Impact of Genomic and Clinical Factors on Outcome of Children ≥18 Months of Age with Stage 3 Neuroblastoma with Unfavorable Histology and without <i>MYCN</i> Amplification: A Children's Oncology Group (COG) Report

神经母细胞瘤 内科学 医学 组织学 阶段(地层学) 肿瘤科 单变量分析 队列 置信区间 临床试验 齿轮 多元分析 生物 遗传学 细胞培养 古生物学 人工智能 计算机科学
作者
Navin Pinto,Arlene Naranjo,Xiangming Ding,Fan F Zhang,Emily Hibbitts,Rebekah Kennedy,Rachelle Tibbetts,Shannon Wong-Michalak,David Craig,Zarko Manojlovic,Michael D. Hogarty,Susan Kreissman,Rochelle Bagatell,Meredith S. Irwin,Julie R. Park,Shahab Asgharzadeh
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:: OF1-OF11
标识
DOI:10.1158/1078-0432.ccr-22-3032
摘要

Abstract Purpose: Patients ≥18 months of age with International Neuroblastoma Staging System (INSS) stage 3 unfavorable histology (UH), MYCN-nonamplified (MYCN-NA) tumors have favorable survival rates compared with other high-risk neuroblastoma populations. The impact of select clinical and biological factors on overall survival (OS) and event-free survival (EFS) were evaluated. Experimental Design: Patients enrolled on Children's Oncology Group (COG) A3973 (n = 34), ANBL0532 (n = 27), and/or biology protocol ANBL00B1 (n = 72) were analyzed. Tumors with available DNA (n = 65) and RNA (n = 42) were subjected to whole-exome sequencing (WES) and RNA sequencing. WES analyses and gene expression profiling were evaluated for their impact on survival. Multivariate analyses of EFS/OS using significant factors from univariate analyses were performed. Results: 5-year EFS/OS for patients treated with high-risk therapy on A3973 and ANBL0532 were 73.0% ± 8.1%/87.9% ± 5.9% and 61.4% ± 10.2%/73.0% ± 9.2%, respectively (P = 0.1286 and P = 0.2180). In the A3973/ANBL0532 cohort, patients with less than partial response (PR; n = 5) at end-induction had poor outcomes (5-year EFS/OS: 0%/20.0% ± 17.9%. Univariate analyses of WES data revealed that subjects whose tumors had chromosome 1p or 11q loss/LOH and chromosome 5 or 9 segmental chromosomal aberrations had inferior EFS compared with those with tumors without these aberrations. Multivariate analysis revealed that 11q loss/LOH was an independent predictor of inferior OS [HR, 3.116 (95% confidence interval, 1.034–9.389), P = 0.0435]. Conclusions: Patients ≥18 months of age at diagnosis who had tumors with UH and MYCN-NA INSS stage 3 neuroblastoma assigned to high-risk therapy had an 81.6% ± 5.3% 5-year OS. Less than PR to induction therapy and chromosome 11q loss/LOH are independent predictors of inferior outcome and identify patients who should be eligible for future high-risk clinical trials.
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