儿童室管膜瘤术后辅助放疗的疗效及预后影响因素分析

Clinical efficacy and prognostic factors of postoperative adjuvant radiotherapy for pediatric ependymoma

目的分析初治儿童室管膜瘤的临床病理学特征、治疗情况及预后。方法回顾性分析2001—2021年上海交通大学医学院附属新华医院收治的儿童室管膜瘤患者127例(确诊年龄0~16岁), 其中女性53例, 男性74例。采用Kaplan-Meier法统计患儿的局部控制(LC)率、无事件生存(EFS)率和总生存(OS)率。采用Cox比例风险回归模型分析临床病理学因素与预后的关系, 以及治疗方式对预后的影响。结果中位随访时间为29(3~251)个月。患儿3年OS率为89.5%, 3年EFS率为71.5%。术后残留患儿辅助放疗后3年LC率可达78.3%, 3年EFS率可达65.8%, 3年OS率可达85.7%。确诊年龄<3岁者43例, ≥3岁者84例, 手术至放疗开始的中位时间分别为91、35.5 d(P<0.001)。<3岁的患儿中, 术后70 d以内开始放疗者中位EFS为90个月, 超过70 d者为43个月(P=0.053)。依据第5版世界卫生组织中枢神经系统肿瘤分类(WHO CNS5)标准, 分子诊断分类为后颅窝室管膜瘤A组(PFA组)者39例, OS、EFS均显著低于其他患儿(PFA组∶其他组的3年OS率为69.2%∶94.6%, P<0.001;3年EFS率为46.9%∶79.1%, P<0.001)。PFA组中有12例患儿接受术后辅助化疗, 14例未接受化疗, 13例化疗情况不详, 其中化疗组与未化疗组之间OS、EFS的差异均无统计学意义(P=0.260、P=0.730)。单因素Cox分析显示, 肿瘤部位、WHO CNS5分子诊断分类与EFS显著相关, WHO CNS5分子诊断分类与OS显著相关。多因素Cox分析显示, 肿瘤位于后颅窝是EFS的独立危险因素(HR=2.72, 95%CI为1.10~6.71, P=0.03)。结论手术联合放疗可使初治儿童室管膜瘤患儿获得较好的生存, 术后肿瘤残留者接受辅助放疗后仍可获得较好的LC和生存。延迟放疗对于初诊年龄<3岁的患儿有带来较差预后的趋势。PFA组与其他患儿相比预后不良。肿瘤部位为后颅窝是儿童室管膜瘤的独立危险因素。

Objective To investigate the clinic opathological features,treatment and prognosis of children newly diagnosed with ependymoma.Methods Clinical data of 127 pediatric ependymoma(EPN)patients(0-16 years old)treated with tumor resection and postoperative radiotherapy at Xinhua Hospital Affiliated to Shanghai Jiao Tong University between 2001 and 2021 were retrospectively analyzed.Among them,53 children were female and 74 were male.Local control(LR),event-free survival(EFS)and overall survival(OS)rates were analyzed by Kaplan-Meier method.The relationship between clinic opathological factors and clinical prognosis,and the effect of treatment on clinical prognosis of patients were analyzed by Cox proportional hazards model.Results At a median follow-up time of 29 months(3-251 months),the 3-year OS and EFS rates were 89.5%and 71.5%,respectively.For patients undergoing incomplete resection followed by postoperative adjuvant radiotherapy,the 3-year LR,OS and EFS rates were 78.3%,65.8%and 85.7%,respectively.A total of 43 children were aged<3 years old when diagnosed and 84 aged≥3 years old.The interval time between surgery and radiotherapy in children aged<3 years old was 91 d,and 35.5 d in those aged≥3 years old(P<0.001).For patients<3 years old,the median EFS was 90 months when initiating radiotherapy within≤70 d after surgery,compared to 43 months for those who initiated radiotherapy at>70 d after surgery(P=0.053).According to fifth edition of the WHO classification of tumors of the central nervous system(WHO CNS5),39 children were classified as posterior fossa ependymoma group A(PFA group).The OS and EFS rates in the PFA group were significantly less than those in other groups(3-year OS rate were 69.2%vs.94.6%,P<0.001;3-year EFS rate were 46.9%vs.79.1%,P<0.001).In the PFA group,12 patients received postoperative adjuvant chemotherapy,14 did not receive chemotherapy,and whether chemotherapy was given was unknown in 13 cases.No significant differences were observed in OS and EFS between patients treated with and without chemotherapy(P=0.260,P=0.730).Univariate Cox analysis showed that tumor location and WHO CNS5 molecular classification were significantly associated with EFS,and WHO CNS5 molecular classification was significantly correlated with OS.Multivariate Cox analysis showed that tumor location in the posterior fossa was an independent risk factor for EFS(HR=2.72,95%CI=1.1~6.71,P=0.03).Conclusions Patients newly diagnosed with pediatric ependymoma can obtain favorable survival after surgery combined with postoperative adjuvant radiotherapy.Patients with residual tumors can achieve favorable LC and survival after postoperative adjuvant radiotherapy.Delaying of radiotherapy tends to lead to poor survival for patients aged<3 years old when diagnosed.Children in the PFA group obtain worse prognosis compared to their counterparts in other groups.The tumor location in the posterior fossa is an independent risk factor for pediatric ependymoma.