title: Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.
abstract: Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations.
  
  
  
  This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence-Based Medicine.
  
  
  
  There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1-2), eight (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4).
  
  
  
  The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. The development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials.
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Ortiz
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kobos
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Michael
authors.initials: M
authors.lastname: Walsh
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Slotkin
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Stephen
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.|Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Meera
authors.initials: M
authors.lastname: Hameed
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: Solit
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.|Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Neerav
authors.initials: N
authors.lastname: Shukla
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Alex
authors.initials: A
authors.lastname: Kentsis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007223:Infant; D008297:Male; D008495:Medical Oncology; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D057285:Precision Medicine / Q000379:methods*; D012189:Retrospective Studies; D055815:Young Adult
keywords: cancer pharmacology; molecular biology; new agents; pediatric oncology