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Advances in Liver Cancer: Radiotherapy, Systemic Therapy and Upcoming Trends

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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: closed (30 September 2023) | Viewed by 6513

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Prof. Dr. Jinsil Seong

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Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Interests: hepatocellular carcinoma; radiotherapy; multimodal therapy

Special Issue Information

Dear Colleagues,

Liver cancer is one of the most prevalent and lethal cancers across the globe. Considering its prevalence in patients between the ages of 40 and 60 years old, which are the main axes of socioeconomic activity, it needs special attention to overcome. During the past few decades, efforts have been focused on how to improve therapeutic outcomes in parallel with how to detect early liver cancer. Indeed, there has been remarkable development, particularly in the therapeutic aspect. The emergence of immunotherapy and upgraded locoregional therapy, as well as the sophisticated use of radiotherapy, has contributed to the improvement in the oncologic outcomes of liver cancer patients. However, there still exists a significant gap between overall survival and progression-free survival, suggesting a strong need for more efficient therapies.

This Special Issue of Cancers is intended to update the readers on the advances in liver cancer treatment involving radiotherapy, systemic therapy and multimodal treatment with the upcoming trends.

Prof. Dr. Jinsil Seong
Guest Editor

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Keywords

liver cancer
multimodal therapy
radiotherapy
locoregional therapy
systemic therapy
immunotherapy

Published Papers (5 papers)

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Research

14 pages, 2726 KiB

Open AccessArticle

Efficacy of Radiomics in Predicting Oncologic Outcome of Liver-Directed Combined Radiotherapy in Locally Advanced Hepatocellular Carcinoma

by Jong Won Park, Hansang Lee, Helen Hong and Jinsil Seong

Cancers 2023, 15(22), 5405; https://doi.org/10.3390/cancers15225405 - 14 Nov 2023

Viewed by 791

Abstract

Purpose: We investigated whether radiomic features extracted from three-phase dynamic contrast-enhanced computed tomography (CECT) can be used to predict clinical outcomes, including objective treatment response (OR) and in-field failure-free survival rate (IFFR), in patients with hepatocellular carcinoma (HCC) who received liver-directed combined radiotherapy (LD-CRT). Methods: We included 409 patients, and they were randomly divided into training (n = 307) and validation (n = 102) cohorts. For radiomics models, we extracted 116 radiomic features from the region of interest on the CECT images. Significant clinical prognostic factors are identified to predict the OR and IFFR in the clinical models. We developed clinical models, radiomics models, and a combination of both features (CCR model). Results: Among the radiomic models evaluated for OR, the OR-PVP-Peri-1cm model showed favorable predictive performance with an area under the curve (AUC) of 0.647. The clinical model showed an AUC of 0.729, whereas the CCR model showed better performance (AUC 0.759). For the IFFR, the IFFR-PVP-Peri-1cm model showed an AUC of 0.673, clinical model showed 0.687, and the CCR model showed 0.736. We also developed and validated a prognostic nomogram based on CCR models. Conclusion: In predicting the OR and IFFR in patients with HCC undergoing LD-CRT, CCR models performed better than clinical and radiomics models. Moreover, the constructed nomograms based on these models may provide valuable information on the prognosis of these patients. Full article

(This article belongs to the Special Issue Advances in Liver Cancer: Radiotherapy, Systemic Therapy and Upcoming Trends)

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16 pages, 8058 KiB

Open AccessArticle

Efficacy of the Combination of Systemic Sequential Therapy and Locoregional Therapy in the Long-Term Survival of Patients with BCLC Stage C Hepatocellular Carcinoma

by Yusuke Kawamura, Norio Akuta, Junichi Shindoh, Masaru Matsumura, Satoshi Okubo, Licht Tominaga, Shunichiro Fujiyama, Tetsuya Hosaka, Satoshi Saitoh, Hitomi Sezaki, Fumitaka Suzuki, Yoshiyuki Suzuki, Kenji Ikeda, Yasuji Arase, Masaji Hashimoto, Takuyo Kozuka and Hiromitsu Kumada

Cancers 2023, 15(15), 3789; https://doi.org/10.3390/cancers15153789 - 26 Jul 2023

