外周血中性粒细胞与淋巴细胞比率对NSCLC患者放疗效果的预测价值
|
摘要
目的探讨放疗前后外周血中性粒细胞与淋巴细胞比率(neutrophil to lymphocyte ratio,NLR)及其变化(ΔNLR)对晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者放疗效果的预测价值。方法回顾性分析2011年3月至2016年5月本院行单纯放疗有完整随访资料的70例晚期NSCLC患者的临床资料,近期疗效分放疗敏感(PR+CR)组和非敏感(SD+PD)组,远期疗效以中位PFS为临界值分两组,分别检测各组放疗前后的血常规。以中位NLR为临界值分为高低两组,以放疗后NLR升高或降低分组,分别对比各组近期疗效的差别。结果放疗前NLR及其他血细胞指标与放疗敏感性、无进展生存期(progression-free survival,PFS)无相关性(P>0.05)。放疗后NLR、ΔNLR与近期疗效呈负相关(P<0.05),而与PFS无明显相关;放疗后NLR中位值为4.93,当NLR<4.93时,客观缓解率(ORR)为69%,NLR≥4.93时,ORR为37%;与放疗前比较,放疗后NLR降低(ΔNLR<0)组ORR为71%,而放疗后NLR升高(ΔNLR≥0)组ORR为45%。放疗后PLR、MLR及ΔPLR、ΔMLR也与近期疗效呈负相关(P<0.05),且放疗后PLR、MLR与NLR存在一致性,ΔPLR、ΔMLR与ΔNLR存在一致性(r>0.5,P<0.001)。结论放疗后的NLR、ΔNLR可作为与放疗近期疗效相关的预测指标。
Objective To investigate the predictive value of neutrophil to lymphocyte ratio(NLR) in the peripheral blood and its changes(ΔNLR) after radiotherapy in advanced non-small cell lung cancer(NSCLC) patients. Methods The clinical data of 70 patients with advanced NSCLC who received simple radiotherapy in our hospital from March 2011 to June 2016 with complete follow-up data were retrospectively analyzed. The patients were divided into 2 groups based on the short-term efficacy: the radiotherapy sensitivity(PR+CR) group and non-sensitivity(SD+PD) group. They were also divided into 2 groups based on the long-term efficacy with median progression-free survival(PFS) as the critical value. Blood routine test was carried out before and after radiotherapy, and the results was compared between the 2 groups. Then with NLR as the critical value, the patients were divided into 2 groups. Differences in short-term efficacy were compared between those with increased NLR and those with decreased NLR. Results Before radiotherapy, NLR and other blood cell parameters had no correlation with radiosensitivity or PFS(P>0.05). After radiotherapy, NLR and ΔNLR were negatively correlated with short-term efficacy(P<0.05), but was not correlated with PFS. After radiotherapy, NLR median value was 4.93, and objective response rate(ORR) was 69% when NLR <4.93; and was 37% when ≥4.93. In the group with decreased NLR(ΔNLR<0) after radiotherapy, ORR was 71%; in the group with increased NLR(ΔNLR≥0) after radiotherapy, ORR was 45%. Platelet to lymphocyte ratio(PLR), monocytes to lymphocyte ratio(MLR), ΔPLR and ΔMLR were also negatively correlated with short-term efficacy after radiotherapy(P<0.05), and PLR, MLR and NLR were consistent, while ΔPLR, ΔMLR and ΔNLR were also consistent after radiotherapy(r>0.5, P<0.001). Conclusion After radiotherapy both NLR and ΔNLR can be used as predictive indicators for the short-term efficacy of radiotherapy in NSCLC patients.
