非吸烟非小细胞肺癌患者的比例和临床特征研究
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摘要
背景与目的非小细胞肺癌(non?small cell lung cancer, NSCLC)患者中非吸烟患者的比例正在增加,但在韩国,这个人数众多的群体并没有得到很好的治疗。本研究旨对NSCLC非吸烟患者的比例和临床特征进行一个单中心评估。方法我们分析了从2011年6月到2014年12月所有新诊断为NSCLC的1860例患者的临床数据。结果在1860例NSCLC患者中,707例(38%)从不吸烟。非吸烟患者中女性(83.7%vs.5.6%)和腺癌(89.8%vs. 44.9%)的比例均高于吸烟患者。非吸烟患者与吸烟患者相比,中位年龄明显更低(65 vs. 68岁,P<0.001),早期肿瘤比例更高(I–II期,44.5%vs. 38.9%,P=0.015)。与吸烟患者相比,表皮生长因子受体突变(57.8%vs. 24.4%,P<0.001)和间变性淋巴瘤激酶重排(7.8%vs. 2.8%,P<0.001)在非吸烟患者中更常见,而Kirsten大鼠肉瘤病毒癌基因同源染色体的基因突变(5.8%vs. 9.6%,P=0.021)出现频率则较低。在对年龄低、女性、腺癌、体能更好、疾病早期、诊断时无症状、曾接受抗肿瘤治疗以及存在驱动基因突变等的有利影响进行校正后,非吸烟患者的生存期比吸烟患者更长(hazard ratio,0.624,95%CI:0.460–0.848; P=0.003)。结论韩国超过三分之一的NSCLC患者是非吸烟者。NSCLC非吸烟患者与吸烟患者相比,有着不同的临床特征和主要驱动基因突变,总生存期更长。
引文
1.Torre LA,Bray F,Siegel R L,Ferlay J,Lortet?Tieulent J,Jemal A.Global cancer statistics,2012.CA Cancer J Clin.2015;65:87-108.
2.Jung KW,Won YJ,Kong HJ,Oh CM,Cho H,Lee DH,et al.Cancer statistics in Korea:incidence,mortality,survival,and prevalence in 2012.Cancer Res Treat.2015;47:127-41.
3.Fang B,Mehran RJ,Heymach JV,Swisher SG.Predictive biomarkers in precision medicine and drug development against lung cancer.Chin J Cancer.2015;34:295-309.
4.Wakelee HA,Chang ET,Gomez SL,Keegan TH,Feskanich D,Clarke CA,et al.Lung cancer incidence in never smokers.J Clin Oncol.2007;25:472-8.
5.Yano T,Miura N,Takenaka T,Haro A,Okazaki H,Ohba T,et al.Neversmoking nonsmall cell lung cancer as a separate entity:clinicopathologic features and sur vival.Cancer.2008;113:1012-8.
6.Parkin DM,Bray F,Ferlay J,Pisani P.Global cancer statistics,2002.CA Cancer J Clin.2005;55:74-108.
7.Toh CK,Gao F,Lim WT,Leong SS,Fong KW,Yap SP,et al.Never?smokers with lung cancer:epidemiologic evidence of a distinct disease entity.J Clin Oncol.2006;24:2245-51.
8.Sun S,Schiller JH,Gazdar AF.Lung cancer in never smokers-a different disease.Nat Rev Cancer.2007;7:778-90.
9.Tam IY,Chung LP,Suen WS,Wang E,Wong MC,Ho KK,et al.Distinct epidermal growth factor receptor and KR ASmutation patterns in non?small cell lung cancer patients with different tobacco exposure and clinicopathologic features.Clin Cancer Res.2006;12:1647-53.
10.Shaw AT,Yeap BY,Mino?Kenudson M,Digumarthy SR,Costa DB,Heist RS,et al.Clinical features and outcome of patients with non?small?cell lung cancer who harbor EML4?ALK.J Clin Oncol.2009;27:4247-53.
11.Fu S,Wang HY,Wang F,Huang MY,Deng L,Zhang X,et al.Clinicopathologic characteristics and therapeutic responses of Chinese patients with non?small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement.Chin J Cancer.2015;34:404-12.
