Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA.
Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Lung Cancer. 2022 Jan;163:35-41. doi: 10.1016/j.lungcan.2021.11.021. Epub 2021 Dec 2.
Elevated pre-treatment neutrophil-to-lymphocyte ratio (NLR) may reflect immune dysfunction and is negatively prognostic in cancer patients treated with immunotherapy, but it is unclear if NLR is predictive of immunotherapy benefit.
We identified stage III non-small-cell lung cancer (NSCLC) patients treated with definitive chemoradiation and adjuvant durvalumab within the national Veterans Affairs system from 2017 to 2021. We compared the prognostic value of NLR measured before durvalumab start to a control group of stage III NSCLC patients treated with definitive chemoradiation alone from 2015 to 2016 (no-durvalumab group) before the approval of adjuvant durvalumab. We estimated the predictive value of NLR through the statistical interaction of durvalumab group by NLR level. Outcomes included progression-free survival (PFS) and overall survival (OS).
The primary analysis for NLR included 821 durvalumab patients and 445 no-durvalumab patients. Higher NLR was associated with inferior PFS in both groups (no-durvalumab: adjusted HR [aHR] 1.14 per 7.43 unit increase in NLR, 95% confidence interval [CI] 1.06-1.23; durvalumab: aHR 1.42, 95% CI 1.23-1.64), though this effect was greater in durvalumab patients (p for interaction = 0.009). Similar results were found for OS (no-durvalumab: aHR 1.16, 95% CI 1.09-1.24; durvalumab: aHR 1.48, 95% CI 1.25-1.76; p for interaction = 0.010). Absolute lymphocytes, eosinophils, and basophils were not prognostic in either group. Estimates of durvalumab treatment efficacy suggested declining efficacy with higher NLR.
Pre-treatment NLR is especially prognostic among stage III NSCLC patients treated with adjuvant immunotherapy compared to control patients treated without immunotherapy and may be a predictive biomarker of immunotherapy benefit.
治疗癌症的免疫疗法患者，治疗前中性粒细胞与淋巴细胞比值（NLR）升高可能反映免疫功能障碍，且预后不良，但 NLR 是否能预测免疫治疗获益尚不清楚。
我们在退伍军人事务部系统中确定了 2017 年至 2021 年期间接受根治性放化疗和辅助度伐利尤单抗治疗的 III 期非小细胞肺癌（NSCLC）患者。我们比较了在度伐利尤单抗批准用于辅助治疗之前（2015 年至 2016 年，无度伐利尤单抗组），单独接受根治性放化疗的 III 期 NSCLC 患者（对照组）治疗前测量的 NLR 的预后价值。我们通过 NLR 水平的度伐利尤单抗组的统计学交互作用来估计 NLR 的预测价值。结局包括无进展生存期（PFS）和总生存期（OS）。
主要 NLR 分析纳入了 821 名度伐利尤单抗患者和 445 名无度伐利尤单抗患者。两组中 NLR 升高均与 PFS 降低相关（无度伐利尤单抗组：调整后的 HR[aHR]每增加 7.43 单位 NLR 为 1.14，95%CI 为 1.06-1.23；度伐利尤单抗组：aHR 为 1.42，95%CI 为 1.23-1.64），但度伐利尤单抗组的影响更大（交互作用 P 值=0.009）。OS 也有类似的结果（无度伐利尤单抗组：aHR 为 1.16，95%CI 为 1.09-1.24；度伐利尤单抗组：aHR 为 1.48，95%CI 为 1.25-1.76；交互作用 P 值=0.010）。两组患者的绝对淋巴细胞、嗜酸性粒细胞和嗜碱性粒细胞均无预后意义。度伐利尤单抗治疗效果的估计表明，随着 NLR 升高，疗效逐渐下降。
与未接受免疫治疗的对照组患者相比，接受辅助免疫治疗的 III 期 NSCLC 患者治疗前 NLR 尤其具有预后意义，且可能是免疫治疗获益的预测生物标志物。
