治疗前淋巴细胞减少与恶性实体瘤患者预后相关性Meta分析
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摘要
目的越来越多的临床研究显示,治疗前淋巴细胞减少能够影响血液系统恶性肿瘤肿瘤患者的抗肿瘤治疗疗效和生存预后。然而,其在恶性实体瘤患者中的预后价值仍然存在一定争议。因此,本研究探讨治疗前淋巴细胞减少与非血液性恶性实体瘤患者预后的关系,以进一步指导临床工作。方法计算机检索PubMed、Web of Science、Medline和EMBASE四大数据库从建库至2017-12公开发表的相关文献。纳入研究确定治疗前淋巴细胞减少与恶性实体瘤患者总生存(overall survival,OS)和无进展生存(progression-free survival,PFS)的关系。计算风险比(hazard ratio,HR)和95%的置信区间(confidence interval,CI),采用Stata 12.0进行Meta分析。结果 32项符合标准的研究共计5 322例恶性实体瘤患者纳入分析。结果显示,治疗前淋巴细胞减少与患者较短的OS相关,HR合并值为1.50,95%CI为1.26~1.78,P<0.001;并且与患者较短的PFS也具有相关性,HR合并值为1.34,95%CI为1.18~1.54,P<0.001。结论治疗前淋巴细胞减少可能是恶性实体瘤患者预后差的一个独立危险因素。
OBJECTIVE At present,more and more clinical studies showed that pretreatment lymphopenia could affect the treatment effect and survival as well as prognosis of patients with hematological malignancies.However,the prognostic significance of pretreatment lymphopenia in non-hematologic malignant solid tumors remains controversial.In this study the Meta-analysis was used to evaluate the correlation between the pretreatment lymphopenia and the prognosis of patients with malignant solid tumors.METHODS Related articles published on PubMed,Web of Science,Medline and EMBASE databases until December 2017 were included in our research to evaluate the relationship between pretreatment lymphopenia and overall survival(OS)or progression-free survival(PFS)in non-hematologic malignant solid tumors.The hazard ratio(HR)and 95%confidence interval(CI)were calculated and the Stata 12.0 software was used for Meta-analysis.RESULTS A total of 5 322 individuals from thirty-two studies were included in the Meta-analysis.The analysis results revealed that the pretreatment lymphopenia was associated with worse OS(pool HR=1.50,95%CI=1.26-1.78,P<0.001)and PFS(pool HR=1.34,95%CI=1.18-1.54,P<0.001)in non-hematologic malignant solid tumors.CONCLUSION Pretreatment lymphopenia may be an independent adverse prognostic indicator for malignant solid tumors.
OBJECTIVE At present,more and more clinical studies showed that pretreatment lymphopenia could affect the treatment effect and survival as well as prognosis of patients with hematological malignancies.However,the prognostic significance of pretreatment lymphopenia in non-hematologic malignant solid tumors remains controversial.In this study the Meta-analysis was used to evaluate the correlation between the pretreatment lymphopenia and the prognosis of patients with malignant solid tumors.METHODS Related articles published on PubMed,Web of Science,Medline and EMBASE databases until December 2017 were included in our research to evaluate the relationship between pretreatment lymphopenia and overall survival(OS)or progression-free survival(PFS)in non-hematologic malignant solid tumors.The hazard ratio(HR)and 95%confidence interval(CI)were calculated and the Stata 12.0 software was used for Meta-analysis.RESULTS A total of 5 322 individuals from thirty-two studies were included in the Meta-analysis.The analysis results revealed that the pretreatment lymphopenia was associated with worse OS(pool HR=1.50,95%CI=1.26-1.78,P<0.001)and PFS(pool HR=1.34,95%CI=1.18-1.54,P<0.001)in non-hematologic malignant solid tumors.CONCLUSION Pretreatment lymphopenia may be an independent adverse prognostic indicator for malignant solid tumors.
引文
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[16]Saroha S,Uzzo RG,Plimack ER,et al.Lymphopenia is an independent predictor of inferior outcome in clear cell renal carcinoma[J].J Urol,2013,189(2):454-461.
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[23]Wu ES,Oduyebo T,Cobb LP,et al.Lymphopenia and its association with survival in patients with locally advanced cervical cancer[J].Gynecol Oncol,2016,140(1):76-82.
[24]Choi Y,Oh DY,Park H,et al.More accurate prediction of metastatic pancreatic cancer patients'survival with prognostic model using both host immunity and tumor metabolic activity[J/CD].PLoS One,2016,11(1):e0145692.
