To compare segmental (s-) and subsegmental (ss-) transarterial chemoembolization (TACE) for small hepatocellular carcinoma (HCC), in terms of early complete response (CR), local tumor progression (LTP) and impact on hepatic function (ALBI score). A single-center retrospective study was conducted on consecutive patients who underwent s-TACE or ss-TACE as exclusive treatment for small (< 3 cm) HCC between 2021 and 2023. The primary endpoints were 1-month CR and LTP rate during follow-up. The effect of the treatments on hepatic function, as assessed by the ALBI score, was analyzed as a secondary endpoint. Propensity score matching (PSM), based on both baseline and procedural data, was applied to minimize selection bias. Eighty-nine patients with a total of 114 lesions were enrolled in a per-lesion analysis. No significant differences were found in terms of 1-month CR (74

Introduction: Low bone mineral density (BMD) is an increasingly recognized marker of skeletal frailty, associated with higher fracture risk and mortality in cancer patients. In advanced hepatocellular carcinoma (HCC), however, the prognostic significance of baseline BMD remains unclear. This exploratory subanalysis of the SORAMIC trial evaluated whether CT-derived BMD predicts overall survival (OS) in patients with unresectable HCC. Methods: In this exploratory post hoc study, 342 patients with unresectable HCC and preserved liver function (Child-Pugh ≤B7) were enrolled in the palliative arm of the SORAMIC trial and randomized to receive either sorafenib monotherapy (n = 170) or selective internal radiation therapy (SIRT) plus sorafenib (n = 172). BMD (in Hounsfield units [HU]) was measured at the third lumbar vertebra on pre-treatment contrast-enhanced CT scans. Patients were stratified into low and high BMD groups using three definitions: the cohort median (139.5 HU for men, 130.0 HU for women), <160 HU for men and <175 HU for women (Meister criteria), and <160 HU (Jang criteria). Cox regression analyses assessed the impact of BMD on OS. Results: Median OS in the overall cohort was 11.1 months. No significant association between BMD and OS was observed in the entire cohort or within the sorafenib and SIRT/sorafenib subgroups. Similar nonsignificant results occurred in alcohol-, viral-, and metabolic dysfunction-associated steatohepatitis/metabolic dysfunction-associated steatotic liver disease-induced HCC subgroups. Conclusion: Baseline CT-derived BMD does not predict OS in advanced HCC patients, indicating it is not a robust prognostic biomarker in this setting. Low BMD does not affect a patient’s resilience to SIRT.

The aim of this survey was to obtain a snapshot of the real-life practice of locoregional treatment in hepatocellular carcinoma patients, which can sometimes greatly diverge from the guidelines. This survey, elaborated before and during the Mediterranean Interventional Oncology Live (MIO-Live) 2024 congress, was based on a pre-congress questionnaire and an in-congress questionnaire via a voting system during an expert panel discussion simulating a multidisciplinary tumor board for hepatocellular carcinoma patients. Voters and the expert panel were from various centers all over the world. Eighty participants answered the pre-congress questionnaire. Seventy-two, 64, and 78 participants answered the in-congress questionnaire through the voting system for the early-, intermediate-, and advanced-stage HCC categories, respectively. Trends in locoregional treatment choice and application were obtained and confronted with current guidelines for hepatocellular carcinoma treatment. The survey showed how hepatocellular carcinoma patients are treated with locoregional techniques in real-life practice, highlighting the difference that can arise between multidisciplinary tumor board decisions and current guidelines.

