cTACE Group Research Articles

Local Efficacy and Safety of Transarterial Chemoembolization for Hepatocellular Carcinoma: Epirubicin-Loaded DC Beads vs. Epirubicin-Lipiodol Emulsion with Gelatin Sponge (cTACE).

Purpose: To compare the efficacy and safety between epirubicin-loaded DC Beads (DCB-TACE) and conventional TACE (cTACE) used in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Materials and Methods: This retrospective study enrolled 64 patients (mean age, 73.3 years; 44 men, 20 women) who underwent initial DCB-TACE between 2014 and 2015, and 66 patients (mean age, 71.3 years; 38 men, 28 women) who underwent initial cTACE between 2011 and 2013 as historical controls. Treatment effects on the target lesions at 3 months after TACE, the period until re-treatment of the target lesion, and adverse events after TACE were compared between the groups. Univariate and multivariate analyses were also performed to estimate the factors influencing the treatment effects. Results: Based on the Response Evaluation Criteria in Cancer of the Liver version 2015, treatment response of the target lesions equivalent to a complete response and termed as TE4, was 51.0% (53/104) in the DCB-TACE group and 74.4% (64/86) in the cTACE group (p<0.001). Multivariate analysis revealed that the TACE procedure, Child-Pugh score, serum aspartate aminotransferase (AST) level, alpha fetoprotein level, and tumor size were independent significant predictors of TE4. The frequencies of elevated serum AST and alanine transaminase levels after TACE were significantly lower in patients in the DCB-TACE group (p<0.001 each). No significant difference in biliary/liver damage was evident between the groups. Conclusion: The local efficacy of cTACE was higher than that of DCB-TACE. Adverse events were milder after DCB-TACE than after cTACE.

Imaging Changes and Clinical Complications After Drug-Eluting Bead Versus Conventional Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Multicenter Study.

BACKGROUND. Drug-eluting bead transarterial chemoembolization (DEB-TACE) has emerged as an alternative to conventional TACE (cTACE) for treatment of hepatocellular carcinoma (HCC), although selection between the approaches remains controversial. OBJECTIVE. The purpose of this study was to compare DEB-TACE and cTACE in the treatment of patients with unresectable HCC in terms of hepatobiliary changes on imaging and clinical complications. METHODS. This retrospective study included 1002 patients (871 men, 131 women; mean age, 59 ± 12 years) from three centers who had previously untreated unresectable HCC and underwent DEB-TACE with epirubicin (780 procedures in 394 patients) or cTACE with ethiodized oil mixed with doxorubicin and oxaliplatin (1187 procedures in 608 patients) between May 2016 and November 2018. Among these patients 83.4% had hepatitis B-related liver disease, 57.6% had Barcelona Clinic Liver Cancer (BCLC) stage A or B HCC, and 42.4% had three or more nodules. Mean tumor size was 6.3 ± 4.2 cm. Hepatobiliary changes and tumor response were evaluated with CT or MRI 1 month after TACE. Clinical records were reviewed for adverse events. RESULTS. Bile duct dilatation (p < .001) and portal vein narrowing (p = .006) on imaging and liver failure (p = .03) and grade 3 abdominal pain (p < .001) in clinical follow-up occurred at higher frequency in the DEB-TACE group (15.5%, 4.6%, 2.3%, and 6.1%) than in the cTACE (7.4%, 1.6%, 0.7%, and 2.1%) group. Higher frequency of bile duct dilation in patients who underwent DEB-TACE was observed in subgroup analyses that included patients with BCLC stage A or B HCC (p = .001), with cirrhosis (p < .001), without cirrhosis (p = .04), and without main portal vein tumor thrombus (p = .002). Total bilirubin level 1 month after treatment was 1.5 ± 2.4 mg/dL (95% CI, 1.2-1.8 mg/dL) for DEB-TACE versus 1.3 ± 2.0 mg/dL (95% CI, 1.1-1.5 mg/dL) for cTACE (p = .02). The cTACE and DEB-TACE groups did not differ in other manifestations of postembolization syndrome or systemic toxicity (p > .05). Local tumor disease control rates did not differ between the cTACE and DEB-TACE groups (1 month, 96.7% vs 98.5%, p = .06; 3 months, 81.8% vs 82.4%, p = .87), but overall DCR was significantly higher in the cTACE than in the DEB-TACE group (1 month, 87.5% vs 80.0%, p = .001; 3 months, 78.5% vs 72.1%, p = .02). CONCLUSION. Compared with cTACE, DEB-TACE was associated with greater frequency of hepatobiliary injury and severe abdominal pain. CLINICAL IMPACT. Greater caution and closer follow-up are warranted for patients who undergo DEB-TACE for unresectable HCC than for those who undergo cTACE.

Efficacy and Safety of Supplemental Transarterial Chemoembolization Through Extrahepatic Collateral Arteries with Drug-eluting Beads: Treatment for Unresectable Hepatocellular Carcinoma.

