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Shen X, Yan W, Zhang E, Zhang Z, Zhang Z, Dong H. Adjuvant PD-1 inhibitors improve recurrence and survival outcomes in high-risk hepatocellular carcinoma patients after curative hepatectomy. Eur J Med Res 2025; 30:196. [PMID: 40119430 PMCID: PMC11929280 DOI: 10.1186/s40001-025-02444-3] [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: 09/18/2024] [Accepted: 03/10/2025] [Indexed: 03/24/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most prevalent malignancy in China, with liver resection recognized as the primary curative intervention. However, HCC patients face an elevated risk of recurrence, thereby significantly impacting prognosis. PURPOSE This study aimed to assess the impact of adjuvant programmed cell death protein-1 (PD-1) inhibitors on survival outcomes in patients with HCC who are at high risk for postoperative recurrence following curative hepatectomy. MATERIALS AND METHODS Among the 199 study participants, 77 received adjuvant PD-1 inhibitors. Propensity score matching (PSM) was used to balance baseline differences between patients who received adjuvant PD-1 inhibitors and those who did not. Assessment of overall survival (OS) and recurrence-free survival (RFS) was conducted using Kaplan-Meier curves, while Cox regression analysis was employed to identify prognostic factors influencing survival. RESULTS After PSM, the 1-year and 2-year RFS were 87.1% and 74.2% in the PD-1 inhibitors group and 44.6% and 37.8% in non-PD-1 inhibitors group (p < 0.001). The 1-year and 2-year OS were 98.5% and 95.7% in the PD-1 inhibitors group compared with 90.7% and 77.0% in non-PD-1 inhibitors group (p = 0.004). Multivariable analyses demonstrated that the use of adjuvant PD-1 inhibitors was significantly associated with improved RFS and OS. Subgroup analysis indicated that adjuvant PD-1 inhibitors group achieved longer RFS than the non-PD-1 inhibitors group in patients without adjuvant transarterial chemoembolization (TACE). CONCLUSION The administration of adjuvant PD-1 inhibitors may effectively reduce the risk of tumor recurrence and improve survival in HCC patients with high risk of recurrence after curative hepatectomy.
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Affiliation(s)
- Xuehan Shen
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Wei Yan
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Erlei Zhang
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhiwei Zhang
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zunyi Zhang
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Hanhua Dong
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Zhang Y, Shi K, Feng Y, Wang XB. Machine learning model using immune indicators to predict outcomes in early liver cancer. World J Gastroenterol 2025; 31:101722. [PMID: 39926221 PMCID: PMC11718606 DOI: 10.3748/wjg.v31.i5.101722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 11/15/2024] [Accepted: 12/09/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND Patients with early-stage hepatocellular carcinoma (HCC) generally have good survival rates following surgical resection. However, a subset of these patients experience recurrence within five years post-surgery. AIM To develop predictive models utilizing machine learning (ML) methods to detect early-stage patients at a high risk of mortality. METHODS Eight hundred and eight patients with HCC at Beijing Ditan Hospital were randomly allocated to training and validation cohorts in a 2:1 ratio. Prognostic models were generated using random survival forests and artificial neural networks (ANNs). These ML models were compared with other classic HCC scoring systems. A decision-tree model was established to validate the contribution of immune-inflammatory indicators to the long-term outlook of patients with early-stage HCC. RESULTS Immune-inflammatory markers, albumin-bilirubin scores, alpha-fetoprotein, tumor size, and International Normalized Ratio were closely associated with the 5-year survival rates. Among various predictive models, the ANN model generated using these indicators through ML algorithms exhibited superior performance, with a 5-year area under the curve (AUC) of 0.85 (95%CI: 0.82-0.88). In the validation cohort, the 5-year AUC was 0.82 (95%CI: 0.74-0.85). According to the ANN model, patients were classified into high-risk and low-risk groups, with an overall survival hazard ratio of 7.98 (95%CI: 5.85-10.93, P < 0.0001) between the two cohorts. CONCLUSION A non-invasive, cost-effective ML-based model was developed to assist clinicians in identifying high-risk early-stage HCC patients with poor postoperative prognosis following surgical resection.
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Affiliation(s)
- Yi Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Ke Shi
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Ying Feng
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xian-Bo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Yang CK, Wei ZL, Shen XQ, Jia YX, Wu QY, Wei YG, Su H, Qin W, Liao XW, Zhu GZ, Peng T. Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy. World J Gastrointest Oncol 2024; 16:4579-4596. [PMID: 39678799 PMCID: PMC11577363 DOI: 10.4251/wjgo.v16.i12.4579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 09/12/2024] [Accepted: 09/29/2024] [Indexed: 11/12/2024] Open
Abstract
BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio (GPR) levels in patients with solitary hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) following radical resection has not been established. AIM To examine the clinical utility of GPR for prognosis prediction in solitary HBV-related HCC patients. METHODS A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed. GPR levels were compared with 908 non-HCC individuals. Overall survival (OS) and recurrence-free survival (RFS) were evaluated, and cox proportional hazard model analyses were performed to identify independent risk factors. Differences in characteristics were adjusted by propensity score matching (PSM). Subgroup and stratified survival analyses for HCC risks were performed, and a linear trend of the hazard ratio (HR) according to GPR levels was constructed. RESULTS GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas, chronic hepatitis B and healthy control (adjusted P < 0.05). Variable bias was diminished after the PSM balance test. The low GPR group had improved OS (P < 0.001) and RFS (P < 0.001) in the PSM analysis and when combined with other variables. Multivariate cox analyses suggested that low GPR levels were associated with a better OS (HR = 0.5, 95%CI: 0.36-0.7, P < 0.001) and RFS (HR = 0.57, 95%CI: 0.44-0.73, P < 0.001). This same trend was confirmed in subgroup analyses. Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction. Moreover, stratified survival analyses found that GPR > 0.6 was associated with a worse OS and higher recurrence rate (P for trend < 0.001). CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBV-related HCC.
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Affiliation(s)
- Cheng-Kun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhong-Liu Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Qiang Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Xuan Jia
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qiong-Yuan Wu
- Department of Tuina, Nanning Hospital of Traditional Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Yong-Guang Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Lau G, Obi S, Zhou J, Tateishi R, Qin S, Zhao H, Otsuka M, Ogasawara S, George J, Chow PKH, Cai J, Shiina S, Kato N, Yokosuka O, Oura K, Yau T, Chan SL, Kuang M, Ueno Y, Chen M, Cheng AL, Cheng G, Chuang WL, Baatarkhuu O, Bi F, Dan YY, Gani RA, Tanaka A, Jafri W, Jia JD, Kao JH, Hasegawa K, Lau P, Lee JM, Liang J, Liu Z, Lu Y, Pan H, Payawal DA, Rahman S, Seong J, Shen F, Shiha G, Song T, Sun HC, Masaki T, Sirachainan E, Wei L, Yang JM, Sallano JD, Zhang Y, Tanwandee T, Dokmeci AK, Zheng SS, Fan J, Fan ST, Sarin SK, Omata M. APASL clinical practice guidelines on systemic therapy for hepatocellular carcinoma-2024. Hepatol Int 2024; 18:1661-1683. [PMID: 39570557 DOI: 10.1007/s12072-024-10732-z] [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: 07/11/2024] [Accepted: 09/16/2024] [Indexed: 11/22/2024]
Abstract
In Asia-Pacific region, hepatocellular carcinoma is a serious health threat attributing to over 600,000 deaths each year and account for over 70% of global cases. Clinically, the major unmet needs are recurrence after curative-intent surgery, liver transplantation or local ablation and disease progression in those with hepatocellular carcinoma not eligible for resection or failed locoregional therapy. In the recent few years, new targeted therapy and immune-checkpoint inhibitors have been registered as systemic therapy to address these issues. Notably, new forms of systemic therapy, either as first-line or second-line therapy for unresectable hepatocellular or those not eligible for locoregional therapy, are now available. New data is also emerging with the use of systemic therapy to prevent hepatocellular carcinoma recurrence after curative-intent resection or local ablation therapy and to retard disease progression after locoregional therapy. In the future, further implementation of immune-checkpoint inhibitors and other forms of immunotherapy are expected to bring a new paradigm to the management of hepatocellular carcinoma. New insight related to immune-related adverse events with the use of immunotherapy has allso enabled optimization of the therapeutic approach to patients with hepatocellular carcinoma. The purpose of this clinical practice guideline is to provide an up-to-date recommendation based on clinical evidence and experience from expert Asia-Pacific key opinion leaders in the field of hepatocellular carcinoma. Three key questions will be addressed, namely: (1) Which patients with hepatocellular carcinoma should be considered for systemic therapy? (2) Which systemic therapy should be used? (3) How should a patient planned for immune checkpoint-based systemic therapy be managed and monitored?
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Affiliation(s)
- George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Zhongshan Hospital, Fudan University, Hong Kong SAR, Shanghai, China.
| | - Shuntaro Obi
- Department of Internal Medicine, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shukui Qin
- Cancer Centre of Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 700-8558, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia
| | - Pierce K H Chow
- Department of HPB Surgery and Transplantation, Duke-NUS Medical School, National Cancer Center Singapore and Singapore General Hospital, Surgery Academic Clinical Program, Singapore, Singapore
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Naoya Kato
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita, Miki, Kagawa, 761-0793, Japan
| | - Thomas Yau
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Stephen L Chan
- Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ming Kuang
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yoshiyuki Ueno
- Faculty of Medicine, Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
| | - Minshan Chen
- Department of Liver Surgery, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Ann-Lii Cheng
- Department of OncologyDepartment of Medical OncologyGraduate Institute of OncologyDepartment of Internal Medicine, National Taiwan University Cancer CenterNational Taiwan University HospitalNational Taiwan University College of Medicine, Taipei, Taiwan
| | - Gregory Cheng
- Humanity and Health Clinical Trial Center, Humanity & Health Medical Group, Hong Kong SAR, China
- Faculty of Health Science, Macau University, Macau SAR, China
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Center for Infectious Disease and Cancer Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Oidov Baatarkhuu
- School of Medicine, Mongolian National University of Medical Sciences, Ulan Bator, Mongolia
| | - Feng Bi
- Department of Medical Oncology, Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Yock Young Dan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Rino A Gani
- Hepatobiliary Division, Staff Medic Group of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, 10430, Indonesia
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Wasim Jafri
- The Aga Khan University Hospital, Karachi, Pakistan
| | - Ji-Dong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jia-Horng Kao
- Department of Internal Medicine Division of Gastroenterology and Hepatology, Department of Internal MedicineHepatitis Research Center, Graduate Institute of Clinical Medicine, National Taiwan University Hospital Bei-Hu BranchNational Taiwan University HospitalNational Taiwan University College of Medicine, Taipei, Taiwan
| | - Kiyoshi Hasegawa
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Patrick Lau
- Humanity and Health Clinical Trial Center, Humanity & Health Medical Group, Hong Kong SAR, China
| | - Jeong Min Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, China
| | - Zhenwen Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation, Army General Hospital, Beijing, China
| | - Yinying Lu
- Department of Comprehensive Liver Cancer Center, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Hongming Pan
- Department of Medical Oncology, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Diana A Payawal
- Department of Medicine, Fatima University Medical Center, Manila, Philippines
| | - Salimur Rahman
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Gamal Shiha
- European Liver Patients' Association (ELPA), Brussels, Belgium
- World Hepatitis Alliance, London, UK
- African Liver Patient Association (ALPA), Cairo, Egypt
- The Association of Liver Patients Care (ALPC), Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansoura, Egypt
| | - Tianqiang Song
- Department of Hepatobiliary, HCC Research Center for Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita, Miki, Kagawa, 761-0793, Japan
| | - Ekaphop Sirachainan
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jose D Sallano
- Section of Gastroenterology, University of Santo Tomas, Manila, Philippines
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Institute of Prevention and Treatment of Cancer of Heilongjiang Province, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - AKadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sheung-Tat Fan
- Liver Surgery and Transplant Centre, Hong Kong Sanatorium and Hospital, Hong Kong, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Prefectural Center Hospital, Kofu-City, Yamanashi, Japan
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Tabrizian P, Marino R, Chow PK. Liver resection and transplantation in the era of checkpoint inhibitors. JHEP Rep 2024; 6:101181. [PMID: 39741696 PMCID: PMC11686060 DOI: 10.1016/j.jhepr.2024.101181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/24/2024] [Accepted: 07/26/2024] [Indexed: 01/03/2025] Open
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape for advanced hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab has demonstrated efficacy, establishing a new standard of care for advanced HCC. Neoadjuvant studies have shown promising results with high response rates, increasing research into ICIs' role. In the peri-operative setting, in addition to adjuvant and neo-adjuvant therapies, strategies for "downstaging" and "bridging" patients to liver transplantation (LT) are being investigated, broadening the eligible candidate pool. Furthermore, therapeutic advances have reshaped conversion strategies for hepatic resection, with emerging evidence indicating a role for adjuvant immunotherapy in patients at high risk of postoperative recurrence. In LT, concerns have arisen over the potential conflict between immunosuppression needs and the immune-enhancing effects of ICIs, with reports of severe rejection. However, liver-specific factors may lessen rejection risks, prompting exploration into the safety of pre-transplant ICI administration. Moreover, ongoing trials must prioritise patient selection and vigilant management protocols. Despite the remarkable progress in immunotherapy, the intricate molecular interactions within the tumour microenvironment and their implications on oncogenic pathways remain incompletely understood. This highlights the need for specialised expertise to effectively integrate immunotherapy into the surgical management of HCC. Key challenges include ensuring safety, optimising oncological outcomes, managing the risk of graft rejection in transplant recipients, and refining patient selection criteria. In this review, we aim to provide a comprehensive overview of the evolving role of immunotherapy in the surgical management of HCC, discussing the rationale for its application in both pre- and post-surgical contexts, leveraging current clinical experience, identifying potential limitations, and envisioning future applications. By integrating existing knowledge and highlighting areas for further investigation, this review seeks to inform clinical practice and guide future research endeavours.
