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Yan H, Li Z, Li N, Yan H, Guo X, Wu M, Kong F, Dong J, Deng M, Xu X. Late course adaptive radiotherapy based on tumor volume reduction decreases Gastrointestinal toxicity for abdominal lymph node metastasis of hepatocellular carcinoma. Sci Rep 2025; 15:17477. [PMID: 40394171 PMCID: PMC12092827 DOI: 10.1038/s41598-025-02363-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 05/13/2025] [Indexed: 05/22/2025] Open
Abstract
This study aimed to quantify tumor volume reduction during radiotherapy for abdominal lymph node metastases (LNM) of hepatocellular carcinoma (HCC) and assess the potential benefits of late-course adaptive radiotherapy. Forty HCC Patients with abdominal LNM treated from January 2021 to March 2024 received radiotherapy in combination with targeted therapy or immunotherapy. Second simulation scan was performed during the fourth week of radiotherapy. Two-thirds of patients underwent redesigned radiotherapy plan as the test group, while remaining patients continued with the original plan as the control group. Dose-volume metrics for organs at risk and toxicities were compared. At the time of second scan, median radiotherapy dose administered to all patients was 38.0 Gy. Mean tumor volume reduction was 56.20cc (95% CI 35.20-77.21cc) and 29.65% (95% CI 24.49%-34.80%). Irradiation dose and volume to stomach, small intestine, colon, liver, and kidneys were significantly reduced in test group. Meanwhile, gastrointestinal toxicities were notablely decreased, including dyspepsia (P = 0.018), nausea (P = 0.013), vomiting (P = 0.041), and diarrhea (P = 0.040). Tumor regression during radiotherapy for abdominal LNM of HCC is significant. A second simulation scan performing when the irradiation dose reaches approximately 40 Gy and applying adaptive radiotherapy in the late course can enhance irradiation accuracy and reduce toxicities.
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Affiliation(s)
- Huamei Yan
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Zhenghuan Li
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Nuoya Li
- Department of Hepatobiliary surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Huaying Yan
- Xinyu people's hospital, Xinyu, 338099, China
| | - Xianyu Guo
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Manya Wu
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Fantu Kong
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Jie Dong
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Meihai Deng
- Department of Hepatobiliary surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
| | - Xiangying Xu
- Department of Radiation Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
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Habu K, Akamoto S, Imura S, Fujiwara Y, Konishi Y, Fukuhara T, Nakagawa K, Okano K. Laparoscopic Distal Pancreatectomy for Lymph Node Metastasis around Splenic Artery from Hepatocellular Carcinoma in a Patient with Portal Annular Pancreas. Surg Case Rep 2025; 11:24-0130. [PMID: 40265139 PMCID: PMC12012305 DOI: 10.70352/scrj.cr.24-0130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 03/27/2025] [Indexed: 04/24/2025] Open
Abstract
INTRODUCTION Lymph node metastases after hepatocellular carcinoma (HCC) resection exist, although they are not common. However, solitary metastasis to the splenic artery lymph node with suspected pancreatic invasion after HCC resection is rare. In certain cases, surgical resection is performed to improve patient outcomes. We report a case of lymph node metastasis resected by laparoscopic distal pancreatectomy (LDP) in a patient with a unique anatomical anomaly known as portal annular pancreas (PAP). CASE PRESENTATION A 79-year-old Japanese man underwent laparoscopic left lateral segmentectomy for HCC. Two months after the surgery, alpha-fetoprotein levels remained elevated. Plain computed tomography revealed a swollen lymph node along the splenic artery involving the pancreas and the PAP. We suspected a solitary metastasis to the lymph node around splenic artery with pancreatic invasion. LDP was performed for complete resection of lymph node metastasis. Although the patient developed a grade B postoperative pancreatic fistula, he was discharged on postoperative day 33 under conservative treatment of antibiotics. He has remained recurrence-free for 4 years and 3 months after surgery. CONCLUSIONS LDP was successfully performed for lymph node metastasis around the splenic artery in an HCC patient and resulted in long-term survival. Surgeons should be aware of the unique anatomical characteristics of PAP during LDP.
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Affiliation(s)
- Kyosuke Habu
- Department of Surgery, Sumitomo Besshi Hospital, Niihama, Ehime, Japan
| | - Shintaro Akamoto
- Department of Surgery, Sumitomo Besshi Hospital, Niihama, Ehime, Japan
| | - Shin Imura
- Department of Surgery, Sumitomo Besshi Hospital, Niihama, Ehime, Japan
| | - Yuta Fujiwara
- Department of Surgery, Sumitomo Besshi Hospital, Niihama, Ehime, Japan
| | - Yusuke Konishi
- Department of Surgery, Sumitomo Besshi Hospital, Niihama, Ehime, Japan
| | - Tetsuji Fukuhara
- Department of Surgery, Sumitomo Besshi Hospital, Niihama, Ehime, Japan
| | - Kazuhiko Nakagawa
- Department of Surgery, Sumitomo Besshi Hospital, Niihama, Ehime, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan
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Ma J, Zhang H, Zheng R, Wang S, Ding L. Radiotherapy with targeted and immunotherapy improved overall survival and progression-free survival for hepatocellular carcinoma with portal vein tumor thrombosis. Oncologist 2025; 30:oyae209. [PMID: 39231443 PMCID: PMC11883153 DOI: 10.1093/oncolo/oyae209] [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: 06/04/2024] [Accepted: 07/16/2024] [Indexed: 09/06/2024] Open
Abstract
BACKGROUND The efficacy of radiotherapy (RT) combined with targeted therapy and immunotherapy in treating hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is still unclear. This study investigated the efficacy and safety of RT combined with targeted therapy and immunotherapy in HCC with PVTT. MATERIALS AND METHODS Seventy-two patients with HCC with PVTT treated with tyrosine kinase inhibitor (TKI) plus programmed cell death protein-1 (PD-1) inhibitor with or without RT from December 2019 to December 2023 were included. After propensity score matching (PSM) for adjusting baseline differences, 32 pairs were identified in RT + TKI + PD-1 group (n = 32) and TKI + PD-1 group (n = 32). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS Median OS (mOS) in RT + TKI + PD-1 group was significantly longer than TKI + PD-1 group (15.6 vs. 8.2 months, P = .008). Median PFS (mPFS) in RT + TKI + PD-1 group was dramatically longer than TKI + PD-1 group (8.1 vs. 5.2 months, P = .011). Patients in TKI + PD-1 + RT group showed favorable ORR and DCR compared with TKI + PD-1 group (78.1% vs. 56.3%, P = .055; 93.8% vs. 81.3%, P = .128). Subgroup analysis demonstrated a remarkable OS and PFS benefit with TKI + PD-1 + RT for patients with main PVTT (type III/IV) and those of Child-Pugh class A. Multivariate analysis confirmed RT + TKI + PD-1 as an independent prognostic factor for longer OS (HR 0.391, P = .024) and longer PFS (HR 0.487, P = .013), with no mortality or severe TRAEs. CONCLUSION RT combined with TKI and PD-1 inhibitor could significantly improve mOS and mPFS without inducing severe TRAEs or mortality.
