Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California.
Keck School of Medicine, Department of Pediatrics, University of Southern California, Los Angeles, California.
Pediatr Blood Cancer. 2022 Sep;69(9):e29719. doi: 10.1002/pbc.29719. Epub 2022 Apr 20.
Minimal disease quantification may predict event-free survival (EFS) and overall survival (OS).
We evaluated mRNA expression of five neuroblastoma-associated genes (NB5 assay) in bone marrows (BM) of patients with newly diagnosed high-risk neuroblastoma who received consistent immunotherapy. mRNA expression of CHGA, DCX, DDC, PHOX2B, and TH genes in BM of 479 patients enrolled on the immunotherapy arm of Children's Oncology Group trials ANBL0032 and ANBL0931 was evaluated using real-time polymerase chain reaction (PCR)-based TaqMan low-density array. Results from end-consolidation and end-therapy were analyzed for association with five-year EFS/OS and patient and tumor characteristics. Tests of statistical significance were two-sided.
NB5 assay detected neuroblastoma-related mRNA in 222 of 286 (77.6%) of BMs obtained at end-consolidation and 188 of 304 (61.8%) at end-therapy. Any mRNA level detected in end-therapy BM correlated with significantly worse EFS (57% [49.6%-63.7%] vs 73.0% [63.5%-80.4%]; P = 0.005), but not OS. Analysis limited to patients in complete response at end-therapy still found a significant difference in EFS with detectable versus not detectable NB5 assay results (58.9% [49.5%-67.1%] vs 76.6% [66.1%-84.2%]; P = 0.01). End-consolidation results did not correlate with EFS or OS. Multivariable analysis determined end-therapy NB5 assay BM results (P = 0.02), age at diagnosis (P = 0.002), and preconsolidation response (P = 0.02) were significantly associated with EFS independent of other clinical and biological parameters evaluated, including end-therapy response.
If further validated in additional patient cohorts, the NB5 assay's ability to independently predict EFS from end-therapy could improve patient stratification for novel maintenance therapy trials after current end-therapy to improve outcome.
微量疾病定量可能预测无事件生存（EFS）和总生存（OS）。
我们评估了 479 例新诊断高危神经母细胞瘤患者骨髓中 5 种神经母细胞瘤相关基因（NB5 检测）的 mRNA 表达，这些患者接受了一致的免疫治疗。使用实时聚合酶链反应（PCR）基于 TaqMan 低密度阵列评估了儿童肿瘤学组试验 ANBL0032 和 ANBL0931 免疫治疗臂中 286 例 BM 中 222 例（77.6%）和 304 例 BM 中 188 例（61.8%）的 CHGA、DCX、DDC、PHOX2B 和 TH 基因的 mRNA 表达。分析了终末巩固和终末治疗结果与 5 年 EFS/OS 和患者及肿瘤特征的相关性。统计检验为双侧检验。
NB5 检测在终末巩固时的 222 例 BM（77.6%）和终末治疗时的 188 例 BM（61.8%）中检测到神经母细胞瘤相关 mRNA。终末治疗 BM 中检测到的任何 mRNA 水平与 EFS 显著相关（57%[49.6%-63.7%]vs73.0%[63.5%-80.4%]；P=0.005），但与 OS 无关。在终末治疗完全缓解的患者中进行分析，仍发现可检测与不可检测 NB5 检测结果的 EFS 差异有统计学意义（58.9%[49.5%-67.1%]vs76.6%[66.1%-84.2%]；P=0.01）。终末巩固结果与 EFS 或 OS 不相关。多变量分析确定终末治疗 NB5 检测 BM 结果（P=0.02）、诊断时年龄（P=0.002）和预巩固反应（P=0.02）与 EFS 显著相关，独立于其他评估的临床和生物学参数，包括终末治疗反应。
如果在其他患者队列中进一步验证，NB5 检测从终末治疗中独立预测 EFS 的能力可能会改善当前终末治疗后新型维持治疗试验的患者分层，以改善预后。
