title: Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma.
abstract: The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes. Sixteen patients with neuroblastoma were enrolled of which fourteen were eligible for this study. Feasibility was defined as completion of tumor biopsy, pathological evaluation, RNA quality control, gene expression profiling, bioinformatics analysis, generation of a drug prediction report, molecular tumor board yielding a treatment plan, independent medical monitor review, and treatment initiation within a 21 day period. All eligible biopsies passed histopathology and RNA quality control. Expression profiling by microarray and RNA sequencing were mutually validated. The average time from biopsy to report generation was 5.9 days and from biopsy to initiation of treatment was 12.4 days. No serious adverse events were observed and all adverse events were expected. Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response. The overall response rate was 7% and the progression free survival was 59 days. This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients.
authors.affiliation: Helen DeVos Children's Hospital, Grand Rapids, Michigan.|Michigan State University College of Medicine, Grand Rapids, Michigan.
authors.forename: Giselle L
authors.initials: GL
authors.lastname: Saulnier Sholler
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Bond
authors.affiliation: Helen DeVos Children's Hospital, Grand Rapids, Michigan.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Bergendahl
authors.affiliation: Helen DeVos Children's Hospital, Grand Rapids, Michigan.
authors.forename: Akshita
authors.initials: A
authors.lastname: Dutta
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Julie
authors.initials: J
authors.lastname: Dragon
authors.affiliation: Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Neville
authors.affiliation: Cardinal Glennon Children's Hospital, St. Louis University, St. Louis, Missouri.
authors.forename: William
authors.initials: W
authors.lastname: Ferguson
authors.affiliation: UC San Diego School of Medicine and Rady Children's Hospital, San Diego, California.
authors.forename: William
authors.initials: W
authors.lastname: Roberts
authors.affiliation: Arnold Palmer Hospital for Children, Orlando, Florida.
authors.forename: Don
authors.initials: D
authors.lastname: Eslin
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kraveka
authors.affiliation: Levine Children's Hospital, Charlotte, North Carolina.
authors.forename: Joel
authors.initials: J
authors.lastname: Kaplan
authors.affiliation: Helen DeVos Children's Hospital, Grand Rapids, Michigan.
authors.forename: Deanna
authors.initials: D
authors.lastname: Mitchell
authors.affiliation: Connecticut Children's Medical Center, Hartford, Connecticut.
authors.forename: Nehal
authors.initials: N
authors.lastname: Parikh
authors.affiliation: NCI Center for Cancer Research, Bethesda, Maryland.
authors.forename: Melinda
authors.initials: M
authors.lastname: Merchant
authors.affiliation: Medical Biostatistics, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Takamaru
authors.initials: T
authors.lastname: Ashikaga
authors.affiliation: Arnold Palmer Hospital for Children, Orlando, Florida.
authors.forename: Gina
authors.initials: G
authors.lastname: Hanna
authors.affiliation: Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, The Marine Biological Laboratory, Woods Hole, Massachusetts.
authors.forename: Pamela Jean
authors.initials: PJ
authors.lastname: Lescault
authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Ashley
authors.initials: A
authors.lastname: Siniard
authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Jason
authors.initials: J
authors.lastname: Corneveaux
authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Matthew
authors.initials: M
authors.lastname: Huentelman
authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Trent
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005240:Feasibility Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D009447:Neuroblastoma / Q000628:therapy*; D061214:Patient Safety; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods; D061665:Time-to-Treatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D012334:RNA, Neoplasm
keywords: Genomic profiling; molecular tumor board; molecular-guided therapy; neuroblastoma; pediatric oncology