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Affiliation(s)
- Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, USA
| | - Rebecca Marino
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, USA
| | - Pierce K.H. Chow
- Department of Hepato-pancreato-Biliary and Transplant Surgery, National Cancer Center Singapore and Singapore General Hospital, Singapore
- Surgery Academic-Clinical Program, Duke-NUS Medical School Singapore, Singapore
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7
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Goh MJ, Park HC, Kim N, Bae BK, Choi MS, Rhu J, Lee MW, Jeong WK, Kim M, Kim K, Yu JI. Modified Albumin-Bilirubin Grade After Curative Treatment: Predicting the Risk of Late Intrahepatic Recurrence of Hepatocellular Carcinoma. J Korean Med Sci 2024; 39:e251. [PMID: 39355950 PMCID: PMC11444816 DOI: 10.3346/jkms.2024.39.e251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 07/18/2024] [Indexed: 10/03/2024] Open
Abstract
BACKGROUND We aimed to identify the prognostic factors for late intrahepatic recurrence (IHR), defined as recurrence more than two years after curative treatment of newly diagnosed hepatocellular carcinoma (HCC). METHODS This retrospective cohort study included patients with newly diagnosed, previously untreated, very early, or early HCC treated with initial curative treatment and followed up without recurrence for more than two years, excluding early IHR defined as recurrence within two years in single center. Late IHR-free survival (IHRFS) was defined as the time interval from initial curative treatment to the first IHR or death without IHR, whichever occurred first. RESULTS Among all the enrolled 2,304 patients, 1,427 (61.9%) underwent curative intent hepatectomy and the remaining 877 (38.1%) underwent local ablative therapy (LAT). During the follow-up after curative treatment (median, 82.6 months; range, 24.1 to 195.7), late IHR was detected in 816 (35.4%) patients. In the multivariable analysis, age, male sex, cirrhotic liver at diagnosis, type of initial treatment, and modified albumin-bilirubin (mALBI) grade were significant prognostic baseline factors. Furthermore, mALBI grade at three (2a vs. 1, P = 0.02, hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.04-1.70; 2b/3 vs. 1, P = 0.03; HR, 1.42; 95% CI, 1.03-1.94) and six months (2b/3 vs. 1; P = 0.006; HR, 1.61; 95% CI, 1.13-2.30) after initial curative treatment was also a significant prognostic factor for late IHR. CONCLUSION After curative treatment for newly diagnosed early HCC, the mALBI grade at three and six months after initial curative treatment, as well as at baseline, was one of the most crucial prognostic factors for late IHR.
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Affiliation(s)
- Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nalee Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Bong Kyung Bae
- Department of Radiation Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min Woo Lee
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Kyoung Jeong
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Minji Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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8
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Wan DL, Sun LQ. Timing of antiviral therapy in patients with hepatitis B virus related hepatocellular carcinoma undergoing hepatectomy. World J Clin Oncol 2024; 15:1251-1255. [PMID: 39351460 PMCID: PMC11438849 DOI: 10.5306/wjco.v15.i9.1251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 08/08/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is among the most prevalent and deadly cancers. Hepatitis B virus (HBV) infection is an important etiology and disease progression factor for HCC. Hepatectomy is a widely accepted curative treatment for HCC, but the long-term survival rate is still unsatisfactory due to the high recurrence rate after resection. Preoperative or postoperative antiviral therapy plays an important role in improving the prognosis for HBV-related HCC patients who underwent hepatectomy. However, many patients miss out on the chance to receive long-term preoperative antiviral medication because their HBV and HCC infections are discovered concurrently, necessitating the start of remedial antiviral therapy in the perioperative phase. Therefore, it is of great value to know when antiviral therapy is more appropriate and whether perioperative rescue antiviral therapy can achieve the effect of preoperative long-term antiviral therapy.
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Affiliation(s)
- Dong-Ling Wan
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Li-Qi Sun
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
- Department of Gastroenterology, 72th Group Army Hospital, Huzhou 313000, Zhejiang Province, China
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9
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Danzeng A, Guo L, Yang ZH, He ZW, Zeng CL, Ciren P, Lan RH, Jiang XW, Wang C, Zhang BH. Postoperative lenvatinib + PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with microvascular invasion (Barcelona Clinic Liver Cancer stage 0 or A): a propensity score matching analysis. J Gastrointest Surg 2024; 28:1104-1112. [PMID: 38723996 DOI: 10.1016/j.gassur.2024.05.001] [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: 02/27/2024] [Revised: 04/22/2024] [Accepted: 05/03/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI). METHODS A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022). CONCLUSION Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals.
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Affiliation(s)
- Awang Danzeng
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Guo
- Division of Hepato-Pancreato-Biliary Surgery, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Zhen-Hua Yang
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng-Wei He
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cheng-Long Zeng
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Pingcuo Ciren
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Run-Hu Lan
- Division of Hepato-Pancreato-Biliary Surgery, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Xue-Wei Jiang
- Division of Hepato-Pancreato-Biliary Surgery, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Chao Wang
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-Hao Zhang
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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10
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Ding J, Yang YY, Li PT, Ma Y, Zhang L, Zhou Y, Jin C, Li HY, Zhu YF, Liu XP, Liu ZJ, Jia HL, Liu PG, Wu J. TGF-β1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma. Cancer Lett 2024; 588:216768. [PMID: 38453045 DOI: 10.1016/j.canlet.2024.216768] [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: 11/27/2023] [Revised: 01/31/2024] [Accepted: 02/26/2024] [Indexed: 03/09/2024]
Abstract
Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-β1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-β1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-β/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.
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Affiliation(s)
- Jia Ding
- Department of Gastroenterology, Shanghai Jing'an District Central Hospital, Fudan University, Shanghai, 200040, China.
| | - Yong-Yu Yang
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Peng-Tao Li
- Department of Hepatobiliary & Pancreatic Surgery, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, China
| | - Yue Ma
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Li Zhang
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Yuan Zhou
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Cheng Jin
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Hui-Yan Li
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Yuan-Fei Zhu
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Xiu-Ping Liu
- Department of Pathology and Laboratory Medicine, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Zheng-Jin Liu
- Department of Pathology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, China
| | - Hu-Liang Jia
- Department of General Surgery, Huashan Hospital of Fudan University, Shanghai, 200041, China
| | - Ping-Guo Liu
- Department of Hepatobiliary & Pancreatic Surgery, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, China.
| | - Jian Wu
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China; Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China; Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China.
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11
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Wang K, Xiang YJ, Yu HM, Cheng YQ, Liu ZH, Qin YY, Shi J, Guo WX, Lu CD, Zheng YX, Zhou FG, Yan ML, Zhou HK, Liang C, Zhang F, Wei WJ, Lau WY, Li JJ, Liu YF, Cheng SQ. Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial. Nat Med 2024; 30:708-715. [PMID: 38242982 DOI: 10.1038/s41591-023-02786-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 12/21/2023] [Indexed: 01/21/2024]
Abstract
Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 .
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Affiliation(s)
- Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- Shanghai Hepatobiliary Cancer Research Center, Naval Medical University, Shanghai, China
| | - Yan-Jun Xiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai, China
| | - Hong-Ming Yu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- Shanghai Hepatobiliary Cancer Research Center, Naval Medical University, Shanghai, China
| | - Yu-Qiang Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
- Shanghai Hepatobiliary Cancer Research Center, Naval Medical University, Shanghai, China
| | - Zong-Han Liu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Ying-Yi Qin
- Department of Health Statistics, Naval Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Chong-De Lu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Ya-Xin Zheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Fei-Guo Zhou
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Mao-Lin Yan
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Hong-Kun Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing College, Jiaxing, China
| | - Chao Liang
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fan Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China
| | - Wen-Jing Wei
- Department of General Surgery, Taiyuan People's Hospital, Taiyuan, China
| | - Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Jing-Jing Li
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Yan-Fang Liu
- National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai, China.
- Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, China.
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
- Shanghai Hepatobiliary Cancer Research Center, Naval Medical University, Shanghai, China.
- Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.
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12
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Hu R, Xu J, Wang H, Wang J, Lei K, Zhao X, Zhang H, You K, Liu Z. Impact of preoperative transcatheter arterial chemoembolization (TACE) on postoperative long-term survival in patients with nonsmall hepatocellular carcinoma: a propensity score matching analysis. BMC Cancer 2024; 24:190. [PMID: 38336712 PMCID: PMC10858462 DOI: 10.1186/s12885-024-11978-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 02/07/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND The purpose of this propensity score matching (PSM) analysis was to compare the effects of preoperative transcatheter arterial chemoembolization (TACE) and non-TACE on the long-term survival of patients who undergo radical hepatectomy. METHODS PSM analysis was performed for 387 patients with hepatocellular carcinoma (HCC) (single > 3 cm or multiple) who underwent radical resection of HCC at our centre from January 2011 to June 2018. The patients were allocated to a preoperative TACE group (n = 77) and a non-TACE group (n = 310). The main outcome measures were progression-free survival (PFS) and overall survival (OS) since the treatment date. RESULTS After PSM, 67 patients were included in each of the TACE and non-TACE groups. The median PFS times in the preoperative TACE and non-TACE groups were 24.0 and 11.3 months, respectively (p = 0.0117). The median OS times in the preoperative TACE and non-TACE groups were 41.5 and 29.0 months, respectively (p = 0.0114). Multivariate Cox proportional hazard regression analysis revealed that preoperative TACE (hazard ratio, 1.733; 95% CI, 1.168-2.570) and tumour thrombosis (hazard ratio, 0.323; 95% CI, 0.141-0.742) were independent risk factors significantly associated with OS. CONCLUSIONS Preoperative TACE is related to improving PFS and OS after resection of HCC. Preoperative TACE and tumour thrombus volume were also found to be independent risk factors associated with OS.
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Affiliation(s)
- Run Hu
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Jie Xu
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Hongxiang Wang
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Jiaguo Wang
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Kai Lei
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Xiaoping Zhao
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Huizhi Zhang
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Ke You
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Zuojin Liu
- The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China.
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13
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Pelizzaro F, Trevisani F, Simeon V, Vitale A, Cillo U, Piscaglia F, Missale G, Sangiovanni A, Foschi FG, Cabibbo G, Caturelli E, Di Marco M, Azzaroli F, Brunetto MR, Raimondo G, Vidili G, Guarino M, Gasbarrini A, Campani C, Svegliati-Baroni G, Giannini EG, Mega A, Masotto A, Rapaccini GL, Magalotti D, Sacco R, Nardone G, Farinati F. Predictors of non-transplantable recurrence in hepatocellular carcinoma patients treated with frontline liver resection. Liver Int 2023; 43:2762-2775. [PMID: 37753540 DOI: 10.1111/liv.15719] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 08/09/2023] [Accepted: 08/21/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non-transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR. METHODS From the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up-to-seven criteria were compared between patients with HCC <4 and ≥4 cm. RESULTS During a median follow-up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up-to-seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence-free survival and overall survival. HCC size ≥4 cm and high alpha-fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up-to-seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non-transplantable recurrence. CONCLUSIONS Despite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long-term survival. Non-transplantable recurrence is predicted by HCC size and AFP levels, among pre-operatively available variables. High-risk patients could be considered for frontline LT or listed for transplantation even before recurrence.
