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Advanced hepatocellular carcinoma treated by radiofrequency ablation combined with oncolytic virus and anti-PD-1 antibody therapy: a case report and literature review.

ABSTRACT: The development of an effective therapy for advanced hepatocellular carcinoma (HCC) represents an important global concern. In recent years, the combination of multiple treatment methods with immunotherapy has achieved great progress in patients with advanced HCC. Patient survival has been significantly prolonged, but cases of complete response (CR) remain rare. Here, we report two cases in which CR was achieved by radiofrequency ablation combined with an oncolytic virus (recombinant human adenovirus type 5) and anti-programmed cell death protein 1 antibody. Additionally, a literature review is presented to describe similar advancements in this field and explore viable methods for the treatment of advanced HCC.

SUBMITTER: Xie A

PROVIDER: S-EPMC8485298 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma: Current status.

Project description:Radiofrequency ablation (RFA) is widely accepted as a first-line interventional oncology approach for hepatocellular carcinoma (HCC) and has the advantages of high treatment efficacy and low complication risk. Local control rates equivalent to hepatic resection can be reached by RFA alone when treating small HCCs (<2?cm) in favorable locations. However, local tumor progression and recurrence rates with RFA monotherapy increase sharply when treating larger lesions (>3?cm). To address this clinical problem, recent efforts have focused on multimodel management of HCC by combining RFA with different techniques, including percutaneous ethanol injection, transarterial chemo-embolization, targeted molecular therapy, nanoparticle-mediated therapy, and immunotherapy. The combination strategy indeed leads to better outcomes in comparison to RFA alone. In this article, we review the current status of RFA-combined multimodal therapies in the management of HCC.

| S-EPMC4686130 | biostudies-literature

Transarterial Chemoembolization Combined with Radiofrequency Ablation in the Treatment of Stage B1 Intermediate Hepatocellular Carcinoma.

Project description:Background:Due to the heterogeneity of patients with Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC), Bolondi criteria were proposed and patients were divided into four substages. The purpose of this study was to compare the survival of substage B1 patients who were initially treated with a combination of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (TACE-RFA) or TACE alone. Methods:404 patients with stage B1 HCC were retrospectively analyzed from January 2005 to December 2012. 209 patients received TACE-RFA, and 195 received TACE alone as initial treatment. The overall survival (OS) and progression-free survival (PFS) rates were estimated by the Kaplan-Meier method and compared by the log-rank test. Results:1-, 3-, and 5-year OS rates were 83.7%, 45.8%, and 24.8% in the TACE-RFA group and 80.7%, 26.4%, and 16.7% in the TACE group, respectively (P=0.003). The corresponding PFS rates were 71.8%, 26.6%, and 13.0% and 59.1%, 11.0%, and 2.2% in the TACE-RFA group and TACE group, respectively (P < 0.001). Multivariate regression analysis indicated that tumor size (OS: hazard ratio (HR)?=?0.683, P=0.001; PFS: HR?=?0.761, P=0.013), along with treatment allocation (OS: HR?=?0.701, P=0.003; PFS: HR?=?0.620, P < 0.001), was the independent prognostic factor for both OS and PFS. Conclusions:Combination TACE and RFA treatment yielded better survival than TACE alone for patients with stage B1 HCC according to the Bolondi criteria.

| S-EPMC6766138 | biostudies-literature

Efficacy and Safety of Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization for Hepatocellular Carcinomas Compared with Radiofrequency Ablation Alone: A Time-to-Event Meta-Analysis.

