A study comparing the cost-effectiveness of conventional and drug-eluting transarterial chemoembolisation (cTACE and DEB-TACE) for the treatment of hepatocellular carcinoma in an Australian public hospital.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and transarterial chemoembolisation (TACE) is an established technique to treat patients with intermediate-stage HCC. The aim of this study was to generate accurate costing data on cTACE and DEB-TACE in an Australian setting and assess whether one of the procedures offers favourable cost-effectiveness. METHODS: Costing study using data from all TACE procedures performed at a single centre between January 2018 and December 2022. Data were included from all direct and indirect costs including operative costs, wages, overheads, ward costs, transfusion, pathology, pharmacy and ward support. Cost-effectiveness was assessed by dividing local costs by existing high-quality data on quality-adjusted life years (QALYs). RESULTS: 64 TACE treatments were performed on 44 patients. Mean age was 66.5 years and 91% were male. Overall median total cost per patient for the entire TACE treatment regime was AUD$7380 (range AUD$3719-$20,258). However, 39% of patients received more than one treatment, and the median cost per individual treatment was AUD$5270 (range AUD$3533-$15,818). The difference in median cost between cTACE (AUD$4978) and DEB-TACE (AUD$9202) was significant, P < 0.001. In calculating cost-effectiveness, each cTACE treatment cost AUD$2489 per QALY gained, while each DEB-TACE cost AUD$3834 per QALY gained. The incremental cost-effectiveness ratio (ICER) for DEB-TACE over cTACE was AUD$10,560 per QALY gained. CONCLUSION: Both cTACE and DEB-TACE are low-cost treatments in Australia. However, DEB-TACE offers a solution with an ICER of AUD$10,560 per QALY gained which is below the Australian government willingness to pay threshold and thus is a more cost-effective treatment.

Transarterial chemoembolization using drug-eluting beads versus lipiodol in the treatment of unresectable hepatocellular carcinoma: propensity score matching.

Background: Since the introduction of drug-eluting beads (DEB), the result comparing transarterial chemoembolization (TACE) using lipiodol, also called conventional transarterial chemoembolization (c-TACE), and DEB-TACE shows considerable controversy. The objective of this study was to compare the safety and efficacy of c-TACE and DEB-TACE to treat unresectable hepatocellular carcinoma (uHCC). Methods: This retrospective study used propensity score matching (PSM) analysis to analyze clinical data from 113 cases of primary hepatocellular carcinoma (HCC) treated at our hospital from September 2016 to July 2021. The safety and efficacy of the two treatment modalities were analyzed after 1:1 matching. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS), disease control rates (DCRs), and objective response rates (ORRs) at 1, 3, 6, and 12 months, and postoperative complications. Results: Twenty-nine patients underwent DEB-TACE and 84 received c-TACE; 28 pairs of patients were eventually matched. After matching, baseline characteristics between groups were comparable. The median PFS of the DEB-TACE group was 10 months compared to 6 months in the c-TACE group (P=0.002). The median OS was 23 months in the DEB-TACE group vs. 14 months in the c-TACE group, but the difference was not statistically significant (P=0.265). The ORR at 1, 3, 6, and 12 months in the DEB-TACE group (69%, 78%, 60%, and 52%) were significantly higher than those in the c-TACE group (39%, 39%, 26%, and 8%) (P<0.05). The DCR at postoperative 3 months was significantly higher in the DEB-TACE group (95%) (P<0.05). There was one case of postoperative liver abscess in the DEB-TACE group, and the patient recovered well after drainage. No serious complications occurred. Conclusions: Compared to c-TACE, DEB-TACE prolonged PFS and exhibited better short-term ORR with a similar level of safety. However, there was no significant advantage in terms of OS.

Prognosis comparison between hepatocellular carcinoma patients with microvascular invasion who received hepatectomy alone and those who underwent early PA-TACE: a retrospective cohort study.

