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Cancers
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New Insights of Management of Hepatocellular Carcinoma
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New Insights of Management of Hepatocellular Carcinoma

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

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 14388

Special Issue Editors

Prof. Dr. Oliver Waidmann

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Guest Editor
Centrum für Hämatologie und Onkologie Bethanien, Im Prüfling 17-19, 60389 Frankfurt/Main, Germany
Interests: hematology/oncology; hepatobiliary cancer; biomarkers; immunotherapy; clinical oncology
Dr. Fabian Finkelmeier

E-Mail Website
Co-Guest Editor
Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt/ Main, Germany
Interests: hematology/oncology; hepatobiliary cancer; clinical oncology
Dr. Vera Himmelsbach

E-Mail Website
Co-Guest Editor
Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt/ Main, Germany
Interests: gastrointestinal oncology; hepatocellular carcinoma; immunotherapy

Special Issue Information

Dear Colleagues,

After a long dry spell, HCC treatment paradigms have rapidly changed in recent years. Introduction of immunotherapy and immunotherapy-based treatment concepts in clinical routine became a door opener for new treatment concepts in this hard-to-treat disease. Immunotherapeutic-based combinations regimens in particular show highly objective responses rates, offering the use of these concepts in advanced disease for downstaging or rendering metastatic disease to potentially curative treatment. This Special Issue of Cancers invites manuscripts focusing on treatment concepts and biomarkers which might help to identify special patient populations, treatment concepts, or biomarkers who show high responses and might guide the choice of treatment.

Prof. Dr. Oliver Waidmann
Dr. Fabian Finkelmeier
Dr. Vera Himmelsbach
Guest Editors

Manuscript Submission Information

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 short 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

  • HCC
  • neoadjuvant treatment
  • oligometastatic disease
  • immunotherapy
  • HCC surgery
  • predictive biomarkers

Published Papers (7 papers)

