Abstract B039: Clinical liquid biopsy testing for detecting actionable genomic alterations in children and young adults with advanced solid tumors
Authors: Roberts Holly J , Comeau Hannah , Dubois Steven G , Hoskova Katerina , Lin Douglas I , Crompton Brian D , Janeway Katherine A , Shulman David S 
Published: November 2024

Introduction: Given the paucity of data regarding circulating tumor DNA (ctDNA) as a modality to guide diagnosis and treatment for children with solid tumors, we conducted a prospective study to determine the frequency of diagnostic and targetable genomic variants identified by clinical ctDNA testing. Methods: GAIN is a prospective, multi-center molecular profiling study that was amended to include clinical ctDNA testing starting in January 2022. Patients were eligible if they were &lt;30 years old with a refractory, recurrent, newly diagnosed with 2-year EFS &lt;50%, or rare solid tumor and had measurable or evaluable disease. Paired tumor and blood samples underwent next generation sequencing (NGS) in CLIA-certified laboratories, with return of results to clinicians. Serial ctDNA samples were analyzed by F1LCDx (FoundationOne® Liquid Companion Diagnostic), an FDA-approved clinical ctDNA test that includes hybrid capture sequencing of a 300+ gene panel, comprehensive multi-omics ctDNA tumor fraction (TF) assessment, tumor mutational burden, and microsatellite instability status. We analyzed comprehensive NGS tissue-based and F1LCDx sequencing data for each participant to compare findings from each sample. The detection of alterations was stratified by ctDNA burden as assessed by ctDNA TF. We calculated the prevalence of ctDNA in our cohort, overall and by disease type. Chart review provided additional patient characteristic, diagnostic, therapeutic, and disease assessment data. The clinical impact of ctDNA results was qualitatively described. Results: The cohort included 35 patients, with a total of 70 F1LCDx samples (range 1-6 samples per patient). There were 16 unique tumor types represented, most commonly osteosarcoma (n = 8), neuroblastoma (n = 8), and Ewing sarcoma (n = 4). 77% of patients had metastatic disease at time of first ctDNA sample collection. 51% of patients had detectable ctDNA TF in at least one sample. Overall, 60% of patients had at least one actionable genomic alteration (range 0-14 variants per patient) identified in liquid biopsy samples, including 3 patients with actionable variants identified with undetectable ctDNA TF. We observed case vignettes in which ctDNA results informed clinical decisions, including disease assessment and treatment guidance. An illustrative example was the identification of ALK variants in relapse blood samples of two patients with neuroblastoma that were not identified in baseline tissue, which were targeted in both instances. Data collection and analyses as described in the methods are ongoing. Conclusion: In this prospective cohort of children and young adults with advanced solid tumors, ctDNA was detectable across a wide range of diagnoses and 60% of patients had at least one diagnostic or potentially targetable alteration identified. These data demonstrate that liquid biopsy yields actionable genomic variants, particularly when ctDNA burden is elevated. We will determine the association of these variants with those identified in tissue samples and their clinical implications in ongoing analyses.

Citation Format: Holly J Roberts, Hannah Comeau, Steven G Dubois, Katerina Hoskova, Douglas I Lin, Brian D Crompton, Katherine A Janeway, David S Shulman. Clinical liquid biopsy testing for detecting actionable genomic alterations in children and young adults with advanced solid tumors [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 B039.