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New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 8050

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Dr. Riccardo Inchingolo

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Ospedale General Regionale F. Miulli, Acquaviva delle Fonti, Italy
Interests: radiology; oncology

Dr. Stavros Spiliopoulos

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New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor, National and Kapodistrian University of Athens, Athens, Greece
Interests: radiology

Dr. Riccardo Memeo

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Unit of Hepato-Pancreatic-Biliary Surgery, "F. Miulli" General Regional Hospital, 70021 Acquaviva Delle Fonti, Italy
Interests: gastroiontestinal cancers; robotic surgery; surgical oncology
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Dear Colleagues,

Hepatocellular carcinoma (HCC) is the most frequently observed primary malignant liver tumor and is a major cause of worldwide mortality. Despite the advent of screening programs for patients with known risk factors, a substantial number of patients are ineligible for curative surgery at presentation. Thus, locoregional treatments now hold a pivotal role in HCC management; trans-arterial chemoembolization, percutaneous ablation and more recently selective internal radiation therapy are often the first-line treatments for selected stages of HCC or serve as a bridge to liver transplantation.

The goal of this Research Topic is to provide a comprehensive overview of various image-guided minimally invasive therapies available for HCC with an assessment of novel combination regimens and future perspectives, to better investigate the role of radiology in the assessment of responses to locoregional treatments for HCC. We welcome you to submit basic and clinical research articles and reviews.

Dr. Riccardo Inchingolo
Dr. Stavros Spiliopoulos
Dr. Riccardo Memeo
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hepatocellular carcinoma
cirrhosis
liver
interventional oncology
trans-arterial chemo embolization
selective internal radiation therapy
ablation
radiology

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Published Papers (9 papers)

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17 pages, 2154 KB

Open AccessArticle

Impact of Serum Albumin Levels on Prognosis and Recurrence in Patients with Hepatocellular Carcinoma

by Naoko Hayata, Atsushi Hosui, Tomohide Kurahashi, Shigeki Suemura, Akane Namiki, Akino Okamoto, Takafumi Tanimoto, Hiroki Murai, Kohsaku Ohnishi, Motohiro Hirao, Takuya Yamada and Naoki Hiramatsu

Cancers 2025, 17(18), 2971; https://doi.org/10.3390/cancers17182971 - 11 Sep 2025

Viewed by 25

Abstract

Background: Liver function is a critical factor, both in the selection of treatment and in the prediction of prognosis in patients with hepatocellular carcinoma (HCC). The ALBI grade, introduced as a more objective method of assessing liver function, utilizes serum albumin (Alb) and total bilirubin (Bil) levels. Although albumin is widely recognized for its role in maintaining colloid osmotic pressure and regulating plasma volume, recent studies have implicated it in tumor progression, invasion, and metastasis. The purpose of this study is to determine the impact of serum albumin levels on overall survival (OS) and tumor invasion/metastasis in HCC patients with the same liver function (ALBI grade) at the time of diagnosis. Methods: In this study, 285 patients diagnosed with primary HCC at our institution from 2015 to 2019 were classified by ALBI grade and analyzed. Among them, 78 patients with ALBI grade 2 status were selected to evaluate the impact of albumin level. To further isolate the effect of albumin rather than bilirubin, patients in the ALBI grade 2 cohort were divided into two groups based on mean values of Alb (3.5 g/dL) and Bil (1.0 mg/dL). Alb normal group (Group A): Alb ≥ 3.5 g/dL, Bil ≥ 1.0 mg/dL (n = 42). Bil normal group (Group T): Alb < 3.5 g/dL, Bil < 1.0 mg/dL (n = 36). Liver function was almost the same in these two groups based on the ALBI grade. OS, progression-free survival (PFS), types of recurrence, and pathological findings were compared between the two groups. OS was analyzed by the log-rank test, and comparisons between the two groups were performed by the t-test and chi-square test, with p < 0.05 indicating statistical significance. Results: OS was significantly worse in Group T than in Group A before and after propensity score matching based on age, performance status, and HCC stage (p < 0.001 and p = 0.011). Among the 44 patients who received curative treatment (surgery or radiofrequency ablation), OS was also significantly worse in Group T (p < 0.001). An analysis of the recurrence patterns of 44 curatively treated patients revealed that Group T had significantly shorter PFS (p < 0.001), and all recurrence patterns were multiple (p = 0.002). Pathological analysis in 28 surgical patients showed that serosal invasion was present in significantly more patients in Group T (p = 0.003). Conclusions: Low serum albumin levels in patients with HCC indicate both liver dysfunction and increased tumor invasion and metastasis. Nutritional support and albumin supplementation may help reduce intrahepatic metastases and improve prognosis. Further studies are needed to explore the underlying mechanisms and therapeutic potential. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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14 pages, 586 KB