[25]Cho O,Chun M,Chang SJ,et al.Prognostic value of severe lymphopenia during pelvic concurrent chemoradiotherapy in cervical cancer[J].Anticancer Res,2016,36(7):3541-3547.
[26]Berardi R,Rinaldi S,Santoni M,et al.Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo-or targeted therapy[J].Oncotarget,2016,7(18):26916-26924.
[27]Kou F,Lu Z,Li J,et al.Pretreatment lymphopenia is an easily detectable predictive and prognostic marker in patients with Metastatic esophagus squamous cell carcinoma receiving first-line chemotherapy[J].Cancer Med,2016,5(5):778-786.
[28]Shaverdian N,Veruttipong D,Wang J,et al.Pretreatment immune parameters predict for overall survival and toxicity in early-stage nonsmall-cell lung cancer patients treated with stereotactic body radiation therapy[J].Clin Lung Cancer,2016,17(1):39-46.
[29]Joseph N,Dovedi SJ,Thompson C,et al.Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer[J].Ann Oncol,2016,27(2):294-299.
[30]Chadha AS,Liu G,Chen HC,et al.Does unintentional splenic radiation predict outcomes after pancreatic cancer radiation therapy?[J].Int J Radiat Oncol Biol Phys,2017,97(2):323-332.
[31]Kozak MM,Von Eyben R,Pai JS,et al.The prognostic significance of pretreatment hematologic parameters in patients undergoing resection for colorectal cancer[J].Am J Clin Oncol,2017,40(4):405-412.
[32]左宏平,周瑜,卢震辉.外周血相关参数对肝癌预后评估价值的研究进展[J].中国卫生标准管理,2017,8(19):78-80.
[33]徐正水,程华.血常规对胃癌的预后的评估价值的研究进展[J].中华胃肠外科杂志,2017,20(2):236-240.
[34]陈欣,张国楠.外周血淋巴细胞计数在恶性肿瘤预后中的研究进展[J].肿瘤预防与治疗,2013,26(6):367-370.
[2]Cho O,Oh YT,Chun M,et al.Minimum absolute lymphocyte count during radiotherapy as a new prognostic factor for nasopharyngeal cancer[J/CD].Head Neck,2016,38(Suppl 1):E1061-1067.
[3]Yellu M,Fakhrejahani F,Ying J,et al.Lymphopenia as a predictor of survival in chemoradiation(CRT)-treated stageⅢnonsmall cell lung cancer(NSCLC)[J].J Clin Oncol,2015,33(15).
[4]Cho O,Oh YT,Chun M,et al.Radiation-related lymphopenia as a new prognostic factor in limited-stage small cell lung cancer[J].Tumour Biol,2016,37(1):971-978.
[5]Davuluri R,Jiang W,Fang P,et al.Lymphocyte nadir and esophageal cancer survival outcomes after chemoradiation therapy[J].Int J Radiat Oncol Biol Phys,2017,99(1):128-135.
[6]Wild AT,Ye X,Ellsworth SG,et al.The association between chemoradiation-related lymphopenia and clinical outcomes in patients with locally advanced pancreatic adenocarcinoma[J].Am J Clin Oncol,2015,38(3):259-265.
[7]Balmanoukian A,Ye X,Herman J,et al.The association between treatment-related lymphopenia and survival in newly diagnosed patients with resected adenocarcinoma of the pancreas[J].Cancer Invest,2012,30(8):571-576.
[8]Ray-Coquard I,Cropet C,Van Glabbeke M,et al.Lymphopenia as a prognostic factor for overall survival in advanced carcinomas,sarcomas,and lymphomas[J].Cancer Res,2009,69(13):5383-5391.
[9]Manuel M,Tredan O,Bachelot T,et al.Lymphopenia combined with low TCR diversity(divpenia)predicts poor overall survival in Metastatic breast cancer patients[J].Oncol Immunol,2012,1(4):432-440.
[10]Vasquez L,Leon E,Beltran B,et al.Pretreatment neutrophil-tolymphocyte ratio and lymphocyte recovery:Independent prognostic factors for survival in pediatric sarcomas[J].J Pediatr Hematol Oncol,2017,39(7):538-546.
[11]Claude L,Perol D,Ray-Coquard I,et al.Lymphopenia:a new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain Metastases from breast carcinoma[J].Radiother Oncol,2005,76(3):334-339.
[12]Seve P,Ray-Coquard I,Trillet-Lenoir V,et al.Low serum albumin levels and liver metastasis are powerful prognostic markers for survival in patients with carcinomas of unknown primary site[J].Cancer,2006,107(11):2698-2705.