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Affiliation(s)
- Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-related diseases, Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Vittorio Simeon
- Medical Statistics Unit, Mental, Physical Health and Preventive Medicine, University of Campania 'Luigi Vanvitelli', Napoli, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gabriele Missale
- Department of Medicine and Surgery, Unit of Infectious Diseases and Hepatology, University of Parma, Parma, Italy
| | - Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesco G Foschi
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | | | | | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maurizia R Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine Unit, University of Pisa, Pisa, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Gianpaolo Vidili
- Department of Medicine Surgery and Pharmacy, Centralized Day Hospital of the medical area, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Napoli 'Federico II', Napoli, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy
| | | | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gian Ludovico Rapaccini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Donatella Magalotti
- Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli 'Federico II', Napoli, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padova, Italy
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14
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Giudicelli H, Andraud M, Wagner M, Bourdais R, Goumard C, Scatton O, Thabut D, Simon J, Allaire M. Portal-hypertension features are associated with ascites occurrence and survival in patients with hepatocellular carcinoma treated by external radiotherapy. United European Gastroenterol J 2023; 11:985-997. [PMID: 38018771 PMCID: PMC10720686 DOI: 10.1002/ueg2.12488] [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: 06/12/2023] [Accepted: 09/19/2023] [Indexed: 11/30/2023] Open
Abstract
BACKGROUND AND AIMS We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC). METHOD All cirrhotic patients that received radiotherapy for HCC between 2012 and 2022 were included. Portal hypertension-Score was built using univariate analysis with the presence of esophageal varices (EV), platelet count, history of acute variceal bleeding (AVB) and spleen size. Time-to-events data were estimated using Kaplan-Meier method with log-rank and Cox-models. RESULTS 60 patients were included (female 27%, age 67 years-old, Child-Pugh A 82%, alcoholic/non-alcoholic steatohepatitis/hepatitis C virus 55/40/32%). 38% and 15% presented history of ascites and AVB respectively, 25% had large EV, 53.5% presented PHT score ≥ 5. 92% were BCLC-0/A, median tumor size was 30 mm. At 6 months, ascites incidence was 19% and precluded access to further HCC treatment for all patients with HCC recurrence. All PHT parameters included in the score and PHT score ≥ 5 (hazard ratio (HR) = 14.07, p = 0.01) were associated with ascites occurrence. Transplantation free survival and recurrence free survival at 1 year were 56% and 47% respectively. Albi grade 3 (HR = 3.01; p = 0.04) was independently associated with Transplantation free survival. CONCLUSION Radiotherapy should be cautiously performed in patients with PHT score ≥ 5 because of ascites occurrence risk precluding access to further HCC treatments.
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Affiliation(s)
- Héloïse Giudicelli
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’Hépato‐gastroentérologieParisFrance
| | - Mickaël Andraud
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de radiothérapieParisFrance
| | - Mathilde Wagner
- AP‐HP, Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’imagerieParisFrance
- Sorbonne UniversitéLaboratoire d’Imagerie biomédicaleUMR 7371 ‐ U1146ParisFrance
| | - Rémi Bourdais
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de radiothérapieParisFrance
| | - Claire Goumard
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de chirurgie digestiveParisFrance
- Sorbonne UniversitéINSERMCentre de recherche Saint‐Antoine (CRSA)Institute of Cardiometabolism and Nutrition (ICAN)ParisFrance
| | - Olivier Scatton
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de chirurgie digestiveParisFrance
- Sorbonne UniversitéINSERMCentre de recherche Saint‐Antoine (CRSA)Institute of Cardiometabolism and Nutrition (ICAN)ParisFrance
| | - Dominique Thabut
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’Hépato‐gastroentérologieParisFrance
- Sorbonne UniversitéINSERMCentre de recherche Saint‐Antoine (CRSA)Institute of Cardiometabolism and Nutrition (ICAN)ParisFrance
| | - Jean‐Marc Simon
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de radiothérapieParisFrance
| | - Manon Allaire
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’Hépato‐gastroentérologieParisFrance
- INSERM UMR 1138Centre de recherche des CordeliersParisFrance
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15
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Li Z, Yu J, Li Y, Liu Y, Zhang M, Yang H, Du Y. Preoperative Radiomics Nomogram Based on CT Image Predicts Recurrence-Free Survival After Surgical Resection of Hepatocellular Carcinoma. Acad Radiol 2023; 30:1531-1543. [PMID: 36653278 DOI: 10.1016/j.acra.2022.12.039] [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: 10/31/2022] [Revised: 12/19/2022] [Accepted: 12/23/2022] [Indexed: 01/19/2023]
Abstract
RATIONALE AND OBJECTIVES To construct preoperative models based on CT radiomics, radiologic and clinical features to predict recurrence-free survival (RFS) after liver resection (LR) of BCLC 0 to B stage hepatocellular carcinoma (HCC) and to classify the prognosis. MATERIALS AND METHODS This study retrospectively analyzed 161 HCC patients who underwent radical LR. Two methods, the least absolute shrinkage and selection operator and random survival forest analysis, were performed for radiomics signature (RS) construction. Univariate and multivariate stepwise Cox regression analyses were performed to establish a combined nomogram (RCN) of RS and clinical parameters and a clinical nomogram (CN). The performance of the models was assessed comprehensively using Harrell's concordance index (C-index), the calibration curve, and decision curve analysis. The discrimination accuracy of the models was compared using integrated discrimination improvement index (IDI). The risk stratification effect was assessed with Kaplan-Meier survival analysis and subgroup analysis. RESULTS The RCN achieved a C-index of 0.792/0.758 in the training/validation set, which was higher than the CN, RS, and BCLC stage system. The discriminatory accuracy of the RCN was improved when compared to the CN, RS, and BCLC staging systems (IDI > 0). Decision curve analysis reflected the clinical net benefit of the RCN. The RCN allows risk stratification of patients in different clinical subgroups. CONCLUSION The integrated model combining RS and clinical factors can more effectively predict RFS after LR of BCLC 0 to B stage HCC patients and can effectively stratify the prognostic risk.
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Affiliation(s)
- Zeyong Li
- Department of Radiology, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, China
| | - Jialin Yu
- Department of Radiology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Shapingba, Chongqing, China
| | - Yehan Li
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000
| | - Ying Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000
| | - Manjing Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000
| | - Hanfeng Yang
- Department of Radiology and Interventional Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yong Du
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000.
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16
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Wang P, Wang X, Liu X, Yan F, Yan H, Zhou D, Yu L, Wang X, Yang Z. Primary non-response to antiviral therapy affects the prognosis of hepatitis B virus-related hepatocellular carcinoma. BMC Cancer 2023; 23:564. [PMID: 37340357 PMCID: PMC10280839 DOI: 10.1186/s12885-023-11059-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 06/12/2023] [Indexed: 06/22/2023] Open
Abstract
BACKGROUND AND AIM Although antiviral treatments have been shown to affect the recurrence and long-term survival of patients with hepatocellular carcinoma (HCC) who have high viral loads, the effect of different responses to antiviral therapy on the clinical outcomes remains unclear. This study aimed to assess the effect of primary non-response (no-PR) to antiviral therapy on the survival or prognosis of patients with HCC with a high load of hepatitis B virus (HBV) DNA. METHODS A total of 493 HBV-HCC patients hospitalized at Beijing Ditan Hospital of Capital Medical University were admitted to this retrospective study. Patients were divided into two groups based on viral response (no-PR and primary response). Kaplan-Meier (KM) curves were used to compare the overall survival of the two cohorts. Serum viral load comparison and subgroup analysis were performed. Additionally, risk factors were screened and the risk score chart was created. RESULTS This study consisted of 101 patients with no-PR and 392 patients with primary response. In the different categories based on hepatitis B e antigen and HBV DNA, no-PR group had a poor 1-year overall survival (OS). In addition, in the alanine aminotransferase < 50 IU/L and cirrhosis groups, primary nonresponse was related to poor overall survival and progression-free survival. Based on multivariate risk analysis, primary non-response (hazard ratio (HR) = 1.883, 95% CI 1.289-2.751, P = 0.001), tumor multiplicity (HR = 1.488, 95% CI 1.036-2.136, P = 0.031), portal vein tumor thrombus (HR = 2.732, 95% CI 1.859-4.015, P < 0.001), hemoglobin < 120 g/L (HR = 2.211, 95% CI 1.548-3.158, P < 0.001) and tumor size ≥ 5 cm (HR = 2.202, 95% CI 1.533-3.163, P < 0.001) were independent risk factors for 1-year OS. According to the scoring chart, patients were divided into three risk groups (high-, medium-, and low-risk groups) with mortality rates of 61.7%, 30.5%, and 14.1%, respectively. CONCLUSIONS The level of viral decline at 3 months post-antiviral treatment may predict the OS of patients with HBV-related HCC, and primary non-response may shorten the median survival time of patients with high HBV-DNA levels.
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Affiliation(s)
- Peng Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Xinhui Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Xiaoli Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Fengna Yan
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Huiwen Yan
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Dongdong Zhou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Lihua Yu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China
| | - Zhiyun Yang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, P.R. China.
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Li M, Huang J, Zhan G, Li Y, Fang C, Xiang B. The Novel-Natural-Killer-Cell-Related Gene Signature Predicts the Prognosis and Immune Status of Patients with Hepatocellular Carcinoma. Int J Mol Sci 2023; 24:ijms24119587. [PMID: 37298537 DOI: 10.3390/ijms24119587] [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: 04/07/2023] [Revised: 05/26/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023] Open
Abstract
The current understanding of the prognostic significance of natural killer (NK) cells and their tumor microenvironment (TME) in hepatocellular carcinoma (HCC) is limited. Thus, we screened for NK-cell-related genes by single-cell transcriptome data analysis and developed an NK-cell-related gene signature (NKRGS) using multi-regression analyses. Patients in the Cancer Genome Atlas cohort were stratified into high- and low-risk groups according to their median NKRGS risk scores. Overall survival between the risk groups was estimated using the Kaplan-Meier method, and a NKRGS-based nomogram was constructed. Immune infiltration profiles were compared between the risk groups. The NKRGS risk model suggests significantly worse prognoses in patients with high NKRGS risk (p < 0.05). The NKRGS-based nomogram showed good prognostic performance. The immune infiltration analysis revealed that the high-NKRGS-risk patients had significantly lower immune cell infiltration levels (p < 0.05) and were more likely to be in an immunosuppressive state. The enrichment analysis revealed that immune-related and tumor metabolism pathways highly correlated with the prognostic gene signature. In this study, a novel NKRGS was developed to stratify the prognosis of HCC patients. An immunosuppressive TME coincided with the high NKRGS risk among the HCC patients. The higher KLRB1 and DUSP10 expression levels correlated with the patients' favorable survival.
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Affiliation(s)
- Minjun Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Juntao Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Guohua Zhan
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Yuankuan Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Chunye Fang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Bangde Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, China
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18
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Seidensticker M, Öcal O, Schütte K, Malfertheiner P, Berg T, Loewe C, Klümpen HJ, van Delden O, Ümütlü MR, Ben Khaled N, de Toni EN, Seidensticker R, Aghdassi A, Tran A, Bronowicki JP, Peynircioglu B, Sangro B, Pech M, Ricke J. Impact of adjuvant sorafenib treatment after local ablation for HCC in the phase II SORAMIC trial. JHEP Rep 2023; 5:100699. [PMID: 36968218 PMCID: PMC10031000 DOI: 10.1016/j.jhepr.2023.100699] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 12/22/2022] [Accepted: 01/17/2023] [Indexed: 03/29/2023] Open
Abstract
Background & Aims The aim of the study was to evaluate the efficacy and safety of adjuvant sorafenib treatment compared with placebo in patients with hepatocellular carcinoma who underwent local ablation. Methods The SORAMIC trial is a randomised controlled trial with diagnostic, local ablation, and palliative sub-study arms. After initial imaging within the diagnostic study, patients were assigned to local ablation or palliative arms. In the local ablation cohort, patients were randomised 1:1 to local ablation + sorafenib vs. local ablation + placebo. The primary endpoint was time-to-recurrence (TTR). Secondary endpoints were local control rate and safety in terms of adverse events and quality-of-life. Results The recruitment was terminated prematurely after 104 patients owing to slow recruitment. One patient was excluded because of a technical failure. Fifty-four patients were randomised to local ablation + sorafenib and 49 to local ablation + placebo. Eighty-eight patients who underwent standardised follow-up imaging comprised the per-protocol population. The median TTR was 15.2 months in the sorafenib arm and 16.4 months in the placebo arm (hazard ratio 1.1; 95% CI 0.53-2.2; p = 0.82). Out of 136 lesions ablated within the trial, there was no difference in local recurrence rate between sorafenib (6/69, 8.6%) and placebo groups (5/67, 5.9%; p = 0.792).Overall (92.5% vs. 71.4%, p = 0.008) and drug-related (81.4% vs. 55.1%, p = 0.003) adverse events were more common in the sorafenib arm compared with the placebo arm. Dose reduction because of adverse events were common in the sorafenib arm (79.6% vs. 30.6%, p <0.001). Conclusions Adjuvant sorafenib did not improve in TTR or local control rate after local ablation in patients with hepatocellular carcinoma within the limitations of an early terminated trial. Impact and implications Local ablation is the standard of care treatment in patients with early stages of hepatocellular carcinoma, along with surgical therapies. However, there is a risk of disease recurrence during follow-up. Sorafenib, an oral medication, is a routinely used treatment for patients with advanced hepatocellular carcinoma. This study found that sorafenib treatment after local ablation in people with early hepatocellular carcinoma did not significantly improve the disease-free period compared with placebo. Clinical trial number EudraCT 2009-012576-27, NCT01126645.