PurposeTo evaluate the therapeutic efficacy and safety of supplement transarterial chemoembolization (TACE) with drug-eluting beads TACE (DEB-TACE) through extrahepatic collateral (EHC) arteries for the treatment of hepatocellular carcinoma (HCC).Patients and MethodsIn this retrospective study, 61 unresectable HCC patients with treatment-naïve EHC blood supplies who received TACE from January 2016 to March 2019 were enrolled; of these patients, 42 (68.9%) received DEB-TACE, and 19 (31.1%) received cTACE. The hepatic tumor feeding arteries were treated in the same TACE session if it presented. The tumor response, time-to-progression (TTP), and overall survival (OS) were analyzed. Safety was assessed based on the occurrence of liver function deterioration and major complications within three months after TACE.ResultsDEB-TACE showed better efficacy than cTACE in the disease control rate (p=0.001), overall response rate (p=0.005), the TTP (eight months vsthree months, p=0.002) and the OS (23.8 months vs nine months, p=0.045). Nine patients in the DEB-TACE group and one patient in the cTACE group were downstaged to resection or liver transplantation (21.4% vs 5.3%, p=0.151). DEB-TACE and cTACE have no difference in the acute and chronic liver toxicity. With regard to complications, there was no significant difference in the occurrence of both major (16.7% vs 21.1%, p=0.72) and minor (57.1% vs 47.4%, p=0.48) complications between DEB-TACE and cTACE.ConclusionDEB-TACE through EHC arteries has a potential therapeutic effect in the treatment of unresectable HCC, with comparable safety compared with cTACE.

Transarterial chemoembolization of colorectal cancer liver metastasis: improved tumor response by DSM-TACE versus conventional TACE, a prospective, randomized, single-center trial.

To prospectively evaluate the therapy response of third-line TACE with DSM or lipiodol in the treatment of CRLM using MRI. In this prospective, randomized, single-center trial, patients were randomly assigned to receive TACE therapy with either lipiodol or DSM as the embolization agent. Therapy response was evaluated using MRI. Local tumor response was determined according to RECIST 1.1, and survival data was analyzed using the Kaplan-Meier estimator. Fifty patients (35 male, 15 female) were randomized and included in the survival analysis, whereas 31 patients completed therapy and were considered for evaluation of tumor responses (cTACE: n = 13, DSM-TACE: n = 18). In the cTACE group, PR was observed in 23%, SD in 15%, and PD in 62%. In the DSM-TACE-group, PR was observed in 22% of patients, SD in 56%, and PD in 22% (p = 0.047). In addition, the DSM-TACE group showed statistically significant tumor volume reduction (p = 0.006). Median apparent diffusion coefficient values were not significantly different between both groups at baseline (p = 0.26) and study endpoint (p = 0.83). Median survival in the cTACE group was 13months (95% confidence interval, range 5-40months) compared to 16months (95% confidence interval, range 1-48months) in the DSM-TACE group, exhibiting no statistically significant difference (p = 0.75). DSM-TACE showed a significant difference reducing tumor volume and in tumor response according to RECIST 1.1 compared to cTACE. Thus, patients with CRLM might not only benefit from short embolization effect of DSM-TACE but also from better tumor responses. Apparent diffusion coefficients were not significantly different between both groups and cannot be used as a biomarker for monitoring for therapeutic effect of TACE. • To our knowledge, this is the first prospective study that directly compared cTACE and DSM-TACE in patients with CRLM. • DSM-TACE showed a significant difference reducing tumor volume (p = 0.006) and in tumor response according to RECIST 1.1 (p = 0.047) compared to cTACE. • Survival analysis showed a median survival of 13months in the cTACE group compared to 16months in the DSM-TACE group (p = 0.75).

Comprehensive predictive factors for CalliSpheres® microspheres (CSM) drug-eluting bead-transarterial chemoembolization and conventional transarterial chemoembolization on treatment response and survival in hepatocellular carcinoma patients

Transarterial chemoembolization (TACE) is widely applied in hepatocellular carcinoma (HCC) patients who are not suitable for surgical treatment. We aimed to investigate the treatment outcomes and comprehensive prognostic factors of CalliSpheres® microspheres (CSM) drug-eluting bead TACE (DEB-TACE) treatment and conventional TACE (cTACE) treatment in HCC patients. Three hundred and thirty-five HCC patients received DEB-TACE or cTACE treatment were consecutively enrolled in multi-center, retrospective cohort study. Treatment response was conducted at M1, M3 or M6 after treatment. Progression free survival (PFS) and overall survival (OS) were recorded. Thirty-seven baseline factors including demographic characteristics, clinical features, biochemical indexes and previous treatment histories were selected. In total patients, history of drink and largest nodule size≥7cm independently predicted worse ORR, DEB-TACE predicted better OS, while largest nodule size≥7cm, increased Child-Pugh stage, ALB abnormal, ALP abnormal or AFP abnormal predicted worse survival. For DEB-TACE group, previous cTACE and ANC abnormal independently predicted worse ORR, and hepatic vein invasion, increased Child-Pugh stage or AFP abnormal independently predicted poor survival. For cTACE group, largest nodule size≥7cm independently predicted poor ORR, and multifocal disease as well as ALB abnormal predicted poor OS. History of drink, largest nodule size≥7cm, DEB-TACE, increased Child-Pugh stage, abnormal ALB, ALP or AFP are potential prognostic factors in total patients, previous cTACE and ANC abnormal, hepatic vein invasion, increased Child-Pugh stage or AFP abnormal are potential prognostic factors in DEB-TA group, and largest nodule size≥7cm, multifocal disease and ALB abnormal are potential prognostic factors in cTACE group.

