A Pilot Trial Testing the Feasibility of Using Molecular-Guided Therapy in Patients with Recurrent Neuroblastoma

Giselle L. Saulnier Sholler, William Ferguson, Genevieve Bergendahl, Erika Currier, Shannon R. Lenox, Jeffrey Bond, Marni Slavik, William Roberts, Deanna Mitchell, Don Eslin, Jacqueline Kraveka, Joel Kaplan, Nehal Parikh, Suman Malempati, Gina Hanna, Emily Eugster, David Cherba, Jeremy Miller, Craig Webb

Cardinal Glennon Children’s Hospital, Saint Louis University School of Medicine, St. Louis University, St. Louis, USA.
Center for Cancer Genomics and Computational Biology, Pediatric Oncology Translational Research Program at the Van Andel Research Institute in Grand Rapids, Grand Rapids, USA.
Center for Children’s Cancer and Blood Disorders, Arnold Palmer Hospital for Children MD Anderson Cancer Center Orlando; Orlando, USA.
Department of Pediatric Oncology, Helen DeVos Children’s Hospital, Michigan State University, Grand Rapids, USA.
Department of Pediatric Oncology, Oregon Health Science University; Portland, USA.
Division of Hematology/Oncology 2J, Connecticut Children’s Medical Center; Hartford, USA.
Pediatric Hematology/Oncology, Medical University of South Carolina; Charleston, USA.
Pediatric Oncology, Levine Children’s Hospital; Charlotte, USA.
Rady Children’s Hospital San Diego, University of California San Diego School of Medicine at the University of California San Diego, San Diego, USA.
Vermont Cancer Center, Department of Medicine, University of Vermont, Burlington, USA.

DOI: 10.4236/jct.2012.35077                

Abstract

Background: Neuroblastoma is the most common extracranial solid tumor in children, and treatment options for recurrent neuroblastoma are limited. Using molecular profiling to target the molecular vulnerabilities of neuroblastoma with existing therapeutic agents may result in a rational, data-driven approach with potential to improve clinical outcomes. Methods: The primary objective of this pilot study was to evaluate the feasibility of supporting real-time treatment decisions through predictive modeling of genome-wide mRNA gene expression data from neuroblastoma tumor biopsies. Feasibility was defined as completion of tumor biopsy, histopathological evaluation, RNA extraction and quality control, gene expression profiling within a CLIA-certified laboratory, bioinformatic analysis, generation of a drug predicttion report, molecular tumor board review yielding a formulated treatment plan, and independent medical monitor review within a 2-week period. Results: Five patients with multiply relapsed or refractory neuroblastoma were enrolled between April and June 2010. All biopsies passed histopathology and RNA quality control. Generation of gene expression data and its analysis (3-7 days), reports which linked this data into medically actionable drug candidates (1-5 days), molecular tumor board (1-3 days) and independent medical monitor review (1 day) were all completed in real-time. The average time was 10.5 days for all patients. Conclusion: This study shows that it is feasible to create therapeutic treatment plans based on genomic profiling in less than 12 days. This warrants further testing in a Phase I study to determine safety of predicted treatments and evaluate whether the information obtained in these analyses would result in patient benefit.

Keywords

Neuroblastoma; Molecular Guided Therapy; Predictive Therapies; Molecular Profiling; Genomic Profiling; Pediatric Cancer

Conflicts of Interest

The authors declare no conflicts of interest.

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