Abstract LB-160: A feasibility trial using molecular-guided therapy for the treatment of patients with refractory or recurrent neuroblastoma.
Authors: Sholler Giselle L. , Bergendahl Genevieve , VanderWerff Alyssa , Ferguson William , Roberts William , Eslin Don , Kraveka Jacqueline , Kaplan Joel , Mitchell Deanna , Parikh Nehal , Neville Kathleen , Ashikaga Takamaru , Bond Jeffrey , Hanna Gina , Merchant Melinda , Huentelman Matt , Corneveaux Jason , Trent Jeffrey 
Published: August 2014

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 individual patient tumors with existing therapeutic agents may result in a rational, data-driven approach to treatment with potential to improve clinical outcomes. Methods: This was a multicenter study through the Neuroblastoma and Medulloblastoma Translational Research Consortium. The primary objective of this 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 prediction report, molecular tumor board review yielding a formulated treatment plan, independent medical monitor review, treatment initiation within a 2-week period and completion of one cycle of therapy. The secondary objectives included a reproducibility study of patient biopsies, safety and response to therapy. Research validation in cell culture models of patient tumors was performed. Results: Fourteen patients with multiply relapsed neuroblastoma were enrolled between July 2011 and November 2012. All biopsies passed histopathology and RNA quality control. Generation of gene expression data and its analysis (3-8 days), reports which linked this data into medically actionable drug candidates (0-3 days), molecular tumor board (1-6 days) and independent medical monitor review (1 -4 days) were all completed in real-time. The average time was 12.4 days from biopsy to initiation of treatment. There were no unexpected serious adverse events on study and patients tolerated therapy well. Clinical benefit was seen 50% of patients. Triplicate biopsies showed reproducible sets of drugs and the comparatively large differences in drug lists between patients show that the drug lists are tailored to patients. Comparison of RNA expression profiles with RNA sequencing from each patient showed strong correlation. Conclusion: This study shows that it is feasible to create therapeutic treatment plans based on genomic profiling in real time and that patients are able to be treated safely on a tumor board derived molecular guided therapy using existing medications. Incorporation of further genomic studies to evaluate additional molecular profiling techniques in order to make more informed individual therapeutic treatment plans will be evaluated in future studies.
Citation Format: Giselle L. Sholler, Genevieve Bergendahl, Alyssa VanderWerff, William Ferguson, William Roberts, Don Eslin, Jacqueline Kraveka, Joel Kaplan, Deanna Mitchell, Nehal Parikh, Kathleen Neville, Takamaru Ashikaga, Jeffrey Bond, Gina Hanna, Melinda Merchant, Matt Huentelman, Jason Corneveaux, Jeffrey Trent. A feasibility trial using molecular-guided therapy for the treatment of patients with refractory or recurrent neuroblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-160. doi:10.1158/1538-7445.AM2013-LB-160