Annual Report 2017

Department of Radiation Oncology

Tetsuo Akimoto, Naoki Nakamura, Sadatomo Zenda, Atsushi Motegi, Hidehiro Hojo, Masaki Nakamura, Masayuki Okumura

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 maintain the severity of radiation-related complications within an acceptable level.

 The primary aims of the Department of Radiation Oncology are 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 cancers and optimal irradiation techniques including total dose, fractionation, and radiation fields.

Our 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 300 or more new patients for PBT every year, and quality assurances of both conventional RT and PBT are 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 a precise radiation dose 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 with 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. Our department is also responsible for PBT that 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. Our department ensures quality assurance and regular maintenance of the PBT machines for precise dose delivery and safe treatment.

Table 1. Changes in the number of patients treated with RT

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 beam

Clinical trials

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

1) The Japan Clinical Oncology Group (JCOG) 0701: Accelerated fractionation vs. conventional fractionation radiation therapy for glottic cancer of T1-2N0M0 phase III study

2) JCOG0701-A1: Evaluation of single-nucleotide polymorphisms (SNPs) in development of acute and late complications after accelerated fractionation and/or conventional fractionation radiation therapy for glottic cancer of T1-2N0M0

3) JCOG1015: A phase II study of intensity modulated radiation therapy (IMRT) with chemotherapy for loco-regionally advanced nasopharyngeal cancer (NPC)

4) Phase II study of PBT for malignant melanoma of nasal cavity

5) Phase II trial of concurrent chemoradiotherapy with 5-FU plus cisplatin for resectable squamous cell carcinoma of cervical esophagus

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

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

8) 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

9) Dose escalation study of PBT combined with concurrent chemotherapy for locally advanced esophageal cancer

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

11) JCOG1315C: Non-randomized prospective comparative study between surgical resection and proton beam therapy for resectable hepatocellular 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. 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 in January 2017 - March 2018

Journal

 1. Takahashi S, Ohno I, Ikeda M, Kobayashi T, Akimoto T, Kojima M, Konishi M, Uesaka K. Neoadjuvant S-1 with concurrent radiotherapy followed by surgery for borderline resectable pancreatic cancer: study protocol for an open-label, multicentre, prospective phase II trial (JASPAC05). BMJ Open, 7:e018445, 2017

 2. Kaito A, Kinoshita T, Tokunaga M, Sunagawa H, Watanabe M, Sugita S, Tonouchi A, Sato R, Abe I, Akimoto T. Prognostic Factors and Recurrence Pattern of Far-advanced Gastric Cancer with Pathologically-positive Para-aortic Lymph Nodes. Anticancer Res, 37:3685-3692, 2017

 3. Hojo H, Dohmae T, Hotta K, Kohno R, Motegi A, Yagishita A, Makinoshima H, Tsuchihara K, Akimoto T. Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak. Radiat Oncol, 12:111, 2017

 4. Nibu KI, Hayashi R, Asakage T, Ojiri H, Kimata Y, Kodaira T, Nagao T, Nakashima T, Fujii T, Fujii H, Homma A, Matsuura K, Monden N, Beppu T, Hanai N, Kirita T, Kamei Y, Otsuki N, Kiyota N, Zenda S, Omura K, Omori K, Akimoto T, Kawabata K, Kishimoto S, Kitano H, Tohnai I, Nakatsuka T. Japanese Clinical Practice Guideline for Head and Neck Cancer. Auris Nasus Larynx, 44:375-380, 2017

 5. Nakamura N, Arahira S, Zenda S, Yoneyama K, Mukai H, Onozawa M, Toshima M, Motegi A, Hirano Y, Hojo H, Kibe Y, Akimoto T. Post-mastectomy radiation therapy without usage of a bolus may be a reasonable option. J Radiat Res, 58:66-70, 2017

 6. Hisakane K, Yoh K, Nakamura N, Udagawa H, Kirita K, Umemura S, Matsumoto S, Niho S, Akimoto T, Tsuboi M, Goto K. Salvage chemoradiotherapy with cisplatin and vinorelbine for postoperative locoregional recurrence of non-small cell lung cancer. Medicine (Baltimore), 96:e8635, 2017

 7. Nakamura N, Zenda S, Tahara M, Okano S, Hayashi R, Hojo H, Hotta K, Kito S, Motegi A, Arahira S, Tachibana H, Akimoto T. Proton beam therapy for olfactory neuroblastoma. Radiother Oncol, 122:368-372, 2017

 8. Kumabe A, Zenda S, Motegi A, Onozawa M, Nakamura N, Kojima T, Daiko H, Shigematsu N, Akimoto T. Long-term Clinical Results of Concurrent Chemoradiotherapy for Patients with Cervical Esophageal Squamous Cell Carcinoma. Anticancer Res, 37:5039-5044, 2017

 9. Yamazaki T, Tahara M, Enokida T, Wakasugi T, Arahira S, Zenda S, Motegi A, Akimoto T, Yoshisue K. Pharmacokinetics of initial full and subsequent reduced doses of S-1 in patients with locally advanced head and neck cancer-effect of renal insufficiency. Jpn J Clin Oncol, 47:407-412, 2017

10. Demizu Y, Mizumoto M, Onoe T, Nakamura N, Kikuchi Y, Shibata T, Okimoto T, Sakurai H, Akimoto T, Ono K, Daimon T, Murayama S. Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan. Cancer Sci, 108:972-977, 2017

11. Lewis SL, Porceddu S, Nakamura N, Palma DA, Lo SS, Hoskin P, Moghanaki D, Chmura SJ, Salama JK. Definitive Stereotactic Body Radiotherapy (SBRT) for Extracranial Oligometastases: An International Survey of >1000 Radiation Oncologists. Am J Clin Oncol, 40:418-422, 2017

12. Iwata H, Ishikawa H, Takagi M, Okimoto T, Murayama S, Akimoto T, Wada H, Arimura T, Sato Y, Araya M, Mizoe JE, Gosho M, Nakamura K, Shirato H, Sakurai H. Long-term outcomes of proton therapy for prostate cancer in Japan: a multi-institutional survey of the Japanese Radiation Oncology Study Group. Cancer Med, 7:677-689, 2018

13. Kodaira T, Kagami Y, Shibata T, Shikama N, Nishimura Y, Ishikura S, Nakamura K, Saito Y, Matsumoto Y, Teshima T, Ito Y, Akimoto T, Nakata K, Toshiyasu T, Nakagawa K, Nagata Y, Nishimura T, Uno T, Kataoka M, Yorozu A, Hiraoka M. Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701). Ann Oncol, 29:992-997, 2018

14. Hashimoto Y, Motegi A, Akimoto T, Mitsuhashi N, Iizuka J, Tanabe K, Ishii Y, Kono S, Izumi S, Karasawa K. The 5-year outcomes of moderately hypofractionated radiotherapy (66 Gy in 22 fractions, 3 fractions per week) for localized prostate cancer: a retrospective study. Int J Clin Oncol, 23:165-172, 2018