Treatment Of Resectable Hepatocellular Carcinoma Research Articles

Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review.

Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC. A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276). This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety. Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.

A prospective, phase II clinical study of tislelizumab monotherapy or in combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma

A prospective, phase II clinical study of tislelizumab monotherapy or in combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma

1015TiP A Prospective, phase II clinical study of tislelizumab monotherapy or in combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma

1015TiP A Prospective, phase II clinical study of tislelizumab monotherapy or in combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma

A phase II/III study of camrelizumab plus apatinib as perioperative treatment of resectable hepatocellular carcinoma at intermediate-high risk of recurrence: Primary results of major pathologic response from phase II stage.

4126 Background: Surgical resection remains an important treatment strategy for patients (pts) with liver cancer. However, the 5-year recurrence rate is still 50-70% in surgically resectable pts. Intermediate-high risk factors of recurrence in HCC include single tumor size > 5 cm, multiple tumors, and microvascular invasion. The standardized perioperative regimen for resectable HCC has not been established. This study aimed to assess the efficacy and safety of camrelizumab plus apatinib (C+A) as a perioperative regimen in resectable HCC at intermediate-high risk of recurrence (Clinical trial: NCT04521153). Methods: In this multicentre, randomised, phase II/III study, eligible HCC pts (CNLC Ib-IIIa) were randomly assigned in a 1:1 ratio to treatment group and control group. Pts in treatment group received 2 cycles of C (200mg Q2W) plus A (250mg QD) followed by surgery and a post-surgical TACE. At least 6 cycles of sequential treatment of C (200mg Q3W) plus A (250mg QD) were performed after TACE. Pts in control group received surgical resection and a post-surgical TACE. Primary endpoint of phase III stage was 3-year EFS, of phase II stage was MPR (defined as less than 50% residual tumor) rate. In the phase II stage, futility analysis on a phase II outcome was performed after pts in treatment group completed surgical resection and pathological evaluation. If < 15% of pts achieved an MPR, or > 20% of pts had progression that precluded surgery, the study would not proceed to phase III stage. Results: In phase II stage, 60 pts were randomly assigned to treatment group, and 59 to control group. As of Nov 4, 2022, the last randomised pt underwent curatively surgical resection and pathological evaluation. The median age was 58 years (range, 21-75). 101(84.9%) were male, and 96 (80.7%) had HBV infection. In treatment group, 58 pts received neoadjuvant therapy, 52 completed 2 cycles of preoperative therapy and proceeded with planned resection. Surgery was aborted for 6 pts: 3 refused surgery, 2 deaths (1 for tumor rupture of HCC, 1 for immune related hepatitis), and 1 had protocol deviation. The MPR rates in the ITT population were 40% (24/60). Among them, 10% pts (6/60) had ≤ 5% surviving tumor cells in tumor bed. The MPR rate in pts who had surgical resection were 46.2% (24/52). 19.3% pts experienced ≥ 3 grade TRAEs, the most common of which were AST increased (5.3%), hypertension (5.3%), and ALT increased (3.5%). Conclusions: The phase II stage of the study did not meet the stopping criteria. Neoadjuvant camrelizumab plus apatinib therapy exhibits promising pathological response in HCC pts at intermediate-high risk of recurrence, with a tolerable safety profile. The phase III stage of the study is currently ongoing. Clinical trial information: NCT04521153 .

Ultra-sensitive baseline-informed MRD assay to predict prognosis outcomes in patients with resectable hepatocellular carcinoma.

e16228 Background: The detection of minimal residual disease (MRD) has been shown to be a potential biomarker for the prognosis and post-surgery treatment of resectable hepatocellular carcinoma (HCC). However, the application of MRD in HCC has been limited by the traditional requirement of carrying out MRD over 30 days post-surgery, which is often incompatible with the time window for adjuvant treatment decisions. Additionally, MRD results may be impacted by post-surgery imbalances if assayed too soon after surgery. Methods: This retrospective study enrolled 255 early-stage HCC patients who received surgical resections and had complete information on relapse and survival. Matched tumor and normal tissue samples were collected at the time of surgery and plasma samples were collected as early as 7 days post-surgery. An ultra-sensitive, baseline-informed MRD assay (PredicineBEACON) was used to evaluate the correlation between peri-surgical MRD status and prognosis outcomes. Somatic mutations were identified through PredicineWES+ whole exon sequencing, and up to 50 somatic mutations were selected for the design of a patient-specific capture panel, in addition to a fixed panel of 500 actionable variants. Results: The study has completed MRD tests for 58 patients, of which 8 were called MRD positive with ≥0.005% tumor fractions. The tumor fraction proportion of MRD-positive patients ranged from 0.008% to 5.653% (median 0.315%). The relapse-free survival (RFS) and overall survival (OS) were correlated with MRD status: the median RFS of MRD-positive patients was 13.9 months compared to not reached after 44.4 months for MRD-negative patients (p = 0.1), and the median OS of MRD-positive patients was 27.2 months compared to not reached after 55.5 months for MRD-negative patients (p = 0.03). Conclusions: Our results demonstrate the feasibility of using an ultra-sensitive, baseline-informed MRD assay to detect strong correlations between MRD status and prognosis outcomes in peri-surgical plasma samples collected as early as 7 days post-surgery in resectable HCC patients. This study highlights the clinical utility of MRD testing in peri-surgical settings.

Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: A multicenter retrospective study.

BackgroundEarly recurrence is common after surgical resection (SR) for hepatocellular carcinoma (HCC) with high risk of recurrence and is associated with poor prognosis. The combinations of lenvatinib (LEN), anti-PD-1 antibodies (PD-1) and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. It is unknown whether triple therapy for neoadjuvant treatment of resectable HCC with high risk of recurrence is effective. This article aimed to compare the outcomes of surgery alone and neoadjuvant combination treatment with triple therapy before SR in patients with HCC with high risk of recurrence.MethodsA retrospective study was conducted on patients diagnosed with HCC with high risk of recurrence who received treatment with or without triple therapy. The records of 24 patients in the triple therapy group and 76 patients in the surgery-alone group were analyzed. Propensity score matching (PSM) was performed to minimize the influence of potential confounders.ResultsOne hundred patients were enrolled. In the triple therapy group, 8 (33.3%) and 12 (50.0%) patients had complete and partial responses, respectively, as assessed by an investigator. Before PSM, the overall survival (OS) rates for the triple therapy group at 6, 12, 18, and 24 months were 100.0%, 100.0%, 100.0%, and 85.7%, respectively, compared with corresponding 92.1%, 73.7%, 53.9%, and 48.7% for the surgery-alone group (P<0.001). The disease-free survival (DFS) rates were 82.2%, 66.95%, 48.8%, and 48.8% for the triple therapy and 41.92%, 28.34%, 27.05%, and 22.99% for the surgery-alone group (P=0.003). After PSM, DFS and OS were significantly longer in the triple therapy group than in the surgery-alone group (DFS, p=0.019; OS, p=0.003).ConclusionsNeoadjuvant combination treatment before SR had a high rate of tumor response and provided significantly better postoperative survival outcomes than surgery alone in patients with HCC with high risk of recurrence.

Racial and socioeconomic disparities in the treatment of resectable hepatocellular carcinoma.

e19026 Background: Cancer surgeries performed at high case volume centers (hCVCs) are associated with improved surgical and clinical outcomes. Resectable hepatocellular carcinoma (rHCC) is not common in the US and the impact of surgery at hCVCs has not been well assessed. We analyzed the impact of surgery at hCVCs on survival, and the potential racial and socioeconomic disparities associated with obtaining care at hCVCs. Methods: We collected demographic, diagnostic, treatment, and survival data of 96,215 patients with stage I-III HCC diagnosed between 2004 – 2015 from the National Cancer Database. To estimate the average surgical volume/year, number of reported cases were divided by the number of years the facility was represented in the database. Logistic regression was used to determine the associations between case volume, facility type and the demographic and clinical variables. We assessed demographic and clinical predictors of overall survival (OS) using Cox proportional hazards regression. Results: In total, 10,419 resected HCC patients were included in the analysis. The median age was 64 (18 – 90), 68.4% were male and 69.5% were white. Facilities were divided into quartiles by average number of surgical CV/year: 1st quartile (1Q) 0.08-1.60, 2Q 1.61 – 3.91, 3Q 3.92 – 8.34, and 4Q 8.35 – 45.34. In a multivariate model, improved OS was seen with each increase in quartiles with the highest CVCs (i.e 4Q) HR 0.70 (95% CI 0.63 – 0.77). Treatment at academic centers did not show an OS advantage (HR 0.93; 95% CI 0.86 – 1.01). Factors including black race (OR 0.83; 95% CI 0.75-0.93), age 65+ (OR 0.91; 95% CI 0.82 – 1.00), and living in a metro area with a population of 250,000 – 1 million people (OR 0.68; 95% CI 0.62 – 0.74) were less likely to be associated with treatment at hCVCs. Conversely, Asians/Pacific Islanders (OR 2.28; 95% CI 2.04 – 2.55) and those with private insurance (OR 1.33; 95% CI 1.18– 1.40) or Medicare (OR 1.21; 95% CI 1.05 – 1.38) were more likely to be treated at hCVCs. Conclusions: rHCC is not common in the US and having surgery at hCVCs improves OS. However, racial and socioeconomic disparities exist in receiving care at these hCVCs.