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Affiliation(s)
- Jianing Ma
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Haifeng Zhang
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Ruipeng Zheng
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Shudong Wang
- Department of Cardiology, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Lijuan Ding
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
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Chlorogiannis DD, Charalampopoulos G, Kontopyrgou D, Gkayfillia A, Nikolakea M, Iezzi R, Filippiadis D. Emerging Indications for Interventional Oncology: A Comprehensive Systematic Review of Image-Guided Thermal Ablation for Metastatic Non-cervical Lymph Node Disease. Curr Oncol Rep 2024; 26:1543-1552. [PMID: 39466479 DOI: 10.1007/s11912-024-01616-4] [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] [Accepted: 10/14/2024] [Indexed: 10/30/2024]
Abstract
INTRODUCTION Lymphatic node metastatic disease encompasses a distinct oncological entity which has been associated with poor prognosis. Image-guided thermal ablation has recently been proposed as a safe and alternative treatment for these lesions. The aim of this systematic review is to evaluate the pooled safety and efficacy of thermal ablation techniques for the treatment of oligometastatic non-cervical lymph nodal disease. RECENT FINDINGS A systematic search of the three major databases (MEDLINE, EMBASE, and CENTRAL) from inception to 30 December 2023 was conducted according to the PRISMA Guidelines. Observational studies reporting technical success, complications and oncologic outcomes were included. Meta- analysis was performed by estimating the pooled incidence rates and risk ratios by fitting random-effect models. Overall, 8 studies were included, comprising of 225 patients and 305 ablated LNMs and a median follow-up of 12 months. The combined data analysis showed that technical success after thermal ablation was 98% (CI: 95%-99%), major complication rate was 1% (CI: 95%-99%), pooled overall response rate was 72% (CI: 54%-87%), local tumor progression rate was 18% (CI: 8%-33%) and disease-free survival rate was 68% (CI: 51%-81%). No difference between radiofrequency ablation and cryoablation was found for every outcome during subgroup analysis. Image-guided percutaneous thermal ablation (with either radiofrequency ablation or cryoablation) is safe and effective for the treatment of oligometastatic LMN disease, however further studies to confirm these findings are still needed.
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Affiliation(s)
- David-Dimitris Chlorogiannis
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 St Francis Str, Boston, MA, 02215, USA
| | - Georgios Charalampopoulos
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, Rimini 1124 62, Athens, Greece
| | - Dimitra Kontopyrgou
- Department If Hygiene, Social-Preventive Medicine and Statistics, Medical School, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece
| | | | - Melina Nikolakea
- Department of Internal Medicine, Hippokrateion General Hospital, 115 27, Athens, Greece
| | - Roberto Iezzi
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Lazio, Italy
- Facoltà Di Medicina E Chirurgia, Università Cattolica del Sacro Cuore, Roma, Lazio, Italy
| | - Dimitrios Filippiadis
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, Rimini 1124 62, Athens, Greece.
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Sun J, Huang L, Liu Y. Leveraging SEER data through machine learning to predict distant lymph node metastasis and prognosticate outcomes in hepatocellular carcinoma patients. J Gene Med 2024; 26:e3732. [PMID: 39188041 DOI: 10.1002/jgm.3732] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 07/09/2024] [Accepted: 08/10/2024] [Indexed: 08/28/2024] Open
Abstract
OBJECTIVES This study aims to develop and validate machine learning-based diagnostic and prognostic models to predict the risk of distant lymph node metastases (DLNM) in patients with hepatocellular carcinoma (HCC) and to evaluate the prognosis for this cohort. DESIGN Utilizing a retrospective design, this investigation leverages data extracted from the Surveillance, Epidemiology, and End Results (SEER) database, specifically the January 2024 subset, to conduct the analysis. PARTICIPANTS The study cohort consists of 15,775 patients diagnosed with HCC as identified within the SEER database, spanning 2016 to 2020. METHOD In the construction of the diagnostic model, recursive feature elimination (RFE) is employed for variable selection, incorporating five critical predictors: age, tumor size, radiation therapy, T-stage, and serum alpha-fetoprotein (AFP) levels. These variables are the foundation for a stacking ensemble model, which is further elucidated through Shapley Additive Explanations (SHAP). Conversely, the prognostic model is crafted utilizing stepwise backward regression to select pertinent variables, including chemotherapy, radiation therapy, tumor size, and age. This model culminates in the development of a prognostic nomogram, underpinned by the Cox proportional hazards model. MAIN OUTCOME MEASURES The outcome of the diagnostic model is the occurrence of DLNM in patients. The outcome of the prognosis model is determined by survival time and survival status. RESULTS The integrated model developed based on stacking demonstrates good predictive performance and high interpretative variability and differentiation. The area under the curve (AUC) in the training set is 0.767, while the AUC in the validation set is 0.768. The nomogram, constructed using the Cox model, also demonstrates consistent and strong predictive capabilities. At the same time, we recognized elements that have a substantial impact on DLNM and the prognosis and extensively discussed their significance in the model and clinical practice. CONCLUSION Our study identified key predictive factors for DLNM and elucidated significant prognostic indicators for HCC patients with DLNM. These findings provide clinicians with valuable tools to accurately identify high-risk individuals for DLNM and conduct more precise risk stratification for this patient subgroup, potentially improving management strategies and patient outcomes.
