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Yan H, Li Z, Li N, Yan H, Guo X, Wu M, Kong F, Dong J, Deng M, Xu X. Late course adaptive radiotherapy based on tumor volume reduction decreases Gastrointestinal toxicity for abdominal lymph node metastasis of hepatocellular carcinoma. Sci Rep 2025; 15:17477. [PMID: 40394171 PMCID: PMC12092827 DOI: 10.1038/s41598-025-02363-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 05/13/2025] [Indexed: 05/22/2025] Open
Abstract
This study aimed to quantify tumor volume reduction during radiotherapy for abdominal lymph node metastases (LNM) of hepatocellular carcinoma (HCC) and assess the potential benefits of late-course adaptive radiotherapy. Forty HCC Patients with abdominal LNM treated from January 2021 to March 2024 received radiotherapy in combination with targeted therapy or immunotherapy. Second simulation scan was performed during the fourth week of radiotherapy. Two-thirds of patients underwent redesigned radiotherapy plan as the test group, while remaining patients continued with the original plan as the control group. Dose-volume metrics for organs at risk and toxicities were compared. At the time of second scan, median radiotherapy dose administered to all patients was 38.0 Gy. Mean tumor volume reduction was 56.20cc (95% CI 35.20-77.21cc) and 29.65% (95% CI 24.49%-34.80%). Irradiation dose and volume to stomach, small intestine, colon, liver, and kidneys were significantly reduced in test group. Meanwhile, gastrointestinal toxicities were notablely decreased, including dyspepsia (P = 0.018), nausea (P = 0.013), vomiting (P = 0.041), and diarrhea (P = 0.040). Tumor regression during radiotherapy for abdominal LNM of HCC is significant. A second simulation scan performing when the irradiation dose reaches approximately 40 Gy and applying adaptive radiotherapy in the late course can enhance irradiation accuracy and reduce toxicities.
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Affiliation(s)
- Huamei Yan
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Zhenghuan Li
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Nuoya Li
- Department of Hepatobiliary surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Huaying Yan
- Xinyu people's hospital, Xinyu, 338099, China
| | - Xianyu Guo
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Manya Wu
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Fantu Kong
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Jie Dong
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Meihai Deng
- Department of Hepatobiliary surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
| | - Xiangying Xu
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
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Yan H, Xu J, Li Z, Li N, Guo X, Wu M, Wang D, Lin N, Dong J, Xu X. Efficacy of radiotherapy combined with targeted therapy and immunotherapy for lymph node metastasis of liver cancer. J Cancer Res Clin Oncol 2025; 151:129. [PMID: 40169437 PMCID: PMC11961524 DOI: 10.1007/s00432-025-06182-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 03/24/2025] [Indexed: 04/03/2025]
Abstract
PURPOSE To investigate the efficacy and safety of radiotherapy combined with targeted therapy and immunotherapy for liver cancer with lymph node metastasis (LNM). METHODS We analysed patients who received radiotherapy for liver cancer with LNM in our hospital from June 2020 to June 2023. 62 patients were enrolled in this study, who received radiotherapy with a median radiation dose of 60.0 Gy, combined with targeted therapy and/or immunotherapy. The objective response rate (ORR), overall survival (OS), progression free survival (PFS), and adverse events were observed to evaluate treatment efficacy and safety. RESULTS With a median follow-up of 18.5 months, the best ORR was 90.3%. The median OS was 26.0 months. The 1-year and 2-year OS rates were 78.93% and 57.37%, respectively. The median PFS was 17.0 months, and the 1-year and 2-year PFS rates were 59.06% and 49.22%, respectively. Multivariate analysis showed that alanine aminotransferase (HR = 2.34, 95% CI 1.07-5.11, P = 0.033), prothrombin time (HR = 4.51, 95% CI 1.76-11.57, P = 0.002), alpha fetal protein (HR = 2.94, 95% CI 1.34-6.45, P = 0.007), and the volume of LNM (HR = 3.05, 95% CI 1.25-7.46, P = 0.014) were independent predictors for OS, while non-regional LNM (HR = 3.19, 95% CI 1.24-8.16, P = 0.016) was an independent predictor for PFS. Toxicity was generally mild and moderate. CONCLUSIONS Radiotherapy combined with targeted therapy and immunotherapy is an effective treatment option, and expected to become new treatment strategy for liver cancer with LNM.