Surgical Resection Versus Conformal Radiotherapy Combined With TACE for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Comparative Study

The aim of this study was to compare the results of surgical resection with three-dimensional conformal radiotherapy (3D-CRT) in the treatment of resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Transarterial chemoembolization (TACE) was given to both groups of patients when possible. A retrospective study of 371 patients with resectable HCC with PVTT was conducted in two tertiary referral centers. The treatment of choice for these patients in one center was surgical resection. In the other center it was 3D-CRT. In the radiotherapy group (RG, n = 185), patients received 3D-CRT to the tumor and PVTT for a total radiation dose of 30-52 Gy (median 40 Gy). In the surgical group (SG, n = 186), patients underwent surgical resection. TACE was applied after surgery or 3D-CRT and then was repeated every 4-6 weeks if the patient tolerated the treatment. The median survival was 12.3 months for RG and 10.0 months for SG. The 1-, 2-, and 3-year overall survivals were 51.6, 28.4, and 19.9 %, respectively, for RG and 40.1, 17.0, and 13.6 %, respectively, for SG (p = 0.029). Stepwise multivariate analysis showed that the extent of PVTT and mode of treatment were independent risk factors of overall survival. The most common cause of death after treatment was liver failure as a consequence of progressive intrahepatic disease. 3D-CRT gave better survival than surgical resection for HCC with PVTT.

Adverse effects of preoperative hepatic artery chemoembolization for resectable hepatocellular carcinoma: A retrospective comparison of 138 liver resections

Abstract During the past 8 years we have treated 268 patients with primary hepatocellular carcinoma (HCC); total extirpation of the tumor was carried out in 138. Thirty-one of the patients with resectable HCCs had already been treated with transcatheter arterial embolization (TAE) of the liver before they were referred to us. The clinical values of preoperative TAE were retrospectively evaluated for those 31 patients and for the remaining 107 patients without TAE. There were no substantial differences between the two study groups in the clinical and histopathologic backgrounds. No differences were observed in the extent of liver resection, estimated blood loss during surgery, and operation time. During surgery, however, troublesome intra-abdominal complications relevant to TAE were encountered in 15 patients, and detection of tumors was impossible, even with intraoperative ultrasonography, in five patients in the group with TAE. Such findings were not present in any of the patients without TAE. Postoperative morbidity and mortality rates were similar in the two groups. There was no significant difference in the rate of recurrence of tumor in the liver, but the recurrence time was significantly shorter in the group with TAE. TAE did not improve the long-term survival rates in patients either with or without cirrhosis. Results of our study seem to indicate that preoperative TAE is meaningless in the treatment of resectable HCCs and therefore should be avoided, particularly in patients with advanced cirrhosis of the liver.

Comparison of resection, liver transplantation and transcatheter oily chemoembolization in treatment of hepatocellular carcinoma

Background/Aims: Resection and liver transplantation are currently considered as the most useful treatments for hepatocellular carcinoma. However, transcatheter oily chemoembolization may be favourably compared with these two surgical treatments in patients with anatomically operable tumors. Methods: Between 1985 and 1991, 122 patients with an Okuda stage I tumor were hospitalized in two French hospitals. Among these patients, 33 remained untreated, 42 were treated by transcatheter oily chemoembolization, 30 by resection and 17 by liver transplantation. The four groups were closely comparable except for age, the patients in the two surgical groups being significantly younger. Moreover, the frequency of pTNM II tumor was significantly higher in the resection group. Results: The 5-year probability of survival was close to 45% in each of the three treated groups and was significantly higher than in the untreated group (0% at 4 years, p<0.0001). The probability of cancer recurrence and/or metastatic dissemination was lower after transcatheter oily chemoembolization than after surgery. Conclusion: Thus, transcatheter oily chemoembolization seems comparable at 5 years with resection or transplantation for the treatment of resectable hepatocellular carcinoma.