Feasibility and clinical integration of molecular profiling for target identification in pediatric solid tumors

The role of tumor molecular profiling in directing targeted therapy utilization remains to be defined for pediatric tumors. We aimed to evaluate the feasibility of a sequencing and molecular biology tumor board (MBB) program, and its clinical impact on children with solid tumors.

We report on a single-center MBB experience of 60 pediatric patients with a poor prognosis or relapsed/refractory solid tumors screened between October 2014 and November 2015. Tumor molecular profiling was performed with panel-based next-generation sequencing and array comparative genomic hybridization.

Mean age was 12 ± 5.7 years (range 0.1-21.5); main tumor types were high-grade gliomas (n = 14), rare sarcomas (n = 9), and neuroblastomas (n = 8). The indication was a poor prognosis tumor at diagnosis for 16 patients and relapsed (n = 26) or refractory disease (n = 18) for the remaining 44 patients. Molecular profiling was feasible in 58 patients. Twenty-three patients (40%) had a potentially actionable finding. Patients with high-grade gliomas had the highest number of targetable alterations (57%). Six of the 23 patients subsequently received a matched targeted therapy for a period ranging from 16 days to 11 months. The main reasons for not receiving targeted therapy were poor general condition (n = 5), pursuit of conventional therapy (n = 6), or lack of pediatric trial (n = 4).

Pediatric molecular profiling is feasible, with more than a third of patients being eligible to receive targeted therapy, yet only a small proportion were treated with these therapies. Analysis at diagnosis may be useful for children with very poor prognosis tumsors.