Hemoglobin-to-red cell distribution width ratio as a practical prognostic tool in second-line immunotherapy for non–small cell lung cancer

Gökhan Şahin; Caner Acar; Salih Tünbekici; Haydar Çağatay Yüksel; Fatma Pınar Açar; Pınar Gürsoy

doi:10.19161/etd.1849122

TR EN

Küçük hücre dışı akciğer kanserinde ikinci basamak immünoterapide hemoglobin–eritrosit dağılım genişliği oranının pratik bir prognostik belirteç olarak değeri

Öz

Amaç: İkinci basamak nivolumab alan metastatik küçük hücreli dışı akciğer kanseri (KHDAK) hastalarında, tedavi öncesi hemoglobin/kırmızı hücre dağılım genişliği oranının (HRR) progresyonsuz sağkalım (PFS) ve genel sağkalım (OS) üzerindeki prognostik değerini değerlendirmek. Gereç ve Yöntem: Metastatik KHDAK tanılı ve ikinci basamak nivolumab tedavisi alan hastalar retrospektif olarak incelendi. Hemoglobin (g/dL) ve RDW (%) tedavi başlangıcından önce ölçülerek HRR (Hb/RDW) hesaplandı. Önceden tanımlı eşik değere göre hastalar düşük HRR (<0,7) ve yüksek HRR (≥0,7) gruplarına ayrıldı. PFS ve OS Kaplan–Meier yöntemiyle analiz edildi; prognostik faktörler Cox regresyon modelleri ile değerlendirildi. Bulgular: Toplam 114 hasta analize dahil edildi. Medyan hemoglobin, RDW ve HRR sırasıyla 11,2 g/dL, %15,4 ve 0,74 idi. Hastaların %57,9’u düşük HRR grubundaydı. Medyan PFS 4,0 ay olup, yüksek HRR grubunda PFS anlamlı olarak daha uzundu (6,5 vs 3,2 ay; p=0,011). Çok değişkenli analizde ECOG performans durumu ≥2, ≥3 metastatik odak ve düşük HRR, daha kısa PFS ile bağımsız olarak ilişkiliydi (HRR: HR=2,00; p=0,007). Medyan OS 10,0 ay olup, yüksek HRR grubunda OS belirgin olarak daha uzundu (18,7 vs 6,0 ay; p<0,001). Düşük HRR, OS için bağımsız kötü prognostik faktör olarak saptandı (HR=2,87; p<0,001). Sonuç: Tedavi öncesi düşük HRR, ikinci basamak nivolumab alan ileri/metastatik KHDAK hastalarında daha kötü sağkalım ile ilişkili, pratik ve düşük maliyetli bir prognostik belirteçtir.

Anahtar Kelimeler

Hemoglobin-to-red cell distribution width ratio as a practical prognostic tool in second-line immunotherapy for non–small cell lung cancer

Abstract

Aim: To evaluate the prognostic value of baseline hemoglobin-to–red cell distribution width ratio (HRR) for progression-free survival (PFS) and overall survival (OS) in patients with advanced or metastatic non–small cell lung cancer (NSCLC) receiving second-line nivolumab. Materials and Methods: Patients with advanced or metastatic NSCLC treated with second-line nivolumab were retrospectively analyzed. Baseline hemoglobin (g/dL) and RDW (%) were obtained prior to treatment initiation, and HRR (Hb/RDW) was calculated. Patients were categorized into low (<0.7) and high (≥0.7) HRR groups using a predefined cutoff. Survival outcomes were assessed using the Kaplan–Meier method, and prognostic factors were evaluated using Cox proportional hazards regression models. Results: A total of 114 patients were included. Median baseline hemoglobin, RDW, and HRR were 11.2 g/dL, 15.4%, and 0.74, respectively; 57.9% of patients had low HRR. Median PFS was 4.0 months, and patients with high HRR had significantly longer PFS than those with low HRR (6.5 vs 3.2 months; p=0.011). In multivariate analysis, ECOG performance status ≥2, ≥3 metastatic sites, and low HRR independently predicted shorter PFS (low HRR: HR=2.00; p=0.007). Median OS was 10.0 months, with significantly longer OS observed in the high HRR group (18.7 vs 6.0 months; p<0.001). Low HRR remained an independent adverse prognostic factor for OS (HR=2.87; p<0.001). Conclusion: Baseline HRR is a simple, inexpensive, and independent prognostic marker associated with inferior survival outcomes in advanced or metastatic NSCLC patients treated with second-line nivolumab.

Keywords

Supporting Institution

This study did not receive any specific funding from public, commercial, or non-profit organizations.

Ethical Statement

Ethical approval This study was approved by the Ethics Committee of Ege University Faculty of Medicine (Decision No: 25-12T/4, Date: 04 December 2025). Due to the retrospective nature of the study, the requirement for informed consent was waived. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Thanks

Not applicable.

References

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2024;74(3):229-63.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.
Schabath MB, Cote ML. Cancer progress and priorities: lung cancer. Cancer epidemiology, biomarkers & prevention. 2019;28(10):1563-79.
Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. New England Journal of Medicine. 2015;373(2):123-35.
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. New England Journal of Medicine. 2015;373(17):1627-39.
Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The lancet. 2016;387(10027):1540-50.
Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, Von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. The Lancet. 2017;389(10066):255-65.
Wang H, Niu X, Jin Z, Zhang S, Fan R, Xiao H, Hu SS. Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities. Journal of Experimental & Clinical Cancer Research. 2025;44(1):250.

