儿童恶性肿瘤相关性间质性肺病5年生存影响因素分析

Analysis of factors affecting 5-year survival in children with malignant tumor-related interstitial lung disease

背景恶性肿瘤相关性间质性肺病(MT-ILD)的发病率低,但6个月生存率中位数仅为58.1%,目前儿童MT-ILD(MT-chILD)的报道不多。目的探讨MT-chILD的临床特征、影像学表现、病理特点、疾病负担和预后,为早期识别及诊断治疗提供临床依据。设计回顾性队列研究。方法回顾性纳入2014年2月至2021年2月复旦大学附属儿科医院(我院)MDT团队确诊的MT-chILD,采集临床表现、影像学表现、病理检查报告、治疗、疾病负担和随访信息。主要结局指标MT-chILD 5年生存影响因素。结果15例MT-chILD均首诊于我院呼吸科,首发症状:咳嗽或气促13例,伴发热9例,伴咯血丝痰4例,胸痛或胸闷4例,伴乏力、腹痛、腹泻各1例;9例肿瘤标记物正常;肺部影像示两肺弥漫性结节影、囊状影、双肺渗出伴多发条索状影、双肺透亮度不均伴磨玻璃影。MT-chILD基础病理分型为:朗格罕斯组织细胞增生症(LCH)5例,神经母细胞瘤4例,肺黏液腺癌、肺乳头状腺癌、T淋巴母细胞瘤、腺泡横纹肌肉瘤、肺纤维母细胞瘤、腺泡软组织肉瘤各1例。起病至确诊的中位时间为6.9个月,平均住院6次,9例被误诊为感染,确诊当次的平均住院费用7.0万元人民币。10例确诊后接受化疗,5例放弃治疗,确诊后的中位生存时间14个月,放弃治疗(OR=1.754,95%CI:1.535~2.519)、营养不良(OR=1.231,95%CI:1.020~1.428)、合并真菌感染(OR=1.232,95%CI:1.018~1.492)、合并纵隔气肿(OR=1.298,95%CI:1.002~1.681)、合并脓毒症(OR=1.251,95%CI:1.035~1.787)为MT-chILD患儿5年生存的独立危险因素,接受化疗(OR=0.658,95%CI:0.525~0.993)为MT-chILD患儿5年生存的保护因素。结论MT-chILD首发以非特异性呼吸道症状和体征为表现,实验室指标不特异,导致误诊率高,医疗费用高,影像学和活检病理对明确诊断有重要价值,不放弃治疗、接受化疗,防止合并症对远期生存有意义。

Background While the incidence of malignant tumor-associated interstitial lung disease(MT-ILD)is low,the median survival rate at 6 months is only 58.1%and few studies on MT-ILD in children(MT-chILD)has been previously reported.Objective To explore clinical features,imaging,pathological features,disease burden and prognosis of MT-chILD,thus providing clinical evidence for early identification,diagnosis and treatment of the MT-chILD.Design Retrospective cohort study.Methods Cases of MT-chILD diagnosed by the MDT team in Children's Hospital of Fudan University from February 2014 to February 2021 were retrospectively included.Clinical manifestations,imaging,pathology,treatment,disease burden and follow-up information were collected.Main outcome measures Factors affecting the 5-year survival of MT-chILD.Results Fifteen cases were firstly diagnosed in our respiratory department with the following symptoms:cough or shortness of breath(13 cases),fever(9 cases),hemoptysis(4 cases),chest pain or chest tightness(4 cases),fatigue(1 case),abdominal pain(1 case),and diarrhea(1 case).There were 9 cases with normal tumor markers.Lung images showed diffuse nodules,cystic shadows in both lungs,exudation in both lungs with multi-window cord shadows,and uneven brightness of both lungs with ground-glass opacity.The basic pathological classification of MT-chILD were 5 cases of Langerhans histiocytosis(LCH),4 cases of neuroblastoma,and 1 case of pulmonary mucinous adenocarcinoma,pulmonary papillary adenocarcinoma,T lymphoblastoma,rhabdomyosarcoma,pulmonary fibroblastoma or acinar soft tissue sarcoma,respectively.The median time from onset to diagnosis of MT-chILD was 6.9 months,with 9 cases(60%)misdiagnosed as infections.The average hospitalization cost was RMB 70,000.While 10 cases received chemotherapy after diagnosis,5 patients gave up treatment.The median survival time after diagnosis was 14 months.There were several independent risk factors affecting the 5-year survival rate of MT-chILD:treatment abandonment(OR=1.754,95%CI:1.535~2.519),malnutrition(OR=1.231,95%CI:1.020~1.428),combined with fungal infection(OR=1.232,95%CI:1.018~1.492),combined with mediastinal emphysema(OR=1.298,95%CI:1.002~1.681),combined with sepsis(OR=1.251,95%CI:1.035~1.787).Chemotherapy(OR=0.658,95%CI:0.525~0.993)was a protective factor for 5-year survival of MT-chILD.Conclusion The onset of MT-chILD presents atypical respiratory symptoms and signs,non-specific laboratory indicators,leading to high misdiagnosis rates and high medical costs.Lung imaging and biopsy pathology are important for the final diagnosis.Active treatment without giving up,receiving chemotherapy and preventing complications are beneficial to long-term survival.