Association of Controlling Nutritional Status score with prognosis and clinicopathological characteristics of patients with non-small cell lung cancer: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

TANG Xianliang ¹ , HE Xiaofeng ² ,  ZHANG Wenping ¹

1. Department of Thoracic Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, 046000, P. R. China;
2. Institute of Evidence-based Medicine, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, 046000, P. R. China;

Corresponding author：

ZHANG Wenping, Email: zhangwenping68@126.com

Keywords：

Controlling nutritional status score; non-small cell lung cancer; clinicopathologic feature; prognosis; systematic review/meta-analysis

DOI：

10.7507/1007-4848.202308011

Video：

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Objective To assess the prognostic significance of the Controlling Nutritional Status (CONUT) score in patients with non-small cell lung cancer (NSCLC) and its association with clinicopathological characteristics. Methods The relevant studies investigating the association between CONUT score and prognosis of NSCLC patients were systematically searched in the PubMed, Web of Science, EMbase, Cochrane Library, CNKI, Wanfang Database and other databases from their inception to July 2023. Two independent researchers screened the references according to predefined inclusion and exclusion criteria, extracted data and conducted quality assessment. The quality of included references was evaluated using New Castle-Ottawa Scale (NOS). The meta-analysis was performed using Stata 17.0 software, and a combined hazard ratio (HR) or odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association of CONUT score with prognosis and clinicopathological characteristics in NSCLC patients. Results A total of 17 cohort studies, comprising 5182 NSCLC patients with stage Ⅰ-Ⅳ, were included in this analysis. All studies had a NOS≥6 points. The meta-analysis showed that there was a significant correlation between CONUT score and overall survival (OS) as well as disease-free survival (DFS) among NSCLC patients: the higher the score, the shorter the OS [HR=1.87, 95%CI (1.58, 2.21), P<0.001] and DFS [HR=1.91, 95%CI (1.63, 2.24), P<0.001]. These differences were statistically significant. Furthermore, CONUT score was significantly associated with age, smoking status, tumor stage, and N stage (P<0.05). Conclusion A higher CONUT score is associated with a poorer OS and DFS in patients with NSCLC, and CONUT score can be used as a potential predictor of NSCLC prognosis.

