术后IB期浸润性肺腺癌不同病理亚型的预后分析
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摘要
目的探讨术后IB期浸润性肺腺癌不同病理亚型对预后的影响,为临床精细化诊疗和生存预后提供更多的有利证据。方法回顾性分析浙江省肿瘤医院2010年7月至2017年9月术后病理确诊为IB期的浸润性肺腺癌295例患者的临床资料。收集患者的性别、年龄、吸烟状况、术后辅助化疗、脉管癌栓、胸模浸润、病理亚型、病理亚型数量,以及术前末次纤维蛋白原、乳酸脱氢酶、超敏C反应蛋白(hsCRP)、白细胞、中性粒细胞水平等资料。采用Kaplan-Meier法进行生存预后分析并行Log-Rank检验,Cox比例风险模型分析影响总生存率(OS)的因素。结果 295例中主要病理亚型排序由高到低依次为腺泡型161例(54.58%),乳头型61例(20.68%),贴壁型41例(13.9%),实性型21例(7.12%),微乳头型11例(3.73%)。单因素生存分析结果显示,性别、吸烟状况、纤维蛋白原、hsCRP、胸膜浸润、脉管癌栓、病理亚型及亚型数量与总生存率存在相关性(P<0.05)。在病理亚型分类中,贴壁为主型患者的预后最好,实性为主型患者预后最差,5年生存率分别为:贴壁为主型82.9%,乳头为主型68.9%,腺泡为主型63.4%,微乳头为主型45.5%,实性为主型38.1%,差异有统计学意义(P<0.01)。在病理亚型数量分类中,以包含2个亚型的患者预后最佳,包含4个亚型的患者预后最差,5年生存率分别为:1个亚型67.8%,2个亚型73.3%,3个亚型56.1%,4个亚型46.2%,差异有统计学意义(P<0.01)。Cox多因素生存分析结果显示,吸烟、病理亚型及亚型数量与总生存率相关(P<0.05),而其他因素与总生存率无明显相关性(P>0.05)。结论吸烟、病理亚型及病理亚型数量是IB期浸润性肺腺癌术后生存的独立影响因素,在包含多个亚型病理分类中以贴壁型为主者预后最佳,对临床精细化诊疗及生存预后具有重要参考和指导意义。
Objective To investigate the effect of different pathological subtypes of invasive lung adenocarcinoma after post-operative IB stage on prognosis and to provide more favorable evidence for clinical fine diagnosis and treatment and survival prognosis.Methods The clinical data of 295 patients with invasive lung adenocarcinoma diagnosed as IB period from July 2010 to September 2017 in Cancer Hospital of Zhejiang Province were analyzed retrospectively. Inclusion criteria:All patients did not have chemotherapy or radiotherapy before surgery,and in accordance with version 2015 who pathological and eighth version of TNM staging,postoperative pathology was confirmed as the IB stage of invasive lung adenocarcinoma patients. The clinical data of patients included gender,age,smoking status,postoperative adjuvant chemotherapy,vascular thrombosis,thoracic model infiltration,pathological subtypes,pathological subtypes,and preoperative fibrinogen,lactate dehydrogenase,hypersensitive C-reactive protein(hsCRP),white blood cells,neutrophils and other levels of retrospective analysis. The survival prognosis analysis was performed by the Kaplan-meier method and log-rank test. The Cox proportional risk model was used to analyze factors affecting overall survival rate(OS).Results Total 295 cases of IB invasive lung adenocarcinoma included in the study. The main tissue subtypes were from high to low,followed by 161 cases(54.58%),nipple type 61 cases(20.68%),41 cases of wall type(13.9%),21 cases of solid type(7.12%),11 cases of micro-nipple type(3.73%). In single-factor survival analysis,gender,smoking status,fibrinogen and hypersensitive C-reactive protein levels,pleural infiltration,vascular thrombosis,pathological subtypes and subtypes were correlated with OS(P<0.05). In the pathological subtype classification,the prognosis of the main type of wall patients is the best,the reality of the main type of patients with the worst prognosis,and5 years survival rate were:wall mainly type 82.9%,nipple type 68.9%,glandular bubble as the main type 63.4%,micro-nipple type 45.5%,solid main type 38.1%. The difference was statistically significant(P<0.01). In the pathological subtype quantity classification,the prognosis of patients with 2 subtypes was the best,and the prognosis of patients with 4 subtypes was the worst,and the 5-year survival rate were:one subtype 67.8%,2 subtypes 73.3%,3 subtypes 56.1%,4 subtypes 46.2%. The difference was statistically significant(P<0.01). In Cox Multi-factor survival analysis,the number of smoking,pathological subtypes and subtypes was associated with OS(P<0.05),while other factors were not significantly correlated with the OS(P>0.05).Conclusion Smoking,pathological subtypes and the number of pathological subtypes are the independent factors affecting the survival of invasive lung adenocarcinoma after IB period,and the prognosis is the best for those with multiple subtypes of pathological classification,which has important reference and guiding significance for clinical fine diagnosis and treatment and survival prognosis.
