Seattle Children's Hospital, Seattle, WA, USA; University of Washington School of Medicine, Seattle, WA, USA.
COG Statistics and Data Center, Department of Biostatistics, University of Florida, Gainesville, FL, USA.
Eur J Cancer. 2019 May;112:66-79. doi: 10.1016/j.ejca.2019.02.003. Epub 2019 Apr 1.
Induction chemotherapy plays an important role in the management of patients with high-risk neuroblastoma. Predictors of response to induction therapy are largely lacking. We sought to describe clinical and biological features associated with induction response.
Patients from four consecutive COG high-risk trials were included. Response was evaluated by the 1993 International Neuroblastoma Response Criteria. The primary end-point was end-induction partial response (PR) or better. Univariate analyses were performed to compare response as a function of clinical or biologic predictors. A multivariate logistic regression model using significant predictors from univariate analyses was constructed to model PR or better.
The analytic cohort included 1242 patients. End-induction response ≥PR was significantly associated with higher event-free and overall survival. Baseline factors associated with ≥PR included age <18 months (87.4% with ≥PR vs. 78.7% if older; p = 0.0103), International Neuroblastoma Staging System non-stage 4 (89.0% vs. 78.4% if stage 4; p = 0.0016), MYCN amplification (85.5% vs. 77.1% if non-amplified; p = 0.0006), 1p loss of heterozygosity (LOH; 85.6% vs. 76.0% if no LOH; p = 0.0085), no 11q LOH (84.8% vs. 70.9% if 11q LOH; p = 0.0004) and high mitosis-karyorrhexis index (MKI; 84.5% vs. 77.5% if low-intermediate MKI; p = 0.0098). On multivariable analysis (n = 407), the absence of 11q LOH was the only factor that remained significantly associated with ≥PR (odds ratio: 1.962 vs. 11q LOH; 95% confidence interval 1.104-3.487; p = 0.0216).
Improved end-induction response in high-risk neuroblastoma is associated with longer survival. Patients with 11q LOH are less likely to respond to induction therapies and should be prioritised for novel approaches in future trials.
诱导化疗在高危神经母细胞瘤患者的治疗中起着重要作用。目前对于诱导治疗反应的预测因素还知之甚少。本研究旨在描述与诱导反应相关的临床和生物学特征。
纳入了来自 COG 四项连续高危试验的患者。通过 1993 年国际神经母细胞瘤反应标准评估反应。主要终点是终末诱导部分缓解（PR）或更好。采用单变量分析比较反应与临床或生物学预测因素的关系。使用单变量分析中显著的预测因素构建多变量逻辑回归模型来预测 PR 或更好。
分析队列包括 1242 例患者。终末诱导反应≥PR 与无事件生存和总生存显著相关。与≥PR 相关的基线因素包括年龄＜18 个月（87.4%有≥PR 与年龄较大者相比；p=0.0103）、国际神经母细胞瘤分期系统非 4 期（89.0%与 4 期相比；p=0.0016）、MYCN 扩增（85.5%与非扩增者相比；p=0.0006）、1p 杂合性缺失（LOH；85.6%与无 LOH 者相比；p=0.0085）、无 11q LOH（84.8%与 11q LOH 者相比；p=0.0004）和高有丝分裂-核碎指数（MKI；84.5%与低-中 MKI 者相比；p=0.0098）。多变量分析（n=407）显示，11q LOH 缺失是唯一与≥PR 显著相关的因素（比值比：1.962；95%置信区间 1.104-3.487；p=0.0216）。
高危神经母细胞瘤的终末诱导反应改善与生存延长相关。存在 11q LOH 的患者对诱导治疗反应的可能性较低，应在未来试验中优先考虑新的治疗方法。