Background. The clinical complexity of patients with hepatocellular carcinoma (HCC), the availability of multiple therapeutic options, and clinical therapeutic intents could make it challenging to identify an unequivocal limit between conversion, downstaging/downsizing, and neoadjuvant therapies and curative or palliative intent treatments and to dimension the most proper sequential therapeutic strategy for each patient. Summary. The concept of converse therapeutic hierarchy could rationally embrace all the different sequential treatment options (e.g., from surgery to systemic therapy) and the different therapeutic clinical intents (e.g., curative, neoadjuvant, downstaging/downsizing, conversion, and palliative), sharing the common goal of converting the patient with HCC from a less to a more favourable condition to improve the chance (higher applicability – conversion or downstaging intent) or the effectiveness (better postoperative outcome – neoadjuvant intent) of “intent-to-cure treatments”. This narrative review aims to introduce and explain the umbrella concept of the converse therapeutic hierarchy as a valuable framework for everyday clinical practice, enabling clinicians to better define ideal candidates and good responders for each sequential strategy. Furthermore, the converse therapeutic hierarchy concept represents a flexible container that should be continuously filled with new scientific evidence to build different sequential treatment strategies in the multidisciplinary and multi-step management of patients with HCC. An operative and pragmatic definition of the various sequential treatment strategies, based on the initial probability of intent to cure therapy for patients with HCC, has also been proposed. This probability varies from very high to low. It is related to the initial treatment choice and the multiparametric patient evaluation (e.g., patient’s fitness, tumour features, liver function, and technical aspects) done by an expert multidisciplinary tumour board. Key messages. The converse therapeutic hierarchy concept represents a valuable and pragmatic framework for everyday clinical practice. It also serves as a flexible container that must be filled with new high-quality evidence and expert consensus to better define the clinical boundaries between the different HCC sequential treatment strategies (e.g., neoadjuvant, downstaging/downsizing, and conversion).

Periinterventional imaging of patients with hepatocellular carcinoma (HCC) during local and locoregional therapies plays a crucial role in clinical outcome by guiding treatment allocation, planning, and application. However, there is a considerable variety in clinical routine in terms of timing, modality, and imaging protocols. This study aimed to guide the standardization of the imaging procedures for patients with HCC by conducting a Delphi consensus-finding survey. A multidisciplinary, multinational survey was conducted to standardize the imaging of patients with HCC using the Delphi method. Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the recommendations for imaging before, during, and after thermal ablation, transarterial chemoembolization, radioembolization, and stereotactic body radiation therapy were established. This consensus protocol provides a foundational guide for imaging in the daily clinical management of HCC patients, as well as for prospective studies assessing local and locoregional therapies. Question There are clear recommendations for the respective therapies/disease stages in HCC, but only to a limited extent for all-around imaging of local therapies. Findings This study conveyed a Delphi consensus-finding survey amongst European experts from multiple medical fields to standardize the periinterventional imaging of HCC patients. Clinical relevance These recommendations can guide both daily clinical practice and prospective trials focused on local and locoregional therapies.

Drug-eluting microsphere transarterial chemoembolization (DEM-TACE) reduces systemic exposure to chemotherapeutic drugs compared with conventional TACE but permanently occludes the embolized vessels, potentially obviating the possibility of re-treatment with TACE. Temporary embolization by resorbable BioPearl (TM) microspheres might facilitate subsequent re-treatments. We herein describe the trial protocol of BIOPEARL-ONE, a prospective, single-arm, multicenter, post-market clinical follow-up study. The primary objectives are technical success and safety following the use. DEM-TACE with doxorubicin-loaded BioPearl (TM) for unresectable hepatocellular carcinoma (HCC). The secondary objectives are tumor response, duration of response, progression-free survival, and survival rate at 18 months. Fifty patients with HCC nodules smaller than 5 cm and within the up-to-7 criteria will be enrolled. Clinical Trial Registration: NCT05911633

Background/Objectives: Transarterial chemoembolization (TACE) is a widely accepted and minimally invasive treatment for primary and metastatic liver cancer. Performing TACE with drug-eluting beads helps obtain a greater drug concentration in the target lesion, significantly reducing systemic drug leakage, liver toxicity, and adverse events. The aim of this study is to describe the safety and feasibility of TACE performed with BioPearlTM, the first biodegradable drug-eluting microspheres. Methods: This was a retrospective observational study on 13 consecutive patients affected by hepatocellular carcinoma (HCC) treated with doxorubicin-loaded-BioPearlTM-TACE. Data on safety, feasibility, and tumor response were collected. Results: One intra-procedural catheter blockage was registered, as well as two post-treatment bilomas that required additional treatment. No severe general drug-related side effects were detected at the follow-up. The 1-month overall disease control was 90.9%, with six complete responses. Conclusions: Data suggest that chemoembolization with BioPearlTM is feasible and safe for the treatment of HCC as indicated by good tolerability.