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Key Words
- Adjuvant
- BCLC, Barcelona Clinic Liver Cancer
- CONSORT, Consolidated Standards of Reporting Trials
- CT, computed tomography
- ECOG PS, Eastern Cooperative Oncology Group Performance Status
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- Hepatocellular carcinoma
- ITT, intention-to-treat
- Local ablation
- MRI, magnetic resonance imaging
- MWA, microwave ablation
- PP, per protocol
- RFA, radiofrequency ablation
- RFS, relapse-free survival
- SIRT, selective internal radiation therapy
- SORAMIC, SORAfenib in combination with local MICro-therapy guided by gadolinium-EOB-DTPA-enhanced MRI
- Sorafenib
- TTR, time-to-recurrence
- Time-to-recurrence
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Affiliation(s)
- Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Osman Öcal
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Kerstin Schütte
- Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken Marienhospital, Osnabrück, Germany
| | | | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie, Sektion Hepatologie, Universitätsklinikum Leipzig, Germany
| | - Christian Loewe
- Section of Cardiovascular and Interventional Radiology, Department of Bioimaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Heinz Josef Klümpen
- Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Otto van Delden
- Department of Radiology and Nuclear Medicine, Academic University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | | | - Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | | | | | - Ali Aghdassi
- Department of Medicine A, University Medicine Greifswald, 17489 Greifswald, Germany
| | - Albert Tran
- Pôle Appareil Digestif, Hôpital l'Archet 2, CHU Nice, Route Saint-Antoine de Ginestière - BP 3079, Nice, France
| | - Jean-Pierre Bronowicki
- Department of Hepatology, INSERM U1254, Hôpital de Brabois, CHU de Nancy, University of Lorraine, Nancy, France
| | - Bora Peynircioglu
- Department of Radiology, Hacettepe University Hospital, Ankara, Turkey
| | - Bruno Sangro
- Liver Unit, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
- Corresponding author. Address: Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. Tel: +49-4400-72750..
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Adwan H, Hammann L, Vogl TJ. Microwave Ablation of Recurrent Hepatocellular Carcinoma after Curative Surgical Resection. J Clin Med 2023; 12:jcm12072560. [PMID: 37048644 PMCID: PMC10094797 DOI: 10.3390/jcm12072560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 03/31/2023] Open
Abstract
Purpose: To evaluate the efficacy and safety of microwave ablation (MWA) as a treatment for recurrent hepatocellular carcinoma (HCC) after initial successful surgical resection. Methods: This retrospective study included 40 patients (11 women and 29 men; mean age: 62.3 ± 11.7 years) with 48 recurrent lesions of HCC after initial surgical resection that were treated by percutaneous MWA. Several parameters including complications, technical success, local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), and progression-free survival (PFS) were evaluated in order to investigate the safety and efficacy of MWA for these recurrent HCC lesions after surgical treatment. Results: All MWA treatments were performed without complications or procedure-related deaths. Technical success was achieved in all cases. Two cases developed LTP at a rate of 5%, and IDR occurred in 23 cases at a rate of 57.5% (23/40). The 1-, 2-, 3-, 4-, and 6-year OS rates were 97%, 89.2%, 80.3%, 70.2%, and 60.2%, respectively. The 1- and 3-year PFS rates were 50.2% and 34.6%, respectively. Conclusion: MWA is effective and safe as a local treatment for recurrent HCC after initial surgical resection.
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Cao L, Wang Q, Hong J, Han Y, Zhang W, Zhong X, Che Y, Ma Y, Du K, Wu D, Pang T, Wu J, Liang K. MVI-TR: A Transformer-Based Deep Learning Model with Contrast-Enhanced CT for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15051538. [PMID: 36900327 PMCID: PMC10001339 DOI: 10.3390/cancers15051538] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/21/2023] [Accepted: 02/24/2023] [Indexed: 03/05/2023] Open
Abstract
In this study, we considered preoperative prediction of microvascular invasion (MVI) status with deep learning (DL) models for patients with early-stage hepatocellular carcinoma (HCC) (tumor size ≤ 5 cm). Two types of DL models based only on venous phase (VP) of contrast-enhanced computed tomography (CECT) were constructed and validated. From our hospital (First Affiliated Hospital of Zhejiang University, Zhejiang, P.R. China), 559 patients, who had histopathological confirmed MVI status, participated in this study. All preoperative CECT were collected, and the patients were randomly divided into training and validation cohorts at a ratio of 4:1. We proposed a novel transformer-based end-to-end DL model, named MVI-TR, which is a supervised learning method. MVI-TR can capture features automatically from radiomics and perform MVI preoperative assessments. In addition, a popular self-supervised learning method, the contrastive learning model, and the widely used residual networks (ResNets family) were constructed for fair comparisons. With an accuracy of 99.1%, a precision of 99.3%, an area under the curve (AUC) of 0.98, a recalling rate of 98.8%, and an F1-score of 99.1% in the training cohort, MVI-TR achieved superior outcomes. Additionally, the validation cohort's MVI status prediction had the best accuracy (97.2%), precision (97.3%), AUC (0.935), recalling rate (93.1%), and F1-score (95.2%). MVI-TR outperformed other models for predicting MVI status, and showed great preoperative predictive value for early-stage HCC patients.
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Affiliation(s)
- Linping Cao
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Qing Wang
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jiawei Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Yuzhe Han
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Weichen Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Xun Zhong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Yongqian Che
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yaqi Ma
- Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Keyi Du
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Dongyan Wu
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Tianxiao Pang
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
- Correspondence: (J.W.); (K.L.)
| | - Kewei Liang
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
- Correspondence: (J.W.); (K.L.)
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Nevola R, Ruocco R, Criscuolo L, Villani A, Alfano M, Beccia D, Imbriani S, Claar E, Cozzolino D, Sasso FC, Marrone A, Adinolfi LE, Rinaldi L. Predictors of early and late hepatocellular carcinoma recurrence. World J Gastroenterol 2023; 29:1243-1260. [PMID: 36925456 PMCID: PMC10011963 DOI: 10.3748/wjg.v29.i8.1243] [Citation(s) in RCA: 87] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/06/2023] [Accepted: 01/30/2023] [Indexed: 02/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
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Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ernesto Claar
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Domenico Cozzolino
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
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Takakusagi S, Tanaka H, Naganuma A, Kakizaki S, Shibuya K, Ohno T, Takagi H, Uraoka T. Two cases of hepatocellular carcinoma successfully treated by carbon ion radiotherapy after atezolizumab plus bevacizumab treatment. Clin J Gastroenterol 2023; 16:407-415. [PMID: 36750524 DOI: 10.1007/s12328-023-01768-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/30/2023] [Indexed: 02/09/2023]
Abstract
We herein report two cases of huge hepatocellular carcinoma (HCC) that were successfully treated by carbon ion radiotherapy after atezolizumab plus bevacizumab treatment. Case 1, an 84-year-old man, was diagnosed with HCC (maximum diameter: 11 cm) with portal invasion and presented HCC rupture. After obtaining hemostasis with transcatheter embolization, three cycles of atezolizumab-bevacizumab therapy were administered, and marked shrinkage of the HCC was confirmed. However, he developed jaundice, liver damage and cerebral subcortical hemorrhage. Thus, atezolizumab-bevacizumab therapy was discontinued. Total bilirubin, transaminase levels, and physical activity improved well with prednisolone, an antihypertensive agent, and rehabilitation. Thus, treatment with carbon ion radiotherapy (CIRT) was added, and the treatment effect at 4 months after CIRT was judged as a complete response (CR) according to the modified response evaluation criteria in solid tumors (mRECIST). Case 2, a 68-year-old man, was diagnosed with HCC (maximum diameter: 14 cm). Hepatic resection was difficult because the residual liver volume after treatment would be insufficient. Five cycles of atezolizumab-bevacizumab therapy were performed, and marked shrinkage of the HCC to a maximum diameter of 9 cm was confirmed. The treatment was converted to CIRT, and atezolizumab-bevacizumab therapy resumed one month after CIRT. The treatment effect at 3 months after CIRT was judged as CR according to mRECIST. Although conversion therapy after atezolizumab-bevacizumab therapy, including surgery and radiofrequency ablation, have been reported, CIRT may be a promising new tool for conversion therapy for HCC.
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Affiliation(s)
- Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka, Gunma, 375-0024, Japan
| | - Hinako Tanaka
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-Cho, Takasaki, Gunma, 370-0829, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-Cho, Takasaki, Gunma, 370-0829, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-Cho, Takasaki, Gunma, 370-0829, Japan.
| | - Kei Shibuya
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Tatsuya Ohno
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-15, Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka, Gunma, 375-0024, Japan.
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma, 371-8511, Japan
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GSPT1 Functions as a Tumor Promoter in Human Liver Cancer. Curr Med Sci 2023; 43:104-114. [PMID: 36459303 DOI: 10.1007/s11596-022-2665-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 09/20/2022] [Indexed: 12/03/2022]
Abstract
OBJECTIVE This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells. METHODS A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays. RESULTS The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo. CONCLUSION In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.
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Hu S, Kang Y, Xie Y, Yang T, Yang Y, Jiao J, Zou Q, Zhang H, Zhang Y. 18F-FDG PET/CT-based radiomics nomogram for preoperative prediction of macrotrabecular-massive hepatocellular carcinoma: a two-center study. Abdom Radiol (NY) 2023; 48:532-542. [PMID: 36370179 DOI: 10.1007/s00261-022-03722-y] [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: 08/25/2022] [Revised: 10/18/2022] [Accepted: 10/18/2022] [Indexed: 11/13/2022]
Abstract
PURPOSE To explore the potential of β-2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the evaluation of macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC) and to apply radiomics approach to build a radiomics nomogram for predicting MTM-HCC. METHODS This study included 140 (training cohort:101; validation cohort:39) HCC patients who underwent preoperative 18F-FDG PET/CT at two institutions. The clinical features and tumor FDG metabolism measured by the tumor-to-liver ratio (TLR) via 18F-FDG PET/CT were retrospectively collected. Radiomics features were extracted from 18F-FDG PET/CT images and a radiomics score (Rad-score) was calculated. A radiomics nomogram was then constructed by combining Rad-score and independent clinical features and was assessed with a calibration curve. The performance of the radiomics nomogram, Rad-score and TLR was evaluated by receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS A total of six top weighted radiomics features were selected from PET/CT images by the least absolute shrinkage and selection operator (LASSO) regression algorithm and were used to construct a Rad-score. Multivariate analysis identified Rad-score (OR = 2.183, P = 0.004), age ≤ 50 years (OR = 3.136, P = 0.036), AST > 40U/L (OR = 0.270, P = 0.017) and TLR (OR = 1.641, P = 0.049) as independent predictors of MTM-HCC. The radiomics nomogram had a higher area under the curves (AUCs) than the Rad-score and TLR for predicting MTM-HCC in both training (0.849 [95% CI 0.774-0.924] vs. 0.764 [95% CI 0.669-0.843], 0.763 [95% CI 0.668-0.842]) and validation (0.749 [95% CI 0.584-0.873] vs. 0.690 [95% CI 0.522-0.828], 0.541 [95% CI 0.374-0.701]) cohorts. DCA showed the radiomics nomogram to be more clinically useful than Rad-score and TLR. CONCLUSIONS Tumor FDG metabolism is significantly associated with MTM-HCC. A 18F-FDG PET/CT-based radiomics nomogram may be useful for preoperatively predicting the MTM subtype in primary HCC patients, contributing to pretreatment decision-making.
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Affiliation(s)
- Siqi Hu
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
| | - Yinqian Kang
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
- Department of Anesthesiology, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng East Road, Yuexiu District, Guangzhou, 510060, China
| | - Yujie Xie
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
| | - Ting Yang
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
| | - Yuan Yang
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
| | - Ju Jiao
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
| | - Qiong Zou
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
| | - Hong Zhang
- Department of Nuclear Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 33 Yingfeng Road, Haizhu District, Guangzhou, 510289, China.
| | - Yong Zhang
- Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China.