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Affiliation(s)
- Huamei Yan
- Department of Radiation Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Jianliang Xu
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Zhenghuan Li
- Department of Radiation Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Nuoya Li
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Xianyu Guo
- Department of Radiation Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Manya Wu
- Department of Radiation Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Donghui Wang
- Department of Radiation Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Nan Lin
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
| | - Jie Dong
- Department of Radiation Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
| | - Xiangying Xu
- Department of Radiation Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
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Van Werkhoven LA, Cammareri E, Hoogeman MS, Nout RA, Milder MTW, Nuyttens JJME. Stereotactic body radiation therapy on abdominal-pelvic lymph node oligometastases: a systematic review on toxicity. Acta Oncol 2024; 63:822-832. [PMID: 39473177 PMCID: PMC11541805 DOI: 10.2340/1651-226x.2024.40681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/05/2024] [Indexed: 11/09/2024]
Abstract
BACKGROUND AND PURPOSE To review available data on toxicity during and/or after treatment of abdominal-pelvic lymph node oligometastases (A-P LN) with stereotactic body radiation therapy (SBRT) and to provide an overview of adverse events and its relation to dose or fractionation. MATERIAL AND METHODS For this systematic review, we searched MEDLINE, Embase, Web of Science Core Collection, and CINAH for studies published between the database inception and October 3rd, 2023. Inclusion criteria were (1) patients with 1-5 A-P LN oligometastases, (2) treatment with SBRT to a median prescribed dose of ≥55 Gy BED10, and (3) description of acute and/or late toxicity. There were no language or date restrictions. RESULTS A total of 35 studies, including 1,512 patients, were selected. Late grade 3 and 4 adverse events occurred in 0.6% and 0.1% of the patients treated for A-P LN oligometastases. All late adverse events grade ≥ 3 occurred after treatment of the tumor with a minimum BED10 of 72 Gy. Of the 11 patients with severe late toxicity, five patients were re-irradiated. Late grade 2 and 1 toxicity was reported in 3.4% and 8.3% of the patients. Acute toxicity grades 4, 3, 2, and 1 occurred in 0.1%, 0.2%, 4.4%, and 19.8% of the patients, respectively. INTERPRETATION SBRT for A-P LN oligometastases show low toxicity rates. Nearly 50% of late adverse events ≥ grade 3 were associated with re-irradiation.
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Affiliation(s)
- Lucy A Van Werkhoven
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, The Netherlands.
| | - Eugenio Cammareri
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Mischa S Hoogeman
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, The Netherlands
| | - Remi A Nout
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, The Netherlands
| | - Maaike T W Milder
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, The Netherlands
| | - Joost J M E Nuyttens
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, The Netherlands
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Choi SH, Lee BM, Kim J, Kim DY, Seong J. Efficacy of stereotactic ablative radiotherapy in patients with oligometastatic hepatocellular carcinoma: A phase II study. J Hepatol 2024; 81:84-92. [PMID: 38467379 DOI: 10.1016/j.jhep.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 03/01/2024] [Accepted: 03/04/2024] [Indexed: 03/13/2024]
Abstract
BACKGROUND & AIMS Stereotactic ablative radiotherapy (SABR) can extend survival and offers the potential for cure in some patients with oligometastatic disease (OMD). However, limited evidence exists regarding its use in oligometastatic hepatocellular carcinoma (HCC). We aimed to prospectively investigate the efficacy and safety of SABR in patients with oligometastatic HCC. METHODS We enrolled patients with controlled primary HCC and one to five metastatic lesions amenable to SABR. The primary endpoint was treatment efficacy defined as overall survival (OS) and progression-free survival (PFS). The secondary endpoints included time to local progression, objective response rate, disease control rate, toxicities, and quality of life (QOL), assessed using the EORTC QLQ-C30 before, and 0, 1, and 3 months after SABR. RESULTS Overall, 40 consecutive patients received SABR on 62 lesions between 2021 and 2022. The most common locations for OMD were the lungs (48.4%), lymph nodes (22.6%), and bone (17.7%). After a median follow-up of 15.5 months, the 2-year OS was 80%. Median PFS was 5.3 months, with 1- and 2-year PFS rates of 21.2% and 0%, respectively. A shorter time to OMD from the controlled primary