Grenader T, Waddell T, Peckitt C, Oates J, Starling N, Cunningham D, Bridgewater J
Oncology Institute, Shaare Zedek Medical Centre, Jerusalem, Israel.
Section of GI and Lymphoma Units, Department of Medicine, The Royal Marsden Hospital, London.
Ann Oncol. 2016 Apr;27(4):687-92. doi: 10.1093/annonc/mdw012. Epub 2016 Jan 19.
The REAL-2 trial demonstrated that capecitabine and oxaliplatin were effective alternatives to fluorouracil and cisplatin, respectively, when used in triplet chemotherapy regimens for previously untreated oesophago-gastric cancer. The aim of the current analysis was to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in the REAL-2 cohort.
A post hoc exploratory analysis was carried out on REAL-2 patients with the available absolute neutrophil count and absolute lymphocyte count. A high NLR was defined using a cut-off value of >3.0. The NLR was then correlated with clinical outcomes including overall survival (OS), progression-free survival (PFS) and objective response rate. Survival curves were generated using the Kaplan-Meier method and comparison between groups was carried out using Cox regression.
Data were available in 908 of the 1002 REAL-2 participants. Of these, 516 (56.8%) were deemed to have a high NLR. In univariate analysis, high NLR was associated with a hazard ratio (HR) for OS of 1.73 (1.50-2.00), P < 0.001, compared with low NLR, equating to median OS values of 9.1 [95% confidence interval (CI) 8.0-9.6] and 12.7 months (95% CI 10.8-14.4), respectively. The NLR remained highly significant for OS (P < 0.001) in a multivariate model including performance status, age, disease extent, presence of liver metastases and presence of peritoneal metastases. For PFS, high NLR was associated with an HR of 1.63 (1.41-1.87), P < 0.001, compared with low NLR in univariate analysis. No significant interaction was found between NLR status and treatment arm, 13% of all patients with low NLR achieving survival beyond 24 months compared with only 6% of patients with high NLR (P < 0.001).
Our results confirm that high NLR status had a significant negative prognostic effect in the REAL-2 trial population. Based on the multivariate analysis, this effect was independent of other known prognostic factors.
REAL-2试验表明，卡培他滨和奥沙利铂分别是氟尿嘧啶和顺铂的有效替代药物，用于既往未治疗的食管胃癌三联化疗方案。本分析的目的是评估中性粒细胞与淋巴细胞比值（NLR）在REAL-2队列中的预后价值。
对REAL-2研究中可获得绝对中性粒细胞计数和绝对淋巴细胞计数的患者进行事后探索性分析。NLR高于3.0定义为高NLR。然后将NLR与包括总生存期（OS）、无进展生存期（PFS）和客观缓解率在内的临床结局进行关联分析。采用Kaplan-Meier法生成生存曲线，并使用Cox回归进行组间比较。
1002名REAL-2参与者中有908人有可用数据。其中，516人（56.8%）被认为NLR较高。单因素分析中，与低NLR相比，高NLR与OS的风险比（HR）为1.73（1.50 - 2.00），P < 0.001，中位OS值分别为9.1个月[95%置信区间（CI）8.0 - 9.6]和12.7个月（95% CI 10.8 - 14.4）。在包括体能状态、年龄、疾病范围、肝转移和腹膜转移的多因素模型中，NLR对OS仍具有高度显著性（P < 0.001）。对于PFS，单因素分析中，与低NLR相比，高NLR与HR为1.63（1.41 - 1.87），P < 0.001。未发现NLR状态与治疗组之间存在显著交互作用，所有低NLR患者中有13%生存期超过24个月，而高NLR患者中只有6%（P < 0.001）。
我们的结果证实，在REAL-2试验人群中，高NLR状态具有显著的负面预后影响。基于多因素分析，这种影响独立于其他已知的预后因素。
