Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VAMC, Richmond, Virginia, USA
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
Correspondence to Dr Amit G Singal, Internal Medicine, University of Texas Southwestern, Dallas, Texas, USA; [email protected]
Abstract
Background Tumour growth patterns have important implications for surveillance intervals, prognostication and treatment decisions but have not been well described for hepatocellular carcinoma (HCC). The aim of our study was to characterise HCC doubling time and identify correlates for indolent and rapid growth patterns.
Methods We performed a systematic literature review of Medline and EMBASE databases from inception to December 2019 and national meeting abstracts from 2010 to 2018. We identified studies reporting HCC tumour growth or tumour volume doubling time (TVDT), without intervening treatment, and abstracted data to calculate TVDT and correlates of growth patterns (rapid defined as TVDT <3 months and indolent as TVDT >9 months). Pooled TVDT was calculated using a random-effects model.
Results We identified 20 studies, including 1374 HCC lesions in 1334 patients. The pooled TVDT was 4.6 months (95% CI 3.9 to 5.3 months I2=94%), with 35% classified as rapid, 27.4% intermediate and 37.6% indolent growth. In subgroup analysis, studies from Asia reported shorter TVDT than studies elsewhere (4.1 vs 5.8 months). The most consistent correlates of rapid tumour growth included hepatitis B aetiology, smaller tumour size (continuous), alpha fetoprotein doubling time and poor tumour differentiation. Studies were limited by small sample sizes, measurement bias and selection bias.
Conclusion TVDT of HCC is approximately 4–5 months; however, there is heterogeneity in tumour growth patterns, including more aggressive patterns in Asian hepatitis B-predominant populations. Identifying correlates of tumour growth patterns is important to better individualise HCC prognostication and treatment decisions.
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