A new study is investigating the benefits of integrating palliative care early in the treatment of hepatocellular carcinoma (HCC). The pragmatic cluster-based randomized controlled trial, conducted across four Australian tertiary ambulatory clinics, aims to demonstrate that early referral to palliative care improves patient outcomes compared to standard HCC care with on-demand palliative care referral.
The study, registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12623000010695), plans to recruit a minimum of 386 eligible participants. These patients will be assigned to either the intervention or control group based on their regular HCC ambulatory clinic location. The intervention involves referral to a palliative care physician for consultation and management of symptoms, quality of life, and caregiver support, triggered by a liver-specific Edmonton Symptom Assessment Scale (ESAS) score of ≥5 on at least one of the ten symptoms. Control sites will continue with standard of care (SOC) and refer to palliative care physician at the current SOC.
Study Design and Objectives
The primary clinical outcome is the improvement of palliative care symptoms, defined as a reduction of ≥50% in the liver-specific ESAS total symptom score ≥5 within 3 months of consultation with the palliative care clinician. The primary implementation outcome assesses adherence rate, targeting 80% or more of eligible patients having a liver-specific ESAS performed at all designated timepoint clinic attendances.
Secondary outcomes include improvements in patient quality of life, palliative care referral rates, input from palliative care consultation, mortality differences, hospital admissions for liver-specific and non-liver-specific causes, cost-effectiveness, and structural and process measures.
Patient Population and Data Collection
Patients attending participating HCC and palliative care centers as outpatients are eligible if they have Barcelona Clinical Liver Cancer (BCLC) stage A disease with active tumor, or current/prior BCLC stage B or C disease, are over 18 years old, and can complete a 0-10 liver-specific ESAS. Exclusion criteria include BCLC stage 0 or D disease, no active HCC, prior palliative care referral, cognitive impairment, or liver transplantation history.
Baseline data includes demographics, cancer history, tumor stage (BCLC coding), Child-Pugh Status, MELD-Na score, current treatment, underlying liver disease, and performance status (Karnofsky Performance Status or ECOG Performance Status).
Statistical and Qualitative Analysis
Linear mixed models will be used for the main analysis, accounting for clustering and longitudinal design. Qualitative studies, involving semi-structured interviews with patients, carers, and HCC care providers, will identify barriers and facilitators to integrating palliative care. Thematic analysis will be used to analyze the qualitative data.
Economic Evaluation
A cost-effectiveness analysis will determine the incremental cost-effectiveness ratio (ICER) at 12 months, considering the costs and effectiveness of the intervention compared to no intervention. Quality of life data will be used to conduct a modelled cost-utility analysis, with sensitivity analysis to examine the effect of assumptions and cost components.
Significance
This study addresses a critical need for improved supportive care in HCC management. By integrating palliative care early, the trial aims to alleviate symptoms, enhance quality of life, and potentially improve survival for patients with this challenging disease. The results will inform clinical practice and health policy regarding the optimal timing and delivery of palliative care in HCC.
