Transarterial Chemoembolization Therapy Research Articles

Pseudo-capsulated Hepatocellular Carcinoma: Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization

The effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) for cases with single pseudo-capsuled hepatocellular carcinoma (pHCC), as well as their survival outcomes, were investigated. A total of 196 cases with single pHCC (diameter >5cm) receiving initial HAIC (n=92) and TACE (n=104) were enrolled. The propensity score match (PSM) approach based on Cox models was employed to tune any possible imbalance in treatment assignment. The overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and partial response rate (PRR) of the subjects were investigated using the log-rank test. The independent risk factors for outcomes were investigated by univariate and multivariate analyses, and the results were analyzed using the Cox regression model. The median follow-up of the subjects was 22.3 months. After PSM, no significant difference was found in the OS of the HAIC and TACE groups (OS, 12.0 vs. 16.8 months; P=.267), while the median PFS of the TACE group was prolonged compared with the HAIC group (PFS, 5.7 vs. 2.8 months; P=.003). Moreover, PRR and ORR of the TACE group were prolonged compared with the HAIC group (PRR, 34.6% vs. 21.7%; P=.046; ORR, 35.6% vs. 21.7%; P=.033). The nomogram model showed high predictive accuracy and significant discrimination. TACE therapy could delay tumor progression compared with HAIC for cases with a single pHCC.

Risk of Hepatic Artery Complications After Liver Transplantation in Patients Who Received Pretransplant Transarterial Chemoembolization Therapy: A Single-Center Experience

Pretransplant transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has been associated with an increased risk of hepatic artery thrombosis (HAT) after liver transplantation (LT). Innovative surgical LT and interventional vascular radiology TACE techniques may mitigate the risk of HAT. We sought to investigate the incidence of HAT after LT in patients who received pre-transplant TACE at our center. We performed a single-center retrospective review of all LT patients, >18 years of age, from October 1, 2012, to May 31, 2018. Outcomes were compared between patients who received pre-LT TACE and those who did not. Median follow-up was 26 months. Among the 162 LT recipients, 110 (67%) patients did not receive pre-LT TACE (Group I), while 52 (32%) received pre-LT TACE (Group II). The <30-day incidence rates of post-LT HAT were as follows: Group I=1.8% and Group II=1.9% (P=.9). Most hepatic arterial complications occurred >30 days after LT. Based on competing risks regression analysis, TACE was not associated with an increased risk of HAT. Patient or graft survivals were comparable between the 2 groups (P=.1 and .2, respectively). Our study shows a similar incidence of hepatic artery complications post-LT in patients who received TACE before LT compared with those who did not. In addition, we suggest that the surgical technique of early vascular control of the common hepatic artery during LT, in combination with a super-selective vascular intervention radiology approach, has clinical utility in reducing the risk of HAT in patients requiring pre-transplant TACE.

A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma: TACTICS-L Trial

Introduction: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14–21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0–2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0–1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1–31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months–NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

The course and prognostic value of tumor stiffness detected by ultrasound elastography for transarterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is recommended as the first-line treatment in intermediate-stage patients with hepatocellular carcinoma (HCC) or as a palliative treatment modality in advanced patients. However, tumor control usually requires multiple TACE interventions due to the presence of residual and recurrent lesions. Elastography can provide information about tumor stiffness (TS) to predict tumor residual or recurrence. In this study, we aimed to analyze the effects of TACE on HCC stiffness using ultrasound elastography (US-E). We investigated whether quantifying TS using US-E could predict the recurrence of HCC. This retrospective cohort study included 116 patients undergoing TACE to treat HCC. US-E was performed to measure the tumor's elastic modulus within 3 days before TACE, in the 2 days after the intervention, and at the 1-month follow-up. The known prognostic factors of HCC were also analyzed. The average TS before TACE was 40.1±14.36 kPa, and the average TS 1 month after TACE was 19.3±9.80 kPa. The mean progression-free survival (PFS) was 39.129 months, and the 1-, 3-, and 5-year PFS rates were 81.0%, 56.9%, and 37.9%, respectively. The mean overall survival (OS) was 48.552 months, and the 1-, 3-, and 5-year OS rates of patients with malignant hepatic tumors were 95.7%, 75.0%, and 49.1%, respectively. Tumor number, tumor location, TS before TACE, and TS 1 month after TACE were significant predictive factors for OS (P=0.02, P=0.03, P<0.001, and P<0.001, respectively). Rank correlation analysis and linear regression revealed that a higher TS before or 1 month after TACE was negatively associated with PFS. The reduction ratio in TS before and 1 month after therapy was positively associated with PFS. The optimal cutoff TS value was set at 46 and 24.5 kPa before and 1 month after TACE according to the optimal Youden index. Kaplan-Meier survival analyses demonstrated that the 2 groups had significant differences in OS and PFS and that a higher TS was positively correlated with OS and PFS. Our results verify that US-E provides additional information to characterize the tumoral stiffness of HCC. These findings indicate that US-E is a valuable tool for evaluating the tumor response after TACE therapy in patients. TS can also be an independent prognostic factor. Patients with a high TS had a higher risk of recurrence and a worse survival time.