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Affiliation(s)
- Jiaxuan Sun
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, China
| | - Lei Huang
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, China
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Liu X, Xia F, Chen Y, Sun H, Yang Z, Chen B, Zhao M, Bi X, Peng T, Ainiwaer A, Luo Z, Wang F, Lu Y, National Clinical Research Center for Infectious Diseases, Society of Hepatology, Beijing Medical Association, Translational Medicine Branch, China Association of Gerontology and Geriatrics. Chinese expert consensus on refined diagnosis, treatment, and management of advanced primary liver cancer (2023 edition). LIVER RESEARCH (BEIJING, CHINA) 2024; 8:61-71. [PMID: 39959878 PMCID: PMC11771258 DOI: 10.1016/j.livres.2024.05.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/10/2024] [Accepted: 05/13/2024] [Indexed: 11/25/2024]
Abstract
Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a major cause of malignant tumors and cancer-related deaths in China, accounting for approximately 85% of all cancer cases in the country. Several guidelines have been used to diagnose and treat liver cancer. However, these guidelines provide a broad definition for classifying advanced liver cancer, with an emphasis on a singular approach, without considering treatment options for individual patients. Therefore, it is necessary to establish a comprehensive and practical expert consensus, specifically for China, to enhance the diagnosis and treatment of HCC using the Delphi method. The classification criteria were refined for Chinese patients with HCC, and the corresponding optimal treatment regimen recommendations were developed. These recommendations took into account various factors, including tumor characteristics, vascular tumor thrombus grade, distant metastasis, liver function status, portal hypertension, and the hepatitis B virus replication status of patients with primary HCC, along with treatment prognosis. The findings and recommendations provide detailed, scientific, and reasonable individualized diagnosis and treatment strategies for clinicians.
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Affiliation(s)
- Xiufeng Liu
- Department of Medical Oncology, Bayi Hospital Affiliated to Nanjing Chinese Medical University, Nanjing, Jiangsu, China
| | - Feng Xia
- Department of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Yue Chen
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Huichuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhengqiang 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
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Zhao
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Xinyu Bi
- 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
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Aizier Ainiwaer
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Zhiwen Luo
- 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
| | - Fusheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - National Clinical Research Center for Infectious Diseases
- Department of Medical Oncology, Bayi Hospital Affiliated to Nanjing Chinese Medical University, Nanjing, Jiangsu, China
- Department of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- 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 Radiation Oncology, 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 Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- 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
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Society of Hepatology, Beijing Medical Association
- Department of Medical Oncology, Bayi Hospital Affiliated to Nanjing Chinese Medical University, Nanjing, Jiangsu, China
- Department of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- 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 Radiation Oncology, 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 Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- 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
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Translational Medicine Branch
- Department of Medical Oncology, Bayi Hospital Affiliated to Nanjing Chinese Medical University, Nanjing, Jiangsu, China
- Department of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- 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 Radiation Oncology, 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 Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- 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
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - China Association of Gerontology and Geriatrics
- Department of Medical Oncology, Bayi Hospital Affiliated to Nanjing Chinese Medical University, Nanjing, Jiangsu, China
- Department of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- 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 Radiation Oncology, 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 Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- 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
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China
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Xiang C, Xiao Y, Ma Z, Peng Y, Li X, Mao X, Li L. Liver resection for large and huge hepatocellular carcinoma: Predictors of failure, recurrence patterns, and prognoses. Asia Pac J Clin Oncol 2023; 19:e60-e70. [PMID: 35404506 DOI: 10.1111/ajco.13777] [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: 10/26/2021] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Characteristic symptoms and signs are often absent in patients with hepatocellular carcinoma (HCC). As a result, many patients are not diagnosed until their tumors have grown to large (> 5cm) or huge sizes (> 10cm). Liver resection has traditionally been reserved for patients with small HCC, but more recently it is being used for patients with large and huge tumors. The aim of this study was to determine risk predictors of recurrence, patterns of recurrence, and survival rates for large and huge HCC patients who underwent curative liver resection. MATERIALS AND METHODS We retrospectively identified a subgroup of patients who underwent liver resection for HCC with diameters 5 cm or larger. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to investigate potential risk factors for recurrence and death. RESULTS Among 897 patients, the median follow-up was 48 (range, 5-140) months. The 1-, 3-, and 5-year RFS rates were 51.6%, 36.1%, and 30.1%, respectively, and OS rates were 80.2%, 55.4%, and 47.7%, respectively. Significant independent predictors of recurrence were preoperative satellite nodule (HR = 2.25; 95% CI, 1.17-4.31; p = .02), preoperative AFP levels above 400 ng/ml (HR = 1.23; 95% CI, 1.04-1.45; p = .01), resection margins of 1 cm or less (HR = 1.21; 95% CI, 1.00-1.46; p = .047), cirrhosis (HR = 2.64; 95% CI, 2.13-3.28; p < .001), and microvascular invasion (HR = 1.71; 95% CI, 1.45-2.20; p < .001). All of these except narrow resection margin were also independent risk factors of OS. CONCLUSIONS Hepatic resection for patients with large and huge HCC without hepatic vascular invasion, extrahepatic metastases, or severe chronic liver disease results in acceptable long-term outcomes.
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Affiliation(s)
- Cailing Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Department II of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yating Xiao
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, UCAS, Hangzhou, China
| | - Zhongzhi Ma
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yuchong Peng
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Xun Li
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xianhai Mao
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Lequn Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 80] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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10
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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11
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Tong VJW, Shelat VG, Chao YK. Clinical application of advances and innovation in radiation treatment of hepatocellular carcinoma. J Clin Transl Res 2021; 7:811-833. [PMID: 34988334 PMCID: PMC8715712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 09/22/2021] [Accepted: 09/29/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) management has evolved over the past two decades, with the development of newer treatment modalities. While various options are available, unmet needs are reflected through the mixed treatment outcome for intermediate-stage HCC. As HCC is radiosensitive, radiation therapies have a significant role in management. Radiation therapies offer local control for unresectable lesions and for patients who are not surgical candidates. Radiotherapy also provides palliation in metastatic disease, and acts as a bridge to resection and transplantation in selected patients. Advancements in radiotherapy modalities offer improved dose planning and targeted delivery, allowing for better tumor response and safer dose escalations while minimizing the risks of radiation-induced liver damage. Radiotherapy modalities are broadly classified into external beam radiation therapy and selective internal radiation therapy. With emerging modalities, radiotherapy plays a complementary role in the multidisciplinary care of HCC patients. AIM We aim to provide an overview of the role and clinical application of radiation therapies in HCC management. RELEVANCE FOR PATIENTS The continuous evolution of radiotherapy techniques allows for improved therapeutic outcomes while mitigating unwanted adverse effects, making it an attractive modality in HCC management. Rigorous clinical studies, quality research and comprehensive datasets will further its application in the present era of evidence-based practice in Medicine.
