Drug-eluting Beads Research Articles

Efficacy and Safety of Drug-Eluting Bead TACE in the Treatment of Primary or Secondary Liver Cancer.

The drug-eluting beads transarterial chemoembolization (DEB-TACE) has already been used in hepatic malignancies. We aim to evaluate the efficacy and safety of DEB-TACE in treating primary or secondary liver cancer. We retrospectively evaluated 59 patients with hepatic malignancies, including 41 patients with primary liver cancer and 18 patients with secondary liver cancer, between September 2016 and February 2019. All patients were treated with DEB-TACE. Objective response rate (ORR) and disease control rate (DCR) were evaluated by mRECIST. The pain was assessed using a numerical rating scale (NRS) where 0 represented no pain, and a score of ten was unbearable. Adverse reactions were assessed according to Common Terminology Criteria for Adverse Events 4.0 (CTCAE4.0). In the subgroup of primary liver cancer, 3 patients (7.32%) got complete response, 13 patients (31.71%) got partial response, 21 patients (51.22%) experienced stable disease, and 4 patients (9.76%) suffered progressive disease; ORR was 39.02% and DCR was 90.24%. In the subgroup of secondary liver cancer, 0 patients (0%) got complete response, 6 patients (33.33%) got partial response, 11 patients (61.11%) experienced stable disease, and 1 patient (5.56%) suffered progressive disease; ORR was 33.33% and DCR was 94.44%. We did not find any difference when comparing the efficacy between primary and secondary liver cancer (P=0.612). The one-year survival rate was 70.73% for primary liver cancer and 61.11% for secondary liver cancer. There was no significant difference between the two groups (P=0.52). For the patients with CR or PR, no factor could predict the efficacy of DEB-TACE. The most common treatment-related adverse reactions were short-term liver function disorders. The symptoms included fever (20.34%), abdomen pain (16.95%), and vomiting (5.08%), all patients with adverse reactions got remission after treatment. DEB-TACE has a promising effect in the treatment of primary or secondary liver cancer. The treatment-related adverse reactions are tolerable.

Clinical Outcomes of DEB-TACE in Hepatic Metastatic Neuroendocrine Tumors: A 5-Year Single-Institutional Experience

To evaluate single-institution outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of locally advanced neuroendocrine tumor (NET) hepatic metastases with a focus on safety and efficacy of treatment. A single-center retrospective cohort study of the outcomes of consecutive patients with NELM who underwent DEB-TACE between 2014 and 2019 was performed. Clinicopathologic characteristics, radiologic response (modified Response Evaluation Criteria in Solid Tumors) at 1-month follow-up, adverse events, progression-free survival (PFS), and overall survival were calculated. Among 287 patients (mean age of 62 years; 39% male: 61% female), disease burden was bilobar (90.2%) with mean largest tumor diameter measuring 4.9±2.8cm. Of these patients, 14.6% had no evidence of tumor in other organs or lymph nodes. Complete response occurred in 60 (20.9%) patients while 133 (46.3%) had partial responses. Major complication occurred in 2.4%. Liver function tests including total bilirubin and AST were overall stable at the 1-month follow-up, with only a small increase in the ALT at +8.9% (p<0.01). Overall survival was 80.1% at 1 year, 49.1% at 3 years, and 12.3% at 5 years with a mean PFS of 14.4±12.5months. Based on this institutional experience, DEB-TACE is an acceptable locoregional therapy choice for hepatic metastases of NET due to its tolerable safety profile and relative efficacy.

In vitro comparative study of multimodal imaging nano-assembled microspheres with two clinical drug-eluting beads loaded with doxorubicin

DC Beads and CalliSpheres are commonly used microspheres in clinical transcatheter arterial chemoembolization, but these microspheres cannot be visualized by themselves. Therefore, in our previous study, we developed multimodal imaging nano-assembled microspheres (NAMs), which are visualized under CT/MR and the location of embolic microspheres can be determined during postoperative review, facilitating the evaluation of embolic areas and guiding subsequent treatment. Moreover, the NAMs can be carried with positively and negatively charged drugs, increasing the choice of drugs. Systematic comparative analysis of the pharmacokinetics of NAMs with commercially available DC Bead and CalliSpheres microspheres is important for evaluating the clinical application of NAMs. In our study, we compared the similarities and differences between NAMs and two drug-eluting beads (DEBs) in respect to drug loading capacity, drug release profiles, diameter variation and morphological characteristics. The results indicate that NAMs had good drug delivery and release characteristics as well as DC Bead and CalliSpheres in vitro experimental stage. Therefore, NAMs have a good application prospect in transcatheter arterial chemoembolization treatment of hepatocellular carcinoma.

