晚期肺炎型肺癌:一项中国单中心临床-放射-病理特征回顾性研究及预后分析
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摘要
背景与目的肺炎型肺癌是一种临床和影像表现特殊的肺癌。本研究旨在总结此类肺癌的临床、影像及病理学特征,诊断手段,治疗方案及预后情况。方法肺炎型肺癌定义为:肺部计算机断层扫描(computed tomography, CT)以磨玻璃或实变影为主要表现,经组织学或细胞学明确诊断的肺癌。收集2013年1月1日-2018年8月30日期间,就诊于北京协和医院呼吸与危重症医学科的晚期肺炎型肺癌病例,回顾性分析这些患者临床资料并进行生存随访。结果共纳入46例患者,均为肺腺癌。咳嗽(41/46, 89.1%)、咳痰(35/46, 76.1%)是最常见的临床表现。胸部CT常见表现为磨玻璃影(87.0%)、实变影(84.8%)、以及多发磨玻璃结节(84.8%),多发囊样变和空洞分别为40.0%和13.0%。同侧及对侧肺转移分别见于95.3%和84.8%的病例。从出现症状到明确诊断的中位时间为214天(95%CI:129-298)。CT引导肺穿刺活检及外科肺活检的确诊率为100%,支气管镜下的支气管肺泡灌洗(BAL)联合经支气管肺活检(TBLB)的确诊率为80.9%(17/21),痰液病理学检查的确诊率为45.0%(9/20)。病理亚型,26例(26/46, 56.5%)为浸润性粘液腺癌,20例患者因缺乏足够的病理标本量而无法进一步区分亚型。38例进行了EGFR基因检测,6例(6/38, 15.8%)有突变。33例进行ALK基因检测,仅1例(1/33, 3.0%)有ALK重排。中位总生存期(overall survival, OS)为522天(95%CI:424-619)。EGFR野生型或ALK融合基因阴性的患者,化疗明显延长中位OS(HR=0.155, P=0.002,2),接受化疗者中位OS 547天(95%CI:492-602),不接受化疗者中位OS 331天(95%CI:22-919)。结论肺炎型肺癌由于其临床和影像特征与肺部感染相似而经常导致延误诊断。支气管镜下的BAL联合TBLB有相当高的确诊率。浸润性粘液腺癌为肺炎型肺癌的主要病理亚型。肺炎型肺癌EGFR突变及ALK重排发生率很低。对于无明确驱动基因的患者,应积极行化疗,延长患者生存期。
Background and objective Pneumonic-type lung carcinoma is a special type of lung cancer both clinically and radiologically. Here we present our experience on pneumonic-type lung carcinoma in an attempt to investigate the clinical, radiological and pathological features, diagnostic procedures, treatment, and prognosis of this type of tumor. Methods Pathologically confirmed lung cancer with a chest CT characterized by ground glass opacity or consolidation was defined as pneumonic-type lung carcinoma. Cases with advanced pneumonic-type lung carcinoma admitted to Peking Union Medical College Hospital(PUMCH) from January 1, 2013 to August 30, 2018 were enrolled. Retrospective analysis of clinical data and survival follow-up of these patients was conducted. Results A total of 46 cases were enrolled, all of which were adenocarcinoma. Cough(41/46, 89.1%) and expectoration(35/46, 76.1%) were the most prominent symptoms. The most frequent chest CT findings were ground glass attenuation(87.0%), patchy consolidation(84.8%), and multiple ground-glass nodules(84.8%). Multiple cystic changes(40%) and cavitation(13%) were also quite frequent. Ipsilateral and contralateral intrapulmonary metastasis were noted in 95.3% and 84.8% of cases respectively. The median duration from symptom onset to diagnosis was 214 days(95%CI: 129-298). Both surgical lung biopsy and CT-guided percutaneous lung biopsy had a diagnostic yield of 100%. Transbronchial lung biopsy(TBLB) combined with bronchoalveolar lavage(BAL) had a diagnostic yield of 80.9%(17/21). Sputum cytology had a diagnostic yield of 45%(9/20). Twenty-six cases were invasive mucinous adenocarcinoma(26/46, 56.5%) and the remainder were unable to identify pathological subtypes due to lack of adequate biopsy sample size. EGFR mutation was detected in 15.8%(6/38) of patients and ALK rearrangement was detected in 3.0%(1/33) of patients. The median overall survival for these patients was 522 d(95%CI: 424-619). In patients without EGFR mutation or ALK rearrangement, chemotherapy significantly improved survival(HR=0.155, P=0.002,2). The median overall survival was 547 d(95%CI: 492-602 d) with chemotherapy and 331 d(95%CI: 22-919) without chemotherapy. Conclusion Diagnosis of pneumonictype carcinoma is usually delayed due to clinical and radiological features mimicking pulmonary infection. TBLB combined with BAL has a quite high diagnostic yield. The most frequent histological type is invasive mucinous adenocarcinoma. The incidence of EGFR mutation or ALK rearrangement is low in pneumonic-type carcinoma. For patients without cancer driver genes, chemotherapy is recommended to improve overall survival.