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Yang J, Jiang S, Chen Y, Zhang J, Deng Y. Adjuvant ICIs Plus Targeted Therapies Reduce HCC Recurrence after Hepatectomy in Patients with High Risk of Recurrence. Curr Oncol 2023; 30:1708-1719. [PMID: 36826093 PMCID: PMC9955678 DOI: 10.3390/curroncol30020132] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The high recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy usually results in poor prognosis. To the best of our knowledge, no study has reported the efficacy of immune checkpoint inhibitors (ICIs) plus targeted therapies on preventing HCC recurrence after hepatectomy. Thus, the aim of this study was to investigate the benefits and safety of applying adjuvant ICIs plus targeted therapies after hepatectomy for patients at high risk of HCC recurrence. METHODS A total of 196 patients with any risk factors for recurrence who underwent hepatectomy for HCC were reviewed in this retrospective study. RESULTS Compared with the control group (n = 158), ICIs plus targeted therapies (n = 38) had a significantly higher recurrence-free survival (RFS) rate in univariate analysis (HR, 0.46; 95% confidence interval [CI], 0.24-0.90; p = 0.020), multivariate analysis (adjusted HR, 0.62; 95%CI, 0.49-0.79; p < 0.001) and propensity score-matched analysis (HR, 0.35; 95%CI, 0.16-0.75; p = 0.005). Subgroup analyses also showed that postoperative adjuvant ICIs plus targeted therapies might reduce HCC recurrence in patients with the most of risk factors. CONCLUSION Postoperative adjuvant ICI plus targeted therapies may reduces early HCC recurrence in patients with a high risk of recurrence, and the treatments are well tolerated.
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Affiliation(s)
| | | | | | | | - Yinan Deng
- Correspondence: ; Tel.: +86-20-85253106; Fax: +86-20-85252276
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Liver Resection and Transplantation Following Yttrium-90 Radioembolization for Primary Malignant Liver Tumors: A 15-Year Single-Center Experience. Cancers (Basel) 2023; 15:cancers15030733. [PMID: 36765691 PMCID: PMC9913597 DOI: 10.3390/cancers15030733] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/13/2023] [Accepted: 01/22/2023] [Indexed: 01/27/2023] Open
Abstract
Radioembolization (RE) may help local control and achieve tumor reduction while hypertrophies healthy liver and provides a test of time. For liver transplant (LT) candidates, it may attain downstaging for initially non-candidates and bridging during the waitlist. METHODS Patients diagnosed with HCC and ICC treated by RE with further liver resection (LR) or LT between 2005-2020 were included. All patients selected were discarded for the upfront surgical approach for not accomplishing oncological or surgical safety criteria after a multidisciplinary team assessment. Data for clinicopathological details, postoperative, and survival outcomes were retrospectively reviewed from a prospectively maintained database. RESULTS A total of 34 patients underwent surgery following RE (21 LR and 13 LT). Clavien-Dindo grade III-IV complications and mortality rates were 19.0% and 9.5% for LR and 7.7% and 0% for LT, respectively. After RE, for HCC and ICC patients in the LR group, 10-year OS rates were 57% and 60%, and 10-year DFS rates were 43.1% and 60%, respectively. For HCC patients in the LT group, 10-year OS and DFS rates from RE were 51.3% and 43.3%, respectively. CONCLUSION Liver resection after RE is safe and feasible with optimal short-term outcomes. Patients diagnosed with unresectable or high biological risk HCC or ICC, treated with RE, and rescued by LR may achieve optimal global and DFS rates. On the other hand, bridging or downstaging strategies to LT with RE in HCC patients show adequate recurrence rates as well as long-term survival.
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Preoperative assessment of microvascular invasion of hepatocellular carcinoma using non-Gaussian diffusion-weighted imaging with a fractional order calculus model: A pilot study. Magn Reson Imaging 2023; 95:110-117. [PMID: 34506910 DOI: 10.1016/j.mri.2021.09.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 09/05/2021] [Accepted: 09/05/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE To assess the clinical potential of a set of new diffusion parameters (D, β, and μ) derived from fractional order calculus (FROC) diffusion model in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Between January 2019 to November 2020, a total of 63 patients with HCC were enrolled in this study. Diffusion-weighted images were acquired by using ten b-values (0-2000 s/mm2). The FROC model parameters including diffusion coefficient (D), fractional order parameter (β), a microstructural quantity (μ) together with a conventional apparent diffusion coefficient (ADC) were calculated. Intraclass coefficients were calculated for assessing the agreement of parameters quantified by two radiologists. The differences of these values between the MVI-positive and MVI-negative HCC groups were compared by using independent sample t-test or the Mann-Whitney U test. Then the parameters showing significant differences between subgroups, including the β and D, were integrated to develop a comprehensive predictive model via binary logistic regression. The diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS Among all the studied diffusion parameters, significant differences were found in D, β, and ADC between the MVI-positive and MVI-negative groups. MVI-positive HCCs showed significantly higher β values (0.65 ± 0.17 vs. 0.51 ± 0.13, P = 0.001), along with lower D values (0.84 ± 0.11 μm2/ms vs. 1.03 ± 0.13 μm2/ms, P < 0.001) and lower ADC values (1.38 ± 0.46 μm2/ms vs. 2.09 ± 0.70 μm2/ms, P < 0.001) than those of MVI-negative HCCs. According to the ROC analysis, the combination of D and β demonstrated the largest area under the ROC curve (0.920) compared with individual parameters (D: 0.912; β: 0.733; and ADC: 0.831) for differentiating MVI-positive from MVI-negative HCCs. CONCLUSIONS The FROC parameters can be used as noninvasive quantitative imaging markers for preoperatively predicting the MVI status of HCCs.
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Huang Z, Shu Z, Zhu RH, Xin JY, Wu LL, Wang HZ, Chen J, Zhang ZW, Luo HC, Li KY. Deep learning-based radiomics based on contrast-enhanced ultrasound predicts early recurrence and survival outcome in hepatocellular carcinoma. World J Gastrointest Oncol 2022; 14:2380-2392. [PMID: 36568943 PMCID: PMC9782621 DOI: 10.4251/wjgo.v14.i12.2380] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/21/2022] [Accepted: 11/21/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary liver malignancy.
AIM To predict early recurrence (ER) and overall survival (OS) in patients with HCC after radical resection using deep learning-based radiomics (DLR).
METHODS A total of 414 consecutive patients with HCC who underwent surgical resection with available preoperative grayscale and contrast-enhanced ultrasound images were enrolled. The clinical, DLR, and clinical + DLR models were then designed to predict ER and OS.
RESULTS The DLR model for predicting ER showed satisfactory clinical benefits [area under the curve (AUC)] = 0.819 and 0.568 in the training and testing cohorts, respectively), similar to the clinical model (AUC = 0.580 and 0.520 in the training and testing cohorts, respectively; P > 0.05). The C-index of the clinical + DLR model in the prediction of OS in the training and testing cohorts was 0.800 and 0.759, respectively. The clinical + DLR model and the DLR model outperformed the clinical model in the training and testing cohorts (P < 0.001 for all). We divided patients into four categories by dichotomizing predicted ER and OS. For patients in class 1 (high ER rate and low risk of OS), retreatment (microwave ablation) after recurrence was associated with improved survival (hazard ratio = 7.895, P = 0.005).
CONCLUSION Compared to the clinical model, the clinical + DLR model significantly improves the accuracy of predicting OS in HCC patients after radical resection.
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Affiliation(s)
- Zhe Huang
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhu Shu
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Rong-Hua Zhu
- Institute of Hepato-pancreato-bililary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Jun-Yi Xin
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Ling-Ling Wu
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Han-Zhang Wang
- PDx Advanced Applications, GE Healthcare, Shanghai 200020, China
| | - Jun Chen
- PDx Advanced Applications, GE Healthcare, Shanghai 200020, China
| | - Zhi-Wei Zhang
- Institute of Hepato-pancreato-bililary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Hong-Chang Luo
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Kai-Yan Li
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Jonas E, Bernon M, Robertson B, Kassianides C, Keli E, Asare KO, Alatise IO, Okello M, Blondel NO, Mulehane KO, Abubeker ZA, Nogoud AA, Nashidengo PR, Chihaka O, Tzeuton C, Dusheiko G, Sonderup M, Spearman CW. Treatment of hepatocellular carcinoma in sub-Saharan Africa: challenges and solutions. Lancet Gastroenterol Hepatol 2022; 7:1049-1060. [PMID: 35810767 DOI: 10.1016/s2468-1253(22)00042-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/30/2022] [Accepted: 02/02/2022] [Indexed: 06/15/2023]
Abstract
Most patients who develop hepatocellular carcinoma reside in resource-poor countries, a category that includes most countries in sub-Saharan Africa. Age-standardised incidence rates of hepatocellular carcinoma in western, central, eastern, and southern Africa is 6·53 per 100 000 inhabitants to 11·1 per 100 000 inhabitants. In high-income countries, around 40% of patients are diagnosed at an early stage, in which interventions with curative intent or palliative interventions are possible. By contrast, 95% of patients with hepatocellular carcinoma in sub-Saharan Africa present with advanced or terminal disease. In high-income countries, targets of 30-40% that have been set for intervention with curative intent are regularly met, with expected 5-year overall survival rates in the region of 70%. These outcomes are in sharp contrast with the very small proportion of patients in sub-Saharan Africa who are treated with curative intent. Primary prevention through the eradication and reduction of risk factors is still suboptimal because of logistical challenges. The challenges facing primary prevention, in combination with difficult-to-manage historic and emerging risk factors, such as ethanol overconsumption and metabolic dysfunction-associated liver disease, mandates secondary prevention for populations at risk through screening and surveillance. Although the increased treatment needs yielded by screening and surveillance in high-income countries are manageable by the incremental expansion of existing interventional resources, the lack of resources in sub-Saharan Africa will undermine the possible benefits of secondary prevention. An estimate of the projected effect of the introduction and expansion of screening and surveillance, resulting in stage migration and possibilities for active interventions for hepatocellular carcinoma, would facilitate optimal planning and development of resources.
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Affiliation(s)
- Eduard Jonas
- Department of Surgery, University of Cape Town, Cape Town, South Africa.
| | - Marc Bernon
- Department of Surgery, University of Cape Town, Cape Town, South Africa
| | - Barbara Robertson
- Division of Radiation Oncology, Department of Radiation Medicine, University of Cape Town, Cape Town, South Africa
| | - Chris Kassianides
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Elie Keli
- Department of General and Digestive Surgery, Hôpital Militaire d'Abidjan, Abidjan, Côte d'Ivoire
| | - Kwaku Offei Asare
- Department of Surgery, Korle Bu Teaching Hospital and the University of Ghana Medical School, Accra, Ghana
| | - Isaac Olusegun Alatise
- Department of Surgery, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospital Complex, Ile Ife, Nigeria
| | - Michael Okello
- Department of Surgery, Uganda Martyrs Hospital Lubaga, Kampala, Uganda
| | - Nana Oumarou Blondel
- Centre Hospitalier d'Essos and Department of Surgery, University of Yaoundé, Yaoundé, Cameroon
| | | | - Zeki Abdurahman Abubeker
- Department of Surgery, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Pueya Rashid Nashidengo
- Department of Surgery, Windhoek Central Hospital, University of Namibia School of Medicine, Windhoek, Namibia
| | - Onesai Chihaka
- Department of Surgery, University of Zimbabwe, Harare, Zimbabwe
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Geoffrey Dusheiko
- Institute of Liver Studies, King's College Hospital, London, UK; University College London Medical School, London, UK
| | - Mark Sonderup
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
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Wang F, Cheng M, Du B, Li LM, Huang WP, Gao JB. Use of radiomics containing an effective peritumoral area to predict early recurrence of solitary hepatocellular carcinoma ≤5 cm in diameter. Front Oncol 2022; 12:1032115. [PMID: 36387096 PMCID: PMC9650218 DOI: 10.3389/fonc.2022.1032115] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 10/07/2022] [Indexed: 01/27/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the sixth leading type of cancer worldwide. We aimed to develop a preoperative predictive model of the risk of early tumor recurrence after HCC treatment based on radiomic features of the peritumoral region and evaluate the performance of this model against postoperative pathology. Method Our model was developed using a retrospective analysis of imaging and clinicopathological data of 175 patients with an isolated HCC ≤5 cm in diameter; 117 patients were used for model training and 58 for model validation. The peritumoral area was delineated layer-by-layer for the arterial and portal vein phase on preoperative dynamic enhanced computed tomography images. The volume area of interest was expanded by 5 and 10 mm and the radiomic features of these areas extracted. Lasso was used to select the most stable features. Results The radiomic features of the 5-mm area were sufficient for prediction of early tumor recurrence, with an area under the curve (AUC) value of 0.706 for the validation set and 0.837 for the training set using combined images. The AUC of the model using clinicopathological information alone was 0.753 compared with 0.786 for the preoperative radiomics model (P >0.05). Conclusions Radiomic features of a 5-mm peritumoral region may provide a non-invasive biomarker for the preoperative prediction of the risk of early tumor recurrence for patients with a solitary HCC ≤5 cm in diameter. A fusion model that combines the radiomic features of the peritumoral region and postoperative pathology could contribute to individualized treatment of HCC.
