İzole akciğer metastazlı renal hücreli karsinomda sistemik inflamatuvar belirteçlerin prognostik önemi: Retrospektif inceleme

Öz

Amaç: İzole akciğer metastazlı metastatik renal hücreli karsinom (mRHK) kötü prognozla ilişkilidir ve potansiyel prognostik göstergeler olarak sistemik inflamatuar belirteçlere artan bir ilgi vardır. Bu çalışmada mRCC hastalarında Sistemik İmmün- İnflamasyon İndeksi (Sİİ), Nötrofil-Lenfosit Oranı (NLO), Trombosit-Lenfosit Oranı (PLO) ve İleri Akciğer Kanseri İnflamasyon İndeksi'nin (İAİİ) prognostik önemi değerlendirilmektedir. Gereç ve Yöntemler: Akciğer metastazları tedavi edilen 76 mRHK hastasının retrospektif bir analizini yaptık. Demografik özellikler, tedavi ayrıntıları ve enflamatuar belirteçler dahil olmak üzere klinik veriler toplandı. Hastalar Uluslararası Metastatik Renal Hücreli Karsinom Veritabanı (IMDC) risk sınıflandırmasına göre tabakalandırıldı. Klinik ve laboratuvar parametrelerinin progresyonsuz sağkalım (PFS) ve genel sağkalım (GS) ile ilişkisi Kaplan-Meier eğrileri ve Cox orantılı tehlikeler modelleri kullanılarak analiz edilmiştir. Bulgular: Hastaların ortanca yaşı 61 (dağılım: 29-84) olup, çoğunluğu erkek (%74) ve sigara içmektedir (%57). Yüksek SII, NLR ve PLR kötü IMDC risk sınıflandırması ile anlamlı olarak ilişkiliydi (sırasıyla p=0.001, p=0.003 ve p=0.001). Çok değişkenli analizde 65 yaş üstü (HR 3.09, %95 CI 1.3-6.9, p=0.006) ve yüksek PLR (HR 5.9, %95 CI 2.2-15.8, p=0.001) daha kötü OS için bağımsız öngörücüler olarak tanımlanmıştır. ALI ile sağkalım sonuçları arasında anlamlı bir ilişki bulunmamıştır. Sonuç: Sistemik inflamatuvar belirteçler, özellikle SII, NLR ve PLR, akciğer metastazı olan mRCC hastalarında kötü prognoz ile güçlü bir şekilde ilişkilidir. Bu belirteçler, risk sınıflandırmasını iyileştirmek ve klinik karar verme sürecini yönlendirmek için mevcut prognostik modellere entegre edilebilir. Bu bulguları doğrulamak ve sistemik enflamasyonu RCC progresyonuna bağlayan altta yatan mekanizmaları keşfetmek için daha fazla araştırma yapılması gerekmektedir.

Anahtar Kelimeler

• Metastatik renal hücreli kanser
• akciğer metastazı
• sistemik immune-inflamatuar indeks
• nötrofil lenfosit oranı
• trombosit lenfosit oranı

Prognostic value of systemic inflammatory markers in renal cell carcinoma with isolated lung metastases: A retrospective analysis

Öz

Aim: Metastatic renal cell carcinoma (mRCC) with lung metastases is associated with poor prognosis, and there is a growing interest in systemic inflammatory markers as potential prognostic indicators. This study evaluates the prognostic significance of the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to- Lymphocyte Ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) in patients with mRCC. Material and Methods: In our retrospective and multicenter study, we analyzed 76 mRCC patients with isolated lung metastases. Clinical data, including demographic characteristics, treatment details, and inflammatory markers, were collected. Patients were stratified according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification. The association of clinical and laboratory parameters with progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards models. Results: The median age of the patients was 61 years (IQR: 29-84), with the majority being male (74%) and smokers (57%). High SII, NLR, and PLR were significantly associated with poor IMDC risk classification (p=0.001, p=0.003, and p=0.001, respectively). Multivariate analysis identified age >65 years (HR 3.09, 95% CI 1.3-6.9, p=0.006) and high PLR (HR 5.9, 95% CI 2.2-15.8, p=0.001) as independent predictors of worse OS. ALI was not significantly associated with survival outcomes. Conclusion: Systemic inflammatory markers, particularly SII, NLR and PLR are strongly associated with poor prognosis in mRCC patients with lung metastases. These markers could be integrated into existing prognostic models to improve risk stratification and guide clinical decision-making. Further research is warranted to validate these findings and explore the underlying mechanisms linking systemic inflammation to RCC progression.