Transarterial Chemoembolization With Drug-Eluting Beads Versus Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Outcomes From a Multicenter, Randomized, Phase 2 Trial (the TRENDY Trial)

To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial. Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients. Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACE-DEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACE-DEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms. In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.

Abstract 1993: Sulfobutylether-β-cyclodextrin hydrogel microspheres delivering TLR 7/8 agonist for transarterial immunoembolization

Abstract Drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) is a treatment procedure for liver cancer that involves the selective catheterization and subsequent embolization of tumor-feeding arteries with drug-eluting beads (DEBs). DEB-TACE elicits ischemic cell death in the embolized tumor while simultaneously delivering a local, sustained release of chemotherapy. We hypothesize that the application of DEBs loaded with an immunostimulatory adjuvant in the DEB-TACE procedure will promote local antigen presenting cells to utilize the antigens released by dying tumor cells to generate a systemic, adaptive anti-tumor immune response. This approach represents a novel form of transarterial immunoembolization (TIE). 558 is a highly potent, small molecule Toll-like receptor 7/8 agonist that activates both innate and adaptive immune responses to eliminate tumor cells in various preclinical tumor models. Hydrogel microspheres composed of cross-linked sulfobutylether-β-cyclodextrin (SBE-βCD) were investigated as DEBs for 558 in the current study. SBE-βCD hydrogel microspheres (SBE-βCDMS) of 10 - 300 μm diameter were synthesized via suspension polymerization of SBE-βCD and ethylene glycol diglycidyl ether followed by wet sieving. 558 loading was achieved by incubating blank SBE-βCDMS in aqueous solutions of 558. Under non-saturating conditions, SBE-βCDMS absorbed almost the entirety of 558 from loading solutions in 4 h. The dose of 558 loaded in SBE-βCDMS was tuned by altering the initial amount of 558 in solution, up to a maximum loading of 0.28 mg 558/mg dry SBE-βCDMS determined under saturating conditions. The time to 50% release of 558 from loaded SBE-βCDMS was less than 30 min when phosphate buffered saline was used as release media. However, the release of 558 was negligible when deionized water was used as release media. The released drug was as effective as free 558 in stimulating cytokine response from human peripheral blood mononuclear cells in vitro. As a surrogate for TIE, we evaluated plasma and tumor pharmacokinetics upon intratumoral injection of 558-loaded SBE-βCDMS (50 - 100 μm diameter) or free 558 at a dose of 100 μg in C57BL/6 mice bearing B16F10-OVA flank tumors. The gradual release of 558 from loaded SBE-βCDMS prevented an initial spike in plasma concentration that was observed for mice administered with free 558, and maintained constant tumor concentrations for at least 4 h post-injection. High-resolution MALDI mass spectrometry imaging of 15 μm-thick tumor cryosections indicated that 558 was initially concentrated within SBE-βCDMS after intratumoral injection, and extensively released into the surrounding tumor tissue 24 h post-injection. Taken together, these results suggest that 558-loaded SBE-βCDMS are a promising platform for local drug delivery and immune cell stimulation via TIE. Citation Format: Joel Updyke, Shubhmita Bhatnagar, Nitu Bhaskar, Rachel Parise, Swati Nagar, John Schultz, David Ferguson, Tamara Kucaba, Thomas Griffith, Ronald Siegel, Jayanth Panyam. Sulfobutylether-β-cyclodextrin hydrogel microspheres delivering TLR 7/8 agonist for transarterial immunoembolization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1993.

Correlation between magnetic resonance images of peritumor margin enhancement and prognosis in hepatocellular carcinoma after drug-eluting bead transcatheter arterial chemoembolization.

