不同转移部位的非小细胞肺癌患者的生存时间比较
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摘要
背景与目的肺癌是全球范围内发病率和死亡率最高的恶性肿瘤,导致其高病死率的主要原因是局部复发和远处转移,而转移部位对患者的预后有一定预测作用,本研究旨在比较不同远处转移部位的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者的生存时间。方法从美国监测、流行病学和最终结果(Surveillance, Epidemiology, and End Result, SEER)数据库中提取出2010年-2014年间确诊的NSCLC患者共117,542例,回顾性分析其远处转移部位与生存时间的关系。结果在确诊的117,542例NSCLC患者中,42,071例(35.8%)患者病史中发生不同程度的远处转移,其中单器官转移26,932例,多器官转移15,139例,分别占转移患者总数的64.0%和36.0%。病史中无转移的患者的中位生存时间是21个月;而在病史中有转移患者中,中位生存时间分别是7个月(肺)、6个月(脑)、5个月(骨)、4个月(肝)、3个月(多器官转移),差异显著(P<0.001,肝转移与多器官转移除外P=0.650);且绝大多数NSCLC患者(88.4%)最终死于肺癌。结论 NSCLC患者远处转移提示预后差,在单器官转移患者中,肺转移预后最佳,肝转移预后最差;多器官转移患者预后差于单器官转移。
Background and objective The purpose of this study is to compare the survival time of non-small cell lung cancer(NSCLC) patients with different organ metastasis. Among all cancers, the morbidity and mortality of lung cancer is the highest worldwide, which may caused by local recurrence and distant metastasis, and the location of metastasis may predict the prognosis of patients. Methods A total of 117,542 patients with NSCLC diagnosed between 2010 and 2014 were enrolled from Surveillance, Epidemiology, and End Result(SEER) databases, and the relationship between distant metastasis and survival time was retrospectively analyzed. Results Of all the 117,542 patients diagnosed with non-small cell lung cancer, 42,071(35.8%) patients had different degrees of distant metastasis during their medical history, including 26,932 single organ metastases and 15,139 multiple organ metastases, accounting for 64.0% and 36.0% of the metastatic patients respectively. Compared with patients with no metastasis, whose median survival time was 21 months, the median survival time of patients with metastases was 7 months(lung), 6 months(brain), 5 months(bone), 4 months(liver), and 3 months(multiple organ) respectively, and the difference was significant(P<0.001, except liver vs multiple organ P=0.650); Most patients with NSCLC(88.4%) eventually died of lung cancer. Conclusion Distant metastasis of NSCLC patients indicates poor prognosis. In NSCLC patients with single organ metastasis, the prognosis of lung metastasis is the best, and liver metastasis is the worst, and multiple organ metastasis is worse than single organ metastasis.
Background and objective The purpose of this study is to compare the survival time of non-small cell lung cancer(NSCLC) patients with different organ metastasis. Among all cancers, the morbidity and mortality of lung cancer is the highest worldwide, which may caused by local recurrence and distant metastasis, and the location of metastasis may predict the prognosis of patients. Methods A total of 117,542 patients with NSCLC diagnosed between 2010 and 2014 were enrolled from Surveillance, Epidemiology, and End Result(SEER) databases, and the relationship between distant metastasis and survival time was retrospectively analyzed. Results Of all the 117,542 patients diagnosed with non-small cell lung cancer, 42,071(35.8%) patients had different degrees of distant metastasis during their medical history, including 26,932 single organ metastases and 15,139 multiple organ metastases, accounting for 64.0% and 36.0% of the metastatic patients respectively. Compared with patients with no metastasis, whose median survival time was 21 months, the median survival time of patients with metastases was 7 months(lung), 6 months(brain), 5 months(bone), 4 months(liver), and 3 months(multiple organ) respectively, and the difference was significant(P<0.001, except liver vs multiple organ P=0.650); Most patients with NSCLC(88.4%) eventually died of lung cancer. Conclusion Distant metastasis of NSCLC patients indicates poor prognosis. In NSCLC patients with single organ metastasis, the prognosis of lung metastasis is the best, and liver metastasis is the worst, and multiple organ metastasis is worse than single organ metastasis.
