年龄相关的中性粒细胞与淋巴细胞比值（NLR）和全身免疫炎症指数（SII）作为接受免疫检查点抑制剂治疗的老年癌症患者炎症生物标志物的特征：对疗效和生存的影响
Characterization of Age-Associated, Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammatory Index (SII) as Biomarkers of Inflammation in Geriatric Patients with Cancer Treated with Immune Checkpoint Inhibitors: Impact on Efficacy and Survival.
作者信息
Choucair Khalil, Nebhan Caroline, Cortellini Alessio, Hentzen Stijn, Wang Yinghong, Liu Cynthia, Giusti Raffaele, Filetti Marco, Ascierto Paolo Antonio, Vanella Vito, Galetta Domenico, Catino Annamaria, Al-Bzour Nour, Saeed Azhar, Cavalcante Ludimila, Pizzutilo Pamela, Genova Carlo, Bersanelli Melissa, Buti Sebastiano, Johnson Douglas B, Fulgenzi Claudia Angela Maria, Pinato David J, Radford Maluki, Kim Chul, Naqash Abdul Rafeh, Saeed Anwaar
机构信息
Barbara Ann Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
出版信息
Cancers (Basel). 2023 Oct 19;15(20):5052. doi: 10.3390/cancers15205052.
BACKGROUND
Geriatric patients (≥80 years) are underrepresented in immune checkpoint inhibitor (ICIs) clinical trials. However, their unique biology may affect their response to ICIs. There are currently no established biomarkers of the response to ICIs in adult patients with cancer that can help with patient selection.
METHODS
We built a multicenter, international retrospective study of 885 patients (<80 years: n = 417, 47.12%; ≥80 years: n = 468, 52.88%) with different tumor types treated with ICIs between 2011 and 2021 from 11 academic centers in the U.S. and Europe. The main outcome measures were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) stratified by age and circulating inflammatory levels (neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII)).
RESULTS
Patients ≥80 years with low NLR (NLR-L) and SII (SII-L) had significantly higher ORR (vs. high NLR [NLR-H], < 0.01 and SII-H, < 0.05, respectively). At median follow-ups (13.03 months), and compared to SII-H, patients with SII-L had significantly longer median PFS and OS in patients <80 ( < 0.001), and ≥80 years ( < 0.001). SII-L was independently associated with longer PFS and OS (HR: 0.61 and 0.62, respectively, < 0.01).
CONCLUSION
Lower inflammation pre-ICI initiation may predict an improved response and survival in geriatric patients with cancer.
背景
老年患者（≥80岁）在免疫检查点抑制剂（ICI）临床试验中的代表性不足。然而，他们独特的生物学特性可能会影响其对ICI的反应。目前，在成年癌症患者中，尚无已确立的可帮助进行患者选择的ICI反应生物标志物。
方法
我们开展了一项多中心、国际性回顾性研究，纳入了2011年至2021年间在美国和欧洲11个学术中心接受ICI治疗的885例不同肿瘤类型的患者（<80岁：n = 417，占47.12%；≥80岁：n = 468，占52.88%）。主要结局指标为按年龄和循环炎症水平（中性粒细胞与淋巴细胞比值[NLR]和全身免疫炎症指数[SII]）分层的客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
结果
≥80岁且NLR低（NLR-L）和SII低（SII-L）的患者ORR显著更高（分别与高NLR [NLR-H]相比，<0.01；与高SII [SII-H]相比，<0.05）。在中位随访期（13.03个月）时，与SII-H相比，SII-L的患者在<80岁（<0.001）和≥80岁（<0.001）的患者中，中位PFS和OS显著更长。SII-L与更长的PFS和OS独立相关（HR分别为0.61和0.62，<0.01）。
结论
ICI开始前炎症水平较低可能预示老年癌症患者的反应改善和生存期延长。
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