1.	Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33.
2.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3.	Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow?. Lancet, 2001, 357(9255): 539-545.
4.	Singh N, Baby D, Rajguru JP, et al. Inflammation and cancer. Ann Afr Med, 2019, 18(3): 121-126.
5.	Wang Y, Li Y, Chen P, et al. Prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with non-small cell lung cancer: A meta-analysis. Ann Transl Med, 2019, 7(18): 433.
6.	Wang Z, Wang Y, Zhang X, et al. Pretreatment prognostic nutritional index as a prognostic factor in lung cancer: Review and meta-analysis. Clin Chim Acta, 2018, 486: 303-310.
7.	吴丽, 郑玲. 炎性复合指标与非小细胞肺癌预后关系的研究进展. 现代肿瘤医学, 2019, 27(2): 342-345.
8.	Gunsel-Yildirim G, Ceylan KC, Dikmen D. The effect of perioperative immunonutritional support on nutritional and inflammatory status in patients undergoing lung cancer surgery: A prospective, randomized controlled study. Support Care Cancer, 2023, 31(6): 365.
9.	Olmez OF, Bilici A, Gursoy P, et al. Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib. Pulmonology, 2023, 29(6): 478-485.
10.	Ignacio de Ulíbarri J, González-Madroño A, de Villar NG, et al. CONUT: A tool for controlling nutritional status. First validation in a hospital population. Nutr Hosp. 2005, 20(1): 38-45.
11.	Asakawa A, Ishibashi H, Matsuyama Y, et al. Preoperative nutritional status is associated with the prognosis for lung cancer. Asian Cardiovasc Thorac Ann, 2021, 29(8): 763-771.
12.	Gul B, Metintas S, Ak G, et al. The relationship between nutritional status and prognosis in patients with locally advanced and advanced stage lung cancer. Support Care Cancer, 2021, 29(6): 3357-3365.
13.	Kuroda D, Sawayama H, Kurashige J, et al. Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer, 2018, 21(2): 204-212.
14.	Takagi K, Domagala P, Polak WG, et al. Prognostic significance of the controlling nutritional status (CONUT) score in patients undergoing hepatectomy for hepatocellular carcinoma: A systematic review and meta-analysis. BMC Gastroenterol, 2019, 19(1): 211.
15.	Iseki Y, Shibutani M, Maeda K, et al. Impact of the preoperative Controlling Nutritional Status (CONUT) score on the survival after curative surgery for colorectal cancer. PLoS One, 2015, 10(7): e0132488.
16.	Nemoto Y, Kondo T, Ishihara H, et al. The Controlling Nutritional Status CONUT score in patients with advanced bladder cancer after radical cystectomy. In Vivo, 2021, 35(2): 999-1006.
17.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
18.	Akamine T, Toyokawa G, Matsubara T, et al. Significance of the preoperative CONUT score in predicting postoperative disease-free and overall survival in patients with lung adenocarcinoma with obstructive lung disease. Anticancer Res, 2017, 37(5): 2735-2742.
19.	Lee SC, Lee JG, Lee SH, et al. Prediction of postoperative pulmonary complications using preoperative controlling nutritional status (CONUT) score in patients with resectable non-small cell lung cancer. Sci Rep, 2020, 10(1): 12385.
20.	Liu XY, Zhang X, Zhang Q, et al. Value of the Controlling Nutritional Status score in predicting the prognosis of patients with lung cancer: A multicenter, retrospective study. JPEN J Parenter Enteral Nutr, 2022, 46(6): 1343-1352.
21.	Miura N, Shoji F, Kozuma Y, et al. Preoperative immune-nutritional abnormality predicts poor outcome in elderly non-small-cell lung cancer patients with comorbidities. Ann Thorac Cardiovasc Surg, 2020, 26(5): 240-247.
22.	Ohba T, Takamori S, Toyozawa R, et al. Prognostic impact of the Controlling Nutritional Status score in patients with non-small cell lung cancer treated with pembrolizumab. J Thorac Dis, 2019, 11(9): 3757-3768.
23.	Shoji F, Haratake N, Akamine T, et al. The preoperative Controlling Nutritional Status score predicts survival after curative surgery in patients with pathological stageⅠnon-small cell lung cancer. Anticancer Res, 2017, 37(2): 741-747.
24.	Shoji F, Miura N, Matsubara T, et al. Prognostic significance of immune-nutritional parameters for surgically resected elderly lung cancer patients: A multicentre retrospective study. Interact Cardiovasc Thorac Surg, 2018, 26(3): 389-394.
25.	Takahashi M, Sowa T, Tokumasu H, et al. Comparison of three nutritional scoring systems for outcomes after complete resection of non-small cell lung cancer. J Thorac Cardiovasc Surg, 2021, 162(4): 1257-1268.
26.	Takamori S, Toyokawa G, Shimokawa M, et al. A novel prognostic marker in patients with non-small cell lung cancer: Musculo-immuno-nutritional score calculated by controlling nutritional status and creatine kinase. J Thorac Dis, 2019, 11(3): 927-935.
27.	Toyokawa G, Kozuma Y, Matsubara T, et al. Prognostic impact of controlling nutritional status score in resected lung squamous cell carcinoma. J Thorac Dis, 2017, 9(9): 2942-2951.
28.	Toyokawa G, Shoji F, Yamazaki K, et al. Significance of the red blood cell distribution width in resected pathologic stageⅠnon-small cell lung cancer. Semin Thorac Cardiovasc Surg, 2020, 32(4): 1036-1045.
29.	Zhang Y, Kong FF, Zhu ZQ, et al. Controlling Nutritional Status (CONUT) score is a prognostic marker in Ⅲ-Ⅳ NSCLC patients receiving first-line chemotherapy. BMC Cancer, 2023, 23(1): 225.
30.	戴宁凰, 郑中锋, 季中华, 等. CONUT评分联合CYFRA21-1表达在NSCLC患者预后评估中的应用. 肿瘤代谢与营养电子杂志, 2021, 8(6): 648-653.
31.	王晓兰, 韩伟, 王莹. 营养免疫与系统炎症参数在非小细胞肺癌患者中的预后意义. 肿瘤代谢与营养电子杂志, 2021, 8(5): 519-524.
32.	张耀森, 卢国杰, 钟惠铃, 等. 术前控制营养状态评分对非小细胞肺癌患者根治术后复发转移的预测价值分析. 肿瘤综合治疗电子杂志, 2022, 8(4): 71-75.
33.	Zhang CL, Gao MQ, Jiang XC, et al. Research progress and value of albumin-related inflammatory markers in the prognosis of non-small cell lung cancer: A review of clinical evidence. Ann Med, 2023, 55(1): 1294-1307.
34.	Peng J, Hao Y, Rao B, et al. Prognostic impact of the pre-treatment controlling nutritional status score in patients with non-small cell lung cancer: A meta-analysis. Medicine (Baltimore), 2021, 100(26): e26488.
35.	Castell JV, Gómez-Lechón MJ, David M, et al. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology, 1990, 12(5): 1179-1186.
36.	Yang Z, Zheng Y, Wu Z, et al. Association between pre-diagnostic serum albumin and cancer risk: Results from a prospective population-based study. Cancer Med, 2021, 10(12): 4054-4065.
37.	Kuzu OF, Noory MA, Robertson GP. The role of cholesterol in cancer. Cancer Res, 2016, 76(8): 2063-2070.
38.	Lee YH, Martin-Orozco N, Zheng P, et al. Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. Cell Res, 2017, 27(8): 1034-1045.
39.	Hughes DA, Townsend PJ, Haslam PL. Enhancement of the antigen-presenting function of monocytes by cholesterol: Possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis. Clin Exp Immunol, 1992, 87(2): 279-286.
40.	Shankaran V, Ikeda H, Bruce AT, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature, 2001, 410(6832): 1107-1111.

