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Multicenter Study
. 2020 Nov;72(5):1654-1665.
doi: 10.1002/hep.31159. Epub 2020 Oct 25.

Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis

Nicole E Rich  1 , Binu V John  2   3 , Neehar D Parikh  4 , Ian Rowe  5   6 , Neil Mehta  7 , Gaurav Khatri  8 , Smitha M Thomas  9 , Munazza Anis  9 , Mishal Mendiratta-Lala  10 , Christopher Hernandez  1 , Mobolaji Odewole  1 , Latha T Sundaram  2 , Venkata R Konjeti  2 , Shishir Shetty  11 , Tahir Shah  12 , Hao Zhu  13 , Adam C Yopp  14 , Yujin Hoshida  1 , Francis Y Yao  7 , Jorge A Marrero  1 , Amit G Singal  1   15
Affiliations
Multicenter Study

Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis

Nicole E Rich et al. Hepatology. 2020 Nov.

Abstract

Background and aims: There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study's aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth.

Approach and results: We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast-enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT > 365 days) and rapid (TDT < 90 days) tumor growth. In the primary cohort (n = 242 patients from four centers), median TDT was 229 days (interquartile range [IQR], 89-627) and median SGR was 0.3% per day (IQR, 0.1%-0.8%). Over one-third (38%) of HCCs had indolent growth, 36.8% intermediate growth, and 25.2% rapid growth. In multivariable analysis, indolent growth was associated with larger tumor diameter (odds ratio [OR], 1.15, 95% confidence interval [CI], 1.03-1.30) and alpha-fetoprotein < 20 ng/mL (OR, 1.90; 95% CI, 1.12-3.21). Indolent growth was more common in nonviral than viral cirrhosis (50.9% versus 32.1%), particularly in patients with T1 HCC (OR, 3.41; 95% CI, 1.08-10.80). Median TDT (169 days; IQR 74-408 days) and SGR (0.4% per day) were similar in an independent cohort (n = 176 patients from two centers).

Conclusions: In a large Western cohort of patients with HCC, we found heterogeneous tumor growth patterns, with one-fourth exhibiting rapid growth and over one-third having indolent growth. Better understanding different tumor growth patterns may facilitate a precision approach to prognostication and treatment.

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Conflict of interest statement

Conflicts of Interest: Amit Singal has served on advisory boards or as a consultant for Gilead, Abbvie, Bayer, Eisai, Exelixis, Bristol Meyers Squibb, Wako Diagnostics, Exact Sciences. Roche, and Glycotest. Binu John has served on medical advisory boards for Gilead and Eisai and has received institutional research funding from Eisai, Bristol Myers Squibb, Bayer, Exact Sciences and Varian. Neehar Parikh serves as a consultant to Exelixis, Eli Lilly and Bristol-Myers Squibb. He has served on advisory boards for Eisai, Wako Diagnostics and Bayer and has received institutional research funding from Bayer and Exact Sciences. Ian Rowe has received honoraria from Abbvie outside the submitted work. Neil Mehta has served on advisory boards and has received institutional research funding from Wako Diagnostics. Shishir Shetty has served as a consultant for Faron Pharmaceuticals. Francis Yao has received institutional research funding from Wako Diagnostics. Jorge Marrero has served as a consultant for Glycotest and received research funding from AstraZeneca.

Figures

Figure 1.
Figure 1.
Distribution of Tumor Doubling Time (TDT) among the 242 patients in the primary cohort
Figure 2.
Figure 2.
Tumor Doubling Time (TDT) in the primary cohort by (panel A) liver disease etiology and (panel B) initial tumor diameter
Figure 3.
Figure 3.
Proportion of rapid, intermediate, and indolent tumors in the overall (panel A) and T1 (panel B) cohorts
See this image and copyright information in PMC

Comment in

References

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