Annual Report 2022
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, hepatoblastoma, and mesenchymal tumors such as Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. These tumors usually develop in children under the age of 15, but can sometimes appear in adolescents and young adults (AYA). The tumors 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 and provides 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 and experimental agents. One of the objectives of the following trials is to gather data on and assess the safety and efficacy of off-label drugs and eventually gain approval from 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 and AYA support team
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 in progress and several projects have already started.
List of papers published in 2022
Journal
1. Shimomura A, Yoshida M, Kubo T, Yamashita S, Noguchi E, Nagayama A, Hanamura T, Okazaki M, Mukohara T, Tsuruga A, Tanaka K, Kawamura Y, Higuchi T, Takahashi Y, Kurozumi S, Hayashida T, Ichikawa H, Ushijima T, Suto A. Clinicopathological features, genetic alterations, and BRCA1 promoter methylation in Japanese male patients with breast cancer. Breast cancer research and treatment, 197:593-602, 2023
2. Tamura K, Mukohara T, Yonemori K, Kawabata Y, Nicolas X, Tanaka T, Iwata H. Phase 1 study of oral selective estrogen receptor degrader (SERD) amcenestrant (SAR439859), in Japanese women with ER-positive and HER2-negative advanced breast cancer (AMEERA-2). Breast cancer (Tokyo, Japan), 30:506-517, 2023
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, 28:1-11, 2023
4. Funasaka C, Naito Y, Kusuhara S, Nakao T, Nakajima H, Kawamoto M, Baba K, Mamishin K, Kondoh C, Harano K, Matsubara N, Hosono A, Sasaki T, Kawasaki T, Mukohara T. Clinical features of CDK4/6 inhibitor-related interstitial lung disease in patients with breast cancer: a case series study. Japanese journal of clinical oncology, 53:105-114, 2023
5. Koganemaru S, Kawai T, Fuchigami H, Maeda N, Koyama K, Kuboki Y, Mukohara T, Doi T, Yasunaga M. Quantitative analysis of drug distribution in heterogeneous tissues using dual-stacking capillary electrophoresis-mass spectrometry. British journal of pharmacology, 180:762-774, 2023
6. Masuda N, Ono M, Mukohara T, Yasojima H, Shimoi T, Kobayashi K, Harano K, Mizutani M, Tanioka M, Takahashi S, Kogawa T, Suzuki T, Okumura S, Takase T, Nagai R, Semba T, Zhao ZM, Ren M, Yonemori K. Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the breast cancer expansion cohort. European journal of cancer (Oxford, England : 1990), 168:108-118, 2022
7. Mizuno M, Chiba I, Mukohara T, Kondo M, Maruo K, Ohigashi T, Naruo M, Asano Y, Onishi T, Tanabe H, Muta R, Mishima S, Okano S, Yuda M, Hosono A, Ueda Y, Bando H, Itagaki H, Ferrans CE, Akimoto T. Effectiveness of an online support program to help female cancer patients manage their health and illness: Protocol for a randomized controlled trial. Contemporary clinical trials communications, 30:101035, 2022
8. Eguchi Y, Nakai T, Kojima M, Wakabayashi M, Sakamoto N, Sakashita S, Miyazaki S, Taki T, Watanabe R, Watanuki R, Yamauchi C, Iwatani T, Mukohara T, Onishi T, Ishii G. Pathologic method for extracting good prognosis group in triple-negative breast cancer after neoadjuvant chemotherapy. Cancer science, 113:1507-1518, 2022
9. Ozaki Y, Tsurutani J, Mukohara T, Iwasa T, Takahashi M, Tanabe Y, Kawabata H, Masuda N, Futamura M, Minami H, Matsumoto K, Yoshimura K, Kitano S, Takano T. Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B). European journal of cancer (Oxford, England : 1990), 171:193-202, 2022
10. Niguma K, Mamishin K, Naito Y, Nomura S, Wakabayashi M, Kusuhara S, Funasaka C, Nakao T, Fukasawa Y, Kondoh C, Harano K, Kogawa T, Matsubara N, Hosono A, Onishi T, Kawasaki T, Mukohara T. Impact of Older Age and Medico-social Factors on the Decision to Offer Adjuvant Chemotherapy to Patients With Breast Cancer. Anticancer research, 42:3743-3751, 2022
11. Ozaki Y, Tsurutani J, Mukohara T, Iwasa T, Takahashi M, Tanabe Y, Kawabata H, Masuda N, Futamura M, Minami H, Matsumoto K, Yoshimura K, Kitano S, Takano T. Data of programmed death-ligand 1 expression and VEGF: Nivolumab, bevacizumab and paclitaxel For HER2-negative metastatic breast cancer. Data in brief, 45:108558, 2022
12. Shirai K, Guan G, Meihui T, Xiaoling P, Oka Y, Takahashi Y, Bhagat AAS, Yanagida M, Iwanaga S, Matsubara N, Mukohara T, Yoshida T. Hybrid double-spiral microfluidic chip for RBC-lysis-free enrichment of rare cells from whole blood. Lab on a chip, 22:4418-4429, 2022