Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial.

BACKGROUND AND AIM: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients. METHODS: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety. RESULTS: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73). CONCLUSION: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.

Prognosis factors of predicting survival in spontaneously ruptured hepatocellular carcinoma.

AIM: To investigate predictors affecting survival in patients with spontaneously ruptured hepatocellular carcinoma (srHCC). METHODS: One-hundred-and-twenty-seven patients experiencing srHCC between January 2010 and December 2020 were enrolled. The clinical features, treatments, and outcomes were reviewed. Statistics included univariate analysis, Kaplan-Meier analysis, multivariate analysis using Cox proportional hazards model and logistic regression model, and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 127 srHCC patients, 24, 42, and 61 patients received conservative treatment, surgical treatment, and transarterial chemoembolization/embolization (TACE/TAE) treatment at HCC rupture, respectively. The largest tumor size [hazard ratio (HR) 1.127; p < 0.001], Barcelona-Clinic Liver Cancer (BCLC) stage (HR 2.184, p = 0.023), international normalized ratio (INR; HR 3.895; p = 0.012), total bilirubin level (TBil; HR 1.014; p = 0.014), TACE after rupture (compared with conservative treatment) (HR 0.549; p = 0.029), TACE/TAE and surgery at rupture, and albumin level (HR 0.949; p = 0.017) were independent predictors affecting overall survival. A survival predictive model for HCC rupture (SPHR) using these predictors was created. ROC analysis showed that the area under the curve (AUC) of the SPHR model for 30 day survival was 0.925, and the AUCs of the model for end-stage liver disease (MELD) score and Child-Pugh score for 30 day survival were 0.767 and 0.757, respectively. CONCLUSION: The largest tumor size, advanced BCLC stage, higher INR and TBil, lower albumin, and conservative treatment were negative independent predictors for overall survival. The SPHR model may be more suitable than the MELD score and Child-Pugh score for predicting 30 day survival in srHCC.

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.

Prognostic factors of spontaneously ruptured hepatocellular carcinoma.

AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model. RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona-Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001). CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival.

[Efficacy and safety of combination of sorafenib and transarterial chemoembolization in treating primary hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of the combination of sorafenib and transarterial chemoembolization (TACE)in the treatment of primary hepatocellular carcinoma (HCC). METHODS: The clinical data of 10 patients with unresectable HCC treated by sorafenib combined with TACE in the Department of Radiology, the First Hospital of China Medical University were retrospectively analyzed. The efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors assessment. Survival was analyzed by Kaplan-Meier method. Safety was evaluated according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0. RESULTS: Among the 10 patients, 2 achieved complete response, 3 achieved partial response, 3 achieved stable disease, and 2 experienced progressive disease. The median overall survival of the cohort was 29.5 months. Different degree of adverse drug reactions (ADRs) occurred in 9 patients but all were at grade 3 or lower. The most common ADRs were hand-foot skin reaction (7/10) and diarrhea (6/10). CONCLUSION: The combination of sorafenib and TACE is an effective and safe treatment for HCC.

Three treatment methods via the hepatic artery for hepatocellular carcinoma - a retrospective study.

BACKGROUND: To evaluate the relative effectiveness of different treatments of hepatocellular carcinoma (HCC) via the hepatic artery. MATERIALS AND METHODS: The study sample group consisted of 418 patients who were randomly selected from 2008 to 2012 with a first diagnosis of HCC and treated with transcatheter arterial chemoembolization (TACE) or without (TAE) chemotherapy or transcatheter arterial infusion (TAI). We collected data including tumor size preoperative and one month thereafter to compare change in areas across the three groups, along with various laboratory indexes for comparison. RESULTS: The overall average change of areas was 240.8 ± 72.1 mm2. In the three groups it was 265.0 ± 58.0 mm2 vs. 250.5 ± 51.9 mm2 vs. 123.7 ± 26.2 mm2. In groups TACE and TAE values were larger than in group TAI (p<0.01), but the difference between the two was not statistically significant (p= 0.191). Additionally, U/L change of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups TACE and TAE was greater than in the TAI cases (24.0 ± 13.5 vs. 20. 9± 12.1 vs. 5.47 ± 8.20 and 25.6 ± 13.5 vs.23.2 ± 12.28 vs.5.48 ± 14.3) on the preoperative day and two days thereafter (p<0.01). Between the two groups there was no significant cariation (p= 0.320 and p= 0.609). However, the AST and ALT recovered to normal levels one month later on therapy with liver protecting drugs. CONCLUSION: The groups TACE and TAE demonstrated more effective reduction of tumor size than group TAI. While lipiodol caused acute liver function damage, this proved reversible.