Annual Report 2023

Department of Pediatric Oncology

Chitose Ogawa, Ayumu Arakawa, Yuko Watanabe, Minako Sugiyama, Kiyotaka Isobe, Eriko Uchida, Natsumi Kikuchi, Bunpei Miyazaki, Kayoko Tao, Nami Shirakawa, Yuki Nogami

Introduction

 Pediatric oncology includes a wide variety of malignancies in children and adolescents such as acute leukemia and malignant lymphoma, as well as solid tumors including osteosarcoma, soft tissue sarcoma, neuroblastoma, liver tumor and retinoblastoma. With appropriate treatment, many diseases are usually chemo-sensitive and curable with appropriate treatment. The common approach to these diseases is the "risk-adapted therapy" strategy, which considers long-term life expectancy. In the Department of Pediatric Oncology, pediatric patients with malignancies are managed by six pediatric oncologists, three residents and two pediatric surgeons. Although pediatric oncologists mainly treat and manage patients, we employ a multidisciplinary team approach involving radiation oncologists, orthopedic surgeons, ophthalmologic surgeons and others for the treatment. To ensure treatment completion and optimal quality of hospital life for children, pediatric nurse specialists, teachers, childcare staff, psychologists and psychiatrists also join our team. For young patients, educational opportunities ranging from elementary school to high school are available in the pediatric ward, where 10 teachers work daily.

The Team and What We Do

 Each year, around 100 new patients come to our department and start treatment. In FY2023, 109 new patients came to our department and 99 patients have started treatment. The number of patients is shown in Table 1. Our daily activity in the pediatric outpatient clinic includes managing new patients, treating patients with chemotherapy or blood transfusion and providing follow-up care for patients who have completed intensive therapy. Patients undergo multidisciplinary therapy, including surgical removal of the tumor, radiation therapy, chemotherapy, and sometimes stem cell transplantation, as indicated.

 A pediatric conference is held every morning, mainly to decide on individual treatment plans. The pediatric staff and trainees discuss various issues regarding pediatric inpatients during the daily rounds. Interdepartmental conferences in cooperation with orthopedics, radiation oncology, and palliative care are individually scheduled every 2 weeks.

Research Activities

1.  For newly diagnosed patients, we participate in several multicenter studies conducted by the Japan Children’s Cancer Group (JCCG), including those by the Japan Ewing Sarcoma Study Group (JESS), Rhabdomyosarcoma Study Group (JRSG) and Japanese Pediatric Leukemia/ Lymphoma Study Group (JPLSG).

2.  For patients who relapsed, we are actively involved in the development of new drugs and treatments, including off-label and unapproved medications.

3.  For individualized treatment, we work continuously to provide investigator-initiated registration trials, and have started two new clinical trials for patient-requested treatment to use off-label drugs following the recommendation by the Genomic Profiling Testing.

4.  For the recuperation environment, we aim to provide support so that patients undergoing treatment can live in the same community as they did before the onset of the disease by using appropriate medical and social resources.

Clinical Trials

 In 2023, we have conducted many clinical trials, including early phase trials, an international study and cooperative studies. Among them, 4 trials were investigator-initiated, registration-directed clinical trials conducted under the Pharmaceutical Affairs Law in Japan.

 To address the new issue of hereditary tumor raised by the introduction of cancer gene panel testing, ‘A multi-institutional prospective clinical trial to determine the feasibility of a cancer surveillance program and to explore new biomarkers for Li-Fraumeni Syndrome (JCCG-LFS20)’ was conducted.

Education

 We provide personnel training and education for the diagnosis and management of pediatric hematological malignancies and solid tumors. Residents also learn skills to treat not only newly diagnosed patients but also patients who relapsed or were refractory to treatments through the global standard of therapy. In addition, senior residents acquire the ability to plan studies for new agents and therapies, which we regard as an important role of this center.

Future Prospects

 We will promote the development of therapies for pediatric malignancies as a top priority. For this mission, we will plan clinical or registration trials in cooperation with domestic and international centers as a core institution in Japan. In particular, for the cure and improvement of QOL of pediatric cancer patients, we promote clinical trials of molecularly targeted drugs for pediatric cancer based on genomic information to provide personalized medicine.

