Two-dimensional perfusion angiography permits direct visualization of redistribution of flow in hepatocellular carcinoma during b-TACE.

OBJECTIVES: To demonstrate in vivo redistribution of the blood flow towards HCC's lesions by utilizing two-dimensional perfusion angiography in b-TACE procedures. MATERIAL AND METHODS: In total, 30 patients with 35 HCC nodules treated in the period between January 2019 and November 2021. For each patient, a post-processing software leading to a two-dimensional perfusion angiography was applied on each angiography performed via balloon microcatheter, before and after inflation. On the colour map obtained, reflecting the evolution of contrast intensity change over time, five regions of interests (ROIs) were assessed: one on the tumour (ROI-t), two in the immediate peritumoural healthy liver parenchyma (ROI-ihl) and two in the peripheral healthy liver parenchyma (ROI-phl). The results have been interpreted with a novel in silico model that simulates the hemodynamics of the hepatic arterial system. RESULTS: Among the ROIs drawn inside the same segment of target lesion, the time-to-peak of the ROI-t and of the ROI-ihl have a significantly higher mean value when the balloon was inflated compared with the ROIs obtained with deflated balloon (10.33 ± 3.66 s vs 8.87 ± 2.60 s (p = 0.015) for ROI-t; 10.50 ± 3.65 s vs 9.23 ± 2.70 s (p = 0.047) for ROI-ihl). The in silico model prediction time-to-peak delays when balloon was inflated, match with those observed in vivo. The numerical flow analysis shows how time-to-peak delays are caused by the obstruction of the balloon-occluded artery and the opening of intra-hepatic collateral. CONCLUSION: The measurements identify predictively the flow redistribution in the hepatic arteries during b-TACE, supporting a proper positioning of the balloon microcatheter.

Balloon occluded TACE (B-TACE) vs DEM-TACE for HCC: a single center retrospective case control study.

BACKGROUND: To compare oncological results and safety profile of balloon micro-catheter trans-arterial chemoembolization (b-TACE) and drug-eluting-microsphere (DEM-TACE) in patients with hepatocellular-carcinoma (HCC). METHODS: This is a case-control, retrospective, single-center study. Between January-2015/March-2019, 149 patients (131 males [87.9%]) with 226 HCC were treated, 22 patients (35 HCC; 19 [86.4%] males) with b-TACE and 127 with DEM-TACE (191 HCC, 112 [88.2%] males). Embolization protocol was standardized (sequential 100 ± 25 and 200 ± 25 µm microspheres). Results were evaluated by modified-response-evaluation-criteria-in-solid-tumor [mRECIST] at 1, 3-6 and 9-12 months and time to recurrence after complete response [TTR] at 1 years. Cox's regression weighted with tumor dimensions was performed. Adverse events (AEs) were recorded. RESULTS: mRECIST oncological response at all time points (1, 3-6 and 9-12 months) for both treatments were similar, with the exception of Objective response rate at 9-12 months. Objective response at 1 and 3-6 months between b-TACE vs DEM-TACE [23/35 (65.7%) vs 119/191 (62.3%), 21/29 (72.4%) vs 78/136 (57.4%) (p > 0.05), respectively]. On the contrary, at 9-12 months, it was significantly higher in b-TACE subgroup than DEM-TACE (15/19 [78.9%] vs 48/89 [53.9%], p = 0.05). TTR for complete response at 1 year had a better trend for b-TACE vs DEM-TACE (278.0 days [196.0-342.0] vs 219.0 days [161.0-238.0], OR 0.68 [0.4-1.0], p = 0.10). The use of balloon micro-catheter reduced the relative risk of the event of recurrence by 0.63 [CI95% 0.38-1.04]; p = 0.07). No significant differences were found in AEs rate. CONCLUSION: b-TACE showed a trend of better oncological response over DEM-TACE with and longer TTR with a similar adverse events rate, in patients presenting with larger tumors.