The aim of this study is to investigate the morphological characteristics and clinical significance of magnetic resonance (MR) images of peritumor margin enhancement in hepatocellular carcinoma (HCC) after drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE). From January 2017 to December 2020, a total of 162 patients who received a diagnosis of HCC were included in our study. We began the follow-up with magnetic resonance imaging (MRI) for complete response assessment, and peritumor margin enhancements were classified as sharp and rough types according to morphology. During the follow-up, data such as progression or remission of the two enhancement modalities, morphological changes in terms of margin enhancements observed in MR images, and alpha-fetoprotein (AFP) levels were recorded. In the follow-up period of 36 months, 70 and 92 patients with sharp- and rough-type peritumor margins, respectively, were observed. At the end of the follow-up, patients with sharp-type margins had lower AFP levels and longer progression-free survival than those with rough-type margins (P < 0.05). Furthermore, the sharp-type margin was thinner than the rough-type margin (all P < 0.05). Moreover, the sharp-type group had a high incidence of tumors with a diameter of < 5cm, whereas the rough-type group had a high incidence of tumors with a diameter of ≥ 5cm. Continuous enhancements of peritumor margins in MRI were greater in the sharp-type group than in the rough-type group. Most of the patients with a sharp-type margin achieved disease remission (94.3%, P < 0.05), whereas most of those with a rough-type margin experienced disease progression (84.8%, P < 0.05). Patients with HCC with a sharp-type margin enhancement on MRI after DEB-TACE mostly demonstrated benign lesions with a good prognosis, whereas those with a rough-type margin mostly demonstrated malignant growth.

D-dimer for assessment of treatment response, and survival to drug-eluting beads transarterial chemoembolization in hepatocellular carcinoma.

D-dimer exhibits a certain prognostic value in hepatocellular carcinoma (HCC) patients who underwent hepatectomy and microwave ablation, while its value in estimating the clinical benefit of drug-eluting beads transarterial chemoembolization (DEB-TACE) remains unclear. Hence, this study aimed to investigate the correlation of D-dimer with tumor features, response and survival to DEB-TACE in HCC patients. Fifty-one HCC patients treated with DEB-TACE were recruited. Their serum samples at baseline and after DEB-TACE were collected and proposed for D-dimer detection by the immunoturbidimetry method. Elevated D-dimer levels were related to a higher Child‒Pugh stage (P=0.013), tumor nodule number (P=0.031), largest tumor size (P=0.004), and portal vein invasion (P=0.050) in HCC patients. Then, patients were classified by the median value of D-dimer, and it was observed that patients with D-dimer >0.7mg/L achieved a lower complete response rate (12.0% vs. 46.2%, P=0.007) but a similar objective response rate (84.0% vs. 84.6%, P=1.000) compared to those with D-dimer ≤0.7mg/L. The Kaplan‒Meier curve showed that D-dimer >0.7mg/L (vs. ≤0.7mg/L) was related to shorter overall survival (OS) (P=0.013). Further univariate Cox regression analyses showed that D-dimer >0.7mg/L (vs. ≤0.7mg/L) was related to unfavorable OS [hazard ratio (HR): 5.524, 95% confidence interval (CI): 1.209-25.229, P=0.027], but it failed to independently estimate OS (HR: 10.303, 95%CI: 0.640-165.831, P=0.100) in multivariate Cox regression analyses. Moreover, D-dimer was elevated during DEB-TACE therapy (P<0.001). D-dimer may be helpful for monitoring prognosis to DEB-TACE therapy in HCC, while further large-scale-study validation is warranted.

Drug-eluting beads loaded with irinotecan to treat synchronous liver-only metastases of colorectal cancer non-responsive to bevacizumab-based chemotherapy.