Objective To investigate the predictive value of neutrophil to lymphocyte ratio(NLR) in the peripheral blood and its changes(ΔNLR) after radiotherapy in advanced non-small cell lung cancer(NSCLC) patients. Methods The clinical data of 70 patients with advanced NSCLC who received simple radiotherapy in our hospital from March 2011 to June 2016 with complete follow-up data were retrospectively analyzed. The patients were divided into 2 groups based on the short-term efficacy: the radiotherapy sensitivity(PR+CR) group and non-sensitivity(SD+PD) group. They were also divided into 2 groups based on the long-term efficacy with median progression-free survival(PFS) as the critical value. Blood routine test was carried out before and after radiotherapy, and the results was compared between the 2 groups. Then with NLR as the critical value, the patients were divided into 2 groups. Differences in short-term efficacy were compared between those with increased NLR and those with decreased NLR. Results Before radiotherapy, NLR and other blood cell parameters had no correlation with radiosensitivity or PFS(P>0.05). After radiotherapy, NLR and ΔNLR were negatively correlated with short-term efficacy(P<0.05), but was not correlated with PFS. After radiotherapy, NLR median value was 4.93, and objective response rate(ORR) was 69% when NLR <4.93; and was 37% when ≥4.93. In the group with decreased NLR(ΔNLR<0) after radiotherapy, ORR was 71%; in the group with increased NLR(ΔNLR≥0) after radiotherapy, ORR was 45%. Platelet to lymphocyte ratio(PLR), monocytes to lymphocyte ratio(MLR), ΔPLR and ΔMLR were also negatively correlated with short-term efficacy after radiotherapy(P<0.05), and PLR, MLR and NLR were consistent, while ΔPLR, ΔMLR and ΔNLR were also consistent after radiotherapy(r>0.5, P<0.001). Conclusion After radiotherapy both NLR and ΔNLR can be used as predictive indicators for the short-term efficacy of radiotherapy in NSCLC patients.
引文
[1] TISSOT C,GAY P,BRUN C,et al.Novel insights into the systemic treatment of lung cancer malignant pleural effusion[J].Clin Respir J,2019,13(3):131-138.DOI:10.1111/crj.13005.
[2] WOOD D E,KAZEROONI E A,BAUM S L,et al.Lung cancer screening,version 3.2018,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2018,16(4):412-441.DOI:10.6004/jnccn.2018.0020.
[3] CHENG M,JOLLY S,QUARSHIE W O,et al.Modern radiation further improves survival in non-small cell lung cancer:An analysis of 288,670 patients[J].J Cancer,2019,10(1):168-177.DOI:10.7150/jca.26600.
[4] XU Z J,YAN Y L,XIAO L F,et al.Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway[J].PLoS ONE,2017,12(4):e0175977.DOI:10.1371/journal.pone.0175977.
[5] MANTOVANI A,ALLAVENA P,SICA A,et al.Cancer-related inflammation[J].Nature,2008,454(7203):436-444.DOI:10.1038/nature07205.
[6] KIM T H,ROWAT A C,SLOAN E K.Neural regulation of cancer:from mechanobiology to inflammation[J].Clin Transl Immunol,2016,5(5):e78.DOI:10.1038/cti.2016.18.
[7] FERNANDES J V,COBUCCI R N,JATOBá C A,et al.The role of the mediators of inflammation in cancer development[J].Pathol Oncol Res,2015,21(3):527-534.DOI:10.1007/s12253-015-9913-z.
[8] TEMPLETON A J,MCNAMARA M G,?ERUGA B,et al.Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors:A systematic review and meta-analysis[J].J Natl Cancer Inst,2014,106(6):dju124.DOI:10.1093/jnci/dju124.
[9] SUN H,HU P,DU J,et al.Predictive value of inflammatory indexes on the chemotherapeutic response in patients with unresectable lung cancer:A retrospective study[J].Oncol Lett,2018,15(3):4017-4025.DOI:10.3892/ol.2018.7781.
[10] MUNN L L.Cancer and inflammation[J].WIREs Syst Biol Med,2017,9(2):e1370.DOI:10.1002/wsbm.1370.
[11] ZHANG H,XIA H G,ZHANG L M,et al.Clinical significance of preoperative neutrophil-lymphocyte vs platelet-lymphocyte ratio in primary operable patients with non-small cell lung cancer[J].Am J Surg,2015,210(3):526-535.DOI:10.1016/j.amjsurg.2015.03.022.
[12] SCILLA K A,BENTZEN S M,LAM V K,et al.Neutrophil-lymphocyte ratio is a prognostic marker in patients with locally advanced (stage ⅢA and ⅢB) non-small cell lung cancer treated with combined modality therapy[J].Oncologist,2017,22(6):737-742.DOI:10.1634/theoncologist.2016-0443.
[13] MOSES K,BRANDAU S.Human neutrophils:Their role in cancer and relation to myeloid-derived suppressor cells[J].Semin Immunol,2016,28(2):187-196.DOI:10.1016/j.smim.2016.03.018.
