Precision-guided treatment improves outcomes for children with high-risk cancers

Abstract Recent reports have shown that precision medicine can identify new treatment strategies for childhood cancer patients. However, it remains unclear which patients will benefit most from precision-guided treatment (PGT). Here we report 384 consecutive high-risk childhood cancer patients (with an expected cure rate of <30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Program PRISM trial. A total of 256 (67%) patients received PGT recommendations, of whom 110 (43%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% vs. 12%; P=0.049) or targeted agents not guided by molecular findings (26% vs. 5.2%; P=0.003). PGT based on Tier 1 evidence, PGT targeting fusions or commenced prior to disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers.