Shi-Ming Lin

Background: Atezolizumab plus bevacizumab is the standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). Immune-related liver injury (IrLI) is common; however, the association between IrLI severity and patient outcomes remains unknown. This study aimed to investigate the prognostic value of irLI in such patients. Methods: One hundred and sixteen patients who fulfilled the IMBrave150 inclusion criteria were enrolled. IrLI was defined as an increase in serum ALT and/or AST levels attributed to treatment and was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: A total of 61 patients (52.6%) developed any grade of irLI, with a median onset time of 1.7 months. Multivariate analysis revealed that grade II ALBI (hazard ratio [HR] = 2.003, p = 0.028) and BCLC stage C (HR = 3.876, p = 0.016) were associated with worse OS and PFS (HR = 1.327, p = 0.044 and HR = 1.790, p = 0.039, respectively), whereas grade 2 irLI was associated with better OS (HR = 0.223, p = 0.046) and PFS (HR = 0.244, p = 0.011). Patients with grade 2 irLI showed better median OS (not reached) than those without irLI (16.7 months), those with grade 1 (17.5 months), and those with grade ≥ 3 (7.3 months) (overall log-rank p = 0.037). Furthermore, patients with grade 2 irLI demonstrated significantly enhanced PFS (not reached) compared to those without irLI (5.7 months), grade 1 (4.6 months), or grade ≥ 3 (2.3 months), with an overall log-rank p = 0.010. In addition, patients with grade 2 irLI had the highest disease control rate (overall p = 0.053). Conclusion: In patients with uHCC treated with Ate/Bev, moderate elevation of liver enzymes (grade 2 irLI) was associated with significantly improved survival and tumor control.

PurposeThe aim of this study was to investigate the factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment.MethodsWe conducted a retrospective study using a multi-institutional electronic medical records database in Taiwan. We included advanced HCC patients newly receiving ramucirumab as second-line or beyond systemic therapy between January 2016 and February 2022. The clinical outcomes were median progression-free survival (PFS) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), overall survival (OS) and adverse events. We applied Kaplan-Meier methods to estimate median PFS and OS. Uni-variable and multi-variable Cox regression models were applied to identify the prognostic factors.ResultsWe included 39 ramucirumab naive users with a median age of 65.5 (IQR: 57.0-71.0) years and treatment time of 5.0 (3.0-7.0) cycles, of whom 82.1% were male and 84.6% were Barcelona Clinic Liver Cancer (BCLC) stage C. After median follow-up time of 6.0 months, 33.3% of patients' AFP level had decreased more than 20% within 12 weeks. The median PFS and OS were 4.1 months and non-reach, respectively. Moreover, tumor burden beyond the up-to-11 criteria (HR: 2.95, 95% CI: 1.04-8.38) and a decrease in estimated glomerular filtration rate of more than 10% within 12 weeks (HR: 0.31, 0.11-0.88) were significantly related to PFS in the multi-variable analysis. No patient discontinued ramucirumab during the treatment on account of side effects.ConclusionRamucirumab was an effective treatment option with good AFP response for advanced HCC patients in real-world experience. Tumor burden beyond the up-to-11 criteria and a decrease in estimated glomerular filtration rate were independent predictive factors for progression-free survival.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.