A prospective randomized controlled trial of selective transarterial chemoembolization using drug-eluting beads loaded with epirubicin versus selective conventional transarterial chemoembolization using epirubicin-lipiodol for hepatocellular carcinoma: The JIVROSG-1302 PRESIDENT study.

4518 Background: Transarterial chemoembolization (TACE) with selective catheterization into the segmental or subsegmental hepatic arteries supplying HCC is often performed to achieve the complete local control of HCC in the patients with a limited number of small sized nodules. To clarify which of TACE with drug-eluting beads loaded with epirubicin (DEB-TACE) or conventional TACE with epirubicin-lipiodol (cTACE) can achieve the complete response (CR) more frequently, we performed a randomized controlled trial of DEB-TACE vs. cTACE. Methods: Between March 2016 and May 2019, unresectable HCC patients with Child-Pugh class A or B who were scheduled to receive selective TACE were randomly assigned 1:1 to the DEB-TACE group and the cTACE group. The primary endpoint was the CR rate at 3 months, and the secondary endpoints were the CR rate at 1 month and rate of adverse events (AEs). The response and AEs were assessed according to the modified RECIST by an independent review committee and the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0., respectively. Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE 101 patients) were enrolled from 22 Japanese institutions. The patient characteristics were well-balanced between the two groups. The median number of tumors was one in both groups and the median tumor size was 20.0 mm in the DEB-TACE group and 20.5 mm in the cTACE group. The table shows the CR rates and frequencies of AEs. The CR rates of cTACE at 3 and 1 months were significantly higher than those of DEB-TACE. The frequency of AEs (all grades), including pyrexia, malaise, increased serum total bilirubin (T-Bil) and increased serum alanine transaminase (ALT), was significantly higher in the cTACE group than in the DEB-TACE group. Conclusions: Selective cTACE appeared to have greater efficacy for local tumor control as compared to selective DEB-TACE, however, the frequencies of post-embolization syndromes were higher in the cTACE group than in the DEB-TACE group. Clinical trial information: UMIN000021250 . [Table: see text]

Comparative Study of Drug-eluting Beads versus Conventional Transarterial Chemoembolization for Treating Peculiar Anatomical Sites of Gastric Cancer Liver Metastasis.

BackgroundThis study aimed to assess the relative safety and short-term efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (c-TACE) for treating peculiar anatomical sites of gastric cancer liver metastasis.Material/MethodsOf the 68 patients with gastric cancer liver metastases confirmed by imaging and pathology, 35 were treated with DEB-TACE and 33 with c-TACE. The DEB-TACE group comprised 26 males and 9 females aged 28–75 years (56.8±6.3), and the c-TACE group included 19 males and 14 females aged 33–77 (60.2±9.4) years. Liver functions of the 2 groups were compared between pre-TACE and 1-week and 1-month after TACE. Computed tomography and magnetic resonance imaging were reexamined at 1, 3, and 6 months after TACE, and short-term efficacy was assessed based on modified response evaluation criteria in solid tumors.ResultsOne month following DEB-TACE and c-TACE, the number of cases with objective response (OR) was 29 cases (29 out of 35 cases, 82.9%) and 20 cases (20 out of 33 cases, 60.6%) and disease control (DC) in the 2 groups was 33 cases (33 out of 35 cases, 94.3%) and 26 cases (26 out of 33 cases, 78.8%) respectively (P=0.041, P=0.031). Alanine transaminase (ALT) and Aspartate transaminase (AST) significantly increased in the DEB-TACE and c-TACE groups 1 week later (P<0.001). There were no serious complications in the 2 groups; incidences of nausea and vomiting were significantly lower, but instances of fever were markedly elevated in the DEB-TACE group (P=0.023, P=0.016, respectively).ConclusionsThe safety, feasibility, and short-term efficacy of DEB-TACE and c-TACE in the treatment of gastric cancer liver metastasis are clear. DEB-TACE leads to less incidences of nausea and vomiting but more incidences of fever than c-TACE.