To evaluate the efficacy of drug-eluting beads loaded with irinotecan (DEBIRI) in colorectal cancer (CRC) patients with synchronous liver-only metastases non-responsive to bevacizumab-based chemotherapy (BBC). Fifty-eight patients were enrolled in this study. Treatment response to BBC and DEBIRI were determined by the morphological criteria and Choi's criteria, respectively. Progression-free survival (PFS) and overall survival (OS) were recorded. The correlation between pre-DEBIRI CT parameters and treatment response to DEBIRI was analyzed. CRC patients were divided into the BBC responsive group (R group) (n = 16) and the non-responsive group (n = 42), which was further divided into the NR group (23 patients who did not receive DEBIRI) and the NR+DEBIRI group (19 patients who received DEBIRI after failing BBC). Among the R, NR and NR+DEBIRI groups, the median PFS were 11, 12, and 4 months, respectively (p < 0.01); median OS were 36, 23, and 12 months, respectively (p = 0.01). In the NR+DEBIRI group, 33 metastatic lesions were treated with DEBIRI, of which 18 (54.5%) reached objective response. The receiver operating characteristic curve showed that the contrast enhancement ratio (CER) before DEBIRI could predict objective response (AUC = 0.737, p < 0.01). In CRC patients, DEBIRI can achieve acceptable objective response for liver metastases non-responsive to BBC. However, this locoregional control does not prolong survival. The pre-DEBIRI CER can predict OR in these patients. DEBIRI can act as an acceptable locoregional management in CRC patients with liver metastases non-responsive to BBC, and the pre-DEBIRI CER is a potential indicator of locoregional control.

Use of doxorubicin-eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein invasion: a prospective study.

To evaluate the applicability of transarterial chemoembolization (TACE) treatment with doxorubicin drug-eluting beads (DEBs) in advanced hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). This prospective study was approved by the institutional review board and informed consent was obtained from all participants. A total of 30 HCC patients with PVI received DEB-TACE between 2015 and 2018. The following parameters were evaluated: complications during DEB-TACE, abdominal pain, fever, and laboratory outcomes, including liver function change. Overall survival (OS), time to progression (TTP), and adverse events were also analyzed and assessed. DEBs measuring 100-300 μm in diameter were loaded with doxorubicin (150 mg per procedure). There were no complications during DEB-TACE and no significant differences in the levels of prothrombin time, serum albumin, or total bilirubin at follow-up compared to baseline. The median TTP was 102 days (95% confidence interval [CI], 42-207 days) and the median OS was 216 days (95% CI, 160-336 days). Three patients (10%) had severe adverse reactions, including transient acute cholangitis (n=1), cerebellar infarction (n=1), and pulmonary embolism (n=1), but no treatment-related death occurred. DEB-TACE may be a therapeutic option for advanced HCC patients with PVI.

Abstract No. 135 Standard Treatment-Refractory/Ineligible Small Cell Lung Cancer Treated with Drug-Eluting Beads Bronchial Arterial Chemoembolization: A Retrospective Analysis

Abstract No. 135 Standard Treatment-Refractory/Ineligible Small Cell Lung Cancer Treated with Drug-Eluting Beads Bronchial Arterial Chemoembolization: A Retrospective Analysis

Preliminary outcomes of DEB-TACE loaded with raltitrexed in the treatment of unresectable or recurrent hepatocellular carcinoma

PurposeRaltitrexed shows therapeutic effects and safety in many types of malignant tumors. However, reports of the clinical outcomes of raltitrexed-based transarterial chemoembolization (TACE) or drug-eluting beads TACE (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC) are rare. We aim to report the preliminary outcomes of DEB-TACE loaded with raltitrexed in patients with unresectable or recurrent HCC.MethodsFrom June 2018 to March 2020, 29 patients with unresectable or recurrent HCC were recruited from our department and treated by DEB-TACE loaded with raltitrexed. Overall survival and progression-free survival were the primary end points. Tumor response was investigated by using the modified response evaluation criteria in solid tumors (mRECIST) criteria.ResultsA total of 49 sessions of DEB-TACE were performed, with a technique success rate of 100%. The overall response rate and disease control rate at 1, 3, and 6 months after DEB-TACE were 72.0% and 96.0%, 57.1% and 85.7%, 47.6% and 66.7% respectively. The median progression-free survival and overall survival was 25.7 and 33.9 months, respectively. The 6-, 24- and 36-month overall survival rates were 88.4%, 66.3% and 46.3%, respectively. Minor complications were observed in 17 patients (58.6%), with no treatment-related mortality or severe adverse events. The most common treatment-related complications were abdominal pain (41.4%) and elevated ALT/AST (27.6%).ConclusionDEB-TACE loaded with raltitrexed is suggested as a safe, feasible, efficacious palliative regimen in unresectable or recurrent HCC patients.

Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study

PurposeTo analyze the efficacy and safety of bronchial arterial embolization (BACE) with drug-eluting beads (DEB) versus bronchial artery infusion (BAI) followed by polyvinyl alcohol (PVA) particle embolization for the treatment of advanced squamous cell lung cancer after the failure of systemic therapy. MethodThirty-six patients with advanced squamous cell lung cancer who underwent bronchial arterial interventional therapy were included in this retrospective study. The DEB group (n = 20) was treated with nedaplatin and DEB loaded with gemcitabine, and the PVA group (n = 16) BAI with nedaplatin and gemcitabine followed by embolization with PVA particles. The treatment efficacy and complications were analyzed. ResultsThe technical success rate was 100 %. The two groups were followed up for a median period of 8.9 months. The mean overall survival (OS) in the DEB group was 12.6 months (95 % CI:9.99–15.21), which was significantly longer than 8.14 months (95 % CI:6.07–10.2) in the PVA group (p = 0.007). The median progression-free survival (PFS) in the DEB group was 4.3 months (95 % CI:2.33–6.27), significantly longer than 3.2 months (95 % CI:2.55–3.85) in the PVA group (p = 0.030). The objective response rate (ORR) six months after the procedure was 50 % in the DEB group and 12.5 % in the PVA group. In the univariate and multivariate analyses, DEB-BACE was an independent prognostic factor for survival. Only grade 1 adverse events like fever, chest pain, and cough were seen. ConclusionsDEB-BACE may be a good choice for patients with advanced lung squamous cell carcinoma, as it could prolong OS and PFS without increasing adverse events.

The impact of drug-eluting bead (vs. conventional) transarterial chemoembolization on hepatic fibrosis in treating intermediate or advanced hepatocellular carcinoma

ABSTRACT Objective Limited studies have reported the impact of drug-eluting bead transarterial chemoembolization (DEB-TACE) on hepatic fibrosis in hepatocellular carcinoma (HCC). This study evaluated multiple hepatic fibrosis indicators, aiming to comprehensively compare the influence of DEB-TACE and conventional transarterial chemoembolization (cTACE) on hepatic fibrosis in treating HCC patients. Methods Intermediate/advanced HCC patients (N = 121) were divided into the DEB-TACE group (n = 62) and the cTACE group (n = 59) based on their chosen treatment. Serum hyaluronic acid (HA), pro-collagen type-III (PC-III), collagen type-IV (IV-C), and laminin (LN) were detected; aminotransferase to platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) were calculated; liver stiffness measurement (LSM) was assessed by real-time shear wave elastography. Results HA, PC-III, IV-C, and LN at 1 month after the second TACE and at 12 months after the first TACE were all decreased in DEB-TACE group compared with cTACE group (all P < .050). Then, APRI, FIB-4, and LSM were further assessed, which also showed a decreasing trend at aforementioned timepoints in DEB-TACE group compared with cTACE group (all P < .050). Additionally, the multivariate logistic regression analysis revealed that DEB-TACE (vs. cTACE) was independently associated with reduced occurrence of severe hepatic fibrosis at 12 months (OR = 0.215, 95%CI: 0.058–0.802, P = .022). Concerning the liver function indexes, alanine aminotransferase, aspartate aminotransferase, and total bilirubin after treatment were not different between the two groups (all P > .050). Conclusion DEB-TACE displays attenuated hepatic fibrosis progression and noninferior tolerance compared to cTACE in treating intermediate- or advanced-stage HCC patients.

Drug-eluting bead transarterial chemoembolization could improve the hepatic hemodynamics of patients with unresectable hepatocellular carcinoma: a retrospective cohort study.

