high-dose-rate brachytherapy with or without external beam radiotherapy for isolated vaginal recurrence of endometrial cancer. Journal of contemporary brachytherapy, 9:209-215, 2017

 5. Okamoto H, Nakamura S, Nishioka S, Iijima K, Wakita A, Abe Y, Tohyama N, Kawamura S, Minemura T, Itami J. Independent assessment of source position for gynecological applicator in high-dose-rate brachytherapy. Journal of contemporary brachytherapy, 9:477-486, 2017

 6. Nakamura S, Imamichi S, Masumoto K, Ito M, Wakita A, Okamoto H, Nishioka S, Iijima K, Kobayashi K, Abe Y, Igaki H, Kurita K, Nishio T, Masutani M, Itami J. Evaluation of radioactivity in the bodies of mice induced by neutron exposure from an epi-thermal neutron source of an accelerator-based boron neutron capture therapy system. Proc Jpn Acad Ser B Phys Biol Sci, 93:821-831, 2017

 7. Nakamura S, Okamoto H, Wakita A, Umezawa R, Takahashi K, Inaba K, Murakami N, Kato T, Igaki H, Ito Y, Abe Y, Itami J. A management method for the statistical results of patient-specific quality assurance for intensity-modulated radiation therapy. J Radiat Res, 58:572-578, 2017

 8. Nakamura S, Wakita A, Ito M, Okamoto H, Nishioka S, Iijima K, Kobayashi K, Nishio T, Igaki H, Itami J. Modeling the detection efficiency of an HP-Ge detector for use in boron neutron capture therapy. Appl Radiat Isot, 125:80-85, 2017

 9. Yamaguchi M, Suzuki R, Oguchi M, Asano N, Amaki J, Akiba T, Maeda T, Itasaka S, Kubota N, Saito Y, Kobayashi Y, Itami J, Ueda K, Miyazaki K, Ii N, Tomita N, Sekiguchi N, Takizawa J, Saito B, Murayama T, Ando T, Wada H, Hyo R, Ejima Y, Hasegawa M, Katayama N. Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan. J Clin Oncol, 35:32-39, 2017

10. Watanabe Y, Kurihara H, Itami J, Sasaki R, Arai Y, Sugimura K. Relationship between the uptake of 18F-borono-L-phenylalanine and L-[methyl-11C] methionine in head and neck tumors and normal organs. Radiat Oncol, 12:17, 2017

11. Kobayashi K, Mori T, Matsumoto F, Murakami N, Teshima M, Fukasawa M, Matsumoto Y, Matsumura S, Itami J, Asai M, Yoshimoto S. Impact of microscopic orbital periosteum invasion in orbital preservation surgery. Jpn J Clin Oncol, 47:321-327, 2017

12. Kono Y, Kurihara H, Kawamoto H, Yasui N, Honda N, Igaki H, Itami J. Radiation absorbed dose estimates for 18F-BPA PET. Acta Radiol, 58:1094-1100, 2017

13. Yoden E, Nose T, Otani Y, Asahi S, Tsukiyama I, Dokiya T, Saeki T, Fukuda I, Sekine H, Shikama N, Kumazaki Y, Takahashi T, Yoshida K, Kotsuma T, Masuda N, Nakashima K, Matsumura T, Nakagawa S, Tachiiri S, Moriguchi Y, Itami J, Oguchi M. Uncertainty of cosmetic evaluation after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study. Jpn J Radiol, 35:381-388, 2017

14. Iwata T, Ueno H, Itami J, Ito Y, Inaba K, Morizane C, Kondo S, Sakamoto Y, Shiba S, Sasaki M, Koga F, Okusaka T. Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors. Jpn J Clin Oncol, 47:826-831, 2017

15. Ishiyama H, Kamitani N, Kawamura H, Kato S, Aoki M, Kariya S, Matsumura T, Kaidu M, Yoshida K, Hashimoto Y, Noda Y, Lim KHC, Kawase T, Takahashi T, Inaba K, Kumano M, Yoshikawa N, Yoshioka Y, Nakamura K, Hiratsuka J, Itami J, Hayakawa K. Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium. Brachytherapy, 16:503-510, 2017

16. Sudo K, Kato K, Kuwabara H, Sasaki Y, Takahashi N, Shoji H, Iwasa S, Honma Y, Okita NT, Takashima A, Hamaguchi T, Yamada Y, Ito Y, Itami J, Fukuda T, Tobinai K, Boku N. Patterns of Relapse after Definitive Chemoradiotherapy in Stage II/III (Non-T4) Esophageal Squamous Cell Carcinoma. Oncology, 94:47-54, 2018

17. Umezawa R, Murakami N, Nakamura S, Wakita A, Okamoto H, Tsuchida K, Kashihara T, Kobayashi K, Harada K, Takahashi K, Inaba K, Ito Y, Igaki H, Masui K, Yoshida K, Jingu K, Tselis N, Itami J. Image-guided interstitial high-dose-rate brachytherapy for locally recurrent uterine cervical cancer: A single-institution study. Brachytherapy, 17:368-376, 2018

18. Morita T, Kurihara H, Hiroi K, Honda N, Igaki H, Hatazawa J, Arai Y, Itami J. Dynamic changes in 18F-borono-L-phenylalanine uptake in unresectable, advanced, or recurrent squamous cell carcinoma of the head and neck and malignant melanoma during boron neutron capture therapy patient selection. Radiat Oncol, 13:4, 2018

19. Okamoto H, Murakami N, Carvajal CC, Miura Y, Wakita A, Nakamura S, Nishioka S, Iijima K, Inaba K, Ito Y, Kato T, Toita T, Itami J. Positional uncertainty of vaginal cuff and feasibility of implementing portable bladder scanner in postoperative cervical cancer patients. Phys Med, 45:1-5, 2018

20. Kashihara T, Nakamura S, Wakita A, Okamoto H, Inaba K, Umezawa R, Shima S, Tsuchida K, Kobayashi K, Takahashi K, Murakami N, Ito Y, Igaki H, Fujimoto H, Uno T, Itami J. Importance of the site of positive surgical margin in salvage external beam radiation therapy for biochemical recurrence of prostate cancer after radical prostatectomy. Cancer Med, 7:1723-1730, 2018

21. Umezawa R, Inaba K, Nakamura S, Wakita A, Okamoto H, Shima S, Tsuchida K, Kashihara T, Kobayashi K, Harada K, Takahashi K, Murakami N, Ito Y, Igaki H, Jingu K, Itami J. Long-term Results of External Beam Radiotherapy for Prostate Cancer with Prostate-specific Antigen of More Than 50 ng/ml and Without Evidence of Lymph Node or Distant Metastasis. Anticancer Res, 38:2303-2309, 2018