Background: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) can achieve longer overall survival (OS) and disease-free survival (DFS) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). We investigated whether this treatment strategy could benefit these patients by mediating the dysfunctional immunological status. Therefore, a retrospective cohort study was conducted to investigate the effect of early PA-TACE in HCC patients with MVI by measuring the levels of T helper cell 17 (Th17) and regulatory T cell (Treg). Methods: This study retrospectively included 472 patients with HCC undergoing hepatectomy between December 2015 and December 2018, and 115 patients with MVI confirmed by postoperative pathology were enrolled and divided into two groups of TACE group and non-TACE group according to whether TACE was performed. HCC patients with MVI. The proportion of Treg and Th17 cells in peripheral blood was measured one day before and four weeks after TACE. All patients in the two groups were followed up until death or until the study ended in December 2023. The rates of OS and progression-free survival (PFS) in patients with MVI were compared between those who received hepatectomy alone and those who underwent early PA-TACE. Results: Among 115 HCC patients with MVI from 472 patients, the study enrolled 51 patients with PA-TACE into the TACE group and 42 patients without TACE into the non-TACE group. There were no statistical differences in baseline data between the two groups (all P>0.05). The frequency of Treg among CD4+ T cells in HCC patients with PA-TACE was significantly lower than baseline (7.34%±3.61% vs. 5.82%±2.76%, P<0.001), and the frequency of Th17 among CD4+ T cells in these patients was significantly higher than baseline (0.49%±0.28% vs. 0.50%±0.25%, P<0.001). Among all the patients, the median OS was 61.8 months. The OS rate and PFS rate at 12, 36, and 60 months in the TACE group were significantly higher than those in the non-TACE group (all P<0.05). Conclusions: PA-TACE may have roles in improving survival outcomes, and restoring immune homeostasis in HCC patients with MVI after hepatectomy.

Transcatheter arterial chemoembolization with tyrosine kinase inhibitor in the 12-year treatment of hepatic metastases from gastrointestinal stromal tumor: a case report.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract, with surgery and tyrosine kinase inhibitor (TKI) therapy being its main treatment options. However, long-term use of TKIs may lead to drug resistance, which poses a challenge to the long-term survival of patients. We explore a new combination of transcatheter arterial chemoembolization (TACE) with TKI for liver metastasis (LM) of GIST to provide patients with more treatment options and better prognosis. Case Description: This case report describes the application of 6 TACE sessions in the 12-year treatment of multiple LM from small intestinal stromal tumors that were resistant to multiple TKIs. The patient, a 58-year-old male, underwent multiple surgical resections and drug therapies for the LM after a primary small bowel stromal tumor had been identified and resected following an onset symptom of abdominal pain in February 2012. Despite the challenges of drug resistance and economic considerations, 6 TACE sessions effectively controlled the tumor, winning valuable treatment time for the patient. Since the initiation of ripretinib 150 mg once daily in July 2023, the tumor has continued to shrink, with satisfactory drug tolerance. Conclusions: For GIST patients with LM, TACE combined with various TKI drugs could effectively control intrahepatic tumor progression and prolong patient survival. During six TACE sessions, the patient experienced liver tumor rupture and massive bleeding. However, the bleeding was completely stopped by embolization, and the lesion shrank. Our findings provide a new perspective and treatment strategy for the treatment of LM from GIST.

Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

Case report: Drug-eluting bead transcatheter arterial chemoembolization in liver metastasis and retroperitoneal lymph node metastases of renal cell carcinoma: effective local therapy with the first report.

The liver is the fourth most common site of metastasis in renal cell carcinoma (RCC), which is usually treated with systemic therapies and local treatments. However, local treatments are challenging in RCC patients with liver metastasis who failed in first-line systemic therapy. Here, we report a case of a patient with both liver-dominant RCC metastasis and recurrence in the operative site who had failed in first-line targeted therapy plus immunotherapy, received drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE), and achieved a complete response.

Outcomes of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma: A tertiary center experience.

