Inflammatory prognostic index score as a new parameter predicting overall survival in renal cell carcinoma

Abstract

Background/Aim: The importance of prognostic markers in the treatment and follow-up of metastatic renal cell carcinoma is gradually increasing. Currently used markers do not meet the exact needs in this regard. In this study, we evaluated the predictive and prognostic values of inflammatory prognostic index (IPI) scoring in metastatic Renal cell carcinoma (RCC) patients. In IPI scoring, we used four biochemical parameters related to inflammation, including albumin, CRP, neutrophils, and lymphocytes. Methods: Medical records of fifty-seven patients with RCC treated in Celal Bayar University Medical Faculty Hospital Medical Oncology Clinic between February 2012 and April 2019 were retrospectively reviewed. The IPI was calculated as C-reactive protein × NLR (neutrophil/lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The cut-off value for IPI in predicting mortality was 1.03 according to ROC curve analysis. Median OS of the patients with IPI ≥1.03 was 8 months (95 %Cl 3-10.9). The relationship between overall survival and IPI score was remarkable. According to this analysis, comorbidity, metastasis to the lung, liver, lymph nodes, bone, the number of metastatic sites (one metastatic area), high NLR, high IPI were also significantly associated with OS (P<0.05 for each). In multivariate analyses, IPI was an independent prognostic factor in RCC. Patients with high IPI (>1.03) had an increased mortality risk compared to those with low IPI (<1.03) (HR: 8.5; 95 %CI, 2.303-31.42; P<0.001). Comorbidity, lung metastasis, lymph nodes and bone metastasis, high NLR, IMDC risk also independently predicted worse OS in RCC. Conclusion: The relationship between many inflammatory markers, such as NLR and RCC, and overall survival was proven earlier, while the relationship with IPI is discussed for the first time. We would like to discuss the findings we obtained in our study in the light of other analyses in the literature investigating the relationship between other inflammation markers and RCC. IPI may be an easily accessible and independent prognostic index for RCC patients, and useful for clinical practice.

Keywords

• Renal cell carcinoma
• IPI scoring
• Overall survival
• Neutrophil/lymphocyte ratio
• Inflammation mediators
• C-reactive protein
• Albumin

Kaynakça

1. 1. Peinemann F, Unverzagt S, Hadjinicolaou AV, Moldenhauer I. Immunotherapy for metastatic renal cell carcinoma: A systematic review. J Evid Based Med. 2019 Nov;12(4):253-62. doi: 10.1111/jebm.12362.
2. 2. Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, et al. Renal Hücreli Karsinomun Epidemiyolojisi. Eur Urol. 2019;75(1):74-84. doi: 10.1016/j.eururo.2018.08.036
3. 3. Jonasch E, Gao J, Rathmell WK. Renal cell carcinoma. BMJ. 2014;75(1):74-84. doi: 10.1016/j.eururo.2018.08.036.
4. 4. Dirican A, Kucukzeybek Y, Erten C, Somali I, Demir L, Can A, et al. Prognostic and predictive value of hematologic parameters in patients with metastatic renal cell carcinoma: second line sunitinib treatment following IFN-alpha. Asian Pac J Cancer Prev. 2013;14(3):2101-5.
5. 5. Roxburgh S, McMillan C. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncology. 2010;6(1):149-63.
6. 6. Grivennikov SI, Greten R, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883-99.
7. 7. Karin M. Nuclear factor-κB in cancer development and progression. Nature. 2006;441(7092):431-6.
8. 8. Mantovani A, Allavena P, Sica A, Balkwill, F. Cancer-related inflammation. Nature. 2008;454(7203):436-44.

9. 9. Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI, et al. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nature Medicine. 2007;13(10):1211-8.
10. 10. Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 2004;6(5):447-58.
11. 11. Vakkila J, Lotze MT. Inflammation and necrosis promote tumour growth. Nature Reviews Immunology. 2004;4(8):641-8.
12. 12. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A.Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073-81.
13. 13. Hussain SP, Hofseth LJ, Harris C.Radical causes of cancer. Nature Reviews Cancer. 2003;3(4):276-85.
14. 14. Okazaki IM, Kotani A, Honjo T. Role of AID in tumorigenesis. Advances in Immunology. 2007;94:245-73.
15. 15. Bui JD, Schreiber RD. Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Current opinion in immunology. 2007;19(2):203-8.
16. 16. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. New England journal of medicine. 1999;340(6):448-54.
17. 17. Morley JE, Thomas DR, Wilson G. Cachexia: pathophysiology and clinical relevance. The American Journal of Clinical Nutrition. 2006;83(4):735-43.
18. 18. Fearon KC, Voss AC, Hustead DS. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. The American Journal of Clinical Nutrition. 2006;83(6):1345-50.
19. 19. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Current Opinion in Clinical Nutrition & Metabolic Care. 2009;12(3):223-6.
20. 20. Dirican N, Dirican A, Anar C, Atalay S, Ozturk O, Bircan A, et al. A new inflammatory prognostic index, based on C-reactive protein, the neutrophil to lymphocyte ratio and serum albumin is useful for predicting prognosis in non-small cell lung cancer cases. Asian Pacific journal of cancer prevention: APJCP. 2016;17(12):5101.
21. 21. Shen J, Chen Z, Fan M, Lu H, Zhuang Q, He X. Prognostic value of pretreatment neutrophil count in metastatic renal cell carcinoma: a systematic review and meta-analysis. Cancer Management and Research. 2019;10(11):5365-74.
22. 22. Tazzyman S, Lewis CE, Murdoch C. Neutrophils: key mediators of tumour angiogenesis. International Journal of Experimental Pathology. 2009;90(3):222-31.
23. 23. Dirkx AE, Egbrink M.G, Wagstaff J, Griffioen AW. Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. Journal of Leukocyte Biology. 2006;80(6):1183-96.
24. 24. Nunno , Mollica V, Gatto L, Santoni M, Cosmai L, Porta C, Massari, F. Prognostic impact of neutrophil-to-lymphocyte ratio in renal cell carcinoma: a systematic review and meta-analysis. Immunotherapy. 2009;11(7):631-43.
25. 25. Tsujino T, Komura K, Hashimoto T, Muraoka R, Satake N, Matsunaga T, et al. C-reactive protein-albumin ratio as a prognostic factor in renal cell carcinoma–A data from multi-institutional study in Japan. In Urologic Oncology: Seminars and Original Investigations. 2019;37(11):812.e1-812.e8.
26. 26. Ishihara H, Kondo T, Yoshida K, Omae K, Takagi T, Iizuka J, et al. Effect of systemic inflammation on survival in patients with metastatic renal cell carcinoma receiving second-line molecular-targeted therapy. Clinical Genitourinary Cancer. 2017;15(4):495-501.
27. 27. Sekar RR, Patil D, Baum Y, Pearl J, Bausum A, Bilen MA, et al. A novel preoperative inflammatory marker prognostic score in patients with localized and metastatic renal cell carcinoma. Asian Journal of Urology. 2017;4(4):230-8.