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Research

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17 pages, 3444 KiB  
Article
Differentiation of Hepatocellular Carcinoma from Intrahepatic Cholangiocarcinoma through MRI Radiomics
by Ning Liu, Yaokun Wu, Yunyun Tao, Jing Zheng, Xiaohua Huang, Lin Yang and Xiaoming Zhang
Cancers 2023, 15(22), 5373; https://doi.org/10.3390/cancers15225373 - 11 Nov 2023
Cited by 1 | Viewed by 1219
Abstract
The purpose of this study was to investigate the efficacy of magnetic resonance imaging (MRI) radiomics in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). The clinical and MRI data of 129 pathologically confirmed HCC patients and 48 ICC patients treated at the [...] Read more.
The purpose of this study was to investigate the efficacy of magnetic resonance imaging (MRI) radiomics in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). The clinical and MRI data of 129 pathologically confirmed HCC patients and 48 ICC patients treated at the Affiliated Hospital of North Sichuan Medical College between April 2016 and December 2021 were retrospectively analyzed. The patients were randomly divided at a ratio of 7:3 into a training group of 124 patients (90 with HCC and 34 with ICC) and a validation group of 53 patients (39 with HCC and 14 with ICC). Radiomic features were extracted from axial fat suppression T2-weighted imaging (FS-T2WI) and axial arterial-phase (AP) and portal-venous-phase (PVP) dynamic-contrast-enhanced MRI (DCE-MRI) sequences, and the corresponding datasets were generated. The least absolute shrinkage and selection operator (LASSO) method was used to select the best radiomic features. Logistic regression was used to establish radiomic models for each sequence (FS-T2WI, AP and PVP models), a clinical model for optimal clinical variables (C model) and a joint radiomics model (JR model) integrating the radiomics features of all the sequences as well as a radiomics–clinical model combining optimal radiomic features and clinical risk factors (RC model). The performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC). The AUCs of the FS-T2WI, AP, PVP, JR, C and RC models for distinguishing HCC from ICC were 0.693, 0.863, 0.818, 0.914, 0.936 and 0.977 in the training group and 0.690, 0.784, 0.727, 0.802, 0.860 and 0.877 in the validation group, respectively. The results of this study suggest that MRI-based radiomics may help noninvasively differentiate HCC from ICC. The model integrating the radiomics features and clinical risk factors showed a further improvement in performance. Full article
(This article belongs to the Special Issue New Insights of Management of Hepatocellular Carcinoma)
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11 pages, 684 KiB  
Article
Long-Term Outcomes of Liver Transplantation in Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Comparison with Portal Vein Tumor Thrombus
by Ji Soo Lee, Jongman Kim, Jinsoo Rhu, Gyu-Seong Choi and Jae-Won Joh
Cancers 2023, 15(17), 4225; https://doi.org/10.3390/cancers15174225 - 23 Aug 2023
Cited by 2 | Viewed by 1114
Abstract
Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) remains controversial. This study analyzed the recurrence and overall survival rates through long-term results after LT in HCC patients with BDTT and compared the results after LT in [...] Read more.
Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) remains controversial. This study analyzed the recurrence and overall survival rates through long-term results after LT in HCC patients with BDTT and compared the results after LT in HCC patients with portal vein tumor thrombus (PVTT). We performed a retrospective study of 45 patients with PVTT, 16 patients with BDTT, and 11 patients with coexisting PVTT and BDTT among HCC patients who underwent LT at a single center from 1999 to 2020. The HCC recurrence rates were 40.4% at 1 year, 30.3.3% at 2 years, and 27.6% at 3 years in the PVTT group; 66.7%, 53.3%, and 46.7% in the BDTT group; and 22.2%, 22.2%, and 0% in the coexisting group (p = 0.183). Overall patient survival rates were 68.4% at 1 year, 54.3% at 2 years, and 41.7% at 3 years in the PVTT group; 81.3%, 62.5%, and 48.2% in the BDTT group; and 63.6%, 27.3%, and 0% in the coexisting group (p = 0.157). In the multivariate analysis, the pre-transplantation model for tumor recurrence after liver transplantation (MoRAL) score and model for end-stage liver disease (MELD) score were found to be independent risk factors for recurrence and survival in all groups. HCC patients with BDTT showed no difference in recurrence and survival compared with HCC patients with PVTT at the long-term follow-up after LT. Full article
(This article belongs to the Special Issue New Insights of Management of Hepatocellular Carcinoma)
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14 pages, 1373 KiB  
Article
LiMAx Prior to Radioembolization for Hepatocellular Carcinoma as an Additional Tool for Patient Selection in Patients with Liver Cirrhosis
by Catherine Leyh, Niklas Heucke, Clemens Schotten, Matthias Büchter, Lars P. Bechmann, Marc Wichert, Alexander Dechêne, Ken Herrmann, Dominik Heider, Svenja Sydor, Peter Lemmer, Johannes M. Ludwig, Josef Pospiech, Jens Theysohn, Robert Damm, Christine March, Maciej Powerski, Maciej Pech, Mustafa Özcürümez, Jochen Weigt, Verena Keitel, Christian M. Lange, Hartmut Schmidt, Ali Canbay, Jan Best, Guido Gerken and Paul P. Mankaadd Show full author list remove Hide full author list
Cancers 2022, 14(19), 4584; https://doi.org/10.3390/cancers14194584 - 21 Sep 2022
Cited by 1 | Viewed by 1702
Abstract
Background and Aims: Radioembolization (RE) has recently demonstrated a non-inferior survival outcome compared to systemic therapy for advanced hepatocellular carcinoma (HCC). Therefore, current guidelines recommend RE for patients with advanced HCC and preserved liver function who are unsuitable for transarterial chemoembolization (TACE) or [...] Read more.
