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

Nicole E. Rich; Binu V. John; Neehar D. Parikh; Ian Rowe; Neil Mehta; Gaurav Khatri; Smitha M. Thomas; Munazza Anis; Mishal Mendiratta-Lala; Christopher Hernandez; Mobolaji Odewole; Latha T. Sundaram; Venkata R. Konjeti; Shishir Shetty; Tahir Shah; Hao Zhu; Adam C. Yopp; Yujin Hoshida; Francis Y. Yao; Jorge A. Marrero; Amit G. Singal

doi:10.1002/hep.31159

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

Nicole E. Rich, Binu V. John, Neehar D. Parikh, Ian Rowe, Neil Mehta, Gaurav Khatri, Smitha M. Thomas, Munazza Anis, Mishal Mendiratta-Lala, Christopher Hernandez, Mobolaji Odewole, Latha T. Sundaram, Venkata R. Konjeti, Shishir Shetty, Tahir Shah, Hao Zhu, Adam C. Yopp, Yujin Hoshida, Francis Y. Yao, Jorge A. MarreroAmit G. Singal

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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.

Original language	English (US)
Pages (from-to)	1654-1665
Number of pages	12
Journal	Hepatology
Volume	72
Issue number	5
DOIs	https://doi.org/10.1002/hep.31159
State	Published - Nov 1 2020

ASJC Scopus subject areas

Hepatology

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Rich, N. E., John, B. V., Parikh, N. D., Rowe, I., Mehta, N., Khatri, G., Thomas, S. M., Anis, M., Mendiratta-Lala, M., Hernandez, C., Odewole, M., Sundaram, L. T., Konjeti, V. R., Shetty, S., Shah, T., Zhu, H., Yopp, A. C., Hoshida, Y., Yao, F. Y., ... Singal, A. G. (2020). Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis. Hepatology, 72(5), 1654-1665. https://doi.org/10.1002/hep.31159

Rich, NE, John, BV, Parikh, ND, Rowe, I, Mehta, N, Khatri, G, Thomas, SM, Anis, M, Mendiratta-Lala, M, Hernandez, C, Odewole, M, Sundaram, LT, Konjeti, VR, Shetty, S, Shah, T, Zhu, H , Yopp, AC , Hoshida, Y, Yao, FY, Marrero, JA & Singal, AG 2020, 'Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis', Hepatology, vol. 72, no. 5, pp. 1654-1665. https://doi.org/10.1002/hep.31159

@article{9b90a3cd0f8641e89a50d92a3f38f9eb,

title = "Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis",

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{\textquoteright}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.",

author = "Rich, {Nicole E.} and John, {Binu V.} and Parikh, {Neehar D.} and Ian Rowe and Neil Mehta and Gaurav Khatri and Thomas, {Smitha M.} and Munazza Anis and Mishal Mendiratta-Lala and Christopher Hernandez and Mobolaji Odewole and Sundaram, {Latha T.} and Konjeti, {Venkata R.} and Shishir Shetty and Tahir Shah and Hao Zhu and Yopp, {Adam C.} and Yujin Hoshida and Yao, {Francis Y.} and Marrero, {Jorge A.} and Singal, {Amit G.}",

note = "Publisher Copyright: {\textcopyright} 2020 by the American Association for the Study of Liver Diseases.",

year = "2020",

month = nov,

day = "1",

doi = "10.1002/hep.31159",

language = "English (US)",

volume = "72",

pages = "1654--1665",

journal = "Hepatology",

issn = "0270-9139",

publisher = "John Wiley and Sons Ltd",

number = "5",

}

TY - JOUR

T1 - Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis

AU - Rich, Nicole E.

AU - John, Binu V.

AU - Parikh, Neehar D.

AU - Rowe, Ian

AU - Mehta, Neil

AU - Khatri, Gaurav

AU - Thomas, Smitha M.

AU - Anis, Munazza

AU - Mendiratta-Lala, Mishal

AU - Hernandez, Christopher

AU - Odewole, Mobolaji

AU - Sundaram, Latha T.

AU - Konjeti, Venkata R.

AU - Shetty, Shishir

AU - Shah, Tahir

AU - Zhu, Hao

AU - Yopp, Adam C.

AU - Hoshida, Yujin

AU - Yao, Francis Y.

AU - Marrero, Jorge A.

AU - Singal, Amit G.

PY - 2020/11/1

Y1 - 2020/11/1

N2 - 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.

AB - 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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U2 - 10.1002/hep.31159

DO - 10.1002/hep.31159

M3 - Article

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JO - Hepatology

JF - Hepatology

IS - 5

ER -

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

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