Clinical Response to a PARP Inhibitor and Chemotherapy in a Child with BARD1-Mutated Refractory Neuroblastoma: A Case Report.

Despite advances in the treatment of high-risk neuroblastoma, approximately half of these patients die from the disease. Targeted therapy based on synthetic lethality associated with homologous recombination deficiency (HRD) caused by germline mutations in homologous recombination repair genes has shown great efficacy in several adult solid tumors. Here we report the first successful treatment of a pediatric patient with refractory neuroblastoma and a germline pathogenic mutation in using a PARP inhibitor, talazoparib, in combination with cytotoxic chemotherapy and radiation therapy. Allele-specific expression in RNA-seq indicates bi-allelic loss of in tumor; however, the HRD score was below the threshold currently used for HRD classification in adult cancers. Our study demonstrates that the use of PARP inhibition in combination with DNA-damaging agents should be considered in children with -mutated neuroblastoma and cautions against the use of HRD score alone as a biomarker for this pediatric population.