Open AccessArticle

Surgical Outcomes of Lenvatinib Treatment Followed by Liver Resection for Advanced Hepatocellular Carcinoma Larger than 10 cm

by Hideki Yokoo, Shoichiro Mizukami, Hiroyuki Takahashi, Tomoki Takizawa, Katsuro Enomoto, Kai Makino, Hiroki Takahata, Yuki Adachi and Koji Imai

Cancers 2025, 17(17), 2818; https://doi.org/10.3390/cancers17172818 - 28 Aug 2025

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Background: Hepatocellular carcinoma (HCC) larger than 10 cm has a poor prognosis, with high recurrence rates, particularly distant metastases. This study examined whether lenvatinib treatment followed by liver resection improves the outcomes for large HCCs compared with upfront surgery. Methods: We retrospectively analyzed 30 patients with HCC larger than 10 cm who underwent hepatectomy at our institution between January 2008 and December 2023. The study cohort included 30 patients: 9 received preoperative lenvatinib treatment followed by hepatectomy (LEN group), while 21 patients underwent upfront surgery (UFS group). We compared the clinicopathological characteristics, surgical outcomes, recurrence patterns, and survival between the two groups. Results: The median duration of lenvatinib administration was 1.8 months, with partial response in two patients (22.2%) and stable disease in seven patients (77.7%). While lenvatinib treatment significantly decreased serum albumin levels (p < 0.05) and increased ALBI scores (p = 0.03), the surgical outcomes including blood loss, operation time, and complication rates were comparable between the two groups. The 3-year recurrence-free survival rate was significantly higher in the LEN group compared with the UFS group (66.7% vs. 16.1%, p = 0.027). The 3-year overall survival rate was also higher in the LEN group, though not statistically significant (85.7% vs. 56.1%, p = 0.059). Notably, distant metastasis rates were lower in the LEN group compared with the UFS group (11.1% vs. 47.6%, p = 0.10). Conclusions: Preoperative lenvatinib treatment followed by hepatectomy for large HCC (> 10 cm) may reduce recurrence, particularly distant metastases, and potentially improve long-term survival. This approach may be a promising strategy for large HCCs, which traditionally have a poor prognosis with upfront surgery alone. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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17 pages, 529 KB

Open AccessArticle

Contemporary Clinical Utilization of Radioembolization with Immune Checkpoint Inhibitors as First-Line Treatment in HCC: Real-World Report on Safety and Outcomes

by Kelley G. Núñez, Tyler Sandow, Alexandre Grahovac, Ricardo Vallejo-Calzada, Juan Gimenez, Humberto Bohorquez, Ari Cohen, Jonathan Mizrahi, Lingling Du and Paul Thevenot

Cancers 2025, 17(17), 2745; https://doi.org/10.3390/cancers17172745 - 23 Aug 2025

