Real-world experience of a pediatric precision oncology protocol utilizing paired somatic and germline sequencing at a single institution: Interim analysis.

10008 Background: While most pediatric oncology patients are cured with upfront therapy, outcomes for patients with metastatic and relapsed/refractory disease remain poor. Salvage therapy is toxic and has marginal success rates, necessitating novel, personalized approaches. We established our pediatric precision oncology program based on integrative clinical sequencing (ICS) in 2012 and present an interim outcomes analysis of this single institution cohort. Methods: Pediatric and AYA oncology patients (age 0-25 years) underwent paired somatic and germline sequencing, including whole exome and transcriptomic analysis. Results were annotated with longitudinal clinical data extracted from the medical record using the NCI-supported tool EMERSE, which has been enhanced by the addition of a beta version of a large language models (LLM) integrated “Chatbot” to implement more efficient data abstraction from clinical notes. Results: Of the 1000 patients enrolled, 925 (92.5%) were sequenced successfully. We present interim analysis of the first 435 patients. Within this interim cohort, 233 (53.56%) of patients were male and 79.8% were non-Hispanic white. Hematologic malignancies accounted for 110 (25.3%) diagnoses, brain tumors 75 (17.2%), and non-brain solid tumors 250 (57.5%). ICS succeeded for 400/435 (92.0%) patients. Overall, 471 actionable alterations (AA) were discovered in 266 (66.5%) patients (mean 1.77 AA/patient). These included 62 actionable germline alterations in 60 patients (15%). There were 195 single nucleotide variants (SNV) in 142 patients, 69 gene fusions in 62 patients, and 145 copy number alterations (CNA) in 92 patients. Actionable findings guided the use of targeted therapies (TT) supported by NCI-MATCH criteria in 116 patients (29.0%) with a total of 209 targeted therapies given (mean 1.80 /patient). Thirty-two patients (8.0%) enrolled on therapeutic clinical trials featuring an identified targeted therapy. Sixteen (4.0%) patients without AAs received 22 TTs based on clinician preference. Additionally, 166 patients (41.5%) did not receive TT despite at least one AA due to lack of availability of a suitable formulation, pursuit of alternative therapy, or death prior to therapy initiation. Repeat ICS (range 1-4) was completed for 115 patients (28.8%), among which 8 (7.0%) had additional AAs identified and 5 (4.4%) received TT based on repeat ICS. Conclusions: This study highlights the importance of ICS based precision oncology with 67% of patients having AAs and 29% receiving TTs. Analyses are ongoing to study the most frequently altered signaling pathways, frequency of targeted agents used, impact of ICS and TT on the clinical outcomes for these patients, barriers in receiving TT despite having AAs, role of longitudinal sequencing, and the impact of LLM based “Chatbot” on data extraction efficiency.