Local Therapies for Hepatocellular Carcinoma and Role of MRI-Guided Adaptive Radiation Therapy.

Hepatocellular carcinoma (HCC) is the most common liver tumor, with a continually rising incidence. The curative treatment for HCC is surgical resection or liver transplantation; however, only a small portion of patients are eligible due to local tumor burden or underlying liver dysfunction. Most HCC patients receive nonsurgical liver-directed therapies (LDTs), including thermal ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and external beam radiation therapy (EBRT). Stereotactic ablative body radiation (SABR) is a specific type of EBRT that can precisely deliver a high dose of radiation to ablate tumor cells using a small number of treatments (or fractions, typically 5 or less). With onboard MRI imaging, MRI-guided SABR can improve therapeutic dose while minimizing normal tissue exposure. In the current review, we discuss different LDTs and compare them with EBRT, specifically SABR. The emerging MRI-guided adaptive radiation therapy has been reviewed, highlighting its advantages and potential role in HCC management.

Radiomic advances in the transarterial chemoembolization related therapy for hepatocellular carcinoma.

Radiomics is a hot topic in the research on customized oncology treatment, efficacy evaluation, and tumor prognosis prediction. To achieve the goal of mining the heterogeneity information within the tumor tissue, the image features concealed within the tumoral images are turned into quantifiable data features. This article primarily describes the research progress of radiomics and clinical-radiomics combined model in the prediction of efficacy, the choice of treatment modality, and survival in transarterial chemoembolization (TACE) and TACE combination therapy for hepatocellular carcinoma.

The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB.

Aim: To analyze the safety of immune checkpoint inhibitors in primary liver cancer patients and to identify the risk factors for immune-related adverse events (irAEs). Methods: The study enrolled 106 patients with primary liver cancer, including 81 with hepatocellular carcinoma and 25 with intrahepatic cholangiocarcinoma. We analyzed the differences between groups in irAE occurrence, including those with and without targeted drugs and those who received interventional therapy. Results: The incidence of irAEs was 39%, with thyroid function, liver function, and skin events being the most common. There was no correlation among irAE incidence and the liver cancer type, stage, or severity; grade of Child-Pugh score; and Barcelona Clinical Liver Cancer classification. However, being overweight was a significant risk factor for irAEs, correlating with high body mass index. The combination of targeted drugs and/or transcatheter arterial chemoembolization therapy did not increase the incidence of irAEs. Conclusion: Being overweight is a potential risk factor for irAEs in primary liver cancer patients. However, there is no correlation between irAE incidence and the liver cancer type, stage, or severity or a combination of targeted drugs or transarterial chemoembolization therapy.

Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma.