Objective To investigate the effect of different pathological subtypes of invasive lung adenocarcinoma after post-operative IB stage on prognosis and to provide more favorable evidence for clinical fine diagnosis and treatment and survival prognosis.Methods The clinical data of 295 patients with invasive lung adenocarcinoma diagnosed as IB period from July 2010 to September 2017 in Cancer Hospital of Zhejiang Province were analyzed retrospectively. Inclusion criteria:All patients did not have chemotherapy or radiotherapy before surgery,and in accordance with version 2015 who pathological and eighth version of TNM staging,postoperative pathology was confirmed as the IB stage of invasive lung adenocarcinoma patients. The clinical data of patients included gender,age,smoking status,postoperative adjuvant chemotherapy,vascular thrombosis,thoracic model infiltration,pathological subtypes,pathological subtypes,and preoperative fibrinogen,lactate dehydrogenase,hypersensitive C-reactive protein(hsCRP),white blood cells,neutrophils and other levels of retrospective analysis. The survival prognosis analysis was performed by the Kaplan-meier method and log-rank test. The Cox proportional risk model was used to analyze factors affecting overall survival rate(OS).Results Total 295 cases of IB invasive lung adenocarcinoma included in the study. The main tissue subtypes were from high to low,followed by 161 cases(54.58%),nipple type 61 cases(20.68%),41 cases of wall type(13.9%),21 cases of solid type(7.12%),11 cases of micro-nipple type(3.73%). In single-factor survival analysis,gender,smoking status,fibrinogen and hypersensitive C-reactive protein levels,pleural infiltration,vascular thrombosis,pathological subtypes and subtypes were correlated with OS(P<0.05). In the pathological subtype classification,the prognosis of the main type of wall patients is the best,the reality of the main type of patients with the worst prognosis,and5 years survival rate were:wall mainly type 82.9%,nipple type 68.9%,glandular bubble as the main type 63.4%,micro-nipple type 45.5%,solid main type 38.1%. The difference was statistically significant(P<0.01). In the pathological subtype quantity classification,the prognosis of patients with 2 subtypes was the best,and the prognosis of patients with 4 subtypes was the worst,and the 5-year survival rate were:one subtype 67.8%,2 subtypes 73.3%,3 subtypes 56.1%,4 subtypes 46.2%. The difference was statistically significant(P<0.01). In Cox Multi-factor survival analysis,the number of smoking,pathological subtypes and subtypes was associated with OS(P<0.05),while other factors were not significantly correlated with the OS(P>0.05).Conclusion Smoking,pathological subtypes and the number of pathological subtypes are the independent factors affecting the survival of invasive lung adenocarcinoma after IB period,and the prognosis is the best for those with multiple subtypes of pathological classification,which has important reference and guiding significance for clinical fine diagnosis and treatment and survival prognosis.
引文
[1]魏雨晴,吕镗烽,刘红兵,等.PD-L1作为PD-1靶向药物治疗非小细胞肺癌疗效预测生物标志的意义及其局限性[J].转化医学电子杂志,2018,5(2):40-44.
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[12] Song Z,Zhu H,Guo Z,et al.Prognostic value of the IASLC/ATS/ERS classification in stage I lung adenocarcinoma patients—Based on a hospital study in China[J].Eur J Surg Oncol,2013,39(11):1262-1268.
[13] Yoshida Y,Nitadori JI,Shinozaki-Ushiku A,et al.Micropapillary histological subtype in lung adenocarcinoma of 2 cm or less:impact on recurrence and clinical predictors[J].Gen Thorac Cardiovasc Surg,2017,65(5):273-279.
[14] Hoshi R,Tsuzuku M,Horai T,et al.Micropapillary clusters in early-stage lung adenocarcinomas:a distinct cytologic sign of significantly poor prognosis[J].Cancer,2004,102(2):81-86.
[15] Amin MB,Tamboli P,Merchant SH,et al.Micropapillary component in lung adenocarcinoma:a distinctive histologic feature with possible prognostic significance[J].Am J Surg Pathol,2002,26(3):358-364.
[16] Miyoshi T,Satoh Y,Okumura S,et al.Early-stage lung adenocarcinomas with a micropapillary pattern,a distinct pathologic marker for a significantly poor prognosis[J].Am J Surg Pathol,2003,27(1):101-109.
[17] Hung JJ.Histologic subtype component predicts lymph node micrometastasis and prognosis in patients with stage I lung adenocarcinoma[J].J Thorac Dis,2017,9(10):3623-3625.
[18] Rosai J.Rosai&Ackerman外科病理学[M].郑杰,主译.北京:北京大学医学出版社,2014:370-373
[19]刘彤华.诊断病理学[M].3版.北京:人民卫生出版社,2013:137-142.
