采用 NANT 缓解标准（v1.0）预测复发/难治性高危神经母细胞瘤的缓解率、无进展生存期和总生存期。
Predictors of response, progression-free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.
机构信息
Department of Pediatrics, Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, California.
Department of Preventative Medicine Statistics, Keck School of Medicine of the University of Southern California, Los Angeles, California.
出版信息
Pediatr Blood Cancer. 2018 May;65(5):e26940. doi: 10.1002/pbc.26940. Epub 2018 Jan 19.
PURPOSE
The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed.
METHODS
A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology).
RESULTS
Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS.
CONCLUSIONS
NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.
目的
新的神经母细胞瘤治疗反应标准（NANTRC）旨在优化复发性/难治性神经母细胞瘤患者的反应评估。分析了 NANTRC 版本 1.0（NANTRCv1.0）的预测指标和预后因素与结果的相关性。
方法
对 2000 年至 2009 年期间在 13 项 NANT 1/2 期试验中招募的复发性/难治性神经母细胞瘤患者进行回顾性分析。采用实体瘤反应评估标准（RECIST）的综合 CT/MRI（反应评估标准）、间碘苄胍（MIBG；居里评分）和骨髓（BM）肿瘤百分比（形态学）对 NANTRC 总体反应进行评估。
结果
在可评估反应的 203 名患者中，有 14 名（6.9%）完全缓解（CR）和 14 名（6.9%）部分缓解（PR）。5 年无进展生存率（PFS）为 16±3%；总生存率（OS）为 27±3%。入组时疾病部位包括 MIBG 阳性病变（100% MIBG 试验；84%非 MIBG 试验）、可测量的 CT/MRI 病变（48%）和 BM（49%）。多变量分析显示，居里评分 0（P<0.001）、居里评分较低（P=0.003）、无可测量的 CT/MRI 病变（P=0.044）和外周血干细胞（PBSC）支持试验（P=0.005）与获得 CR/PR 相关。稳定疾病（SD）或更好的总体反应与更好的 OS 相关（P<0.001）。多变量分析显示，MYCN 扩增（P=0.037）与 PFS 较差相关；可测量的 CT/MRI 病变（P=0.041）与 OS 较差相关；先前进展性疾病（PD；P<0.001/P<0.001）、居里评分≥1（P<0.001；P=0.001）、居里评分较高（P=0.048/0.037）和非 PBSC 试验治疗（P<0.001/0.003）与较差的 PFS 和 OS 相关。
结论
NANTRCv1.0 的至少 SD 反应与复发性/难治性神经母细胞瘤患者的更好 OS 相关。患者和肿瘤特征可能预测反应和结果。确定这些变量可以优化 1/2 期试验设计，以选择新的药物进行进一步测试。
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