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Threatment Strategies for Recurrent Hepatocellular Carcinoma Patients: Ablation and its Combination Patterns.

ABSTRACT: With the development of guidance technology and ablation equipment, ablative procedures have emerged as important loco-regional alternatives to surgical resection for recurrent hepatocellular carcinoma (rHCC) patients. Currently, ablation modalities used in clinical practice mainly include radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), cryoablation (CRA), high-intensity focused ultrasound (HIFU), and irreversible electroporation (IRE). Accumulated comparative data of ablation versus surgical resection reveal noninferior responses and outcomes but superior adverse effects. Moreover, studies demonstrate that ablation may serve as an excellent procedure for rHCC given its exact minimal invasiveness and immune modulation. We focus on the current status of ablation in clinical practice for rHCC and discuss new research in the field, including ablation combined with these other modalities, such as targeted therapy and immunotherapy.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC10937274 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Threatment Strategies for Recurrent Hepatocellular Carcinoma Patients: Ablation and its Combination Patterns.

Zhao Ya'ning Y Bai Jun J Wang Xi X Zhang Yaoren Y Yan Xiaohong X Qi Jun'an J Xia Xueyan X Feng Yuansong Y Duan Baojun B

Journal of Cancer 20240225 8

With the development of guidance technology and ablation equipment, ablative procedures have emerged as important loco-regional alternatives to surgical resection for recurrent hepatocellular carcinoma (rHCC) patients. Currently, ablation modalities used in clinical practice mainly include radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), cryoablation (CRA), high-intensity focused ultrasound (HIFU), and irreversible electroporation (IRE). Accumulated comparative data ...[more]

PMID: 38495485

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Project description:Background & aimsTremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of activated T lymphocytes. Ablative therapies induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced hepatocellular carcinoma (HCC). This study aimed to demonstrate whether tremelimumab could be combined safely and feasibly with ablation.MethodsThirty-two patients with HCC were enrolled: male:female: 28:4; median age: 62 (range 36-76). Patients were given tremelimumab at two dose levels (3.5 and 10mg/kg i.v.) every 4weeks for 6 doses, followed by 3-monthly infusions until off-treatment criteria were met. On day 36, patients underwent subtotal radiofrequency ablation or chemoablation. Staging was performed by contrast-enhanced CT or MRI scan every 8weeks.ResultsNo dose-limiting toxicities were encountered. The most common toxicity was pruritus. Of the 19 evaluable patients, five (26.3%; 95% CI: 9.1-51.2%) achieved a confirmed partial response. Twelve of 14 patients with quantifiable HCV experienced a marked reduction in viral load. Six-week tumor biopsies showed a clear increase in CD8+ T cells in patients showing a clinical benefit only. Six and 12-month probabilities of tumor progression free survival for this refractory HCC population were 57.1% and 33.1% respectively, with median time to tumor progression of 7.4months (95% CI 4.7 to 19.4months). Median overall survival was 12.3months (95% CI 9.3 to 15.4months).ConclusionsTremelimumab in combination with tumor ablation is a potential new treatment for patients with advanced HCC, and leads to the accumulation of intratumoral CD8+ T cells. Positive clinical activity was seen, with a possible surrogate reduction in HCV viral load.Lay summaryStudies have shown that the killing of tumors by direct methods (known as ablation) can result in the immune system being activated or switched on. The immune system could potentially also recognize and kill the cancer that is left behind. There are new drugs available known as immune checkpoint inhibitors which could enhance this effect. Here, we test one of these drugs (tremelimumab) together with ablation.Clinical trial numberClinicalTrials.gov: NCT01853618.

