Precision Medicine in Relapsed and Refractory Childhood Cancers: Single-center Experience, Literature Review, and Meta-analysis

OBJECTIVE: To date, the understanding of pediatric tumor genomics and how these genetic aberrations correlate with clinical outcome is lacking. Here, we report our experience with the next-generation sequencing (NGS) test program and discuss implications for the inclusion of molecular profiling into clinical pediatric oncology trials. We also aimed to explore studies on NGS in pediatric cancers and to quantify the variability of finding actionable mutations and the clinical implications. METHODS: We present a retrospective case series of all patients whose tumor tissue underwent NGS tests during treatment in our department. We also reviewed the literature and carried out a meta-analysis to explore studies on NGS in pediatric cancers. RESULTS: In 35/37 (94%) patients, we found at least one genomic alteration (GA); mean number of GAs per patient was 2 (range, 0–67), while 164 GAs were detected. Only 3 (8%) patients received precision medicine due to their GAs for a mean of 9 months (range, 5–14 months). Four studies were included in the meta-analysis. The pooled positive actionable mutation rate was 52% (95% CI 39%–66%), and the pooled rate of children who received precision medicine was 10% (95% CI 3%–20%). CONCLUSIONS: In children and young adults with high-risk, recurrent, or refractory malignancies, tumor profiling results have clinical implications, despite barriers to the use of matched precision therapy.