Background and objective Pneumonic-type lung carcinoma is a special type of lung cancer both clinically and radiologically. Here we present our experience on pneumonic-type lung carcinoma in an attempt to investigate the clinical, radiological and pathological features, diagnostic procedures, treatment, and prognosis of this type of tumor. Methods Pathologically confirmed lung cancer with a chest CT characterized by ground glass opacity or consolidation was defined as pneumonic-type lung carcinoma. Cases with advanced pneumonic-type lung carcinoma admitted to Peking Union Medical College Hospital(PUMCH) from January 1, 2013 to August 30, 2018 were enrolled. Retrospective analysis of clinical data and survival follow-up of these patients was conducted. Results A total of 46 cases were enrolled, all of which were adenocarcinoma. Cough(41/46, 89.1%) and expectoration(35/46, 76.1%) were the most prominent symptoms. The most frequent chest CT findings were ground glass attenuation(87.0%), patchy consolidation(84.8%), and multiple ground-glass nodules(84.8%). Multiple cystic changes(40%) and cavitation(13%) were also quite frequent. Ipsilateral and contralateral intrapulmonary metastasis were noted in 95.3% and 84.8% of cases respectively. The median duration from symptom onset to diagnosis was 214 days(95%CI: 129-298). Both surgical lung biopsy and CT-guided percutaneous lung biopsy had a diagnostic yield of 100%. Transbronchial lung biopsy(TBLB) combined with bronchoalveolar lavage(BAL) had a diagnostic yield of 80.9%(17/21). Sputum cytology had a diagnostic yield of 45%(9/20). Twenty-six cases were invasive mucinous adenocarcinoma(26/46, 56.5%) and the remainder were unable to identify pathological subtypes due to lack of adequate biopsy sample size. EGFR mutation was detected in 15.8%(6/38) of patients and ALK rearrangement was detected in 3.0%(1/33) of patients. The median overall survival for these patients was 522 d(95%CI: 424-619). In patients without EGFR mutation or ALK rearrangement, chemotherapy significantly improved survival(HR=0.155, P=0.002,2). The median overall survival was 547 d(95%CI: 492-602 d) with chemotherapy and 331 d(95%CI: 22-919) without chemotherapy. Conclusion Diagnosis of pneumonictype carcinoma is usually delayed due to clinical and radiological features mimicking pulmonary infection. TBLB combined with BAL has a quite high diagnostic yield. The most frequent histological type is invasive mucinous adenocarcinoma. The incidence of EGFR mutation or ALK rearrangement is low in pneumonic-type carcinoma. For patients without cancer driver genes, chemotherapy is recommended to improve overall survival.
