炎症及营养指标与直肠癌新辅助放化疗病理反应及患者预后的相关性研究

Correlation between inflammatory-nutritional biomarkers and pathologic response and prognosis in rectal cancer patients undergoing neoadjuvant chemoradiotherapy

目的:分析不同的炎症及营养相关指标与直肠癌新辅助放化疗后肿瘤病理反应状态及患者预后的相关性,探讨其临床应用价值。方法:回顾性分析2012年10月至2019年2月在南京中医药大学附属医院接受新辅助放化疗及根治性手术的211例Ⅱ、Ⅲ期直肠癌患者的临床病理资料,依据患者放化疗前1周内血常规和肝肾功能检查结果,计算基线中性粒细胞/淋巴细胞之值(NLR)、血小板/淋巴细胞之值(PLR)、淋巴细胞/单核细胞之值(LMR)及预后营养指数(PNI)。根据患者术后病理结果,基于肿瘤消退分级(TRG)标准评价肿瘤病理反应状态。采用Logistic模型、Kaplan-Meier法、Cox回归模型分析各炎症及营养相关指标与直肠癌新辅助放化疗肿瘤病理反应状态及患者预后的相关性。结果:新辅助放化疗后病理反应(TRG 0~1级)患者共135例(64.0%),非病理反应(TRG 2~3级)患者76例(36.0%)。多因素Logistic回归分析结果显示,基线PNI(OR=1.245,95%CI 1.123~1.380,P<0.001)及癌胚抗原(OR=0.500,95%CI 0.255~0.979,P=0.043)是病理反应状态的独立影响因素。多因素预后分析显示性别、淋巴(ypN)分期、基线NLR及PNI是无病生存期(DFS)的独立影响因素;性别、ypN分期及基线PNI是总生存期(OS)的独立影响因素。分层分析显示ypN阳性患者中高PNI组(PNI>45)5年DFS和OS显著长于低PNI组(无病生存率63.6%vs.48.0%,P=0.002;总生存率69.2%vs.51.9%,P=0.005),而ypN阴性患者中高PNI组与低PNI组预后差异无统计学意义(无病生存率83.2%vs.79.5%,P=0.252;总生存率89.2%vs.85.1%,P=0.299)。结论:基线PNI水平与Ⅱ、Ⅲ期直肠癌新辅助放化疗后肿瘤病理反应状态及患者预后相关,其疗效预测价值优于NLR、PLR及LMR。PNI简单无创、经济有效,可作为临床预后预测指标的补充,值得进一步研究。

Objective:To evaluate the correlation between inflammatory-nutritional biomarkers and pathologic response and prognosis in rectal cancer patients undergoing neoadjuvant chemoradiotherapy,and to explore the clinical value of these biomarkers.Methods:Clinical and pathological data of 211 stage II-III rectal cancer patients treated with neoadjuvant chemoradiotherapy(nCRT)and subsequent surgery between October 2012 and February 2019 were retrospectively analyzed.Neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),lymphocyte-to-monocyte ratio(LMR)and prognostic nutritional index(PNI)were calculated according to routine laboratory data within 1 week prior nCRT.Pathological response was assessed using the tumor regression grade(TRG)system according to postoperative specimen histopathologic examinations.The relationship between inflammatory-nutritional biomarkers and pathologic response and prognosis were evaluated by Logistic regression analysis,Kaplan-Meier method and Cox regression analyses.Results:Totally,135 patients(64.0%)achieved good-response(TRG 0-1)and 76 patients(36.0%)achieved poor-response(TRG 2-3)after nCRT.Logistic regression analysis identified that PNI(OR=1.245,95%CI 1.123-1.380,P<0.001)and CEA(OR=0.500,95%CI 0.255-0.979,P=0.043)were the independent predictors for pathologic response to nCRT.Multivariate analysis identified gender,ypN stage,NLR and PNI were independent prognostic factors for disease-free survival(DFS)and gender,ypN stage and PNI were independent prognostic factors for overall survival(OS).A high PNI(>45)was significantly associated with better DFS and OS in patients with ypN positive subgroup(DFS 63.6%vs.48.0%,P=0.002;OS 69.2%vs.51.9%,P=0.005)but not in patients with ypN negative subgroup(DFS 83.2%vs.79.5%,P=0.252;OS 89.2%vs.85.1%,P=0.299).Conclusion:Pretreatment PNI is associated with pathologic response and prognosis in rectal cancer patients undergoing nCRT,superior to the established systemic inflammation markers including NLR,PLR and LMR.Its simplicity,noninvasion,low cost and effectiveness make the PNI a promising supplemental tool in predicting and prognosis marker for patients with rectal cancer.