tjcl Turkish Journal of Clinics and Laboratory 2149-8296 DNT Ortadoğu Yayıncılık A.Ş. 10.18663/tjcl.1849630 Clinical Oncology Klinik Onkoloji Nivolumab ile tedavi edilen ileri evre küçük hücreli dışı akciğer kanserinde tedavi sırasındaki dNLR ve metastatik yük sağkalımı öngörür On-treatment dNLR and metastatic burden predict survival in advanced non-small-cell lung cancer treated with nivolumab https://orcid.org/0000-0003-1281-942X Doğan Tolga Denizli State Hospital, Department Of Medical Oncology https://orcid.org/0000-0002-9441-9210 Taş Semra Pamukkale University, Department of Medical Oncology https://orcid.org/0000-0002-7836-4272 Güçlü Kantar Taliha Denizli State Hospital, Department Of Medical Oncology https://orcid.org/0000-0002-3893-5739 İspir Emre İzmir City Hospital, Department of Biochemistry https://orcid.org/0000-0001-6291-851X Hafızoğlu Emre Afyonkarahisar State Hospital, Department of Medical Oncology https://orcid.org/0000-0003-1894-9743 Özdemir Melek Denizli State Hospital, Department Of Medical Oncology https://orcid.org/0000-0002-3766-4383 Bir Ferda Pamukkale University, Department of Pathology https://orcid.org/0000-0003-4755-2753 Yapar Taşköylü Burcu Pamukkale University, Department of Medical Oncology https://orcid.org/0000-0003-4397-5468 Demiray Atike Gökçen Pamukkale University, Department of Medical Oncology https://orcid.org/0000-0003-1436-8650 Yaren Arzu Pamukkale University, Department of Medical Oncology https://orcid.org/0000-0001-8142-0362 Gokoz Dogu Gamze Pamukkale University, Department of Medical Oncology 03 28 2026 1 12 26 2025 02 10 2026 Copyright © 2010, Turkish Journal of Clinics and Laboratory 2010 Turkish Journal of Clinics and Laboratory

Amaç: İleri evre küçük hücreli dışı akciğer kanserinde (KHDAK) immün kontrol noktası inhibitörleri ile sağkalım avantajı elde edilmesine rağmen, sonuçlar heterojen kalmaktadır. PD-L1 ekspresyonu yerleşik bir biyobelirteç olsa da, tedavi sırasındaki sistemik inflamatuar dinamiklerin prognostik önemi ve immünoterapi alan hastalarda Endotel Aktivasyon ve Stres İndeksi (EASIX) gibi endotel stres tabanlı indekslerin kullanımı hakkında daha az bilgi mevcuttur.Gereç ve Yöntemler: Nivolumab ile tedavi edilen ileri evre KHDAK'li hastalar retrospektif olarak değerlendirildi. PD-L1 ekspresyonu, metastatik yük, bazal inflamatuar parametreler ve bazal EASIX kaydedildi. 3. aydaki türetilmiş nötrofil-lenfosit oranı (dNLR) ve NLR'deki boylamsal değişimler (ΔNLR) dahil olmak üzere tedavi sırasındaki inflamatuar belirteçler analiz edildi. Genel sağkalım (OS) ve progresyonsuz sağkalım (PFS), Kaplan–Meier ve Cox regresyon modelleri kullanılarak değerlendirildi. Zaman bağımlı yanlılığı (time-dependent bias) önlemek amacıyla 3. ay landmark (sınır değer) analizleri yapıldı.Bulgular: Çalışmaya 81 hasta dahil edildi. Yüksek PD-L1 ekspresyonu (≥%50), OS'de anlamlı iyileşme ile ilişkili bulundu ancak PFS için bağımsız prognostik önemi korunmadı. Özellikle dört veya daha fazla metastatik organ tutulumu başta olmak üzere yüksek metastatik yük, daha kötü OS ile ilişkilendirildi. Landmark düzeltmeli analizlerde, 3. aydaki dNLR hem OS hem de PFS ile bağımsız olarak ilişkili bulunurken; ΔNLR'nin OS ile ilişkili olması, tedavi sırasındaki olumlu immün-inflamatuar değişikliklerin sağkalım iyileşmesiyle korele olduğunu gösterdi. Bazal EASIX skorunun ise OS veya PFS ile ilişkisi saptanmadı.Sonuç: Nivolumab alan ileri evre KHDAK'de sağkalım sonuçları; temel olarak tümör biyolojisi, hastalık yükü ve tedavi sırasında gelişen immün-inflamatuar dinamikler tarafından yönlendirilmektedir. Tedavi sırasındaki inflamatuar belirteçler, özellikle dNLR ve ΔNLR, bazal indekslerden daha klinik olarak ilgili prognostik bilgiler sağlarken; bazal EASIX'in bu ortamda sınırlı kullanışlılığa sahip olduğu görülmektedir. Bu bulgular, immünoterapide biyobelirteç temelli risk sınıflamasında tedaviye özgü ve zamana bağımlı bir yaklaşımı desteklemektedir.

Aim: Despite the survival benefit achieved with immune checkpoint inhibitors in advanced non–small-cell lung cancer (NSCLC), outcomes remain heterogeneous. While PD-L1 expression is an established biomarker, less is known about the prognostic relevance of on-treatment systemic inflammatory dynamics and the utility of endothelial stress–based indices such as the Endothelial Activation and Stress Index (EASIX) in patients receiving immunotherapy.Material and Methods: We retrospectively evaluated patients with advanced NSCLC treated with nivolumab. PD-L1 expression, metastatic burden, baseline inflammatory parameters, and baseline EASIX were recorded. On-treatment inflammatory markers, including derived neutrophil-to-lymphocyte ratio (dNLR) at 3 months and longitudinal changes in NLR (ΔNLR), were analyzed. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier and Cox regression models. To account for time-dependent bias, 3-month landmark analyses were performed.Results: Eighty-one patients were included. High PD-L1 expression (≥50%) was associated with significantly improved OS but did not retain independent prognostic significance for PFS. A high metastatic burden, particularly involvement of four or more metastatic organs, was associated with inferior OS. In landmark-adjusted analyses, dNLR at 3 months was independently associated with both OS and PFS, while ΔNLR was associated with OS, indicating that favorable on-treatment immune–inflammatory changes correlated with improved survival. Baseline EASIX was not associated with either OS or PFS.Conclusion: In nivolumab-treated advanced NSCLC, survival outcomes are primarily driven by tumor biology, disease burden, and immune–inflammatory dynamics evolving during therapy. On-treatment inflammatory markers, particularly dNLR and ΔNLR, provide more clinically relevant prognostic information than baseline indices, whereas baseline EASIX appears to have limited utility in this setting. These findings support a treatment-specific, time-dependent approach to biomarker-based risk stratification in immunotherapy.

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