A higher frequency of ALKm at NB relapse has been demonstrated, suggesting clonal evolution of a minor ALK-mutated subclone to a dominant ALK mutated clone at relapse, but these cases might not represent clinically unfavorable cases initially.23,52,53 Further studies focusing on serial blood samples for ctDNA studies will further elucidate clonal evolution, also under targeted therapy.54 This evidence concerns the gene ALK and neuroblastoma.