To compare the clinical benefit and tolerability of triple therapy of lenvatinib, programmed death 1 (PD-1) inhibitor, and transarterial chemoembolization (TACE) versus dual therapy of lenvatinib and PD-1 inhibitor in unresectable hepatocellular carcinoma (HCC) patients. Between October 2018 and September 2021, patients with unresectable HCC who received triple therapy of lenvatinib, PD-1 inhibitor, and TACE or dual therapy of lenvatinib and PD-1 inhibitor participated in this study. The efficacy was evaluated by survival and therapeutic response, and the tolerability was evaluated by the frequency and severity of key adverse events (AEs). In total, 118 eligible patients with unresectable HCC who received combination therapy were included in this study. Among them, 60 patients received triple therapy of lenvatinib, PD-1 inhibitor, and TACE (L-P-T group), and 58 eligible patients received dual therapy of lenvatinib and PD-1 inhibitor (L-P group). Patients who received triple therapy had better overall survival (OS) [median, 29.0 vs. 17.8months, p < 0.01] and progression-free survival (PFS) [median, 16.2 vs. 10.2months, p < 0.01] than those who received dual therapy. The objective response rate (76.7 vs. 44.9%, p < 0.01) and disease control rate (96.7 vs. 75.9%, p < 0.01) in the L-P-T group were higher than in the L-P group, respectively. Multivariate analyses revealed that the treatment option and BCLC stage were independent prognostic factors for OS, while treatment option and tumor number were independent prognostic factors for PFS. The incidence and severity of AEs in the L-P-T group were comparable to those in the L-P group (any grade, 95.0 vs. 94.8%, p = 1.00; grade ≥ 3, 30.0 vs. 27.6%, p = 0.93). Triple therapy of lenvatinib, PD-1 inhibitor, and TACE may achieve more favorable survival benefits than dual therapy of lenvatinib and PD-1 inhibitor in unresectable HCC patients with manageable safety profiles.

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment.

The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0-4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

An exosome-related lncRNA signature correlates with prognosis, immune microenvironment, and therapeutic responses in hepatocellular carcinoma

BackgroundExosomes act as essential modulators of cancer development and progression in hepatocellular carcinoma. However, little is known about the potential prognostic value and underlying molecular features of exosome-related long non-coding RNAs. MethodsGenes associated with exosome biogenesis, exosome secretion, and exosome biomarkers were collected. Exosome-related lncRNA modules were identified using PCA and WGCNA analysis. A prognostic model based on data from the TCGA, GEO, NODE, and ArrayExpress was developed and validated. A comprehensive analysis of the genomic landscape, functional annotation, immune profile, and therapeutic responses underlying the prognostic signature was performed on multi-omics data, and bioinformatics methods were also applied to predict potential drugs for patients with high risk scores. qRT-PCR was used to validate the differentially expressed lncRNAs in normal and cancer cell lines. ResultsTwenty-six hub lncRNAs were identified as highly correlated with exosomes and overall survival and were used for prognosis modeling. Three cohorts consistently showed higher scores in the high-risk group, with an AUC greater than 0.7 over time. These higher scores implied poorer overall survival, higher genomic instability, higher tumor purity, higher tumor stemness, pro-tumor pathway activation, lower anti-tumor immune cell and tertiary lymphoid structure infiltration, and poor responses to immune checkpoint blockade therapy and transarterial chemoembolization therapy. ConclusionThrough developing an exosome-related lncRNA predictor for HCC patients, we revealed the clinical relevance of exosome-related lncRNAs and their potential as prognostic biomarkers and therapeutic response predictors.

Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma.

