非小细胞肺癌的转移特征及预后分析
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摘要
目的基于大量人群的数据集,分析非小细胞肺癌(non-small cell lung cancer, NSCLC)转移部位的特异性及不同转移模式的预后差异。方法从SEER(Surveillance, Epidemiology, and End Results)数据库中收集2010-2014年诊断为NSCLC的转移性患者,利用Kaplan-Meier法和对数秩检验进行生存分析,通过Cox比例风险模型分析改善总体生存(overall survival, OS)的相关因素。结果从SEER数据库中收集到38 755例具有骨、肝、脑、肺任一部位转移的NSCLC患者。诊断时,年龄超过50岁的患者占93.89%,且以白种人为主(77.38%)。入组患者中,肿瘤中度分化(Ⅱ级)患者约占12.50%,肿瘤低分化(Ⅲ级)患者占25.55%,组织学亚型以腺癌为主,约占72.52%。对于所有NSCLC患者,最常见的单转移部位是骨(22.43%),最少累及的部位是肝(5.87%),骨和肺是最常见的双部位转移组合(7.40%),骨、肝和肺是最常见的三部位转移组合(3.16%)。孤立性肝转移在单转移中具有最差的OS(P<0.001),多部位转移中,含有肝转移的组合也具有更差的OS(P<0.001)。结论 NSCLC不论是单个还是多个器官转移,骨都是最常累及的靶器官。单独肝转移或多部位联合肝转移的NSCLC患者预后较差,孤立性肺转移预后最好。
Objective To analyze the specificity of metastatic sites and prognostic differences of different metastatic patterns in non-small cell lung cancer(NSCLC) based on a large population-based dataset. Methods The metastatic NSCLC patients diagnosed between 2010 and 2014 were collected from the Surveillance, Epidemiology, and End Results(SEER) database. Kaplan-Meier survival analysis and log-rank test were used for survival analysis, and Cox proportional hazard model was performed to determine the factors related to improved overall survival(OS). Results A total of 38 755 NSCLC cases with metastases to bone, liver, brain and/or lungs were collected from the SEER database. At the time of diagnosis, 93.89% of the patients were over the age of 50 years, and the caucasian accounted for 77.38%. Among all enrolled cases, the moderately differentiated tumors(grade Ⅱ) accounted for 12.50%, and those with poor differentiation(grade Ⅲ) for 25.55%. The major histological subtype was adenocarcinoma, accounting for 72.52%. The most common single metastatic site was bone(22.43%), and the least common was liver(5.87%) for NSCLC. As for multi-site metastases, bone and lung was the most common 2-site metastasis(7.40%), and bone, liver and lung was the most common 3-site metastasis(3.16%). An isolated liver metastasis had the worst OS among single metastasis(P<0.001). Furthermore, for patients with multi-site metastases, liver combined metastases had worst OS among various combinations(P<0.001). Conclusion For NSCLC, bone is the most commonly targeted site, no matter for single-or multi-organ metastases. NSCLC patients with metastasis to liver alone or in combination with other organs have a poorer prognosis, while isolated lung metastasis has the best outcomes.
Objective To analyze the specificity of metastatic sites and prognostic differences of different metastatic patterns in non-small cell lung cancer(NSCLC) based on a large population-based dataset. Methods The metastatic NSCLC patients diagnosed between 2010 and 2014 were collected from the Surveillance, Epidemiology, and End Results(SEER) database. Kaplan-Meier survival analysis and log-rank test were used for survival analysis, and Cox proportional hazard model was performed to determine the factors related to improved overall survival(OS). Results A total of 38 755 NSCLC cases with metastases to bone, liver, brain and/or lungs were collected from the SEER database. At the time of diagnosis, 93.89% of the patients were over the age of 50 years, and the caucasian accounted for 77.38%. Among all enrolled cases, the moderately differentiated tumors(grade Ⅱ) accounted for 12.50%, and those with poor differentiation(grade Ⅲ) for 25.55%. The major histological subtype was adenocarcinoma, accounting for 72.52%. The most common single metastatic site was bone(22.43%), and the least common was liver(5.87%) for NSCLC. As for multi-site metastases, bone and lung was the most common 2-site metastasis(7.40%), and bone, liver and lung was the most common 3-site metastasis(3.16%). An isolated liver metastasis had the worst OS among single metastasis(P<0.001). Furthermore, for patients with multi-site metastases, liver combined metastases had worst OS among various combinations(P<0.001). Conclusion For NSCLC, bone is the most commonly targeted site, no matter for single-or multi-organ metastases. NSCLC patients with metastasis to liver alone or in combination with other organs have a poorer prognosis, while isolated lung metastasis has the best outcomes.