Cited by 2 | Viewed by 1243

Abstract

Background: The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). Methods: Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP). Results: R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively; p = 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio [HR]; 0.053, p = 0.006 and 0.189, p < 0.001, respectively) compared with that for STP (HR; 0.279, p = 0.003). Conclusions: MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment. Full article

(This article belongs to the Special Issue Advances in Liver Cancer: Radiotherapy, Systemic Therapy and Upcoming Trends)

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13 pages, 2358 KiB

Open AccessArticle

Efficacy of Liver-Directed Combined Radiotherapy in Locally Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

by Jina Kim, Jason Chia-Hsien Cheng, Taek-Keun Nam, Jin Hee Kim, Byoung Kuk Jang, Wen-Yen Huang, Hiroshi Aikata, Myungsoo Kim, Jung Hyun Kwon, Jinbo Yue, Victor Ho Fun Lee, Zhaochong Zeng and Jinsil Seong

Cancers 2023, 15(12), 3164; https://doi.org/10.3390/cancers15123164 - 13 Jun 2023

Cited by 1 | Viewed by 1271

Abstract

Purpose: Although systemic treatment is the mainstay for advanced hepatocellular carcinoma (HCC), numerous studies have highlighted the added value of local treatment. This study aimed to investigate the clinical efficacy of liver-directed combined radiotherapy (LD combined RT) compared with that of sorafenib, a recommended treatment until recently for locally advanced HCC presenting portal vein tumor thrombosis (PVTT), using a multinational patient cohort. Materials and Methods: We identified patients with HCC presenting PVTT treated with either sorafenib or LD combined RT in 10 tertiary hospitals in Asia from 2005 to 2014. Propensity score matching (PSM) was performed to minimize the imbalance between the two groups. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and treatment-related toxicity. Results: A total of 1035 patients (675 in the LD combined RT group and 360 in the sorafenib group) were included in this study. After PSM, 305 patients from each group were included in the analysis. At a median follow-up of 22.5 months, the median OS was 10.6 and 4.2 months for the LD combined RT and sorafenib groups, respectively (p < 0.001). The conversion rate to curative surgery was significantly higher (8.5% vs. 1.0%, p < 0.001), while grade ≥ 3 toxicity was fewer (9.2% vs. 16.1%, p < 0.001) in the LD combined RT group. Conclusions: LD combined RT improved survival outcomes with a higher conversion rate to curative surgery in patients with locally advanced HCC presenting PVTT. Although further prospective studies are warranted, active multimodal local treatment involving radiotherapy is suggested for locally advanced HCC presenting PVTT. Full article

(This article belongs to the Special Issue Advances in Liver Cancer: Radiotherapy, Systemic Therapy and Upcoming Trends)

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13 pages, 785 KiB

Open AccessArticle

Inverse Propensity Score-Weighted Analysis of Entecavir and Tenofovir Disoproxil Fumarate in Patients with Chronic Hepatitis B: A Large-Scale Multicenter Study

by Jihye Kim, Moon Haeng Hur, Seung Up Kim, Jin-Wook Kim, Dong Hyun Sinn, Hyun Woong Lee, Moon Young Kim, Jae Youn Cheong, Yong Jin Jung, Han Ah Lee, Young-Joo Jin, Jun Sik Yoon, Sung-Jae Park, Chang Hun Lee, In Hee Kim, June Sung Lee, Young Youn Cho, Hyung Joon Kim, Soo Young Park, Yeon Seok Seo, Hyunwoo Oh, Dae Won Jun, Mi Na Kim, Young Chang, Jae Young Jang, Sang Youn Hwang and Yoon Jun Kim Show full author list Hide full author list

Cancers 2023, 15(11), 2936; https://doi.org/10.3390/cancers15112936 - 26 May 2023

