伴肺或胸膜受累的神经母细胞瘤患儿临床分析

Clinical analysis of neuroblastoma with pulmonary or pleural involvement

目的总结伴肺或胸膜受累的神经母细胞瘤(NB)患儿的临床特征,探讨其与患儿近期疗效的相关性,为指导临床诊疗提供依据.方法回顾性分析首都医科大学附属北京儿童医院血液肿瘤中心2007年12月至2017年12月收治的36例首次确诊为NB且伴肺或胸膜侵犯患儿的临床资料,包括性别、发病年龄、原发灶位置、危险度、神经元特异性烯醇化酶(NSE)、N-myc基因扩增情况及临床转归等资料.入组患儿的诊断标准、治疗方案和疗效判定标准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)制定,疾病分期依据国际NB临床分期(INSS分期)进行,依据BCH-NB危险度分组标准进行分层治疗.随访时间至2018年10月31日.结果1.入组患儿的一般临床特征:入组36例患儿,占总同期NB住院患儿的5.99%(36/601例);患儿均<10岁,18个月以下10例,中位年龄29.5个月(9~105个月);男20例,女16例;原发瘤灶位于腹膜后19例(52.78%),肾上腺9例(25.00%),纵隔8例(22.22%).危险度分组:高危组29例,中危组6例,低危组1例.主要症状以疼痛起病8例,发热、局部肿物各6例,腹部包块4例,纵隔占位、面色苍白各3例,皮下结节、腹胀各2例,下肢肿胀、腹泻各1例,其中有呼吸系统首发症状16例,占44.4%.2.实验室检查:36例患儿初诊时97.22%(35例)NSE≥25μg/L,其中11例患儿NSE>370μg/L,血清乳酸脱氢酶(LDH)≥717.5 U/L者25例(69.44%),伴N-myc基因扩增患儿10例.3.影像学检查:初诊时胸部/腹部CT示胸膜或肺受累75.75%(24/33例),正电子发射计算机断层显像(PET-CT)示胸膜或肺受累81.82%(27/33例),B超示胸膜或肺受累41.67%(5/12例),3项影像学检查比较示:1项阳性16例,2项阳性16例,3项均阳性4例.4.胸膜与肺侵犯临床特点比较:30例伴胸膜受累的患儿中以呼吸道症状起病6例,6例仅肺受累的患儿以呼吸道症状起病3例,4例伴胸膜和肺受累的患儿初诊时均无呼吸系统症状.5.治疗与转归:36例患儿中2例因确诊后病情危重死亡,5例确诊后未完成规律治疗回当地或外院治疗,29例患儿接受规律分层治疗.低危组患儿1例,INSS-Ⅳ期,完全缓解(CR);中危组患儿4例,INSS-Ⅳ期,CR 2例,部分缓解(PR)1例,进展1例,停化疗后13个月后出现新瘤灶;高危组患儿24例,7例(29.17%)患儿发生事件,1例术后评估时出现进展,4例患几分别于停化疗1.5、2.0、3.0、6.0个月出现进展,2例分别于停化疗11、17个月复发.Kaplan-Merier分析所有患儿总生存率(OS)为41.4%,预计3年无事件生存率为32.9%.结论儿童NB伴肺或胸膜受累的患儿无特异性的呼吸系统症状,伴肺或胸膜受累的NB多为Ⅳ期的高危组患儿,胸部CT敏感度高,可作为临床常规筛查手段,N-myc基因状态与患儿的生存预后相关.

Objective To analyze the clinical characteristics of children with neuroblastoma(NB)complicated with lung or pleural metastasis,further to explore the correlation between characteristics and short-term outcome of NB,so as to provide a basis for clinical diagnosis and treatment.Methods A retrospective analysis was performed concerning the age of onset,clinical features,treatment and outcome of 36 patients with NB who were admitted at Blood Tumor Center,Beijing Children's Hospital of Capital Medical University from December 2007 to December 2017.The diagnostic criteria,therapeutic regimen and therapeutic efficacy criteria of the enrolled children were all based on the NB protocol of Beijing Children's Hospital of Capital Medical University(BCH-NB-2007),the clinical stage was based on international clinical stage of neuroblastoma(INSS stage),and stratified treatment was conducted according to the BCH-NB risk grouping standard.The follow-up period lasted till October 31,2018.Results(1)The common clinical features of grouped children:36 patients were selected into the group,accounted for 5.99%(36/601 cases)in total hospitalized NB children,they were less than 10 years old,10 cases under 18 months,and the median age was 29.5 months(9-105 months);20 cases were male,and 16 cases were female;the primary tumor was located in the retroperitoneal site in 19 cases,accounting for 52.78%,9 cases in adrenal site,accounting for 25.00%,and 8 cases in mediastinal site,accounting for 22.22%.Risk groups:29 cases were in high-risk group,6 cases were in medium-risk group and 1 case was in low-risk group.The main symptoms were of pain onset in 8 cases,fever in 6 cases,local mass in 6 cases,abdominal mass in 4 cases,mediastinal mass in 3 cases,paleness in 3 cases,subcutaneous nodules in 2 cases,abdominal distension in 2 cases,lower limb swelling in 1 case,and diarrhea in 1 case.Among them,16 cases had respiratory system symptoms first,accounting for 44.4%.(2)Laboratory examination:there were 35 patients of neuron-specific enolase(NSE)≥25μg/L on the initial diagnosis,of which 11 cases were more than 370μg/L,the value of serum lactate dehydrogenase(LDH)≥717.5 U/L in 25 patients,accounting for 69.44%,and 10 cases were accompanied by N-myc gene amplification.(3)Imaging examination:on the first diagnosis,chest/abdomen CT showed 75.75%(24/33 cases)of pleural or lung involvement,PET-CT showed 81.8%(27/33 cases)of pleural or lung involvement,B-ultrasound showed 41.67%(5/12 cases)of pleural or lung involvement;3 imaging examinations showed:1 positive in 16 cases,2 positive in 16 cases,and 3 positive in 4 cases.(4)Comparison of clinical features of pleural and pulmonary involvement:among the 30 children with pleural involvement,6 cases had respiratory symptoms,3 cases had respiratory symptoms on the 6 cases with pulmonary involvement only,and 4 cases with pleural and pulmonary involvement had no respiratory symptoms at first diagnosis.(5)Treatment and outcome:2 cases died because of critical condition after diagnosis,5 cases didn't receive the law treatment,29 cases accepted law stratification treatment,among them,1 case in low risk group,INSS-Ⅳ,alleviate current(CR);4 cases in the moderate group,INSS-Ⅳ,CR in 2 cases,partial response(PR)in 1 case,progress in 1 case,new tumor foci occurring after chemotherapy discontinuation for 13 months.Twenty-four cases were in the high-risk group,event occurred in 7 cases(29.17%)of them,1 case had progression by postoperative evaluation,4 cases of progression at 1.5,2.0,3.0 and 6.0 months after cessation of chemotherapy,and 2 cases had recurrence at 11 and 17 months after cessation of chemotherapy.Overall survival rate(OS)was 41.4%for all children analyzed by Kaplan-Merier,and 32.9%of them were predicted to have 3-year event-free survival.Conclusions Children with pulmonary or pleural metastasis of neuroblastoma have no specific respiratory symptoms.CT scan might be a useful method for diagnosing the groupⅣchildren with pulmonary or pleural metastasis of neuroblastoma.Moreover,there seemed to be no significant correlation between the N-myc gene expression and survival prognosis of these children.