Hepatic fibrosis and short-term clinical efficacy after hepatic artery embolization for unresectable hepatocellular carcinoma using doxorubicin-eluting HepaSphere.

BackgroundHepatocellular carcinoma (HCC) is most common malignancies around world. Transcatheter arterial chemoembolization (TACE) is recognized as the first-line treatment for HCC by NCCN, and its efficacy is widely reported. However, repeated TACE induces hepatic fibrosis. How to reduce hepatic fibrosis and retard cirrhosis is an urgent problem in treatment of HCC. To verify the efficacy of doxorubicin-eluting HepaSphere for TACE in the treatment of unresectable HCC.MethodsWe retrospectively analyzed 91 patients with unresectable HCC underwent TACE from June 2015 to June 2018. Among which, 51 cases were treated with HepaSphere-and 40 cases were treated with iodized oil. The primary endpoint was got according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Type IV collagen (IV-C), layer mucin (LN), amino-terminal propeptide of type III procollagen (PIIINP), and hyaluronic acid (HA) were tested before and after TACE treatment.ResultsSerologic factors of the groups were re-examined 3 days after TACE, which showed higher ALT and AST in the conventional TACE group than in the HepaSphere-TACE group (P<0.05). The postoperative efficacies were evaluated according to the mRECIST criteria. No difference in the short-term efficacy between these two groups (P>0.05) were found. Moreover, serologic factors for fibrosis were further re-examined 6 months later, showing no differences for IV-C and PIIINP (P=0.906 and 0.574, respectively). However, LN and HA were slightly higher in C-TACE group than HepaSphere-TACE group (P=0.045 and 0.048, respectively).ConclusionsHepaSphere-TACE is prevents the occurrence of late hepatic fibrosis effectively.

Abstract No. 535 Drug-eluting bead transarterial chemoembolization versus conventional transarterial chemoembolization in colorectal liver metastasis: efficacy and safety and prognostic factors

To evaluate the efficacy, safety and prognostic factors of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) in the treatment of colorectal liver metastasis (CRLM). This study retrospectively analyzed 75 patients with CRLM who received DEB-TACE treatment (36 cases) or cTACE treatment (39 cases) between January 2016 and December 2017. Local control, survival outcome and complications were compared between the two groups. Univariate and multivariate analyses of prognostic factors affecting progression-free survival (PFS) and total survival (OS) were performed. The median duration of follow-up in the two groups was 10.49 months (range, 0.5-22). The median PFS and OS in DEB-TACE group were 10.0 months and 13.0 months, respectively, and in the cTACE group were 6.0 months and 8.5 months (P = 0.009 and 0.008). The 3-, 6- and 12-month survival rates in DEB-TACE group were 100.0%, 94.4%, and 55.6%, respectively. The survival rates in the cTACE group were 92.3%, 71.8%, and 35.9%, respectively. There was no statistically significant difference in the 3-month survival rate (P = 0.083), but significant statistical difference in the 6-month and 12-month survival rates (P = 0.008 and 0.030). Univariate and multivariate survival analyses showed that different treatment methods, tumor size and tumor number were important prognostic factors for PFS and OS. DEB-TACE has advantages over cTACE in prolonging PFS and OS in CRLM patients. Different treatment methods, tumor number and tumor size are important prognostic factors affecting PFS and OS. However, further randomized, multicenter and prospective trials are still needed to confirm the results of this study.Tabled 1Local tumor control and survival of two treatment cohorts.ParameterDEB-TACE (N=36)cTACE (N=39)Z, χ2or t valuePmRECIST (%)Z = 8.8160.032 CR16.7 (6/36)12.8 (5/39) PR41.7 (15/36)15.4 (6/39) SD25.0 (9/36)30.8 (12/39) PD16.7 (6/36)41.0 (16/39)Response rate (%)83.3 (30/36)59.0 (23/39)χ2 = 5.5390.025PFS (months)χ2 = 6.8970.009 Median10.06.0 IQR6.0-14.02.0-10.0OS (months)χ2 = 7.1280.008 Median13.08.5 IQR9.0-16.05.0-12.5OS rate (%) 3 months100.0 (36/36)92.3 (36/39)t = 1.7800.083 6 months94.4 (34/36)71.8 (28/39)t = 2.7410.008 12 months55.6 (20/36)35.9 (14/39)t = 2.2140.030 Open table in a new tab

Initial lenvatinib therapy with no prior TACE in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and Child-Pugh A liver function: A proof-of-concept study.

522 Background: Intermediate-stage HCC is a heterogenous population with subgroups of patients that do not benefit from TACE. Hence, we conducted a matched cohort study to compare the efficacy of lenvatinib to TACE in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-7 criteria. Methods: This study first identified 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-7 criteria, without prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected. Propensity score matching was used to adjust for patients’ demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials [1 Phase II and 13 Phase III REFLECT trial], 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The lenvatinib group showed a higher objective response rate (73.3% vs. 33.3%; p &lt; 0.001) and longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p &lt; 0.001). Median overall survival was also significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p &lt; 0.01). The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p &lt; 0.01), respectively. Conclusions: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-7 criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib is associated with better outcome than TACE. In particular, leventinib is associated with preservation of hepatic function during treatment while TACE is associated with deterioration of hepatic function.