Unresectable hepatocellular carcinoma treatment with doxorubicin-eluting polyethylene glycol microspheres: a single-center experience.

BACKGROUND: Transarterial chemoembolization (TACE) is indicated for unresectable hepatocellular carcinoma. METHODS: This was a retrospective study of 50 hepatocellular carcinoma patients treated with TACE using doxorubicin-loaded LifePearl™ to investigate the safety and efficacy of TACE. RESULTS: There was no 30-day mortality, and limited adverse events were reported. At best tumor response, complete response and disease control were 58% and 94%, respectively, with a median of 4.5 months of follow-up. Median overall survival was 33.8 months. Patients with Barcelona Clinic Liver Cancer stage 0 and stage A at best tumor response showed a higher complete response rate (83%) than patients with Barcelona Clinic Liver Cancer stage B (complete response: 50%; p = 0.0414). CONCLUSION: Doxorubicin-loaded LifePearl™ TACE might be an effective treatment, with a good safety profile, for patients with early/intermediate-stage hepatocellular carcinoma. Further prospective data, especially with a small cohort of selected patients, are required to confirm these results.

Real Life Prospective Evaluation of New Drug-Eluting Platform for Chemoembolization of Patients with Hepatocellular Carcinoma: PARIS Registry.

BACKGROUND AND AIM: Transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended for patients with BCLC stage B hepatocellular carcinoma (HCC) and stage 0-A unsuitable for curative treatments. We assessed efficacy and safety along with hepatobiliary toxicities (HBT) of DEM-TACE using a novel microsphere, LifePearlTM, loaded with anthracyclines. MATERIALS AND METHODS: 97 patients diagnosed with HCC were prospectively enrolled and treated using LifePearlTM loaded with doxorubicin (77%) or idarubicin (23%). Safety and tolerability were assessed using CTCAE, HBT by CT/MRI scans, and tumor response by applying modified Response Evaluation Criteria in Solid Tumors (mRECIST). Follow-up was after 2 years. RESULTS: Adverse events (AE) were reported in 73.2% of patients, majority being Grade 1-2. Grade ≥ 3 AE reported in 13.4% of patients were mainly related to postembolization syndrome. HBT were observed after 15.5% (29/187) of the DEM-TACEs. Objective response and disease control rates were 81% and 99%, respectively, as the best responses. Survival rates at one and two years were 81% and 66%, respectively, while the median overall survival (OS) was not reached. Median progression free survival was 13.7 months (95% CI: 11.3; 15.6) and median time to TACE untreatable progression was 16.7 months (95% CI: 12.7; not estimable (n.e.)). CONCLUSIONS: DEM-TACE using LifePearlTM provides a high tumor response rate in HCC patients. HBT rates within or below previously reported results for cTACE and DEM-TACE indicate a good safety profile for LifePearlTM. The trial was registered in ClinicalTrials.gov National Library of Medicine (ID: NCT03053596).

Update on Transarterial Chemoembolization with Drug-Eluting Microspheres for Hepatocellular Carcinoma.

Conventional transcatheter arterial chemoembolization (c-TACE) is a widely used first-line palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). Despite the effectiveness of c-TACE, to date, technique and procedure scheduling has not yet been standardized. Drug-eluting microspheres (DEMs) were therefore introduced to ensure more sustained and tumor-selective drug delivery for permanent embolization. These DEMs can load various drugs and release them in a sustained manner over a prolonged period. This approach ensures the delivery of high concentrations of chemotherapeutic agents to tumors, without increasing systemic concentrations, and promote tumor ischemia and necrosis. This review summarizes the recent advances in the use of DEM-TACE to treat HCC.

Balloon-Occluded Transcatheter Arterial Chemoembolization (b-TACE) for Hepatocellular Carcinoma Performed with Polyethylene-Glycol Epirubicin-Loaded Drug-Eluting Embolics: Safety and Preliminary Results.