An international survey was conducted by the Cardiovascular Interventional Radiological Society of Europe (CIRSE) to evaluate radioembolization practice and capture opinions on real-world clinical and technical aspects of this therapy. A survey with 32 multiple choice questions was sent as an email to CIRSE members between November and December 2022. CIRSE group member and sister societies promoted the survey to their local members. The dataset was cleaned of duplicates and entries with missing data, and the resulting anonymized dataset was analysed. Data were presented using descriptive statistics. The survey was completed by 133 sites, from 30 countries, spanning 6 continents. Most responses were from European centres (87/133, 65

In this issue, Edeline et al compared the results of standard systemic chemotherapy (gemcitabine and cisplatin or gemcitabine and oxaliplatin) versus the combination of selective internal radiation therapy (SIRT) and chemotherapy, as first-line treatment in patients with liver-only intrahepatic cholangiocarcinoma (iCCA).1 By collecting individual patients data from 5 large prospective clinical trials of systemic therapy alone and 1 trial of systemic therapy plus SIRT (MISPHEC) and applying the emulated target trial paradigm as a statistical method, the authors showed that the combination of SIRT and chemotherapy is able to improve both overall survival (OS) and progression-free survival.1 The inverse probability treatment weighting using a propensity score was also implemented to balance confounding factors between groups. Although prospective randomized trials are still desirable to confirm these findings, these results, derived from a solid statistical method, represent a step forward to better delineate the role of SIRT in the treatment algorithm of iCCA. Moreover, the absolute gain of about 6 months in both OS and progression-free survival is also relevant from a clinical point of view in a population of unresectable, liver-only iCCA. The low rate of secondary resections (8% vs. 3% after adjustment) further highlights the challenging patient population analyzed. Numerous publications reported the safety and efficacy of SIRT both in first-line and at disease progression or recurrence, with a median OS of ~14 months, consistent across the different studies.2,3 The longer median OS (21.7 mo) reported by Edeline et al in the combination arm may be the result of multiple factors.1,4 The MISPHEC trial included only treatment-naïve patients with liver-only disease or very limited extrahepatic disease.4 Moreover, the trial investigated a combined approach in which SIRT was to be performed at predefined time points (days 3–21 of cycles 1 and 3 in patients with unilobar and bilobar disease, respectively), with no delays in chemotherapy.4 The rational of this combination and the potential synergistic effects between chemotherapy and SIRT are not yet fully understood, although it is acknowledged that the radiation damage induced by SIRT may enhance the susceptibility of cancer cells to chemotherapy. Finally, the dosimetric approach proposed by the MISPHEC trial was different compared with previous studies. Together with the standard dosimetry adopted with glass microspheres (administered activity of 120 Gy to the target liver volume), the protocol allowed to use the intensified personalized dosimetry derived from the experience gained treating HCC (at least 205 Gy to the tumor and 150 Gy to the target liver), and authors reported 120 Gy median absorbed dose to the target liver and 317 Gy to the tumor, much higher compared with other studies.2 Dosimetry data on iCCA are still lacking. However, preliminary observations suggested that a mean tumor absorbed dose of at least 75 Gy with resin microspheres and 150 Gy using glass spheres are needed to significantly improve survival,5 in line with what is reported in the MISPHEC study.4 However, achieving higher tumor absorbed doses without harming the nontarget liver volume requires some specific anatomical features. The tumors should be confined, possibly to 1 hemiliver or contiguous segments, and should display a sufficient arterial vascularization as to allow selective intratumoral uptake of the microparticles. In this scenario, naïve patients represent the ideal candidates, devoid of the risk of vascular impairments caused by previous loco-regional or systemic treatments. Finally, as suggested for HCC,6 the preliminary diagnostic work-up with the prevision of the expected tumor absorbed dose should represent the main driver to select iCCA patients for SIRT and should become part of the inclusion criteria in future clinical studies. The study showed that SIRT has an effect on controlling tumor progression, as demonstrated by the longer progression-free survival in the combination treatment arm.1 Moreover, in the unadjusted population, the rate of secondary resections was higher in patients treated with SIRT, possibly determined by the tumor downsizing and stimulation of contralateral liver hypertrophy.7 Indeed, the MISPHEC trial pointed out that a more intensive regimen aiming to convert patients to resection could be justified in patients with unilobar disease and no cirrhosis, who are initially considered unresectable due to close proximity to major vessels and/or insufficient liver remnant.4 As pointed out by the authors, the study included only patients treated with standard chemotherapy, not considering the more recent introduction of durvalumab in the first line following the positive results of the phase 3 TOPAZ-1 trial.8 Also, considering the positive results of the KEYNOTE-966 phase 3 trial9 further supporting the role of chemoimmunotherapy as the standard of care in the first-line setting, future studies are needed to understand if and to what extent the addition of SIRT may further enhance the benefits of immunotherapy. Furthermore, any future investigation will have to take into account the tumor molecular profiling, assessing how SIRT could be integrated into the rapidly evolving scenario of iCCA treatments. The natural conclusion of the presented findings is that there is a need for further prospective and, possibly, randomized trials. However, previous experiences (such as the SIRCCA trial) have shown that randomized controlled trials are difficult to be completed in the setting of a highly selected population, such as the one suggested by this analysis (ie, with unresectable, liver-only disease, in which high selective tumor absorbed dose should be achieved). There is a need to exploit and verify alternative, more realistic and less resource-consuming models that can produce high-quality scientific evidence that may impact guidelines, recommendations, and clinical practice. The debate is open, but in the present study, Edeline et al are showing how to build evidence creating a sort of "scientific consortium," sharing data collected from previous prospective trials and analyzing these data through solid statistical analysis. The study is based on the emulated target trial paradigm that aims to overcome the challenges and limitations of randomized controlled trials by simulating the randomization process and evaluating the treatment effects in a hypothetical cohort of patients.10 To mitigate the well-known limitations of this paradigm and strengthen the robustness of their findings, the authors combined multiple data sources and several statistical methods. The obtained results are convincing and provide valuable clinical information, useful as a starting point for future investigations. In conclusion, the study by Edeline et al deserves attention since it sets the basis for a better definition of the role of SIRT in combination with systemic therapy as first-line approach for patients with liver-only unresectable iCCA. Future studies are warranted to investigate how results may be affected by the tumor molecular profile, to improve the personalized dosimetry approach, and to test newer combinations of SIRT with chemoimmunotherapy, in the rapidly evolving field of iCCA. Efforts are needed in the scientific community to conceive newer strategies to produce solid scientific evidence in a realistic, sustainable, and ethical way.