12.Gainor JF,Varghese A M,Ou SH,Kabraji S,Awad M M,K ataya ma R,et al.ALK rearrangements are mutually exclusive with mutations in EGFR or KR AS:an analysis of1,683 patients with non?small cell lung cancer.Clin Cancer Res.2013;19:4273-81.
13.Edge SB,Byrd DR,Compton CC,Fritz AG,Greene FL,Trotti A,et al.AJCC cancer staging manual.7th ed.New York:Springer;2010.
14.K im Y T,Seong Y W,Jung Y J,Jeon Y K,Park I K,K ang CH,et al.The presence of mutations in epidermal growth factor receptor gene is not a prognostic factor for long?term outcome after surgical resection of non?small?cell lung cancer.J Thorac Oncol.2013;8:171-8.
15.Han HS,Lim SN,An JY,Lee KM,Choe KH,Lee KH,et al.Detection of EGFR mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods of differential sensitivity.J Thorac Oncol.2012;7:355-64.
16.Rodig SJ,M ino?Kenudson M,Dacic S,Yeap BY,Shaw A,Barletta JA,et al.Unique clinicopathologic features characterize ALK?rearranged lung adenocarcinoma in the western population.Clin Cancer Res.2009;15:5216-23.
17.Kwak EL,Bang YJ,Camidge DR,Shaw AT,Solomon B,Maki RG,et al.Anaplastic lymphoma kinase inhibition in non?small?cell lung cancer.N Engl J Med.2010;363:1693-703.
18.Nordquist LT,Simon GR,Cantor A,Alberts WM,Bepler G.Improved survival in never?smokers vs current smokers with primary adenocarcinoma of the lung.Chest.2004;126:347-51.
19.Brow nson RC,A lava nja MC,Caporaso N,Simoes EJ,Chang JC.Epidemiology and prevention of lung cancer in nonsmokers.Epidemiol Rev.1998;20:218-36.
20.Dibble R,Langeburg W,Bair S,Ward J,Akerley W,editors.Natual history of non?small cell lung cancer in non?smokers.In:ASCO Annual Meeting Proceedings;2005.
21.Dearden S,Stevens J,Wu YL,Blowers D.Mutation incidence and coincidence in non small?cell lung cancer:meta?analyses by ethnicity and histology(mutMap).Ann Oncol.2013;24:2371-6.
22.Riely GJ,Kris MG,Rosenbaum D,Marks J,Li A,Chitale DA,et al.Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma.Clin Cancer Res.2008;14:5731-4.
23.Maus MKH,Grimminger PP,Mack PC,Astrow S H,Stephens C,Zeger G,et al.KRAS mutations in non?small?cell lung cancer and colorectal cancer:implications for EGFR?targeted therapies.Lung Cancer.2014;83:163-7.
24.Kim EY,Kim A,Kim SK,Kim HJ,Chang J,Ahn CM,et al.KR AS oncogene substitutions in Korean NSCLC patients:clinical implication and relationship with pAKT and RalGTPases expression.Lung Cancer.2014;85:299-305.
2.Jung KW,Won YJ,Kong HJ,Oh CM,Cho H,Lee DH,et al.Cancer statistics in Korea:incidence,mortality,survival,and prevalence in 2012.Cancer Res Treat.2015;47:127-41.
3.Fang B,Mehran RJ,Heymach JV,Swisher SG.Predictive biomarkers in precision medicine and drug development against lung cancer.Chin J Cancer.2015;34:295-309.
4.Wakelee HA,Chang ET,Gomez SL,Keegan TH,Feskanich D,Clarke CA,et al.Lung cancer incidence in never smokers.J Clin Oncol.2007;25:472-8.
5.Yano T,Miura N,Takenaka T,Haro A,Okazaki H,Ohba T,et al.Neversmoking nonsmall cell lung cancer as a separate entity:clinicopathologic features and sur vival.Cancer.2008;113:1012-8.
6.Parkin DM,Bray F,Ferlay J,Pisani P.Global cancer statistics,2002.CA Cancer J Clin.2005;55:74-108.
