Transarterial chemoembolization (TACE) is the preferred treatment for unresectable,
intermediate-stage hepatocellular carcinoma (HCC). However, survival after TACE can
be highly variable, suggesting the need for more accurate patient selection to improve
therapeutic outcome. We have explored the prognostic ability of the blood neutrophil-to-lymphocyte
ratio (NLR), a biomarker of systemic inflammation, as a predictor of survival after
TACE. Fifty-four patients with a diagnosis of HCC eligible for TACE were selected.
Clinicopathologic variables were collected, including demographics, tumor staging,
liver functional reserve, and laboratory variables. Dynamic changes in the NLR before
and after TACE were studied as predictors of survival using both a univariate and
multivariate Cox regression model. Patients in whom the NLR remained stable or normalized
after TACE showed a significant improvement in overall survival of 26 months compared
with patients showing a persistently abnormal index (P = 0.006). Other predictors of survival on univariate analysis were Cancer of the
Liver Italian Program score (P = 0.05), intrahepatic spread (P = 0.01), tumor diameter > 5 cm (P = 0.02), > 1 TACE (P = 0.01), alpha-fetoprotein ≥ 400 (P = 0.002), and radiologic response to TACE (P < 0.001). Improved NLR after TACE (P = 0.03) and radiologic response after TACE (P = 0.003) remained independent predictors of survival on multivariate analysis. Changes
in alpha-fetoprotein after treatment did not predict survival. Patients with a persistently
increased NLR have a worse outcome after TACE. NLR is a simple and universally available
stratifying biomarker that can help identify patients with a significant survival
advantage after TACE.
Abbreviations:
AFP (alpha-fetoprotein), BCLC (Barcelona Clinic Liver Cancer), CI (confidence interval), HCC (hepatocellular carcinoma), IL (interleukin), NLR (neutrophil-to-lymphocyte ratio), TACE (transarterial chemoembolization)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Novel advancements in the management of hepatocellular carcinoma in 2008.J Hepatol. 2008; 48: S20-S37
- Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.Hepatology. 2003; 37: 429-442
- Loco-regional treatment of hepatocellular carcinoma.Hepatology. 2010; 52: 762-773
- Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version.Dig Dis. 2011; 29: 339-364
- Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization.Cancer Treat Rev. 2011; 37: 212-220
- Management of hepatocellular carcinoma.Hepatology. 2005; 42: 1208-1236
- Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials.Radiology. 2002; 224: 47-54
- Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.Cardiovasc Intervent Radiol. 2007; 30: 6-25
- Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation.Aliment Pharmacol Ther. 2011; 34: 196-204
- Chronic inflammation and hepatocellular carcinoma.Recent Results Cancer Res. 2011; 185: 135-148
- An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study.Br J Cancer. 2011; 104: 726-734
- Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe.Clin Cancer Res. 2009; 15: 425-430
- The causes and consequences of cancer-associated malnutrition.Eur J Oncol Nurs. 2005; 9: S51-S63
- Baseline insulin-like growth factor-I plasma levels, systemic inflammation, weight loss and clinical outcome in metastatic non-small cell lung cancer patients.Oncology. 2011; 81: 113-118
- Systemic inflammatory response predicts prognosis in patients with advanced-stage colorectal cancer.Clin Colorectal Cancer. 2008; 7: 331-337
- Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer.Br J Cancer. 2011; 104: 1288-1295
- High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy.Clin Cancer Res. 2010; 16: 5805-5813
- Systemic inflammation and prediction of chemotherapy outcomes in patients receiving docetaxel for advanced cancer.Support Care Cancer. 2011 Oct 11; ([Epub ahead of print])
- Use of inflammatory markers to guide cancer treatment.Clin Pharmacol Ther. 2011; 90: 475-478
- Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma.J Clin Oncol. 1995; 13: 575-582
- Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas.Cancer Res. 2009; 69: 5383-5391
- The relationship between the local and systemic inflammatory responses and survival in patients undergoing curative surgery for colon and rectal cancers.J Gastrointest Surg. 2009; 13: 2011-2019
- Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma.Ann Surg. 2009; 250: 141-151
- Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma.World J Surg. 2008; 32: 1757-1762
- Blood neutrophil-to-lymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization.J Vasc Interv Radiol. 2011; 22: 702-709
- Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.J Hepatol. 2001; 35: 421-430
- Early on-treatment predictions of clinical outcomes using AFP and DCP responses in patients with advanced hepatocellular carcinoma.J Gastroenterol Hepatol. 2011 Jul 28; ([Epub ahead of print])
- The significance of early alpha-fetoprotein level changes in predicting clinical and survival benefits in advanced hepatocellular carcinoma patients receiving sorafenib.Oncologist. 2011; 16: 1270-1279
- Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.Lancet. 2002; 359: 1734-1739
- Chemoembolization for hepatocellular carcinoma.Gastroenterology. 2004; 127: S179-S188
- Predictive factors of tumor response to trans-catheter treatment in cirrhotic patients with hepatocellular carcinoma: a multivariate analysis of pre-treatment findings.World J Gastroenterol. 2007; 13: 6022-6026
- Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation.J Gastroenterol Hepatol. 2011 Sep 13; ([Epub ahead of print])
- A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study.Eur J Cancer. 2011; 47: 2633-2641
- Role of systemic inflammatory response in predicting survival in patients with primary operable cancer.Future Oncol. 2010; 6: 149-163
- Evaluation of an inflammation-based prognostic score in patients with advanced ovarian cancer.Eur J Cancer. 2008; 44: 251-256
- Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG) in patients receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer.Br J Cancer. 2004; 90: 1704-1706
- Diagnosis and treatment of hepatocellular carcinoma.Gastroenterology. 2008; 134: 1752-1763
- Inflammation and liver cancer: new molecular links.Ann N Y Acad Sci. 2009; 1155: 206-221
- Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma.J Hepatol. 2011; 54: 948-955
- FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis.Clin Cancer Res. 2007; 13: 902-911
- Increased liver-infiltrating CD8+FoxP3+ regulatory T cells are associated with tumor stage in hepatocellular carcinoma patients.Hum Immunol. 2010; 71: 1180-1186
- Neutrophils promote motility of cancer cells via a hyaluronan-mediated TLR4/PI3K activation loop.J Pathol. 2011; 225: 438-447
- Locoregional radiological treatment for hepatocellular carcinoma; Which, when and how?.Cancer Treat Rev. 2012; 38: 54-62
- Treatment of intermediate/advanced hepatocellular carcinoma in the clinic: how can outcomes be improved?.Oncologist. 2010; 15: 42-52
Article info
Publication history
Published online: February 10, 2012
Accepted:
January 10,
2012
Received:
December 1,
2011
Footnotes
Conflict of Interest: none
Funding: This work was supported in part by the Fondazione DeAgostini Research Grant for PhD studies to DJP.
Identification
Copyright
© 2012 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