independently correlated with PFS (p = 0.039, hazard ratio 2.127) alongside age, Child-Pugh class, and alpha-fetoprotein (p = 0.002, 0.004, 0.019, respectively). The 2-year time to local progression, objective response rate, and disease control rate were 91.1%, 75.8%, and 98.4%, respectively. Overall, 10% of patients experienced acute toxicity, and 7.5% experienced late toxicity, with no grade 3+ toxicity. All QOL scores remained stable, whereas the patients without systemic treatments had improved insomnia and social functioning scores. CONCLUSIONS SABR is an effective and feasible option for oligometastatic HCC that leads to excellent local tumor control and improves survival without adversely affecting QOL. IMPACT AND IMPLICATIONS Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment approach capable of efficiently ablating the target lesion; however, neither the oligometastatic disease concept nor the potential benefits of SABR have been well-defined in hepatocellular carcinoma (HCC). According to this study, SABR is an effective and safe treatment option for oligometastatic HCC, yielding excellent local tumor control and survival improvement without worsening patients' quality of life, regardless of tumor sites. We also demonstrated that patients with a later presentation of OMD from the controlled primary and lower alpha-fetoprotein levels achieved better survival outcomes. This is the first prospective study of SABR in oligometastatic HCC, providing insights for the development of novel strategies to improve oncologic outcomes. CLINICAL TRIAL NUMBER NCT05173610.
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Byung Min Lee
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jina Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Kim S, Lee J, Rim CH. Local Treatment of Hepatocellular Carcinoma with Oligometastases: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:3467. [PMID: 37444577 DOI: 10.3390/cancers15133467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 06/28/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
Although recent studies have shown favorable results after local treatment for oligometastases, the clinical decision of applying local treatment for oligometastatic hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aimed to investigate the benefits of local treatment for HCC oligometastases. Pubmed, Embase, Medline, and the Cochrane library were searched for studies until 1 May 2022. Clinical studies involving at least five cases of HCC oligometsatases treated with local modalities were included. The primary endpoint was overall survival (OS). The benefit of local treatment was assessed as the pooled odds ratio (OR) among comparative series, and the pooled OS percentile was calculated from all studies including patients treated with local treatment. Complications of grade ≥ 3 were assessed subjectively. A total of 10 studies involving 527 patients were included. Radiotherapy and radiofrequency ablation (RFA) were mainly performed (six and five studies) as local modalities treating oligometastases. Pooled OR of comparative series favored the use of local treatment (4.664, 95% confidence interval [CI]: 2.595-8.380, p < 0.001, I2: ~0.0%). Including all cohorts with patients who underwent local treatment, pooled rates of 1-year OS were 71.8% (95% CI: 59.0-81.9; I2 = 81.5%), and pooled 2-year OS were 43.3% (95% CI: 29.1-59.6; I2 = 85.4%). Except for temporal or pre-existing toxicities, grade ≤ 3 complications were reported less than 10% in most studies, although common toxicities include pneumothorax and hematologic deficiency after RFA and radiotherapy, respectively. Grade 5 toxicity has not yet been reported. This systematic review supports the application of local treatment for treating HCC oligometastases.
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Affiliation(s)
- Sooyeon Kim
- College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - Jungsue Lee
- College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - Chai Hong Rim
- College of Medicine, Korea University, Seoul 02841, Republic of Korea
- Department of Radiation Oncology, Korea University Ansan Hospital, Ansan 15355, Republic of Korea
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Chen YX, Yang P, Du SS, Zhuang Y, Huang C, Hu Y, Zhu WC, Yu YY, Liu TS, Zeng ZC. Stereotactic body radiotherapy combined with sintilimab in patients with recurrent or oligometastatic hepatocellular carcinoma: A phase II clinical trial. World J Gastroenterol 2023; 29:3871-3882. [PMID: 37426321 PMCID: PMC10324536 DOI: 10.3748/wjg.v29.i24.3871] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/06/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Stereotactic body radiotherapy (SBRT) and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma (HCC) in retrospective studies.
AIM To evaluate the efficacy of combining SBRT with sintilimab for patients with recurrent or oligometastatic HCC.
