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目的:评估和分析神经母细胞瘤（neuroblastoma，NB）患儿采用危险因素分层治疗的结果。方法:收集2002年9月至2018年12月中山大学肿瘤防治中心收治的483例采用危险因素分层治疗的初诊为NB患儿的临床资料。其中，男290例[60.0% （290/483）] ，女193例[40.0% （193/483）] ；患儿的中位年龄为3.48岁，年龄范围为7 d至18岁；按国际NB分期系统分期，1期19例，2期25例，3期95例，4期334例，4S期10例。按照年龄、临床分期、病理类型和N-MYC基因状态分为低危、中危和高危组。低危组46例[9.5% （46/483）] ，中危组102例[21.1% （102/483）] ，高危组335例[69.4% （335/483）] 。低危组采用手术+观察或手术+低强度化疗4~6个疗程的治疗方案；中危组采用手术+中等强度化疗6~8个疗程+放疗（按需实施）的治疗方案；高危组2013年前采用“环磷酰胺、长春新碱、吡柔比星”与“顺铂、依托泊苷”方案交替化疗8个疗程+手术+自体造血干细胞移植（autologous hematopoietic stem cell transplantation，ASCT）（按需实施）+放疗+生物治疗（按需实施）+异维甲酸维持治疗1年的治疗方案；2013年后采用“环磷酰胺、长春新碱、吡柔比星”与“依托泊苷、异环磷酰胺、顺铂”方案交替化疗8个疗程+手术+放疗+生物治疗（按需实施）+口服化疗药物维持治疗1年的治疗方案。复发患儿采用再次手术、化疗或放疗等挽救治疗。结果:全组322例行N-MYC基因检测，N-MYC基因扩增阳性率为22.4% （72/322），高危组N-MYC基因扩增阳性率为33.8%（72/213）。高危患儿行ASCT仅15例，占4.5%（15/335 ）。中位随访时间为38.1个月，范围在2.5~208.0个月。低危组3年无事件生存率（event free survival，EFS）和总生存率（overall survival，OS）分别为（86.5±5.1）%和100%，中危组为（79.1±4.3）%和（89.2±3.3）%，高危组为（30.6±2.7）%和（60.3±2.9）%。335例高危组单因素和多因素生存分析显示，临床分期4期、单纯化疗和（或）腹部原发病灶是影响EFS和OS的独立不良预后因素（n P均<0.05）。N-MYC基因扩增阳性和阴性的高危患儿3年EFS为（27.4±6.3）%和（36.7±4.4）%，组间比较差异有统计学意义（n P=0.049）。N-MYC基因扩增阳性的4期高危患儿3年EFS为（18.7±6.7）%，N-MYC基因扩增阳性的3期和4S期高危患儿，3年EFS为（49.4±13.1）%，组间比较差异有统计学意义（n P=0.009）。未行ASCT治疗的完全缓解或部分缓解的高危患儿，口服异维甲酸维持治疗，3年EFS为（28.0±5.1）%，而口服化疗药物维持治疗，3年EFS为（42.1±5.1）%，组间比较差异有统计学意义（n P=0.019）。采用化疗+手术+放疗治疗模式的高危患儿，3年EFS为37.1 %；采用化疗+手术治疗模式的高危患儿，3年EFS为19.0%；单纯化疗的高危患儿，3年EFS为7.7%，组间比较差异有统计学意义（n P<0.001）。2013年前后高危组3年EFS为（21.5±4.1）%和（34.9±3.6）%，组间比较差异有统计学意义（n P=0.004）；3年OS为（47.7±4.9）%和（66.7±3.6）%，组间比较差异有统计学意义（n P<0.001 ）。n 结论:采用危险因素分层治疗低危和中危NB患儿生存率高，高危患儿预后仍差，还需要探索新的治疗方式。复发患儿挽救治疗仍可有生存获益。“,”Objective:To evaluate the results of neuroblastoma (NB) based upon risk-adapted therapy.Methods:From September 2002 to December 2018, clinical data were reviewed for 483 newly diagnosed NB patients aged ≤18 years based on risk-adapted therapy. They were stratified into low, intermediate and high-risk groups by age, stage, histological category and MYCN status. There were 290 males and 193 females with a median diagnostic age of 3.5 years (7 days to 18 years). The stages were 1 (n=19) , 2 (n=25) , 3 (n=95) , 4 (n=334) and 4S (n=10). Surgery alone or surgery plus low intensive chemotherapy for low-risk group (n=46, 9.5%) ; Surgery plus moderate intensive chemotherapy with or without radiotherapy for intermediate-risk group (n=102, 21.1%) ; For high-risk group (n=335, 69.4%) , before 2013, the treatment strategies included 8 cycles of alternating chemotherapy of cyclophosphamide (CTX) + vincristine (VCR) + pirarubicin (THP) and cisplatin (DDP) + etoposide (VP16) , surgery, with or without autologous hematopoietic stem cell transplantation (ASCT) , radiotherapy, with or without biotherapy and isotretinoin maintenance