伴胰腺浸润的神经母细胞瘤患儿临床特征及预后分析

摘要

目的 总结伴胰腺浸润的神经母细胞瘤(NB)患儿的临床资料及特点,分析伴胰腺浸润神经母细胞瘤(NB)的临床特征及其与预后的关系.方法 回顾性分析2012年7月至2016年12月在首都医科大学附属北京儿童医院血液肿瘤中心诊治的NB患儿,随访至2017年3月31日.入组患儿的诊断标准、国际神经母细胞瘤临床分期(INSS分期)、治疗和疗效评估均根据首都医科大学附属北京儿童医院NB方案(BCH-NB-2007方案).根据危险度分组标准将患几分为低危(LR)组、中危(MR)组和高危(HR)组,进行分层治疗.回顾性总结和分析指标包括初诊时原发瘤灶和转移瘤灶部位、肿瘤标志物、临床分期、分组、影像学检查以及治疗过程.结果 1.伴胰腺浸润NB患儿一般临床特征:共50例患儿入组,男23例,女27例;中位年龄33个月(7～ 129个月),其中年龄≤18个月10例,＞18个月40例.INSS-Ⅲ期3例,INSS-Ⅳ期47例.LR 2例,MR 3例,HR 45例.主要症状包括发热28例,腹部包块27例,腹痛14例,肢体疼痛9例,呕吐5例,腹泻4例,黄疸1例.原发瘤灶位于腹膜后肾上腺区49例,盆腔1例.肿瘤直径≥10 cm 32例.2.肿瘤标志物和影像学检查特征:50例患儿血清乳酸脱氢酶(LDH)中位值669 U/L(263～6 762 U/L),其中19例＞1 000 U/L.80％的患儿神经元特异性烯醇化酶(neuron-specific enolase,NSE) ＞0.15 ng/L.9例初诊时血清淀粉酶(amylase,AMY)升高,7例脂肪酶(lipase,LPS)升高,AMY和LPS同时升高5例.初诊肿瘤原发部位B超提示82.0％(41/50例)胰腺浸润,腹部增强CT示91.7％(44/48例)胰腺浸润,腹部增强MRI示100.0％(14/14例)胰腺浸润,18氟-脱氧葡萄糖-PET/CT (18F-FDG-PET/CT)提示41.3％(19/46例)NB胰腺浸润.以上4项影像学检查比较显示:1项阳性7例,占14.0％;2项阳性26例,占52.0％;3项阳性15例,占30.0％;4项阳性2例,占4.0％.3.治疗结果:50例患儿中2例LR组,INSS-Ⅲ,1例完全缓解(CR),另1例维持治疗中,病情稳定.3例MR组INSS-Ⅳ,完全切除瘤灶,1例在维持治疗期间出现颅内转移死亡,另2例处于维持治疗中,目前已达CR.45例HR组中位随访时间15个月(4～53个月),16例患儿(35.6％)出现事件,其中3例停化疗后2、3、18个月复发,12例治疗中出现肿瘤进展,1例并发重症感染,临终放弃.Kaplan-Meier法对50例患儿进行生存率分析,预计全部患儿3年的无事件生存(EFS)率为22.1％,3年总生存(OS)率为38.5％.结论 90％伴胰腺浸润的NB为Ⅳ期的高危组患儿,且大多数原发瘤灶位于腹膜后区域.病初临床表现隐匿,且无特异性,需结合影像学检查进一步判断胰腺转移情况.腹部增强MRI对胰腺转移病灶的敏感性和特异性较高,可作为早期诊断的依据.出现胰腺浸润的NB患儿总体预后较差,预计3年EFS率为22.1％,3年OS率为38.5％.%Objective To summarize the clinical data and characteristics of neuroblastoma (NB) with pancreatic infiltration and to assess the clinical features and the prognosis of NB.Methods According to NB protocol at Beijing Children's Hospital,Capital Medical University(BCH-NB-2007),based on Hong Kong NB protocol,the patients were divided into 3 groups of low-risk (LR) group,medium risk (MR) group and high-risk (HR) group.All children were followed up till March 31,2017.Diagnosis of pancreatic infiltration of NB was made by abdominal enhancement of CT,enhanced magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose-positron emission tomography-computed tomography(18F-FDG-PET/CT),any of which could suggest NB pancreatic infiltration or postoperative pathology prompted NB to infiltrate the pancreas.Retrospective summary and analysis of indicators were performed,which included the initial diagnosis of primary tumor and metastatic tumor site,tumor markers,clinical stage,risk group,imaging features and treatment.Results (1) Totally 50 eligible patients were included:27 females,23 males,median age of 33 months (7-129 months),10 cases ≤ 18 months,40 cases ＞ 18 months;3 cases were of International Neuroblastoma Staging System(INSS)-Ⅲ,47 cases of INSS-Ⅳ;2 caes of LR,3 cases of MR,45 cases of HR;28 cases had a fever,27 cases with abdominal mass,14 cases with abdominal pain,9 cases with limb pain,5 cases with vomiting,4 cases with diarrhea,and 1 case with jaundice.Forty-nine cases of primary tumor were located in the retroperitoneal adrenal gland,and 1 case in the pelvic cavity.Thirty-two cases had tumor diameter≥ 10 cm.(2)Tumor markers and imaging features:the median serum lactate dehydrogenase (LDH) value in 50 cases was 669 U/L (263-6 762 U/L),of them 19 cases ＞ 1 000 U/L.A total of 80％ cases had neuron specific enolase (NSE) ＞ 0.15 ng/L.Nine cases had elevated amylase (AMY),and 7 cases had elevated lippase (LPS),and all the levels were elevated in 5 cases.A total of 41 cases had pancreas infiltration by abdominal ultrasound,44 cases had pancreas infiltration by abdominal enhancement computed tomography (CT),100％ (14/14 cases)of pancreas infiltration was confirmed by abdominal reconstruction enhancement nuclear imaging MRI,and NB pancreas infiltration was proved in 41.3％ (19/46 cases) by 18F-FDG-PET/CT.Comparison of the above 4 imaging studies:one imaging examination index was positive in 7 cases,accounting for 14.0％,2 positive in 26 cases,accounting for 52.0％,3 positive in 15 cases,accounting for 30.0％,and 4 positive in 2 cases,accounting for 4.0％.(3) Treatment outcomes:totally 50 cases received treatment,including 2 cases of LR,all cases were of INSS-Ⅲ,and 1 case with complete remission (CR).Three cases of MR belonging to INSS-Ⅳ had complete resection of the tumor,1 case had recurrence and died,and the other two were stable.Forty-five cases with HR,median follow-up lasting for 15 (4-53) months,16 cases had occurrence (35.6％),3 cases were relapsed after stopping treatment for 2,3,18 months,respectively;tumor progressed in 12 patients during treatment,and 1 case got severe intracranial infection and gave up treatment before death.Kaplan-Meier analysis showed the expected 3-year event free survival(EFS) rate was 22.1％,and 3-year overall survival(OS) rate was 38.5％.Conclusions Preliminary results show that 90％ with pancreatic infiltration of NB belong to Ⅳ HR group of children,and almost primary tumor is almost located in the retroperitoneal ragion.NB with pancreatic infiltration clinical manifestations is hidden and nonspecific.More than half of the children have no obvious abdominal pain or vomiting,and so imaging examination is needed to determine the situation of pancreatic metastasis further.Abdominal reconstruction enhancement MRI has a high sensitivity and specificity for pancreatic metastatic lesions,which can be used as the basis for early diagnosis.The overall prognosis is poor.The expected 3-year EFS rate can be 22.1％,3-year OS rate was 38.5％.