引文
1 Siegel RL,Miller KD,Jemal A.Cancer Statistics,2017.CA Cancer Clin,2017,67(1):7-30.doi:10.3322/caac.21387
2 Li T,Kung HJ,Mack PC,et al.Genotyping and genomic profiling of non-small-cell lung cancer:implications for current and future therapies.J Clin Oncol,2013,31(8):1039-1049.doi:10.1200/JCO.2012.45.3753
3 Travis WD,Brambilla E,Noguchi M,et al.International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.J Thorac Oncol,2011,6(2):244-285.doi:10.1097/JTO.0b013e318206a221
4 Cha YJ,Kim HR,Lee HJ,et al.Clinical course of stage IV invasive mucinous adenocarcinoma of the lung.Lung Cancer,2016,102:82-88.doi:10.1016/j.lungcan.2016.11.004
5 Detterbeck FC,Boffa DJ,Tanoue LT.The new lung cancer staging system.Chest,2009,136(1):260-271.doi:10.1378/chest.08-0978
6 Eisenhauer EA,Therasse P,Bogaerts J,et al.New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1).Eur JCancer,2009,45(2):228-247.doi:10.1016/j.ejca.2008.10.026
7 Kim TH,Kim SJ,Ryu YH,et al.Differential CT features of infectious pneumonia versus bronchioloalveolar carcinoma(BAC)mimicking pneumonia.Eur Radiol,2006,16(8):1763-1768.doi:10.1007/s00330-005-0101-5
8 Watanabe H,Saito H,Yokose T,et al.Relation between thinsection computed tomography and clinical findings of mucinous adenocarcinoma.Ann Thorac Surg,2015,99(3):975-981.doi:10.1016/j.athoracsur.2014.10.065
9 Boland JM,Maleszewski JJ,Wampf ler JA,et al.Pulmonary invasive mucinous adenocarcinoma and mixed invasive mucinous/nonmucinous adenocarcinoma-a clinicopathological and molecular genetic study with survival analysis.Hum Pathol,2018,71:8-19.doi:10.1016/j.humpath.2017.08.002
10 Righi L,Vatrano S,Di Nicolantonio F,et al.Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung.J Thorac Oncol,2016,11(4):504-515.doi:10.1016/j.jtho.2016.01.004
11 Kadota K,Yeh YC,D'Angelo SP,et al.Associations between mutations and histologic patterns of mucin in lung adenocarcinoma:invasive mucinous pattern and extracellular mucin are associated with KRASmutation.Am J Surg Pathol,2014,38(8):1118-1127.doi:10.1097/PAS.0000000000000246
12 Fernandez-Cuesta L,Plenker D,Osada H,et al.CD74-NRG1 fusions in lung adenocarcinoma.Cancer Discov,2014,4(4):415-422.doi:10.1158/2159-8290.CD-13-0633
13 Nakaoku T,Tsuta K,Ichikawa H,et al.Druggable oncogene fusions in invasive mucinous lung adenocarcinoma.Clin Cancer Res,2014,20(12):3087-3093.doi:10.1158/1078-0432.CCR-14-0107
14 Shin DH,Lee D,Hong DW,et al.Oncogenic function and clinical impl icat ions of SLC3A2-NRG1 fusion i n invasive mucinous adenocarcinoma of the lung.Oncotarget,2016,7(43):69450-69465.doi:10.18632/oncotarget.11913
15 Duruisseaux M,McLeer-Florin A,Antoine M,et al.NRG1 fusion in a French cohort of invasive mucinous lung adenocarcinoma.Cancer Med,2016,5(12):3579-3585.doi:10.1002/cam4.838
16 Duruisseaux M,Antoine M,Rabbe N,et al.Lepidic predominant adenocarcinoma and invasive mucinous adenocarcinoma of the lung exhibit specific mucin expression in relation with oncogenic drivers.Lung Cancer,2017,109:92-100.doi:10.1016/j.lungcan.2017.05.007
17 Guo M,Tomoshige K,Meister M,et al.Gene signature driving invasive mucinous adenocarcinoma of the lung.EMBO Mol Med,2017,9(4):462-481.doi:10.15252/emmm.201606711