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Immune checkpoint inhibitors (ICIs) have emerged as first-line therapy for advanced-stage HCC with modest response rates (<33%). Combination treatments offer the potential to improve response rates while improving outcomes. This study evaluates the safety and outcomes of first-line Yttrium-90 plus ICI (⁹⁰Y-ICI). A retrospective, multi-center study was conducted in HCC patients receiving first-line ⁹⁰Y-ICI with atezolizumab plus bevacizumab (Atezo/Bev) or tremelimumab plus durvalumab (Treme/Durva). Treatment response was evaluated at follow-up for planned ⁹⁰Y treatment cycle. Time-to-event measures of time to progression (TTP), progression-free survival (PFS), and overall survival (OS) served as primary endpoints, with first cycle response rates and AEs as secondary outcomes. This study included 37 patients receiving ⁹⁰Y-ICI from 2021 to 2024 (16-month median follow-up). The cohort was predominantly Child-Pugh A (92%) with HCV-related cirrhosis (67%), advanced stage (54%), and a median index HCC size of 8.0 cm (IQR: 6—12 cm). Grade 3–4 AEs occurred in six patients (16%). The target objective response (OR) rate was 83%, with a 50% target complete response (CR) rate. Overall OR was 61% with an overall CR of 39%. Median PFS was 11 months with 1-year rates of 50%. Patients with a target CR had improved TTP (p = 0.004), PFS (p = 0.003), and OS (p = 0.003). The cohort’s 2-year OS was 41% with a median OS of 19 months (CI: 12–37 months). First-line ⁹⁰Y-ICI therapy in HCC is safe and effective, with no deviation in anticipated results. Patients achieving target CR showed significantly improved TTP, PFS, and OS, supporting target CR as an optimal treatment target. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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9 pages, 563 KB

Open AccessArticle

A Retrospective Study on Biliary Cooling During Thermal Ablation of Central Liver Tumors in Taiwan

by Yi-Chun Chou, Chih-Wei Tseng, Ping-Hung Ko, Tsung-Hsing Hung, Hsing-Feng Li, Kuo-Chih Tseng, Ching-Sheng Hsu and Chih-Ying Wang

Cancers 2025, 17(11), 1859; https://doi.org/10.3390/cancers17111859 - 31 May 2025

Viewed by 611

Abstract

Background: Thermal ablation of centrally located liver tumors carries an increased risk of bile duct injury due to their proximity to the biliary tree. We aim to evaluate whether biliary cooling using a nasobiliary tube can effectively mitigate bile duct injury during the ablation process. Methods: We retrospectively analyzed the data of 322 patients who underwent thermal ablation at Dalin Tzu Chi Hospital from July 2020 to June 2023 and identified those who received prophylactic biliary cooling during thermal ablation for central liver tumors. Data including demographics, tumor characteristics, procedural details, and clinical outcomes were analyzed. Results: Among the 322 patients who underwent thermal ablation, 9 with central liver tumors received prophylactic biliary cooling. The median distance between the tumor and the central bile duct was 1 mm (range: 0–4 mm), the temperature of the cold normal saline was 4 °C, and the mean volume of normal saline infused was 150 mL (range: 100–200 mL). Complete ablation was achieved in all patients in a single session without any biliary injury. One patient developed acute cholangitis after ENBD placement, which resolved with antibiotic therapy. Conclusions: Biliary cooling with 4 °C cold saline through a nasobiliary tube can improve the safety and effectiveness of thermal ablation for central liver tumors. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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14 pages, 2421 KB

Open AccessArticle

Application and Validation of a transRADial Access Score (RAD-Access) in Patient Selection for Safe Radial Access in Liver Cancer Intra-Arterial Procedures

by Roberto Iezzi, Alessandro Posa, Andrea Contegiacomo, Alessandro Maresca, Elena Rodolfino, Biagio Merlino, Tiago Bilhim and Marcelo Guimaraes

Cancers 2025, 17(9), 1385; https://doi.org/10.3390/cancers17091385 - 22 Apr 2025

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Abstract

Objectives: To develop and internally validate a pre-treatment score for the safe selection of the best candidates for the transradial approach when performing liver cancer intra-arterial procedures. Methods: One hundred and twenty-two patients undergoing hepatic endovascular treatments via radial access between January and December 2022 were retrospectively selected to develop a prediction model. Pre-procedural imaging data were analyzed, and variables were selected to develop the RAD-access score. Intra-procedural data were analyzed to assess effective procedural complexity (ePC). The relationship between ePC and pre-procedural variables was statistically tested, and cutoff points were defined. Results: A final score (RAD-access) was created and prospectively validated on 139 patients enrolled between June and September 2023. Aortic arch diameter and angulation, left subclavian artery angulation, suprarenal abdominal aorta diameter, celiac trunk take-off angle, and radial artery diameter were the significant variables used to build the score. In the validation cohort, based on the pre-treatment RAD-access score, 69 patients underwent a transradial approach, with a significantly lower ePC rate obtained (78.2% easy, 20.3% intermediate, 1.5% complex). No major adverse events occurred. Conclusions: Pre-treatment RAD-access score provides a good prediction for the procedural complexity of the transradial approach in patients undergoing liver cancer intra-arterial treatments, identifying the best candidates for an easy and safe transradial procedure. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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10 pages, 986 KB