Objective: To assess the overall survival in patients with intermediate stage hepatocellular carcinoma following transarterial chemoembolization. Methods: It is a retrospective descriptive study carried out in the Department of Radiology of Liaquat National Hospital Karachi, Pakistan. Seventy-two patients were enrolled from July 2014 to December 2021 and had chemoembolization therapy. Patients were followed till their demise. Mean and Median survivals were calculated. Results: A total of 72 patients had a median survival of 15 months with 95% confidence interval (11 months was lower bound and 18 months was upper bound), 19 months was the mean survival time with 95% confidence interval (14.7 months was lower limit and 22.6 months the upper limit). The factors which had a significant impact on the median survival time were Child-Pugh classification, average size of tumor and embolization pattern. Conclusion: Transarterial chemoembolization (TACE) increases the median survival time effectively and safely in patients with hepatocellular carcinoma. However complete resolution of disease is not possible with TACE, with most patient eventually succumbing to the disease. The overall survival for TACE in this study correlates well with other studies. Child Pugh Class, tumor size and embolization pattern have significant effect on survival of patients.

Vessel-targeted compensation of deformable motion in interventional cone-beam CT.

The present standard of care for unresectable liver cancer is transarterial chemoembolization (TACE), which involves using chemotherapeutic particles to selectively embolize the arteries supplying hepatic tumors. Accurate volumetric identification of intricate fine vascularity is crucial for selective embolization. Three-dimensional imaging, particularly cone-beam CT (CBCT), aids in visualization and targeting of small vessels in such highly variable anatomy, but long image acquisition time results in intra-scan patient motion, which distorts vascular structures and tissue boundaries. To improve clarity of vascular anatomy and intra-procedural utility, this work proposes a targeted motion estimation and compensation framework that removes the need for any prior information or external tracking and for user interaction. Motion estimation is performed in two stages: (i) a target identification stage that segments arteries and catheters in the projection domain using a multi-view convolutional neural network to construct a coarse 3D vascular mask; and (ii) a targeted motion estimation stage that iteratively solves for the time-varying motion field via optimization of a vessel-enhancing objective function computed over the target vascular mask. The vessel-enhancing objective is derived through eigenvalues of the local image Hessian to emphasize bright tubular structures. Motion compensation is achieved via spatial transformer operators that apply time-dependent deformations to partial angle reconstructions, allowing efficient minimization via gradient backpropagation. The framework was trained and evaluated in anatomically realistic simulated motion-corrupted CBCTs mimicking TACE of hepatic tumors, at intermediate (3.0 mm) and large (6.0 mm) motion magnitudes. Motion compensation substantially improved median vascular DICE score (from 0.30 to 0.59 for large motion), image SSIM (from 0.77 to 0.93 for large motion), and vessel sharpness (0.189 mm-1 to 0.233 mm-1 for large motion) in simulated cases. Motion compensation also demonstrated increased vessel sharpness (0.188 mm-1 before to 0.205 mm-1 after) and reconstructed vessel length (median increased from 37.37 to 41.00 mm) on a clinical interventional CBCT. The proposed anatomy-aware motion compensation framework presented a promising approach for improving the utility of CBCT for intra-procedural vascular imaging, facilitating selective embolization procedures.

Incorporating Inflammatory Markers and Clinical Indicators into a Predictive Model of Single Small Hepatocellular Carcinoma Recurrence After Primary Locoregional Treatments.

Purpose: We explored the role of tumor size and number in the prognosis of HCC patients who underwent ablation and created a nomogram based on machine learning to predict the recurrence. Patients and Methods: A total of 990 HCC patients who underwent transcatheter arterial chemoembolization (TACE) combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were prospectively enrolled, including 478 patients with single small HCC (S-S), 209 patients with single large (≥30mm) HCC (S-L), 182 patients with multiple small HCC (M-S), and 121 patients with multiple large HCC (M-L). S-S patients were randomized in a 7:3 ratio into the training cohort (N=334) and the validation cohort (N=144). Lasso-Cox regression analysis was carried out to identify independent risk factors, which were used to construct a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves. Patients in the training and validation cohorts were divided into low-risk, intermediate-risk, and high-risk groups based on the risk scores of the nomogram. Results: The median recurrence-free survival (mRFS) in S-S patients was significantly longer than the S-L, M-S, and S-L patients (P<0.0001). The content of the nomogram includes age, monocyte-to-lymphocyte (MLR), gamma-glutamyl transferase-to-lymphocyte (GLR), International normalized ratio (INR), and Erythrocyte (RBC). The C-index (0.704 and 0.71) and 1-, 3-, and 5-year AUCs (0.726, 0.800, 0.780, and 0.752, 0.761, 0.760) of the training and validation cohorts proved the excellent predictive performance of the nomogram. Calibration curves the DCA curves showed that the nomogram had good consistency and clinical utility. There were apparent variances in RFS between the low-risk, intermediate-risk, and high-risk groups (P<0.0001). Conclusion: S-S patients who underwent ablation had the best prognosis. The nomogram developed and validated in the study had good predictive ability for S-S patients.

