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Annual Report 2018

Department of Pediatric Oncology

Toru Mukouhara, Ako Hosono

Introduction

 The Department of Pediatric Oncology was established in December 2011 to provide treatment for pediatric cancers including a wide variety of diseases such as embryonal tumors comprising neuroblastomas, nephroblastomas, and hepatoblastomas, and mesenchymal tumors comprising Ewing sarcomas, rhabdomyosarcomas, and osteosarcomas. Although they usually occur in children under the age of 15, they occasionally occur in adolescents and young adults (AYA). Most pediatric cancers are highly chemosensitive as well as radiosensitive. They are possibly curable in a certain situation where the intensity of multidisciplinary treatment and disease characteristics are balanced well. However, there are absolute refractory cases that need new treatments other than standard chemotherapy. Moreover, long-term survivors of pediatric cancers often suffer from complications secondary to chemotherapy and radiotherapy.

The Team and What We Do

 The pediatric outpatient service is open three days a week: Monday, Wednesday, and Friday to treat newly diagnosed patients and patients who received chemotherapy in the outpatient setting, and to provide follow-up treatment for patients who have completed an intensive treatment course. The care for children receiving palliative treatment is also carried out with the Palliative Care and Psycho-Oncology group. A daily ward round and a conference are held every morning. We also attend conferences with the Departments of Breast and Medical Oncology, Musculoskeletal Oncology and Rehabilitation, Thoracic Surgery, and Urology at any time.

Research activities

 Our projects include treatment development using relatively new off-label drugs as well as experimental agents. One of the objectives of the following trials is gathering data on, and assessing the safety and efficacy date of, such off-label drugs and eventually getting them approved by the Ministry of Health, Labour and Welfare.

Clinical trials

 The three clinical trials described below are currently active.

1) Phase II study of vincristine, actinomycin-D, cyclophosphamide and irinotecan for patients with newly diagnosed intermediate rhabdomyosarcoma. (Phase II study of VAC2.2/VI therapy for patients with newly diagnosed intermediate rhabdomyosarcoma.)

2) JCOG0905: A Phase III Study Comparing Methotrexate, Adrimycin and Cisplatin (MAP) with MAP + Ifosfamide (MAP + IF) for the Treatment of Osteosarcoma (OS-MAP + IF-P3)

3) A Phase 2 Trial of Multimodal Treatment based on VDC-IE with Interval Compressed Schedule by using G-CSF for Patients with Non-metastatic Ewing Sarcoma Family Tumor (JESS14)

Future prospects

 There are three major missions in the Department of Pediatric Oncology of the National Cancer Center Hospital East (NCCHE) as follows:

1) To provide a state-of-the-art treatment for AYA patients in collaboration with the Medical Oncology group

2) To develop new treatments for pediatric cancer by sharing agents and knowledge with the Clinical Development Center

3) To provide less toxic proton-beam radiation therapy as one of the three proton centers for children in Japan

 All three activities are currently in process and several projects have already started.

List of papers published in 2018

Journal

1. Chayahara N, Mukohara T, Tachihara M, Fujishima Y, Fukunaga A, Washio K, Yamamoto M, Nakata K, Kobayashi K, Takenaka K, Toyoda M, Kiyota N, Tobimatsu K, Doi H, Mizuta N, Marugami N, Kawaguchi A, Nishigori C, Nishimura Y, Minami H. Adapalene Gel 01% Versus Placebo as Prophylaxis for Anti-Epidermal Growth Factor Receptor-Induced Acne-Like Rash: A Randomized Left-Right Comparative Evaluation (APPEARANCE). Oncologist, 2019

2. Goto H, Shimono Y, Funakoshi Y, Imamura Y, Toyoda M, Kiyota N, Kono S, Takao S, Mukohara T, Minami H. Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin. Oncogene, 38:767-779, 2019

3. Goto H, Kiyota N, Otsuki N, Imamura Y, Chayahara N, Suto H, Nagatani Y, Toyoda M, Mukohara T, Nibu KI, Kasahara T, Ito Y, Miya A, Hirokawa M, Miyauchi A, Minami H. Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria. Auris Nasus Larynx, 45:1249-1252, 2018

4. Tatara T, Mukohara T, Tanaka R, Shimono Y, Funakoshi Y, Imamura Y, Toyoda M, Kiyota N, Hirai M, Kakeji Y, Minami H. 3D Culture Represents Apoptosis Induced by Trastuzumab Better than 2D Monolayer Culture. Anticancer Res, 38:2831-2839, 2018

5. Tatara T, Mukohara T, Shimono Y, Yamasaki T, Imamura Y, Funakoshi Y, Toyoda M, Kiyota N, Takao S, Kono S, Kakeji Y, Minami H. Expression of programmed death-1 in sentinel lymph nodes of breast cancer. J Surg Oncol, 117:1131-1136, 2018

6. Nishimura M, Hayashi M, Mizutani Y, Takenaka K, Imamura Y, Chayahara N, Toyoda M, Kiyota N, Mukohara T, Aikawa H, Fujiwara Y, Hamada A, Minami H. Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging. Oncotarget, 9:18540-18547, 2018