METHODS This trial involved patients with recurrent or oligometastatic HCC intravenously treated with SBRT plus sintilimab every 3 wk for 12 mo or until disease progression. The primary endpoint was progression-free survival (PFS).
RESULTS Twenty-five patients were enrolled from August 14, 2019, to August 23, 2021. The median treatment duration was 10.2 (range, 0.7-14.6) months. SBRT was delivered at a median dose of 54 (range, 48-60) Gy in 6 (range, 6-10) fractions. The median follow-up time was 21.9 (range, 10.3-39.7) mo, and 32 targeted lesions among 25 patients were evaluated for treatment response according to the Response Evaluation Criteria in Solid Tumors version 1.1. The median PFS was 19.7 mo [95% confidence interval (CI): 16.9-NA], with PFS rates of 68% (95%CI: 52-89) and 45.3% (95%CI: 28-73.4) at 12 and 24 mo, respectively. The median overall survival (OS) was not reached, with OS rates of 91.5% (95%CI: 80.8-100.0) and 83.2% (95%CI: 66.5-100.0) at 12 and 24 mo, respectively. The 1- and 2-year local control rate were 100% and 90.9% (95%CI: 75.4%-100.0%), respectively. The confirmed objective response rate and disease control rate was 96%, and 96%, respectively. Most adverse events were graded as 1 or 2, and grade 3 adverse events were observed in three patients.
CONCLUSION SBRT plus sintilimab is an effective, well-tolerated treatment regimen for patients with recurrent or oligometastatic HCC.
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Affiliation(s)
- Yi-Xing Chen
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ping Yang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Shi-Suo Du
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yuan Zhuang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Cheng Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yong Hu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Wen-Chao Zhu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yi-Yi Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Tian-Shu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhao-Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Luo Y, Cuneo KC, Lawrence TS, Matuszak MM, Dawson LA, Niraula D, Ten Haken RK, El Naqa I. A human-in-the-loop based Bayesian network approach to improve imbalanced radiation outcomes prediction for hepatocellular cancer patients with stereotactic body radiotherapy. Front Oncol 2022; 12:1061024. [PMID: 36568208 PMCID: PMC9782976 DOI: 10.3389/fonc.2022.1061024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 11/01/2022] [Indexed: 12/13/2022] Open
Abstract
Background Imbalanced outcome is one of common characteristics of oncology datasets. Current machine learning approaches have limitation in learning from such datasets. Here, we propose to resolve this problem by utilizing a human-in-the-loop (HITL) approach, which we hypothesize will also lead to more accurate and explainable outcome prediction models. Methods A total of 119 HCC patients with 163 tumors were used in the study. 81 patients with 104 tumors from the University of Michigan Hospital treated with SBRT were considered as a discovery dataset for radiation outcomes model building. The external testing dataset included 59 tumors from 38 patients with SBRT from Princess Margaret Hospital. In the discovery dataset, 100 tumors from 77 patients had local control (LC) (96% of 104 tumors) and 23 patients had at least one grade increment of ALBI (I-ALBI) during six-month follow up (28% of 81 patients). Each patient had a total of 110 features, where 15 or 20 features were identified by physicians as expert knowledge features (EKFs) for LC or I-ALBI prediction. We proposed a HITL based Bayesian network (HITL-BN) approach to enhance the capability of selecting important features from imbalanced data in terms of accuracy and explainability through humans' participation by integrating feature importance ranking and Markov blanket algorithms. A pure data-driven Bayesian network (PD-BN) method was applied to the same discovery dataset of HCC patients as a benchmark. Results In the training and testing phases, the areas under receiver operating characteristic curves of the HITL-BN models for LC or I-ALBI prediction during SBRT are 0.85 (95% confidence interval: 0.75-0.95) or 0.89 (0.81-0.95) and 0.77 or 0.78, respectively. They significantly outperformed the during-treatment PD-BN model in predicting LC or I-ALBI based on the discovery cross-validation and testing datasets from the Delong tests. Conclusion By allowing the human expert to be part of the model building process, the HITL-BN approach yielded significantly improved accuracy as well as better explainability when dealing with imbalanced outcomes in the prediction of post-SBRT treatment response of HCC patients when compared to the PD-BN method.