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Affiliation(s)
- Valerie J. W. Tong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Vishal G. Shelat
- Department of General Surgery, Tan Tock Seng Hospital, 308433, Singapore
| | - Yew Kuo Chao
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 308433, Singapore
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12
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Long HY, Huang TY, Xie XY, Long JT, Liu BX. Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis. World J Clin Cases 2021; 9:5754-5768. [PMID: 34368295 PMCID: PMC8316954 DOI: 10.12998/wjcc.v9.i21.5754] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has increasingly been seen due to improved survival with effective management of intrahepatic lesions. The presence of EHM indicates an advanced stage of HCC, for which systemic therapy serves as the standard treatment modality. Since the approval of Sorafenib as the first systemic agent in 2007, it took almost a decade to show its efficacy in both first and further lines of setting until the landscape of systemic drugs was finally expanded. Moreover, with inspiring results from immunotherapy trials in HCC, it appears that the introduction of immunotherapy may lead to an evolution in the portfolio of HCC treatment. Although the locoregional approach in the management of EHM is not recommended for advanced-stage HCC, efforts have been made to demonstrate its efficacy in symptom relief and potential benefit for overall survival. This review provides a summary of recent updates of the systemic agents in the treatment of advanced HCC, with an emphasis on aggressive locoregional management of EHM by various treatment modalities.
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Affiliation(s)
- Hai-Yi Long
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Tong-Yi Huang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Jian-Ting Long
- Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Xian Liu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
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13
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Xu X, Ding Y, Pan T, Gao F, Huang X, Sun Q. CT-Guided 125I Brachytherapy in the Treatment of Hepatocellular Carcinoma Refractory to Conventional Transarterial Chemoembolization: A Pilot Study. Cancer Manag Res 2021; 13:3317-3326. [PMID: 33883943 PMCID: PMC8055363 DOI: 10.2147/cmar.s305422] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 03/25/2021] [Indexed: 01/22/2023] Open
Abstract
PURPOSE To investigate the efficacy and safety of CT-guided 125I brachytherapy in the treatment of hepatocellular carcinoma (HCC) refractory to conventional transarterial chemoembolization (TACE). METHODS Nineteen patients with TACE-refractory HCC treated with CT-guided 125I brachytherapy between June 2017 and June 2020 at Jiangyin People's Hospital were enrolled in this study. In addition, we used the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria to evaluate the treatment response after 125I brachytherapy. RESULTS Twenty-one tumours were treated with CT-guided 125I brachytherapy in nineteen patients. Twelve tumours (57.1%) showed a complete response, and a partial response was observed in seven tumours (33.3%). The six-month objective response rate was 90.5% (19/21). The adverse effects of CT-guided 125I brachytherapy were tolerable. CONCLUSION Our preliminary clinical experience demonstrated that CT-guided 125I brachytherapy was effective and well tolerated for the treatment of TACE-refractory HCC, suggesting that CT-guided 125I brachytherapy has the potential to become an effective alternative treatment for TACE-refractory HCC.
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Affiliation(s)
- Xinjian Xu
- Department of Interventional Radiology, Jiangyin People's Hospital, Jiang Yin City, Jiangsu Province, 214400, People’s Republic of China
| | - Yiwen Ding
- Department of Interventional Radiology, Jiangyin People's Hospital, Jiang Yin City, Jiangsu Province, 214400, People’s Republic of China
| | - Tianfan Pan
- Department of Interventional Radiology, Jiangyin People's Hospital, Jiang Yin City, Jiangsu Province, 214400, People’s Republic of China
| | - Feng Gao
- Department of Interventional Radiology, Jiangyin People's Hospital, Jiang Yin City, Jiangsu Province, 214400, People’s Republic of China
| | - Xiangzhong Huang
- Department of Interventional Radiology, Jiangyin People's Hospital, Jiang Yin City, Jiangsu Province, 214400, People’s Republic of China
| | - Qiulian Sun
- Department of Radiology, Zhejiangtaizhou Hospital, Taizhou City, Zhejiang Province, 317000, People’s Republic of China
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14
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Yoon SM. External Beam Radiotherapy for Hepatocellular Carcinoma: a Review of the Current Guidelines in the East and the West. JOURNAL OF LIVER CANCER 2021; 21:25-33. [PMID: 37384266 PMCID: PMC10035720 DOI: 10.17998/jlc.21.1.25] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/11/2021] [Accepted: 01/20/2021] [Indexed: 06/30/2023]
Abstract
The incidence of hepatocellular carcinoma (HCC) is geographically heterogeneous depending on the underlying liver disease. Moreover, the decisions and recommendations about standard treatments differ between countries, especially between the East and the West. Because of the complexity of treatment decisions for the management of HCC, a multidisciplinary approach is recommended to maximize the therapeutic efficacy. External beam radiotherapy (RT) has been increasingly used to manage HCC when recommended treatments cannot be applied in real-world clinical practice. However, Western guidelines for the management of HCC do not recommend RT as a treatment option due to the lack of clinical evidence. RT has often been used more in Eastern countries than in Western countries; hence, it is necessary to review both Eastern and Western guidelines for HCC treatment regarding the recommendations about RT. In this study, the comments and potential roles of external beam RT are summarized from several treatment guidelines for the management of HCC.
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Affiliation(s)
- Sang Min Yoon
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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15
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Matoba M, Tsuchiya H, Kondo T, Ota K. Stereotactic body radiotherapy delivered with IMRT for oligometastatic regional lymph node metastases in hepatocellular carcinoma: a single-institutional study. JOURNAL OF RADIATION RESEARCH 2020; 61:776-783. [PMID: 32845298 PMCID: PMC7482167 DOI: 10.1093/jrr/rraa067] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 07/01/2020] [Indexed: 06/11/2023]
Abstract
The optimal treatment to lymph node metastases in hepatocellular carcinoma (HCC) has not been established, yet. Our aim was to evaluate the local control, the survival benefit and the toxicity of stereotactic body radiotherapy (SBRT) delivered with intensity-modulated radiotherapy (IMRT) to oligometastatic regional lymph node in HCC patients. We retrospectively analyzed 15 patients with HCC treated with SBRT delivered using IMRT to 24 regional lymph node metastases. Dose prescriptions were set to 45 Gy in 6 fractions of 7.5 Gy for solitary lesions and 49.5 Gy in 9 fractions of 5.5 Gy for multiple lesions. For the planning target volume, the plan was optimized aiming for a V95% > 90%. The study endpoints were freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS) and toxicity. The median follow-up was 18.1 months. The 1-year and 2-year FFLP rates were 100 and 90 ± 9.5%, respectively. The 1-year PFS rate was 46.7 ± 12.9%, and the 1-year and 2-year OS rates were 73.3 ± 11.4 and 28.6 ± 12.7%, respectively. Only one patient had a duodenal ulcer and three patients had liver enzyme elevation in sub-acute toxicity, however there was no grade ≥ 3 toxicity. In conclusion, SBRT delivered with IMRT to lymph node metastases can offer excellent local control with minimal toxicity, and SBRT may improve HCC patients' survival more than conventional radiotherapy.