Comparison of chemoembolization with CalliSpheres® microspheres and conventional chemoembolization in the treatment of hepatocellular carcinoma: a multicenter retrospective study.

PurposeThis study aimed to compare the efficacy and safety between transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM-TACE) and conventional TACE (cTACE) in patients with hepatocellular carcinoma (HCC).Patients and MethodsThree hundred and thirty-five HCC patients receiving CSM-TACE or cTACE were consecutively enrolled in this multi-center, retrospective cohort study, and then divided into CSM-TACE group and cTACE group accordingly. Complete response (CR), objective response (ORR) and disease control response (DCR) was assessed according to mRECIST criteria at 1 month (M1), 3 months(M3) and 6 months(M6) after treatment. Progression-free survival (PFS) and overall survival (OS) were assessed. Liver function indexes and adverse events (AEs) were also evaluated.ResultsCR at M3 (P=0.020) and ORR at M1 (P<0.001), M3 (P<0.001) and M6 (P=0.017) after treatment were significantly higher in the CSM-TACE compared with cTACE group. DCRs, PFS (25.3 months vs 24.2 months, P=0.503) and OS (27.8 months vs 25.3 months, P=0.203) were similar between the two groups. CSM-TACE was independently correlated with higher ORR at M1 (P=0.002) and longer OS (P=0.023). Abnormal alkaline phosphatase (ALP) (P=0.049) was independently associated with lower ORR at M3, and history of alcohol intake (P=0.019) and largest nodule size ≥7 cm (P=0.015) independently correlated with lower ORR at M6 (P=0.015). Largest nodule size ≥7 cm (P=0.029) and abnormal albumin (ALB) (P=0.046) were independently associated with shorter PFS. Child-Pugh stage B/C (P=0.023), abnormal ALB (P=0.001), ALP (P=0.008) and alpha-fetoprotein (AFP) (P=0.005) were independently associated with shorter OS. Most liver function indexes and AEs were similar between the two groups (P>0.05), except that ALP (P=0.005), total bilirubin (P=0.031), pain during procedure (P=0.034) and occurrence of fever post(treatment (P=0.017) were significantly elevated in the CSM-TACE compared with cTACE group.ConclusionCSM-TACE presents with a better treatment response and similar survival profile compared with cTACE in HCC patients.

Conventional versus drug-eluting beads chemoembolization for infiltrative hepatocellular carcinoma: a comparison of efficacy and safety

BackgroundTo compare the efficacy and safety between conventional transarterial chemoembolization (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with infiltrative hepatocellular carcinoma (iHCC).MethodsA total of 89 iHCC patients who were treated with either cTACE (n = 33) or DEB-TACE (n = 56) between April 2013 and September 2017 were included in this retrospective study. Patients with the situations that might have a poor outcome were defined as advanced disease including Child-Pugh class B, bilobar lesions, tumor size greater than 10 cm, ECOG 1–2, tumor burden of 50–70%, and the presence of ascites, arterioportal shunt (APS), and portal venous tumor thrombus (PVTT). The tumor response was measured 1-month and 3-month after the procedure. Progression-free survival (PFS) was calculated. Toxicity was graded by Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The differences in tumor response, PFS, and toxicity were compared between the DEB-TACE group and cTACE group.ResultsAt 1-month and 3-month after the procedure, the objective response rate (ORR) in the overall study population was similar in DEB-TACE group and cTACE group. The disease control rate (DCR), at 1-month after the procedure, was significantly higher in the patients treated with DEB-TACE relative to those treated with cTACE (P = 0.034), while after 3 months, the difference did not differ between two groups. DEB-TACE showed a higher DCR than cTACE in patients with tumor size greater than 10 cm (P = 0.036) or associated with APS (P = 0.030) at 1-month after the procedure, while after 3 months, the difference was only noted in patients with APS (P = 0.036). The median PFS in DEB-TACE group was 96 days, while in cTACE group was 94 days, and there was no difference in PFS between two groups (P = 0.831). In the side effect analysis, abdominal pain (P = 0.034) and fever (P = 0.009) were more frequently present in the cTACE group than DEB-TACE group, but there was no difference in high grade liver toxicity between the two groups.ConclusionsCompared to cTACE, DEB-TACE offers slightly better DCR and tolerability for iHCC patients, particularly in patients associated with APS and large tumor size. However, DEB-TACE does not provide higher PFS than cTACE.

Hepatic Arterial Chemoembolization With Arsenic Trioxide Eluting CalliSpheres Microspheres Versus Lipiodol Emulsion: Pharmacokinetics And Intratumoral Concentration In A Rabbit Liver Tumor Model.

