Association of adverse events and quality of life in patients with unresectable hepatocellular carcinoma

Purpose Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths globally. Patients are often diagnosed with advanced disease, in which systemic and locoregional therapies are commonly used as first-line treatment. Such treatments can cause adverse events (AEs) that negatively affect quality of life (QoL), which is particularly undesirable where prognosis is poor. The aim of the present study was to evaluate the impact of common AEs on QoL in patients with HCC. Methods Data from the SARAH randomized controlled trial (RCT) were analyzed. Given the large number of distinct AEs that occurred in the trial, AEs were grouped as in the SARAH trial and prioritized using principal component analysis (PCA). Linear mixed-effects models were then applied with age, ECOG status, and AEs as predictors of the QoL change as measured with the EORTC Core Quality of Life Questionnaire (QLQ-C30). Results The PCA resulted in the selection of 28 AEs for inclusion in the linear mixed-effects models. Of the 28 AEs, diarrhea, decreased appetite, abdominal pain, and palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome) were significant drivers of reductions in QoL as measured using the QLQ-C30 global health status scale. Diarrhea, abdominal pain, and hand-foot syndrome were also significant drivers of reduced QoL outcomes. Conclusion The present analysis showed that diarrhea, decreased appetite, abdominal pain, and palmar-plantar erythrodysesthesia were significantly associated with reduced QoL in patients with unresectable HCC. Reducing the incidence and/or severity of these AEs should therefore be a key focus when selecting the optimal treatments for these patients. Plain English summary Patients with advanced liver cancer can have a poor prognosis, and preservation of quality of life is an important consideration when choosing appropriate treatments. The SARAH clinical study looked at two treatment options for primary liver cancer — sorafenib and selective internal radiation therapy or SIRT — and collected data on quality of life and how often patients experienced adverse events. Our study used these data to understand which adverse events may have had the largest effect on quality of life. We found that, no matter how severe, gastrointestinal disorders (such as diarrhea, vomiting, nausea, and anorexia) were associated with significant reductions in patient quality of life. We also found that severe constitutional symptoms (such as fever, fatig