Department of Pediatric Oncology

Toru Mukouhara, Ako Hosono

Introduction

The Department of Pediatric Oncology was established in December 2011 to treat a variety of pediatric cancers, including embryonal tumors such as neuroblastoma, nephroblastoma, and hepatoblastoma, and mesenchymal tumors such as Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. These tumors usually develop in children under the age of 15, but sometimes do so in adolescents and young adults (AYA). Also, they are characterized by high sensitivity to chemotherapy and radiation therapy. If the intensity of multidisciplinary treatment is well tailored to the characteristics of the disease, curing it is possible. For this reason, it is important to make appropriate treatment choices. However, some cases are refractory and may require new treatments other than standard chemotherapy. In addition, long-term survivors of childhood cancer often suffer from complications secondary to chemotherapy and radiation therapy.

The Team and What We Do

The pediatric outpatient department treats newly diagnosed patients and patients undergoing outpatient chemotherapy every Wednesday, as well as providing follow-up treatment for patients who have completed an intensive course of treatment. Flexible arrangements are made for outpatient treatment of patients on days other than Wednesdays. Cancer patients of the AYA generation are treated jointly with the Department of Oncology every Monday and Friday. Ward rounds and conferences are held each morning jointly with the Medical Oncology group. Sarcoma conferences are held every other Tuesday. For patients undergoing proton beam therapy, a conference is always held with the participation of the radiation therapy department, nurses, and technicians.

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 of, such off-label drugs and eventually getting them approved by the Ministry of Health, Labour and Welfare.

Clinical trials

The six clinical trials described below are currently active.

1) Phase II study of VAC1.2 (vincristine, actinomycin-D, cyclophosphamide) followed by VA for patients with newly diagnosed low-risk subset A rhabdomyosarcoma. (JRS-II LRA)

2) Phase II study of vincristine, actinomycin-D, cyclophosphamide and irinotecan for patients with newly diagnosed low-risk subset B rhabdomyosarcoma. (JRS-II LRB)

3) 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.)

4) Phase II study of VI (vincristine, irinotecan) / VPC (vincristine, pirarubicin, cyclophosphamide) / IE (ifosfamide, etoposide) / VAC (vincristine, actinomycin D, cyclophosphamide) for patients with newly diagnosed high-risk rhabdomyosarcoma. (JRS-II HR)

5) JCOG1802: A randomized phase II trial of 2nd line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib (2ND-STEP)

6) 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 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 progress and several projects have already started.

List of papers published

Journal

1. Ozeki R, Iihara H, Shimokawa M, Hashimoto H, Abe M, Mukohara T, Bando H, Hayashi T, Kawazoe H, Komoda M, Yanai Takahashi T, Saito M. Study protocol for a double-blind, comparative, randomised Japanese trial of triplet standard antiemetic therapies with or without 5 mg olanzapine to prevent chemotherapy-induced nausea and vomiting for patients with breast cancer treated with an anthracycline/cyclophosphamide regimen (JTOP-B). BMJ open, 12:e058755, 2022

2. Nakajima H, Harano K, Nakai T, Kusuhara S, Nakao T, Funasaka C, Kondoh C, Matsubara N, Naito Y, Hosono A, Mitsunaga S, Ishii G, Mukohara T. Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer. Breast (Edinburgh, Scotland), 61:136-144, 2022

3. Kunisada T, Nakata E, Fujiwara T, Hosono A, Takihira S, Kondo H, Ozaki T. Soft-tissue sarcoma in adolescents and young adults. International journal of clinical oncology, 2022

4. Mamishin K, Naito Y, Nomura S, Ogawa G, Niguma K, Baba K, Sakaeda S, Nakajima H, Kusuhara S, Funasaka C, Nakao T, Fukasawa Y, Kondoh C, Harano K, Kogawa T, Matsubara N, Hosono A, Kawasaki T, Mukohara T. Comparison of Treatment Completion Rate Between Conventional and Dose-dense Doxorubicin and Cyclophosphamide (AC) Followed by a Taxane in Patients With Breast Cancer: A Propensity Score-matched Analysis. Anticancer research, 41:6217-6224, 2021

5. El Bairi K, Haynes HR, Blackley E, Fineberg S, Shear J, Turner S, de Freitas JR, Sur D, Amendola LC, Gharib M, Kallala A, Arun I, Azmoudeh-Ardalan F, Fujimoto L, Sua LF, Liu SW, Lien HC, Kirtani P, Balancin M, El Attar H, Guleria P, Yang W, Shash E, Chen IC, Bautista V, Do Prado Moura JF, Rapoport BL, Castaneda C, Spengler E, Acosta-Haab G, Frahm I, Sanchez J, Castillo M, Bouchmaa N, Md Zin RR, Shui R, Onyuma T, Yang W, Husain Z, Willard-Gallo K, Coosemans A, Perez EA, Provenzano E, Ericsson PG, Richardet E, Mehrotra R, Sarancone S, Ehinger A, Rimm DL, Bartlett JMS, Viale G, Denkert C, Hida AI, Sotiriou C, Loibl S, Hewitt SM, Badve S, Symmans WF, Kim RS, Pruneri G, Goel S, Francis PA, Inurrigarro G, Yamaguchi R, Garcia-Rivello H, Horlings H, Afqir S, Salgado R, Adams S, Kok M, Dieci MV, Michiels S, Demaria S, Loi S. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group. NPJ breast cancer, 7:150, 2021

6. Funasaka C, Naito Y, Kusuhara S, Nakao T, Fukasawa Y, Mamishin K, Komuro A, Okunaka M, Kondoh C, Harano K, Kogawa T, Matsubara N, Hosono A, Kawasaki T, Mukohara T. The efficacy and safety of paclitaxel plus bevacizumab therapy in breast cancer patients with visceral crisis. Breast (Edinburgh, Scotland), 58:50-56, 2021

7. Mizumoto M, Fuji H, Miyachi M, Soejima T, Yamamoto T, Aibe N, Demizu Y, Iwata H, Hashimoto T, Motegi A, Kawamura A, Terashima K, Fukushima T, Nakao T, Takada A, Sumi M, Oshima J, Moriwaki K, Nozaki M, Ishida Y, Kosaka Y, Ae K, Hosono A, Harada H, Ogo E, Akimoto T, Saito T, Fukushima H, Suzuki R, Takahashi M, Matsuo T, Matsumura A, Masaki H, Hosoi H, Shigematsu N, Sakurai H. Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines. Cancer treatment reviews, 98:102209, 2021

8. Umeda K, Miyamura T, Yamada K, Sano H, Hosono A, Sumi M, Okita H, Kumamoto T, Kawai A, Hirayama J, Jyoko R, Sawada A, Nakayama H, Hosoya Y, Maeda N, Yamamoto N, Imai C, Hasegawa D, Chin M, Ozaki T. Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group. Cancer reports (Hoboken, N.J.), 4:e1329, 2021

9. Mukohara T, Hosono A, Mimaki S, Nakayama A, Kusuhara S, Funasaka C, Nakao T, Fukasawa Y, Kondoh C, Harano K, Naito Y, Matsubara N, Tsuchihara K, Kuwata T. Effects of Ado-Trastuzumab Emtansine and Fam-Trastuzumab Deruxtecan on Metastatic Breast Cancer Harboring HER2 Amplification and the L755S Mutation. The oncologist, 26:635-639, 2021