therapy for 1 year; after 2013, 8 cycles of alternating chemotherapy of CTX + VCR + THP and VP16 + ifosfamide + DDP protocol, surgery, radiotherapy, with or without biological therapy and oral maintenance chemotherapy drugs for 1 year. Recurrent patients received salvage therapy.Results:MYCN amplification was 22.4 % (72/322) in all groups and 33.8%(72/213) in high-risk group. ASCT was performed for only 15 cases. During a median follow-up period of 38(2.5-208) months, 3-year event-free survival (EFS) and overall survival (OS) were (86.5±5.1) % and 100% for low-risk group ; (79.1±4.3)% and (89.2±3.3) % for intermediate-risk group ; (30.6±2.7)% and (60.3±2.9)% for high-risk group respectively. Univariate survival analysis of 335 high-risk patients indicated that stage 4 and chemotherapy alone were poor prognostic factors for EFS/OS. Multivariate survival analysis showed that stage 4 and chemotherapy alone were independent adverse prognostic factors for EFS in high-risk NB patients while stage 4, chemotherapy alone and primary abdominal lesions were independent adverse prognostic factors for OS in high-risk NB patients. The 3-year EFS for MYCN positive high-risk patients was (27.4±6.3) % and for MYCN negative high-risk patients (36.7±4.4) % and the inter-group difference was statistically significant (n P=0.049). The 3-year EFS for MYCN positive high-risk patients with stage 4 was (18.7±6.7) % and for MYCN positive high-risk patients with stage 3/4S was (49.4±13.1) % and the inter-group difference was statistically significant (n P=0.009). In high-risk complete/partial remission patients without ASCT, 3-year EFS of oral isotretinoin maintenance therapy was (28.0±5.1)% while 3- year EFS of oral chemotherapy maintenance therapy was (42.1±5.1)% and the inter-group difference was statistically significant (n P=0.019). In high-risk patients, 3-year EFS for the therapeutic model of chemotherapy + surgery + radiotherapy was 37.1% , 19.0% for chemotherapy + surgery and 7.7% for chemotherapy alone. And the inter-group differences were statistically significant (n P<0.001). The 3-year EFS in high-risk group was (21.5±4.1 ) % before 2013 and (34.9±3.6) % after 2013. And the inter-group difference was statistically significant (n P=0.004) ; 3- year OS in high-risk group was (47.7±4.9)% before 2013 and (66.7±3.6) % after 2013. And the inter-group difference was statistically significant (n P<0.001).n Conclusions:NB may be stratified into low, intermediate and high-risk groups based upon age, stage, histological category and MYCN status. For risk-adapted therapy, low and intermediate groups have better survival. High-risk patients have poor survival and new therapy should be explored. Salvage therapy for recurrent NB offers a survival benefit.