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Affiliation(s)
- Munetaka Matoba
- Corresponding author. Department of Radiology, Kanazawa Medical University, Daigaku 1-1, Uchinada, Kahoku, Ishikawa, 920-0293, Japan. Tel: +8176 2862211, Fax: +81762868096;
| | | | - Tamaki Kondo
- Department of Radiology, Kanazawa Medical University
| | - Kiyotaka Ota
- Department of Radiology, Kanazawa Medical University
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16
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Walburn T, Moon AM, Hayashi PH, Gerber D, Sanoff HK, McGinty KA, Mauro D, Tepper J, Wang K. Stereotactic Body Radiation Therapy for Recurrent, Isolated Hepatocellular Carcinoma Lymph Node Metastasis With or Without Prior Liver Transplantation. Cureus 2020; 12:e9988. [PMID: 32983688 PMCID: PMC7511077 DOI: 10.7759/cureus.9988] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Lymph node metastases from hepatocellular carcinoma (HCC) represents a challenging clinical scenario with a poor prognosis, especially in the setting of prior liver transplant. Long-term survival is achievable in select patients with isolated lymph node metastases who undergo surgical resection, but little data exist regarding non-surgical options. For intrahepatic HCC, stereotactic body radiation therapy (SBRT) has emerged as a standard and effective nonsurgical treatment option. Here, we present three patients (two with prior liver transplant) with isolated lymph node metastases treated with curative intent using SBRT to doses of 30-45 Gy in three to five fractions. Two patients (with follow-up of 27 and 31 months) had a complete or near-complete response and remain cancer-free. One patient had intrahepatic HCC recurrence shortly after SBRT but stable disease in the treated lymph node metastasis at 20 months. Liver function remained excellent after radiation in all three patients, but one patient developed a grade 3 duodenal ulcer at 20 months that resolved with medical management. These cases illustrate the potential utility of SBRT as a non-invasive, definitive treatment option for patients with isolated lymph node metastases from HCC.
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Affiliation(s)
- Tyler Walburn
- Department of Radiation Oncology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - Paul H Hayashi
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - David Gerber
- Division of Abdominal Transplant, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - Hanna K Sanoff
- Division of Hematology and Oncology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - Katrina A McGinty
- Department of Radiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - David Mauro
- Division of Vascular Interventional Radiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - Joel Tepper
- Department of Radiation Oncology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
| | - Kyle Wang
- Department of Radiation Oncology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA
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17
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Zhang Q, He Y, Luo N, Patel SJ, Han Y, Gao R, Modak M, Carotta S, Haslinger C, Kind D, Peet GW, Zhong G, Lu S, Zhu W, Mao Y, Xiao M, Bergmann M, Hu X, Kerkar SP, Vogt AB, Pflanz S, Liu K, Peng J, Ren X, Zhang Z. Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma. Cell 2019; 179:829-845.e20. [PMID: 31675496 DOI: 10.1016/j.cell.2019.10.003] [Citation(s) in RCA: 976] [Impact Index Per Article: 162.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 06/14/2019] [Accepted: 10/03/2019] [Indexed: 02/08/2023]
Abstract
The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.
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Affiliation(s)
- Qiming Zhang
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Yao He
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
| | - Nan Luo
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Ninth School of Clinical Medicine, Peking University, Beijing 100038, China
| | - Shashank J Patel
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
| | - Yanjie Han
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Ranran Gao
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Madhura Modak
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - Sebastian Carotta
- Department of Cancer Cell Signaling, Boehringer Ingelheim RCV GmBH & Co KG., Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria
| | - Christian Haslinger
- Department of Computational Biology and Genomics, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - David Kind
- Department of Computational Biology and Genomics, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - Gregory W Peet
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
| | - Guojie Zhong
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Shuangjia Lu
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Weihua Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Beijing 100730, China
| | - Mengmeng Xiao
- Department of Retroperitoneal Tumor Surgery, Peking University International Hospital, Beijing 102206, China
| | - Michael Bergmann
- Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Xueda Hu
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China
| | - Sid P Kerkar
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
| | - Anne B Vogt
- Department of Human Cancer Immunology, Boehringer Ingelheim RCV GmBH & Co KG., Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria
| | - Stefan Pflanz
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma, Birkendorfer Str. 65, 88400 Biberach, Germany
| | - Kang Liu
- Department of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
| | - Jirun Peng
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Ninth School of Clinical Medicine, Peking University, Beijing 100038, China.
| | - Xianwen Ren
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
| | - Zemin Zhang
- BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
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18
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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19
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Ma J, Zhang L, Bian HR, Lu ZG, Zhu L, Yang P, Zeng ZC, Xiang ZL. A Noninvasive Prediction Nomogram for Lymph Node Metastasis of Hepatocellular Carcinoma Based on Serum Long Noncoding RNAs. BIOMED RESEARCH INTERNATIONAL 2019; 2019:1710670. [PMID: 31355249 PMCID: PMC6634290 DOI: 10.1155/2019/1710670] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 05/17/2019] [Accepted: 05/23/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Lymph node metastasis (LNM) is common in hepatocellular carcinoma (HCC). In order to intervene HCC LNM in advance, we developed a prediction nomogram based on serum long noncoding RNA (lncRNA). METHODS Serum samples from 242 HCC patients were gathered and randomly enrolled into the training and validation cohorts. LncRNAs screened out from microarray were quantified with qRT-PCR. Univariate and multivariate analyses were applied for screening independent risk factors. A prediction nomogram was ultimately developed for HCC LNM. The nomogram was estimated by discrimination and calibration tests in the validation cohort. The effects of the candidate lncRNA on the malignant phenotypes of HCC cells were further explored by wound healing assay and colony formation assay. RESULTS ENST00000418803, lnc-ZNF35-4:1, lnc-EPS15L1-2:1, BCLC stage, and vascular invasion were selected as components of the nomogram according to the adjusted multivariate analysis. The nomogram effectively predicted the HCC LNM risk among the cohorts with suitable calibration fittings and displayed high discrimination with C-index of 0.89 and 0.85. Moreover, the abnormally high expression of lnc-EPS15L1-2:1 in HCC cell lines showed significant carcinogenic effects. CONCLUSIONS The noninvasive nomogram may provide more diagnostic basis for treatments of HCC. The biomarkers identified can bring new clues to basic researches.