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Affiliation(s)
- Fang Wang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ming Cheng
- Information Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Binbin Du
- Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li-ming Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wen-peng Huang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jian-bo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Jian-bo Gao,
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Chen FM, Du M, Qi X, Bian L, Wu D, Zhang SL, Wang J, Zhou Y, Zhu X. Nomogram Estimating Vessels Encapsulating Tumor Clusters in Hepatocellular Carcinoma From Preoperative Gadoxetate Disodium-Enhanced MRI. J Magn Reson Imaging 2022; 57:1893-1905. [PMID: 36259347 DOI: 10.1002/jmri.28488] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 10/04/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Vessels encapsulating tumor clusters (VETC) pattern is a novel microvascular pattern associated with poor outcomes of hepatocellular carcinoma (HCC). Preoperative estimation of VETC has potential to improve treatment decisions. PURPOSE To develop and validate a nomogram based on gadoxetate disodium-enhanced MRI for estimating VETC in HCC and to evaluate whether the estimations are associated with recurrence after hepatic resection. STUDY TYPE Retrospective. POPULATION A total of 320 patients with HCC and histopathologic VETC pattern assessment from three centers (development cohort:validation cohort = 173:147). FIELD STRENGTH/SEQUENCE A3.0 T/turbo spin-echo T2-weighted, spin-echo echo-planar diffusion-weighted, and 3D T1-weighted gradient-echo sequences. ASSESSMENT A set of previously reported VETC- and/or prognosis-correlated qualitative and quantitative imaging features were assessed. Clinical and imaging variables were compared based on histopathologic VETC status to investigate factors indicating VETC pattern. A regression-based nomogram was then constructed using the significant factors for VETC pattern. The nomogram-estimated VETC stratification was assessed for its association with recurrence. STATISTICAL TESTS Fisher exact test, t-test or Mann-Whitney test, logistic regression analyses, Harrell's concordance index (C-index), nomogram, Kaplan-Meier curves and log-rank tests. P value < 0.05 was considered statistically significant. RESULTS Pathological VETC pattern presence was identified in 156 patients (development cohort:validation cohort = 83:73). Tumor size, presence of heterogeneous enhancement with septations or with irregular ring-like structures, and necrosis were significant factors for estimating VETC pattern. The nomogram incorporating these indicators showed good discrimination with a C-index of 0.870 (development cohort) and 0.862 (validation cohort). Significant differences in recurrence rates between the nomogram-estimated high-risk VETC group and low-risk VETC group were found (2-year recurrence rates, 50.7% vs. 30.3% and 49.6% vs. 31.8% in the development and validation cohorts, respectively). DATA CONCLUSION The nomogram integrating gadoxetate disodium-enhanced MRI features was associated with VETC pattern preoperatively and with postoperative recurrence in patients with HCC. EVIDENCE LEVEL 4 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Fang-Ming Chen
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, China.,Department of Radiology, the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Mingzhan Du
- Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiumin Qi
- Department of Pathology, the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Linjie Bian
- Department of Radiology, the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Danping Wu
- Department of Radiology, the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Shuang-Lin Zhang
- Department of Radiology, the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Jitao Wang
- Department of Hepatobiliary Surgery, Xingtai Institute of Cancer Control, the Affiliated Xingtai People's Hospital of Hebei Medical University, Xingtai, China
| | - Yongping Zhou
- Department of Hepatobiliary Surgery, the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Xiaoli Zhu
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, China
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Orimo T, Kamiyama T, Kakisaka T, Nagatsu A, Asahi Y, Aiyama T, Kamachi H, Taketomi A. Hepatectomy is Beneficial in Select Patients with Multiple Hepatocellular Carcinomas. Ann Surg Oncol 2022; 29:8436-8445. [DOI: 10.1245/s10434-022-12495-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/14/2022] [Indexed: 01/27/2023]
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Contrast-enhanced magnetic resonance imaging perfusion can predict microvascular invasion in patients with hepatocellular carcinoma (between 1 and 5 cm). ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3264-3275. [PMID: 35113174 DOI: 10.1007/s00261-022-03423-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 01/18/2023]
Abstract
PURPOSE To evaluate the role of perfusion parameters with MR imaging of the liver in diagnosing MVI in hepatocellular carcinoma (HCC) (between 1 and 5 cm). MATERIALS AND METHODS This retrospective study was approved by the institutional review board. In 80 patients with 43 MVI( +) and 42 MVI( -) HCC, whole-liver perfusion MR imaging with Cartesian k-space undersampling and compressed sensing reconstruction was performed after injection of 0.1 mmol/kg gadopentetate dimeglumine. Parameters derived from a dual-input single-compartment model of arterial flow (Fa), portal venous flow (Fp), total blood flow (Ft = Fa + Fp), arterial fraction (ART), distribution volume (DV), and mean transit time (MTT) were measured. The significant parameters between the two groups were included to correlate with the presence of MVI at simple and multiple regression analysis. RESULTS In MVI-positive HCC, Fp was significantly higher than in MVI-negative HCC, whereas the reverse was seen for ART (p < 0.001). Tumor size (β = 1.2, p = 0.004; odds ratio, 3.20; 95% CI 1.45, 7.06), Fp (β = 1.1, p = 0.004; odds ratio, 3.09; 95% CI 1.42, 6.72), and ART (β = - 3.1, p = 0.001; odds ratio, 12.13; 95% CI 2.85, 51.49) were independent risk factors for MVI. The AUC value of the combination of all three metrics was 0.931 (95% CI 0.855, 0.975), with sensitivity of 97.6% and specificity of 76.2%. CONCLUSION The combination of Fp, ART, and tumor size demonstrated a higher diagnostic accuracy compared with each parameter used individually when evaluating MVI in HCC (between 1 and 5 cm).
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Sun L, Sun Z, Wang C, Cheng S, Wang K, Huang M. PCformer: an MVI recognition method via classification of the MVI boundary according to histopathological images of liver cancer. JOURNAL OF THE OPTICAL SOCIETY OF AMERICA. A, OPTICS, IMAGE SCIENCE, AND VISION 2022; 39:1673-1681. [PMID: 36215636 DOI: 10.1364/josaa.463439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/03/2022] [Indexed: 06/16/2023]
Abstract
Liver cancer is one of the most common cancers leading to death in the world. Microvascular invasion (MVI) is a principal reason for the poor long-term survival rate after liver cancer surgery. Early detection and treatment are very important for improving the survival rate. Manual examination of MVI based on histopathological images is very inefficient and time consuming. MVI automatic diagnosis based on deep learning methods can effectively deal with this problem, reduce examination time, and improve detection efficiency. In recent years, deep learning-based methods have been widely used in histopathological image analysis because of their impressive performance. However, it is very challenging to identify MVI directly using deep learning methods, especially under the interference of hepatocellular carcinoma (HCC) because there is no obvious difference in the histopathological level between HCC and MVI. To cope with this problem, we adopt a method of classifying the MVI boundary to avoid interference from HCC. Nonetheless, due to the specificity of the histopathological tissue structure with the MVI boundary, the effect of transfer learning using the existing models is not obvious. Therefore, in this paper, according to the features of the MVI boundary histopathological tissue structure, we propose a new classification model, i.e., the PCformer, which combines the convolutional neural network (CNN) method with a visual transformer and improves the recognition performance of the MVI boundary histopathological image. Experimental results show that our method has better performance than other models based on a CNN or a transformer.
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Wee IJY, Moe FNN, Sultana R, Ang RWT, Quek PPS, Goh BKP, Chan CY, Cheow PC, Chung AYF, Jeyaraj PR, Koh YX, Mack POP, Ooi LLPJ, Tan EK, Teo JY, Kam JH, Chua JSS, Ng AWY, Goh JSQ, Chow PKH. Extending Surgical Resection for Hepatocellular Carcinoma Beyond Barcelona Clinic for Liver Cancer (BCLC) Stage A: A Novel Application of the Modified BCLC Staging System. J Hepatocell Carcinoma 2022; 9:839-851. [PMID: 35999856 PMCID: PMC9393033 DOI: 10.2147/jhc.s370212] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 08/07/2022] [Indexed: 11/23/2022] Open
Abstract
Objective We aimed to prognosticate survival after surgical resection of HCC stratified by stage with amalgamation of the modified Barcelona Clinic Liver Cancer (BCLC) staging system and location of tumour. Methods This single-institutional retrospective cohort study included patients with HCC who underwent surgical resection between 1st January 2000 to 30th June 2016. Participants were divided into 6 different subgroups: A-u) Within MC with Unilobar lesions; A-b) Within MC + Bilobar lesions; B1-u) Out of MC + within Up-To-7 + Unilobar lesions; B1-b) Out of MC + within Up-to-7 + Bilobar lesions; B2-u) Out of MC + Out of Up-To-7 + Unilobar lesions; B2-b) Out of MC + Out of Up-To-7 + Bilobar lesions. A separate survival analysis was conducted for solitary HCC lesions according to three subgroups: A-S (Within MC); B1-S (Out of MC + within Up-To-7); B2-S (Out of MC + out of Up-To-7). Results A total of 794 of 1043 patients with surgical resection for HCC were analysed. Groups A-u (64.6%), A-b (58.4%) and B1-u (56.2%) had 5-year cumulative overall survival (OS) rates above 50% after surgical resection and median OS exceeding 60 months (P = 0.0001). The 5-year cumulative recurrence-free survival rates (RFS) were 40.4% (group A-u), 38.2% (group A-b), 36.3% (group B1-u), 24.6% (group B2-u), and 7.3% (group B2-b)(P=0.0001). For solitary lesions, the 5-year OS for the subgroups were A-S (65.1%), B1-S (56.0%) and B2-S (47.1%) (P = 0.0003). Compared to A-S, there was also a significant trend towards relatively poorer OS as the lesion sizes increased in B1-S (HR 1.46, 95% CI 1.03–2.08) and B2-S (HR 1.65, 95% CI 1.25–2.18). Conclusion We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection in intermediate stage HCC can be robustly prognosticated. We found that size prognosticates resection outcomes in solitary tumours.
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Affiliation(s)
- Ian J Y Wee
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Fiona N N Moe
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Rehena Sultana
- Center of Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore
| | - Reiko W T Ang
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | | | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Peter O P Mack
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - London Lucien P J Ooi
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Ek Khoon Tan
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Jacelyn S S Chua
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Ashley W Y Ng
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Jade S Q Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
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Wang K, Xiang Y, Yan J, Zhu Y, Chen H, Yu H, Cheng Y, Li X, Dong W, Ji Y, Li J, Xie D, Lau WY, Yao J, Cheng S. A deep learning model with incorporation of microvascular invasion area as a factor in predicting prognosis of hepatocellular carcinoma after R0 hepatectomy. Hepatol Int 2022; 16:1188-1198. [PMID: 36001229 DOI: 10.1007/s12072-022-10393-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 07/08/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Microvascular invasion (MVI) is a known risk factor for prognosis after R0 liver resection for hepatocellular carcinoma (HCC). The aim of this study was to develop a deep learning prognostic prediction model by incorporating a new factor of MVI area to the other independent risk factors. METHODS Consecutive patients with HCC who underwent R0 liver resection from January to December 2016 at the Eastern Hepatobiliary Surgery Hospital were included in this retrospective study. For patients with MVI detected on resected specimens, they were divided into two groups according to the size of the maximal MVI area: the small-MVI group and the large-MVI group. RESULTS Of 193 patients who had MVI in the 337 HCC patients, 130 patients formed the training cohort and 63 patients formed the validation cohort. The large-MVI group of patients had worse overall survival (OS) when compared with the small-MVI group (p = 0.009). A deep learning model was developed based on the following independent risk factors found in this study: MVI stage, maximal MVI area, presence/absence of cirrhosis, and maximal tumor diameter. The areas under the receiver operating characteristic of the deep learning model for the 1-, 3-, and 5-year predictions of OS were 80.65, 74.04, and 79.44, respectively, which outperformed the traditional COX proportional hazards model. CONCLUSION The deep learning model, by incorporating the maximal MVI area as an additional prognostic factor to the other previously known independent risk factors, predicted more accurately postoperative long-term OS for HCC patients with MVI after R0 liver resection.