Transarterial chemoembolization (TACE) is widely used for patients with unresectable hepatocellular carcinoma (HCC); however, previous studies have demonstrated that conventional TACE (cTACE) might affect hepatic hemodynamics, which both associate with liver cirrhosis and survival. Drug-eluting bead TACE (DEB-TACE) improves treatment efficacy and safety, but its effects on the hepatic hemodynamics of HCC patients with cirrhosis remain unknown. This retrospective cohort study included unresectable HCC patients treated with DEB-TACE from April 2018 to September 2020, who had limited tumor burden and liver function. The hepatic hemodynamics was measured by hepatic venous pressure gradient (HVPG) using occlusion balloon catheter before and after treatment. Baseline characteristics of demography, laboratory (tumoral and liver-function) and hepatic hemodynamics were compared between patients with and without clinically significant portal hypertension (CSPH). Laboratory examination and imaging assessments were performed 4-6 weeks; overall survival (OS) was defined as the time from DEB-TACE initiation until death or last follow-up. Twenty-four eligible consecutive HCC patients were included, with a median age of 58.0 years and 54.2% in Child-Pugh A class. During a median follow-up of 9.8 months, median OS for the whole cohort of patients reached 10.0 months. Kaplan-Meier survival curves and Cox regression analyses demonstrated that age >60 years, ascites, Eastern Cooperative Oncology Group (ECOG) score of 1, Child-Pugh B class, Model for End-Stage Liver Disease (MELD) score >10, and albumin (ALB) <35 g/L were prognostic factors for decreased OS (P<0.05). Importantly, hepatic hemodynamics were significantly improved in patients after treatment with DEB-TACE (7.5 vs. 5.3 mmHg of HVPG, P<0.001), especially for those with CSPH (13.6 vs. 10.2 mmHg of HVPG, P=0.014). DEB-TACE can improve hepatic hemodynamics in HCC patients, especially those with CSPH. Combing these findings with its effects on tumor, DEB-TACE might be more suitable for HCC patients with cirrhosis.

Safety of drug-eluting beads transarterial chemoembolization under the combination therapy with immune checkpoint inhibitors in unresectable hepatocellular carcinoma.

556 Background: To analyze the safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) under the combination treatment with immune checkpoint inhibitors (ICI) in unresectable hepatocellular carcinoma (HCC). Methods: In this retrospective single-institution study, 208 HCC patients (152 male and 56 female; mean age, 64.70±11.46 years) who received DEB-TACE between 2018.Nov and 2021.Dec were enrolled. There were 74.0% patients had Barcelona Clinic Liver Cancer stage B HCC, 90.4% were Child-pugh A patients, 63.0% patients had albumin-bilirubin (ALBI) grade 2, and 51.0% patients were up-to-seven out. Among them, 50 patients (24.0%) who received ICI with interval less than 30 days with DEB-TACE were categorized as DEB-ICI group; the remaining 158 patients (76.0%) were categorized as DEB group. ALBI grade before and 90 days after DEB-TACE were recorded to evaluate liver function change. Complications within 90 days after DEB-TACE were considered as TACE-related and were compared between two groups. Results: DEB-ICI group had significant higher incidence rate of liver abscess than DEB group (14.0% versus 5.1%, p=0.0337); other TACE-related complications showed no difference between two groups. There were 23.9% patients in DEB-ICI group had elevated ALBI grade after DEB-TACE, which revealed no difference in comparison with 22.4% in DEB group ( p=0.8460). Univariate analysis confirmed that combination with ICI was an independent risk factor of liver abscess formation after DEB-TACE (odds ratio = 3.0523, 95% confidence interval: 1.0474-8.8947, p=0.0409). Among DEB-ICI group, patients received ICI before DEB-TACE had a trend to have higher risk of liver abscess formation than those who received DEB-TACE before ICI (23.8% versus 6.9%, p-value=0.0922). Conclusions: Combination treatment of ICI with DEB-TACE with interval less than 30 days increased risk of liver abscess formation after DEB-TACE.

A novel method for predicting hepatocellular carcinoma response to chemoembolization using an intraprocedural CT hepatic arteriography-based enhancement mapping: a proof-of-concept analysis

BackgroundTo evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method.MethodsThis three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (TPost/pre-RE) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (TPost-RE > 1) versus non-residual (TPost-RE ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries.ResultsCTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on TPost-RE (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0–99.9) and specificity of 100% (95% CI, 87.2–100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE).ConclusionCTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Taiwan perspective.