Project description:BackgroundIntrahepatic distant recurrence (IDR) is a significant problem for patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The objective of the study was to investigate risk factors and to predict outcomes of recurrent IDR within Milan criteria after complete RFA for primary early-stage HCC.MethodThis retrospective study reviewed 449 patients with intrahepatic distant recurrent HCC after complete RFA for early-stage HCC. After excluding 100 patients who were beyond Milan criteria, with incomplete lab data, or had follow-up less than three months, a total of 349 patient cases were compiled and their baseline characteristics, further treatment modalities after tumor recurrence and survival were analyzed.ResultsAfter a median follow-up of 36.2 months, 92 patients had expired. The majority of patients were male (59.9%) with a median age of 64.3 years (range:38-88). The cumulative 5-year overall survival (OS) rates after treatment for recurrent HCC was 67.2%. On multivariate analysis, end-stage renal disease(Hazard ratio (H.R.) = 2.33, p = 0.021), m-ALBI grade 2a (H.R. = 2.86, p = 0.003) and m-ALBI grades 2b or 3 (H.R. = 2.30, p = 0.009), APRI greater than 1 (H.R. = 1.92, p = 0.036) and 2nd recurrence occurring within 1 year (H.R. = 2.69, p<0.001) were significantly associated with worse survival. The cumulative 5-year 2nd recurrence rate was 87.4%. On multivariate analysis, male gender (H.R. = 1.47, p = 0.01), age greater than 65 years (H.R. = 1.72, p<0.001), an alpha fetoprotein level greater than 20ng/ml (H.R. = 1.41, p = 0.016), surgical treatment for recurrent HCC (H.R. = 0.25, p = 0.007), tumor number greater than 1 (H.R. = 1.35, p = 0.046), and IDR developing within 2 years (H.R. = 1.67, p = 0.001) were prognostic factors for 2nd recurrence.ConclusionOur study suggested that presence of end-stage renal disease, m-ALBI grades 2 and 3, APRI >1 and time to 2nd HCC recurrence were all associated with overall survival while the 2nd HCC recurrence was associated with male gender, age ≥65 years, α-fetoprotein level >20 ng/mL, non-surgical therapy, time to IDR, and tumor number> 1.

Project description:BACKGROUND:To date, no standard follow-up guidelines exist regarding patients receiving ablation for initial recurrent hepatocellular carcinoma (HCC). We aimed to explore whether intensive follow-up could benefit these patients. METHODS:We reviewed the clinical data of patients who received complete ablation for initial HCC recurrence after curative treatments in our institution from January 2005 to June 2017. Risk factors for second recurrence of HCC were identified by univariate and multivariate analyses. Patients were classified into low- and high-risk groups according to the outcome of the classification and regression model. The patients were further categorized into short- (< 3 months) and long-interval (3-6 months) follow-up subgroups based on their surveillance in the first 2 years after complete ablation for initial recurrence. The Kaplan-Meier method with log-rank test was performed to compare the overall survival (OS) based on follow-up intervals in each risk group. We also validated our results by stratifying patients into subgroups with different numbers of risk factors and comparing the OS between patients with different follow-up intervals. RESULTS:A total of 361 patients were enrolled. The risk factors for secondary recurrence included the Barcelona Clinic Liver Cancer (BCLC) stage at initial recurrence and first recurrence-free survival after curative treatments for primary HCC (p < 0.001 and p = 0.002). Two risk groups (low and high) were identified. In both the low- and high-risk groups, the OS of patients was not associated with intervals of follow-up (p = 0.29 and 0.49). No significant difference was found in the rates of BCLC 0/A stage, tumor location or curative treatments for the second recurrence by different follow-up intervals in each risk group (p = 0.34 and 0.87; p = 0.69 and 0.97). The same tendency was found in subgroups with 0/1/2 risk factors for secondary recurrence during validation. CONCLUSION:The long-interval follow-up did not compromise the survival of patients with complete ablation for initial recurrent HCC.

Dataset Information

Threatment Strategies for Recurrent Hepatocellular Carcinoma Patients: Ablation and its Combination Patterns.

Publications

Threatment Strategies for Recurrent Hepatocellular Carcinoma Patients: Ablation and its Combination Patterns.

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