[14] ZHOU X,DU Y P,HUANG Z B,et al.Prognostic value of PLR in various cancers:A meta-analysis[J].PLoS ONE,2014,9(6):e101119.DOI:10.1371/journal.pone.0101119.
[15] SOYDAL C,KESKIN O,KUCUK O N,et al.Prognostic factors for prediction of survival of hepatocellular cancer patients after selective internal radiation therapy[J].Ann Nucl Med,2015,29(5):426-430.DOI:10.1007/s12149-015-0962-x.
[16] GRIVENNIKOV S I,GRETEN F R,KARIN M.Immunity,inflammation,and cancer[J].Cell,2010,140(6):883-899.DOI:10.1016/j.cell.2010.01.025.
[17] HANAHAN D,COUSSENS L M.Accessories to the crime:functions of cells recruited to the tumor microenvironment[J].Cancer Cell,2012,21(3):309-322.DOI:10.1016/j.ccr.2012.02.022.
[18] YODYING H,MATSUDA A,MIYASHITA M,et al.Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer:A systematic review and meta-analysis[J].Ann Surg Oncol,2016,23(2):646-654.DOI:10.1245/s10434-015-4869-5.
[19] XUE T C,JIA Q A,GE N L,et al.Imbalance in systemic inflammation and immune response following transarterial chemoembolization potentially increases metastatic risk in huge hepatocellular carcinoma[J].Tumor Biol,2015,36(11):8797-8803.DOI:10.1007/s13277-015-3632-7.
[20] FAN W,ZHANG Y,WANG Y,et al.Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of survival and metastasis for recurrent hepatocellular carcinoma after transarterial chemoembolization[J].PLoS ONE,2015,10(3):e0119312.DOI:10.1371/journal.pone.0119312.
[21] MIZUNUMA M,YOKOYAMA Y,FUTAGAMI M,et al.The pretreatment neutrophil-to-lymphocyte ratio predicts therapeutic response to radiation therapy and concurrent chemoradiation therapy in uterine cervical cancer[J].Int J Clin Oncol,2015,20(5):989-996.DOI:10.1007/s10147-015-0807-6.
[22] PENG W,LI C,WEN T F,et al.Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival[J].J Surg Res,2014,192(2):402-408.DOI:10.1016/j.jss.2014.05.078.
[23] TEMPLETON A J,KNOX J J,LIN X,et al.Change in neutrophil-to-lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy[J].Eur Urol,2016,70(2):358-364.DOI:10.1016/j.eururo.2016.02.033.
[24] LALANI A A,XIE W,MARTINI D J,et al.Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma[J].J Immunother Cancer,2018,6(1):5.DOI:10.1186/s40425-018-0315-0.
[25] JIN F,HAN A,SHI F,et al.The postoperative neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after the complete resection of stage I non-small cell lung cancer[J].Oncotargets Ther,2016,9:6529-6537.DOI:10.2147/OTT.S117290.
[2] WOOD D E,KAZEROONI E A,BAUM S L,et al.Lung cancer screening,version 3.2018,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2018,16(4):412-441.DOI:10.6004/jnccn.2018.0020.
[3] CHENG M,JOLLY S,QUARSHIE W O,et al.Modern radiation further improves survival in non-small cell lung cancer:An analysis of 288,670 patients[J].J Cancer,2019,10(1):168-177.DOI:10.7150/jca.26600.
[4] XU Z J,YAN Y L,XIAO L F,et al.Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway[J].PLoS ONE,2017,12(4):e0175977.DOI:10.1371/journal.pone.0175977.
[5] MANTOVANI A,ALLAVENA P,SICA A,et al.Cancer-related inflammation[J].Nature,2008,454(7203):436-444.DOI:10.1038/nature07205.
[6] KIM T H,ROWAT A C,SLOAN E K.Neural regulation of cancer:from mechanobiology to inflammation[J].Clin Transl Immunol,2016,5(5):e78.DOI:10.1038/cti.2016.18.
[7] FERNANDES J V,COBUCCI R N,JATOBá C A,et al.The role of the mediators of inflammation in cancer development[J].Pathol Oncol Res,2015,21(3):527-534.DOI:10.1007/s12253-015-9913-z.
[8] TEMPLETON A J,MCNAMARA M G,?ERUGA B,et al.Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors:A systematic review and meta-analysis[J].J Natl Cancer Inst,2014,106(6):dju124.DOI:10.1093/jnci/dju124.
