title: Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study.
abstract: OBJECTIVE
  Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, and targeted therapies are less available. Consequently, it is unknown whether clinical sequencing can be of benefit.
  
  
  OBJECTIVE
  To assess the feasibility of identifying actionable alterations and making individualized cancer therapy (iCat) recommendations in pediatric patients with extracranial solid tumors.
  
  
  METHODS
  Clinical sequencing study at 4 academic medical centers enrolling patients between September 5, 2012, and November 19, 2013, with 1 year of clinical follow-up. Participants were 30 years or younger with high-risk, recurrent, or refractory extracranial solid tumors. The data analysis was performed October 28, 2014.
  
  
  METHODS
  Tumor profiling performed on archived clinically acquired specimens consisted of mutation detection by a Sequenom assay or targeted next-generation sequencing and copy number assessment by array comparative genomic hybridization. Results were reviewed by a multidisciplinary expert panel, and iCat recommendations were made if an actionable alteration was present, and an appropriate drug was available.
  
  
  METHODS
  Feasibility was assessed using a 2-stage design based on the proportion of patients with recommendations.
  
  
  RESULTS
  Of 100 participants (60 male; median [range] age, 13.4 [0.8-29.8] years), profiling was technically successful in 89 (89% [95% CI, 83%-95%]). Median (range) follow-up was 6.8 (2.0-23.6) months. Overall, 31 (31% [95% CI, 23%-41%]) patients received an iCat recommendation and 3 received matched therapy. The most common actionable alterations leading to an iCat recommendation were cancer-associated signaling pathway gene mutations (n = 10) and copy number alterations in MYC/MYCN (n = 6) and cell cycle genes (n = 11). Additional alterations with implications for clinical care but not resulting in iCat recommendations were identified, including mutations indicating the possible presence of a cancer predisposition syndrome and translocations suggesting a change in diagnosis. In total, 43 (43% [95% CI, 33%-53%]) participants had results with potential clinical significance.
  
  
  CONCLUSIONS
  A multi-institution clinical genomics study in pediatric oncology is feasible and a substantial proportion of relapsed or refractory pediatric solid tumors have actionable alterations.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01853345.
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Marian H
authors.initials: MH
authors.lastname: Harris
authors.affiliation: Division of Pediatric Hematology Oncology, University of California-San Francisco Benioff Children's Hospital.
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
authors.affiliation: Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Glade Bender
authors.affiliation: Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC.
authors.forename: AeRang
authors.initials: A
authors.lastname: Kim
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Crompton
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
authors.forename: Erin
authors.initials: E
authors.lastname: Parker
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Dumont
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Hong
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
authors.forename: Dongjing
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Alanna
authors.initials: A
authors.lastname: Church
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts6Harvard Medical School, Boston, Massachusetts.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Stegmaier
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts6Harvard Medical School, Boston, Massachusetts.
authors.forename: Charles W M
authors.initials: CWM
authors.lastname: Roberts
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts6Harvard Medical School, Boston, Massachusetts.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Shusterman
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts6Harvard Medical School, Boston, Massachusetts.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.affiliation: Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts8Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Laura E
authors.initials: LE
authors.lastname: MacConaill
authors.affiliation: Harvard Medical School, Boston, Massachusetts8Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Neal I
authors.initials: NI
authors.lastname: Lindeman
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts6Harvard Medical School, Boston, Massachusetts.
authors.forename: Lisa
authors.initials: L
authors.lastname: Diller
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts6Harvard Medical School, Boston, Massachusetts.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts6Harvard Medical School, Boston, Massachusetts.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Janeway