Delta-He as a Novel Predictive and Prognostic Biomarker in Patients With NSCLC Treated With PD–1/PD-L1 Inhibitors

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-04-05 DOI:10.1002/cam4.70826

Green Hong, Song-I Lee, Da Hyun Kang, Chaeuk Chung, Hee Sun Park, Jeong Eun Lee

{"title":"Delta-He as a Novel Predictive and Prognostic Biomarker in Patients With NSCLC Treated With PD–1/PD-L1 Inhibitors","authors":"Green Hong, Song-I Lee, Da Hyun Kang, Chaeuk Chung, Hee Sun Park, Jeong Eun Lee","doi":"10.1002/cam4.70826","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Lung cancer treatment has rapidly advanced, particularly with immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1. However, there are variable responses, such as immune-related adverse events. Several factors predicting the prognosis of lung cancer ICI treatment have been studied so far, but they have limitations, leaving an unmet need. This study aims to investigate delta-He, a novel marker reflecting the iron availability and inflammation through the difference in hemoglobin content between reticulocytes and erythrocytes, as a potential prognostic factor in patients with NSCLC undergoing PD-1/PD-L1 inhibitor therapy.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This research was conducted at Chungnam National University Hospital, analyzing 79 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors. The study population had a mean age of 70 years, with the majority being male (82.3%) and former or current smokers (84.8%). Blood samples collected before therapy initiation were examined for hematological parameters, including delta-He, using Sysmex XN-550 and XN-20 analyzers. The study employed receiver operating characteristic (ROC) curves and Kaplan–Meier curves for the statistical analysis, using SPSS version 26 (IBM Corp., USA) and MedCalc version 22 (MedCalc Software Ltd., Belgium) to evaluate the sensitivity and specificity of delta-He, and to analyze progression-free survival (PFS) and overall survival (OS).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The study revealed that delta-He is a significant prognostic marker in patients with NSCLC treated with PD-1/PD-L1 inhibitors. A delta-He cutoff value of 3.3 pg was identified based on ROC analysis. Patients with high delta-He values (> 3.3 pg) showed significantly longer median PFS (9.6 vs. 3.0 months, <i>p</i> = 0.024) and OS (not reached vs. 12.2 months, <i>p</i> = 0.010) than those with low values. The high delta-He group also had higher objective response rate (41.4% vs. 26.0%) and disease control rate (86.2% vs. 52.0%). Multivariate analysis highlighted higher delta-He (> 3.3 pg), along with other factors such as FEV1 and smoking status, as important predictors of survival, underscoring its potential role in guiding therapeutic decisions of ICIs in NSCLC (PFS: HR 0.874, 95% CI 0.264-0.874, <i>p</i> = 0.016; OS: HR 0.327, 95% CI 0.150-0.715, <i>p</i> = 0.005).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our study shows delta-He as a promising prognostic biomarker for lung cancer patients treated with PD-1/PD-L1 inhibitors, highlighting its potential to guide therapeutic decisions and improve patient management in a non-invasive manner. Further research is necessary to validate delta-He's predictive and prognostic value across broader populations and in combination with other biomarkers, emphasizing its role in advancing personalized oncology.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70826","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70826","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Lung cancer treatment has rapidly advanced, particularly with immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1. However, there are variable responses, such as immune-related adverse events. Several factors predicting the prognosis of lung cancer ICI treatment have been studied so far, but they have limitations, leaving an unmet need. This study aims to investigate delta-He, a novel marker reflecting the iron availability and inflammation through the difference in hemoglobin content between reticulocytes and erythrocytes, as a potential prognostic factor in patients with NSCLC undergoing PD-1/PD-L1 inhibitor therapy.

Methods

This research was conducted at Chungnam National University Hospital, analyzing 79 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors. The study population had a mean age of 70 years, with the majority being male (82.3%) and former or current smokers (84.8%). Blood samples collected before therapy initiation were examined for hematological parameters, including delta-He, using Sysmex XN-550 and XN-20 analyzers. The study employed receiver operating characteristic (ROC) curves and Kaplan–Meier curves for the statistical analysis, using SPSS version 26 (IBM Corp., USA) and MedCalc version 22 (MedCalc Software Ltd., Belgium) to evaluate the sensitivity and specificity of delta-He, and to analyze progression-free survival (PFS) and overall survival (OS).