List of papers published in 2023

Journal

1. Takamizawa S, Koyama T, Sunami K, Sudo K, Hirata M, Kubo T, Tao K, Cho H, Narita Y, Kato K, Yamazaki N, Ohe Y, Okusaka T, Matsui Y, Ogawa C, Yonemori K, Yamamoto N. Identification of barriers to implementation of precision oncology in patients with rare cancers. Cancer science, 115:2023-2035, 2024

2. Aiba H, Kojima Y, Shimoi T, Sudo K, Yazaki S, Imai T, Yoshida A, Iwata S, Kobayashi E, Kawai A, Arakawa A, Ogawa C, Kimura H, Yonemori K. Incidence of skeletal-related events in patients with Ewing sarcoma: An observational retrospective study in Japan. Cancer medicine, 13:e7060, 2024

3. Wada S, Nakano E, Nakajima M, Kishikawa S, Yoshida A, Mori T, Osada A, Ogata D, Namikawa K, Yamazaki N. Congenital dermatofibrosarcoma protuberans on the scalp enlarging and shrinking repeatedly. The Journal of dermatology, 51:e196-e197, 2024

4. Sugiyama M, Arakawa A, Kogure Y, Shirakawa N, Watanabe M, Ito Y, Tanimura K, Tao K, Nakajima M, Watanabe Y, Miyagi-Maeshima A, Fukuhara S, Kataoka K, Izutsu K, Fukuda T, Ogawa C. Different phenotype relapse of myeloid/lymphoid neoplasms with FGFR1 rearrangement with long remission. Pediatric blood & cancer, 71:e30721, 2024

5. Kaimi Y, Takahashi Y, Taniguchi H, Ochi T, Makino H, Makita S, Iwaki N, Fukuhara S, Munakata W, Ogawa C, Izutsu K, Maeshima AM. Loss of or decrease in CD30 expression in four patients with anaplastic large cell lymphoma after brentuximab vedotin-containing therapy. Virchows Archiv, 484:465-473, 2024

6. Ishimaru S, Shimoi T, Sunami K, Nakajima M, Ando Y, Okita N, Nakamura K, Shibata T, Fujiwara Y, Yamamoto N. Platform trial for off-label oncology drugs using comprehensive genomic profiling under the universal public healthcare system: the BELIEVE trial. International journal of clinical oncology, 29:89-95, 2024

7. Ueki H, Ogawa C, Goto H, Nishi M, Yamanaka J, Mochizuki S, Nishikawa T, Kumamoto T, Nishiuchi R, Kikuta A, Yamamoto S, Igarashi S, Sato A, Hori T, Saito AM, Watanabe T, Deguchi T, Manabe A, Horibe K, Toyoda H. TBI, etoposide, and cyclophosphamide conditioning for intermediate-risk relapsed childhood acute lymphoblastic leukemia. International journal of hematology, 119:450-458, 2024

8. Kubo T, Sone M, Sugawara S, Kusumoto M, Arakawa A, Ogawa C, Suzuki S, Arai Y, Abe O. Technical Feasibility and Safety of Central Venous Ports for Intravenous Chemotherapy in Infants With Retinoblastoma: A Retrospective Study. Cureus, 16:e52231, 2024

9. Arakawa A, Tao K, Kohno T, Ogawa C. Cross-individual cancer transmission to children during the gestational and perinatal periods. Cancer science, 115:1039-1047, 2024

10. Ogawa A, Kawamoto H, Hara J, Kikuta A, Ogawa C, Hiraga H, Yoshimura K, Miyairi K, Omori R, Ro T, Kamei Y, Kimura T. Phase 2 study of glucarpidase in patients with delayed methotrexate elimination after high-dose methotrexate therapy. Cancer chemotherapy and pharmacology, 2024

11. Akahane K, Kasai S, Watanabe A, Kagami K, Komatsu C, Tamai M, Goi K, Oishi N, Yoshida A, Ogawa C, Kobayashi E, Inukai T. FGFR1 tyrosine kinase domain duplication in infantile soft tissue spindle cell tumor. Pediatric blood & cancer, e30354, 2023

12. Sugiyama M, Arakawa A, Shirakawa N, Tao K, Tanimura K, Nakajima M, Watanabe Y, Kumamoto T, Maniwa J, Yoneda A, Iwata S, Kobayashi E, Kawai A, Ogawa C. Safety and efficacy of multiple tyrosine kinase inhibitors in pediatric/adolescent and young adult patients with relapsed or refractory osteosarcomas: A single-institution retrospective analysis. Pediatric blood & cancer, 70:e30360, 2023

13. Aiba H, Kojima Y, Shimoi T, Sudo K, Yazaki S, Imai T, Yoshida A, Iwata S, Kobayashi E, Kawai A, Arakawa A, Ogawa C, Kimura H, Yonemori K. Clinical characteristics of primary cutaneous and subcutaneous Ewing sarcoma. Japanese journal of clinical oncology, 53:604-610, 2023

14. Tao K, Inamoto Y, Furukawa H, Hosoba R, Takeda W, Maeshima A, Aoki J, Ito A, Tanaka T, Kim SW, Makita S, Fukuhara S, Kogure Y, Kataoka K, Izutsu K, Fukuda T. Romidepsin-induced durable remission for relapsed nodal peripheral T-cell lymphoma with T follicular helper phenotype after allogeneic hematopoietic cell transplantation. International journal of hematology, 118:292-298, 2023