Project description:To compare the efficacy and safety of combined radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA alone for hepatocellular carcinomas (HCC).Randomized controlled trial (RCT) studies that compared the clinical or oncologic outcomes of combination therapy of TACE and RFA versus RFA for the treatment of HCC were identified through literature searches of electronic databases (Pubmed, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, and Google Scholar). Hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95% confidence interval (CI) were combined as the effective value to assess the summary effects. The strength of evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation system.Six RCTs with 534 patients were eligible for inclusion in this meta-analysis. The meta-analysis showed that the combination of TACE and RFA is associated with a significantly longer overall survival (HR = 0.62, 95% CI: 0.49-0.78, p < 0.001) and recurrence-free survival (HR = 0.55, 95% CI: 0.40-0.76, p < 0.001) in contrast with RFA monotherapy. The seemingly higher incidence of major complications in the combination group compared with RFA group did not reach statistical significance (OR = 1.17, 95% CI: 0.39-3.55, p = 0.78).In patients with HCC, the combination of TACE and RFA is associated with significantly higher overall survival and recurrence-free survival, as compared with RFA monotherapy, without significant difference in major complications.

| S-EPMC4720818 | biostudies-other

Clinical application of autologous tumor infiltrating lymphocytes combined with anti-PD-1 antibody in the treatment of advanced hepatocellular carcinoma

Project description:To study the safety and efficacy of clinical application of autologous tumor infiltrating lymphocytes (TIL) after in vitro amplification，in combination with anti-PD-1 monoclonal antibody for the treatment of advanced hepatocellular carcinoma (HCC)

2023-02-01 | GSE220670 | GEO

Comparison of dexmedetomidine vs. remifentanil combined with sevoflurane during radiofrequency ablation of hepatocellular carcinoma: a randomized controlled trial.

Project description:BackgroundRemifentanil is widely used for ultrasound-guided percutaneous radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC). We determined whether dexmedetomidine could be an alternative to remifentanil for RFA of HCC under general anesthesia with sevoflurane.MethodsWe prospectively randomized patients scheduled to undergo RFA for HCC to a dexmedetomidine (DEX) group or remifentanil (REMI) group (47 patients each). In the DEX group, a bolus infusion (0.4 ?g kg-?1) was started 15 min before anesthesia induction and continued at 0.2 ?g kg-?1 h-?1 until 10 min before the end of surgery. In the REMI group, 3 ?g kg-?1 h-?1 of remifentanil was administered from 15 min before anesthesia induction to the end of the surgery. The primary endpoint was postoperative pain intensity. Secondary endpoints included analgesic requirement, postoperative liver function, patient comfort, and hemodynamic changes. Group allocation was concealed from patients and data analysts but not from anesthesiologists.ResultsPostoperative pain intensity, analgesic consumption, comfort, liver function, and time to emergence and extubation did not differ between the two groups. Heart rate, but not mean arterial pressure, was significantly lower in the DEX group than in the REMI group, at 1 min after intubation and from 30 min after the start of the surgery until anesthesia recovery. Sevoflurane concentration and dosage were significantly lower in the DEX group than in the REMI group.ConclusionDuring RFA for HCC, low-dose dexmedetomidine reduced the heart rate and need for inhalational anesthetics, without exacerbating postoperative discomfort or liver dysfunction. Although it did not exhibit outstanding advantages over remifentanil in terms of pain management, dexmedetomidine could be a safe alternative adjuvant for RFA under sevoflurane anesthesia.Trial registrationChinese Clinical Trial Registry, ChiCTR-OPC-15006613 . Registered on 16 June 2015.

| S-EPMC6326039 | biostudies-literature

Transcriptomics characterization of hepatocellular carcinoma (HCC) after incomplete radiofrequency ablation (iRFA)

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2022-09-05 | GSE212604 | GEO

