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Outcome analysis of non-high-risk neuroblastoma patients enrolled on Children’s Oncology Group trials P9641 and A3961.
Session Type and Session Title:
Poster Discussion Session, Pediatric Oncology
J Clin Oncol 30, 2012 (suppl; abstr 9533)
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Background: Patients with non-high-risk neuroblastoma (low- and intermediate-risk) generally have an excellent event free (EFS) and overall (OS) survival with current therapy. However, within this heterogeneous patient population, there are patients that may benefit from further therapy reduction and patients that may benefit from augmented therapy. Methods: Survival tree regression analysis was performed in patients enrolled on P9641 and A3961 with OS the primary endpoint. Univariate Cox proportional hazards models determined statistically significant prognostic factors. Secondary analysis of cases with MYCN non-amplified, non-high-risk neuroblastoma classified patients by age, INSS stage, Shimada histology and genomic features to determine 5-year EFS and OS. Favorable genomics were defined as hyperdiploid tumors without 1p or 11q loss of heterozygosity (LOH). Those with LOH at 1p or 11q or with a diploid DNA index were considered unfavorable. Patients without genomic data were excluded. Results: In the survival tree analysis, ploidy and genomic features were found to be statistically significant. In the secondary analysis, patients <18 months of age with stage 2 or 3, favorable histology tumors with favorable genomic profile had 5-year EFS and OS rates of 92.9±3.9% and 100% respectively. Patients with stage 2 and 3 tumors, unfavorable histology and unfavorable genomic features had EFS of 68.4±8.0% and OS of 78.4±7.0%. Patients <12 months of age with stage 4 disease and either unfavorable histologic or genomic features had EFS of 69.1±5.4% and OS of 88.5±3.8%. Conclusions: Excellent outcomes in non-high-risk neuroblastoma patients with favorable histologic and genomic features suggest further reduction in therapy is possible in this cohort while maintaining survival and decreasing side effects. Select patients with unfavorable features have suboptimal OS and would benefit from modifications in therapy. Histologic and genomic criteria can be used to identify patients with non-high-risk neuroblastoma that may benefit from modifications in therapy. These data support the conduct of a cooperative group clinical trial to refine therapy for patients with non-high-risk disease.
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