Annual Report 2018

Department of Radiation Oncology

Tetsuo Akimoto, Naoki Nakamura, Sadatomo Zenda, Atsushi Motegi, Hidehiro Hojo, Masaki Nakamura, Yasuhiro Hirano, 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 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.

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 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 multidetector-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 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 equipment. 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. Number of patients treated with radiation therapy during 2014-2018

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 radiationrelated complications

8) Exploration of biomarker for head and neck cancer

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

10)  Efficacy of liquid biopsy in patients with oligo-metastases.

Clinical trials

 The following in-house and multiinstitutional 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 three-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 2018

Journal

 1. Nozaki M, Kagami Y, Shibata T, Nakamura K, Ito Y, Nishimura Y, Kawaguchi Y, Saito Y, Nagata Y, Matsumoto Y, Akimoto T, Hiraoka M. A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906. Jpn J Clin Oncol, 49:57-62, 2019

 2. Matsuzuka T, Kiyota N, Mizusawa J, Akimoto T, Fujii M, Hasegawa Y, Iwae S, Monden N, Matsuura K, Onozawa Y, Hayashi R, Tahara M. Clinical impact of cachexia in unresectable locally advanced head and neck cancer: supplementary analysis of a phase II trial (JCOG0706-S2). Jpn J Clin Oncol, 49:37-41, 2019

 3. Okano S, Enokida T, Onoe T, Ota Y, Motegi A, Zenda S, Akimoto T, Tahara M. Induction TPF chemotherapy followed by CRT with fractionated administration of cisplatin in patients with unresectable locally advanced head and neck cancer. Int J Clin Oncol, 2019

 4. Zenda S, Ota Y, Kiyota N, Okano S, Fujii M, Kitamura M, Takahashi S, Ueda T, Monden N, Yamanaka T, Tahara M. A Multicenter Phase II Trial of Docetaxel, Cisplatin, and Cetuximab (TPEx) Followed by Cetuximab and Concurrent Radiotherapy for Patients With Local Advanced Squamous Cell Carcinoma of the Head and Neck (CSPOR HN01: ECRIPS Study). Front Oncol, 9:6, 2019

 5. Hashimoto J, Kato K, Ito Y, Kojima T, Akimoto T, Daiko H, Hamamoto Y, Matsushita H, Katano S, Hara H, Tanaka Y, Saito Y, Nagashima K, Igaki H. Phase II feasibility study of preoperative concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil and elective lymph node irradiation for clinical stage II/III esophageal squamous cell carcinoma. Int J Clin Oncol, 24:60-67, 2019

 6. Nakamura M, Kageyama SI, Niho S, Okumura M, Hojo H, Motegi A, Nakamura N, Zenda S, Yoh K, Goto K, Akimoto T. Impact of EGFR Mutation and ALK Translocation on Recurrence Pattern After Definitive Chemoradiotherapy for Inoperable Stage III Non-squamous Non-small-cell Lung Cancer. Clin Lung Cancer, 20:e256-e264, 2019

 7. Motegi K, Tachibana H, Motegi A, Hotta K, Baba H, Akimoto T. Usefulness of hybrid deformable image registration algorithms in prostate radiation therapy. J Appl Clin Med Phys, 20:229-236, 2019

 8. Journy N, Indelicato DJ, Withrow DR, Akimoto T, Alapetite C, Araya M, Chang A, Chang JH, Chon B, Confer ME, Demizu Y, Dendale R, Doyen J, Ermoian R, Gurtner K, Hill-Kayser C, Iwata H, Kim JY, Kwok Y, Laack NN, Lee C, Lim DH, Loredo L, Mangona VS, Mansur DB, Murakami M, Murayama S, Ogino T, Ondrova B, Parikh RR, Paulino AC, Perkins S, Ramakrishna NR, Richter R, Rombi B, Shibata S, Shimizu S, Timmermann B, Vern-Gross T, Wang CJ, Weber DC, Wilkinson JB, Witt Nystrom P, Yock TI, Kleinerman RA, Berrington de Gonzalez A. Patterns of proton therapy use in pediatric cancer management in 2016: An international survey. Radiother Oncol, 132:155-161, 2019

 9. Nakamura M, Nishikawa R, Mayahara H, Uezono H, Harada A, Hashimoto N, Nishimura H. Pattern of recurrence after CyberKnife stereotactic body radiotherapy for peripheral early nonsmall cell lung cancer. J Thorac Dis, 11:214-221, 2019

10. Ueno T, Zenda S, Konishi T, Yurikusa T, Shibasaki Y, Nagamoto H, Fujii M. The post hoc analysis comparing the severity grades of chemoradiotherapy-induced oral mucositis scored between the central and local assessors in a multicenter, randomized controlled trial of rebamipide for head and neck cancer. Int J Clin Oncol, 24:241-247, 2019

