Erlotinib for Hepatocellular Carcinoma Chemoprevention

Modulation of serum protein signature associated with hepatocellular carcinoma (HCC) risk

The relationship between the treatment and modulation of a serum protein signature associated with HCC risk (PLSec) will be assessed. PLSec-based HCC risk level (i.e., PLSec score) will be compared between baseline and at the end of treatment, and magnitude of the modulation will be measured as delta-PLSec and compared between the treatment groups by t-test and Wilcoxon rank-sum test.

Overall adverse event profile for erlotinib hydrochloride

Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. The maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events will be tabulated and summarized across all grades. Grade 3+ adverse events will be similarly described and summarized separately. Overall toxicity incidence, as well as toxicity profiles will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

Change in quality of life (QOL)

QOL will be measured by using Chronic Liver Disease Questionnaire (CLDQ), and compared between baseline and end of the treatment. Frequency distributions, graphical techniques and other descriptive measures will be used to summarize the results. Paired t-test will be used to assess change of the measurements.

Molecular tissue transcriptome signature associated with HCC risk

When optional liver biopsy tissues are obtained, the relationship between the treatment and modulation of a gene expression signature associated with HCC risk will be assessed. Expression levels of the signature genes will be compared between baseline and at the end of treatment, and magnitude of the modulation will be measured by Kolmogorov-Smirnov statistic-based Combined Enrichment Score (CES) and tested by t-test and Wilcoxon rank-sum test.

Changes in phospho-ERK levels in the liver

When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using analysis of variance (ANOVA) or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.

Changes in PCNA levels in the liver

When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.

Changes in EGF levels in the liver

When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.