Clinical significance of serial tumor next generation sequencing (NGS) in 155 pediatric cancer patients

e13666 Background: Molecular profiling using NGS technology is critical for tumor diagnosis, risk stratification, and treatment selection. There are limited data in childhood cancers regarding evolution of genomic changes under the selective pressure of chemoradiotherapy. Here we report on serial testing of hematologic and solid pediatric tumor specimens across the spectrum of diagnosis, during treatment and disease relapse. Methods: Since 2016, 2,144 somatic NGS assays from 1,727 unique cancer patients were performed using the Comprehensive Hematological Malignancy Panel (CHMP) or the Comprehensive Solid Tumor Panel (CSTP). Serial tumor analysis was performed on 155 patients. All tumors were profiled for SNVs/indels, copy number alterations (CNAs), and fusions. The clinical impact on diagnosis, prognosis, and therapy was assessed. Results: 85 and 70 patients were tested with CHMP and CSTP, respectively. 86.5% (134/155) of patients underwent 1 subsequent genetic testing, while 13.5% (21/155) were serially tested for 3 - 6 times. Relapsed or therapy-refractory tumor was the most common indication for repeat CHMP and CSTP analysis of tumor genomics (64.5%, 100/155), primarily to survey for new targetable cancer driver mutations. The second most common reason for serial testing with CHMP was to monitor clonal evolution for patients with bone marrow failure syndromes and/or myelodysplastic syndromes, which resulted in a new cancer diagnosis in 14.6% (6/41) patients. For CSTP, the second most common reason for serial testing was to test a different part of the same tumor for tumors with histologic and/or radiographic heterogeneity (27.1%, 19/70). Of all patients with serial testing, 70 had at least one clinically significant new SNV/indel, 44 had distinct CNAs, and 4 had new clinically actionable fusions. Overall, clinically significant new results were detected in 81 (52.3%) patients, including 53 patients with new clonal changes indicating disease evolution, 31 of diagnostic significance, 9 of prognostic significance, and 8 suggesting new treatment options. Conclusions: Taken together, these data highlight the clinical importance of serial testing of pediatric tumors for potential biomarkers that may impact patients’ care at various time points across the spectrum of their diseases.