Elevated SLC1A5 associated with poor prognosis and therapeutic resistance to transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor, and glutamine is vital for tumor cells. The role of glutamine transporter SLC1A5 in tumor progression and transarterial chemoembolization (TACE) efficacy is under study. This research seeks to determine the impact of SLC1A5 expression on the prognosis and TACE efficacy of HCC and elucidate its mechanisms. METHODS: SLC1A5 expression in HCC, correlation with patient outcomes, and response to TACE were studied in an open access liver cancer dataset and confirmed in our cohort. Additionally, the correlation between SLC1A5 expression and hypoxia, angiogenesis and immune infiltration was analyzed and verified by immunohistochemistry, immunofluorescence and transcriptome sequencing. Liver cancer cell lines with SLC1A5 expression knockdown or overexpression were constructed, and cell proliferation, colony formation, apoptosis, migration and drug sensitivity as well as in vivo xenograft tumor were measured. A gene set enrichment analysis was conducted to determine the signaling pathway influenced by SLC1A5, and a western blot analysis was performed to detect protein expression alterations. RESULTS: SLC1A5 expression was higher in HCC tissue and associated with poor survival and TACE resistance. Hypoxia could stimulate the upregulation of glutamine transport, angiogenesis and SLC1A5 expression. The SLC1A5 expression was positively correlated with hypoxia and angiogenesis-related genes, immune checkpoint pathways, macrophage, Tregs, and other immunosuppressive cells infiltration. Knockdown of SLC1A5 decreased proliferation, colony formation, and migration, but increased apoptosis and increased sensitivity to chemotherapy drugs. Downregulation of SLC1A5 resulted in a decrease in Vimentin and N-cadherin expression, yet an increase in E-cadherin expression. Upregulation of SLC1A5 increased Vimentin and N-cadherin expression, while decreasing E-cadherin. Overexpression of ß-catenin in SLC1A5-knockdown HCC cell lines could augment Vimentin and N-cadherin expression, suppress E-cadherin expression, and increase the migration and drug resistance. CONCLUSIONS: Elevated SLC1A5 was linked to TACE resistance and survival shortening in HCC patients. SLC1A5 was positively correlated with hypoxia, angiogenesis, and immunosuppression. SLC1A5 may mediate HCC cell migration and drug resistance via Epithelial-mesenchymal transition (EMT) pathway.

Real-world efficacy and safety of TACE-HAIC combined with TKIs and PD-1 inhibitors in initially unresectable hepatocellular carcinoma.

BACKGROUND: Local treatment may function synergistically with immunotherapy and targeted agents. This study aimed to assess the effectiveness and safety of transcatheter arterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma (uHCC). METHODS: A retrospective study was conducted on patients diagnosed with initially uHCC who received combined treatment of TACE-HAIC combined with TKIs and PD-1 inhibitors from July 2020 to February 2023. The primary endpoints were overall survival (OS) and progression free survival (PFS) and adverse events (AEs). Objective response rate (ORR), disease control rate (DCR) and conversion surgery rate (CSR), whereas the secondary endpoints. RESULTS: After screening, a total of 62 patients were selected for this study. The overall median OS was 18.2 (95% CI 16.24-20.16) months and median PFS was 9.2 (95% CI 7.24-11.16) months. Based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and RECIST v1.1 criteria, ORR was 67.7% (42/62), and the DCR was 90.3% (56/62), the CSR was 27.4% (17/62). The most common treatment-emergent adverse events (TEAEs) were transaminitis (56.4%, 35/62), nausea and vomiting (43.5%, 27/62), thrombocytopenia (37.1%, 23/62), abdominal pain (33.9%, 21/62), and fever (33.9%, 21/62). CONCLUSIONS: TKIs combined with PD-1 inhibitors plus TACE-HAIC therapy represents an effective and tolerable treatment option in patients with uHCC. Patients undergoing surgery after combination therapy may have survival benefits.

