Transarterial Radioembolization Research Articles

Clinical and genomic characteristics of hepatocellular carcinoma-cholangiocarcinoma: Insights from real-world data.

556 Background: Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) is a rare and complex liver cancer with features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), making its management challenging. This study aims to analyze the clinical characteristics, genomic profiles, and treatment outcomes of cHCC-CCA patients in a real-world setting. Methods: We conducted a retrospective analysis of cHCC-CCA patients across three first-line treatment groups: chemotherapy alone(Gemcitabine/Cisplatin, FOLFOX), HCC-directed therapies (atezolizumab/bevacizumab, lenvatinib, nivolumab, durvalumab, sorafenib), and chemoimmunotherapy (Gemcitabine/Cisplatin combined with immunotherapy). This international study, involving Mayo Clinic and the National Cancer Center East (Japan), assessed overall survival (OS) using Kaplan-Meier and Cox regression models. Results: A total of 68 patients were included, with a mean age of 66 years; 74% were male and 66% were White Non-Hispanics. Cirrhosis was present in 74% of patients at diagnosis, and Hepatitis B and C were common etiologies in 57%. Prior primary resection and regional therapies (Transarterial chemoembolization (TACE), Transarterial radioembolization (TARE)) were recorded in 39% and 50% of patients, respectively. Advanced/metastatic disease was present in 52% of the cohort. The distribution of first-line treatments was as follows: 47% received chemotherapy alone, 39% received HCC-directed therapy, and 14% received chemoimmunotherapy. Genomic alterations were detected in 44% patients, with TP53 (28%), ARID1A (25%), and TERT (22%) being the most frequent. The HCC-directed therapy group demonstrated the best overall response rate (52%) and had a median OS of 15.8 months (mo), compared to 11.8 mo for chemotherapy and 4.7 mo for chemoimmunotherapy (p=0.8). Patients who received regional treatments had a longer median OS of 15.8 mo compared to those who did not (10.2 mo) (p=0.4). Conclusions: HCC-directed therapy showed a trend towards better survival outcomes compared to other treatments, though not statistically significant. A considerable proportion of patients had genomic alterations, which may have influenced survival outcomes. Ongoing research with larger cohorts is underway to further elucidate the impact of genomic variations on treatment efficacy and refine therapeutic strategies for this challenging malignancy. Baseline characteristics of patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA). Total(N=68) Mean age at diagnosis, years (SD) 66(6.4) Gender, n (%) Male 50 (74%) Ethnicity, n (%) White, Non-Hispanic 45 (66%) Cirrhosis at diagnosis, n (%) 50 (74%) Etiology of Liver disease, n (%) Viral (Hepatitis B and C) 39 (57%) History of Primary resection, n (%) 27 (39%) Regional treatment, n (%) 34 (50%) Afp, n (%) < 200 23 (64%) ca19_9, n (%) < 50 27 (82%)

Real-world treatment patterns among U.S. adults with unresectable hepatocellular carcinoma (uHCC) eligible for locoregional therapy (LRT).