引文
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[2] CRINò L,WEDER W,VAN MEERBEECK J,et al.Early stage and locally advanced(non-metastatic) non-small-cell lung cancer:ESMO clinical practice guidelines for diagnosis,treatment and follow-up[J].Ann Oncol,2010,21(Suppl 5):v103-v115.DOI:10.1093/annonc/mdq207.
[3] ZAGO G,MULLER M,VAN DEN HEUVEL M,et al.New targeted treatments for non-small-cell lung cancer—role of nivolumab[J].Biologics,2016,10:103-117.DOI:10.2147/BTT.S87878.
[4] LORUSSO G,IMBIMBO M,GARASSINO M C.Is the chemotherapy era in advanced non-small cell lung cancer really over?maybe not yet[J].Tumori,2016,102(3):223-225.DOI:10.5301/tj.5000479.
[5] MORGENSZTERN D,NG S H,GAO F,et al.Trends in stage distribution for patients with non-small cell lung cancer:a national cancer database survey[J].J Thorac Oncol,2010,5(1):29-33.DOI:10.1097/JTO.0b013e3181c5920c.
[6] DETTERBECK F C,BOFFA D J,KIM A W,et al.The eighth edition lung cancer stage classification[J].Chest,2017,151(1):193-203.DOI:10.1016/j.chest.2016.10.010.
[7] REN Y J,DAI C Y,ZHENG H,et al.Prognostic effect of liver metastasis in lung cancer patients with distant metastasis[J].Oncotarget,2016,7(33):53245-53253.DOI:10.18632/oncotarget.10644.
[8] CHANG Y P,CHEN Y M,LAI C H,et al.The impact of de novo liver metastasis on clinical outcome in patients with advanced non-small-cell lung cancer[J].PLoS ONE,2017,12(6):e0178676.DOI:10.1371/journal.pone.0178676.
[9] EBERHARDT W E,MITCHELL A,CROWLEY J,et al.The IASLC lung cancer staging project:proposals for the revision of the M descriptors in the forthcoming eighth edition of the TNM classification of lung cancer[J].J Thorac Oncol,2015,10(11):1515-1522.DOI:10.1097/JTO.000000000000 0673.
[10] TAMURA T,KURISHIMA K,NAKAZAWA K,et al.Specific organ metastases and survival in metastatic non-small-cell lung cancer[J].Mol Clin Oncol,2015,3(1):217-221.DOI:10.3892/mco.2014.410.
[11] RIIHIM?KI M,HEMMINKI A,FALLAH M,et al.Metastatic sites and survival in lung cancer[J].Lung Cancer,2014,86(1):78-84.DOI:10.1016/j.lungcan.2014.07.020.
[12] WU K L,TSAI M J,YANG C J,et al.Liver metastasis predicts poorer prognosis in stage IV lung adenocarcinoma patients receiving first-line gefitinib[J].Lung Cancer,2015,88(2):187-194.DOI:10.1016/j.lungcan.2015.02.012.
[13] PAZ-ARES L G,SHEN K,HIGGS B W,et al.Association of liver metastases(LM) with survival in NSCLC patients treated with durvalumab(D) in two independent clinical trials[J].J Clin Oncol,2017,35(15_suppl):3038.DOI:10.1200/jco.2017.35.15_suppl.3038.
[14] PILLAI R N,KAMPHORST A O,OWONIKOKO T K,et al.Liver metastases and sensitivity to checkpoint inhibition in patients with non-small cell lung cancer(NSCLC)[J].J Clin Oncol,2016,34(15_suppl):e20665.DOI:10.1200/jco.2016.34.15_suppl.e20665.
[15] TUMEH P C,HELLMANN M D,HAMID O,et al.Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC[J].CancerImmunol Res,2017,5(5):417-424.DOI:10.1158/2326-6066.CIR-16-0325.
[16] YANG J,ZHANG Y,SUN X T,et al.The prognostic value of multiorgan metastases in patients with non-small cell lung cancer and its variants:a SEER-based study[J].J Cancer Res Clin Oncol,2018,144(9):1835-1842.DOI:10.1007/s00432-018-2702-9.