Kuzman James A, Stenehjem David D, Merriman Joseph, Agarwal Archana M, Patel Shiven B, Hahn Andrew W, Alex Anitha, Albertson Dan, Gill David M, Agarwal Neeraj
University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
BMC Urol. 2017 Jan 5;17(1):1. doi: 10.1186/s12894-016-0192-0.
Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting.
Patients with clear cell mRCC treated with HD-IL2 were identified from an institutional database from 2003-2012. Baseline variables for the assessment of IMDC risk criteria, and neutrophil and lymphocyte count, were collected. Best response criteria were based on RECIST 1.0. Wilcoxon rank-sum test was used to evaluate the association of continuous baseline variables with disease control. NLR was stratified by ≤4 or >4. Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and Cox proportional hazard models assessed associations of NLR with survival.
In 71 eligible patients, median NLR in those with an objective response (n = 14, 20%) was 2.3 vs 3.4 in those without (n = 57, 80%, p = 0.02). NLR ≤4 was associated with improved progression free and overall survival. After adjustment for IMDC risk criteria, NLR remained a significant predictor of OS (ANC/ALC ≤4 vs >4, HR 0.41, 95% CI 1.09-5.46, p = 0.03; ANC/ALC continuous variable per unit change in NLR, HR 1.08, 95% CI 1.01-1.14, p = 0.03).
In this discovery set, NLR predicts overall survival in patients treated with HD-IL2 in mRCC, and may allow better patient selection in this setting. Data needs validation in an independent cohort.
高剂量白细胞介素-2（HD-IL2）免疫疗法可使部分转移性肾细胞癌（mRCC）患者长期存活，但具有显著的急性毒性。需要生物标志物来预测治疗反应，以便更好地选择最可能受益的患者。中性粒细胞与淋巴细胞比值（NLR，即绝对中性粒细胞计数（ANC）/绝对淋巴细胞计数（ALC））是多种恶性肿瘤中的一种预后和预测生物标志物。本研究旨在确定在这种情况下NLR是否能预测HD-IL2治疗的反应。
从2003年至2012年的机构数据库中识别接受HD-IL2治疗的透明细胞mRCC患者。收集用于评估国际转移性肾细胞癌数据库（IMDC）风险标准的基线变量以及中性粒细胞和淋巴细胞计数。最佳反应标准基于RECIST 1.0。采用Wilcoxon秩和检验评估连续基线变量与疾病控制的相关性。NLR按≤4或>4分层。采用Kaplan-Meier法估计无进展生存期（PFS）和总生存期（OS），并使用Cox比例风险模型评估NLR与生存的相关性。
在71例符合条件的患者中，有客观反应者（n = 14，20%）的中位NLR为2.3，无客观反应者（n = 57，80%）为3.4（p = 0.02）。NLR≤4与改善的无进展生存期和总生存期相关。在调整IMDC风险标准后，NLR仍然是总生存期的显著预测因子（ANC/ALC≤4 vs >4，风险比（HR）0.41，95%置信区间（CI）1.09 - 5.46，p = 0.03；ANC/ALC作为NLR每单位变化的连续变量，HR 1.08，95% CI 1.01 - 1.14，p = 0.03）。
在这个发现队列中，NLR可预测mRCC患者HD-IL2治疗的总生存期，并可能有助于在这种情况下更好地选择患者。数据需要在独立队列中进行验证。