Anahtar Kelimeler

• Metastatic renal cell carcinoma
• Lung metastases
• Systemic immune-inflammation index
• Neutrophil-to- lymphocyte ratio
• Platelet-to-lymphocyte ratio

Kaynakça

1. “RCC UPTODATE”.
2. Z. Zhang, C. Liang, B. Hou, and L. Zhou, “Population-based evaluation of the risk factors and prognosis among renal cell carcinoma patients with initially diagnosed lung metastases,” Actas Urológicas Españolas (English Edition), vol. 45, no. 7, pp. 498–506, Sep. 2021, doi: 10.1016/j.acuroe.2021.06.004.
3. D. Işık et al., “Clinical Effectiveness of Targeted Therapies Following Nivolumab Therapy in Patients with Metastatic Renal Cell Carcinoma: A Real-World Study,” Medicina (B Aires), vol. 60, no. 7, p. 1088, Jul. 2024, doi: 10.3390/medicina60071088.
4. P. Ding et al., “Combined systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: a prospective study,” BMC Gastroenterol, vol. 22, no. 1, p. 121, Dec. 2022, doi: 10.1186/ s12876-022-02199-9.
5. T. Horino, R. Tokunaga, Y. Miyamoto, and H. Baba, “Advanced Lung Cancer Inflammation Index: A Novel Comprehensive Biomarker of Host Status for Patients with Metastatic Colorectal Cancer,” J Anus Rectum Colon, vol. 8, no. 3, pp. 2023–077, Jul. 2024, doi: 10.23922/jarc.2023-077.
6. W. Chen, S. Xin, and B. Xu, “Value Research of NLR, PLR, and RDW in Prognostic Assessment of Patients with Colorectal Cancer,” J Healthc Eng, vol. 2022, pp. 1–6, Apr. 2022, doi: 10.1155/2022/7971415.
7. M. Capone et al., “Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab,” J Immunother Cancer, vol. 6, no. 1, p. 74, Dec. 2018, doi: 10.1186/s40425-018-0383-1.
8. G. Jiang, S. Chen, and M. Chen, “Exploration of IMDC model in patients with metastatic renal cell carcinoma using targeted agents: a meta-analysis,” International braz j urol, vol. 46, no. 3, pp. 328–340, Jun. 2020, doi: 10.1590/s1677-5538.ibju.2019.0423.

9. M. Zhu et al., “The Systemic Inflammation Response Index as an Independent Predictor of Survival in Breast Cancer Patients: A Retrospective Study,” Front Mol Biosci, vol. 9, Feb. 2022, doi: 10.3389/fmolb.2022.856064.
10. T. Horino et al., “The advanced lung cancer inflammation index is a novel independent prognosticator in colorectal cancer patients after curative resection,” Ann Gastroenterol Surg, vol. 6, no. 1, pp. 83–91, Jan. 2022, doi: 10.1002/ags3.12499.
11. J. F. Feng, S. Chen, and X. Yang, “Systemic immune-inflammation index (SII) is a useful prognostic indicator for patients with squamous cell carcinoma of the esophagus,” Medicine (United States), vol. 96, no. 4, 2017, doi: 10.1097/MD.0000000000005886.
12. R. H. Wang et al., “The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet- to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage,” Front Immunol, vol. 14, 2023, doi: 10.3389/fimmu.2023.1115031.
13. A. J. Templeton et al., “Prognostic Role of Neutrophil-to- Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis,” JNCI: Journal of the National Cancer Institute, vol. 106, no. 6, Jun. 2014, doi: 10.1093/jnci/dju124.
14. Y. H. Park, H. G. Yi, M. H. Lee, C. S. Kim, and J. H. Lim, “Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy,” Acta Haematol, vol. 137, no. 2, pp. 76–85, 2017, doi: 10.1159/000452991.
15. Q. Li, F. Ma, and J. feng Wang,“Advanced lung cancer inflammation index predicts survival outcomes of hepatocellular carcinoma patients receiving immunotherapy,” Front Oncol, vol. 13, Mar. 2023, doi: 10.3389/fonc.2023.997314.
16. J. Liu et al., “Systemic immune‐inflammation index, neutrophil‐ to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio can predict clinical outcomes in patients with metastatic non‐small‐cell lung cancer treated with nivolumab,” J Clin Lab Anal, vol. 33, no. 8, Oct. 2019, doi: 10.1002/jcla.22964.
17. M. Song et al., “The advanced lung cancer inflammation index is the optimal inflammatory biomarker of overall survival in patients with lung cancer,” J Cachexia Sarcopenia Muscle, vol. 13, no. 5, pp. 2504–2514, Oct. 2022, doi: 10.1002/jcsm.13032.
18. H. Mandaliya, M. Jones, C. Oldmeadow, and I. I. C. Nordman, “Prognostic biomarkers in stage IV non-small cell lung cancer (NSCLC): neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI),” Transl Lung Cancer Res, vol. 8, no. 6, pp. 886–894, Dec. 2019, doi: 10.21037/tlcr.2019.11.16.
19. A. Y. Gasparyan, L. Ayvazyan, U. Mukanova, M. Yessirkepov, and G. D. Kitas, “The Platelet-to-Lymphocyte Ratio as an Inflammatory Marker in Rheumatic Diseases,” Ann Lab Med, vol. 39, no. 4, pp. 345–357, Jul. 2019, doi: 10.3343/alm.2019.39.4.345.
20. S. Lattanzi, F. Brigo, E. Trinka, C. Cagnetti, M. Di Napoli, and M. Silvestrini, “Neutrophil-to-Lymphocyte Ratio in Acute Cerebral Hemorrhage: a System Review,” Transl Stroke Res, vol. 10, no. 2, pp. 137–145, Apr. 2019, doi: 10.1007/s12975-018-0649-4.
21. J. Tu et al., “Advanced lung cancer inflammation index is associated with long-term cardiovascular death in hypertensive patients: national health and nutrition examination study, 1999–2018,” Front Physiol, vol. 14, May 2023, doi: 10.3389/ fphys.2023.1074672.