Annual Report 2022
Department of Pediatric Oncology
Chitose Ogawa, Ayumu Arakawa, Masanaka Sugiyama, Yuko Watanabe, Miho Nakajima, Kazuki Tanimura, Eriko Uchida, Bunpei Miyazaki, Nami Shirakawa, Kayoko Tao, 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. 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 five 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, child care 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, with 80 patients starting treatment. In FY2022, 97 new patients came to our department, with 90 patients starting 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 the 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.
Table 1. Number of patients between April 2022 and Mach 2023
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 have initiated ‘A Multi-institutional Prospective Observational Study to Assess the Feasibility of Clinical Implementation of Genomic Profiling Testing for Pediatric Solid Tumors (JCCG-TOP2)’.
4. To provide an environment during therapy similar to that before the onset of the patient’s disease, we plan to construct a medical care system through the use of appropriate medical and social resources in the patients' local communities.
Clinical Trials
In 2022, we have conducted 20 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 started.
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 abilities 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 cancers based on genomic information to provide personalized medical treatments.
List of papers published in 2022
Journal
1. 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, 2023
2. 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
3. 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
4. Isobe T, Takagi M, Sato-Otsubo A, Nishimura A, Nagae G, Yamagishi C, Tamura M, Tanaka Y, Asada S, Takeda R, Tsuchiya A, Wang X, Yoshida K, Nannya Y, Ueno H, Akazawa R, Kato I, Mikami T, Watanabe K, Sekiguchi M, Seki M, Kimura S, Hiwatari M, Kato M, Fukuda S, Tatsuno K, Tsutsumi S, Kanai A, Inaba T, Shiozawa Y, Shiraishi Y, Chiba K, Tanaka H, Kotecha RS, Cruickshank MN, Ishikawa F, Morio T, Eguchi M, Deguchi T, Kiyokawa N, Arakawa Y, Koh K, Aoki Y, Ishihara T, Tomizawa D, Miyamura T, Ishii E, Mizutani S, Wilson NK, Göttgens B, Miyano S, Kitamura T, Goyama S, Yokoyama A, Aburatani H, Ogawa S, Takita J. Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia. Nature communications, 13:4501, 2022
5. Ida H, Koyama T, Mizuno T, Sunami K, Kubo T, Sudo K, Tao K, Hirata M, Yonemori K, Kato K, Okusaka T, Ohe Y, Matsui Y, Yamazaki N, Ogawa C, Kawai A, Narita Y, Esaki M, Yamamoto N. Clinical utility of comprehensive genomic profiling tests for advanced or metastatic solid tumor in clinical practice. Cancer science, 113:4300-4310, 2022
6. Fukuhara S, Oshikawa-Kumade Y, Kogure Y, Shingaki S, Kariyazono H, Kikukawa Y, Koya J, Saito Y, Tabata M, Yoshifuji K, Mizuno K, Miyagi-Maeshima A, Matsushita H, Sugiyama M, Ogawa C, Inamoto Y, Fukuda T, Sugano M, Yamauchi N, Minami Y, Hirata M, Yoshida T, Kohno T, Kohsaka S, Mano H, Shiraishi Y, Ogawa S, Izutsu K, Kataoka K. Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies. Cancer science, 113:2763-2777, 2022
7. Ohkawa T, Nishimura A, Kosaki K, Aoki-Nogami Y, Tomizawa D, Kashimada K, Morio T, Kato M, Mizutani S, Takagi M. PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma in Schuurs-Hoeijmakers syndrome. Journal of human genetics, 67:51-54, 2022