Background and AimsOur purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. MethodsThis is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index >= 25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) x SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. ResultsIn the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. ConclusionsMyosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. Impact and implicationsAssociations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC. image

Hepatocellular carcinoma represents an important cause of death worldwide. Early-stage hepatocellular carcinoma patients not suitable for surgery can be treated with a variety of minimally invasive locoregional interventional oncology techniques. Various guidelines in different countries address the treatment of hepatocellular carcinoma, but the actual treatment is usually discussed by a multidisciplinary tumor board in a personalized manner, leading to potential treatment differences based on Western and Eastern perspectives. The aim of this paper is to integrate literature evidence with the eminent experiences collected during a focused session at the Mediterranean Interventional Oncology (MIO) Live Congress 2023.

BACKGROUND:Body composition parameters have been reported to be prognostic factors in patients with oncologic diseases. However, the available data on patients with HCC are conflicting. The aim of this study was to assess the impact of body composition on survival in patients with HCC treated with sorafenib or selective internal radioembolization (SIRT) and sorafenib.METHODS:This is an exploratory subanalysis of the prospective, randomized controlled SORAMIC trial. Within the palliative arm of the study, patients were selected if a baseline abdominal CT was available. A broad set of skeletal muscle and adipose tissue parameters were measured at the L3 level. Low skeletal muscle mass (LSMM) and density parameters were defined using published cutoffs. The parameters were correlated with overall survival.RESULTS:Of 424 patients in the palliative study arm, 369 patients were included in the analysis. There were 192 patients in the combined sorafenib/SIRT and 177 patients in the sorafenib group. Median overall survival was 9.9 months for the entire cohort and 10.8 and 9.2 months for the SIRT/sorafenib and sorafenib groups, respectively. There was no relevant association of either body composition parameter with overall survival in either the overall cohort or in the SIRT/sorafenib or sorafenib subgroups.CONCLUSIONS:This subanalysis of the prospective SORAMIC trial does not suggest a relevant influence of body composition parameters of survival in patients with advanced HCC. Body composition parameters therefore do not serve in patient allocation in this palliative treatment cohort.

