Abstract B009: Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers

Abstract While the use of ctDNA-based minimal residual disease (MRD) monitoring is gaining popularity in adult cancers, this approach is not yet widely adopted in pediatric cancers (PCs). We developed a robust and sensitive assay to monitor ctDNA in PCs, which overcomes PC-specific challenges including low tumor mutational burden, paucity of hotspot mutations and low blood volume. To address these challenges, our innovations include personalized panel design that targets primary tumor mutations from each patient, a fixed panel targeting hotspot mutations, error suppression from duplex deep sequencing and customized pipeline for tumor burden estimation. We retrospectively analyzed 661 blood or cerebrospinal fluid (CSF) samples from 168 patients. We achieved an average detection limit of 0.005% ctDNA purity leading to MRD detected ranging from 0.001% to 100% with brain tumor consistently showing a low MRD. At disease diagnosis, progression and relapse, our assay identified ctDNA in over 93% of extra- cranial solid tumors, 90% of leukemia, 89% of sarcoma, and 90% of neuroblastoma. For brain tumors, we detected MRD in ∼90% of CSF samples, and in ∼60% of blood samples, a major advance over previous approaches. Importantly, we detected MRD in ∼ 20% of cases with a clinically complete response, predicting relapse up to 6 months before clinical confirmation. Overall, these results demonstrate that our monitoring assay for PCs is an important addition to standard of care for precision-guided treatment. Citation Format: Rob Salomon, Wenhan Chen, Charles Shale, Mojgan Toumari, Aileen Lowe, Wenyan Li, Jingwei Chen, Sajad Razavi-Bazaz, Paulette Barahona, Louise Cui, Chelsea Mayoh, Sam El-Kamand, Vanessa Tyrrell, Marie Wong-Erasmus, Loretta MS Lau, Noemi Fuentes-Bolanos, Edwin Cuppen, Dong-Anh Khoung-Quang, Jordan Staunton, Marion K Mateos, Toby Trahair, Michelle Haber, David S Ziegler, Paul Ekert, Peter Priestley, Mark Cowley. Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B009.