BackgroundThe objective of this study was to investigate the plasma pharmacokinetic profiles, intratumoral concentration and tissue distribution of arsenic trioxide (ATO) by drug-eluting beads (DEB)-transcatheter arterial chemoembolization (TACE) compared with conventional TACE (cTACE) in a rabbit liver tumor model.MethodsSixty-four rabbits with VX2 liver tumor were established and randomly assigned to four groups equally. The calliSpheres microspheres (CSM)-ATO group received DEB-TACE treatment using ATO-loaded CSM; the cTACE-ATO group received cTACE treatment using ATO mixed with lipiodol; the CSM-normal control (NC) group received DEB-TACE treatment using blank CSM; the TAE-lipiodol group received cTACE treatment using saline mixed with lipiodol. ATO concentration in plasma, tumor and normal tissues, and liver and kidney function indexes were evaluated.ResultsThe CSM-ATO group exhibited lower plasma ATO concentrations at 10 minutes and 20 minutes post treatment compared with the cTACE-ATO group. Meanwhile, intratumoral ATO concentrations were higher in the CSM-ATO group compared with the cTACE-ATO group at 3-, 7- and 14-days post treatment. In normal liver tissue, heart and muscle tissues, ATO concentrations between the CSM-ATO and cTACE groups were similar at each time point; in kidney and lung tissues, ATO concentrations were lower in the CSM-ATO group at 1-day post treatment while they were similar at 3, 7 and 14 days post treatment. Also, liver or kidney function indexes were of no difference at each time point between CSM-ATO and cTACE-ATO groups.ConclusionAdministration of ATO via DEB-TACE decreases systemic concentration while increasing intratumoral concentration of ATO without increasing liver or kidney toxicity compared with cTACE.

Chemoembolization of liver cancer with doxorubicin-loaded CalliSpheres microspheres: plasma pharmacokinetics, intratumoral drug concentration, and tumor necrosis in a rabbit model.

The purpose of this work was to investigate the plasma pharmacokinetics, intratumoral drug concentration, and tumor necrosis after transarterial chemoembolization (TACE) with doxorubicin-loaded CalliSpheres microspheres (CSMs). Sixty rabbits with liver VX2 tumors were assigned into five groups of 12 rabbits each, which received 4mg of doxorubicin via intravenous injection (IV group), hepatic arterial infusion (IA group), conventional TACE (cTACE group), CSM-TACE (CSM low-dose group), and 8mg of doxorubicin via CSM-TACE (CSM high-dose group), respectively. Doxorubicin concentrations in plasma, tumor, and adjacent hepatic parenchyma were measured at various timepoints after treatment, and tumor necrosis percentage and liver enzymes were also assessed. The peak plasma concentration of doxorubicin was significantly lower in the three TACE groups compared to IV and IA group (P < 0.05), while doxorubicin concentrations in tumor and adjacent hepatic parenchyma were higher in the two CSM groups compared with IV, IA, and cTACE groups at 3days and 7days after treatment (P < 0.05). The percentages of tumor necrosis at 3 and 7days after treatment were significantly higher in three TACE groups (all higher than 50%) compared with IV group and IA group (both lower than 25%) (P < 0.05), and the highest tumor necrosis percentage was achieved in CSM high-dose group. The three TACE groups showed transient increases in transaminases levels after treatment, in which the peak transaminases levels were significantly lower in the two CSM groups than those in cTACE group (P < 0.05). CSM achieves an effective delivery of doxorubicin into liver cancer. High-dose doxorubicin improves tumoricidal capacity while not impairing the safety of the doxorubicin-loaded CSM.

Comparison of liver function and safety in hepatocellular cancer patients treated with DEB-TACE and cTACE: a multi-center, retrospective cohort study.

BackgroundThis study aimed to compare the live function change and adverse events (AEs) between drug-eluting beads (DEB) transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM) and conventional TACE (cTACE) in treating hepatocellular carcinoma (HCC) patients.MethodsThree hundred and thirty-five HCC patients underwent DEB-TACE with CSM (n=171, DEB-TACE group) or cTACE (n=164, cTACE group) were consecutively enrolled in this multi-center, retrospective cohort study. Liver function indexes were reviewed before treatment (W0), at 1 week (W1) and 1 month (M1) post treatment. Moreover, AEs during operation and hospitalization were retrieved as well.ResultsThe changes of albumin (ALB) [–3.55 (–6.25 to –0.43) vs. –2.20 (–4.63–0.00), P=0.043] and total protein (TP) [–4.62 (–10.18–0.43) vs. –2.50 (–7.08–1.08), P=0.013] from W1 to W0 were lower in DEB-TACE group compared to cTACE group, while no difference was observed referring to the change of alanine aminotransferase (ALT) (P=0.494), aspartate aminotransferase (AST) (P=0.747), alkaline phosphatase (ALP) (P=0.895), total bilirubin (TBIL) (P=0.059), total bile acid (TBA) (P=0.491) from W1 to W0. And the changes of these seven indexes from M1 to W0 were all similar between DEB-TACE group and cTACE group (all P>0.05). Besides, the occurrence of pain during treatment (19.3% vs. 11.0%, P=0.034) and the occurrence of fever during hospitalization (18.1% vs. 9.1%, P=0.017) were both increased in DEB-TACE group compared to cTACE group.ConclusionsDEB-TACE with CSM is non-inferior to cTACE in terms of liver function change, while DEB-TACE with CSM leads to higher incidences of pain and fever.

Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study.

Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child–Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were −2.61 to −2.61 for 30 patients in the lenvatinib group (p = 0.254) and −2.66 to −2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child–Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE.

Comparison of lipiodol infusion and drug-eluting beads transarterial chemoembolization of hepatocellular carcinoma in a real-life setting

Aim: Doxorubicin-eluting beads transarterial chemoembolization (DEB-TACE) is reported to improve survival and tolerability when compared with conventional lipiodol-TACE (cTACE) for the treatment of hepatocellular carcinoma (HCC). The aim of this study was to evaluate tolerability and long-term survival in patients treated with cTACE or DEB-TACE in a real-life setting.Methods: Incidence of adverse events and overall survival in HCC patients treated with either cTACE or DEB-TACE at Karolinska University Hospital 2004–2012 were analyzed retrospectively. Median follow-up was 7.1 years. Patients were censored when transplanted or at the end of follow-up. Patients receiving both cTACE and DEB-TACE, or treated with resection or ablation post-TACE were excluded from the survival analysis.Results: A total of 202 patients (76 cTACE and 126 DEB-TACE) were eligible for analysis of adverse events, and 179 patients (69 cTACE and 110 DEB-TACE) were included in the survival analysis. cTACE patients were younger and had fewer tumors but higher BCLC stage than DEB-TACE. Child-Pugh and ECOG performance status were similar between groups. Adverse events (abdominal pain, nausea and vomiting, fever, fatigue) were significantly less common in the DEB-TACE group. Median survival was 17.1 months in the cTACE group and 19.1 months in the DEB-TACE (NS). In multivariate Cox regression analysis, portal vein thrombosis and tumor size were associated with increased, and sorafenib treatment post-TACE with decreased mortality.Conclusion: In this retrospective real-life analysis, DEB-TACE had better tolerability compared to cTACE, but overall survival did not differ between the two treatments. Portal vein thrombosis, tumor size and sorafenib treatment after TACE influence survival.

03:00 PM Abstract No. 208 Conventional versus Drug-eluting bead transarterial chemoembolization for nodular hepatocellular carcinoma in a superselective fashion using cone-beam CT: analysis of a five-year outcome

To compare the clinical outcomes of conventional transarterial chemoembolization (cTACE) and drug-eluting bead (DEB-TACE) used in a superselective fashion using cone-beam computed tomography (CBCT) for nodular hepatocellular carcinoma (HCC). A total of 198 consecutive patients with nodular HCC (tumor number ≤ 5) who were initially treated with cTACE (n=125) or DEB-TACE (n=57) were retrospectively included. The primary endpoint was progression-free survival (PFS). Secondary endpoints included time-to-local progression (TTLP), time-to-progression (TTP), overall survival (OS), and safety. During the follow-up of median 62 months (range, 1–87 months), 122 patients developed tumor progression and 54 patients died. The PFS was significantly longer in the cTACE group than in the DEB-TACE group (hazard ratio [HR], 0.658; 95% confidence interval [CI], 0.445–0.973; log-rank P=0.031). Median PFS was 18 months in the cTACE group and 7 months in the DEB-TACE group. In multivariable analysis, cTACE showed significantly lower risk of tumor progression or death (adjusted HR, 0.624; 95% CI, 0.418–0.931; P=0.021). Moreover, both TTLP (median, 34 months vs 11 months; log-rank P < 0.001) and TTP (median, 18 months vs 7 months; log-rank P=0.025) were significantly longer in the cTACE group than in the DEB-TACE group. OS was not statistically different between cTACE and DEB-TACE groups (5-year OS: 74.5% vs 70.0%; log-rank P=0.299). Post embolization syndrome occurred more frequently in the cTACE group (odds ratio, 2.44; P=0.006). cTACE showed significantly longer PFS and TTP than DEB-TACE, although it failed to increase OS. DEB-TACE showed fewer cases of postembolization syndrome.