Background and Aims: Radioembolization (RE) has recently demonstrated a non-inferior survival outcome compared to systemic therapy for advanced hepatocellular carcinoma (HCC). Therefore, current guidelines recommend RE for patients with advanced HCC and preserved liver function who are unsuitable for transarterial chemoembolization (TACE) or systemic therapy. However, despite the excellent safety profile of RE, post-therapeutic hepatic decompensation remains a serious complication that is difficult to predicted by standard laboratory liver function parameters or imaging modalities. LiMAx® is a non-invasive test for liver function assessment, measuring the maximum metabolic capacity for 13C-Methacetin by the liver-specific enzyme CYP 450 1A2. Our study investigates the potential of LiMAx® for predicting post-interventional decompensation of liver function. Patients and methods: In total, 50 patients with HCC with or without liver cirrhosis and not amenable to TACE or systemic treatments were included in the study. For patients prospectively enrolled in our study, LiMAx® was carried out one day before RE (baseline) and 28 and 90 days after RE. Established liver function parameters were assessed at baseline, day 28, and day 90 after RE. The relationship between baseline LiMAx® and pre-and post-interventional liver function parameters, as well as the ability of LiMAx® to predict hepatic decompensation, were analyzed. Results: We observed a strong association between baseline LiMAx® and bilirubin, albumin, ALBI grade, and MELD score. Patients presenting with Child–Pugh score B 28 days after RE or with a deterioration in Child–Pugh score by at least one point had a significantly lower baseline LiMAx® compared to those with Child–Pugh score A or with stable Child–Pugh score. The ability of LiMAx® to predict hepatic decompensation after RE was determined using ROC curve analysis and was compared to MELD score and ALBI grade. LiMAx® achieved a substantial AUC of 0.8117, comparable to MELD score and ALBI grade. Conclusion: Patients with lower LiMAx® values at baseline have a significantly increased risk for hepatic decompensation after RE, despite being categorized as Child–Pugh A. Therefore, LiMAx® can be used as an additional tool to identify patients at high risk of post-interventional hepatic failure. Full article
(This article belongs to the Special Issue New Insights of Management of Hepatocellular Carcinoma)
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13 pages, 2294 KiB  
Article
Association between Adverse Events and Prognosis in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study
by Shigeo Shimose, Hideki Iwamoto, Masatoshi Tanaka, Takashi Niizeki, Masahiko Kajiwara, Satoshi Itano, Etsuko Moriyama, Tomotake Shirono, Yu Noda, Naoki Kamachi, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga and Takumi Kawaguchi
Cancers 2022, 14(17), 4284; https://doi.org/10.3390/cancers14174284 - 1 Sep 2022
Cited by 11 | Viewed by 2068
Abstract
This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had [...] Read more.
This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longer survival (median survival time (MST): not reached vs. 14.3 months and not reached vs. 14.8 months, p = 0.001 and p = 0.047, respectively). In contrast, liver injuries were significantly correlated with shorter survival (MST: 14.7 months vs. not reached, p = 0.036), and the median development time was 21 days. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin–bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. The OS in the no discontinuation due to AE group was significantly longer than that in the discontinuation due to AEs group (MST not reached vs. 11.2 months, p = 0.001). We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments. Full article
(This article belongs to the Special Issue New Insights of Management of Hepatocellular Carcinoma)
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18 pages, 12584 KiB  
Article
Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150
by Takuya Sho, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Koji Ogawa, Akinori Kubo, Yoshimasa Tokuchi, Qingjie Fu, Zijian Yang, Megumi Kimura, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Tomofumi Takagi, Jun Ito, Tomoe Kobayashi, Takuto Miyagishima and Naoya Sakamotoadd Show full author list remove Hide full author list
Cancers 2022, 14(16), 3938; https://doi.org/10.3390/cancers14163938 - 15 Aug 2022
Cited by 7 | Viewed by 2184
Abstract
The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria [...] Read more.
The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. −2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed. Full article
(This article belongs to the Special Issue New Insights of Management of Hepatocellular Carcinoma)
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13 pages, 1534 KiB  
Article
Sorafenib Versus Lenvatinib-Based Sequential Systemic Therapy for Advanced Hepatocellular Carcinoma: A Real-World Analysis
by Catherine Leyh, Ursula Ehmer, Daniel Roessler, Alexander B. Philipp, Florian P. Reiter, Petia Jeliazkova, Leonie S. Jochheim, Matthias Jeschke, Janina Hammig, Johannes M. Ludwig, Jens M. Theysohn, Andreas Geier and Christian M. Lange
Cancers 2022, 14(8), 1975; https://doi.org/10.3390/cancers14081975 - 13 Apr 2022
Cited by 5 | Viewed by 2259
Abstract
The optimal treatment sequence of tyrosine kinase inhibitor (TKI)-based therapy in patients with hepatocellular carcinoma (HCC) remains unclear. Therefore, sequential systemic therapy after first-line therapy with sorafenib or lenvatinib was compared in a retrospective real-world cohort. In total, 164 patients with HCC were [...] Read more.
The optimal treatment sequence of tyrosine kinase inhibitor (TKI)-based therapy in patients with hepatocellular carcinoma (HCC) remains unclear. Therefore, sequential systemic therapy after first-line therapy with sorafenib or lenvatinib was compared in a retrospective real-world cohort. In total, 164 patients with HCC were included. Child B cirrhosis was present in 26 patients (16.5%), whereas 132 patients (83.5%) had preserved liver function. In total, 72 patients (44%) discontinued systemic therapy after first-line therapy while 51 (31%) and 31 (19%) patients received 2 or more treatment lines. Most notably, median overall survival (mOS) was influenced by liver functional status and patient performance status at the beginning of first-line therapy. Patients receiving a sequential therapy regimen had significantly longer mOS compared to patients that discontinued systemic therapy after omitting first-line treatment. The choice of the initial TKI did not impact mOS. A clear deterioration of liver function could be observed during the course of TKI-based treatment. Full article
(This article belongs to the Special Issue New Insights of Management of Hepatocellular Carcinoma)
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17 pages, 697 KiB  
Review
Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma
by Perla Chami, William Jarnagin, Ghassan K. Abou-Alfa, James Harding, Neal Kim, Haibo Lin, Maria El Homsi, Christopher Crane and Carla Hajj
Cancers 2023, 15(6), 1748; https://doi.org/10.3390/cancers15061748 - 14 Mar 2023
Cited by 3 | Viewed by 3061
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials. Full article
(This article belongs to the Special Issue New Insights of Management of Hepatocellular Carcinoma)
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