Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study
Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study
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DOI：
10.1002/pbc.27363
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发表时间：
2018-11-01
影响因子：
3.2
通讯作者：
Ladenstein, Ruth
中科院分区：
文献类型：
--
作者：
Morgenstern, Daniel A.;Poetschger, Ulrike;Ladenstein, Ruth
背景：风险分层对神经母细胞瘤的治疗决策至关重要。本研究旨在探讨年龄为18个月的转移性神经母细胞瘤患者诊断时影响预后的因素，并建立一种简单的预后风险评分。数据来自欧洲高危神经母细胞瘤1 (HR-NBL1)/国际儿科肿瘤学会欧洲神经母细胞瘤（SIOPEN）试验，该试验的分析仅限于18个月大的转移性疾病患者，并且在引入免疫治疗之前接受过治疗。主要终点为5年无事件生存期（EFS）。评估的预后因素包括性别、年龄、肿瘤MYCN扩增（MNA）状态、血清乳酸脱氢酶(LDH)/铁蛋白、原发肿瘤和转移部位。将单变量分析中的重要因素纳入多变量模型，并根据估计的对数累积风险比开发了一个加性评分系统。结果该队列纳入1053例患者，中位随访时间为5.5年，EFS为271%。在单变量分析中，年龄；血清LDH和铁蛋白；骨髓、骨、肝、肺受累；和bbb1转移系统/隔室与较差的EFS相关。肿瘤MNA与较差的EFS无关。建立多变量模型和风险评分，包括年龄（bbb50岁，2分）、血清LDH （>1250U/L， 1分）和转移系统数量（> 1,2分）。EFS与风险评分显著相关：评分=0时，EFS为52 +/- 9%，评分=5时，EFS为6 +/- 3% (P
BackgroundRisk stratification is crucial to treatment decision-making in neuroblastoma. This study aimed to explore factors present at diagnosis affecting outcome in patients aged18 months with metastatic neuroblastoma and to develop a simple risk score for prognostication.ProcedureData were derived from the European high-risk neuroblastoma 1 (HR-NBL1)/International Society for Paediatric Oncology European Neuroblastoma (SIOPEN) trial with analysis restricted to patients aged 18 months with metastatic disease and treated prior to the introduction of immunotherapy. Primary endpoint was 5-year event-free survival (EFS). Prognostic factors assessed were sex, age, tumour MYCN amplification (MNA) status, serum lactate dehydrogenase (LDH)/ferritin, primary tumour and metastatic sites. Factors significant in univariate analysis were incorporated into a multi-variable model and an additive scoring system developed based on estimated log-cumulative hazard ratios.ResultsThe cohort included 1053 patients with median follow-up 5.5years and EFS 271%. In univariate analyses, age; serum LDH and ferritin; involvement of bone marrow, bone, liver or lung; and >1 metastatic system/compartment were associated with worse EFS. Tumour MNA was not associated with worse EFS. A multi-variable model and risk score incorporating age (>5 years, 2 points), serum LDH (>1250U/L, 1 point) and number of metastatic systems (>1, 2 points) were developed. EFS was significantly correlated with risk score: EFS 52 +/- 9% for score=0versus 6 +/- 3% for score=5 (P