547 Background: Treatment (tx) in uHCC has mostly relied on locoregional liver-directed tx, such as transarterial chemoembolization (TACE) or radioembolization (TARE), but recent pharmacotherapy advances have provided more tx options. This study aims to describe current real-world tx patterns and clinical outcomes of uHCC eligible for LRT. Methods: uHCC patients enrolled in TARGET-HCC (an ongoing, 5-year, longitudinal, observational cohort of HCC patients receiving usual care at academic and community sites in the U.S.), who initiated tx between 6/1/2020-6/1/2023 were included and followed until 12/31/2023 (data cutoff). Patients receiving curative HCC tx (ablation, resection, or transplant) or with metastatic HCC, portal vein involvement, or Child-Pugh-C liver disease at diagnosis (dx) were excluded. Patient and disease characteristics, and txs data were abstracted from electronic health records. Index tx was defined as first tx after dx, with a 30-day grace period for combination txs. Subsequent tx was defined as first tx after the grace period; for index systemic therapies, the subsequent tx differed from the index tx. Real-world progression-free survival (rwPFS) was defined as time from index tx to first event: radiological progression (including new lesions, extrahepatic involvement, vascular invasion, or >20% increase in tumor burden from baseline), death, or hospice entry. Real-world time to progression (rwTTP) was defined as time from index tx to first radiological progression. Results: A total of 115 patients were included; mean age was 65.1 years and 77% were male. At dx, 41% of patients were BCLC B, 14% were non-metastatic BCLC C, and 38% were BCLC A with lesion >5 cm, rapidly progressive disease, or contraindications to LRT. Tx initiation with TACE/TARE was common, either alone (n=59, 51%) or in combination with systemic tx (n=5, 4%). Among patients initiating systemic tx (n=46 ,40%), 30 received IO-IO (immuno-oncology) combinations, 12 received IO only, and 4 received a TKI only (tyrosine kinase inhibitor). Following index tx, 21 (18%) patients died receiving no subsequent tx and 27 (23%) were censored at data cutoff. Among those who received subsequent tx (n=67, 58%), there was heterogeneity in tx choice: TACE/TARE (n=32), systemic tx (n=16) other LRT (n=10), multimodal therapy (n=5), and transplant (n=4). We observed 60 progression events and 38 deaths corresponding to a median rwPFS and rwTTP of 7.9 (95% CI: 5.0, 13.3) months and 11.3 (95% CI: 6.7, 28.9) months, respectively. Conclusions: Our results showed high variability in management of uHCC eligible for LRT with TACE/TARE commonly utilized. Tx choice may be influenced by factors beyond staging criteria. Prognosis for uHCC eligible for LRT remains poor, and further research on adaptive, multimodal tx strategies is needed to inform tx guidelines and improve outcomes.

Safety, efficacy, and outcomes of 90-yttrium radioembolization in combination with immune checkpoint inhibitors as a definitive first-line treatment approach in non-surgical hepatocellular carcinoma.

617 Background: Immune checkpoint inhibitors (ICI) have emerged as first line therapy for advanced-stage hepatocellular carcinoma (HCC). However, response rates remain modest (<20%). Combination treatments offer potential to improve initial response rates while extending duration of response. While early studies of 90 Yttrium transarterial radioembolization ( 90 Y)-ICI showed fewer adverse events (AE) and improved objective responses (OR) (30-40%), there were no improvements in time to progression (TTP) and overall survival (OS). This study evaluates safety, efficacy, and outcomes of first line 90 Y-ICI while evaluating the role of ICI regimen and treatment sequencing. Methods: A retrospective, multi-center study was conducted in BCLC A-C stage HCC patients (ECOG 0-1) receiving first line 90 Y-ICI with atezolizumab/bevacizumab (A+B) or tremelimumab/durvalumab (STRIDE). Treatment response was recorded at 90 Y follow-up. TTP, progression-free survival (PFS), and OS were primary endpoints, with AE and safety as secondary outcomes. Results: The study included 40 patients receiving 90 Y-ICI from 2021–2024, with a median follow-up of 12 months. The cohort was predominantly Child-Pugh A (96%) with HCV-related cirrhosis (76%), BCLC-C stage (51%), and a median target HCC size of 7.7 cm (IQR, 6-11 cm). Grade 3-4 AEs occurred in 15 patients (37%), leading to steroid use (12, 29%), treatment delays (13, 31%), or discontinuation (4, 10%). The first cycle target OR rate was 82% (32/39), with a 51% (20/39) complete response (CR) rate. The first cycle overall OR was 59% (23/39), with a 41% (16/39) CR rate. No significant differences were found in adverse events, delays, or discontinuations based on sequencing or regimen. Sequencing had no significant effect on target or overall OR with no downstream effect on TTP (P = 0.968) or PFS (P = 0.906). Similarly, there was no effect of ICI regimen on OR, TTP (P = 0.813) or PFS (P = 0.904), although the data trended toward higher response rates with the STRIDE regimen. Log-rank analysis revealed target CR was associated with improved TTP (P = 0.004) and PFS (P = 0.009), but not OS (P = 0.237). Achieving an overall CR was associated with further improvements in TTP (P < 0.001) and PFS (P < 0.001). The cohort 2-year OS was 55% with median OS not yet reached. Conclusions: First line 90 Y-ICI therapy in BCLC A-C stage HCC is an effective treatment strategy with AEs in the expected range of systemic therapy and low rates of treatment discontinuation. Sequencing and ICI regimen did not significantly impact AEs or treatment outcomes. However, patients achieving CR showed significantly improved TTP and PFS. Although follow-up is limited, these findings suggest achieving CR is key to optimal long-term outcomes. We anticipate long-term follow-up will demonstrate an OS benefit linked to first line CR rate.