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Affiliation(s)
- Jie Ma
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li Zhang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hai-Rong Bian
- Department of Radiation Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zheng-Guo Lu
- Department of Radiation Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lian Zhu
- Department of Radiation Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ping Yang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhao-Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zuo-Lin Xiang
- Department of Radiation Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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20
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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21
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Han B, Li C, Meng H, Gomes Romeiro F, Mancuso A, Zhou Z, Levi Sandri GB, Xu Y, Han T, Han L, Shao L, Qi X. Efficacy and safety of external-beam radiation therapy for hepatocellular carcinoma: An overview of current evidence according to the different target population. Biosci Trends 2019; 13:10-22. [PMID: 30799321 DOI: 10.5582/bst.2018.01261] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. During the recent years, external-beam radiation therapy (EBRT) has been safely and effectively employed for the management of HCC. We overviewed the current evidence regarding the efficacy and safety of EBRT for HCC according to the different target population. PubMed database was searched for identifying English-language full-text articles regarding EBRT for the treatment of HCC. Search items were "hepatocellular carcinoma AND radiation therapy". Until now, preliminary evidence has suggested the following role of EBRT for HCC. 1) EBRT, especially stereotactic body radiation therapy, is an emerging choice of therapy for small HCC. 2) EBRT combined with non-surgical treatment can achieve an excellent intrahepatic tumor control and a potential survival benefit for huge HCC. 3)Adjunctive EBRT may improve the efficacy of transarterial chemoembolization for HCC with portal vein tumor thrombosis. 4) EBRT can relieve the pain and improve the quality of life for patients with extrahepatic metastases. 5) EBRT may be a bridge to liver transplantation by minimizing the tumor progression. 6) Adjunctive EBRT may reduce the tumor recurrence and improve the survival after resection. In summary, EBRT is a promising choice of treatment of HCC. However, more high-quality evidence is needed to further establish the status of EBRT for the management of HCC.
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Affiliation(s)
- Bing Han
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
- Postgraduate College, Jinzhou Medical University
- Department of Gastroenterology, No. 463 Hospital of Chinese PLA
| | - Chuan Li
- Section of Medical Service, General Hospital of Norther Northern Command (formerly General Hospital of Shenyang Military Area)
| | - Hao Meng
- Department of Thoracic Surgery, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Fernando Gomes Romeiro
- Department of Internal Medicine, Botucatu Medical School, Universidade Estadual Paulista (UNESP)
| | - Andrea Mancuso
- Epatologiae Gastroenterologia, Ospedale Niguarda Ca' Granda
- Medicina Internal, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico - Di Cristina - Benfratelli
| | - Zhirui Zhou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center
| | | | - Ying Xu
- Department of Radiotherapy, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Tao Han
- Department of Oncology, Cancer Center, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Lei Han
- Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
| | - Lichun Shao
- Department of Gastroenterology, No. 463 Hospital of Chinese PLA
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area)
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22
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Zhang XP, Gao YZ, Jiang YB, Wang K, Chen ZH, Guo WX, Shi J, Zhang YJ, Chen MS, Lau WY, Cheng SQ. A serological scoring system to predict lymph node metastasis in patients with hepatocellular carcinoma. HPB (Oxford) 2019; 21:335-344. [PMID: 30104175 DOI: 10.1016/j.hpb.2018.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 06/25/2018] [Accepted: 07/09/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Lymph node metastasis (LNM)has widely been recognized as a poor prognostic indicator for hepatocellular carcinoma (HCC) patients. Preoperative prediction of LNM is important for clinicians to decide on treatment. This study was designed to develop a simple and convenient system to predict LNM. METHODS Consecutive HCC patients who were suspected to have LNM were divided into a training, an internal validation and an external validation cohort. The receiver operating characteristic (ROC) analysis was used to determine the threshold value of the preoperative serological variables. A nomogram visualization system model was then established. RESULT Of the 287 patients, there were 31 patients who had LNM (10.8%), and 21 of 203 patients (10.3%) were in the training cohort and 10 of 84 patients (11.9%) in the internal validation cohort. Sixteen of 176 patients (9.1%) in the external validation cohort had LNM. The serological indices including neutrophil/lymphocyte rate, age, platelet, prothrombin time, and total protein, were included in the nomogram. The areas of the ROC curve were 0.846, 0.679 and 0.738 in predicting LNM in the training cohort, the internal validation cohort and the external validation cohort, respectively. CONCLUSION The scoring system constructed using the preoperative serological variables predicted LNM in HCC patients.