1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33.
2. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3. Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow?. Lancet, 2001, 357(9255): 539-545.
4. Singh N, Baby D, Rajguru JP, et al. Inflammation and cancer. Ann Afr Med, 2019, 18(3): 121-126.
5. Wang Y, Li Y, Chen P, et al. Prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with non-small cell lung cancer: A meta-analysis. Ann Transl Med, 2019, 7(18): 433.
6. Wang Z, Wang Y, Zhang X, et al. Pretreatment prognostic nutritional index as a prognostic factor in lung cancer: Review and meta-analysis. Clin Chim Acta, 2018, 486: 303-310.
7. 吴丽, 郑玲. 炎性复合指标与非小细胞肺癌预后关系的研究进展. 现代肿瘤医学, 2019, 27(2): 342-345.
8. Gunsel-Yildirim G, Ceylan KC, Dikmen D. The effect of perioperative immunonutritional support on nutritional and inflammatory status in patients undergoing lung cancer surgery: A prospective, randomized controlled study. Support Care Cancer, 2023, 31(6): 365.
9. Olmez OF, Bilici A, Gursoy P, et al. Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib. Pulmonology, 2023, 29(6): 478-485.
10. Ignacio de Ulíbarri J, González-Madroño A, de Villar NG, et al. CONUT: A tool for controlling nutritional status. First validation in a hospital population. Nutr Hosp. 2005, 20(1): 38-45.
11. Asakawa A, Ishibashi H, Matsuyama Y, et al. Preoperative nutritional status is associated with the prognosis for lung cancer. Asian Cardiovasc Thorac Ann, 2021, 29(8): 763-771.
12. Gul B, Metintas S, Ak G, et al. The relationship between nutritional status and prognosis in patients with locally advanced and advanced stage lung cancer. Support Care Cancer, 2021, 29(6): 3357-3365.
13. Kuroda D, Sawayama H, Kurashige J, et al. Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer, 2018, 21(2): 204-212.
14. Takagi K, Domagala P, Polak WG, et al. Prognostic significance of the controlling nutritional status (CONUT) score in patients undergoing hepatectomy for hepatocellular carcinoma: A systematic review and meta-analysis. BMC Gastroenterol, 2019, 19(1): 211.
15. Iseki Y, Shibutani M, Maeda K, et al. Impact of the preoperative Controlling Nutritional Status (CONUT) score on the survival after curative surgery for colorectal cancer. PLoS One, 2015, 10(7): e0132488.
16. Nemoto Y, Kondo T, Ishihara H, et al. The Controlling Nutritional Status CONUT score in patients with advanced bladder cancer after radical cystectomy. In Vivo, 2021, 35(2): 999-1006.
17. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
18. Akamine T, Toyokawa G, Matsubara T, et al. Significance of the preoperative CONUT score in predicting postoperative disease-free and overall survival in patients with lung adenocarcinoma with obstructive lung disease. Anticancer Res, 2017, 37(5): 2735-2742.
19. Lee SC, Lee JG, Lee SH, et al. Prediction of postoperative pulmonary complications using preoperative controlling nutritional status (CONUT) score in patients with resectable non-small cell lung cancer. Sci Rep, 2020, 10(1): 12385.
20. Liu XY, Zhang X, Zhang Q, et al. Value of the Controlling Nutritional Status score in predicting the prognosis of patients with lung cancer: A multicenter, retrospective study. JPEN J Parenter Enteral Nutr, 2022, 46(6): 1343-1352.
21. Miura N, Shoji F, Kozuma Y, et al. Preoperative immune-nutritional abnormality predicts poor outcome in elderly non-small-cell lung cancer patients with comorbidities. Ann Thorac Cardiovasc Surg, 2020, 26(5): 240-247.