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Affiliation(s)
- Yi Luo
- Department of Machine Learning, Moffitt Cancer Center, Tampa, FL, United States,*Correspondence: Yi Luo,
| | - Kyle C. Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Theodore S. Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Martha M. Matuszak
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Laura A. Dawson
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Dipesh Niraula
- Department of Machine Learning, Moffitt Cancer Center, Tampa, FL, United States
| | - Randall K. Ten Haken
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Issam El Naqa
- Department of Machine Learning, Moffitt Cancer Center, Tampa, FL, United States
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Long HY, Huang TY, Xie XY, Long JT, Liu BX. Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis. World J Clin Cases 2021; 9:5754-5768. [PMID: 34368295 PMCID: PMC8316954 DOI: 10.12998/wjcc.v9.i21.5754] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has increasingly been seen due to improved survival with effective management of intrahepatic lesions. The presence of EHM indicates an advanced stage of HCC, for which systemic therapy serves as the standard treatment modality. Since the approval of Sorafenib as the first systemic agent in 2007, it took almost a decade to show its efficacy in both first and further lines of setting until the landscape of systemic drugs was finally expanded. Moreover, with inspiring results from immunotherapy trials in HCC, it appears that the introduction of immunotherapy may lead to an evolution in the portfolio of HCC treatment. Although the locoregional approach in the management of EHM is not recommended for advanced-stage HCC, efforts have been made to demonstrate its efficacy in symptom relief and potential benefit for overall survival. This review provides a summary of recent updates of the systemic agents in the treatment of advanced HCC, with an emphasis on aggressive locoregional management of EHM by various treatment modalities.
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Affiliation(s)
- Hai-Yi Long
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Tong-Yi Huang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Jian-Ting Long
- Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Xian Liu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
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Pérez-Romasanta LA, González-Del Portillo E, Rodríguez-Gutiérrez A, Matías-Pérez Á. Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination. Cancers (Basel) 2021; 13:cancers13020192. [PMID: 33430362 PMCID: PMC7825787 DOI: 10.3390/cancers13020192] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 01/03/2021] [Accepted: 01/05/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Radiotherapy is rapidly turning into a crucial component of multidisciplinary treatment for liver cancer because many patients are not surgical treatment candidates. Thanks to technical developments, radiotherapy have achieved high precision treatments, making it possible to eliminate tumor cells without severe damage to the liver and other organs. Stereotactic Body Radiation Therapy is an advanced radiotherapy technique able to eradicate malignant tumors wherever they are located in properly selected patients. The best use of radiotherapy, the most fruitful radiotherapy strategy, and the best way to combine it with other treatments for liver cancer are largely unknown. Radiosensitizers, agents that can potentiate radiotherapy, could broaden the radiotherapeutic landscape. Radiotherapy potentiation can be achieved with diverse treatments, not only drugs but also nanoparticles. In order to clear up the performance of radiotherapy in liver cancer management in the future and the best ways to potentiate its effects, considerable medical research is needed. Abstract Stereotactic body radiotherapy (SBRT) is an emerging ablative modality for hepatocellular carcinoma (HCC). Most patients with HCC have advanced disease at the time of diagnosis, and therefore, are not candidates for definitive-intent therapies such as resection or transplantation. For this reason, various alternative local and regional therapies have been used to prevent disease progression, palliate symptoms, and delay liver failure. Stereotactic body radiation therapy is a non-invasive technique of delivering ablative doses of radiation to tumors while sparing normal or non-tumor hepatic tissue. Incorporation of SBRT in multidisciplinary HCC management is gradual, initially applied when other liver-directed therapies have failed or are contraindicated, and tried in combination with other locoregional or systemic therapies for more unfavorable conditions by more experienced teams. In order to improve SBRT therapeutic ratio, there has been much interest in augmenting the effect of radiation on tumors by combining it with chemotherapy, molecularly targeted therapeutics, nanoparticles, and immunotherapy. This review aims to synthesize available evidence to evaluate the clinical feasibility and efficacy of SBRT for HCC, and to explore novel radio-potentiation concepts by combining SBRT with novel therapeutics. It is expected that those approaches would result in improved therapeutic outcomes, even though many questions remain with regard to the optimal way to assemble treatments. Further trials are needed to evaluate and consolidate these promising therapies for HCC.
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