引文
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2 Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China;2014. Chin J Cancer Res, 2018, 30(1):1-12. doi:10.21147/j.issn. 1000-9604.2018.01.01
3 Chen JH, Zhang LM, Zhou H, et al. Metastasis features of 482 patients with stage IV Non-small cell lung cancer and retrospective analysis of its relationship with clinicopathologic factors. Progress in Modern Biomedicine, 2015, 15(35):6900-6903.[陈建华,张乐蒙,周辉,等. 482例非小细胞肺癌远处转移临床特征的回顾性分析.现代生物医学进展,2015,15(35):6900-6903.] doi:10.13241/j.cnki.pmb.2015.35.026
4 Wood SL, Pernemalm M, Crosbie PA, et al. The role of the tumormicroenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev, 2014, 40(4):558-566. doi:10.1016/J.ctrv.2013.10.001
5 Ali A, Goffin JR, Arnold A, et al. Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases. Curr Oncol, 2013, 20:e300-e306. doi, 10.3747/co.20.1481
6 Cui SH, Bai H, Dong LL, et al. Analysis of survival predictors in patients with lung cancer and brain metastases. Zhongguo Fei Ai Za Zhi 2015, 18(7):436-442.[崔少华,白皓,董莉莉,等.肺癌脑转移生存预测因素分析,2015, 18(7):436-442.] doi:10.3779/j.issn.1009-3419.2015.07.08
7 Schapira E, Hubbeling H, Yeap BY, et al. Improved overall survival and locoregional disease control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for lung cancer patients with brain metastases.Int J Radiat Oncol Biol Phys, 2018, 101:624-629. doi:10.1016/j.ijrobp.2018.02.175
8 Sung S, Lee SW, Kwak YK, et al. Intracranial control and survival outcome of tyrosine kinase inhibitor(TKI)alone versus TKI plus radiotherapy for brain metastasis of epidermal growth factor receptor-mutant non-small cell lungcancer.J Neurooncol, 2018,139:205-213. doi:10.1007/s11060-018-2861-1
9 Rief H, Muley T, Bruckner T, et al. Survival and prognostic factors in nonsmall cell lung cancer patients with spinal bone metastases:a retrospective analysis of 303 patients. Strahlenther Onkol, 2014, 190:59-63. doi:10.1007/s00066-013-0431-1
10 Ren Y, Dai C, Zheng H, et al. Prognostic effect of liver metastasis in lung cancer patients with distant metastasis. Oncotarget, 2016, 7:53245-53253.doi:10.18632/oncotarget. 10644
11 He YF, Luo HQ, Wang W, et al. Clinical features and prognosis-associated factors of non-small cell lung cancer exhibiting symptoms of bone metastasis at the time of diagnosis. Oncol Lett, 2015, 9(6):2706-2712. doi:10.3892/ol.2015.3081
12 Zhang C, Liao C, Penney BC, et al. Relationship between overall survival of patients with non-small cell lung cancer and whole-body metabolic tumor burden seen on postsurgical fluorodeoxyglucose PET images. Radiology,2015, 275(3):862-869. doi:10.1148/radiol.14141398
13 Eberhardt WE, 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 Thorac Oncol,2015,10(11):1515-1522. doi:10.1097/JT0.0000000000000673
14 Bragstad S, Flateb(?)M, Natvig G, et al. Predictors of quality of life and survival following Gamma Knife surgery for lung cancer brain metastases:a prospective study. J Neurosurg, 2018, 129(1):71-83. doi:10.3171/2017.2.JNS161659
15 Schapira E, Hubbeling H, Yeap B, et al. Improved overall survival and locoregional disease control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for lung cancer patients with brain metastases.Int J Radiat Oncol Biol Phys, 2018, 101(3):624-629. doi:10.1016/j.ijrobp.2018.02.175
16 Liu Y, Deng L, Zhou X, et al. Concurrent brain radiotherapy and EGFR-TKI may improve intracranial metastases control in non-small cell lung cancer and have survival benefit in patients with low DS-GPA score. Oncotarget,2017, 8(67):111309-111317. doi:10.18632/oncotarget.22785
17 Yokes EE, Ready N, Felip E, et al. Nivolumab versus docetaxel inpreviously treated advanced non-small-cell lung cancer(CheckMate 017and CheckMate 057):3-year update and outcomes in patients with liver metastases. Ann Oncol, 2018, 29(4):959-965. doi:1093/annonc/mdy041.
