Background: Neuroblastoma is the most common extracranial solid tumor in children. The prognosis for infants with neuroblastoma is good, while only 30% of children diagnosed after 12-15 months of age survive despite aggressive multimodal therapies. There are currently few treatment options from which pediatric oncologists can select with any degree of confidence to improve the management of multiply recurrent neuroblastoma patients. The identification of agents through genomic profiling that target specific molecular pathways associated with the development and/or progression of neoplastic diseases holds promise. Improved approaches that identify effective existing agents in a rational, data-driven fashion may result in a survival benefit in the clinical setting, while avoiding the toxicity associated with agents that are unlikely to be beneficial.

Method: The primary objective of this pilot study was to evaluate the feasibility of using predictive modeling based on genome-wide mRNA expression profiles of neuroblastoma tumor biopsies to make real-time treatment decisions. Feasibility was defined as the completion of the following in a two week time period: tumor biopsy, quality RNA extraction, mRNA U133 2+ Affymetrix gene chip hybridization, analysis utilizing a series of predictive methodologies, report generation, tumor board review with formulated treatment plan, and medical monitor review.

Results: There were 5 patients enrolled between April-June 2010 with multiply relapsed or refractory neuroblastoma. Patients had received between 2-13 previous relapsed therapies and were between 2-6.5 years post diagnosis. All patients had soft tissue disease which was able to be biopsied. All biopsies were adequate by pathology evaluation (>75% viable tumor) and RNA quality (>6.5 RIN). Gene chips were completed in 3-7 days, report generation was 1-5 days, tumor board was 1-3 days, medical monitor sign off was 1 day. The total time was 10-12 days for all patients. The tumor board was able to create individualized therapy regimens for all patients. Correlative biology specimens were obtained and grown in culture. Mice xenografts of 2/5 patients were established. Cultures and xenografts were used for validation studies of predicted drug sensitivity.

Conclusion: It is feasible to obtain real-time genomic profiling for molecularly guided therapy for use in treatment decision making. This warrants further testing in a Phase I study.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3942. doi:10.1158/1538-7445.AM2011-3942