Abstract No. 518 Comprehensive analysis of treatment response and survival profiles in hepatocellular carcinoma patients: drug-eluting beads transarterial chemoembolization with CalliSpheres microspheres versus conventional transarterial chemoembolization

The aim of this study was to compare the treatment response and survival profiles between drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres® microspheres (CSM) and conventional transarterial chemoembolization (cTACE) in hepatocellular carcinoma (HCC) patients. Three hundred and thirty-five HCC patients receiving DEB-TACE with CSM or cTACE were consecutively enrolled in this multi-center, retrospective cohort study, whom were divided into DEB-TACE group and cTACE group accordingly. Treatment response were assessed by enhanced CT or MRI according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) at month 1 (M1), M3, and M6 after treatment. Progression free survival (PFS) and overall survival (OS) were assessed. Complete response (CR) at M3 (P=0.020) and objective response rate (ORR) at M1 (P<0.001), M3 (P<0.001) and M6 (P=0.018) were elevated in DEB-TACE group compared with cTACE group. In addition, progression free survival (PFS) (P=0.503) and overall survival (OS) (P=0.203) did not vary between DEB-TACE and cTACE group. DEB-TACE independently correlated with elevated ORR at M1 (P=0.002) and more prolonged OS (P=0.023). In addition, ALP abnormal independently associated with lower ORR at M3, history of drink and largest nodule size ≥7 cm were independent predictive factors for decreased ORR at M6. Largest nodule size ≥7 cm and ALB abnormal were independent predicting factors for shorter PFS, Child-Pugh stage B/C, ALB abnormal, ALP abnormal and AFP abnormal were independently associated with unfavorable OS. DEB-TACE with CSM presents with more favorable treatment response and survival profile compared with cTACE in HCC patients.TableComparison of Treatment Response Between the DEB-TACE and cTACE GroupsM1M1M1M2M2M2M3M3M3DEB-TACE GroupcTACE GroupP ValueDEB-TACE GroupcTACE GroupP ValueDEB-TACE GroupcTACE GroupP ValueNumber of assessed patients10712482555445CR (n/%)13(12.1)10(8.1)0.30116(19.5)3(5.5)0.0209(16.7)3(6.7)0.129PR (n/%)64(59.8)48(38.7)0.00147(57.3)22(40.0)0.04729(53.7)18(40.0)0.174SD (n/%)19(17.8)50(40.3)<0.0015(6.1)21(38.1)<0.00110(18.5)15(33.3)0.091PD (n/%)11(10.3)16(12.9)0.53614(17.1)9(16.4)0.9136(11.1)9(20.0)0.219ORR (n/%)77(71.9)58(46.8)<0.00163(76.8)25(45.5)<0.00138(70.4)21(46.7)0.018DCR (n/%)96(89.7)108(87.1)0.53668(82.9)46(83.6)0.91348(88.9)36(80.0)0.219 Open table in a new tab

03:45 PM Abstract No. 426 Balloon-occluded vs. conventional transarterial chemoembolization in a rabbit model to assess the doxorubicin concentration in the VX2 tumor and liver parenchyma

To evaluate the effectiveness of balloon-occluded TACE (b-TACE) vs conventional-TACE by measuring doxorubicin concentration in the VX2 tumors and normal liver parenchyma. This study was conducted with OHSU’s institutional animal care and use committee for approval. A total of 17 rabbits subsequently underwent surgical implantation of two VX2 tumors in their medial and lateral lobes. The b-TACE (8 rabbits) or c-TACE (9 rabbits) was performed approximately 3 weeks after the implantation. Emulsion of 5 mg/ml doxorubicin and Lipiodol in 1:1 ratio was delivered at proper hepatic arteries through 1.8-French-tip balloon microcatheters for b-TACE group or 1.9-French-tip non-balloon microcatheters for c-TACE group. The tumors were harvested immediately after the procedure and the tumors were processed for tissue liquid chromatography-tandem mass spectrometry (LC-MS/MS) doxorubicin analysis. A total of 34 tumors (16 tumors and 18 tumors, b-TACE vs. c-TACE) were harvested and analyzed with LC-MS/MS. The maximum diameters of the tumors were 22.6±6.94 mm vs. 21.7±6.97 mm. The amount of doxorubicin given was 3.60±0.97 mg vs. 3.61±1.17 mg. The doxorubicin concentrations of both peripheral and central portions of the tumors were 1.95±1.67 vs.1.22±1.67 mcg/ml (b-TACE vs. c-TACE, p=0.203) and 1.14±1.22 vs. 0.76±1.22 mcg/ml (b-TACE vs. c-TACE, p=0.334). The doxorubicin concentrations of normal liver tissue were 1.18±1.32 vs. 0.72±0.70 mcg/ml (b-TACE vs. c-TACE, p=0.07). Combined the both groups, concentration of doxorubicin in peripheral portion of the tumors were statistically significantly higher than that of in central portion (1.65±1.37 vs. 0.90±0.89 mcg/ml, p=0.044). The b-TACE may introduce higher dose of doxorubicin into the tumors and normal liver parenchyma as well compared with c-TACE. The doxorubicin concentration was significantly higher in the peripheral portion of the tumors than that of central.