儿童髓母细胞瘤的预后因素和生存分析

Analysis of prognostic factors and survival status of children with medulloblastoma

目的回顾性分析儿童髓母细胞瘤(MB)的预后影响因素和生存状况。方法2011年2月至2017年12月在首都医科大学附属北京世纪坛医院儿科接受治疗的MB患儿共224例,采用Kaplan-Meier法计算总体生存(OS)率和无进展生存(PFS)率,采用Log-rank比较不同组间的差异性,采用COX回归模型研究影响生存的多种因素。结果截至2018年12月30日,224例患儿中位生存时间为4.1年,存活率为74.6%,完全缓解率为60.3%,复发率为31.7%,5年PFS率和OS率分别为(58.2±3.6)%和(72.5±3.3)%。高危、术后转移、年龄<3岁、脑脊液肿瘤细胞阳性患儿的5年OS率分别为(54.8±5.3)%、(57.7±5.9)%、(41.6±8.7)%和(53.0±7.3)%;MB大细胞/间变型患儿5年OS率为(35.3±13.6)%;MB 3型患儿5年OS率仅为(25.0±13.0)%。标危组、术后无转移、非大细胞/间变型、年龄≥3岁、脑脊液肿瘤细胞阴性患儿预后较好,5年OS率达70.0%以上,分别为(87.5±3.5)%、(80.3±3.7)%、(70.6±5.5)%、(78.3±3.3)%和(78.4±3.5)%。WNT分子亚型患儿预后最好,5年OS率为100.0%,而SHH分子亚型患儿5年OS率逊于4型患儿,差异有统计学意义[(64.8±5.8)%比(83.5±3.8)%,χ^2=5.417,P=0.015]。年龄和脑脊液肿瘤细胞是影响患儿PFS和OS的独立危险因素(PFS:Wald=8.485、11.702,P=0.004、0.001;OS:Wald=16.274、7.191,P=0.000、0.007)。结论3岁及3岁以上MB患儿的疗效已达较高水平,年龄和脑脊液存在肿瘤细胞是影响患儿OS率的独立危险因素,MB大细胞/间变型、脑脊液肿瘤细胞阳性、MB 3型和<3岁患儿的预后较差,需给予强化治疗。

Objective To investigate the prognostic factors and survival status of children with medulloblastoma(MB)by using retrospective analysis.Methods From February 2011 to December 2017,224 children with newly-diagnosed MB were enrolled in this study,which was carried out at Department of Pediatrics,Beijing Shijitan Hospital,Capital Medical University.The overall survival(OS)rate and progression-free survival(PFS)rate were calcula-ted by using Kaplan-Meier method,the difference between 2 groups was tested by Log-rank method,and prognostic factors were analyzed by COX regression.Results Until December 30,2018,the median survival time of all these 224 children was 4.1 years,the survival rate was 74.6%,complete response(CR)rate was 60.3%,and the relapse rate was 1.7%.The 5-year PFS rate and 5-year OS rate of all patients were(58.2±3.6)%and(72.5±3.3)%,respectively.Survival rates of children in the high-risk group,with metastatic disease,aged<3 years,and with positive tumor cells in the cerebrospinal fluid(CSF)were very low.The 5-year OS rates were(54.8±5.3)%,(57.7±5.9)%,(41.6±8.7)%,and(53.0±7.3)%,respectively.Compared to others,the children with MB large-cell/anaplastic histology[5-year OS rate was(35.3±13.6)%]and MB group 3 subtype[3-year OS rate was(25.0±13.0)%]lived a miserable life.Meanwhile,the children in the stand-risk group,without metastatic disease,no large-cell/anaplastic histology,age older than 3 years,and with tumor cell negative in CSF,lived a better life.The 5-year OS rates were(87.5±3.5)%,(80.3±3.7)%,(70.6±5.5)%,(78.3±3.3)%,and(78.4±3.5)%,respectively,and all of them were over 70.0%.No WNT tumors progressed or relapsed,and 5-year OS rate was 100.0%.The survival status of SHH subgroup was inferior to that of group 4 subtype[(64.8±5.8)%vs.(83.5±3.8)%,χ^2=5.417,P=0.015].With COX analysis,age and tumor cells in CSF at the time of diagnosis were independent risk factors for OS and PFS of MB(PFS:Wald=8.485,P=0.004;Wald=11.702,P=0.001;OS:Wald=16.274,P=0.000;Wald=7.191,P=0.007).Conclusions Survival of children with MB more than 3 years old has been reached a perfectly high level.Age and tumor cells in CSF are independent risk factors for the OS and PFS.However,the prognosis of large-cell/anaplastic histology,malignancy cell positive in CSF,group 3 and children under 3 years old,is still poor,and intensive treatment is needed urgently for those patients.