22. Ohba T, Takamori S, Toyozawa R, et al. Prognostic impact of the Controlling Nutritional Status score in patients with non-small cell lung cancer treated with pembrolizumab. J Thorac Dis, 2019, 11(9): 3757-3768.
23. Shoji F, Haratake N, Akamine T, et al. The preoperative Controlling Nutritional Status score predicts survival after curative surgery in patients with pathological stageⅠnon-small cell lung cancer. Anticancer Res, 2017, 37(2): 741-747.
24. Shoji F, Miura N, Matsubara T, et al. Prognostic significance of immune-nutritional parameters for surgically resected elderly lung cancer patients: A multicentre retrospective study. Interact Cardiovasc Thorac Surg, 2018, 26(3): 389-394.
25. Takahashi M, Sowa T, Tokumasu H, et al. Comparison of three nutritional scoring systems for outcomes after complete resection of non-small cell lung cancer. J Thorac Cardiovasc Surg, 2021, 162(4): 1257-1268.
26. Takamori S, Toyokawa G, Shimokawa M, et al. A novel prognostic marker in patients with non-small cell lung cancer: Musculo-immuno-nutritional score calculated by controlling nutritional status and creatine kinase. J Thorac Dis, 2019, 11(3): 927-935.
27. Toyokawa G, Kozuma Y, Matsubara T, et al. Prognostic impact of controlling nutritional status score in resected lung squamous cell carcinoma. J Thorac Dis, 2017, 9(9): 2942-2951.
28. Toyokawa G, Shoji F, Yamazaki K, et al. Significance of the red blood cell distribution width in resected pathologic stageⅠnon-small cell lung cancer. Semin Thorac Cardiovasc Surg, 2020, 32(4): 1036-1045.
29. Zhang Y, Kong FF, Zhu ZQ, et al. Controlling Nutritional Status (CONUT) score is a prognostic marker in Ⅲ-Ⅳ NSCLC patients receiving first-line chemotherapy. BMC Cancer, 2023, 23(1): 225.
30. 戴宁凰, 郑中锋, 季中华, 等. CONUT评分联合CYFRA21-1表达在NSCLC患者预后评估中的应用. 肿瘤代谢与营养电子杂志, 2021, 8(6): 648-653.
31. 王晓兰, 韩伟, 王莹. 营养免疫与系统炎症参数在非小细胞肺癌患者中的预后意义. 肿瘤代谢与营养电子杂志, 2021, 8(5): 519-524.
32. 张耀森, 卢国杰, 钟惠铃, 等. 术前控制营养状态评分对非小细胞肺癌患者根治术后复发转移的预测价值分析. 肿瘤综合治疗电子杂志, 2022, 8(4): 71-75.
33. Zhang CL, Gao MQ, Jiang XC, et al. Research progress and value of albumin-related inflammatory markers in the prognosis of non-small cell lung cancer: A review of clinical evidence. Ann Med, 2023, 55(1): 1294-1307.
34. Peng J, Hao Y, Rao B, et al. Prognostic impact of the pre-treatment controlling nutritional status score in patients with non-small cell lung cancer: A meta-analysis. Medicine (Baltimore), 2021, 100(26): e26488.
35. Castell JV, Gómez-Lechón MJ, David M, et al. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology, 1990, 12(5): 1179-1186.
36. Yang Z, Zheng Y, Wu Z, et al. Association between pre-diagnostic serum albumin and cancer risk: Results from a prospective population-based study. Cancer Med, 2021, 10(12): 4054-4065.
37. Kuzu OF, Noory MA, Robertson GP. The role of cholesterol in cancer. Cancer Res, 2016, 76(8): 2063-2070.
38. Lee YH, Martin-Orozco N, Zheng P, et al. Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. Cell Res, 2017, 27(8): 1034-1045.
39. Hughes DA, Townsend PJ, Haslam PL. Enhancement of the antigen-presenting function of monocytes by cholesterol: Possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis. Clin Exp Immunol, 1992, 87(2): 279-286.
40. Shankaran V, Ikeda H, Bruce AT, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature, 2001, 410(6832): 1107-1111.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesAssociation of Controlling Nutritional Status score with prognosis and clinicopathological characteristics of patients with non-small cell lung cancer: A systematic review and meta-analysis

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