Glasgow prognostic score predicts survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib: a multicenter analysis

Objective The use of Glasgow prognostic score (GPS), calculated using the serum C-reactive protein and albumin levels, to predict the outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib was investigated in this study. Methods A total of 508 patients with Child-Pugh class A HCC treated with lenvatinib were included in this study. Results The median overall and progression-free survivals were 20.4 months [95% confidence interval (CI), 17.7–23.2 months] and 7.5 months (95% CI, 6.8–8.5 months), respectively. The median overall survivals of patients with a GPS of 0, 1, and 2 were 28.5, 16.0, and 9.1 months, respectively (P < 0.001). When adjusted for age, sex, performance status, etiology, α-fetoprotein, macroscopic vascular invasion, extrahepatic spread, history of sorafenib therapy, and GPS, a GPS of 1 [hazard ratio (HR), 1.664; 95% CI, 1.258–2.201; P < 0.001] and a GPS of 2 (HR, 2.664; 95% CI, 1.861–3.813; P < 0.001) were found to be independently associated with overall survival. The median progression-free survivals of patients with a GPS of 0, 1, and 2 were 8.8, 6.8, and 3.8 months, respectively (P < 0.001). When adjusted for the same factors of overall survival, a GPS of 2 (HR, 2.010; 95% CI, 1.452–2.784; P < 0.001) was found to be independently associated with progression-free survival. As the albumin–bilirubin with tumor node metastasis score increased, the proportion of patients with a GPS of 1 or 2 increased (P < 0.001). Conclusions GPS can be used to predict survival in patients with unresectable HCC who were treated with lenvatinib.

[1]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[2]  I. Sakaida,et al.  Albumin-bilirubin score as a useful predictor of energy malnutrition in patients with hepatocellular carcinoma. , 2020, Clinical nutrition.

[3]  J. Marrero,et al.  Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference , 2020, Hepatology.

[4]  Yulei N. Wang,et al.  Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. , 2020, The New England journal of medicine.

[5]  Y. Hiasa,et al.  Neutrophil‐to‐lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib , 2020, Liver international : official journal of the International Association for the Study of the Liver.

[6]  Versione,et al.  Common Terminology Criteria for Adverse Events , 2020, Definitions.

[7]  T. Murakami,et al.  Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH‐HCC guidelines) 2019 update , 2019, Hepatology research : the official journal of the Japan Society of Hepatology.

[8]  G. Che,et al.  The prognostic value of pretreatment Glasgow Prognostic Score in patients with esophageal cancer: a meta-analysis , 2019, Cancer management and research.

[9]  Leizhen Zheng,et al.  Prognostic value of the Glasgow prognostic score in colorectal cancer: a meta-analysis of 9,839 patients , 2018, Cancer management and research.

[10]  M. Kudo,et al.  Impact of Advanced Age on Survival in Patients Undergoing Resection of Hepatocellular Carcinoma: Report of a Japanese Nationwide Survey , 2017, Annals of surgery.

[11]  M. Kudo,et al.  Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial , 2018, The Lancet.

[12]  H. Toyoda,et al.  Differences in the impact of prognostic factors for hepatocellular carcinoma over time , 2017, Cancer science.

[13]  Lu Wan,et al.  Association between pretreatment Glasgow prognostic score and gastric cancer survival and clinicopathological features: a meta-analysis , 2016, OncoTargets and therapy.

[14]  M. Kanda,et al.  Clinical Implication of Inflammation-Based Prognostic Score in Pancreatic Cancer , 2016, Medicine.

[15]  H. Toyoda,et al.  Usefulness of albumin–bilirubin grade for evaluation of prognosis of 2584 Japanese patients with hepatocellular carcinoma , 2016, Journal of gastroenterology and hepatology.

[16]  H. Toyoda,et al.  Impact of the branched‐chain amino acid to tyrosine ratio and branched‐chain amino acid granule therapy in patients with hepatocellular carcinoma: A propensity score analysis , 2015, Journal of gastroenterology and hepatology.

[17]  H. Toyoda,et al.  A laboratory marker, FIB-4 index, as a predictor for long-term outcomes of hepatocellular carcinoma patients after curative hepatic resection. , 2015, Surgery.

[18]  H. Toyoda,et al.  Tumor Markers for Hepatocellular Carcinoma: Simple and Significant Predictors of Outcome in Patients with HCC , 2015, Liver Cancer.

[19]  B. Sangro,et al.  Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  E. Elinav,et al.  Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms , 2013, Nature Reviews Cancer.

[21]  D. McMillan The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. , 2013, Cancer treatment reviews.

[22]  Y. Kanda,et al.  Investigation of the freely available easy-to-use software ‘EZR' for medical statistics , 2012, Bone Marrow Transplantation.

[23]  Y. Maehara,et al.  Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. , 2013, Journal of hepatology.

[24]  Shahid A. Khan,et al.  A novel and validated prognostic index in hepatocellular carcinoma: the inflammation based index (IBI). , 2012, Journal of hepatology.

[25]  M. Morimoto,et al.  Inflammation-based prognostic score for hepatocellular carcinoma patients on sorafenib treatment. , 2012, Anticancer research.

[26]  Masato Kato,et al.  Impact of an inflammation-based prognostic system on patients undergoing surgery for hepatocellular carcinoma: a retrospective study of 398 Japanese patients. , 2012, American journal of surgery.

[27]  Masato Kato,et al.  Usefulness of a modified inflammation‐based prognostic system for predicting postoperative mortality of patients undergoing surgery for primary hepatocellular carcinoma , 2011, Journal of surgical oncology.

[28]  J. Bruix,et al.  Management of hepatocellular carcinoma: An update , 2011, Hepatology.

[29]  Jun Hee Lee,et al.  Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression , 2010, Cell.

[30]  Yoon-Koo Kang,et al.  Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. , 2009, The Lancet. Oncology.

[31]  Dieter Häussinger,et al.  Sorafenib in advanced hepatocellular carcinoma. , 2008, The New England journal of medicine.

[32]  G. Morris-Stiff,et al.  C-reactive protein in liver cancer surgery. , 2008, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[33]  P. Allavena,et al.  Cancer-related inflammation , 2008, Nature.

[34]  D. Lawlor,et al.  A systematic review of the association between circulating concentrations of C reactive protein and cancer , 2007, Journal of Epidemiology and Community Health.

[35]  J. Bruix,et al.  Management of hepatocellular carcinoma , 2005, Hepatology.

[36]  R. Groszmann,et al.  American association for the study of liver diseases , 1992 .

[37]  D C McMillan,et al.  Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer , 2003, British Journal of Cancer.

[38]  J. Bruix,et al.  Prognosis of Hepatocellular Carcinoma: The BCLC Staging Classification , 1999, Seminars in liver disease.

[39]  R. Pugh,et al.  Transection of the oesophagus for bleeding oesophageal varices , 1973, The British journal of surgery.