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Affiliation(s)
- Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Zhen Gao
- Department of Molecular Diagnosis, Clinical Medical College, Yangzhou University, China
| | - Ya-Bo Jiang
- 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
| | - Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yao-Jun Zhang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Min-Shan Chen
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wan Y Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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23
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Yuan Z, Xing A, Zheng J, Li W. Safety and technical feasibility of percutaneous ablation for lymph node metastases of hepatocellular carcinoma. Int J Hyperthermia 2019; 36:160-168. [PMID: 30776925 DOI: 10.1080/02656736.2018.1542510] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- Zhuhui Yuan
- Center of Interventional Oncology and Liver Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Aili Xing
- Center of Interventional Oncology and Liver Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Jiasheng Zheng
- Center of Interventional Oncology and Liver Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Wei Li
- Center of Interventional Oncology and Liver Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, China
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24
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Lee J, Yoon WS, Koom WS, Rim CH. Role of local treatment including radiotherapy in Barcelona Clinic of Liver Cancer stage C patients: a nationwide cohort analysis in South Korea. Cancer Manag Res 2019; 11:1373-1382. [PMID: 30809102 PMCID: PMC6376887 DOI: 10.2147/cmar.s193761] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Purpose Sorafenib is recommended as the standard treatment for hepatocellular carcinoma (HCC) of Barcelona Clinic of Liver Cancer stage C (BCLC C). However, local treatment including radiation therapy (LRT) is also widely administered in practice. The aim of our study was to define the role of LRT among BCLC C patients. Patients and methods Of the patients with HCC enrolled the Korean Central Cancer Registry from 2008 to 2014, the Korean Liver Cancer Study Group randomly extracted 10,580 patient data from ~50 hospitals nationwide. Among them, 3,401 patients were categorized to have BCLC C HCC. Among them, patients with information on initial treatments, defined as the first and secondary treatment within 60 days after the first treatment, were selected and classified into three initial treatment groups: LRT, sorafenib, and no treatment. Results Among 3,401 BCLC C HCC patients, 1,486 were included in the study and the remaining patients were excluded as they did not meet the criteria (eg, underwent local treatments without radiotherapy [RT] or received chemotherapy other than sorafenib). Of these, 266 were assigned to LRT (17.9%), 316 to sorafenib (21.3%), and 904 to no treatment group (60.8%). Median survival time of the sorafenib group was shorter than that of the LRT group (3.8 vs 7.6 months, P<0.001). In multivariable analysis, sorafenib group showed significantly higher risk related to mortality compared to LRT group, not only among all patients (HR: 1.50, 95% CI: 1.23-1.84) but also between subgroup cohorts with portal invasions (1.55, 1.23-1.84), with lymph node metastases (2.42, 1.53-3.83), without distant metastases (1.43, 1.10-1.87), and with distant metastases (1.57, 1.13-2.19). Additionally, no treatment group showed the worst survival among the three treatment groups not only in all patients, but also in all subgroups of patients (P<0.001 in all). Conclusion LRT as an initial treatment showed survival benefit as compared to sorafenib in HCC patients of BCLC C.
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Affiliation(s)
- Jeongshim Lee
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Radiation Oncology, Inha University Hospital, Incheon, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Republic of Korea,
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Republic of Korea,
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25
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Chen S, Gao Y, Li Z, Jia J, Fang M, Wang M, Feng H, Chen Q, Guan W, Wang Z, Gao C. A Nomogram Predicting Extrahepatic Metastases for Patients with Adjuvant Transarterial Chemoembolization after Hepatectomy. J Cancer 2018; 9:4223-4233. [PMID: 30519323 PMCID: PMC6277617 DOI: 10.7150/jca.25886] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 08/15/2018] [Indexed: 01/27/2023] Open
Abstract
Background: Prognosis remains poor for hepatocellular carcinoma (HCC) patients with extrahepatic metastases (EHMs). This study aimed to develop a nomogram to predict EHMs in HCC patients who underwent adjuvant transarterial chemoembolization (TACE) following hepatectomy. Methods: Data of 578 HCC patients who underwent TACE after hepatectomy at the Eastern Hepatobiliary Surgery Hospital was retrospectively reviewed. Cox regression analyses was used to select variables to construct the nomogram. Predictive accuracy and discriminative ability of the model were performed using concordance index (C-index), calibration curve and the area under time-dependent receiver operating characteristic (ROC) curve. Results: Postoperative EHMs were detected in 89 and 31 patients in the training cohort (n = 453) and validation cohort (n = 125), respectively. Multivariate analysis showed that tumor size (HR, 1.099; 95% CI, 1.049-1.152), coarse beam type of tumor histopathological structure (HR, 2.382; 95% CI, 1.030-5.512), presence of satellite nodules (HR, 1.936; 95% CI, 1.156-3.244) and alpha-fetoprotein (AFP) (HR, 1.399; 95% CI, 1.098-1.783) were independent risk factors for EHMs (all p < 0.05). The nomogram incorporated these factors achieved good agreement between prediction and actual observation with a concordance index (C-index) of 0.73 (95% CI, 0.68 to 0.78) and 0.71 (95% CI, 0.63 to 0.79) in the training cohort and validation cohort, respectively. In addition, patients who had a nomogram score > 17 were considered to have higher risk for EHMs compared with those scored ≤ 12. Furthermore, the time-dependent area under the ROC curve indicated comparative stability and adequate discriminative ability of the model. Conclusions: This novel nomogram can identify those with high risk of EHMs after adjuvant TACE following hepatectomy. The validation cohort showed a good performance, suggesting it could benefit surgeons on decision-making.
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Affiliation(s)
- Shipeng Chen
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China.,Clinical Medical College, Fujian Medical University, Fuzhou, China
| | - Yuzhen Gao
- Department of Molecular Diagnosis, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Zheng Li
- Department of Hepatic Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Jian'an Jia
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Meng Fang
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Mengmeng Wang
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Huijuan Feng
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Qinjunjie Chen
- Department of Hepatic Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Wenqian Guan
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China.,Clinical Medical College, Fujian Medical University, Fuzhou, China
| | - Ziyi Wang
- Shanghai Institute of Technology, Shanghai, China
| | - Chunfang Gao
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
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26
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Sorin Y, Ikeda K, Kawamura Y, Fujiyama S, Kobayashi M, Hosaka T, Sezaki H, Akuta N, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H. Effectiveness of Particle Radiotherapy in Various Stages of Hepatocellular Carcinoma: A Pilot Study. Liver Cancer 2018; 7:323-334. [PMID: 30488022 PMCID: PMC6249594 DOI: 10.1159/000487311] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 01/30/2018] [Indexed: 02/04/2023] Open
Abstract
AIM We analyzed the effectiveness of external particle radiotherapy (PRT) as an alternative therapy for various stages of hepatocellular carcinoma (HCC). METHODS Eighty-three patients with HCC underwent PRT in our hospital from 2007 to 2015 (proton beam radiation in 58 patients and carbon ion radiation in 25 patients), including patients with early-stage HCC (single HCC measuring ≤3 cm, Barcelona Clinic Liver Cancer [BCLC] stage 0 or A) (group A, n = 30), those with intermediate-stage HCC (HCCs measuring ≥3 cm but inoperable or multinodular and transcatheter arterial embolization [TACE]-refractory, BCLC stage B) (group B, n = 31), and those with advanced-stage HCC (HCC with portal invasion or extrahepatic metastasis) (group C, n = 22). The median radiation dose was 72.6 GyE (range 50-74) for proton beam radiation and 45.0 GyE (range 45-52.8) for carbon beam radiation. Local control ability was defined as continuous shrinkage of the tumor size without development of new lesions for ≥6 months after PRT. RESULTS The rates of local control of the target tumor at 6 months, 1 year, and 2 years were 91.9, 86.3, and 84.8%, respectively. The overall survival rates at 1, 2, and 3 years were 83.0, 65.6, and 55.1%, respectively. Patients in group A showed the best survival rates (100.0% at 1 year and 85.9% at 2 years). The 1-year survival rate was poor in group C (63.6%) despite a good local tumor control rate of 74.7%. The overall survival rates were significantly better in groups A and B than in group C. CONCLUSIONS The local control rates after PRT were sufficiently high compared to TACE or sorafenib. Thus, PRT should be adopted for patients with difficult-to-treat HCC in the early and intermediate stages.