Open AccessArticle

Robotic Liver Resection for Hepatocellular Carcinoma: A Multicenter Case Series

by Silvio Caringi, Antonella Delvecchio, Maria Conticchio, Francesca Ratti, Paolo Magistri, Andrea Belli, Graziano Ceccarelli, Francesco Izzo, Marcello Giuseppe Spampinato, Nicola De’Angelis, Patrick Pessaux, Tullio Piardi, Fabrizio Di Benedetto, Luca Aldrighetti and Riccardo Memeo

Cancers 2025, 17(3), 415; https://doi.org/10.3390/cancers17030415 - 27 Jan 2025

Cited by 2 | Viewed by 1619

Abstract

Background: Liver resection is the standard treatment for resectable hepatocellular carcinoma (HCC). The advent of robotic surgery has extended its application in liver surgery, reducing post-operative complications without compromising oncological safety. This study is a retrospective series with the aim of analyzing the preoperative patient’s and tumor’s characteristics and evaluating intraoperative and post-operative data in terms of hospital stay, complications, and oncological radicality. Methods: Data were collected from a multicenter retrospective database that includes 1070 consecutive robotic liver resections (RLRs) performed in nine European hospital centers from 2011 to 2023. Of the entire series, 343 liver resections were performed for HCC. Results: A total of 247 patients (72.3%) had mono-focal lesions. Major hepatectomies and anatomical resections have been perfomed in 87% and 55% of patients, respectively. All 17 conversions (4.95%) were to the open approach. The operative mean time was 239.56 min and the estimated blood loss was 229.45 mL. The overall post-operative complication rate was 22.74%, but severe complications occurred in 4.08% of patients and one of them (0.29%) was reoperated on. The mean hospital stay was 5.82 days with a mean ICU stay of 0.9 days. Twenty-six resections (7.6%) were R1 parenchymal. Forty-six patients (4.08%) were readmitted to the hospital within 90 days after discharge and seventy-eight patients (22.74%) had disease recurrence. Total deaths included 36 (10.5%) patients with a 90-day mortality of 0.9%. Conclusions: Robotic liver resection for HCC is feasible and safe when performed in experienced centers by surgeons who have completed the learning curve. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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16 pages, 3526 KB

Open AccessArticle

Evaluation of Predictive Factors for Transarterial Bleomycin–Lipiodol Embolization Success in Treating Giant Hepatic Hemangiomas

by Arkadiusz Kacała, Mateusz Dorochowicz, Adrian Korbecki, Michał Sobański, Agata Zdanowicz-Ratajczak, Dariusz Patrzałek, Dariusz Janczak and Maciej Guziński