CRAFITY score benefits hepatocellular carcinoma patients treated with transarterial chemoembolization and lenvatinib.

BACKGROUND: The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib. METHODS: This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort. RESULTS: We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS. CONCLUSIONS: The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.

Combined transarterial chemoembolization and thermal ablation in candidates to liver transplantation with hepatocellular carcinoma: pathological findings and post-transplant outcome.

OBJECTIVES: Evaluating the pathological response and the survival outcomes of combined thermal ablation (TA) and transarterial chemoembolization (TACE) as a bridge or downstaging for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) > 3 cm. MATERIALS AND METHODS: A retrospective review encompassed 36 consecutive patients who underwent combined TA-TACE as bridging or downstaging before LT. Primary objectives included necrosis of the target lesion at explant pathology, post-LT overall survival (OS) and post-LT recurrence-free survival (RFS). For OS and RFS, a comparison with 170 patients subjected to TA alone for nodules <3 cm in size was also made. RESULTS: Out of the 36 patients, 63.9% underwent TA-TACE as bridging, while 36.1% required downstaging. The average node size was 4.25 cm. All cases were discussed in a multidisciplinary tumor board to assess the best treatment for each patient. Half received radiofrequency (RF), and the other half underwent microwave (MW). All nodes underwent drug-eluting beads (DEB) TACE with epirubicin. The mean necrosis percentage was 65.9% in the RF+TACE group and 83.3% in the MW+TACE group (p-value = 0.099). OS was 100% at 1 year, 100% at 3 years and 94.7% at 5 years. RFS was 97.2% at 1 year, 94.4% at 3 years and 90% at 5 years. Despite the different sizes of the lesions, OS and RFS did not show significant differences with the cohort of patients subjected to TA alone. CONCLUSIONS: The study highlights the effectiveness of combined TA-TACE for HCC>3 cm, particularly for bridging and downstaging to LT, achieving OS and RFS rates significantly exceeding 80% at 1, 3 and 5 years.

Comparison of efficacy and safety of conventional transarterial chemoembolization and drug-eluting bead transarterial chemoembolization in unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective cohort study.

PURPOSE: The efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional TACE (c-TACE) in the treatment of patients with unresectable intrahepatic cholangiocarcinoma (ICC) remained controversial. Therefore, we aimed to compare the efficacy and safety between c-TACE and DEB-TACE among patients with ICC. METHOD: Between June 10, 2016 and November 19, 2022, consecutive patients with pathological diagnoses of ICC were divided into the DEB-TACE group and the c-TACE group based on the type of TACE treatment they received. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) between the two groups. Propensity score matching (PSM) was used to balance the characteristics between the c-TACE group and the DEB-TACE group. RESULTS: A total of 132 patients were included in this study, with 64 patients in the c-TACE group and 68 patients in the DEB-TACE group. The median OS for c-TACE and DEB-TACE was 5 and 12 months, respectively. The objective response rate (ORR) for c-TACE and DEB-TACE was 0 % and 66.2 %, respectively; the disease control rate (DCR) was 37.5 % and 91.2 %. There were no significant differences between c-TACE and DEB-TACE among adverse effects at 3 months after treatment (P > 0.05). The results remained consistent after PSM. The Cox regression demonstrated that the DEB-TACE was an independent protective factor for OS. CONCLUSIONS: Patients in the DEB-TACE group had longer OS and higher ORR and DCR than those in the c-TACE group, but no significant difference was observed between the two groups regarding adverse effects.

Safety, efficacy, and survival of different transarterial chemoembolization techniques in the management of unresectable hepatocellular carcinoma: a comparative single-center analysis.