Dosimetry Assessment in Predicting Treatment Outcomes Following Yttrium-90 Transarterial Radioembolization of Hepatic Tumors.

Purpose: To evaluate the use of yttrium-90 (Y90) dosimetry in predicting treatment outcomes when used following transarterial radioembolization with SIR-Spheres® (Resin Y90) in patients with hepatic tumors. Materials and Methods: This single institution retrospective analysis included 100 patients with hepatocellular carcinoma, colorectal carcinoma or other liver metastases who underwent transarterial radioembolization with resin Y90 and had imaging follow-up within one year of treatment. Mean tumor dose and mean dose to nontumor was calculated using voxel-based dosimetry software. Descriptive statistics were reported and methods of analyses included simple and multivariable linear regression, contingency table analyses, Kaplan-Meier estimation, and Cox proportional hazards models. Results: Of 100 patients included, 65 demonstrated tumor shrinkage following transarterial radioembolization. Of these, 20 (30.8%) had hepatocellular carcinoma, 22 (33.8%) had colorectal carcinoma, and 23 (35.4%) had other types of metastases. There was an association between tumor shrinkage and mean tumor dose (p = 0.0285) and mean dose to nontumor (p = 0.0028) in hepatocellular carcinoma patients, but not colorectal carcinoma, or the other subgroup. For all 100 patients, time to death and mean tumor dose was associated only in the other subgroup (p = 0.0260), but not in the hepatocellular or colorectal carcinoma groups. Time to death and mean dose to nontumor was associated in hepatocellular carcinoma patients (p = 0.0421), but not the colorectal carcinoma or other subgroup. Conclusions: Voxel-based dosimetry assessment is a tool that may be utilized to assist in predicting treatment outcomes in responders to transarterial radioembolization.

Transarterial Radioembolisation with Y90 Resin Microspheres and the Effect of Reimbursement Criteria in France: Final Results of the CIRT-FR Prospective Observational Study.

This analysis of the CIRSE Registry for SIR-Spheres Therapy in France, CIRT-FR, reports on real-world outcomes of transarterial radioembolisation (TARE) with Y90 resin microspheres for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRLM) patients in France, focusing on safety, effectiveness and health-related quality of life (HRQoL). Results on patients treated based on national reimbursement criteria are discussed here. Prospective, multicentre, observational study of HCC and CRLM patients treated between August 2017 and July 2020 with TARE Y90 resin microspheres. Patients were assigned to different analysis groups based on reimbursement recommendations. Follow-up period was at least 24months with patient data collected every 3months. In total, 252 (193 HCC, 59 CRLM) patients of CIRT-FR were included in the analysis. No differences in effectiveness, safety and HRQoL were found between analysis groups based on reimbursement recommendations. Median overall survival for HCC and CRLM was 19.0 (95% CI, 16.1-22.4) and 10.8 (95% CI, 8.0-13.5) months, respectively. Serious procedure-related adverse events occurred in 13% of the patients. HRQoL generally remained stable, with some fluctuations in function scores and symptoms. In our cohorts, patients performed similarly regarding clinical outcomes irrespective of their analysis group based on reimbursement recommendations. Our results suggest that instead of restrictive reimbursement criteria, more decision-making power in selecting suitable patient groups could be given to multidisciplinary tumour boards. Results confirm that TARE with Y90 resin microspheres is an effective and safe treatment for liver cancer, with maintained HRQoL in most patients.

Hepatocellular Carcinoma with Vascular Invasion Treated with Resin Yttrium-90 Transarterial Radioembolization Using Single Compartment Dosimetry.