[9] SUN H,HU P,DU J,et al.Predictive value of inflammatory indexes on the chemotherapeutic response in patients with unresectable lung cancer:A retrospective study[J].Oncol Lett,2018,15(3):4017-4025.DOI:10.3892/ol.2018.7781.
[10] MUNN L L.Cancer and inflammation[J].WIREs Syst Biol Med,2017,9(2):e1370.DOI:10.1002/wsbm.1370.
[11] ZHANG H,XIA H G,ZHANG L M,et al.Clinical significance of preoperative neutrophil-lymphocyte vs platelet-lymphocyte ratio in primary operable patients with non-small cell lung cancer[J].Am J Surg,2015,210(3):526-535.DOI:10.1016/j.amjsurg.2015.03.022.
[12] SCILLA K A,BENTZEN S M,LAM V K,et al.Neutrophil-lymphocyte ratio is a prognostic marker in patients with locally advanced (stage ⅢA and ⅢB) non-small cell lung cancer treated with combined modality therapy[J].Oncologist,2017,22(6):737-742.DOI:10.1634/theoncologist.2016-0443.
[13] MOSES K,BRANDAU S.Human neutrophils:Their role in cancer and relation to myeloid-derived suppressor cells[J].Semin Immunol,2016,28(2):187-196.DOI:10.1016/j.smim.2016.03.018.
[14] ZHOU X,DU Y P,HUANG Z B,et al.Prognostic value of PLR in various cancers:A meta-analysis[J].PLoS ONE,2014,9(6):e101119.DOI:10.1371/journal.pone.0101119.
[15] SOYDAL C,KESKIN O,KUCUK O N,et al.Prognostic factors for prediction of survival of hepatocellular cancer patients after selective internal radiation therapy[J].Ann Nucl Med,2015,29(5):426-430.DOI:10.1007/s12149-015-0962-x.
[16] GRIVENNIKOV S I,GRETEN F R,KARIN M.Immunity,inflammation,and cancer[J].Cell,2010,140(6):883-899.DOI:10.1016/j.cell.2010.01.025.
[17] HANAHAN D,COUSSENS L M.Accessories to the crime:functions of cells recruited to the tumor microenvironment[J].Cancer Cell,2012,21(3):309-322.DOI:10.1016/j.ccr.2012.02.022.
[18] YODYING H,MATSUDA A,MIYASHITA M,et al.Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer:A systematic review and meta-analysis[J].Ann Surg Oncol,2016,23(2):646-654.DOI:10.1245/s10434-015-4869-5.
[19] XUE T C,JIA Q A,GE N L,et al.Imbalance in systemic inflammation and immune response following transarterial chemoembolization potentially increases metastatic risk in huge hepatocellular carcinoma[J].Tumor Biol,2015,36(11):8797-8803.DOI:10.1007/s13277-015-3632-7.
[20] FAN W,ZHANG Y,WANG Y,et al.Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of survival and metastasis for recurrent hepatocellular carcinoma after transarterial chemoembolization[J].PLoS ONE,2015,10(3):e0119312.DOI:10.1371/journal.pone.0119312.
[21] MIZUNUMA M,YOKOYAMA Y,FUTAGAMI M,et al.The pretreatment neutrophil-to-lymphocyte ratio predicts therapeutic response to radiation therapy and concurrent chemoradiation therapy in uterine cervical cancer[J].Int J Clin Oncol,2015,20(5):989-996.DOI:10.1007/s10147-015-0807-6.
[22] PENG W,LI C,WEN T F,et al.Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival[J].J Surg Res,2014,192(2):402-408.DOI:10.1016/j.jss.2014.05.078.
[23] TEMPLETON A J,KNOX J J,LIN X,et al.Change in neutrophil-to-lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy[J].Eur Urol,2016,70(2):358-364.DOI:10.1016/j.eururo.2016.02.033.
[24] LALANI A A,XIE W,MARTINI D J,et al.Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma[J].J Immunother Cancer,2018,6(1):5.DOI:10.1186/s40425-018-0315-0.
[25] JIN F,HAN A,SHI F,et al.The postoperative neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after the complete resection of stage I non-small cell lung cancer[J].Oncotargets Ther,2016,9:6529-6537.DOI:10.2147/OTT.S117290.