Systemic Treatment of Advanced Unresectable Hepatocellular Carcinoma after First-Line Therapy: Expert Recommendations from Hong Kong, Singapore, and Taiwan.

Background: Asia has a high burden of hepatocellular carcinoma (HCC) due to the high rates of chronic hepatitis B infection and accounts for 70% of HCC cases globally. In the past 20 years, the systemic treatment landscape of advanced HCC has evolved substantially - from tyrosine kinase inhibitors to immune-oncology agents plus anti-vascular endothelial growth factor agents. The appropriate sequence of therapies has become critical in optimizing patient outcomes given the increase in systemic therapeutic options. This article evaluates the evidence and provides expert recommendations for the use of systemic therapies after first-line treatment in patients with advanced HCC. Summary: Based on three virtual meetings held in early 2021, a team of 17 experts comprising oncologists, a hepatologist, and a hepatobiliary surgeon from Hong Kong, Singapore, and Taiwan reviewed available data about systemic treatments for HCC after first line and formulated 28 statements. These statements aimed to provide expert guidance on selecting first and subsequent lines of therapies as well as recommending therapies in special circumstances, such as poor liver function, posttransplantation, recent gastrointestinal bleeding, or autoimmune diseases. Data supporting the statements were drawn from clinical trials and real-world studies. The 28 statements were then evaluated anonymously using a 5-point Likert scale, and 24 reached consensus, predefined as achieving 75% agreement. Statements generated covered the selection of first-line systemic therapy, considerations and goals of second-line systemic therapies, treatment selection following first-line therapy, and treatment recommendations following first-line tyrosine kinase inhibitors, immune-oncology monotherapy, or immune-oncology combination therapy. The authors also shared expert opinion on the use of second-line systemic therapy in patients with liver dysfunction, liver transplantation, and recent gastrointestinal or autoimmune disease. Key Messages: These expert statements summarize the latest data and expert opinion on selecting systemic treatment following first-line therapy in patients with unresectable advanced or metastatic HCC.

The Use of Cabozantinib in Advanced Hepatocellular Carcinoma in Hong Kong-A Territory-Wide Cohort Study.

(1) Background: Cabozantinib is approved in sorafenib-exposed advanced hepatocellular carcinoma (aHCC). We evaluated the real-life pattern of use, efficacy, and tolerability of cabozantinib in aHCC. (2) Methods: This territory-wide study included consecutive aHCC patients who received cabozantinib between February 2018 and September 2020 in Hong Kong. The objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events (AE) were assessed. (3) Results: Overall, 42 patients were included. Approximately 83.3% had Child-Pugh A cirrhosis. About 64.3% received cabozantinib as a single agent, and the remaining 35.7% received cabozantinib as an add-on to immune checkpoint inhibitors (ICIs). For single-agent patients, the median follow-up was 6.7 months. The ORR was 3.7%, DCR was 44.4%, and the median OS was 8.28 months. About 74.1% of patients experienced any AEs with 7.4% having grade ≥3 AEs. Among patients who received prior ICIs (n = 16), the ORR was 6.3%, and the median OS was 8.28 months. An exploratory analysis of patients who received cabozantinib as an add-on to ICIs showed an ORR of 6.7% and a median OS of 15.1 months, with 73.3% having any AE and 13.3% having grade ≥3 AEs. (4) Conclusions: Cabozantinib had good anti-tumor activity, survival benefits, and acceptable tolerability in real-life aHCC patients.

Palliative Liver Radiotherapy (RT) for Symptomatic Hepatocellular Carcinoma (HCC).

This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.

Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B-C hepatocellular carcinoma.

PURPOSE: We retrospectively evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with trans-arterial chemoembolization (TACE) as initial therapy in Barcelona Clinic Liver Cancer (BCLC) system stage B-C hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Seventy-two patients received a single dose of TACE followed by SBRT 4 weeks later. All patients had tumor sizes ≥5 cm, at least 700 ml of disease-free liver, Child-Pugh (CP) score ≤ B7 and tumor nodules ≤5. SBRT dose, ranging from 6â€¯× 5-8 Gy or 5-10â€¯× 4 Gy, was individualized according to normal tissue constraints. No subsequent scheduled treatment was delivered unless disease progression was observed. Local control (LC), overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity were evaluated. RESULTS: The patients' characteristics were: median age 60 years (range 28-87 years); CP score A/B (n = 68/4); BCLC stage B/C (n = 51/21); solitary/multifocal (n = 37/35); portal vein invasion (n = 18). The median tumor size and GTV were 11.2 cm (range 5.0-23.6 cm) and 751 cm3 (range 41-4009 cm3), respectively. The median equivalent dose in 2 Gy per fraction (EQD2, α/ß = 10) was 37.3 Gy2 (range, 28-72 Gy2). The median follow-up time was 16.8 months (range, 3-96 months). The objective RR was 68% and the 1­year LC rate was 93.6% (95% CI, 87.6-100%). The median OS was 19.8 months (95% CI, 11.6-30.6 months). SBRT-related grade 3 or higher adverse gastrointestinal events and treatment-related death occurred in three (2.8%) and one patient (1.4%) respectively. No patient developed classical radiation-induced liver injury. CONCLUSION: Our experience suggests that combined TACE and SBRT can be a safe and effective initial therapy for BCLC stage B-C HCC with appropriate patient selection. Further prospective trials are warranted.

Comparison of platelet-albumin-bilirubin (PALBI), albumin-bilirubin (ALBI), and child-pugh (CP) score for predicting of survival in advanced hcc patients receiving radiotherapy (RT).

PURPOSE: This work evaluated the prognostic performance of Child-Pugh (CP), albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) scores in hepatocellular carcinoma (HCC) patients undergoing radiotherapy (RT). RESULTS: The study included 174 consecutive patients with 63% at CP A5 (n = 110) and 34% at CP A6 (n = 64). The median ALBI score was -2.39 (range: -3.61 to -1.41) with 34.5% at grade A1 (n = 60) and 65.5% at grade A2 (n = 114). The median PALBI score was -2.39 (range -3.39 to -1.24) with 33.3% at grade 1 (n = 58), 41.4% at grade 2 (n = 72) and 25.3% at grade 3 (n = 44). With a median follow-up of 21.7 months, the median OS of the entire cohort was 22.2 months. OS was significantly associated with the PALBI grade (p = 0.002) and for the ALBI grade (p = 0.00495), but not for the CP score (p = 0.46). The PALBI grade has a significantly higher AUC compared than the ALBI grade or CP scores in predicting OS. The PALBI grade was predictive of CP score decline ≥2 (20% grade 3 vs. 5.3% grade 1/2 p = 0.05) but the ALBI and CP scores were not. CONCLUSION: Among CP A HCC patients receiving radiotherapy, the PALBI and ALBI grade maybe a better prognostic tool than the CP score. The role of PALBI in predicting liver toxicity warranted further exploration. METHODS: We retrospectively reviewed HCC patients treated with individualized hypo-fractionated radiotherapy (IHRT) using stereotactic technique from 2006 to 2015. We collected CP, ALBI and PALBI scores prior to treatment and analyzed their correlation with overall survival (OS) and liver toxicity.