To report outcomes in hepatocellular carcinoma (HCC) patients with lobar and segmental vascular invasion treated with resin Yttrium-90 transarterial radioembolization (Y90-TARE) with single-compartment MIRD (Medical Internal Radiation Dose) model. This was a retrospective IRB approved study of patients with a diagnosis of HCC with vascular invasion undergoing resin Y90-TARE from 2014 to 2022 (n = 61). Patients with Body Surface Area dosimetry (n = 20), main portal vein invasion (n = 6) and patients with an ECOG of > 2 were excluded (n = 1) with a final cohort of 34 patients. Study population consisted of 34 patients, median age 62years [60-71], tumor size 4.2 (2.8-7.4) cm, and 82% male. The median prescribed dose was 170 (126-200) Gy. The objective response rate at 6months was 67% and disease control rate was 72%. The median survival was 18months, median progression-free survival was 9.8months. The 1- and 3-year survival rates were 76% and 57% in patients prescribed > 180Gy, compared to 29% and 15% in patients with < 180Gy (p = 0.01). Five of 15 Childs-Pugh A, ECOG < 1 patients (33%) were downstaged to resection, with complete pathologic necrosis in 40%, and 1 and 3-year survival rates of 100%. Grade-3 adverse events were seen in only 5/34 (15%), with no grade-4 or 5 adverse events. Resin Y90-TARE using single compartment MIRD model for HCC with segmental and lobar vascular invasion can result in downstaging to resection in 33% of patients and higher prescribed doses (> 180Gy) result in improved survival.

A bibliometric analysis of 30years of research on transarterial radioembolization (TARE) for hepatocellular carcinoma.

Patients with advanced hepatocellular carcinoma (HCC) have very limited treatment options, among which transarterial radioembolization (TARE) receives increasing attention, relying on its promising efficacy and fewer side effect. However, a bibliometric analysis of TARE for HCC is still lacking. This study employed bibliometric methods to analyze the related articles over the past three decades, and aimed to identify trends in clinical research comparing TARE to other treatments. Articles related with TARE for HCC were obtained from the Web of Science (WoS). After screening, the R package Bibliometrix was employed to explore the primary bibliometric characteristics. The number of publications was analyzed and mathematically fitted to a curve using Microsoft Excel 2021 and SPSS 25, and then was plotted in the graph using GraphPad Prism 8.0. VOSviewer, SCImago Graphica, and Pajek were utilized for the analysis of researchers' co-authorship, co-occurrence, and visualization. Keywords citation burst was detected by CiteSpace software. A total of 1,110 articles from 1993 to 2023 were included in our final analysis, among which the United States not only ranked the first in term of the number of published articles, also was at the forefront in other important indicators, including the total number of article citations and the average citation frequency. Riad Salem from Northwestern University, also being the organization with the greatest number of research papers, was the most active author and has published 96 papers. The keywords were classified into three clusters: 90Y microspheres for TARE, Basic research on TARE, and Clinical trial of TARE for HCC. Furthermore, we identified the most frequently cited keywords with strong citation bursts since 2020 were "multicenter," "overall survival" and "PET/CT." Our study employed a bibliometric approach to achieve the visualization research on TARE for HCC, and further revealed the trends and frontiers of TARE research, providing valuable information for researchers to identify the critical and persistent challenges and select potential partners in related area. Based on our analysis, future research focus include the clinical comparative studies on the effect of TARE and TACE combined with immunotherapies or targeted therapy, dosimetry, and personalized TARE therapy for HCC.

Landscape of transarterial chemoembolization represented interventional therapy for hepatocellular carcinoma.

This article discusses the article written by Tan et al. Transarterial chemoembolization (TACE) is one of the main treatment methods for advanced hepatocellular carcinoma (HCC). There are other vascular interventional therapies, including drug-eluting bead TACE, transarterial radioembolization, and hepatic arterial infusion chemotherapy. TACE combined with anti-angiogenesis therapy may improve tumor control and prolong progression free survival. The combination therapy of TACE and immunotherapy may improve the clinical efficacy of HCC. In future research, more basic and clinical studies are needed to explore the immunogenic intervention therapy.

Iodine-131 radioembolization boosts the immune activation enhanced by icaritin/resiquimod in hepatocellular carcinoma.

Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) 131I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 (131I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation. Decellularized liver model and SPECT/CT imaging revealed high specificity and long retention of microspheres. Radioactive distribution of 131I in tumor on 7 d following 131I-MS injection was over 7 times of that in normal liver tissue (4.26 ± 1.21 % ID/g vs 0.57 ± 0.23 % ID/g). 131I-ICT/R848-MS embolization brought significant immune activation, where the ratio of cytotoxic T lymphocytes to regulatory T cells in tumor sites upregulated from 1.75 ± 0.20 to 24.31 ± 1.79, and DC maturation in lymph nodes increased from 8.90 ± 1.51 % to 34.70 ± 3.12 %. Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE).