Results

The study revealed that delta-He is a significant prognostic marker in patients with NSCLC treated with PD-1/PD-L1 inhibitors. A delta-He cutoff value of 3.3 pg was identified based on ROC analysis. Patients with high delta-He values (> 3.3 pg) showed significantly longer median PFS (9.6 vs. 3.0 months, p = 0.024) and OS (not reached vs. 12.2 months, p = 0.010) than those with low values. The high delta-He group also had higher objective response rate (41.4% vs. 26.0%) and disease control rate (86.2% vs. 52.0%). Multivariate analysis highlighted higher delta-He (> 3.3 pg), along with other factors such as FEV1 and smoking status, as important predictors of survival, underscoring its potential role in guiding therapeutic decisions of ICIs in NSCLC (PFS: HR 0.874, 95% CI 0.264-0.874, p = 0.016; OS: HR 0.327, 95% CI 0.150-0.715, p = 0.005).

Conclusion

Our study shows delta-He as a promising prognostic biomarker for lung cancer patients treated with PD-1/PD-L1 inhibitors, highlighting its potential to guide therapeutic decisions and improve patient management in a non-invasive manner. Further research is necessary to validate delta-He's predictive and prognostic value across broader populations and in combination with other biomarkers, emphasizing its role in advancing personalized oncology.

Abstract Image

查看原文本刊更多论文

Delta-He作为PD-1 /PD-L1抑制剂治疗的非小细胞肺癌患者的一种新的预测和预后生物标志物

肺癌治疗进展迅速，特别是针对PD-1和PD-L1的免疫检查点抑制剂（ICIs）。然而，有不同的反应，如免疫相关的不良事件。目前已经研究了预测肺癌ICI治疗预后的几个因素，但它们有局限性，留下了一个未满足的需求。delta-He是一种通过网状红细胞和红细胞之间血红蛋白含量的差异来反映铁可用性和炎症的新标志物，本研究旨在探讨delta-He作为接受PD-1/PD-L1抑制剂治疗的非小细胞肺癌患者的潜在预后因素。方法在忠南大学附属医院对79例接受PD-1/PD-L1抑制剂治疗的晚期非小细胞肺癌患者进行分析。研究人群的平均年龄为70岁，大多数为男性（82.3%），以前或现在吸烟（84.8%）。治疗开始前采集的血液样本使用Sysmex XN-550和XN-20分析仪检测血液参数，包括delta-He。本研究采用受试者工作特征（ROC）曲线和Kaplan-Meier曲线进行统计分析，使用SPSS version 26 （IBM Corp.，美国）和MedCalc version 22 （MedCalc Software Ltd.，比利时）评估delta-He的敏感性和特异性，分析无进展生存期（PFS）和总生存期（OS）。结果研究显示，delta-He是PD-1/PD-L1抑制剂治疗的非小细胞肺癌患者的重要预后指标。根据ROC分析，delta-He临界值为3.3 pg。高δ - he值患者(>；3.3 pg)的中位PFS （9.6 vs. 3.0个月，p = 0.024）和OS（未达到vs. 12.2个月，p = 0.010）明显长于低值患者。高delta-He组客观有效率（41.4%比26.0%）和疾病控制率（86.2%比52.0%）也较高。多变量分析显示，δ - he (>；3.3 pg)，以及其他因素，如FEV1和吸烟状况，作为生存的重要预测因素，强调其在指导非小细胞肺癌ICIs治疗决策中的潜在作用(PFS: HR 0.874, 95% CI 0.264-0.874, p = 0.016；OS: HR 0.327, 95% CI 0.150 ~ 0.715, p = 0.005)。结论：我们的研究表明，delta-He是一种有希望的预后生物标志物，可用于PD-1/PD-L1抑制剂治疗的肺癌患者，突出了其指导治疗决策和以非侵入性方式改善患者管理的潜力。需要进一步的研究来验证delta-He在更广泛人群中的预测和预后价值，并与其他生物标志物结合，强调其在推进个性化肿瘤学方面的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.