Programmed death receptor-1 (PD-1) inhibitors have been approved as second-line treatment regimen in hepatocellular carcinoma (HCC), but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy. To estimate the clinical outcome of transarterial chemoembolization (TACE) and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC (uHCC). We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022. 45 patients received the PD-1 inhibitors, lenvatinib, TACE (PD-1-Lenv-T) therapy, and 20 received the lenvatinib, TACE (Lenv-T) therapy. In terms of the dose of lenvatinib, 8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg. Of the patients in the PD-1 inhibitor combination group, 15 received Toripalimab, 14 received Toripalimab, 14 received Camrelizumab, 4 received Pembrolizumab, 9 received Sintilimab, and 2 received Nivolumab, 1 with Tislelizumab. According to the investigators' assessment, TACE was performed every 4-6 wk when the patient had good hepatic function (Child-Pugh class A or B) until disease progression occurred. We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors (mRECIST criteria). We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0. The key adverse events (AEs) after the initiation of combination therapy were observed. Patients with uHCC who received PD-1-Lenv-T therapy (n = 45) had a clearly longer overall survival than those who underwent Lenv-T therapy (n = 20, 26.8 vs 14.0 mo; P = 0.027). The median progression-free survival time between the two treatment regimens was also measured {11.7 mo [95% confidence interval (CI): 7.7-15.7] in the PD-1-Lenv-T group vs 8.5 mo (95%CI: 3.0-13.9) in the Lenv-T group (P = 0.028)}. The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4% and 20% (P = 0.059) according to the mRECIST criteria, meanwhile the disease control rates were 93.3% and 64.0% (P = 0.003), respectively. The type and frequency of AEs showed little distinction between patients received the two treatment regimens. Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.

Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials.

TREM2+ macrophages suppress CD8+ T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma

The immune landscape of hepatocellular carcinoma (HCC) following transarterial chemoembolisation (TACE) remains to be clarified. This study aimed to characterise the immune landscape following TACE and the underlying mechanism of HCC progression. Tumour samples from five patients with treatment-naive HCC and five patients who received TACE therapy were collected and subjected to single-cell RNA sequencing. Another 22 paired samples were validated using immunofluorescence staining and flow cytometry. To clarify the underlying mechanisms, invitro co-culture experiments and two types of TREM2-KO/WT mouse models, namely, an HCC cell orthotopic injection model and a spontaneous HCC model, were used. A reduced number of CD8+ T cells and an increased number of tumour-associated macrophages (TAMs) were observed in the post-TACE microenvironment. TACE therapy reduced the cluster CD8_C4, which was highly enriched with tumour-specific CD8+ T cells of pre-exhausted phenotype. TREM2 was found to be highly expressed in TAMs following TACE, which was associated with a poor prognosis. TREM2+ TAMs secreted less CXCL9 but more galectin-1 than did TREM2- TAMs. Galectin-1 promoted PD-L1 overexpression in vessel endothelial cells, impeding CD8+ T cell recruitment. TREM2 deficiency also increased CD8+ T cell infiltration, which inhibited tumour growth in both invivo HCC models. More importantly, TREM2 deficiency enhanced the therapeutic effect of anti-PD-L1 blockade. This study shows that TREM2+ TAMs play an important role in suppressing CD8+ T cells. TREM2 deficiency increased the therapeutic effect of anti-PD-L1 blockade by enhancing antitumour activity of CD8+ T cells. These findings explain the reasons for recurrence and progression after TACE and provide a new target for HCC immunotherapy after TACE. Studying the immune landscape in post-TACE HCC is important to uncover the mechanisms of HCC progression. By using scRNA sequencing and functional assays, we discovered that both the number and function of CD8+ T cells are compromised, whereas the number of TREM2+ TAMs is increased in post-TACE HCC, correlating with worse prognosis. Moreover, TREM2 deficiency dramatically increases CD8+ T cell infiltration and augments the therapeutic efficacy of anti-PD-L1 blockade. Mechanistically, TREM2+ TAMs display lower CXCL9 and increased Gal-1 secretion than do TREM2- TAMs, with Gal-1 mediating the overexpression of PD-L1 in vessel endothelial cells. These results suggest that TREM2 could be a novel immunotherapeutic target for patients treated with TACE in HCC. This provides an opportunity to break the plateau of limited therapeutic effect. This study has the value of understanding the tumour microenvironment of post-TACE HCC and thinking a new strategy of immunotherapy in the field of HCC. It is therefore of key impact for physicians, scientists and drug developers in the field of liver cancer and gastrointestinal oncology.

The Allelic Expression of RNA Editing Gene ADARB1 in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE. In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes (ADARB1, ADAR, ADARB2 and AIMP2) in two independent TACE patient cohorts. We found that ADARB1 rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in ADARB1 3'-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated ADARB1 levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced ADARB1 expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic ADARB1 profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs. Our findings highlighted the value of ADARB1 polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.