11. 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

12. Zenda S, Yamaguchi T, Yokota T, Miyaji T, Mashiko T, Tanaka M, Yonemura M, Takeno M, Okano T, Kawasaki T, Nakamori Y, Ishii S, Shimada S, Kanamaru M, Uchitomi Y. Topical steroid versus placebo for the prevention of radiation dermatitis in head and neck cancer patients receiving chemoradiotherapy: the study protocol of J-SUPPORT 1602 (TOPICS study), a randomized double-blinded phase 3 trial. BMC Cancer, 18:873, 2018

13. Nakamura M, Onozawa M, Motegi A, Hojo H, Zenda S, Nakamura N, Udagawa H, Kirita K, Matsumoto S, Umemura S, Yoh K, Niho S, Goto K, Akimoto T. Impact of prophylactic cranial irradiation on pattern of brain metastases as a first recurrence site for limited-disease small-cell lung cancer. J Radiat Res, 59:767-773, 2018

14. Nakamura N, Kunishima N, Nishimura N, Suzuki K, Matsusako M, Hori T, Sekiguchi K. Spontaneous Regression of Small Cell Lung Cancer:A Case Report. J Clin Case Rep, 8:1105, 2018

15. Nakamura N, Hojo H, Inoue K, Hotta K, Zenda S, Baba H, Onozawa M, Motegi A, Nakamura M, Kibe Y, Akimoto T. Late radiological changes after passive scattering proton beam therapy for Stage I lung cancer. J Radiat Res, 59:456-461, 2018

16. Kako J, Morita T, Yamaguchi T, Kobayashi M, Sekimoto A, Kinoshita H, Ogawa A, Zenda S, Uchitomi Y, Inoguchi H, Matsushima E. Fan Therapy Is Effective in Relieving Dyspnea in Patients With Terminally Ill Cancer: A Parallel-Arm, Randomized Controlled Trial. J Pain Symptom Manage, 56:493-500, 2018

17. Nakamura M, Hashimoto N, Mayahara H, Uezono H, Harada A, Nishikawa R, Matsuo Y, Kawaguchi H, Nishimura H. Additional chemotherapy improved local control and overall survival after stereotactic body radiation therapy for patients with oligo-recurrence. Radiat Oncol, 13:75, 2018

18. Kako J, Morita T, Yamaguchi T, Sekimoto A, Kobayashi M, Kinoshita H, Ogawa A, Zenda S, Uchitomi Y, Inoguchi H, Matsushima E. Evaluation of the Appropriate Washout Period Following Fan Therapy for Dyspnea in Patients With Advanced Cancer: A Pilot Study. Am J Hosp Palliat Care, 35:293-296, 2018

19. Hirano Y, Onozawa M, Hojo H, Motegi A, Zenda S, Hotta K, Moriya S, Tachibana H, Nakamura N, Kojima T, Akimoto T. Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma. Radiat Oncol, 13:23, 2018

20. Nakamura N, Kawamori J, Takahashi O, Shikama N, Sekiguchi K, Takahashi T, Kato S, Ogita M, Motegi A, Akimoto T. Palliative radiotherapy for breast cancer patients with skin invasion: a multi-institutional prospective observational study. Jpn J Clin Oncol, 48:555-558, 2018

21. Patel A, Dong T, Ansari S, Cohen-Gadol A, Watson GA, Moraes FY, Nakamura M, Murovic J, Chang SD, Hatiboglu MA, Chung C, Miller JC, Lautenschlaeger T. Toxicity of Radiosurgery for Brainstem Metastases. World Neurosurg, 119:e757-e764, 2018

22. Ishibashi N, Soejima T, Kawaguchi H, Akiba T, Hasegawa M, Isobe K, Ito H, Imai M, Ejima Y, Hata M, Sasai K, Shimoda E, Maebayashi T, Oguchi M, Akimoto T. National survey of myeloablative total body irradiation prior to hematopoietic stem cell transplantation in Japan: survey of the Japanese Radiation Oncology Study Group (JROSG). J Radiat Res, 59:477-483, 2018

23. Mizumoto M, Murayama S, Akimoto T, Demizu Y, Fukushima T, Ishida Y, Oshiro Y, Numajiri H, Fuji H, Okumura T, Shirato H, Sakurai H. Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan. Cancer Med, 7:1870-1874, 2018

24. Hashimoto H, Abe M, Yanai T, Yamaguchi T, Zenda S, Uchitomi Y, Fukuda H, Mori M, Iwasa S, Yamamoto N, Ohe Y. Study protocol for J-SUPPORT 1604 (J-FORCE): a randomized, double blind, placebo-controlled Phase III study evaluating olanzapine (5 mg) plus standard triple antiemetic therapy for prevention of chemotherapy induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy. Jpn J Clin Oncol, 48:950-952, 2018