外周血炎症细胞比值对Ⅱ、Ⅲ期可切除直肠癌术后同步放化疗患者急性不良反应和预后的影响

Effect of peripheral blood inflammatory cell ratios on acute adverse reactions and prognosis of patients with resectable stage Ⅱ, Ⅲ rectal cancer after concurrent radiotherapy and chemotherapy

摘要:

目的 探讨外周血炎症细胞比值对Ⅱ、Ⅲ期可切除直肠癌术后同步放化疗患者急性不良反应和预后的影响。方法 选取2014年11月—2016年11月甘肃省兰州市第一人民医院收治的Ⅱ、Ⅲ期可切除直肠癌患者81例作为研究对象，均行R0全直肠系膜切除术及术后放化疗，中位随访时间5年。收集所有患者临床资料，包括中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、中性粒细胞与白蛋白比值（NAR），记录同步放化疗急性不良反应分级，分析影响直肠癌患者预后的因素及生存状况。结果 白细胞< 2级组与 ≥ 2级组患者外周血NLR比较，差异无统计学意义（P >0.05）；白细胞< 2级组外周血PLR、NAR低于≥ 2级组（P <0.05）。腹泻< 2级组与 ≥ 2级组患者外周血NLR、PLR比较，差异无统计学意义（P >0.05）；腹泻 < 2级组外周血NAR低于≥ 2级组（P <0.05）。放射性皮炎< 2级组与≥ 2级组患者外周血NLR、PLR比较，差异无统计学意义（P >0.05）；放射性皮炎< 2级组外周血NAR低于≥ 2级组（P <0.05）。逐步多因素Cox比例风险回归分析结果显示：病理分期［R^R=6.044（95% CI：2.657，13.748）］、分化程度［R^R=5.557（95% CI：2.443，12.640）］、淋巴结转移［R^R=4.540（95% CI：1.996，10.328）］及NAR［R^R=4.047（95% CI：1.779，9.206）］是直肠癌患者复发转移的独立危险因素（P <0.05）；病理分期［R^R=3.850（95% CI：1.692，8.757）］、分化程度［R^R=3.785（95% CI：1.664，8.610）］及NAR［R^R=3.857（95% CI：1.696，8.775）］是直肠癌患者死亡的独立危险因素（P <0.05）。ROC曲线结果显示，外周血NAR最佳截断值为0.05时，预测直肠癌患者无病生存的敏感性为76.09%（95% CI：0.609，0.869），特异性为72.00%（95% CI：0.504，0.871），曲线下面积（AUC）为0.766（95% CI：0.669，0.862）；外周血NAR最佳截断值为0.06时，预测直肠癌患者生存的敏感性为75.00%（95% CI：0.608，0.855），特异性为73.68%（95% CI：0.486，0.899），AUC为0.730（95% CI：0.627，0.833）。NAR高水平组与低水平组患者的无病生存曲线、总生存曲线比较，差异均有统计学意义（P <0.05）。结论 Ⅱ、Ⅲ期可切除直肠癌患者外周血NAR水平与直肠癌术后放化疗急性不良反应及预后有关，NAR高水平患者发生高级别急性不良反应和预后不良的风险较高。

Abstract:

Objective To explore the effect of peripheral blood inflammation cell ratios on the acute adverse reactions and prognosis of patients with resectable stage Ⅱ, Ⅲ rectal cancer after concurrent radiotherapy and chemotherapy.Methods A total of 81 patients with resectable stage Ⅱ, Ⅲ rectal cancer who were admitted to the hospital from November 2014 to November 2016 were selected. All patients underwent R0 total mesorectal excision and postoperative radiotherapy and chemotherapy, and were followed up for a median duration of 5 years. The clinical data including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and neutrophil to albumin ratio (NAR) of all patients were collected. The peripheral blood NLR, PLR, and NAR of patients with different levels of acute adverse reactions after radiotherapy and chemotherapy were recorded, and the factors affecting the prognosis and survival status of patients with rectal cancer were analyzed.Results There was no statistically significant difference in NLR between patients with leukopenia less than grade 2 and those with leukopenia no less than grade 2 (P > 0.05), while PLR and NAR in patients with leukopenia less than grade 2 were lower than those in patients with leukopenia no less than grade 2 (P < 0.05). The NAR of patients with diarrhea less than grade 2 was lower than that of patients with diarrhea no less than grade 2 (P < 0.05), while there was no difference in NLR and PLR between the patients with diarrhea less than grade 2 and those with diarrhea no less than grade 2 (P > 0.05). As for radiation dermatitis, NLR and PLR were not different between patients with radiation dermatitis less than grade 2 and no less than grade 2 (P > 0.05), while NAR in patients with radiation dermatitis less than grade 2 was lower than that of patients with radiation dermatitis no less than grade 2 (P < 0.05). The multivariable Logistic regression analysis showed that pathological stage [ R^R = 6.044 (95% CI: 2.657, 13.748) ], degree of differentiation [ R^R = 5.557 (95% CI: 2.443, 12.640) ], lymph node metastasis [ R^R = 4.540 (95% CI: 1.996, 10.328) ] and NAR [ R^R = 4.047 (95% CI: 1.779, 9.206) ] were independent factors affecting the recurrence and metastasis of patients with rectal cancer (P < 0.05), and that pathological stage [ R^R = 3.850 (95% CI: 1.692, 8.757) ], degree of differentiation [ R^R = 3.785 (95% CI: 1.664, 8.610) ] and NAR [ R^R = 3.857 (95% CI: 1.696, 8.775) ] were independent factors affecting the survival of patients with rectal cancer (P < 0.05). The receiver operating characteristic (ROC) curve analysis revealed that the sensitivity, specificity and the area under the ROC curve (AUC) of peripheral blood NAR, with an optimal cutoff value of 0.05, for predicting disease-free survival of patients with resectable stage Ⅱ, Ⅲ rectal cancer were 76.09% (95% CI: 60.90%, 86.90%), 72.00% (95% CI: 50.40%, 87.10%), and 0.766 (95% CI: 0.669, 0.862), respectively. In addition, the sensitivity, specificity and AUC of peripheral blood NAR with an optimal cutoff value of 0.06 for predicting the overall survival of patients with resectable stage Ⅱ, Ⅲ rectal cancer were 75.00% (95% CI: 60.80%, 85.50%), 73.68% (95% CI: 48.60%, 89.90%), and 0.730 (95% CI: 0.627, 0.833), respectively. The differences in the disease-free survival curves and overall survival curves between patients with high-level and low-level NAR were statistically significant (P < 0.05).Conclusions Peripheral blood NAR in patients with resectable stage Ⅱ, Ⅲ rectal cancer is related to high-grade acute adverse reactions and prognosis after radiotherapy and chemotherapy. Patients with high NAR tend to develop high-grade acute adverse reactions and have a poor prognosis.