Nicole E Rich1, Binu V John2,3, Neehar D Parikh4, Ian Rowe5,6, Neil Mehta7, Gaurav Khatri8, Smitha M Thomas9, Munazza Anis9, Mishal Mendiratta-Lala10, Christopher Hernandez1, Mobolaji Odewole1, Latha T Sundaram2, Venkata R Konjeti2, Shishir Shetty11, Tahir Shah12, Hao Zhu13, Adam C Yopp14, Yujin Hoshida1, Francis Y Yao7, Jorge A Marrero1, Amit G Singal1,15. 1. Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 2. Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, VA. 3. Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA. 4. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI. 5. Leeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom. 6. Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. 7. Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA. 8. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX. 9. Department of Radiology, McGuire VA Medical Center, Richmond, VA. 10. Department of Radiology, University of Michigan, Ann Arbor, MI. 11. Centre for Liver Research, University of Birmingham and Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. 12. Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. 13. Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX. 14. Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX. 15. Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX.
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.
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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