Abstract 3398: Clinical use of next-generation sequencing panel in pediatric oncology patients
Authors: Choi Jung Yoon , Park Hyun Jin , Kim Bo Kyung , Hong Kyung Taek , Koh Jaemoon , Park Sung-Hye , Bae Jeong Mo , Yun Hongseok , Kang Hyoung Jin 
Published: April 2023

Abstract
Background: Next-generation sequencing (NGS) technology is gradually expanding in cancer diagnosis and therapeutic decision-making. However, reports on the clinical performance and utility of pan-cancer NGS panel in pediatric patients are still lacking.
Methods: We analyzed the patients who underwent brain tumor or pan-cancer NGS panel sequencing at Seoul National University Children’s Hospital. DNA-based NGS panel testing was started in April 2018, and RNA panel was added from January 2022. Single nucleotide variants/small insertions and deletions (SNV/INDEL), fusion, copy number alteration (CNA), microsatellite instability (MSI) and tumor mutational burden (TMB) were evaluated.
Results: A total of 140 patients were analyzed between August 2018 and March 2022. The median age at diagnosis was 8.5 (range 0.0-31.8) years. The diagnoses were CNS tumors in 56 (40.0%), sarcoma in 45 (32.1%), other solid tumors in 36 (25.7%) and histiocytosis in 3 (2.1%) patients. At the time of NGS testing, 115 patients (75.2%) were newly diagnosed and 38 patients (24.8%) were in relapsed or refractory status. In all patients, 85.7% had at least one pathogenic or likely pathogenic variant. Diagnosis was refined or changed in five patients (3.6%) after the NGS panel results were reported. Oncogenic gene fusions were discovered in 45 (32.1%) patients. EWSR1, BRAF, NTRK and RET-related fusions were the most common. Frequent SNV/INDEL included BRAF, CTNNB1 and TP53 mutations. Common CNA were CDKN2A and CDKN2B loss, MYCN amplification, CCND3 amplification and PTEN loss. Nine (6.4%) patients were identified with germline alteration, additionally. No patient had MSI, and two patients had high TMB. Fifteen patients (10.7%) were enrolled in clinical trials or compassionate use program according to molecular profiling (DAY101 [BRAF inhibitor] in 3, selpercatinib in 3, palbociclib in 2, olaparib in 2, alectinib in 1, repotrectinib in 1, larotrectinib in 1, atezolizumab in 1 and erdafitinib in 1). Two (1.4%), one (0.7%) and one (0.7%) patients received vemurafenib, larotrectinib, and pembrolizumab with non-reimbursement. Best responses included two complete response (1 high grade glioma [HGG] and 1 renal cell carcinoma), five partial responses (2 low grade glioma, 1 HGG, 1 Langerhans cell histiocytosis, and 1 papillary thyroid carcinoma), two stable disease and six progressive diseases. Four patients were not evaluable due to short duration of drug administration. One-year progression free survival and overall survival was 54.5% and 52.7%, respectively.
Conclusions: Application of NGS panel in pediatric cancer aid in diagnosis, treatment decision, clinical trial enrollment and germline risk determination. Although there are not many cases linked with molecular target-based therapy, it is leading to clinical benefits in pediatric patients and more understanding genomic profiling of pediatric cancer.
Citation Format: Jung Yoon Choi, Hyun Jin Park, Bo Kyung Kim, Kyung Taek Hong, Jaemoon Koh, Sung-Hye Park, Jeong Mo Bae, Hongseok Yun, Hyoung Jin Kang. Clinical use of next-generation sequencing panel in pediatric oncology patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3398.