Tumor growth rates and recurrence-free survival in chronic viral hepatitis patients with hepatocellular carcinoma

Abstract

Aim: Survival in patients with hepatocellular carcinoma (HCC) is impacted by stage of liver disease, tumor characteristics, and HCC surveillance in high-risk individuals. Factors associated with HCC tumor growth rate (TGR) and its influence on recurrence-free survival after treatment was investigated.

Methods: TGR was calculated in 164 HCC patients with chronic viral hepatitis who had two consecutive magnetic resonance imaging or computed tomography scans ≥ 30 days apart prior to treatment and who were followed prospectively to determine the rates of recurrence-free survival.

Results: The median TGR in 164 patients was 17.8% per month (mean 33.3% per month). Regression tree analysis indicated that the top three predictors of TGR were alpha-fetoprotein (AFP) levels (≥ 16.7 ng/mL), platelet counts (≥ 140,000 mm³), and serum albumin level (< 3.55 g/dL). The regression tree identified patient groups with TGRs ranging from 0.65% to 39.4% per month. At a median follow-up of 22 months, the overall recurrence-free survival was 53.8%. The Cox model with backwards AIC search identified TGR (HR = 1.34, P = 0.029), age > 56 years (HR = 1.08, P = 0.072), hepatitis C virus (HR = 1.44, P = 0.091), macrovascular invasion (HR = 1.94, P = 0.092), and the most definitive treatments (orthotopic liver transplantation, HR 0.14, P < 0.001; surgical resection, HR = 0.54, P = 0.072; radiofrequency ablation, HR = 0.58, P = 0.060) as independent predictors of recurrence-free survival. For all treatment modalities, slow TGR was significant for prolonged survival (P = 0.029). The poorest survival rates were observed in patients with fast TGRs treated by transarterial chemoembolization.

Conclusion: The TGR correlated with AFP, platelet count, and albumin level. Patients with fast TGRs had shorter recurrence-free survival after HCC treatments. TGR is a potential imaging biomarker to predict clinical outcomes in HCC.

Keywords

Liver cancer / growth rates / hepatitis B / hepatitis C / hepatocellular carcinoma treatments

References

[1] Bertuccio P,Carioli G,La Vecchia C.Global trends and predictions in hepatocellular carcinoma mortality..J Hepatol2017;67:302-9

[2] Rahib L,Aizenberg R,Fleshman JM.Projecting cancer incidence and deaths to 2030: the unexpected Burden of thyroid, liver, and pancreas cancers in the United States..Cancer Res2014;74:2913-21

[3] Jinjuvadia R,Lenhart A,Liangpunsakul S.Hepatocellular carcinoma: a decade of hospitalizations and financial Burden in the United States..Am J Med Sci2017;354:362-9 PMCID:PMC5986560

[4] de Martel C,Plummer M.World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma..Hepatology2015;62:1190-200 PMCID:PMC5019261

[5] Tong MJ,Huynh CT,Lu DSK.Long-term survival after surveillance and treatment in patients with chronic viral hepatitis and hepatocellular carcinoma..Hepatol Commun2017;1:595-608 PMCID:PMC5721434

[6] Sheu JC,Chen DS,Lai MY.Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications..Gastroenterology1985;89:259-66

[7] Taouli B,Lu Y,Yeh BM.Growth rate of hepatocellular carcinoma: evaluation with serial computed tomography or magnetic resonance imaging..J Comput Assist Tomogr2005;29:425-9

[8] Okazaki N,Yoshida T,Moriyama N.Evaluation of the prognosis for small hepatocellular carcinoma based on tumor volume doubling time: a preliminary report..Cancer1989;63:2207-10

[9] Cucchetti A,Piscaglia F,Montalti R.Tumor doubling time predicts recurrence after surgery and describes the histological pattern of hepatocellular carcinoma on cirrhosis..J Hepatol2005;43:310-6

[10] Park Y,Lim HK,Kim Y.Growth rate of new hepatocellular carcinoma after percutaneous radiofrequency ablation: evaluation with multiphase CT..Am J Roentgenol2008;191:215-20

[11] Mehrara E,Ahlman H.Specific growth rate versus doubling time for quantitative characterization of tumor growth rate..Cancer Res2007;67:3970-5

[12] Bruix J.Management of hepatocellular carcinoma: an update..Hepatology2011;53:1020-2 PMCID:PMC3084991

[13] Bruix J.Managemtn of hepatocellular carcinoma..Hepatology2005;42:1208-36

[14] Schwartz M.A Biomathematical approach to clinical tumor growth..Cancer1961;14:1272-94

[15] Breiman L.Classification and Regression Trees.1998;Boca RatonChapman & Hall [u.a.]358

[16] Siripongsakun S,Raman SS,Sayre J.MRI detection of intratumoral fat in hepatocellular carcinoma: potential biomarker for a more favorable prognosis..Am J Roentgenol2012;199:1018-25

[17] Lu DS,Kyong Lee J,Cheng PM.Complete tumor encapsulation on magnetic resonance imaging: a potentially useful imaging biomarker for better survival in solitary large hepatocellular carcinoma..Liver Transpl2013;19:283-91

[18] Chernyak V, Sirlin CB. The LI-RADS v2018 CT/MRI Manual [Internet]. The American College of Radiology; 2018 Jul. Available from: https://www.acr.org/-/media/ACR/Files/RADS/LI-RADS/LI-RADS-2018-Core.pdf?la=en. [Last accessed on 20 Sep 2019]

[19] Rosenkrantz AB,Wehrli N,Kim S.New OPTN/UNOS classification system for nodules in cirrhotic livers detected with MR imaging: effect on hepatocellular carcinoma detection and transplantation allocation..Radiology2015;274:426-33

[20] An C,Choi D,Ahn SH.Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease..Clin Mol Hepatol2015;21:279 PMCID:PMC4612289

[21] Hwang SJ,Li CP,Wu JC.Thrombocytosis: a paraneoplastic syndrome in patients with hepatocellular carcinoma..World J Gastroenterol2004;10:2472-7 PMCID:PMC4572144

[22] Carr BI.Thrombocytosis and hepatocellular carcinoma..Dig Dis Sci2013;58:1790-6 PMCID:PMC3665764

[23] JK,Jun MJ,Shim JH.Tumor volume doubling time as a dynamic prognostic marker for patients with hepatocellular carcinoma..Dig Dis Sci2017;62:2923-31