18 Ishige F, Takayama W, Chiba S, et al. Hepatectomy for oligo-recurrence of non-small cell lung cancer in the liver. Int J Clin Oncol, 2018, 23(4):647-651. doi:10.1007/s10147-018-1262-y
19 Abdel-Rahman O. Predictors of skeletal-related events among cancer patients with bone metastases treated with zoledronic acid:a secondary analysis of a randomized study. Expert Opin Drug Saf, 2018, 17(8):757-761.doi:10.1080/14740338.2018.1497157
20 Francini F, Pascucci A, Bargagli G, et al. Effects of intravenous zoledronic acid and oral ibandronate on early changes in markers of bone turnover in patients with bone metastases from non-small cell lung cancer. Int J Clin Oncol, 2011,16(3):264-269. doi:10.1007/s10147-010-0179-x
21 Utzschneider S, Wicherek E, Weber P, et al. Surgical treatment of bone metastases in patients with lung cancer. Int Orthop, 2011, 35(5):731-736.doi:10.1007/s00264-010-1074-9
22 Willeumier JJ, van der Hoeven NM, Bollen L, et al. Epidermal growth factor receptor mutations should be considered as a prognostic factor for survival of patients with pathological fractures or painful bone metastases from non-small cell lung cancer. Bone Joint J, 2017, 99-b(4):516-521. doi:10.1302/0301-620X.99B4.BJJ-2016-0872.81
23 Tonnies M, Kollmeier J, Bauer TT, et al. Curative surgical treatment options for patients with non-small cell lung cancer(NSCLC)and solitary pulmonary metastasis. Pneumologie, 2012, 66(4):218-223. doi:10.1055/s-0032-1308917
24 Baba F, Shibamoto Y, Tomita N, et al. Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis:evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results. Radiat Oncol, 2009,4:15. doi:10.1186/1748-717X-4-15
2 Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China;2014. Chin J Cancer Res, 2018, 30(1):1-12. doi:10.21147/j.issn. 1000-9604.2018.01.01
3 Chen JH, Zhang LM, Zhou H, et al. Metastasis features of 482 patients with stage IV Non-small cell lung cancer and retrospective analysis of its relationship with clinicopathologic factors. Progress in Modern Biomedicine, 2015, 15(35):6900-6903.[陈建华,张乐蒙,周辉,等. 482例非小细胞肺癌远处转移临床特征的回顾性分析.现代生物医学进展,2015,15(35):6900-6903.] doi:10.13241/j.cnki.pmb.2015.35.026
4 Wood SL, Pernemalm M, Crosbie PA, et al. The role of the tumormicroenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev, 2014, 40(4):558-566. doi:10.1016/J.ctrv.2013.10.001
5 Ali A, Goffin JR, Arnold A, et al. Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases. Curr Oncol, 2013, 20:e300-e306. doi, 10.3747/co.20.1481
6 Cui SH, Bai H, Dong LL, et al. Analysis of survival predictors in patients with lung cancer and brain metastases. Zhongguo Fei Ai Za Zhi 2015, 18(7):436-442.[崔少华,白皓,董莉莉,等.肺癌脑转移生存预测因素分析,2015, 18(7):436-442.] doi:10.3779/j.issn.1009-3419.2015.07.08
7 Schapira E, Hubbeling H, Yeap BY, et al. Improved overall survival and locoregional disease control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for lung cancer patients with brain metastases.Int J Radiat Oncol Biol Phys, 2018, 101:624-629. doi:10.1016/j.ijrobp.2018.02.175
8 Sung S, Lee SW, Kwak YK, et al. Intracranial control and survival outcome of tyrosine kinase inhibitor(TKI)alone versus TKI plus radiotherapy for brain metastasis of epidermal growth factor receptor-mutant non-small cell lungcancer.J Neurooncol, 2018,139:205-213. doi:10.1007/s11060-018-2861-1
9 Rief H, Muley T, Bruckner T, et al. Survival and prognostic factors in nonsmall cell lung cancer patients with spinal bone metastases:a retrospective analysis of 303 patients. Strahlenther Onkol, 2014, 190:59-63. doi:10.1007/s00066-013-0431-1
