Project title: Integration of treatment strategies and molecular diagnosis for childhood cancers in Taiwan

Integration of Treatment Strategies and Molecular Diagnosis for Childhood Cancers in Taiwan

T.T. Wong1#, J.S. Cheng2#, S.F. Huang3, S.H. Chen4, H.C. Liu5, C.W. Tsai6, K.S. Wu1, S.T. Jou7, J.M. Sheen8, J.D. Wang6, J.C. Wu9, A.L. Yu9*

黃棣棟，鄭竹珊，黃秀芬，陳世翔，劉希哲，蔡紀葦，吳國盛，周獻堂，沈俊明， 王榮德， 吳任傑，陳鈴津

1Division of Neurosurgery, Taipei Medical Collage Hospital, 2Clinical Informatics & Medical Statistics Research Center, Chang Gung University, 3Institute of Molecular and Genomic Medicine, National Health Research Institute, 4Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, 5Pediatric Hematology and Oncology, MacKay Children’s Hospital, 6Department of Public Health College of Medicine, National Cheng Kung University, 7Department of Pediatrics, National Taiwan University Hospital, 8Department of Pediatrics, Chang Gung Memorial Hospital, Kaosiung, 9Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital
#Co-first authors; *Corresponding author, Email: aliceyu@cgmh.org.tw

According to the Taiwan Cancer Registry, the age-standardized rate of childhood cancer in Taiwan has been increasing at a rate of 1~1.2% per year over the last 2 decades. More children are lost to cancer than any other childhood diseases combined. However, a majority of children with cancer can be cured with proper treatment nowadays, adding decades of life years. In view of the declining birth rate in Taiwan, the issue of childhood cancer care demands immediate attention and action. Since 2016, we have pursued the following three aims with the support from the MOHW:

1) Develop uniform treatment strategies and provide sustained support for standardized molecular diagnostic tests for childhood brain tumor, and initiate the first clinical trial of upfront chemotherapy in combination with anti-GD2 immunotherapy in high-risk neuroblastoma;

We aim to integrate molecular parameters and clinical risk factors so as to provide up to date adaptive optimal treatment for different risk subgroups of patients. We have analyzed 52 cases of medulloblastoma combining pathological diagnosis with gene profiling and classified them into SHH, WNT, Group 3 and 4. After several multidisciplinary meetings, a consensus has been reached for the treatment regimens based on molecular subtypes of medulloblastoma. As to the high risk neuroblastoma, we have developed a treatment protocol for a pilot clinical trial combining dinutuximab with upfront chemotherapy. The protocol has been presented and discussed at TPOG meetings. We plan to submit it to T-FDA for IND and for CIRB approval.

2) Establish and maintain the clinical database for childhood brain tumor and neuroblastoma patients enrolled on TPOG protocol and provide bioinformatic support;
We have set up a prototype for “Taiwan Pediatric Cancer Web-based BioPlatform” to capture childhood brain tumor data including clinical data, medical images, biobank linkage or specimen database, consensus standard treatment of pediatric cancers (pediatric brain tumors, neuroblastoma, and other cancers), the archiving and management of the biological database, and biostatistics. As to the childhood cancer biobank, we have set up the standard of operation for sample collection and shipment, and are in the process of application for NHRI Biobank. Upon its approval, it will be followed by CIRB application. Through the establishment of the infrastructure and platform, it will greatly facilitate the progress of Taiwan childhood cancer care and research.

3) Analyze the health economics of acute lymphoblastic leukemia (ALL).
ALL is the most common cancer in children. The intensity and duration of treatment can impose high financial burden to patients, their families, and the health care system. This study aims to examine entire costs of care for children with ALL. Children newly diagnosed with ALL were identified from the Cancer Registry data and participating medical centers. Based on the costs of health services retrieved from the National Health Insurance claims database of 300 patients, the mean annual ALL-related medical costs were NT$944,276, $329,411, $201,505, $122,743, and
$77,123, during the first five years after diagnosis respectively, accounting for more than 90% of yearly total medical costs. Cost due to hospitalization accounts for the majority of the expenses. Our preliminary findings demonstrated that childhood ALL incurred high costs, particularly in the first year after diagnosis, and mostly due to hospitalization.
Through these endeavors, we hope to improve the treatment outcome and promote research advances in childhood cancer, and thereby minimizing the socio-economic impacts of decreasing birth rate in Taiwan.