Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care System
Abstract Background Hepatocellular carcinoma (HCC) has limited treatment options in patients with advanced stage disease and early detection of HCC through surveillance programs is a key component towards reducing mortality. The current practice guidelines recommend that high-risk cirrhosis patients...
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doaj-955ac4cd27824bea9cb5d32f95e49f152020-11-25T00:55:43ZengBMCBMC Medical Research Methodology1471-22882018-01-0118111310.1186/s12874-017-0458-6Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care SystemNabihah Tayob0Peter Richardson1Donna L. White2Xiaoying Yu3Jessica A. Davila4Fasiha Kanwal5Ziding Feng6Hashem B. El-Serag7Department of Biostatistics, The University of Texas MD Anderson Cancer CenterBaylor College of MedicineBaylor College of MedicineUniversity of Texas Medical Branch at GalvestonBaylor College of MedicineBaylor College of MedicineDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterBaylor College of MedicineAbstract Background Hepatocellular carcinoma (HCC) has limited treatment options in patients with advanced stage disease and early detection of HCC through surveillance programs is a key component towards reducing mortality. The current practice guidelines recommend that high-risk cirrhosis patients are screened every six months with ultrasonography but these are done in local hospitals with variable quality leading to disagreement about the benefit of HCC surveillance. The well-established diagnostic biomarker α-Fetoprotein (AFP) is used widely in screening but the reported performance varies widely across studies. We evaluate two biomarker screening approaches, a six-month risk prediction model and a parametric empirical Bayes (PEB) algorithm, in terms of their ability to improve the likelihood of early detection of HCC compared to current AFP alone when applied prospectively in a future study. Methods We used electronic medical records from the Department of Veterans Affairs Hepatitis C Clinical Case Registry to construct our analysis cohort, which consists of serial AFP tests in 11,222 cirrhosis control patients and 902 HCC cases prior to their HCC diagnosis. The six-month risk prediction model incorporates routinely measured laboratory tests, age, the rate of change in AFP over the past year with the current AFP. The PEB algorithm incorporates prior AFP screening values to identify patients with a significant elevated level of AFP at their current screen. We split the analysis cohort into independent training and validation datasets. All model fitting and parameter estimation was performed using the training data and the algorithm performance was assessed by applying each approach to patients in the validation dataset. Results When the screening-level false positive rate was set at 10%, the patient-level true positive rate using current AFP alone was 53.88% while the patient-level true positive rate for the six-month risk prediction model was 58.09% (4.21% increase) and PEB approach was 63.64% (9.76% increase). Both screening approaches identify a greater proportion of HCC cases earlier than using AFP alone. Conclusions The two approaches show greater potential to improve early detection of HCC compared to using the current AFP only and are worthy of further study.http://link.springer.com/article/10.1186/s12874-017-0458-6Early detectionHepatocellular carcinomaLongitudinal biomarkersα-fetoproteinParametric empirical BayesShort-term risk prediction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nabihah Tayob Peter Richardson Donna L. White Xiaoying Yu Jessica A. Davila Fasiha Kanwal Ziding Feng Hashem B. El-Serag |
spellingShingle |
Nabihah Tayob Peter Richardson Donna L. White Xiaoying Yu Jessica A. Davila Fasiha Kanwal Ziding Feng Hashem B. El-Serag Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care System BMC Medical Research Methodology Early detection Hepatocellular carcinoma Longitudinal biomarkers α-fetoprotein Parametric empirical Bayes Short-term risk prediction |
author_facet |
Nabihah Tayob Peter Richardson Donna L. White Xiaoying Yu Jessica A. Davila Fasiha Kanwal Ziding Feng Hashem B. El-Serag |
author_sort |
Nabihah Tayob |
title |
Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care System |
title_short |
Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care System |
title_full |
Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care System |
title_fullStr |
Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care System |
title_full_unstemmed |
Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran’s Affairs Health Care System |
title_sort |
evaluating screening approaches for hepatocellular carcinoma in a cohort of hcv related cirrhosis patients from the veteran’s affairs health care system |
publisher |
BMC |
series |
BMC Medical Research Methodology |
issn |
1471-2288 |
publishDate |
2018-01-01 |
description |
Abstract Background Hepatocellular carcinoma (HCC) has limited treatment options in patients with advanced stage disease and early detection of HCC through surveillance programs is a key component towards reducing mortality. The current practice guidelines recommend that high-risk cirrhosis patients are screened every six months with ultrasonography but these are done in local hospitals with variable quality leading to disagreement about the benefit of HCC surveillance. The well-established diagnostic biomarker α-Fetoprotein (AFP) is used widely in screening but the reported performance varies widely across studies. We evaluate two biomarker screening approaches, a six-month risk prediction model and a parametric empirical Bayes (PEB) algorithm, in terms of their ability to improve the likelihood of early detection of HCC compared to current AFP alone when applied prospectively in a future study. Methods We used electronic medical records from the Department of Veterans Affairs Hepatitis C Clinical Case Registry to construct our analysis cohort, which consists of serial AFP tests in 11,222 cirrhosis control patients and 902 HCC cases prior to their HCC diagnosis. The six-month risk prediction model incorporates routinely measured laboratory tests, age, the rate of change in AFP over the past year with the current AFP. The PEB algorithm incorporates prior AFP screening values to identify patients with a significant elevated level of AFP at their current screen. We split the analysis cohort into independent training and validation datasets. All model fitting and parameter estimation was performed using the training data and the algorithm performance was assessed by applying each approach to patients in the validation dataset. Results When the screening-level false positive rate was set at 10%, the patient-level true positive rate using current AFP alone was 53.88% while the patient-level true positive rate for the six-month risk prediction model was 58.09% (4.21% increase) and PEB approach was 63.64% (9.76% increase). Both screening approaches identify a greater proportion of HCC cases earlier than using AFP alone. Conclusions The two approaches show greater potential to improve early detection of HCC compared to using the current AFP only and are worthy of further study. |
topic |
Early detection Hepatocellular carcinoma Longitudinal biomarkers α-fetoprotein Parametric empirical Bayes Short-term risk prediction |
url |
http://link.springer.com/article/10.1186/s12874-017-0458-6 |
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