Aslan Volkan, Karabörk Kılıç Atiye Cenay, Rustamova Cennet Nigar, Yücel Talha Alperen, Kurt Inci Bediz, Gürler Fatih, Özet Ahmet, Özdemir Nuriye, Kilic Huseyin Koray, Yazıcı Ozan
Department of Medical Oncology, Gazi University, Ankara, Turkey.
Department of Radiology, Gazi University, Ankara, Turkey.
Sci Rep. 2025 May 6;15(1):15781. doi: 10.1038/s41598-025-00708-w.
Introduction Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have emerged as promising treatments for advanced NSCLC patients without actionable mutations. However, predicting treatment response remains challenging, especially in second-line settings. Although PD-L1 is the only validated biomarker, additional prognostic tools are needed. Systemic inflammation markers such as the neutrophil-to-lymphocyte ratio (NLR) show potential but remain underused. Myeloid-derived suppressor cells (MDSCs), linked to immunotherapy resistance, are associated with increased splenic volume. Therefore this study introduces a splenic index score, combining pre-immunotherapy splenic volume and NLR, to evaluate its prognostic value in NSCLC patients treated with nivolumab in the second-line setting. We analyzed 50 patients with metastatic non-small cell lung cancer (NSCLC) who received nivolumab as second-line or later therapy. Baseline splenic volume and neutrophil-to-lymphocyte ratio (NLR) were assessed using imaging and laboratory data prior to nivolumab initiation. The Splenic Index Score for each patient was calculated using the formula: (baseline splenic volume) × (NLR). Additionally, we evaluated the impact of other factors, including body mass index (BMI), tumor PD-L1 expression, Eastern Cooperative Oncology Group (ECOG) performance status, and sites of metastasis. The median Splenic Index score was 877.3 (range: 180-4830). A higher Splenic Index score was significantly associated with worse overall survival (OS) and progression-free survival (PFS) (p = 0.001 and p = 0.03, respectively). Specifically, patients with a high Splenic Index score had a median PFS of 3 months, compared to 8 months in those with a low Splenic Index score (HR 1.96, 95% CI 1-3.7, p = 0.03). Similarly, the median OS was 4 months for patients with a high Splenic Index score, while it was 15 months for those with a low score (HR 3.5, 95% CI 1.6-7.3, p = 0.001). Baseline splenic volume, basal NLR, and tumor PD-L1 expression were also evaluated; however, no significant differences in PFS or OS were observed for these parameters. Our study demonstrates that the splenic index score, derived from combining radiological and peripheral inflammatory biomarkers, serves as a predictive tool for progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients receiving second-line nivolumab therapy.
靶向程序性死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1）的免疫检查点抑制剂已成为治疗无可操作突变的晚期非小细胞肺癌（NSCLC）患者的有前景的疗法。然而，预测治疗反应仍然具有挑战性，尤其是在二线治疗中。尽管PD-L1是唯一经过验证的生物标志物，但仍需要额外的预后评估工具。中性粒细胞与淋巴细胞比值（NLR）等全身炎症标志物显示出潜力，但仍未得到充分利用。与免疫治疗耐药相关的髓源性抑制细胞（MDSC）与脾脏体积增加有关。因此，本研究引入了一种脾脏指数评分，将免疫治疗前的脾脏体积和NLR相结合，以评估其在接受二线纳武利尤单抗治疗的NSCLC患者中的预后价值。我们分析了50例接受纳武利尤单抗作为二线或更晚期治疗的转移性非小细胞肺癌（NSCLC）患者。在开始纳武利尤单抗治疗前，使用影像学和实验室数据评估基线脾脏体积和中性粒细胞与淋巴细胞比值（NLR）。使用公式：（基线脾脏体积）×（NLR）计算每位患者的脾脏指数评分。此外，我们评估了其他因素的影响，包括体重指数（BMI）、肿瘤PD-L1表达、东部肿瘤协作组（ECOG）体能状态和转移部位。脾脏指数评分的中位数为877.3（范围：180-4830）。较高的脾脏指数评分与较差的总生存期（OS）和无进展生存期（PFS）显著相关（分别为p = 0.001和p = 0.03）。具体而言，脾脏指数评分高的患者的中位PFS为3个月，而脾脏指数评分低的患者为8个月（风险比1.96，95%置信区间1-3.7，p = 0.03）。同样，脾脏指数评分高的患者的中位OS为4个月，而评分低的患者为15个月（风险比3.5，95%置信区间1.6-7.3，p = 0.001）。还评估了基线脾脏体积、基础NLR和肿瘤PD-L1表达；然而，这些参数在PFS或OS方面未观察到显著差异。我们的研究表明，结合放射学和外周炎症生物标志物得出的脾脏指数评分可作为接受二线纳武利尤单抗治疗的转移性NSCLC患者无进展生存期（PFS）和总生存期（OS）的预测工具。