To assess the cost-utility of initial treatment with drug-eluting microspheres (DEM) transarterial chemoembolization (TACE) versus conventional (C)-TACE in patients with hepatocellular carcinoma considering the perspective of a Local Healthcare Authority in Italy. The economic evaluation is based on a retrospective single-center study and individual patients’ data whose details have been previously reported. The impact of initial treatment with DEM-TACE or C-TACE on disease progression, mortality, and direct health costs over a lifetime horizon were simulated and compared in terms of incremental cost-utility ratio expressed as costs per quality adjusted life years (QALY). Costs included direct health costs related to the first chemoembolization procedure and all subsequent follow-up costs associated with health care resources used for disease management. Probabilistic (PSA) sensitivity analysis was used to assess the robustness of the results. A total of 101 patients in each treatment group were considered. All over the time-horizon median costs were €3,145.14 and €2,158.32 in the DEM-TACE and C-TACE group, respectively (p < 0.001); while mean costs were € 24,619 and € 17,001, respectively (p < 0.001). The ICUR was 6,461.86 €/QALY when using median costs derived from the study population as input for the health-economic evaluation and 49,932.15 €/QALY when the mean costs were considered. Results from PSA highlighted that using median costs DEM-TACE was always cost-effective, while using mean costs, it was preferable only 24.7% of times. The higher prices of DEMs are counterbalanced by the positive impact on QALY.

Using data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours. We analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS). All-cause AEs were reported in 401/1027 (39.1

Abstract Background Parameters of body composition have prognostic potential in patients with oncologic diseases. The aim of the present study was to analyse the prognostic potential of radiomics‐based parameters of the skeletal musculature and adipose tissues in patients with advanced hepatocellular carcinoma (HCC). Methods Radiomics features were extracted from a cohort of 297 HCC patients as post hoc sub‐study of the SORAMIC randomized controlled trial. Patients were treated with selective internal radiation therapy (SIRT) in combination with sorafenib or with sorafenib alone yielding two groups: (1) sorafenib monotherapy (n = 147) and (2) sorafenib and SIRT (n = 150). The main outcome was 1‐year survival. Segmentation of muscle tissue and adipose tissue was used to retrieve 881 features. Correlation analysis and feature cleansing yielded 292 features for each patient group and each tissue type. We combined 9 feature selection methods with 10 feature set compositions to build 90 feature sets. We used 11 classifiers to build 990 models. We subdivided the patient groups into a train and validation cohort and a test cohort, that is, one third of the patient groups. Results We used the train and validation set to identify the best feature selection and classification model and applied it to the test set for each patient group. Classification yields for patients who underwent sorafenib monotherapy an accuracy of 75.51% and area under the curve (AUC) of 0.7576 (95% confidence interval [CI]: 0.6376–0.8776). For patients who underwent treatment with SIRT and sorafenib, results are accuracy = 78.00% and AUC = 0.8032 (95% CI: 0.6930–0.9134). Conclusions Parameters of radiomics‐based analysis of the skeletal musculature and adipose tissue predict 1‐year survival in patients with advanced HCC. The prognostic value of radiomics‐based parameters was higher in patients who were treated with SIRT and sorafenib.

The value of gadoxetic acid in the diagnosis of hepatocellular carcinoma (HCC), based on perfusion criteria, is under dispute. This post-hoc analysis of the prospective, phase II, randomized, controlled SORAMIC study compared the accuracy of gadoxetic acid-enhanced dynamic magnetic resonance imaging (MRI) (arterial, portovenous, and venous phase only) versus contrast-enhanced computed tomography (CT) for stratifying patients with HCC to curative ablation or palliative treatment. Two reader groups (radiologists, R1 and R2) performed blind reads of CT and gadoxetic acid-enhanced MRI (contrast dynamics only). A truth panel, with access to clinical and imaging follow-up data, served as reference. Primary endpoint was non-inferiority (margin: 5% points) of MRI vs. CT (lower 95% confidence interval [CI] > 0.75) in a first step and superiority (complete 95% CI > 1) in a second step. The intent-to-treat population comprised 538 patients. Accuracy of treatment decisions was 73.4% and 70.8% for CT (R1 and R2, respectively) and 75.1% and 70.3% for gadoxetic acid-enhanced dynamic MRI. Non-inferiority but not superiority of gadoxetic acid-enhanced dynamic MRI versus CT was demonstrated (odds ratio 1.01; CI 0.97–1.05). Despite a theoretical disadvantage in wash-out depiction, gadoxetic acid-enhanced dynamic MRI is non-inferior to CT in accuracy of treatment decisions for curative ablation versus palliative strategies. This outcome was not subject to the use of additional MR standard sequences.

A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the “ideal” intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73