Cancers 2025, 17(1), 42; https://doi.org/10.3390/cancers17010042 - 26 Dec 2024

Cited by 1 | Viewed by 1053

Abstract

Introduction: Giant hepatic hemangiomas are challenging to manage, requiring effective therapeutic approaches. Transarterial bleomycin–lipiodol embolization (TACE) has shown promise as a treatment option, yet predictive factors for its success are not well defined. This study aimed to assess the efficacy of TACE for giant hepatic hemangiomas and identify factors influencing treatment outcomes. Methods: A retrospective analysis of 31 adult patients who underwent TACE with bleomycin and lipiodol between December 2014 and October 2022 was conducted. Clinical parameters including age, sex, hemangioma location, lesion size, bleomycin dose, number of TACE sessions, and follow-up duration were evaluated. The primary outcome was hemangioma volume reduction, with statistical analyses identifying factors associated with significant lesion regression. Results: Higher bleomycin doses and longer intervals from procedure to follow-up were positively correlated with hemangioma volume reduction, while variables such as patient sex and lesion location showed no statistically significant impact on clinical success. The findings suggest that increased bleomycin dosage and extended follow-up periods may enhance treatment efficacy. Conclusions: The study identifies bleomycin dose and follow-up duration as predictive factors for TACE success in treating giant hepatic hemangiomas, underscoring their role in optimizing therapeutic strategies. These insights contribute to improved treatment personalization for patients with giant hepatic hemangiomas and highlight the need for further prospective studies to validate and expand upon these findings. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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11 pages, 3964 KB

Open AccessArticle

Adverse Events in Targeted Therapy for Unresectable Hepatocellular Carcinoma Predict Clinical Outcomes

by Kenji Imai, Koji Takai, Masashi Aiba, Shinji Unome, Takao Miwa, Tatsunori Hanai, Atsushi Suetsugu and Masahito Shimizu

Cancers 2024, 16(18), 3150; https://doi.org/10.3390/cancers16183150 - 14 Sep 2024

Cited by 3 | Viewed by 1747

Abstract

To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532–1.450–2.361 (p for trend 0.037), 1.057–1.691–3.364 (p for trend 0.004), 1.176–0.686–0.281 (p for trend 0.002), 0.639–0.759–1.820 (p for trend 0.462), 1.030–0.959–0.147 (p for trend 0.011), and 0.697–0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592–1.073–2.811 (p for trend 0.255), 1.161–1.282–4.324 (p for trend 0.03), 0.965–0.781–0.655 (p for trend 0.095), 0.737–0.623–2.147 (p for trend 0.153), 1.061–0.832–0.800 (p for trend 0.391), and 1.412–0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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29 pages, 1268 KB

Open AccessSystematic Review

Clinical and Imaging-Based Prognostic Models for Recurrence and Local Tumor Progression Following Thermal Ablation of Hepatocellular Carcinoma: A Systematic Review

by Coosje A. M. Verhagen, Faeze Gholamiankhah, Emma C. M. Buijsman, Alexander Broersen, Gonnie C. M. van Erp, Ariadne L. van der Velden, Hossein Rahmani, Christiaan van der Leij, Ralph Brecheisen, Rodolfo Lanocita, Jouke Dijkstra and Mark C. Burgmans

Cancers 2025, 17(16), 2656; https://doi.org/10.3390/cancers17162656 - 14 Aug 2025

Viewed by 541

Abstract

Background: Early detection of patients at high risk for recurrence or local tumor progression (LTP) following thermal ablation of hepatocellular carcinoma (HCC) is essential for treatment selection and individualized follow-up. This systematic review aims to assess and compare the performance of prognostic models predicting recurrence or LTP in patients with HCC treated with thermal ablation. Methods: PubMed, Web of Science, Cochrane, and Embase were searched for studies developing models to predict recurrence after thermal ablation in treatment-naïve HCC patients, using imaging and clinical data with reported test set performance. Risk of bias and applicability were assessed by the Prediction model Risk of Bias Assessment Tool. Data on model performance, feature extraction and modeling technique was collected. Results: In total, 16 studies comprising 39 prognostic models were included, all developed using retrospective data from China or Korea. Outcomes included recurrence-free survival, (intrahepatic) early recurrence, LTP, late recurrence and aggressive intrasegmental recurrence. Predictive parameters varied across models addressing identical outcomes. Outcome definitions also differed. Nine models were externally validated. Most studies had a high risk of bias due to methodological limitations. Conclusions: Variability in model development methodology and type of predictors was found. Models that integrated multiple types of predictors consistently outperformed those relying on one type. To advance predictive tools toward clinical implementation, future research should prioritize standardized outcome definitions, external testing, and transparent reporting. Until these challenges are addressed, current evaluated models should be regarded as promising but preliminary tools. Full article

(This article belongs to the Special Issue New Approaches in the Treatment of Hepatocellular Carcinoma and Liver Tumor)

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