Annual Report 2019
Department of Pediatric Oncology
Chitose Ogawa, Tadashi Kumamoto, Ayumu Arakawa, Masanaka Sugiyama, Yuko Watanabe, Miho Nakajima, 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. Many diseases are usually chemo-sensitive and curable with appropriate treatment. The common approach to these diseases is a “risk-adapted therapy” strategy considering long-term life expectancy. In the Department of Pediatric Oncology, patients with pediatric malignancies are managed by five pediatric oncologists and pediatric surgeons. Although pediatric oncologists mainly treat and manage patients, a multidisciplinary team approach including radiation oncologists, orthopedic surgeons, ophthalmologic surgeons and others is incorporated for the treatment. To achieve 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
More than 100 new patients come to our department and about 80 patients start treatment every year. The number of patients is shown in Table 1. Our daily activities in the pediatric outpatient clinic are to manage new patients, to treat patients with chemotherapy or blood transfusion and to provide follow-up care for patients who have completed intensive treatment. Patients receive multidisciplinary therapy, including surgical removal of tumors, radiation therapy, chemotherapy and sometimes SCT, 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 on daily rounds. Inter-department conferences in cooperation with orthopedics, radiation oncology, and palliative care are individually scheduled every two weeks.
Table 1. Number of patients between April 2019 and March 2020
Research activities
1. For newly diagnosed patients, we participate in several multicenter studies in Japan Children’s Cancer Group (JCCG), including those by Japan Ewing Sarcoma Study Group (JESS), Rhabdomyosarcoma Study Group (JRSG) and Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).
2. For relapsed patients, we are actively involved in the development of new drugs and treatments including off-label and unapproved medications.
3. For individualized treatment, we expanded the TOP-GEAR project, implementation of clinical sequencing, to children and started the recruitment of pediatric patients. One hundred and nine samples had been analyzed by the end of March 2020 and the results were explained to each patient.
4. For provision of a similar environment during the treatment to that of before patients’ disease onset, we plan to construct a medical care system through the use of appropriate medical and social resources in their local communities.
Clinical trials
In 2019, we were doing 18 clinical trials, including early phase trials, an international study and cooperative studies. All clinical trials are listed in Table 2. The six trials, including one started in 2019, are investigator-initiated registration-directed clinical trials conducted under the Pharmaceutical Affairs Law in Japan. Two international cooperative trials are IntReALL2010, which is in collaboration with International BFM group in Europe, and is ongoing, and AHEP 0731 with Children's Oncology Group in the USA, completed patient recruitment.
Education
We provide personnel training and education for the skills of diagnosis and management for pediatric hematological malignancies and solid tumors. Residents also learn skills to treat not only newly diagnosed patients but also relapsed or refractory patients with global standard therapy. In addition, senior residents acquire abilities to plan studies for new agents or new therapies, which we regard as an important role of this center.
Future prospects
We promote development of therapies for pediatric malignancies as a top priority. For this mission, we need to plan clinical or registration trials in cooperation with domestic and international centers as a core institution in Japan.
Our other mission is to provide individualized medicine for children with cancer. For this aim, we plan to expand the subjects in the comprehensive genetic testing project in our center to the pediatric age group. In addition, we promote clinical trials using molecular targeted agents for pediatric malignancies.