PURPOSE: Transarterial chemoembolization (TACE) has become the standard of care for the treatment of intermediate-stage hepatocellular carcinoma (HCC). However, current clinical practice guidelines lack consensus on the best selection of a specific TACE technique. This study aims to compare safety, tumor response, and progression-free survival (PFS) of conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), and degradable starch microsphere TACE (DSM-TACE). METHODS: This retrospective study included n = 192 patients with HCC who underwent first TACE with unbiased follow-up at 4-6 weeks at our center between 2008 and 2021. Eligibility for TACE was BCLC intermediate stage B, bridging/down-staging (B/D) to liver transplantation (LT), or any other stage when patients were not suitable for resection, LT, local ablation, or systemic therapy. Patients were grouped into three cohorts (n = 45 cTACE, n = 84 DEB-TACE, n = 63 DSM-TACE), and further categorized by TACE indication (B/D or palliative). Liver function and adverse events, response assessed by the modified response evaluation criteria in solid tumors (mRECIST) 4-6 weeks post-TACE and PFS were analyzed. RESULTS: There were no significant differences in age, gender distribution, BCLC stage, or etiology of liver disease among the three TACE groups, even in the B/D or palliative subgroups. DEB-TACE induced slight increases in bilirubin in the palliative subgroup and in lactate dehydrogenase in the entire cohort 4-6 weeks post-TACE, and more adverse events in the palliative subgroup. DEB-TACE and DSM-TACE showed significantly higher disease control rates (complete and partial response, stable disease) compared to cTACE, especially in the B/D setting (p < 0.05). There was no significant difference in PFS between the groups [median PFS (months): cTACE, 10.0 vs. DEB, 7.0 vs. DSM, 10.0; p = 0.436]. CONCLUSION: Our study provides valuable perspectives in the decision-making for a specific TACE technique: DEB-TACE and DSM-TACE showed improved tumor response. DEB-TACE showed a prolonged impact on liver function and more side effects, so patients with impaired liver function should be more strictly selected, especially in the palliative subgroup.

Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness.

PURPOSE: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D-Ligand Interaction after Cryo-Thermal Therapy.

In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy. Consequently, overcoming MDSC immunosuppression is essential for maintaining the long-term efficacy of immunotherapy. In this study, we revealed that NK cells considerably diminish MDSC accumulation at the late stage after CTT, boost T cell production, increase T cell activation, and promote MDSC maturation, culminating in Th1-dominant CD4+ T cell differentiation and enhancing NK and CD8+ T cell cytotoxicity. Additionally, NK cells activate ERK signaling in MDSCs through NKG2D-ligand interaction to increase the activity of tumor necrosis factor (TNF)-α converting enzyme (TACE)-cleaved membrane TNF-α. Furthermore, Increased TACE activity releases more soluble TNF-α from MDSCs to promote MDSC maturation. In our studies, we propose a novel mechanism by which NK cells can overcome MDSC-induced immunosuppression and maintain CTT-induced persistent anti-tumor immunity, providing a prospective therapeutic option to improve the performance of cancer immunotherapy.

The Effect of Low HBV-DNA Viral Load on Recurrence in Hepatocellular Carcinoma Patients Who Underwent Primary Locoregional Treatment and the Development of a Nomogram Prediction Model.

(1) Background: HBV-DNA is an essential clinical indicator of primary hepatocellular carcinoma (HCC) prognosis. Our study aimed to investigate the prognostic implication of a low load of HBV-DNA in HCC patients who underwent local treatment. Additionally, we developed and validated a nomogram to predict the recurrence of patients with low (20-100 IU/mL) viral loads (L-VL). (2) Methods: A total of 475 HBV-HCC patients were enrolled, including 403 L-VL patients and 72 patients with very low (<20 IU/mL) viral loads (VL-VL). L-VL HCC patients were randomly divided into a training set (N = 282) and a validation set (N = 121) at a ratio of 7:3. Utilizing the Lasso-Cox regression analysis, we identified independent risk factors for constructing a nomogram. (3) Results: L-VL patients had significantly shorter RFS than VL-VL patients (38.2 m vs. 23.4 m, p = 0.024). The content of the nomogram included gender, BCLC stage, Glob, and MLR. The C-index (0.682 vs. 0.609); 1-, 3-, and 5-year AUCs (0.729, 0.784, and 0.783, vs. 0.631, 0.634, the 0.665); calibration curves; and decision curve analysis (DCA) curves of the training and validation cohorts proved the excellent predictive performance of the nomogram. There was a statistically significant difference in RFS between the low-, immediate-, and high-risk groups both in the training and validation cohorts (p < 0.001); (4) Conclusions: Patients with L-VL had a worse prognosis. The nomogram developed and validated in this study has the advantage of predicting patients with L-VL.

