Abstract
Purpose
As a novel immune-nutritional biomarker, the controlling nutritional status (CONUT) score has been reported to predict outcomes in cancer patients. We aimed to elucidate the prognostic value of preoperative CONUT score and construct a CONUT score-based nomogram to predict individual survival of patients with hepatitis B viral (HBV)-associated hepatocellular carcinoma (HCC) after curative hepatectomy.
Methods
Preoperative CONUT score was retrospectively calculated in 380 HBV-associated HCC patients undergoing radical resection between 2006 and 2012. Patients were assigned to two groups: CONUT-low ( < 2) and CONUT-high ( ≥ 2), according to the optimal cut-off value determined using receiver operating characteristic analysis. Associations of CONUT score with oncological outcomes were evaluated. The Cox proportional hazard model was used to identify predictors of survival and a new nomogram was developed based on the independent prognostic factors for overall survival (OS).
Results
The CONUT score exhibited a higher area under the curve value than the other immune-nutritional parameters. The CONUT-high group had significant poorer OS and recurrence-free survival compared with CONUT-low group (P < 0.001 and P = 0.016, respectively). Multivariate analyses identified CONUT score, liver cirrhosis, tumor size and differentiation as independent prognostic factors for OS. And the nomogram based on these four variables had superior discriminative ability to predict survival compared with other conventional staging systems.
Conclusions
Preoperative CONUT score is an effective independent predictor of OS in patients with resected HBV-related HCC. This novel nomogram based on CONUT may provide accurate and individualized survival prediction for HCC patients undergoing surgical resection.
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References
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.
Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014;60(6):2099–108.
Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11(4):317–70.
Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014;63(5):844–55.
Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010;30(1):61–74.
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9.
Llovet JM, Bruix J. Prospective validation of the Cancer of the Liver Italian Program (CLIP) score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology. 2000;32(3):679–80.
Baracos VE. Cancer-associated malnutrition. Eur J Clin Nutr. 2018;72(9):1255–9.
Alwarawrah Y, Kiernan K, MacIver NJ. Changes in nutritional status impact immune cell metabolism and function. Front Immunol. 2018;9:1055.
Du XJ, Tang LL, Mao YP, Guo R, Sun Y, Lin AH, et al. Value of the prognostic nutritional index and weight loss in predicting metastasis and long-term mortality in nasopharyngeal carcinoma. J Transl Med. 2015;13:364.
Kuroda D, Sawayama H, Kurashige J, Iwatsuki M, Eto T, Tokunaga R, et al. Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer. 2018;21(2):204–12.
Wu SJ, Lin YX, Ye H, Li FY, Xiong XZ, Cheng NS. Lymphocyte to monocyte ratio and prognostic nutritional index predict survival outcomes of hepatitis B virus-associated hepatocellular carcinoma patients after curative hepatectomy. J Surg Oncol. 2016;114(2):202–10.
Mano Y, Shirabe K, Yamashita Y, Harimoto N, Tsujita E, Takeishi K, et al. Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg. 2013;258(2):301–5.
Zhao T, Cui L, Li A. The significance of RDW in patients with hepatocellular carcinoma after radical resection. Cancer Biomark. 2016;16(4):507–12.
Kaida T, Nitta H, Kitano Y, Yamamura K, Arima K, Higashi T, et al. Preoperative platelet-to-lymphocyte ratio can predict recurrence beyond the Milan criteria after hepatectomy for patients with hepatocellular carcinoma. Hepatol Res. 2017;47(10):991–9. https://doi.org/10.1111/hepr.12835.
de Ulibarri Perez JI, Fernandez G, Rodriguez Salvanes F, Diaz Lopez AM. Nutritional screening; control of clinical undernutrition with analytical parameters. Nutr Hosp. 2014;29(4):797–811.
Tokunaga R, Sakamoto Y, Nakagawa S, Ohuchi M, Izumi D, Kosumi K, et al. CONUT: a novel independent predictive score for colorectal cancer patients undergoing potentially curative resection. Int J Colorectal Dis. 2017;32(1):99–106.
Harimoto N, Yoshizumi T, Sakata K, Nagatsu A, Motomura T, Itoh S, et al. Prognostic significance of preoperative controlling nutritional status (CONUT) score in patients undergoing hepatic resection for hepatocellular carcinoma. World J Surg. 2017;41(11):2805–12.
Franssen B, Alshebeeb K, Tabrizian P, Marti J, Pierobon ES, Lubezky N, et al. Differences in surgical outcomes between hepatitis B- and hepatitis C-related hepatocellular carcinoma: a retrospective analysis of a single North American center. Ann Surg. 2014;260(4):650–6.
Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.
Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550–8.
Lin ZX, Ruan DY, Li Y, Wu DH, Ma XK, Chen J, et al. Lymphocyte-to-monocyte ratio predicts survival of patients with hepatocellular carcinoma after curative resection. World J Gastroenterol. 2015;21(38):10898–906.
Alberino F, Gatta A, Amodio P, Merkel C, Di Pascoli L, Boffo G, et al. Nutrition and survival in patients with liver cirrhosis. Nutrition. 2001;17(6):445–50.
Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493–503.
Jiang SS, Weng DS, Jiang L, Zhang YJ, Pan K, Pan QZ, et al. The clinical significance of preoperative serum cholesterol and high-density lipoprotein-cholesterol levels in hepatocellular carcinoma. J Cancer. 2016;7(6):626–32.
Schutte K, Tippelt B, Schulz C, Rohl FW, Feneberg A, Seidensticker R, et al. Malnutrition is a prognostic factor in patients with hepatocellular carcinoma (HCC). Clin Nutr. 2015;34(6):1122–7.
Nojiri S, Fujiwara K, Shinkai N, Iio E, Joh T. Effects of branched-chain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: a randomized trial. Nutrition. 2017;33:20–7.
Fu YP, Yi Y, Huang JL, Jing CY, Sun J, Ni XC, et al. Prognostic nomograms stratify survival of patients with hepatocellular carcinoma without portal vein tumor thrombosis after curative resection. Oncologist. 2017;22(5):561–9.
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The authors thank all the surgeons for treating patients in this study in The Third Affiliated Hospital of Sun Yat-sen University.
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The study protocol was approved by the Clinical Ethics Review Board of The Third Affiliated Hospital of Sun Yat-sen University. And it was conducted in accordance with the Declaration of Helsinki.
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Lin, ZX., Ruan, DY., Jia, CC. et al. Controlling nutritional status (CONUT) score-based nomogram to predict overall survival of patients with HBV-associated hepatocellular carcinoma after curative hepatectomy. Clin Transl Oncol 22, 370–380 (2020). https://doi.org/10.1007/s12094-019-02137-4
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DOI: https://doi.org/10.1007/s12094-019-02137-4