8. Horak P, Griffith M, Danos AM, Pitel BA, Madhavan S, Liu X, Chow C, Williams H, Carmody L, Barrow-Laing L, Rieke D, Kreutzfeldt S, Stenzinger A, Tamborero D, Benary M, Rajagopal PS, Ida CM, Lesmana H, Satgunaseelan L, Merker JD, Tolstorukov MY, Campregher PV, Warner JL, Rao S, Natesan M, Shen H, Venstrom J, Roy S, Tao K, Kanagal-Shamanna R, Xu X, Ritter DI, Pagel K, Krysiak K, Dubuc A, Akkari YM, Li XS, Lee J, King I, Raca G, Wagner AH, Li MM, Plon SE, Kulkarni S, Griffith OL, Chakravarty D, Sonkin D. Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC). Genetics in medicine, 24:986-998, 2022
9. Tanimura K, Nakano Y, Sato-Otsubo A, Yamasaki K, Fukushima H, Tanaka M, Yoshioka T, Okita H, Kunihiro N, Sakamoto H, Inoue T, Fujisaki H, Hara J. Radiation-induced osteosarcoma in a patient with DICER1 syndrome. Pediatric blood & cancer, 69:e29782, 2022
10. Takagi M, Ogawa C, Iehara T, Aoki-Nogami Y, Ishibashi E, Imai M, Kimura T, Nagata M, Yasuhara M, Masutani M, Yoshimura K, Tomizawa D, Ogawa A, Yonemori K, Morishita A, Miyamoto S, Takita J, Kihara T, Nobori K, Hasebe K, Miya F, Ikeda S, Shioda Y, Matsumoto K, Fujimura J, Mizutani S, Morio T, Hosoi H, Koike R. First phase 1 clinical study of olaparib in pediatric patients with refractory solid tumors. Cancer, 128:2949-2957, 2022
11. Nakayama H, Ogawa C, Sekimizu M, Fujisaki H, Kosaka Y, Hashimoto H, Saito AM, Horibe K. A phase I study of inotuzumab ozogamicin as a single agent in pediatric patients in Japan with relapsed/refractory CD22-positive acute lymphoblastic leukemia (INO-Ped-ALL-1). International journal of hematology, 116:612-621, 2022
12. Clark KA, Paquette A, Tao K, Bell R, Boyle JL, Rosenthal J, Snow AK, Stark AW, Thompson BA, Unger J, Gertz J, Varley KE, Boucher KM, Goldgar DE, Foulkes WD, Thomas A, Tavtigian SV. Comprehensive evaluation and efficient classification of BRCA1 RING domain missense substitutions. American journal of human genetics, 109:1153-1174, 2022
13. Goto H, Ogawa C, Iida H, Horibe K, Oh I, Takada S, Maeda Y, Minami H, Nakashima Y, Morris JD, Kormany W, Chen Y, Miyamoto T. Safety and Efficacy of Blinatumomab in Japanese Adult and Pediatric Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Final Results from an Expansion Cohort. Acta haematologica, 145:592-602, 2022
14. Tanaka K, Kato I, Dobashi Y, Imai JI, Mikami T, Kubota H, Ueno H, Ito M, Ogawa S, Nakahata T, Takita J, Toyoda H, Ogawa C, Adachi S, Watanabe S, Goto H. The first Japanese biobank of patient-derived pediatric acute lymphoblastic leukemia xenograft models. Cancer science, 113:3814-3825, 2022
15. Ueda S, Yamashita S, Nakajima M, Kumamoto T, Ogawa C, Liu YY, Yamada H, Kubo E, Hattori N, Takeshima H, Wakabayashi M, Iida N, Shiraishi Y, Noguchi M, Sato Y, Ushijima T. A quantification method of somatic mutations in normal tissues and their accumulation in pediatric patients with chemotherapy. Proceedings of the National Academy of Sciences of the United States of America, 119:e2123241119, 2022
16. Shinohara H, Sawado R, Nakagawa M, Hattori A, Yamagata K, Tauchi K, Ito J, Kuwahara Y, Okuda T, Ogawa C, Kitabayashi I. Dual targeting of EZH1 and EZH2 for the treatment of malignant rhabdoid tumors. Molecular therapy oncolytics, 27:14-25, 2022