2 Li T,Kung HJ,Mack PC,et al.Genotyping and genomic profiling of non-small-cell lung cancer:implications for current and future therapies.J Clin Oncol,2013,31(8):1039-1049.doi:10.1200/JCO.2012.45.3753
3 Travis WD,Brambilla E,Noguchi M,et al.International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.J Thorac Oncol,2011,6(2):244-285.doi:10.1097/JTO.0b013e318206a221
4 Cha YJ,Kim HR,Lee HJ,et al.Clinical course of stage IV invasive mucinous adenocarcinoma of the lung.Lung Cancer,2016,102:82-88.doi:10.1016/j.lungcan.2016.11.004
5 Detterbeck FC,Boffa DJ,Tanoue LT.The new lung cancer staging system.Chest,2009,136(1):260-271.doi:10.1378/chest.08-0978
6 Eisenhauer EA,Therasse P,Bogaerts J,et al.New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1).Eur JCancer,2009,45(2):228-247.doi:10.1016/j.ejca.2008.10.026
7 Kim TH,Kim SJ,Ryu YH,et al.Differential CT features of infectious pneumonia versus bronchioloalveolar carcinoma(BAC)mimicking pneumonia.Eur Radiol,2006,16(8):1763-1768.doi:10.1007/s00330-005-0101-5
8 Watanabe H,Saito H,Yokose T,et al.Relation between thinsection computed tomography and clinical findings of mucinous adenocarcinoma.Ann Thorac Surg,2015,99(3):975-981.doi:10.1016/j.athoracsur.2014.10.065
9 Boland JM,Maleszewski JJ,Wampf ler JA,et al.Pulmonary invasive mucinous adenocarcinoma and mixed invasive mucinous/nonmucinous adenocarcinoma-a clinicopathological and molecular genetic study with survival analysis.Hum Pathol,2018,71:8-19.doi:10.1016/j.humpath.2017.08.002
10 Righi L,Vatrano S,Di Nicolantonio F,et al.Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung.J Thorac Oncol,2016,11(4):504-515.doi:10.1016/j.jtho.2016.01.004
11 Kadota K,Yeh YC,D'Angelo SP,et al.Associations between mutations and histologic patterns of mucin in lung adenocarcinoma:invasive mucinous pattern and extracellular mucin are associated with KRASmutation.Am J Surg Pathol,2014,38(8):1118-1127.doi:10.1097/PAS.0000000000000246
12 Fernandez-Cuesta L,Plenker D,Osada H,et al.CD74-NRG1 fusions in lung adenocarcinoma.Cancer Discov,2014,4(4):415-422.doi:10.1158/2159-8290.CD-13-0633
13 Nakaoku T,Tsuta K,Ichikawa H,et al.Druggable oncogene fusions in invasive mucinous lung adenocarcinoma.Clin Cancer Res,2014,20(12):3087-3093.doi:10.1158/1078-0432.CCR-14-0107
14 Shin DH,Lee D,Hong DW,et al.Oncogenic function and clinical impl icat ions of SLC3A2-NRG1 fusion i n invasive mucinous adenocarcinoma of the lung.Oncotarget,2016,7(43):69450-69465.doi:10.18632/oncotarget.11913
15 Duruisseaux M,McLeer-Florin A,Antoine M,et al.NRG1 fusion in a French cohort of invasive mucinous lung adenocarcinoma.Cancer Med,2016,5(12):3579-3585.doi:10.1002/cam4.838
16 Duruisseaux M,Antoine M,Rabbe N,et al.Lepidic predominant adenocarcinoma and invasive mucinous adenocarcinoma of the lung exhibit specific mucin expression in relation with oncogenic drivers.Lung Cancer,2017,109:92-100.doi:10.1016/j.lungcan.2017.05.007
17 Guo M,Tomoshige K,Meister M,et al.Gene signature driving invasive mucinous adenocarcinoma of the lung.EMBO Mol Med,2017,9(4):462-481.doi:10.15252/emmm.201606711