PURPOSE: To report technical success, safety profile and oncological results of balloon-occluded transcatheter arterial chemoembolization using a balloon micro-catheter and epirubicin-loaded polyethylene-glycol (PEG) microsphere (100 ± 25 µm and 200 ± 50 µm) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This is a single-centre, single-arm, retrospective study with 6-month follow-up. Twenty-two patients (Child-Pugh A 68% [15/22], B in 32% [7/22]; age 67.05 ± 14 years) with 29 HCC were treated in 24 procedures. Technical success is defined: ability to place the balloon micro-catheter within the required vascular segment, balloon-occluded arterial stump pressure drops and assessment of microsphere deposition. Laboratory assessment pre/post-procedural and complications were analysed, respectively, according to Common Terminology Criteria for Adverse Events (CTCAEv5) and CIRSE system. Postembolization syndrome (PES) was defined as fever and/or nausea and/or pain onset. Oncological results were evaluated using m-RECIST criteria with CT/MRI imaging at 1 and 3-6 months. In partial responder patients, pre/post-procedural tumour volume was compared. RESULTS: Pre-planned feeder was reached in all cases. Pressure drop average was 51.1 ± 21.6 mmHg. Exclusive target embolization was achieved in 14/24 procedures (58.3%). Laboratory test modifications were all grade 1. 4/24 adverse events occurred (17%): pseudo-aneurysm of the feeder (grade 3), liver abscess (grade 2) and 2 asymptomatic segmentary biliary tree dilatations (grade 2). PES occurred in 8/24 (33%). The complete response at 1 and 3-6 months was 44.8% (13/29) and 52.9% (9/17), respectively. The partial response at 1 and 3-6 months was 55% (16/29) and 4/17 (23.5%), respectively. Among partial responder patients, the average percentage of tumour volume reduction was 64.9 ± 27.3%. CONCLUSION: Epirubicin-loaded PEG microsphere b-TACE is technically feasible, safe and effective procedure for HCC treatment.

Five-Years Outcome Analysis of 142 Consecutive Hepatocellular Carcinoma Patients Treated with Doxorubicin Eluting Microspheres 30-60 µm: Results from a Single-Centre Prospective Phase II Trial.

PURPOSE: To assess prospectively long-term results of doxorubicin-loaded HepaSphere 30-60 µm in consecutive patients with hepatocellular carcinoma (HCC) not amenable to curative treatments. PATIENTS AND METHODS: Single-center study from June 2011 to December 2015 in 151 patients treated with 75 mg of doxorubicin per HepaSphere vial. Baseline: Barcelona Clinic Liver Cancer BCLC A/B was 49.3%/50.7%, and median diameter 6.1 cm (mean 6.7 ± 2.0). Liver function, local response (mRECIST), liver time to progression (LTTP), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were recorded. RESULTS: Final analysis included 142 patients with median follow-up of 46.8 months (range 4-72) without grade 4/5 AEs, and 30-day mortality was 0%. Mean number of scheduled treatments was 2.6 (range 1-3) and on demand 3 (range 1-8). Complete response for single tumor ≤ 5 cm was 75.0% and 66.7% for Child A and Child B, while for > 5 cm was 28.6% and 11.8%, respectively. OS was 31.0 months (mean 33.3 ± 15.2; range 8-69), notably for BCLC A 41 months (mean 41.1 ± 15.3; range 13-69) and for BCLC B 26.0 (mean 26.0 ± 10.5; range 8-51). OS at 1, 3 and 5 years: 95.8%, 75.7% and 21.4% for BCLC A, and 94.4%, 36.1% and 2.7% for BCLC B. Median LTTP for BCLC A was 11 months (mean 11.9 ± 4.7; range 3-24) and 7.5 for BCLC B (mean 7.9 ± 2.9). Local response was significant for OS and LTTP (p < 0.0001), while size and lesion number affected LPFS and OS (p < 0.001). CONCLUSIONS: HepaSphere 30-60 µm loaded with doxorubicin provides a safe and effective treatment option for patients with HCC.