Yang X, Luo B, Tian J, Wang Y, Lu X, Ni J, et al. Biomarkers and ImmuneScores in lung cancer: predictive insights for immunotherapy and combination treatment strategies. Biological Procedures Online. 2025;27(1):1-18.
Wojas-Krawczyk K, Kubiatowski T. Imperfect predictors for lung cancer immunotherapy—A field for further research. Frontiers in oncology. 2020;10:568174.
Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nature Reviews Cancer. 2016;16(5):275-87.
Longueville E, Dewolf M, Dalstein V, Durlach A, Vivien A, Nawrocki-Raby B, et al. Comparing neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil count (ANC) and derived NLR as predictive biomarkers in first-line immunotherapy for non-small cell lung cancer: a retrospective study. Translational Lung Cancer Research. 2025;14(4):1212.
Mezquita L, Auclin E, Ferrara R, Charrier M, Remon J, Planchard D, et al. Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non–small cell lung cancer. JAMA oncology. 2018;4(3):351-7.
Coradduzza D, Medici S, Chessa C, Zinellu A, Madonia M, Angius A, et al. Assessing the predictive power of the hemoglobin/red cell distribution width ratio in cancer: a systematic review and future directions. Medicina. 2023;59(12):2124.
Chi G, Lee JJ, Montazerin SM, Marszalek J. Prognostic value of hemoglobin-to-red cell distribution width ratio in cancer: a systematic review and meta-analysis. Biomarkers in Medicine. 2022;16(6):473-82.
Giudice GC, Rebuzzi SE, Mazzaschi G, Pecci F, Maffezzoli M, Acunzo A, et al. The prognostic value of the Haemoglobin/Red cell Distribution Width Ratio in a cohort of pre-treated patients with Renal Cell Carcinoma receiving nivolumab. Cancer Treatment and Research Communications. 2025:100927.
Pecci F, Mazzaschi G, Dodi A, Tamarozzi P, Manini M, Peroni M, et al. EP. 11.05 Prognostic Value of Hb/RDW and Its Correlation With Immune-Inflammatory Profile in NSCLC Receiving First-Line Immunotherapy. Journal of Thoracic Oncology. 2025;20(10):S784.
Wu F, Yang S, Tang X, Liu W, Chen H, Gao H. Prognostic value of baseline hemoglobin‐to‐red blood cell distribution width ratio in small cell lung cancer: A retrospective analysis. Thoracic Cancer. 2020;11(4):888-97.
Petrella F, Casiraghi M, Radice D, Cara A, Maffeis G, Prisciandaro E, et al. Prognostic value of the hemoglobin/red cell distribution width ratio in resected lung adenocarcinoma. Cancers. 2021;13(4):710.
Koma Y, Onishi A, Matsuoka H, Oda N, Yokota N, Matsumoto Y, et al. Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer. PloS one. 2013;8(11):e80240.
McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer treatment reviews. 2013;39(5):534-40.
Petrelli F, Cabiddu M, Coinu A, Borgonovo K, Ghilardi M, Lonati V, Barni S. Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies. Acta oncologica. 2015;54(7):961-70.
Şahin G, Acar C, Yüksel HÇ, Tunbekici S, Açar FP, Çelebi G, Karaca B. Dynamic blood-based biomarkers predict early response to ipilimumab and nivolumab in advanced melanoma. Clinical and Translational Oncology. 2025:1-10.
Sun P, Zhang F, Chen C, Bi X, Yang H, An X, et al. The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China. Oncotarget. 2016;7(27):42650.
Bagley SJ, Kothari S, Aggarwal C, Bauml JM, Alley EW, Evans TL, et al. Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung cancer. 2017;106:1-7.

Details

Primary Language

English

Subjects

Clinical Oncology

Journal Section

Research Article

Authors

Gökhan Şahin ^*
0000-0003-1478-9383
Türkiye

Caner Acar
0000-0002-9782-6807
Türkiye

Salih Tünbekici
0000-0001-8804-7636
Türkiye

Haydar Çağatay Yüksel
0000-0001-8857-2983
Türkiye

Fatma Pınar Açar
0009-0000-2749-8732
Türkiye

Pınar Gürsoy
0000-0003-1392-6753
Türkiye

Publication Date

March 9, 2026

Submission Date

December 29, 2025

Acceptance Date

January 3, 2026

Published in Issue

Year 2026 Volume: 65 Number: 1

DOI

https://doi.org/10.19161/etd.1849122

IZ

https://izlik.org/JA65LY88SF

Cite

RIS / Bibtex

Vancouver

1.Gökhan Şahin, Caner Acar, Salih Tünbekici, Haydar Çağatay Yüksel, Fatma Pınar Açar, Pınar Gürsoy. Hemoglobin-to-red cell distribution width ratio as a practical prognostic tool in second-line immunotherapy for non–small cell lung cancer. EJM. 2026 Mar. 1;65(1):131-8. doi:10.19161/etd.1849122