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Affiliation(s)
- Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Yanjun Xiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Jiangpeng Yan
- Tencent AI Lab, Building A 12#, Shenzhenwan Science and Technology Ecological Garden, Nanshan District Shenzhen, Guangdong, China
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China
| | - Yuyao Zhu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Hanbo Chen
- Tencent AI Lab, Building A 12#, Shenzhenwan Science and Technology Ecological Garden, Nanshan District Shenzhen, Guangdong, China
| | - Hongming Yu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Yuqiang Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Xiu Li
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China
| | - Wei Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Yan Ji
- Tencent AI Lab, Building A 12#, Shenzhenwan Science and Technology Ecological Garden, Nanshan District Shenzhen, Guangdong, China
| | - Jingjing Li
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Dong Xie
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Wan Yee Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Jianhua Yao
- Tencent AI Lab, Building A 12#, Shenzhenwan Science and Technology Ecological Garden, Nanshan District Shenzhen, Guangdong, China.
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
- Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
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Feng ZH, Wang MD, Chen Z, Sun LY, Xu X, Kong QY, Chen ZX, Zeng YY, Liang YJ, Chen ZY, Wang H, Zhou YH, Chen TH, Yao LQ, Li C, Pawlik TM, Lau WY, Shen F, Yang T. Risk factors and long-term prognosis of beyond-Milan recurrence after hepatectomy for BCLC stage 0/A hepatocellular carcinoma: A large-scale multicenter study. Surgery 2022; 172:1147-1155. [PMID: 35868902 DOI: 10.1016/j.surg.2022.05.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/18/2022] [Accepted: 05/20/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Data on recurrence are important to inform surveillance and improve long-term surgical outcomes for patients with hepatocellular carcinoma. We sought to identify risk factors and long-term prognosis among patients who experienced beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. METHODS Patients who underwent hepatectomy for Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma were identified from a multi-institutional database. Predictors of beyond-Milan recurrence and risk factors associated with post-recurrence survival among patients with beyond-Milan recurrence were assessed using univariate and multivariate Cox regression analyses. RESULTS Among 753 patients (median follow-up, 51.8 months), 138 (18.3%) developed beyond-Milan recurrence. Regular surveillance (interval follow-up ≤3 months within 1 year and ≤6 months in subsequent years after surgery) was not carried out for 53 (38.4%) patients who developed beyond-Milan recurrence. On multivariate analysis, increased risk of beyond-Milan recurrence was independently associated with preoperative alpha-fetoprotein level >400 ng/mL, tumor size >5.0 cm, multifocal disease, microvascular invasion, and no/irregular recurrence surveillance. Median post-recurrence survival among patients with beyond-Milan recurrence was only 8.4 months (95% confidence interval: 7.0-9.8 months). Among patients who developed beyond-Milan recurrence, Child-Pugh grade B/C, early recurrence within 1 year after surgery, macrovascular invasion/distant metastasis, and noncurative treatment of recurrence were independent risk factors associated with worse post-recurrence survival. CONCLUSION Nearly 1 in 5 patients developed beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. Patients with beyond-Milan recurrence had a median survival of less than 1 year after diagnosis of the recurrence. Regular surveillance is an important and actionable measure to decrease beyond-Milan recurrence and, in turn, improve long-term survival among patients treated with hepatectomy for hepatocellular carcinoma.
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Affiliation(s)
- Zi-Han Feng
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, China; Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Zhong Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Li-Yang Sun
- Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, China
| | - Xiao Xu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Qing-Yu Kong
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Zi-Xiang Chen
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, China
| | - Zhi-Yu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, China; Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China.
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Bai S, Hu L, Liu J, Sun M, Sun Y, Xue F. Prognostic Nomograms Combined Adjuvant Lenvatinib for Hepatitis B Virus–related Hepatocellular Carcinoma With Microvascular Invasion After Radical Resection. Front Oncol 2022; 12:919824. [PMID: 35898866 PMCID: PMC9309730 DOI: 10.3389/fonc.2022.919824] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/08/2022] [Indexed: 11/20/2022] Open
Abstract
Background and Aim Microvascular invasion (MVI) has been established as one of the most important contributors to the prognosis of primary hepatocellular carcinoma (HCC). The objective of this study was to investigate the potential effect of postoperative adjuvant therapy with lenvatinib on the long-term prognosis after radical resection in hepatitis B virus (HBV)-related HCC patients with MVI, as well as to predict the long-term survival based on nomograms. Methods Data from 293 HBV-related hepatocellular carcinoma patients with histologically confirmed MVI who underwent R0 resection at Eastern Hepatobiliary Surgery Hospital (EHBH) was retrospectively analyzed. 57 patients received postoperative adjuvant therapy with lenvatinib, while 236 patients did not. The survival outcome of patients who received postoperative adjuvant lenvatinib versus those who did not was analyzed. Results The 1-year, 2-year recurrence rates and survival rates of the lenvatinib group were improved compared to the non-lenvatinib group (15.9%, 43.2% vs 40.1%, 57.2%, P=0.002; 85.8%, 71.2% vs 69.6%, 53.3%, P=0.009, respectively). Similar findings were also observed after Propensity Score Matching (PSM) compared to non-PSM analyses The 1-year, 2-year recurrence rates and survival rates were more favorable for the lenvatinib group compared to the non-lenvatinib group (15.9%, 43.2% vs 42.1%, 57.4%, P=0.028; 85.8%, 71.2% vs 70.0%, 53.4%, P=0.024, respectively). As shown by univariate and multivariate analyses, absence of adjuvant lenvatinib treatment was identified as an independent risk factor for recurrence and survival. The established nomograms displayed good performance for the prediction of recurrence and survival, with a C-index of 0.658 and 0.682 respectively. Conclusions Postoperative adjuvant therapy with lenvatinib was associated with improved long-term prognosis after R0 Resection in HBV-related HCC patients with MVI, which could be accurately predicted from nomograms.
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Affiliation(s)
- Shilei Bai
- Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Lei Hu
- Department of Hepatic Surgery I, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Jianwei Liu
- Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Minmin Sun
- Department of Hepatic Surgery I, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Yanfu Sun
- Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- *Correspondence: Mr. Feng Xue, ; Mr. Yanfu Sun,
| | - Feng Xue
- Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
- *Correspondence: Mr. Feng Xue, ; Mr. Yanfu Sun,
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Radiomics Analysis on Noncontrast CT for Distinguishing Hepatic Hemangioma (HH) and Hepatocellular Carcinoma (HCC). CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:7693631. [PMID: 35833080 PMCID: PMC9252683 DOI: 10.1155/2022/7693631] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/16/2022] [Accepted: 05/31/2022] [Indexed: 11/24/2022]
Abstract
Background To form a radiomic model on the basis of noncontrast computed tomography (CT) to distinguish hepatic hemangioma (HH) and hepatocellular carcinoma (HCC). Methods In this retrospective study, a total of 110 patients were reviewed, including 72 HCC and 38 HH. We accomplished feature selection with the least absolute shrinkage and operator (LASSO) and built a radiomics signature. Another improved model (radiomics index) was established using forward conditional multivariate logistic regression. Both models were tested in an internal validation group (38 HCC and 21 HH). Results The radiomic signature we built including 5 radiomic features demonstrated significant differences between the hepatic HH and HCC groups (P < 0.05). The improved model demonstrated a higher net benefit based on only 2 radiomic features. In the validation group, radiomics signature and radiomics index achieved great diagnostic performance with AUC values of 0.716 (95% confidence interval (CI): 0.581, 0.850) and 0.870 (95% CI: 0.782, 0.957), respectively. Conclusions Our developed radiomics-based model can successfully distinguish HH and HCC patients, which can help clinical decision-making with lower cost.
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Zane KE, Nagib PB, Jalil S, Mumtaz K, Makary MS. Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma. World J Hepatol 2022; 14:885-895. [PMID: 35721283 PMCID: PMC9157708 DOI: 10.4254/wjh.v14.i5.885] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 02/20/2022] [Accepted: 04/26/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common cause of liver malignancy and the fourth leading cause of cancer deaths universally. Cure can be achieved for early stage HCC, which is defined as 3 or fewer lesions less than or equal to 3 cm in the setting of Child-Pugh A or B and an ECOG of 0. Patients outside of these criteria who can be down-staged with loco-regional therapies to resection or liver transplantation (LT) also achieve curative outcomes. Traditionally, surgical resection, LT, and ablation are considered curative therapies for early HCC. However, results from recently conducted LEGACY study and DOSISPHERE trial demonstrate that transarterial radio-embolization has curative outcomes for early HCC, leading to its recent incorporation into the Barcelona clinic liver criteria guidelines for early HCC. This review is based on current evidence for curative-intent loco-regional therapies including radioembolization for early-stage HCC.
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Affiliation(s)
- Kylie E Zane
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Paul B Nagib
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Sajid Jalil
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Khalid Mumtaz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Mina S Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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Yang Y, Zhou Y, Zhou C, Ma X. Deep learning radiomics based on contrast enhanced computed tomography predicts microvascular invasion and survival outcome in early stage hepatocellular carcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1068-1077. [PMID: 34862094 DOI: 10.1016/j.ejso.2021.11.120] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/25/2021] [Accepted: 11/17/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To evaluate the performance of a deep learning (DL)-based radiomics strategy on contrast-enhanced computed tomography (CT) to predict microvascular invasion (MVI) status and clinical outcomes, recurrence-free survival (RFS) and overall survival (OS) in patients with early stage hepatocellular carcinoma (HCC) receiving surgical resection. METHODS All 283 eligible patients were included retrospectively between January 2008 and December 2015, and assigned into the training cohort (n = 198) and the testing cohort (n = 85). We extracted radiomics features via handcrafted radiomics analysis manually and DL analysis of pretrained convolutional neural networks via transfer learning automatically. Support vector machine was adopted as the classifier. A clinical-radiological model for MVI status integrated significant clinical features and the radiological signature generated from the radiological model with the optimal area under the receiver operating characteristics curve (AUC) in the testing cohort. Otherwise, DL-based prognostic models were constructed in prediction of recurrence and mortality via Cox proportional hazard analysis. RESULTS The clinical-radiological model for MVI represented an AUC of 0.909, accuracy of 96.47%, sensitivity of 90.91%, specificity of 97.30%, positive predictive value of 83.33%, and negative predictive value of 98.63% in the testing cohort. The clinical-radiological models for identification of RFS and OS outperformed prediction performance of the clinical model or the DL signature alone. The DL-based integrated model for prognostication showed great predictive value with significant classification and discrimination abilities after validation. CONCLUSIONS The integrated DL-based radiomics models achieved accurate preoperative prediction of MVI status, and might facilitate predicting tumor recurrence and mortality in order to optimize clinical decisions for patients with early stage HCC.
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Affiliation(s)
- Yuhan Yang
- West China School of Medicine, Sichuan University, No.17 People's South Road, Chengdu, 610041, Sichuan, China.
| | - Yin Zhou
- West China Hospital, Sichuan University, Guoxue Road 37, Chengdu, 610041, China.
| | - Chen Zhou
- West China School of Medicine, Sichuan University, No.17 People's South Road, Chengdu, 610041, Sichuan, China.
| | - Xuelei Ma
- Department of Biotherapy and Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Guoxue Road 37, Chengdu, 610041, China.
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Mahmoud K, Swidan S, El-Nabarawi M, Teaima M. Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances. J Nanobiotechnology 2022; 20:109. [PMID: 35248080 PMCID: PMC8898455 DOI: 10.1186/s12951-022-01309-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 02/12/2022] [Indexed: 12/12/2022] Open
Abstract
Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles-specifically lipid based nanoparticles-are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive nanoparticles. In this review, the effect of utilizing lipidic nanoparticles is being discussed as well as the different tumor uptake enhancement techniques used.
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Affiliation(s)
- Khaled Mahmoud
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt
- The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt
| | - Shady Swidan
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt.
- The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt.
| | - Mohamed El-Nabarawi
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Mahmoud Teaima
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
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Papaconstantinou D, Hewitt DB, Brown ZJ, Schizas D, Tsilimigras DI, Pawlik TM. Patient stratification in hepatocellular carcinoma: impact on choice of therapy. Expert Rev Anticancer Ther 2022; 22:297-306. [PMID: 35157530 DOI: 10.1080/14737140.2022.2041415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION HCC comprises around 60 to 80% of all primary liver cancers and exhibits wide geographical variability. Appropriate treatment allocation needs to include both patient and tumor characteristics. AREAS COVERED Current HCC classification systems to guide therapy are either liver function-centric and evaluate physiologic liver function to guide therapy or prognostic stratification classification systems broadly based on tumor morphologic parameters, patient performance status, and liver reserve assessment. This review focuses on different classification systems for HCC, their strengths, and weaknesses as well as the use of artificial intelligence in improving prognostication in HCC. EXPERT OPINION Future HCC classification systems will need to incorporate clinic-pathologic data from a multitude of sources and emerging therapies to develop patient-specific treatment plans targeting a patient's unique tumor profile.