Stronger Neo‐Minophagen C (SNMC): A stronger adjuvant for TACE?

Stronger <scp>Neo‐Minophagen</scp> C (<scp>SNMC</scp>): A stronger adjuvant for <scp>TACE</scp>?

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (<3 cm) Nonfunctional Pancreatic Neuroendocrine Tumors?

Autophagy-Targeted Calcium Phosphate Nanoparticles Enable Transarterial Chemoembolization for Enhanced Cancer Therapy.

Transarterial chemoembolization (TACE) is commonly used for treating advanced hepatocellular carcinoma (HCC). However, the instability of lipiodol-drug emulsion and the altered tumor microenvironment (TME, such as hypoxia-induced autophagy) postembolization are responsible for the unsatisfactory therapeutic outcomes. Herein, pH-responsive poly(acrylic acid)/calcium phosphate nanoparticles (PAA/CaP NPs) were synthesized and used as the carrier of epirubicin (EPI) to enhance the efficacy of TACE therapy through autophagy inhibition. PAA/CaP NPs have a high loading capacity of EPI and a sensitive drug release behavior under acidic conditions. Moreover, PAA/CaP NPs block autophagy through the dramatic increase of intracellular Ca2+ content, which synergistically enhances the toxicity of EPI. TACE with EPI-loaded PAA/CaP NPs dispersed in lipiodol shows an obvious enhanced therapeutic outcome compared to the treatment with EPI-lipiodol emulsion in an orthotopic rabbit liver cancer model. This study not only develops a new delivery system for TACE but also provides a promising strategy targeting autophagy inhibition to improve the therapeutic effect of TACE for the HCC treatment.

Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.

Multimodality annotated hepatocellular carcinoma data set including pre- and post-TACE with imaging segmentation

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm, and its incidence has doubled over the past two decades owing to increasing risk factors. Despite surveillance, most HCC cases are diagnosed at advanced stages and can only be treated using transarterial chemo-embolization (TACE) or systemic therapy. TACE failure may occur with incidence reaching up to 60% of cases, leaving patients with a financial and emotional burden. Radiomics has emerged as a new tool capable of predicting tumor response to TACE from pre-procedural computed tomography (CT) studies. This data report defines the HCC-TACE data collection of confirmed HCC patients who underwent TACE and have pre- and post-procedure CT imaging studies and available treatment outcomes (time-to-progression and overall survival). Clinically curated segmentation of pre-procedural CT studies was done for the purpose of algorithm training for prediction and automatic liver tumor segmentation.

Systemtherapie des hepatozellulären Karzinoms: mehr als eine „palliative“ Therapie?

BackgroundMost patients with hepatocellular carcinoma (HCC) are diagnosed in advanced stages where treatment with curative intent is no longer possible. Because of the low efficacy of cytotoxic chemotherapies in HCC, effective systemic therapies were not available for many years. In 2008, the approval of the tyrosine kinase inhibitor (TKI) sorafenib ended this era. Since then, several further substances such as TKIs, anti-VEGF antibodies and immunotherapeutics have proven their efficacy in the treatment of advanced HCC. Here the advent of immune checkpoint inhibitors (CPIs) in particular represented a major advance in systemic therapy for HCC.ObjectivesIn this work, we provide an overview of the development of systemic therapy for HCC.Materials and methodsRelevant articles were identified in public databases. Clinical trial information was obtained from the Clinicaltrials.gov trial registry. Reported drug approvals were obtained from publicly available information of the European Medicines Agency and the U.S. Food and Drug Administration.ConclusionsCPI-based combination therapies have revolutionized the treatment of HCC. In clinical trials, which led to approval, good efficacy was observed in the form of significantly higher objective antitumoral responses compared to sorafenib, which translated to long-term survival that had not been previously attained. Current clinical trials are investigating the use of CPI with transarterial chemoembolization or other local therapies for earlier tumor stages, as well as new CPI-based combination therapies. These efforts may help to further improve the prognosis of patients with HCC. Inclusion of HCC patients in these clinical trials is therefore highly recommended.