Division of Hospital Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH, USA.
Division of Medical Oncology, Department of Internal Medicine, Ohio State University Wexner Medical Center, 320 W 10th Ave, A450B Starling Loving Hall, Columbus, OH, 43210, USA.
J Cancer Res Clin Oncol. 2019 Oct;145(10):2541-2546. doi: 10.1007/s00432-019-02982-4. Epub 2019 Jul 31.
The neutrophil to lymphocyte ratio (NLR) is known to be prognostic for patients with advanced cancers treated with immune checkpoint inhibitors (ICI), but has generally been evaluated as a single threshold value at baseline. We evaluated NLR at baseline and within first month during treatment in patients who received ICI for advanced cancer to evaluate the prognostic value of baseline and of changes from baseline to on-treatment NLR.
A retrospective review of patients with advanced cancer treated with ICI from 2011 to 2017 at the Ohio State University was performed. NLR was calculated at the initiation of ICI and repeated at median of 21 days. Overall survival (OS) was calculated from the initiation of ICI to date of death or censored at last follow-up. Significance of Cox proportional hazards models were evaluated by log-rank test. Calculations were performed using the survival and survminer packages in R, and SPSS.
509 patients were identified and included in the analysis. Patients with baseline and on-treatment NLR < 5 had significantly longer OS (P < 0.001). The change in NLR overtime was a predictor of OS and was observed to be non-linear in nature. This property remained statistically significant with P < 0.05 after adjusting for age, body mass index, sex, cancer type, performance status, and days to repeat NLR measurement. Patients with a moderate decrease in NLR from baseline had the longest OS of 27.8 months (95% CI 21.8-33.8). Patients with significant NLR decrease had OS of 11.4 months (95% CI 6.1-16.7). Patients with a significant increase in NLR had the shortest OS of 5.0 months (95% CI 0.9-9.1).
We confirmed the prognostic value of NLR in patients with advanced cancer treated with ICIs. We found that change in NLR over time is a non-linear predictor of patient outcomes. Patients who had moderate decrease in NLR during treatment with ICI were found to have the longest survival, whereas a significant decrease or increase in NLR was associated with shorter survival. To our knowledge, this is the first study to demonstrate a non-linear change in NLR over time that correlates with survival.
中性粒细胞与淋巴细胞比值（NLR）已知可预测接受免疫检查点抑制剂（ICI）治疗的晚期癌症患者的预后，但通常在基线时评估为单一阈值。我们评估了接受 ICI 治疗的晚期癌症患者在基线和治疗后第一个月的 NLR，以评估基线和从基线到治疗中 NLR 变化的预后价值。
对 2011 年至 2017 年在俄亥俄州立大学接受 ICI 治疗的晚期癌症患者进行了回顾性研究。在开始 ICI 时计算 NLR，并在中位数 21 天重复计算。从开始 ICI 到死亡日期或最后一次随访时进行总体生存（OS）计算。Cox 比例风险模型的显著性通过对数秩检验进行评估。计算使用 R 中的 survival 和 survminer 包以及 SPSS 进行。
共确定 509 例患者并纳入分析。基线和治疗中 NLR<5 的患者的 OS 明显更长（P<0.001）。NLR 随时间的变化是 OS 的预测指标，并且观察到其呈非线性。在调整年龄、体重指数、性别、癌症类型、表现状态和重复 NLR 测量的天数后，这一特性仍然具有统计学意义（P<0.05）。从基线 NLR 中度下降的患者 OS 最长，为 27.8 个月（95%CI 21.8-33.8）。NLR 显著下降的患者 OS 为 11.4 个月（95%CI 6.1-16.7）。NLR 显著增加的患者 OS 最短，为 5.0 个月（95%CI 0.9-9.1）。
我们证实了 NLR 在接受 ICI 治疗的晚期癌症患者中的预后价值。我们发现 NLR 随时间的变化是患者结局的非线性预测指标。在接受 ICI 治疗期间 NLR 中度下降的患者发现生存时间最长，而 NLR 显著下降或增加与生存时间缩短相关。据我们所知，这是第一项证明 NLR 随时间非线性变化与生存相关的研究。