15. Tanimura K, Nakajima M, Shirakawa N, Tao K, Sugiyama M, Watanabe Y, Arakawa A, Kikuchi M, Takahashi M, Narita Y, Shiotsuka M, Kobayashi O, Iwata S, Yoshida A, Abe M, Yamagoe S, Miyazaki Y, Ogawa C. Surgical site infection caused by Rhizopus caespitosus after metastasectomy for osteosarcoma: First report of infection in humans. Pediatric blood & cancer, 70:e30049, 2023

16. Fukuta T, Tanaka T, Hashimoto T, Isahaya K, Kubo Y, Yamano Y, Satomi K, Hiraoka N, Shirakawa N, Arakawa A, Ogawa C, Nishimura N, Aoki J, Ito A, Inamoto Y, Kim SW, Fukuda T. Nelarabine-induced myelopathy in patients undergoing allogeneic hematopoietic cell transplantation: a report of three cases. International journal of hematology, 117:933-940, 2023

17. Miyagawa N, Goto H, Ogawa A, Kikuta A, Kosaka Y, Sekimizu M, Tomizawa D, Toyoda H, Hiramatsu H, Hara J, Mochizuki S, Nakayama H, Yoshimura K, Iijima-Yamashita Y, Sanada M, Ogawa C. Phase 2 study of combination chemotherapy with bortezomib in children with relapsed and refractory acute lymphoblastic leukemia. International journal of hematology, 118:267-276, 2023

18. Naito Y, Mishima S, Akagi K, Hayashi N, Hirasawa A, Hishiki T, Igarashi A, Ikeda M, Kadowaki S, Kajiyama H, Kato M, Kenmotsu H, Kodera Y, Komine K, Koyama T, Maeda O, Miyachi M, Nishihara H, Nishiyama H, Ohga S, Okamoto W, Oki E, Ono S, Sanada M, Sekine I, Takano T, Tao K, Terashima K, Tsuchihara K, Yatabe Y, Yoshino T, Baba E. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors. International journal of clinical oncology, 28:827-840, 2023

19. Mishima S, Naito Y, Akagi K, Hayashi N, Hirasawa A, Hishiki T, Igarashi A, Ikeda M, Kadowaki S, Kajiyama H, Kato M, Kenmotsu H, Kodera Y, Komine K, Koyama T, Maeda O, Miyachi M, Nishihara H, Nishiyama H, Ohga S, Okamoto W, Oki E, Ono S, Sanada M, Sekine I, Takano T, Tao K, Terashima K, Tsuchihara K, Yatabe Y, Yoshino T, Baba E. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with high tumor mutational burden tumors. International journal of clinical oncology, 28:941-955, 2023

20. Tao K, Yamazaki F, Kubo T, Sunami K, Kumamoto T, Arakawa A, Sugiyama M, Watanabe Y, Nakajima M, Shirakawa N, Tanimura K, Koyama T, Hirata M, Sudo K, Tanabe N, Watanabe T, Yoshida T, Kitami M, Yoshida A, Yatabe Y, Nakano Y, Ohira M, Kamijo T, Nakazawa A, Kato M, Ichimura K, Kohno T, Yamamoto N, Hishiki T, Ichikawa H, Ogawa C. Pediatric Precision Medicine at the National Cancer Center Japan: Prospective Genomic Study of Pediatric Patients with Cancer as Part of the TOP-GEAR Project. JCO precision oncology, 7:e2200266, 2023

21. Mishima S, Naito Y, Akagi K, Hayashi N, Hirasawa A, Hishiki T, Igarashi A, Ikeda M, Kadowaki S, Kajiyama H, Kato M, Kenmotsu H, Kodera Y, Komine K, Koyama T, Maeda O, Miyachi M, Nishihara H, Nishiyama H, Ohga S, Okamoto W, Oki E, Ono S, Sanada M, Sekine I, Takano T, Tao K, Terashima K, Tsuchihara K, Yatabe Y, Yoshino T, Baba E. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with DNA mismatch repair deficient (dMMR) tumors, third edition. International journal of clinical oncology, 28:1237-1258, 2023

22. Motoi T, Hirata M, Kukita Y, Satomi K, Tamura H, Adachi S, Matsushita Y, Horiguchi SI, Hishima T, Ikegami M, Okuma T, Tao K, Arakawa A, Ogawa C, Matsuda K, Ichimura K, Nakamura H, Mori T, Yoshida A. KDM2B-Rearranged Soft Tissue Sarcomas Expand the Concept of BCOR-Associated Sarcoma. Modern pathology, 36:100317, 2023

23. Miyazaki B, Ueno T, Sugiyama M, Kojima S, Arakawa A, Tao K, Tanimura K, Shiraishi K, Yagishita S, Kohsaka S, Kato M, Kiyokawa N, Goto Y, Yatabe Y, Hamada A, Mano H, Ogawa C, Tanaka Y. Promoter swapping of truncated PDGFRB drives Ph-like acute lymphoblastic leukemia. NPJ precision oncology, 7:132, 2023