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Project description:G47Δ is a triple-mutated oncolytic herpes simplex virus type 1 designed to induce antitumor immune responses efficiently. We examine the usefulness of G47Δ as a neoadjuvant therapy for radiofrequency ablation (RFA), a standard local treatment for certain cancers such as liver cancer, but remote recurrences within the same organ often occur. In A/J mice harboring bilateral subcutaneous Neuro2a tumors, the left tumors were treated with G47Δ intratumoral injections followed by RFA. Whereas the RFA-treated tumors were all eradicated, the growth of the right tumors was evaluated and tumor-infiltrating lymphocytes were analyzed. The G47Δ+RFA treatment caused smaller volumes of right tumors, accompanied by increased CD8+/CD45+ T cells, compared with G47Δ monotherapy. After depletion of CD8+ T cells, the enhanced efficacy on the contralateral tumors was completely abolished. Neoadjuvant G47Δ led to rejection of rechallenged tumors, which was caused by efficient induction of specific antitumor immune responses shown by enzyme-linked immunospot (ELISPOT) assays. Treatment of tumor-harboring animals with an anti-programmed cell death 1 ligand 1 (PD-L1) antibody led to even greater efficacy on contralateral tumors. Our study indicates that the neoadjuvant use of G47Δ effectively enhances the efficacy of RFA via CD8+ T cell-dependent immunity that is further augmented by an immune checkpoint inhibitor.

| S-EPMC7501409 | biostudies-literature

N7-Methylguanosine tRNA modification promotes hepatocellular carcinoma metastasis after insufficient radiofrequency ablation

Project description:Radiofrequency heat ablation is an ideal radical cure for HCC treatment; however, insufficient radiofrequency ablation (IRFA) could lead to a high recurrence rate. N7-methylguanosine (m7G) on tRNAs is a heat-responding modification that is critical for yeast survival under high temperature, while its function and mechanism in HCC recurrence after IRFA are unknown. Here, we found that IRFA significantly up-regulates the level of m7G tRNA modification and its methyltransferase complex components METTL1 and WDR4 in multiple systems including HCC patient-derived xenograft (PDX) mouse, HCC tissues of patients, sublethal-heat-treated models of HCC cell lines and organoids. Functionally, gain- or loss-of function assays showed that METTL1 mediated m7G tRNA modification promotes HCC metastasis under sublethal heat exposure both in vitro and in vivo. Mechanistically, we found that METTL1 and m7G tRNA modification enhance the translation of SLUG and SNAIL in a codon frequency dependent manner under sublethal heat exposure. Overexpression of SLUG and SNAIL rescued the malignant potency of METTL1 knockdown HCC cells after sublethal heat stress. Our study uncovers the important physiological functions of m7G tRNA modification in heat stress responses and HCC recurrence after IRFA and suggests that targeting METTL1-m7G-SLUG and SNAIL axis could be a promising strategy to prevent HCC metastasis after radiofrequency heat ablation treatment.

2022-11-20 | GSE199966 | GEO

PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses against Tumor.

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| S-EPMC4780056 | biostudies-literature

Scientific Rationale for Combined Immunotherapy with PD-1/PD-L1 Antibodies and VEGF Inhibitors in Advanced Hepatocellular Carcinoma.

Project description:A successful phase III trial for the combination of atezolizumab and bevacizumab (the IMbrave150 trial) in advanced hepatocellular carcinoma has recently been reported. This is groundbreaking because nivolumab and pembrolizumab, both programmed cell death-1 (PD-1) antibodies, have failed to show efficacy as first- and second-line therapeutics, respectively, in phase III clinical trials. Immunotherapy with a combination of atezolizumab and bevacizumab resulted in better survival than treatment with sorafenib for the first time since sorafenib was approved in 2007. The high efficacy of the combination of PD-1/programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) antibodies is not only due to their additive effects on tumor growth, but also to their reprogramming of the immunosuppressive microenvironment into an immunostimulatory microenvironment. These results were confirmed in a phase Ib trial that showed significantly longer progression-free survival in the atezolizumab plus bevacizumab group than in patients that received atezolizumab alone. These results demonstrate that immunotherapy with a combination of PD-1/PD-L1 and VEGF inhibitors is effective and may result in a reprogramming of the tumor microenvironment. The results of an ongoing phase III trial of a PD-1 antibody in combination with the VEGF receptor tyrosine kinase inhibitor (TKI) are highly anticipated.

| S-EPMC7281246 | biostudies-literature

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