Abstract
Background
Pan-immune-inflammation value (PIV) is an easily accessible immune marker based on peripheral blood to estimate prognosis in patients with cancer. This study evaluates the prognostic value of PIV in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.
Methods
In this retrospective cohort study, patients with mRCC treated with nivolumab in the second line and beyond were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. PIV was calculated using the following formula: neutrophil (103/mm3) x monocyte (103/mm3) x platelet (103/mm3)/lymphocyte (103/mm3).
Results
A total of 152 patients with mRCC were included in this study. According to cut-off value for PIV, 77 (50.7%) and 75 (49.3%) patients fell into PIV-low (\(\le\) 372) and PIV-high (> 372) groups, respectively. In multivariate analysis, PIV-high (HR: 1.64, 95% CI 1.04–2.58, p = 0.033 for overall survival (OS); HR: 1.55, 95% CI 1.02–2.38, p = 0.042 for progression-free survival (PFS)) was independent risk factor for OS and PFS after adjusting for confounding variables, such as performance score, the International mRCC Database Consortium (IMDC) risk score, and liver metastasis.
Conclusion
This study established that pre-treatment PIV might be a prognostic biomarker in patients with mRCC treated with nivolumab in the second line and beyond.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Bilen MA et al (2018) Association between pretreatment neutrophil-to-lymphocyte ratio and outcome of patients with metastatic renal-cell carcinoma treated with nivolumab. Clin Genitourin Cancer 16:e563–e575. https://doi.org/10.1016/j.clgc.2017.12.015
Choueiri TK et al (2021) Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 384:829–841. https://doi.org/10.1056/NEJMoa2026982
Corti F et al (2021) The pan-immune-inflammation value in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors. Eur J Cancer 150:155–167. https://doi.org/10.1016/j.ejca.2021.03.043
De Giorgi U et al (2019) Association of systemic inflammation index and body mass index with survival in patients with renal cell cancer treated with nivolumab. Clin Cancer Res 25:3839–3846. https://doi.org/10.1158/1078-0432.CCR-18-3661
Dudani S et al (2020) Application of IMDC criteria across first-line (1L) and second-line (2L) therapies in metastatic renal-cell carcinoma (mRCC): new and updated benchmarks of clinical outcomes. J Clin Oncol 38:5063–5063. https://doi.org/10.1200/JCO.2020.38.15_suppl.5063
Dymicka-Piekarska V, Koper-Lenkiewicz OM, Zinczuk J, Kratz E, Kaminska J (2021) Inflammatory cell-associated tumors. not only macrophages (TAMs), fibroblasts (TAFs) and neutrophils (TANs) can infiltrate the tumor microenvironment the unique role of tumor associated platelets (TAPs). Cancer Immunol Immunother 70:1497–1510. https://doi.org/10.1007/s00262-020-02758-7
Fuca G et al (2020) The pan-immune-Inflammation value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the valentino and TRIBE first-line trials. Br J Cancer 123:403–409. https://doi.org/10.1038/s41416-020-0894-7
Fuca G et al (2021) The pan-immune-inflammation value in patients with metastatic melanoma receiving first-line therapy target. Oncol 16:529–536. https://doi.org/10.1007/s11523-021-00819-0
Gambichler T, Said S, Abu Rached N, Scheel CH, Susok L, Stranzenbach R, Becker JC (2022) Pan-immune-inflammation value independently predicts disease recurrence in patients with Merkel cell carcinoma. J Cancer Res Clin Oncol. https://doi.org/10.1007/s00432-022-03929-y
Gao Y et al (2019) Systemic immune-inflammation index (SII) is useful to predict survival outcomes in patients with surgically resected esophageal squamous cell carcinoma. J Cancer 10:3188–3196. https://doi.org/10.7150/jca.30281
Garcia-Rojo D, Prera A, Munoz-Rodriguez J, Oliva JC, Dominguez A, Prats J (2021) Prognostic value of lymphocyte-to-monocyte ratio previously determined to surgery in patients with non-metastatic renal cell carcinoma: a systematic review and a prisma-compliant meta-analysis. Med (Baltimore) 100:e24152. https://doi.org/10.1097/MD.0000000000024152
Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899. https://doi.org/10.1016/j.cell.2010.01.025
Heng DY et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799. https://doi.org/10.1200/JCO.2008.21.4809
Hizal M et al (2020) Neutrophil-lymphocyte ratio as a prognostic factor for survival in patients with advanced renal cell carcinoma (Turkish oncology group study). J Oncol Pharm Pract 26:1583–1589. https://doi.org/10.1177/1078155219900908
Jeyakumar G et al (2017) Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy J Immunother. Cancer 5:82. https://doi.org/10.1186/s40425-017-0287-5
Lalani AA et al (2018) Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. J Immunother Cancer 6:5. https://doi.org/10.1186/s40425-018-0315-0