[20] Westaway DD,Toon CW,Farzin M,et al.The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society grading system has limited prognostic significance in advanced resected pulmonary adenocarcinoma[J].Pathology,2013,45(6):553-558
[21] Ujiie H,Kadota K,Chaft JE,et al.Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early,Extrathoracic,Multisite Recurrence and of Poor Postrecurrence Survival[J].J Clin Oncol,2015,33(26):2877-2884.
[22] Tsubokawa N,Mimae T,Sasada S,et al.Negative prognostic influence of micropapillary pattern in stage IA lung adenocarcinoma[J].Eur J Cardiothorac Surg,2016,49(1):293-299.
[2] Wang A,Wang HY,Liu Y,et al.The prognostic value of PD-L1expression for non-small cell lung cancer patients:a meta-analysis[J].Eur J Surg Oncol,2015,41(4):450-456.
[3]陈海瑞,李文才,陈天东,等.原发性肺腺癌组织亚型及预后[J].河南医学研究,2017,26(18):3271-3273.
[4] Warth A,Muley T,Meister M,et al.The novel histologic international association for the study of lung cancer/American thoracic society/European respiratory society classification system of lung adenocarcinoma is a stage independent predictor of survival[J].J Clin Oncol,2012,30(13):1438-1446.
[5]杜海磊,车嘉铭,朱良纲,等.病理T1期浸润性肺腺癌不同病理亚型的临床特征及其预后分析[J].诊断学理论与实践,2018,17(1):82-86.
[6]曹玉娟,王德林,刘承伟,等.肺腺癌新分类在预测Ⅰb期非小细胞肺癌预后中的价值[J].肿瘤学杂志,2014,20(6):448-451.
[7]田璇,孙蕾娜,王静,等.最新国际肺腺癌分类方法回顾性分析具有细支气管肺泡癌特征的肺腺癌209例[J].中国肿瘤临床,2013,40(8):475-478.
[8] Strand TE,Rostad H,Str?m EH,et al.The percentage of lepidic growth is an independent prognostic factor in invasive adenocarcinoma of the lung[J].Diagn Pathol,2015,10(1):94.
[9] Luo J,Huang Q,Wang R,et al.Prognostic and predictive value of the novel classification of lung adenocarcinoma in patients with stage IB[J].J Cancer Res Clin Oncol,2016,142(9):2031-2040.
[10]杨欣,林冬梅.2015版WHO肺癌组织学分类变化及其临床意义[J].中国肺癌杂志,2016,19(6):332-336.
[11]朱萌,孙武刚.不同病理类型Ⅰ期肺腺癌患者的生存状况研究[J].中国医药科学,2018,8(9):200-203.
[12] Song Z,Zhu H,Guo Z,et al.Prognostic value of the IASLC/ATS/ERS classification in stage I lung adenocarcinoma patients—Based on a hospital study in China[J].Eur J Surg Oncol,2013,39(11):1262-1268.
[13] Yoshida Y,Nitadori JI,Shinozaki-Ushiku A,et al.Micropapillary histological subtype in lung adenocarcinoma of 2 cm or less:impact on recurrence and clinical predictors[J].Gen Thorac Cardiovasc Surg,2017,65(5):273-279.
[14] Hoshi R,Tsuzuku M,Horai T,et al.Micropapillary clusters in early-stage lung adenocarcinomas:a distinct cytologic sign of significantly poor prognosis[J].Cancer,2004,102(2):81-86.
[15] Amin MB,Tamboli P,Merchant SH,et al.Micropapillary component in lung adenocarcinoma:a distinctive histologic feature with possible prognostic significance[J].Am J Surg Pathol,2002,26(3):358-364.
[16] Miyoshi T,Satoh Y,Okumura S,et al.Early-stage lung adenocarcinomas with a micropapillary pattern,a distinct pathologic marker for a significantly poor prognosis[J].Am J Surg Pathol,2003,27(1):101-109.
[17] Hung JJ.Histologic subtype component predicts lymph node micrometastasis and prognosis in patients with stage I lung adenocarcinoma[J].J Thorac Dis,2017,9(10):3623-3625.
[18] Rosai J.Rosai&Ackerman外科病理学[M].郑杰,主译.北京:北京大学医学出版社,2014:370-373
[19]刘彤华.诊断病理学[M].3版.北京:人民卫生出版社,2013:137-142.
[20] Westaway DD,Toon CW,Farzin M,et al.The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society grading system has limited prognostic significance in advanced resected pulmonary adenocarcinoma[J].Pathology,2013,45(6):553-558
[21] Ujiie H,Kadota K,Chaft JE,et al.Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early,Extrathoracic,Multisite Recurrence and of Poor Postrecurrence Survival[J].J Clin Oncol,2015,33(26):2877-2884.
[22] Tsubokawa N,Mimae T,Sasada S,et al.Negative prognostic influence of micropapillary pattern in stage IA lung adenocarcinoma[J].Eur J Cardiothorac Surg,2016,49(1):293-299.