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: exploring the influence of prior transarterial chemoembolization and additional transarterial chemoembolization on survival outcomes.

Background: The selection of an efficacious treatment modality for patients with hepatocellular carcinoma (HCC) diagnosed as refractory to transarterial chemoembolization (TACE) presents numerous challenges. In addition to systemic therapies, hepatic arterial infusion chemotherapy (HAIC) may serve as an alternative option. However, it is imperative to identify patients who are appropriate candidates for HAIC to confer a survival benefit. Our study aimed to evaluate the impact of the number of TACE sessions prior to HAIC treatment and the addition of TACE during HAIC on the survival of HCC patient's refractory to TACE. Methods: This retrospective study included 82 patients with HCC refractory to TACE (mean age 60.5 years, 75 males). Survival analysis was conducted using the Kaplan-Meier method, with comparison between two groups via the log-rank test; the Cox regression model was utilized to identify factors influencing survival. Results: The overall response rate (ORR) was observed to be 29.3%, with a disease control rate (DCR) of 56.1%. Patients receiving more than four TACE sessions prior to HAIC exhibited a significantly poorer survival prognosis compared to those receiving fewer than four TACE sessions, with a hazard ratio (HR) of 0.151 (P=0.02). The median overall survival (OS) was markedly different, being 3.4 (range, 0.5-13.6) months for the former group and 14 (range, 8.5-19.5) months for the latter (P=0.01). Furthermore, patients undergoing additional TACE while receiving HAIC treatment demonstrated improved survival outcomes compared to those who did not, with an HR of 0.491 (P=0.02); the respective OS for these groups was 14 (range, 3.6-14.4) and 6.7 (range, 2.8-11) months (P=0.02). Conclusions: HAIC can be a suitable alternative treatment for HCC patient's refractory to TACE. For those with a history of more than 4 TACE sessions, other alternative treatments should be considered. The addition of TACE during HAIC treatment may extend patient OS time, provided it is balanced with maintaining safe liver function.

Efficacy and safety analysis of selective hepatic vein occlusion combined with arterial chemoembolization versus conventional transarterial chemoembolization in the treatment of hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) is a non-radical treatment. How to improve the local response rate of tumor is the direction we have been exploring. The purpose of this study is to compare the efficacy and safety of occlusion-TACE (O-TACE) versus conventional TACE (C-TACE) in the treatment of patients with early to mid-stage hepatocellular carcinoma (HCC) of lesions being confined to the same hepatic venous drainage area. Methods: In this study, 40 patients with HCC were prospectively enrolled and randomly assigned to the O-TACE and C-TACE groups, and the efficacy of all patients was assessed at 1, 2, and 3 months after the first treatment, and adverse events (AEs) occurring during the treatment period were also recorded. Results: At 1, 2 and 3 months after the first treatment, patients in the O-TACE group had significantly better complete response (CR) rates (35% vs. 5%, P=0.04; 50% vs. 15%, P=0.04; 70% vs. 30%, P=0.02) than those in the C-TACE group. The most common AE was abdominal pain, and the liver function indexes of patients in both groups returned to the baseline level at 1 month after the first treatment, and there was no statistically significant difference in the rate of AEs between the two groups. Conclusions: O-TACE has a better CR rate and a favorable safety profile in patients with early to mid-stage HCC of lesions being confined to the same hepatic venous drainage area.