Laubli H, Spanaus KS, Borsig L (2009) Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes. Blood 114:4583–4591. https://doi.org/10.1182/blood-2008-10-186585
Ligorio F et al (2021) The pan-immune-inflammation-value predicts the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer treated with first-line taxane-trastuzumab-pertuzumab. Cancers (Basel). https://doi.org/10.3390/cancers13081964
Liu J et al (2019) 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 33:e22964. https://doi.org/10.1002/jcla.22964
Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444. https://doi.org/10.1038/nature07205
Motzer RJ et al (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1803–1813. https://doi.org/10.1056/NEJMoa1510665
Motzer RJ et al (2018) Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378:1277–1290. https://doi.org/10.1056/NEJMoa1712126
Motzer R et al (2021) Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 384:1289–1300. https://doi.org/10.1056/NEJMoa2035716
Na N, Yao J, Cheng C, Huang Z, Hong L, Li H, Qiu J (2016) Meta-analysis of the efficacy of the pretreatment neutrophil-to-lymphocyte ratio as a predictor of prognosis in renal carcinoma patients receiving tyrosine kinase inhibitors. Oncotarget 7:44039–44046. https://doi.org/10.18632/oncotarget.9836
National comprehensive cancer network-kidney cancer (2021). https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed 21 Jul2021
Nishiyama N et al (2020) The neutrophil-lymphocyte ratio has a role in predicting the effectiveness of nivolumab in Japanese patients with metastatic renal cell carcinoma: a multi-institutional retrospective study. BMC Urol 20:110. https://doi.org/10.1186/s12894-020-00679-2
Posadas EM, Limvorasak S, Figlin RA (2017) Targeted therapies for renal cell carcinoma. Nat Rev Nephrol 13:496–511. https://doi.org/10.1038/nrneph.2017.82
Rebuzzi SE et al (2020) Baseline lymphocyte to monocyte ratio (LMR) and systemic inflammation index (SII) as prognostic factors in metastatic renal cell carcinoma (mRCC) patients treated with nivolumab: preliminary results of the Meet-URO 15 (I-BIO-REC) study. J of Clin Oncol 38:751–751. https://doi.org/10.1200/JCO.2020.38.6_suppl.751
Susok L, Said S, Reinert D, Mansour R, Scheel CH, Becker JC, Gambichler T (2022) The pan-immune-inflammation value and systemic immune-inflammation index in advanced melanoma patients under immunotherapy. J Cancer Res Clin Oncol. https://doi.org/10.1007/s00432-021-03878-y
Teishima J et al (2020) Impact of the systemic immune-inflammation index for the prediction of prognosis and modification of the risk model in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. Can Urol Assoc J 14:E582–E587. https://doi.org/10.5489/cuaj.6413
Templeton AJ et al (2016) Change in neutrophil-to-lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy. Eur Urol 70:358–364. https://doi.org/10.1016/j.eururo.2016.02.033
Vicente Conesa MA, Garcia-Martinez E, Gonzalez Billalabeitia E, Chaves Benito A, Garcia Garcia T, Vicente Garcia V, de la Pena FA (2012) Predictive value of peripheral blood lymphocyte count in breast cancer patients treated with primary chemotherapy. Breast 21:468–474. https://doi.org/10.1016/j.breast.2011.11.002
Wang Q, Zhu D (2019) The prognostic value of systemic immune-inflammation index (SII) in patients after radical operation for carcinoma of stomach in gastric cancer. J Gastrointest Oncol 10:965–978. https://doi.org/10.21037/jgo.2019.05.03
Wu L, Saxena S, Awaji M, Singh RK (2019) Tumor-associated neutrophils in cancer: going pro. Cancers (Basel). https://doi.org/10.3390/cancers11040564
Xu JX et al (2017) FDA approval summary: nivolumab in advanced renal cell carcinoma after anti-angiogenic therapy and exploratory predictive biomarker analysis. Oncologist 22:311–317. https://doi.org/10.1634/theoncologist.2016-0476
Yasar HA et al (2020) The relationship between prognostic nutritional index and treatment response in patients with metastatic renal cell cancer. J Oncol Pharm Pract 26:1110–1116. https://doi.org/10.1177/1078155219883004
Yip SM et al (2018) Checkpoint inhibitors in patients with metastatic renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Cancer 124:3677–3683. https://doi.org/10.1002/cncr.31595
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no relevant financial or non-financial interests to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yekedüz, E., Tural, D., Ertürk, İ. et al. The relationship between pan-immune-inflammation value and survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab in the second line and beyond: a Turkish oncology group kidney cancer consortium (TKCC) study. J Cancer Res Clin Oncol 148, 3537–3546 (2022). https://doi.org/10.1007/s00432-022-04055-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-022-04055-5