SHH型髓母细胞瘤患儿临床特点及预后因素分析

Clinical features and prognostic factors of SHH medulloblastoma in children

目的回顾性分析SHH(sonic hedgehog)型髓母细胞瘤(medulloblastoma,MB)患儿的临床特点,探讨其预后影响因素。方法回顾性分析2015年6月至2019年10月儿科收治的SHH型MB患儿的临床资料。通过Kaplan-Meier法计算总体生存率及无事件生存率,组间生存率比较采用log-rank检验,采用Cox比例风险回归模型进行多因素分析。结果共纳入99例SHH型MB患儿。中位年龄6.0(3.3~6.0)岁,≥3岁75例,<3岁24例;男62例,女37例;M_(0)66例,M_(+)33例;手术全切72例,近全切27例。病理分型以促纤维/结节型(DMB)为主,肿瘤起源部位以中线部位(四脑室、后颅窝、小脑蚓部)多见,2例存在SUFU胚系变异。中位随访时间3.2(2.2~4.1)年,3年EFS率(61.0±5.0)%,3年OS率(72.2±4.6)%,39例(39.4%)出现进展或复发。<3岁DMB、广泛结节型MB(MBEN)的3年OS率分别为(80.0±10.3)%、(57.1±18.7)%,其中12例M_(0)、无MYCN扩增及SUFU胚系变异者仅行化疗未放疗。Cox回归模型分析发现M^(+),存在TP53变异或MYCN、GLI2扩增,病理分型为大细胞/间变型者为影响预后的独立危险因素(P<0.05)。结论SHH型MB患儿的预后与M分期、病理分型、TP53变异、MYCN或GLI2扩增相关。病理分型为DMB及MBEN的婴幼儿无上述危险因素且无SUFU胚系变异者预后较好,可不放疗。

Objective To retrospectively analyze the clinical characteristics of sonic hedgehog(SHH)medulloblastoma(MB)in children,and to explore the prognostic factors.Methods The clinical data of SHH MB children from June 2015 to October 2019 were retrospectively analyzed.The overall survival rate and event-free survival rate were calculated by the Kaplan-Meier method.The survival rate between groups was compared by log-rank test.Cox proportional hazards regression model was used for multivariate analysis.Results A total of 99 children(62 boys and 37 girls)with SHH MB were enrolled.The median age was 6.0(3.3-6.0)years,of which 75 children were≥3 years old and 24 children were<3 years old.There were 66 cases of M_(0) stage and 33 cases of M^(+) stage.Total resection was performed in 72 children and near total resection in 27 children.The main pathological type was desmoplastic/nodular MB(DMB).Tumor origin sites were commoner in midline sites(fourth ventricle,posterior fossa,cerebellar vermis).SUFU germline variation was found in two children.The median follow-up time was 3.2(2.2-4.1)years,the 3-year EFS rate was(61.0±5.0)%,the 3-year OS rate was(72.2±4.6)%,and 39 children(39.4%)had progression or recurrence.The 3-year OS rates of DMB and MB with extensive nodularity(MBEN)<3 years old are(80.0±10.3)%and(57.1±18.7)%,respectively.Among them,12 patients with M_(0) stage,without MYCN amplification and SUFU germline variation only received chemotherapy without radiotherapy.Cox regression model analysis showed that M^(+) stage,TP53 mutation or MYCN,GLI2 amplification,and pathological type of large-cell/anaplastic was an independent risk factor for the prognosis of the disease(P<0.05).Conclusions The prognosis of SHH MB children is related to M stage,pathological type,TP53 mutation,MYCN or GLI2 amplification.Infants with pathological types of DMB and MBEN without the above risk factors and SUFU germline variation have a better prognosis,so radiotherapy is not necessary.