title: Feasibility and clinical integration of molecular profiling for target identification in pediatric solid tumors.
abstract: 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.
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pincez
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Clément
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Lapouble
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Département d'oncologie médicale, Institut Curie, Paris et Saint Cloud, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Kamal
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bernard
authors.affiliation: Département de pathologie, Institut Curie, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Fréneaux
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aerts
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Pacquement
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.|Laboratoire de recherche translationnelle en oncologie pédiatrique, Institut Curie, Paris, France.|Inserm U830 Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.|Laboratoire de recherche translationnelle en oncologie pédiatrique, Institut Curie, Paris, France.
authors.forename: Irene
authors.initials: I
authors.lastname: Jiménez
authors.affiliation: Service d'hématologie et oncologie pédiatrique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Thébaud
authors.affiliation: Service d'onco-hématologie pédiatrique, Hôpital mère-enfant, Centre Hospitalier Universitaire de Limoges, Limoges, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Oudot
authors.affiliation: Unité d'hématologie pédiatrique, Groupe Hospitalier Pellegrin, Bordeaux, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Vérité
authors.affiliation: Département de médecine de l'enfant et de l'adolescent, Centre Hospitalier Universitaire de Rennes, Rennes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Taque
authors.affiliation: National Pediatric Haematology/Oncology Centre, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Cormac
authors.initials: C
authors.lastname: Owens
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.|University Paris Descartes, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Doz
authors.affiliation: Département d'oncologie médicale, Institut Curie, Paris et Saint Cloud, France.|EA7285, Paris Saclay University, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Le Tourneau
authors.affiliation: Inserm U830 Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.affiliation: Département d'oncologie pédiatrique, adolescents et jeunes adultes, Institut Curie, Paris, France.|Service de Génétique, Institut Curie, Paris, France.|Laboratoire de recherche translationnelle en oncologie pédiatrique, Institut Curie, Paris, France.|Inserm U830 Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy
keywords: array comparative genomic hybridization; clinical trial; molecular profiling; next-generation sequencing; solid tumor