Outcomes of hepatocellular carcinoma (HCC) lesions >3.0 cm in size including Barcelona Clinic Liver Cancer (BCLC) stage B after radiofrequency ablation (RFA) with a single electrode remain unsatisfactory. This study aimed to investigate the outcomes of RFA with multiple electrodes (ME-RFA) for HCC tumors 3.1-7.0 cm in size and BCLC stage B. This retrospective study included 70 consecutive patients with 58 medium- (3.1-5.0 cm) and 17 large- (5.1-7.0 cm) sized HCCs after ME-RFA using a controller. Outcomes in terms of complete response, primary technique effectiveness, local tumor progression, and overall survival were investigated. After 1-4 applications of ME-RFA, the rates of complete response and PTE in medium-sized tumors were 79.3% and 91.4%, respectively, and in large tumors were 76.5% and 94.1%, respectively. Overall, the major complication rate was 5.7%. After a median 21-month follow-up period, both two- and three-year estimated overall survival rates were above 80%. There were no significant differences in overall survival and local tumor progression rates between medium- and large-size tumors and among BCLC stages A, B1 and B2. A complete response to ME-RFA was the only significant factor associated with improved survival (p=0.008). In conclusion, ME-RFA can effectively treat 3.1-7.0-cm sized HCCs with a comparable outcome between medium- and large-size tumors and among BCLA stages A to B2.

Aim: The aim of the study was to investigate the impact of early response (ER) to hepatic arterial infusion chemotherapy (HAIC) on outcomes of patients with advanced hepatocellular carcinoma (HCC) complicated with major portal vein tumor thrombosis (PVTT). Methods: Thirty-nine patients receiving HAIC with low-dose cisplatin, 5-fluorouracil (5FU), and leucovorin were enrolled. One course of HAIC consisted of 5 days of treatment and 2 days rest per week for 4 consecutive weeks. ER was categorized as complete response, partial response, or minor response and was determined by World Health Organization criteria with dynamic computed tomography findings performed within 1 week after the first course of HAIC. Results: Thirteen (33%) patients achieved an ER. Twelve (92.3%) of these 13 ER patients achieved a higher overall response than all but one (3.8%) of the 26 non-early responders (NERs) (pConclusions: HAIC can yield a satisfactory ER for advanced HCC with PVTT. Moreover, achievement of ER after HAIC in advanced HCC with PVTT is strongly associated with better overall survival and PFS.

Tumor recurrence in hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) remains common; some studies have reported that insufficient ablative margin after RFA might contribute to HCC recurrence. The aim of this study was to investigate whether insufficient ablative safety margins determined by early computed tomography (CT) predicts HCC recurrence after RFA. This retrospective study recruited patients with a single HCC lesion after RFA in our department between May 2013 and March 2014. Early follow-up CT was performed within 7 days after RFA. An adequate ablative margin assessed by follow-up CT was defined as (maximum post-RFA CT radius)³/(maximum pre-RFA CT radius + 5 mm)³> 1. All patients in whom complete ablation was achieved underwent a CT scan every 3 months for early detection of HCC recurrence. In total, 72 patients (48 male, mean age 69.4 years) were analyzed. Of these, eight patients had local tumor progression, four had intra-hepatic distant recurrence, and two had extra-hepatic metastasis. Insufficient ablative margin, defined as an ablative volume with a safety margin of less than 5 mm, was an important predictor of local tumor progression (LTP) (p = 0.015) and overall recurrence (p = 0.012). The sensitivity, specificity, and positive and negative predictive values of an insufficient ablative margin for predicting LTP and overall recurrence were 36.4%, 97.2%, 50.0%, and 87.9%, and 46.2%, 89.7%, 42.9%, and 87.9%, respectively. An ablative volume with an ablative margin of less than 5 mm is associated with higher rates of both LTP and overall recurrence in HCC after RFA.