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Affiliation(s)
- Dimitrios Papaconstantinou
- Third Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - D Brock Hewitt
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Zachary J Brown
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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Liu L, Xie S, Teng YX, Deng ZJ, Chen K, Liu HT, Huo RR, Liang XM, Guo PP, Yang DL, Ma L, Xiang BD, Li LQ, Zhong JH. Outcomes of Liver Resection for Metabolic Dysfunction-Associated Fatty Liver Disease or Chronic Hepatitis B-Related HCC. Front Oncol 2022; 11:783339. [PMID: 35127490 PMCID: PMC8810487 DOI: 10.3389/fonc.2021.783339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 12/29/2021] [Indexed: 01/27/2023] Open
Abstract
AimsThis study aims to determine differences in severity of background liver disease at hepatocellular carcinoma (HCC) diagnosis and long-term survival outcomes among patients undergoing liver resection for HCC in the background of metabolic dysfunction-associated fatty liver disease (MAFLD) compared to chronic hepatitis B (CHB) alone or concurrent CHB (CHB/MAFLD).MethodsPatient demographics and comorbidities, clinicopathologic data, perioperative and long-term outcomes among patients who underwent liver resection for HCC were reviewed. Overall and recurrence-free survival were calculated with the Kaplan-Meier method, with the values compared using the log-rank test.ResultsFrom January 2014 to December 2018, 1325 patients underwent potential curative liver resection of HCC; 67 (5.0%), 176 (13.3%), and 1082 (81.7%) patients had MAFLD alone, CHB concurrent with MAFLD, and CHB alone, respectively. At HCC diagnosis, fewer MAFLD patients had cirrhosis, alpha fetoprotein concentration ≥ 400 ng/mL, tumor size ≥ 5 cm, mulinodular, microvascular invasion, receiving major hepatectomy, and receiving adjuvant transarterial chemoembolization. After a median follow-up of 47 months after liver resection, MAFLD (or MAFLD plus CHB/MAFLD) patients had significantly higher overall and recurrence-free survival than CHB patients before or after propensity score analysis (all P<0.05).ConclusionPatients with HCC in the setting of MAFLD have less-severe background liver disease at HCC diagnosis and better long-term survival after curative liver resection compared to counterparts with CHB/MAFLD or CHB.
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Affiliation(s)
- Lei Liu
- Hepatobiliary Surgery Department, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Workers Hospital, Liuzhou, China
| | - Si Xie
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yu-Xian Teng
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhu-Jian Deng
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Kang Chen
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Hao-Tian Liu
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Rong-Rui Huo
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiu-Mei Liang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Ping-Ping Guo
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Da-Long Yang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Bang-De Xiang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Le-Qun Li
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China
- *Correspondence: Jian-Hong Zhong,
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Xiang YJ, Wang K, Zheng YT, Yu HM, Cheng YQ, Wang WJ, Shan YF, Cheng SQ. Prognostic Value of Microvascular Invasion in Eight Existing Staging Systems for Hepatocellular Carcinoma: A Bi-Centeric Retrospective Cohort Study. Front Oncol 2022; 11:726569. [PMID: 34976789 PMCID: PMC8716381 DOI: 10.3389/fonc.2021.726569] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
Background Microvascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). However, whether the existing staging systems of hepatocellular carcinoma can distinguish the prognosis of patients with MVI and the prognostic value of MVI in different subtypes of hepatocellular carcinoma remains to be clarified. Methods A dual-center retrospective data set of 1,198 HCC patients who underwent R0 LR was included in the study between 2014 and 2016. Baseline characteristics and staging information were collected. Homogeneity and modified Akaike information criterion (AICc) were compared between each system. And the prognostic significance of MVI for overall survival (OS) was studied in each subgroup. Results In the entire cohort, there were no significant survival differences between Cancer of the Liver Italian Program (CLIP) score 2 and 3 (p = 0.441), and between Taipei Integrated Scoring System (TIS) score 3 and 4 (p = 0.135). In the MVI cohort, there were no significant survival differences between Barcelona Clinic Liver Cancer stages B and C (p=0.161), CLIP scores 2 and 3 (p = 0.083), TIS scores 0 and 1 (p = 0.227), TIS scores 2 and 3 (p =0.794), Tokyo scores 3 and 4 (p=0.353), and American Joint Committee on Cancer Tumor-Node-Metastasis 7th stage I and II (p=0.151). Among the eight commonly used HCC staging systems, the Hong Kong Liver Cancer (HKLC) staging system showed the highest homogeneity and the lowest AICc value in both the entire cohort and MVI cohort. In each subgroup of the staging systems, MVI generally exhibited poor survival outcomes. Conclusions The HKLC staging system was the most accurate model for discriminating the prognosis of MVI patients, among the eight staging systems. Meanwhile, our findings suggest that MVI may be needed to be incorporated into the current HCC staging systems as one of the grading criteria.
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Affiliation(s)
- Yan-Jun Xiang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.,Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yi-Tao Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Hong-Ming Yu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Qiang Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Jun Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yun-Feng Shan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Shu-Qun Cheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.,Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Wei S, Yang M, Geng X, Xiong Q, Hou H, Zhou D, Cui X. Prognostic factors in hepatocellular carcinoma patients with Child-Pugh A liver function after hepatectomy: Not related to the surgical approach. Ann Hepatol 2022; 27 Suppl 1:100580. [PMID: 34788657 DOI: 10.1016/j.aohep.2021.100580] [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: 03/20/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Improving the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is critical. This article aims to investigate the risk factors affecting the prognosis of HCC patients with Child-Pugh A (CPA) liver function after hepatectomy and to compare the prognosis of patients with anatomical resection (AR) and nonanatomical resection (NAR). METHODS In total, 186 patients diagnosed with HCC between 2013 and 2019 were retrospectively enrolled. Univariate and multivariate analyses were performed using a Cox proportional hazard regression model to explore the factors related to prognosis. Overall survival (OS) and progression-free survival (PFS) were analyzed by log-rank tests and are shown by Kaplan-Meier curves. Chi-square tests and Mann-Whitney U tests were used to compare the difference in clinical characteristics between AR and NAR patients. RESULTS Among the 186 enrolled patients, only 73 were followed over 60 months. The 1-, 3-, and 5-year survival rates were 74.5%, 46.7% and 26.0%, respectively. Multivariate analyses demonstrated that portal vein invasion (PVI) and tumor size were independent risk factors for OS and PFS. Preoperative hepatitis B surface antigen (HBsAg) and a-fetoprotein (AFP) levels were identified as independent risk factors only for PFS. In univariate analysis, the NAR group had a better OS rate than the AR group (1-year: 80.4% vs. 63.6%, 3-year: 55.9% vs. 30.3%, 5-year: 34.8% vs. 11.1%), but this was not confirmed by multivariate analysis. CONCLUSIONS PVI and tumor size > 5 cm are risk factors for the prognosis of CPA HCC patients after hepatectomy, but the surgical type is not.
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Affiliation(s)
- Sheng Wei
- Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China
| | - Minghao Yang
- Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China
| | - Xiaoping Geng
- Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China
| | - Qiru Xiong
- Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China
| | - Hui Hou
- Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China
| | - Dachen Zhou
- Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China.
| | - Xiao Cui
- Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China.
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Zheng Z, Guan R, Jianxi W, Zhao Z, Peng T, Liu C, Lin Y, Jian Z. Microvascular Invasion in Hepatocellular Carcinoma: A Review of Its Definition, Clinical Significance, and Comprehensive Management. JOURNAL OF ONCOLOGY 2022; 2022:9567041. [PMID: 35401743 PMCID: PMC8986383 DOI: 10.1155/2022/9567041] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 02/28/2022] [Accepted: 03/14/2022] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of malignancies in the world, and most HCC patients undergoing liver resection relapse within five years. Microvascular invasion (MVI) is an independent factor for both the disease-free survival and overall survival of HCC patients. At present, the definition of MVI is still controversial, and a global consensus on how to evaluate MVI precisely is needed. Moreover, this review summarizes the current knowledge and clinical significance of MVI for HCC patients. In terms of management, antiviral therapy, wide surgical margins, and postoperative transcatheter arterial chemoembolization (TACE) could effectively reduce the incidence of MVI or improve the disease-free survival and overall survival of HCC patients with MVI. However, other perioperative management practices, such as anatomical resection, radiotherapy, targeted therapy and immune therapy, should be clarified in future investigations.
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Affiliation(s)
- Zehao Zheng
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Renguo Guan
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Wang Jianxi
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zhen Zhao
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of General Surgery, School of Medicine, Southern China University of Technology, Guangzhou, China
| | - Tianyi Peng
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Chunsheng Liu
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ye Lin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Abstract
We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.
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Affiliation(s)
- E Rio
- Service de radiothérapie, institut de cancérologie de l'Ouest, boulevard Jacques-Monod, 44805 Saint-Herblain, France.
| | - F Mornex
- Département de radiothérapie-oncologie, centre hospitalier Lyon Sud, 165, chemin du Grand-Revoyet, 69310 Pierre-Bénite, France; EMR 3738, université Claude-Bernard Lyon 1, 165, chemin du Grand-Revoyet, 69310 Pierre-Bénite, France
| | - P Maingon
- Service d'oncologie radiothérapie, groupe hospitalier La Pitié Salpêtrière, Sorbonne université, AP-HP, 47/83, boulevard de l'Hôpital, 75013 Paris, France
| | - D Peiffert
- Service de radiothérapie, institut de cancérologie de Lorraine Alexis-Vautrin, 6, avenue de Bourgogne, 54511 Vandœuvre-lès-Nancy, France
| | - L Parent
- Département d'ingénierie et de physique médicale, institut Claudius-Regaud (ICR), institut universitaire du cancer de Toulouse-Oncopole (IUCT-O), 1, avenue Irène-Joliot-Curie, 31059 Toulouse cedex 9, France
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Xin Y, Zhang X, Yang Y, Chen Y, Wang Y, Zhou X, Li X. Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study. J Gastrointest Oncol 2021; 12:2930-2942. [PMID: 35070419 PMCID: PMC8748026 DOI: 10.21037/jgo-21-506] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/03/2021] [Indexed: 09/07/2023] Open
Abstract
BACKGROUND Long-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS). METHODS A retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort. RESULTS Patients with aMAP scores ≤63.8, 63.8-67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700-0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697-10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097-6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772-0.870)]. CONCLUSIONS This study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.
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Affiliation(s)
- Yujing Xin
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyuan Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Chen
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Yanan Wang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Wang G, Jian W, Cen X, Zhang L, Guo H, Liu Z, Liang C, Zhou W. Prediction of Microvascular Invasion of Hepatocellular Carcinoma Based on Preoperative Diffusion-Weighted MR Using Deep Learning. Acad Radiol 2021; 28 Suppl 1:S118-S127. [PMID: 33303346 DOI: 10.1016/j.acra.2020.11.014] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/03/2020] [Accepted: 11/05/2020] [Indexed: 02/06/2023]
Abstract
RATIONALE AND OBJECTIVES To investigate the value of diffusion-weighted magnetic resonance imaging for the prediction of microvascular invasion (MVI) of Hepatocellular Carcinoma (HCC) using Convolutional Neural Networks (CNN). MATERIAL AND METHODS This study was approved by the local institutional review board and the patients' informed consent was waived. Consecutive 97 subjects with 100 HCCs from July 2012 to October 2018 with surgical resection were retrieved. All subjects with diffusion-weighted imaging (DWI) examinations were performed with single-shot echo-planar imaging in a breath-hold routine. DWI parameters were three b values of 0,100,600 sec/mm2. First, apparent diffusion coefficients (ADC) images were computed by mono-exponentially fitting the three b-value points. Then, multiple 2D axial patches (28 × 28) of HCCs from b0, b100, b600, and ADC images were extracted to increase the dataset for training the CNN model. Finally, the fusion of deep features derived from three b value images and ADC was conducted based on the CNN model for MVI prediction. The data set was split into the training set (60 HCCs) and the independent test set (40 HCCs). The output probability of the deep learning model in the MVI prediction of HCCs was assessed by the independent student's t-test for data following a normal distribution and Mann-Whitney U test for data violating the normal distribution. Receiver operating characteristic curve and area under the curve (AUC) were also used to assess the performance for MVI prediction of HCCs in the fixed test set. RESULTS Deep features in b600 images yielded better performance (AUC = 0.74, p = 0.004) for MVI prediction than b0 (AUC = 0.69, p = 0.023) and b100 (AUC = 0.734, p = 0.011). Comparatively, deep features in the ADC map obtained lower performance (AUC = 0.71, p = 0.012) than that of the higher b value images (b600) for MVI prediction. Furthermore, the fusion of deep features from the b0, b100, b600, and ADC images yielded the best results (AUC = 0.79, p = 0.002) for MVI prediction. CONCLUSION Fusion of deep features derived from DWI images concerning the three b-value images and the ADC image yields better performance for MVI prediction.
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