Viewed by 1580

Abstract

Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) in preventing hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients; however, it remains controversial. This study aimed to conduct comprehensive comparisons between the two antivirals. CHB patients initially treated with ETV or TDF between 2012 and 2015 at 20 referral centers in Korea were included. The primary outcome was the cumulative incidence of HCC. The secondary outcomes included death or liver transplantation, liver-related outcome, extrahepatic malignancy, development of cirrhosis, decompensation events, complete virologic response (CVR), seroconversion rate, and safety. Baseline characteristics were balanced using the inverse probability of treatment weighting (IPTW). Overall, 4210 patients were enrolled: 1019 received ETV and 3191 received TDF. During the median follow-ups of 5.6 and 5.5 years, 86 and 232 cases of HCC were confirmed in the ETV and TDF groups, respectively. There was no difference in HCC incidence between the groups both before (p = 0.36) and after IPTW was applied (p = 0.81). Although the incidence of extrahepatic malignancy was significantly higher in the ETV group than in the TDF group before weighting (p = 0.02), no difference was confirmed after IPTW (p = 0.29). The cumulative incidence rates of death or liver transplantation, liver-related outcome, new cirrhosis development, and decompensation events were also comparable in the crude population (p = 0.24–0.91) and in the IPTW-adjusted population (p = 0.39–0.80). Both groups exhibited similar rates of CVR (ETV vs. TDF: 95.1% vs. 95.8%, p = 0.38), and negative conversion of hepatitis B e antigen (41.6% vs. 37.2%, p = 0.09) or surface antigen (2.8% vs. 1.9%, p = 0.10). Compared to the ETV group, more patients in the TDF group changed initial antivirals due to side effects, including decreased kidney function (n = 17), hypophosphatemia (n = 20), and osteoporosis (n = 18). In this large-scale multicenter study, ETV and TDF demonstrated comparable effectiveness across a broad range of outcomes in patients with treatment-naïve CHB during similar follow-up periods. Full article

(This article belongs to the Special Issue Advances in Liver Cancer: Radiotherapy, Systemic Therapy and Upcoming Trends)

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13 pages, 989 KiB

Open AccessArticle

Beneficial Effect of Combining Radiotherapy and Transarterial Chemoembolization on Patient Survival in Hepatocellular Carcinomas and Macrovascular Invasion Treated with Sorafenib

by Meng-Chuan Lu, Wen-Yen Huang, Hsiu-Lung Fan, Teng-Wei Chen, Wei-Chou Chang, Hsuan-Hwai Lin, Yu-Lueng Shih, Tsai-Yuan Hsieh and Wei-Chen Huang

Cancers 2023, 15(10), 2687; https://doi.org/10.3390/cancers15102687 - 10 May 2023

Viewed by 1205

Abstract

Background: Approximately 10–40% of hepatocellular carcinoma (HCC) patients have definite vascular invasion at the time of diagnosis. Without curative treatment options, these patients have an abysmal prognosis with a median survival of only a few months following systemic therapy. However, supportive evidence of combining multiple locoregional treatments with systemic therapy is limited. This study compared the outcomes of sorafenib alone versus multimodality therapy with sorafenib, radiotherapy (RT), and transarterial chemoembolization (TACE) in advanced HCC patients with macrovascular invasion (MaVI). Methods: The process took place over a nine-year period between March 2009 and October 2017, wherein 78 HCC patients with MaVI who underwent either sorafenib therapy alone (n = 49) or combined sorafenib/RT/TACE (n = 29) therapy were chosen for the retrospective study. We compared the overall survival (OS) between the two groups using the Cox regression hazard model and adjusted imbalances using propensity score matching (PSM). Results: At the last follow-up, 76 patients had died, with a median follow-up time of 4.8 months for all patients and 31 months for those who were alive. Patients treated with sorafenib/RT/TACE had superior OS compared to those treated with sorafenib alone, showing a median survival of 9.3 vs. 2.7 months and a one-year survival of 37.1% vs. 6.1% (p < 0.001). In the multivariable analysis, new diagnosis or recurrence of HCC and treatment modalities (sorafenib alone vs. sorafenib/RT/TACE) were independent prognostic factors for OS. Compared to patients treated with sorafenib alone, significantly better OS was further verified using PSM (p < 0.001) in patients who received multiple therapeutic modalities. Conclusion: Multimodality therapy with sorafenib/RT/TACE increased OS threefold versus sorafenib therapy alone in HCC patients with MaVI. This study offers promising benefits of combined locoregional and systemic therapy for advanced HCC in current patient management and prospective clinical trials. Full article

(This article belongs to the Special Issue Advances in Liver Cancer: Radiotherapy, Systemic Therapy and Upcoming Trends)

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