Radiofrequency ablation (RFA) is more effective for hepatocellular carcinoma (HCC) < 3 cm. Combining percutaneous ethanol injection and RFA for HCC can increase ablation; however, the long‐term outcome remains unknown. The aim of this study was to compare long‐term outcomes between patients with HCC of 2–3 cm versus 3.1–4 cm and in high‐risk versus non‐high‐risk locations after combination therapy. The primary endpoint was overall survival and the secondary endpoint was local tumor progression (LTP). Fifty‐four consecutive patients with 72 tumors were enrolled. Twenty‐two (30.6%) tumors and 60 (83.3%) tumors were of 3.1–4 cm and in high‐risk locations, respectively. Primary technique effectiveness was comparable between HCC of 2–3 cm versus 3.1–4 cm (98% vs. 95.5%, p = 0.521), and HCC in non‐high risk and high‐risk locations (100% vs. 96.7%, p = 1.000). The cumulative survival rates at 1 year, 3 years, and 5 years were 90.3%, 78.9%, and 60.3%, respectively, in patients with HCC of 2–3 cm; 95.0%, 84.4%, and 69.3% in HCC of 3.1–4.0 cm (p = 0.397); 90.0%, 71.1%, and 71.1% in patients with HCC in non‐high‐risk locations; and 92.7%, 81.6%, and 65.4% in high‐risk locations (p = 0.979). The cumulative LTP rates at 1 year, 3 years, and 5 years were 10.2%, 32.6%, and 32.6%, respectively, in all HCCs; 12.6%, 33.9%, and 33.9% in HCC of 2–3 cm; 4.8%, 29.5%, and 29.5% in HCC of 3.1–4 cm (p = 0.616); 16.7%, 50.0%, and 50.0% in patients with HCC in non‐high‐risk locations; and 8.8%, 29.9%, and 29.9% in patients with HCC in high‐risk locations (p = 0.283). The cumulative survival and LTP rates were not significantly different among the various subgroups. Combining RFA and percutaneous ethanol injection achieved comparable long‐term outcomes in HCCs of 2–3 cm versus 3.1–4.0 cm and in high‐risk versus non‐high‐risk locations. A randomized controlled or cohort studies with larger sample size are warranted.

Diabetes mellitus (DM) is prevalent in patients with hepatocellular carcinoma (HCC) but its effects on post-radiofrequency ablation (RFA) have not been elucidated. This study aims to determine whether DM significantly impacts the outcomes in patients with HCC after RFA. This retrospective study included 161 HCC patients successfully treated with RFA. Intra-hepatic HCC recurrence and survival were analysed. No significant difference was found for 1-, 2-, 3- year's intra-hepatic HCC recurrence rates (DM: 45%, 61%, 74% vs. non-DM: 42%, 62%, 75%;p=0.935) and survival rates (DM: 83%, 80%, 73% vs. non-DM: 92%, 84%, 79%; p=0.218) between diabetics (53 patients) and non-diabetics (108 patients). In subgroup analysis of viral etiology and HCC, no significant difference was noted for intra-hepatic HCC recurrence or survival in hepatitis B virus-related or hepatitis C virus-related HCC. Multivariate analysis showed only persistent hepatitis influenced intra-hepatic HCC recurrence (p=0.021) and survival (p=0.022). DM may not affect the intra-hepatic HCC recurrence and survival in patients with HCC after RFA. However, persistent hepatitis after RFA may affect intra-hepatic HCC recurrence and survival.

Background The aim of this study was to evaluate the impact of the interval between diagnosis and treatment using radiofrequency (RF) ablation on the survival of patients with HCC detected through a surveillance program. Methods Between January 2004 and July 2007, 121 cirrhotic patients with 157 tumours detected through a surveillance program underwent RF ablation. A delay in treatment was defined as >5 weeks. The mean length of follow-up was 25 months (range 8–55 months). Cumulative survival of patients was analysed using the Kaplan–Meier method. Cox regression models were used to identify factors associated with patient survival. Results The 1-, 2- and 3-year survival rates were 92.5%, 78.5% and 67.2%. The independent predictors of poorer patient survival were time from diagnosis to treatment >5 weeks (pooled odds ratio [OR], 3.59; 95% confidence interval [CI], 1.58–8.18; P = 0.002), absence of complete ablation after the initial RF session (OR, 2.42; 95% CI 1.07–5.45; P = 0.033) and Child-Pugh B liver cirrhosis (OR, 2.46; 95% CI 1.06–5.70; P = 0.036). Conclusions Delay in the start of effective treatment for HCC using RF ablation may be associated with poorer patient survival. J. Surg. Oncol. 2011; 103:133–139.