Radioembolization for Hepatocellular Carcinoma: a Comparison on Dual-phase Cone-beam CT, Contrast-enhanced CT (CECT)and 99mTc-macroaggregated albumin-SPECT/CT in predicting final distribution volumes and dosimetry of the post-embolization 90Y PET/CT.

Personalized treatment schemes are being systematically applied to ensure best treatment outcome in oncologic patients. This is true also for personalized dosimetry in transarterial radioembolization (TARE) in hepatocellular carcinoma (HCC) patients. Precise and detailed volumetric and functional data derived from radiological and nuclear imaging methods are essential for personalized dosimetry. We sought to evaluate accuracy of dual-phase cone-beam CT (CBCT) in comparison to pre-treatment contrast-enhanced CT (CECT), and 99mTc-macroaggregated albumin-SPECT/CT ([99mTc]MAA SPECT/CT) to predict and assess the efficacy of TARE based on post-treatment 90Y PET/CT. Thirty consecutive patients with HCC treated with TARE were included. Intraprocedural dual-phase CBCT acquisition protocol was developed to distinguish tumor volume in the early arterial phase and perfused volume of non-affected liver in the late arterial phase. Volumetric data obtained from pre-treatment CECT, dual-phase CBCT and [99mTc]MAA SPECT/CT were compared to post-treatment 90Y PET/CT considered the standard reference. Treatment simulations for final calculated dose from the different imaging derived volumes were then compared to post-treatment 90Y PET/CT. CBCT resulted as the most accurate method in predicting tumor- (R2 0.88) and perfused volumes (R2 0.82). Dosimetry prediction planning performed on derived volumes from the different methods did not show significant difference (p < 0.05), yet highest concordance with 90Y PET/CT data was observed with dual-phase CBCT. Our study shows that dual-phase CBCT acquisition is a novel alternative method for correctly and safely administering more accurate and defined doses during TARE. gov ID: NCT03981497.

Temporary Flow Diversion in Oncological Embolization Procedures Using Degradable Starch Microspheres.

This study aims to report on the application of degradable starch microspheres to provide flow diversion by means of temporary embolization of healthy tissues in oncological endovascular procedures when tumor feeding vessels are not selectively accessible. This is a multicenter retrospective analysis of patients undergoing visceral embolization procedures of malignancies. The inclusion criteria were as follows: flow diversion performed by injection of degradable starch microspheres, visceral embolization procedures with unfeasible superselective catheterism of the target, and a malignant pathology. Technical success was defined as complete flow diversion with temporary exclusion of the non-target district from arterial flow, associated with successful embolization of the target. Clinical success was intended as procedural achievement with patient clinical improvement. Sixteen patients were included in this analysis. Peripheral embolization procedures were performed in the coeliac visceral district all in oncologic patients, including 4 transarterial radioembolization work-up procedures in patients with hepatocarcinoma, 10 chemioembolization procedures in patients with hepatocarcinoma (8) or cholangiocarcinoma (2), and 2 palliative transarterial embolizations in patients with gastric cancer. Technical success was obtained in 100% of the cases, while clinical success was reached in 87.5%: in two chemioembolization procedures, despite technical success, the procedural clinical benefits were partial, with an incomplete target lesion response. Minor complications occurred in five patients (31.2%). In this study, temporary flow diversion with degradable starch microspheres during oncological embolization procedures was safe and effective; this approach is suitable to protect healthy surrounding tissues when vessels feeding the target cannot be selected with the microcatheter.

99mTc/90Y radiolabeled biodegradable gel microspheres for lung shutting fraction assessment and radioembolization in hepatocellular carcinoma theranostics

Transarterial radioembolization (TARE) is a well-established clinical therapy for the treatment of patients with intermediate to advanced hepatocellular carcinoma (HCC) or those who are ineligible for radical treatment. However, commercialized radioactive microspheres still have some issues, such as high density, complicated preparation, non-biodegradability. Furthermore, the use of different radioactive microspheres during TARE and lung shunt fraction assessment has led to inconsistencies in biodistribution in certain cases. This study employed biodegradable hyaluronic acid (HA) as the backbone and modified with bisphosphonate and methacrylic acid to prepare biodegradable gel microspheres (HAMS) using the water-in-oil emulsification and photo-crosslinking for labeling the diagnostic radionuclide of 99mTc and therapeutic radionuclide of 90Y. Both 99mTc radiolabeled HAMS (99mTc-HAMS) and radiolabeled 90Y-HAMS (90Y-HAMS) were highly efficient in radiolabeling and exhibited excellent radiostability in vitro and in vivo. 99mTc-HAMS are highly effective in assessing the LSF, while 90Y-HAMS, administered though TARE, are effective in inhibiting the growth of in situ HCC without any side effects. Both 99mTc-HAMS and 90Y-HAMS have promising clinical applications in HCC theranostics.