Hepatocellular carcinoma (HCC) is the fourth most common cancer and the second leading cause of cancer-related death in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan developed and updated the guidelines for HCC management in 2020. In clinical practice, we follow these guidelines and the reimbursement policy of the government. In Taiwan, abdominal ultrasonography, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) tests are performed for HCC surveillance every 6 months or every 3 months for high-risk patients. Dynamic computed tomography, magnetic resonance imaging, and contrast-enhanced ultrasound have been recommended for HCC surveillance in extremely high-risk patients or those with poor ultrasonographic visualization results. HCC is usually diagnosed through dynamic imaging, and pathological diagnosis is recommended. Staging of HCC is based on a modified version of the Barcelona Clinic Liver Cancer (BCLC) system, and the HCC management guidelines in Taiwan actively promote curative treatments including surgery and locoregional therapy for BCLC stage B or C patients. Transarterial chemoembolization (TACE), drug-eluting bead TACE, transarterial radioembolization, and hepatic artery infusion chemotherapy may be administered for patients with BCLC stage B or C HCC. Sorafenib and lenvatinib are reimbursed as systemic therapies, and regorafenib and ramucirumab may be reimbursed in cases of sorafenib failure. First-line atezolizumab with bevacizumab is not yet reimbursed but may be administered in clinical practice. Systemic therapy and external beam radiation therapy may be used in specific patients. Early switching to systemic therapy in TACE-refractory patients is a recent paradigm shift in HCC management.

Efficacy and Safety of Combined Ethanol-Lipiodol Mixture and Drug-Eluting Bead TACE for Large HCC.

To evaluate treatment response, survival and safety of a novel TACE using combination of ethanol-Lipiodol mixture and drug-eluting beads in patients with large unresectable HCC, single tumor >8 cm or multiple tumors with the largest tumor diameter >5 cm and total tumor diameter >10 cm. Between June 2016 and February 2020, a total of 27 patients were enrolled in this retrospective cohort study. Treatment response was assessed at first month after the treatment; progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded. The maximum diameter of the tumors ranged from 5 cm to 17 cm (mean 10.48 cm). The objective response and disease control rates were 56% and 78%, respectively, at 1-month follow-up. The median survival time was 15.9 months (95% CI, 9.03-34.76 months). The OS rates were 76.9% at six months, 65.2% at one year and 44.8% at two years. AFP >400 ng/mL (p = 0.0306), maximum tumor size >10cm (p = 0.0240) were potential risk factors for OS. Regarding safety, major complications occurred in one patient (1/27, 3.7%), presenting with transient hepatic encephalopathy. Combined DEB-TACE appeared to have favorable objective tumor response. It can be an effective treatment option for large unresectable HCC.

Transarterial Chemoembolization for Hepatocellular Carcinoma: 2023 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post-procedural patient care.

Apatinib plus drug-eluting bead transarterial chemoembolization as bridging therapy to surgical resection displays an acceptable efficacy and safety profile in hepatocellular carcinoma patients.

Apatinib exhibits a synergistic effect with transarterial chemoembolization (TACE) by inhibiting TACE-induced neoangiogenic reaction in hepatocellular carcinoma (HCC) patients. But apatinib plus drug-eluting bead TACE (DEB-TACE) is rarely reported as a bridging therapy to surgery. This study aimed to evaluate the efficacy and safety of apatinib plus DEB-TACE as a bridge to surgical resection in intermediate-stage HCC patients. Thirty-one intermediate-stage HCC patients who received apatinib plus DEB-TACE as a bridging therapy to surgery were enrolled. After the bridging therapy, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and objective response rate (ORR) were evaluated; meanwhile, relapse-free survival (RFS) and overall survival (OS) were determined. After the bridging therapy, three (9.7%), twenty one (67.7%), seven (22.6%), and twenty four (77.4%) patients achieved CR, PR, SD, and ORR, respectively; besides, PD did not occur. The successful downstaging rate was 18 (58.1%). The median (95% confidence interval [CI]) accumulating RFS was 33.0 (19.6 - 46.6) months. Besides, the median (95% CI) accumulating OS was 37.0 (24.8 - 49.2) months. HCC patients with successful downstaging showed a higher accumulating RFS rate ( P = 0.038) and similar accumulating OS rate ( P = 0.073) compared to those without successful downstaging. The overall incidence of adverse events was relatively low. Besides, all the adverse events were mild and controllable. The most frequent adverse events included pain (14 [45.2%]) and fever (9 [29.0%]). Apatinib plus DEB-TACE as a bridging therapy to surgical resection displays good efficacy and safety profile in intermediate-stage HCC patients.