10 Ren Y, Dai C, Zheng H, et al. Prognostic effect of liver metastasis in lung cancer patients with distant metastasis. Oncotarget, 2016, 7:53245-53253.doi:10.18632/oncotarget. 10644
11 He YF, Luo HQ, Wang W, et al. Clinical features and prognosis-associated factors of non-small cell lung cancer exhibiting symptoms of bone metastasis at the time of diagnosis. Oncol Lett, 2015, 9(6):2706-2712. doi:10.3892/ol.2015.3081
12 Zhang C, Liao C, Penney BC, et al. Relationship between overall survival of patients with non-small cell lung cancer and whole-body metabolic tumor burden seen on postsurgical fluorodeoxyglucose PET images. Radiology,2015, 275(3):862-869. doi:10.1148/radiol.14141398
13 Eberhardt WE, 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 Thorac Oncol,2015,10(11):1515-1522. doi:10.1097/JT0.0000000000000673
14 Bragstad S, Flateb(?)M, Natvig G, et al. Predictors of quality of life and survival following Gamma Knife surgery for lung cancer brain metastases:a prospective study. J Neurosurg, 2018, 129(1):71-83. doi:10.3171/2017.2.JNS161659
15 Schapira E, Hubbeling H, Yeap B, et al. Improved overall survival and locoregional disease control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for lung cancer patients with brain metastases.Int J Radiat Oncol Biol Phys, 2018, 101(3):624-629. doi:10.1016/j.ijrobp.2018.02.175
16 Liu Y, Deng L, Zhou X, et al. Concurrent brain radiotherapy and EGFR-TKI may improve intracranial metastases control in non-small cell lung cancer and have survival benefit in patients with low DS-GPA score. Oncotarget,2017, 8(67):111309-111317. doi:10.18632/oncotarget.22785
17 Yokes EE, Ready N, Felip E, et al. Nivolumab versus docetaxel inpreviously treated advanced non-small-cell lung cancer(CheckMate 017and CheckMate 057):3-year update and outcomes in patients with liver metastases. Ann Oncol, 2018, 29(4):959-965. doi:1093/annonc/mdy041.
18 Ishige F, Takayama W, Chiba S, et al. Hepatectomy for oligo-recurrence of non-small cell lung cancer in the liver. Int J Clin Oncol, 2018, 23(4):647-651. doi:10.1007/s10147-018-1262-y
19 Abdel-Rahman O. Predictors of skeletal-related events among cancer patients with bone metastases treated with zoledronic acid:a secondary analysis of a randomized study. Expert Opin Drug Saf, 2018, 17(8):757-761.doi:10.1080/14740338.2018.1497157
20 Francini F, Pascucci A, Bargagli G, et al. Effects of intravenous zoledronic acid and oral ibandronate on early changes in markers of bone turnover in patients with bone metastases from non-small cell lung cancer. Int J Clin Oncol, 2011,16(3):264-269. doi:10.1007/s10147-010-0179-x
21 Utzschneider S, Wicherek E, Weber P, et al. Surgical treatment of bone metastases in patients with lung cancer. Int Orthop, 2011, 35(5):731-736.doi:10.1007/s00264-010-1074-9
22 Willeumier JJ, van der Hoeven NM, Bollen L, et al. Epidermal growth factor receptor mutations should be considered as a prognostic factor for survival of patients with pathological fractures or painful bone metastases from non-small cell lung cancer. Bone Joint J, 2017, 99-b(4):516-521. doi:10.1302/0301-620X.99B4.BJJ-2016-0872.81
23 Tonnies M, Kollmeier J, Bauer TT, et al. Curative surgical treatment options for patients with non-small cell lung cancer(NSCLC)and solitary pulmonary metastasis. Pneumologie, 2012, 66(4):218-223. doi:10.1055/s-0032-1308917
24 Baba F, Shibamoto Y, Tomita N, et al. Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis:evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results. Radiat Oncol, 2009,4:15. doi:10.1186/1748-717X-4-15