Locoregional Therapies for Hepatocellular Carcinoma

Several locoregional therapies (LRTs) for nonmetastatic hepatocellular carcinoma (HCC) are available; however, a global comparison of the relative efficacy of each is needed. To conduct a systematic review and direct, pairwise meta-analytic comparison of all identified randomized clinical trials evaluating the treatment of nonmetastatic HCC. A comprehensive search of PubMed and the proceedings of the American Society of Clinical Oncology and American Society for Radiation Oncology annual meetings from January 1, 2010, to November 1, 2023, was performed. Randomized clinical trials using a form of LRT (surgery with or without adjuvant therapy, radiofrequency ablation [RFA], microwave ablation [MWA], radiotherapy [RT], hepatic arterial infusion chemotherapy [HAIC], transarterial bland embolization [TAE], transarterial chemoembolization [TACE], or transarterial radioembolization [TARE]). Study eligibility and data extraction were each reviewed by 2 authors independently. Random-effects meta-analyses were used to compare treatment categories. Progression-free survival (PFS) was the primary outcome; overall survival (OS) was the secondary outcome. Forty randomized clinical trials reporting on comparative outcomes of 11 576 total patients with localized HCC treated with LRT were included. The median follow-up was 30.0 (IQR, 18.5-40.8) months. Direct pooled comparisons between treatment classes suggested improved outcomes for surgery combined with adjuvant therapy over surgery alone (PFS: hazard ratio [HR], 0.62 [95% CI, 0.51-0.75]; P < .001; OS: HR, 0.61 [95% CI, 0.48-0.78]; P < .001), surgery over RFA (PFS: HR, 0.74 [95% CI, 0.63-0.87]; P < .001; OS: HR, 0.71 [95% CI, 0.54-0.95]; P = .02), RT over TACE (PFS: HR, 0.35 [95% CI, 0.21-0.60]; P < .001; OS: HR, 0.35 [95% CI, 0.13-0.97]; P = .04), and HAIC over TACE (PFS: HR, 0.57 [95% CI, 0.45-0.72]; P < .001; OS: HR, 0.58 [95% CI, 0.45-0.75]; P < .001). No substantial heterogeneity was noted for any pairwise comparison with the exception of RT-based regimens compared with tyrosine kinase inhibitor therapy. The findings of this systematic review and direct, pairwise meta-analysis suggest that all LRTs are not equivalent for the treatment of localized HCC. The efficacy of LRTs appears hierarchical, with surgery-based management outcomes associated with the best treatment outcomes and embolization-based treatment options associated with the worst treatment outcomes.

Efficacy of Antivascular Ultrasound (AVUS) in Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is a prevalent type of primary liver cancer and one of the leading causes of cancer-related mortality worldwide. Antivascular Ultrasound (AVUS) is a novel therapy approach that utilizes the mechanical and thermal interactions between ultrasound and microbubbles to disrupt tumor vasculature or potentiate effects of chemotherapy or radiation therapy in a dose-dependent fashion. In this review, we aim to illustrate the mechanisms of AVUS, focusing on the preclinical and clinical evidence of AVUS applications in HCC. Peer-reviewed publications pertaining to the use of AVUS in HCC were collected and analyzed. 12 preclinical studies and 1 clinical trial were analyzed. At lower energy levels, AVUS can enhance tumor perfusion, facilitating the delivery of chemotherapy agents and resulting in improved therapeutic outcomes. Conversely, at higher energy levels, AVUS can disrupt tumor perfusion, leading to ischemic damage of the tumors. Combining AVUS with other therapeutic approaches, such as chemotherapy, radiation therapy, and transarterial radioembolization (TARE), can synergistically enhance therapeutic outcomes. AVUS is a promising novel treatment modality for HCC. Current evidence suggests that AVUS exhibits a dose-dependent nature, making it a versatile approach that can be effectively combined with other therapeutic regimens. Further clinical studies and long-term follow-ups are needed to establish the optimal clinical protocol and safety profile of AVUS.