[13]Le Scodan R,Massard C,Mouret-Fourme E,et al.Brain metastases from breast carcinoma:validation of the radiation therapy oncology group recursive partitioning analysis classification and proposition of a new prognostic score[J].Int J Radiat Oncol Biol Phys,2007,69(3):839-845.
[14]Ceze N,Thibault G,Goujon G,et al.Pre-treatment lymphopenia as a prognostic biomarker in colorectal cancer patients receiving chemotherapy[J].Cancer Chemother Pharmacol,2011,68(5):1305-1313.
[15]De Giorgi U,Mego M,Scarpi E,et al.Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in Metastatic breast cancer[J].Clin Breast Cancer,2012,12(4):264-269.
[16]Saroha S,Uzzo RG,Plimack ER,et al.Lymphopenia is an independent predictor of inferior outcome in clear cell renal carcinoma[J].J Urol,2013,189(2):454-461.
[17]De Giorgi U,Rihawi K,Aieta M,et al.Lymphopenia and clinical outcome of elderly patients treated with sunitinib for Metastatic renal cell cancer[J].J Geriatr Oncol,2014,5(2):156-163.
[18]Mehrazin R,Uzzo RG,Kutikov A,et al.Lymphopenia is an independent predictor of inferior outcome in papillary renal cell carcinoma[J/CD].Urol Oncol,2015,33(9):388.e319-325.
[19]Ku JH,Kang M,Kim HS,et al.The prognostic value of pretreatment of systemic inflammatory responses in patients with urothelial carcinoma undergoing radical cystectomy[J].Br J Cancer,2015,112(3):461-467.
[20]Santoni M,Buti S,Conti A,et al.Prognostic significance of host immune status in patients with late relapsing renal cell carcinoma treated with targeted therapy[J].Target Oncol,2015,10(4):517-522.
[21]Wild AT,Herman JM,Dholakia AS,et al.Lymphocyte-sparing effect of stereotactic body radiation therapy in patients with unresectable pancreatic cancer[J].Int J Radiat Oncol Biol Phys,2016,94(3):571-579.
[22]Mendez JS,Govindan A,Leong J,et al.Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma[J].J Neurooncol,2016,127(2):329-335.
[23]Wu ES,Oduyebo T,Cobb LP,et al.Lymphopenia and its association with survival in patients with locally advanced cervical cancer[J].Gynecol Oncol,2016,140(1):76-82.
[24]Choi Y,Oh DY,Park H,et al.More accurate prediction of metastatic pancreatic cancer patients'survival with prognostic model using both host immunity and tumor metabolic activity[J/CD].PLoS One,2016,11(1):e0145692.
[25]Cho O,Chun M,Chang SJ,et al.Prognostic value of severe lymphopenia during pelvic concurrent chemoradiotherapy in cervical cancer[J].Anticancer Res,2016,36(7):3541-3547.
[26]Berardi R,Rinaldi S,Santoni M,et al.Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo-or targeted therapy[J].Oncotarget,2016,7(18):26916-26924.
[27]Kou F,Lu Z,Li J,et al.Pretreatment lymphopenia is an easily detectable predictive and prognostic marker in patients with Metastatic esophagus squamous cell carcinoma receiving first-line chemotherapy[J].Cancer Med,2016,5(5):778-786.
[28]Shaverdian N,Veruttipong D,Wang J,et al.Pretreatment immune parameters predict for overall survival and toxicity in early-stage nonsmall-cell lung cancer patients treated with stereotactic body radiation therapy[J].Clin Lung Cancer,2016,17(1):39-46.
[29]Joseph N,Dovedi SJ,Thompson C,et al.Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer[J].Ann Oncol,2016,27(2):294-299.
[30]Chadha AS,Liu G,Chen HC,et al.Does unintentional splenic radiation predict outcomes after pancreatic cancer radiation therapy?[J].Int J Radiat Oncol Biol Phys,2017,97(2):323-332.
[31]Kozak MM,Von Eyben R,Pai JS,et al.The prognostic significance of pretreatment hematologic parameters in patients undergoing resection for colorectal cancer[J].Am J Clin Oncol,2017,40(4):405-412.
[32]左宏平,周瑜,卢震辉.外周血相关参数对肝癌预后评估价值的研究进展[J].中国卫生标准管理,2017,8(19):78-80.
[33]徐正水,程华.血常规对胃癌的预后的评估价值的研究进展[J].中华胃肠外科杂志,2017,20(2):236-240.
[34]陈欣,张国楠.外周血淋巴细胞计数在恶性肿瘤预后中的研究进展[J].肿瘤预防与治疗,2013,26(6):367-370.