List of papers published in 2019
Journal
1. Ito M, Fujiwara Y, Kubo T, Matsushita H, Kumamoto T, Suzuki T, Sunami K, Yamamoto N, Kohno T. Clonal Hematopoiesis From Next Generation Sequencing of Plasma From a Patient With Lung Adenocarcinoma: A Case Report. Front Oncol, 10:113, 2020
2. Goto H, Yoshino Y, Ito M, Nagai J, Kumamoto T, Inukai T, Sakurai Y, Miyagawa N, Keino D, Yokosuka T, Iwasaki F, Hamanoue S, Shiomi M, Goto S. Aurora B kinase as a therapeutic target in acute lymphoblastic leukemia. Cancer Chemother Pharmacol, 85:773-783, 2020
3. Miyazaki R, Saiga H, Kato T, Bakoshi T, Senba R, Shintani A, Suzuki M, Takao K, Sasaki I, Iizuka A, Sugiyama M, Iwami N, Fukuda-Ohta Y, Hemmi H, Tanaka T, Miyake M, Kaisho T, Hoshino K. The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene. Biochem Biophys Res Commun, 525:477-482, 2020
4. Mizumoto Y, Hemmi H, Katsuda M, Miyazawa M, Kitahata Y, Miyamoto A, Nakamori M, Ojima T, Matsuda K, Nakamura M, Hayata K, Fukuda-Ohta Y, Sugiyama M, Ohta T, Orimo T, Okura S, Sasaki I, Tamada K, Yamaue H, Kaisho T. Anticancer effects of chemokine-directed antigen delivery to a cross-presenting dendritic cell subset with immune checkpoint blockade. Br J Cancer, 122:1185-1193, 2020
5. Sunami K, Ichikawa H, Kubo T, Kato M, Fujiwara Y, Shimomura A, Koyama T, Kakishima H, Kitami M, Matsushita H, Furukawa E, Narushima D, Nagai M, Taniguchi H, Motoi N, Sekine S, Maeshima A, Mori T, Watanabe R, Yoshida M, Yoshida A, Yoshida H, Satomi K, Sukeda A, Hashimoto T, Shimizu T, Iwasa S, Yonemori K, Kato K, Morizane C, Ogawa C, Tanabe N, Sugano K, Hiraoka N, Tamura K, Yoshida T, Fujiwara Y, Ochiai A, Yamamoto N, Kohno T. Feasibility and utility of a panel testing for 114 cancer-associated genes in a clinical setting: A hospital-based study. Cancer Sci, 110:1480-1490, 2019
6. Inagaki C, Shimoi T, Sumiyoshi Okuma H, Kawachi A, Sudo K, Shimomura A, Noguchi E, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Arakawa A, Ogawa C, Yoshida A, Fujiwara Y, Tamura K. Bone marrow examination in patients with Ewing sarcoma/peripheral primitive neuroectodermal tumor without metastasis based on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. Med Oncol, 36:58, 2019
7. Kawajiri A, Kitano S, Maeshima AM, Inamoto Y, Tajima K, Takemura T, Tanaka T, Ito A, Okinaka K, Kurosawa S, Kim SW, Taniguchi H, Ogawa C, Izutsu K, Yamamoto N, Fukuda T. Association of CD204+ macrophages with poor outcomes of malignant lymphomas not in remission treated by allogeneic HCT. Eur J Haematol, 103:578-587, 2019
8. Yoshida A, Wakai S, Ryo E, Miyata K, Miyazawa M, Yoshida KI, Motoi T, Ogawa C, Iwata S, Kobayashi E, Watanabe SI, Kawai A, Mori T. Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion. Am J Surg Pathol, 43:1622-1630, 2019
9. Hasegawa D, Yoshimoto Y, Kimura S, Kumamoto T, Maeda N, Hara J, Kikuta A, Kada A, Kimura T, Iijima-Yamashita Y, Saito AM, Horibe K, Manabe A, Ogawa C. Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia. Int J Hematol, 110:627-634, 2019
10. Nakano Y, Tsunematsu Y, Yamazaki F, Manabe A, Nakagawara A, Hiyama E, Kumamoto T. Pediatric patients with cancer predisposition in Japan: Results of a questionnaire survey. Pediatr Blood Cancer, 66:e27937, 2019
11. Saito Y, Kumamoto T, Arima T, Shirakawa N, Ishimaru S, Sonoda T, Nakajima M, Sugiyama M, Arakawa A, Hashimoto H, Makino Y, Ogawa C, Yamaguchi M. Evaluation of aprepitant and fosaprepitant in pediatric patients. Pediatr Int, 61:235-239, 2019
12. Sugiyama M, Hamanoue S, Nagai JI, Tsurusaki Y, Kurosawa K, Tanaka M, Tanaka Y, Goto H. Hemoglobin beta Kanagawa [c.443A>C; p.(Ter148Serext*21)]: A novel β-globin gene mutation causing dominantly inherited β-thalassemia. Pediatr Blood Cancer, 66:e27871, 2019
13. Takachi T, Arakawa Y, Nakamura H, Watanabe T, Aoki Y, Ohshima J, Takahashi Y, Hirayama M, Miyamura T, Sugita K, Koh K, Horibe K, Ishii E, Mizutani S, Tomizawa D. Personalized pharmacokinetic targeting with busulfan in allogeneic hematopoietic stem cell transplantation in infants with acute lymphoblastic leukemia. Int J Hematol, 110:355-363, 2019