Impact of IL-8 on survival after TARE in HCC: a comprehensive investigation and external validation from the SORAMIC trial.

In the treatment of hepatocellular carcinoma (HCC) with transarterial radioembolization (TARE), identifying reliable biomarkers for predicting survival outcomes remains a critical challenge. We aimed to address this gap by investigating the significance of serum cytokines associated with inflammation as potential biomarkers for the selection of patients for TARE. Our retrospective study involved 161 patients diagnosed with HCC who underwent Y90 radioembolization at our medical center between 2010 and 2020. Serum samples from a subset of 78 patients were retrospectively analyzed to determine the concentrations of pro-inflammatory cytokines. The results from the prospective SORAMIC trial were used for independent validation. With a median overall survival of 36 weeks (range 4-436), our study showed the strongest correlation between 12-week survival and IL-8 levels before treatment (p < 0.001), while other relevant interleukins, interferon-α2, INF-γ, TNF-α and MCP-1 were not associated with survival. IL-8 levels below the cut-off of 190 pg/mL were significantly associated with increased 12-week and 24-week survival, with hazard ratios of 19.01 (95% CI: 2.29-157.89) and 2.57 (95% CI: 1.05-6.31), respectively (p = 0.006 and p = 0.039, respectively). In the adjusted multivariate analysis, the 190 pg/mL cut-off for IL-8 remained independently associated with 12- (p = 0.011) and 24-week survival (p = 0.039). Similarly, the SORAMIC population showed a strong association between IL-8 levels and 36-week survival (p = 0.03). Our study emphasizes the pivotal role of IL-8 as a valuable parameter, demonstrating its potential for predicting treatment outcomes and assessing liver function in patients with HCC undergoing TARE. The robustness of these findings warrants further validation.

Correspondence to letter to the editor on "Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis".

Correspondence to letter to the editor on "Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis".

The Objective Response and Disease Control Rates in Patients with Liver Metastastic Breast Cancer Receiving Transarterial Radioembolization: A Meta-Analysis.

To meta-analyze the utility of transarterial radioembolization (TARE) in patients with liver metastatic breast cancer (BC), based on the objective response rate (ORR) and disease control rate (DCR). A literature search was performed retrieving studies with (1) at least 10 patients with liver metastatic BC treated with TARE and (2) adequate information to derive ORR and DCR. The ORR is the ratio between patients with liver lesions showing complete response (CR) or partial response (PR) over the total number of patients treated with TARE; the DCR is the ratio between patients with CR, PR, or stable disease (SD) over the total number of patients treated with TARE. Eighteen studies (650 patients) were eligible; the ORR of TARE resulted 50.71% (95% C.I.: 40.04-61.36) and the DCR resulted 88.37% (95% C.I.: 81.89-93.57). Taking into account resin spheres (395 patients), the ORR was 60.35% (95% C.I.: 46.55-73.36) and the DCR was 92.73% (95% C.I.: 87.17-96.80%). Considering glass spheres (144 patients), the ORR was 32.38% (95% C.I.: 18.43-48.16) and the DCR was 82.69% (95% C.I.: 59.29-97.26). This meta-analysis favors the use of TARE in patients with liver metastatic BC either with resin or glass spheres.

Localized hepatocellular carcinoma: Is liver-directed therapy alone as efficacious as surgical resection?