7.Toh CK,Gao F,Lim WT,Leong SS,Fong KW,Yap SP,et al.Never?smokers with lung cancer:epidemiologic evidence of a distinct disease entity.J Clin Oncol.2006;24:2245-51.
8.Sun S,Schiller JH,Gazdar AF.Lung cancer in never smokers-a different disease.Nat Rev Cancer.2007;7:778-90.
9.Tam IY,Chung LP,Suen WS,Wang E,Wong MC,Ho KK,et al.Distinct epidermal growth factor receptor and KR ASmutation patterns in non?small cell lung cancer patients with different tobacco exposure and clinicopathologic features.Clin Cancer Res.2006;12:1647-53.
10.Shaw AT,Yeap BY,Mino?Kenudson M,Digumarthy SR,Costa DB,Heist RS,et al.Clinical features and outcome of patients with non?small?cell lung cancer who harbor EML4?ALK.J Clin Oncol.2009;27:4247-53.
11.Fu S,Wang HY,Wang F,Huang MY,Deng L,Zhang X,et al.Clinicopathologic characteristics and therapeutic responses of Chinese patients with non?small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement.Chin J Cancer.2015;34:404-12.
12.Gainor JF,Varghese A M,Ou SH,Kabraji S,Awad M M,K ataya ma R,et al.ALK rearrangements are mutually exclusive with mutations in EGFR or KR AS:an analysis of1,683 patients with non?small cell lung cancer.Clin Cancer Res.2013;19:4273-81.
13.Edge SB,Byrd DR,Compton CC,Fritz AG,Greene FL,Trotti A,et al.AJCC cancer staging manual.7th ed.New York:Springer;2010.
14.K im Y T,Seong Y W,Jung Y J,Jeon Y K,Park I K,K ang CH,et al.The presence of mutations in epidermal growth factor receptor gene is not a prognostic factor for long?term outcome after surgical resection of non?small?cell lung cancer.J Thorac Oncol.2013;8:171-8.
15.Han HS,Lim SN,An JY,Lee KM,Choe KH,Lee KH,et al.Detection of EGFR mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods of differential sensitivity.J Thorac Oncol.2012;7:355-64.
16.Rodig SJ,M ino?Kenudson M,Dacic S,Yeap BY,Shaw A,Barletta JA,et al.Unique clinicopathologic features characterize ALK?rearranged lung adenocarcinoma in the western population.Clin Cancer Res.2009;15:5216-23.
17.Kwak EL,Bang YJ,Camidge DR,Shaw AT,Solomon B,Maki RG,et al.Anaplastic lymphoma kinase inhibition in non?small?cell lung cancer.N Engl J Med.2010;363:1693-703.
18.Nordquist LT,Simon GR,Cantor A,Alberts WM,Bepler G.Improved survival in never?smokers vs current smokers with primary adenocarcinoma of the lung.Chest.2004;126:347-51.
19.Brow nson RC,A lava nja MC,Caporaso N,Simoes EJ,Chang JC.Epidemiology and prevention of lung cancer in nonsmokers.Epidemiol Rev.1998;20:218-36.
20.Dibble R,Langeburg W,Bair S,Ward J,Akerley W,editors.Natual history of non?small cell lung cancer in non?smokers.In:ASCO Annual Meeting Proceedings;2005.
21.Dearden S,Stevens J,Wu YL,Blowers D.Mutation incidence and coincidence in non small?cell lung cancer:meta?analyses by ethnicity and histology(mutMap).Ann Oncol.2013;24:2371-6.
22.Riely GJ,Kris MG,Rosenbaum D,Marks J,Li A,Chitale DA,et al.Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma.Clin Cancer Res.2008;14:5731-4.
23.Maus MKH,Grimminger PP,Mack PC,Astrow S H,Stephens C,Zeger G,et al.KRAS mutations in non?small?cell lung cancer and colorectal cancer:implications for EGFR?targeted therapies.Lung Cancer.2014;83:163-7.
24.Kim EY,Kim A,Kim SK,Kim HJ,Chang J,Ahn CM,et al.KR AS oncogene substitutions in Korean NSCLC patients:clinical implication and relationship with pAKT and RalGTPases expression.Lung Cancer.2014;85:299-305.