ObjectiveStudies of the efficacy of nonsurgical methods of liver-directed therapy (percutaneous microwave or radiofrequency ablation, transarterial bland embolization, chemoembolization, and/or radioembolization) in the treatment of hepatocellular cancer lack contemporaneous comparative surgical cohorts. The role of these methods of liver-directed therapy as destination treatment in hepatocellular cancer is not well defined. MethodsWe queried our institutional registry for patients undergoing resection or liver-directed therapy alone for clinical stage I to IVa hepatocellular cancer between 2012 and 2022. Multivariable regression and Cox modeling were used to identify factors associated with resection and all-cause mortality. Patients undergoing resection were 1:3 propensity matched for age, Mayo End-Stage Liver Disease score and clinical stage to those undergoing liver-directed therapy. Kaplan-Meier methods were used to compare 5-year disease-specific and overall survival for matched cohorts. ResultsThree hundred thirty patients met inclusion criteria; 45 underwent resection, and 285 liver-directed therapy. On multivariable regression, factors associated with resection included age (adjusted odds ratio: 0.96, P = .007) and Mayo End-Stage Liver Disease score (adjusted odds ratio: 0.92, P = .033). On Cox modeling, factors associated with mortality-risk included Mayo End-Stage Liver Disease score (adjusted hazards ratio: 1.03, P = .01), advanced clinical stage (stage III adjusted hazards ratio: 1.9, P = .002), and resection (adjusted hazards ratio: 0.43, P = .001). Forty-five patients undergoing resection were matched to 135 undergoing liver-directed therapy. On Kaplan-Meier comparison of matched cohorts, patients undergoing resection demonstrated improved overall survival (38.1 vs 8.4%, P = .015) but disease-specific survival similar to that for those undergoing liver-directed therapy (84.0 vs 74.0%, P = .095). ConclusionLiver-directed therapy is effective as treatment for patients with localized hepatocellular cancer providing disease-specific survival similar to that provided by surgical resection.

Is liver resection still required for patients who have predictive factors for complete pathologic necrosis after downstaging treatments of locally advanced hepatocellular carcinoma?

BackgroundLiver resection can induce complete remission after tumor downstaging in patients with locally advanced hepatocellular carcinoma. However, additional benefits of liver resection have not been investigated in patients expected to have complete pathological necrosis (CPN) following HCC downstaging. MethodsBetween 2002 and 2019, 999 patients with locally advanced HCC underwent concurrent chemoradiotherapy (CCRT) (n = 800) or transarterial radioembolization (TARE) (n = 199). Among these patients, excluding those who underwent liver transplantation, 94 who underwent liver resection (OP group) and 867 who did not undergo surgical treatment (non-OP group) were included in this study. CPN predictive factors in the OP group were analyzed using logistic regression analysis. Long-term outcomes were compared between patients with CPN (op-CPN) and those with CPN predictive factors in the non-OP group (nop-CPNPF). ResultsOf the 94 patients in the OP group, 38 (40.4 %) had CPN (CCRT, n = 72; TARE, n = 22). In the multivariate analysis, CPN predictive factors were complete radiologic response and tumor marker responders (odds ratio [OR] 18.468, p = 0.006; OR 3.698, p = 0.045). Among the non-OP group, 21 patients were in the nop-CPNPF group. There was no difference in DFS between the nop-CPNPF and op-CPN groups (40.0 ± 18.3 vs. 60.0 ± 14.0 months, p = 0.838). The OS of the op-CPN group was not higher than that of the nop-CPNPF group (5-year OS: 39.4 % vs. 33.3 %, p = 0.328). ConclusionsThe nop-CPNPF group showed long-term outcomes similar to those of the op-CPN group, suggesting that liver resection may not provide additional benefits for long-term outcomes in patients with CPN-PF after HCC downstaging.

LI-RADS radiation-based treatment response algorithm for HCC: what to know and how to use it.

Locoregional treatments (LRT) continue to advance for hepatocellular carcinoma (HCC). Selective internal radiation therapy (SIRT) or transarterial radioembolization (TARE) with radioactive 90 Yttrium (Y90) microspheres is currently widely accepted, and external beam and stereotactic body radiation (EBRT/SBRT) are increasingly used as LRT1-5. Assessment of treatment response after these radiation-based therapies can be challenging, given that the adjacent liver also undergoes treatment related changes, inflammatory changes occur, and there is a variable time for response to develop. In 2017, the liver imaging reporting and data system (LI-RADS) workgroup initially developed a single algorithm for the imaging assessment of treatment response encompassing all types of locoregional therapies, the LI-RADS treatment response (LR-TR) algorithm. Recognizing that response and imaging patterns differ between radiation and non-radiation based therapies, the LR-TR working group recently updated the algorithm to reflect the unique characteristics of tumor response for therapies involving radiation. This article aims to elucidate the changes in the new version of the LI-RADS TR, with a guide for algorithm utilization and illustration of expected and unexpected findings post liver directed therapies for HCC.