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Affiliation(s)
- Yushi Sorin
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan,*Yushi Sorin, MD, Department of Hepatology, Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo 105-8470 (Japan), E-Mail
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Shunichiro Fujiyama
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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27
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Rim CH, Kim CY, Yang DS, Yoon WS. The role of external beam radiotherapy for hepatocellular carcinoma patients with lymph node metastasis: a meta-analysis of observational studies. Cancer Manag Res 2018; 10:3305-3315. [PMID: 30233246 PMCID: PMC6132227 DOI: 10.2147/cmar.s175703] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Purpose Lymph node metastasis of hepatocellular carcinoma is categorized as advanced in Barcelona Clinic of Liver Cancer staging, and sorafenib is a sole treatment recommended. However, appliance of local treatment including external beam radiotherapy (EBRT) has not been uncommon. We performed a meta-analysis and systemically reviewed current literature to evaluate the efficacy and safety of EBRT. Methods PubMed, Medline, Cochrane library, and Embase were systemically searched until December 17, 2017. The primary endpoint of analyses was response rate (RR), and 1-year overall survival and complication rates of grade ≥3 were secondary endpoints. Complications were primarily assessed descriptively. Results A total of 8 studies comprising 521 patients were included. The pooled RR was 73.1% (95% confidence interval [CI]: 63.6–80.9), and high-dose EBRT groups had better RR than the low-dose group (82.2% [95% CI: 74.4–88.1] vs 51.1% [95% CI: 40.3–61.7]; P=0.001]. The pooled 1-year overall survival rate was 41.0% (95% CI: 32.9–49.6). Six studies assessed the survival benefit according to RR, and 5 (83.3%) of these 6 studies reported statistically significant survival benefit. The most common grade ≥3 toxicities were thrombocytopenia and gastrointestinal complication, with pooled rates of 3.4% (95% CI: 1.2–9.5) and 3.5% (95% CI:1.7–7.2), respectively. Conclusion EBRT showed a pooled RR of 73.1% and was safely performed. EBRT might palliate symptoms through tumor reductions and improve survival. Use of sorafenib combined or sequentially with EBRT can be recommended rather than monotherapy.
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Affiliation(s)
- Chai Hong Rim
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Gyeonggi-do, Republic of Korea,
| | - Chul Yong Kim
- Department of Radiation Oncology, Anam Hospital, Korea University Medical College, Seoul, Republic of Korea
| | - Dae Sik Yang
- Department of Radiation Oncology, Guro Hospital, Korea University Medical College, Seoul, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Gyeonggi-do, Republic of Korea,
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28
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Zhou J, Sun HC, Wang Z, Cong WM, Wang JH, Zeng MS, Yang JM, Bie P, Liu LX, Wen TF, Han GH, Wang MQ, Liu RB, Lu LG, Ren ZG, Chen MS, Zeng ZC, Liang P, Liang CH, Chen M, Yan FH, Wang WP, Ji Y, Cheng WW, Dai CL, Jia WD, Li YM, Li YX, Liang J, Liu TS, Lv GY, Mao YL, Ren WX, Shi HC, Wang WT, Wang XY, Xing BC, Xu JM, Yang JY, Yang YF, Ye SL, Yin ZY, Zhang BH, Zhang SJ, Zhou WP, Zhu JY, Liu R, Shi YH, Xiao YS, Dai Z, Teng GJ, Cai JQ, Wang WL, Dong JH, Li Q, Shen F, Qin SK, Fan J. Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition). Liver Cancer 2018; 7:235-260. [PMID: 30319983 PMCID: PMC6167671 DOI: 10.1159/000488035] [Citation(s) in RCA: 441] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 02/24/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.
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Affiliation(s)
- Jian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Hui-Chuan Sun
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Zheng Wang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Wen-Ming Cong
- Department of Pathology, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jian-Hua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia-Mei Yang
- Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ping Bie
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Lian-Xin Liu
- Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tian-Fu Wen
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Guo-Hong Han
- Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Mao-Qiang Wang
- Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, China
| | - Rui-Bao Liu
- Department of Interventional Radiology, the Tumor Hospital of Harbin Medical University, Harbin, China
| | - Li-Gong Lu
- Department of Interventional Oncology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zheng-Gang Ren
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Min-Shan Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhao-Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Chang-Hong Liang
- Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Min Chen
- Editorial Department of Chinese Journal of Digestive Surgery, Chongqing, China
| | - Fu-Hua Yan
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Wu Cheng
- Department of integrated treatment, Tumor Hospital of Fudan University, Shanghai, China
| | - Chao-Liu Dai
- Department of Hepatobiliary and Spleenary Surgery, the Affiliated Shengjing Hospital, China Medical University, Shenyang, China
| | - Wei-Dong Jia
- Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China
| | - Ya-Ming Li
- Department of Nuclear Medicine, the First Hospital of China Medical University, Shenyang, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Oncology, Peking University International Hospital, Beijing, China
| | - Tian-Shu Liu
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guo-Yue Lv
- Department of General Surgery, the First Hospital of Jilin University, Jilin, China
| | - Yi-Lei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Wei-Xin Ren
- Department of Interventional Radiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Hong-Cheng Shi
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Tao Wang
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Xiao-Ying Wang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Bao-Cai Xing
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jian-Ming Xu
- Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China
| | - Jian-Yong Yang
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ye-Fa Yang
- Department of Hepatic Surgery and Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Sheng-Long Ye
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Zheng-Yu Yin
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Bo-Heng Zhang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Shui-Jun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei-Ping Zhou
- Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ji-Ye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ying-Hong Shi
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Yong-Sheng Xiao
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Zhi Dai
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Gao-Jun Teng
- Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jian-Qiang Cai
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei-Lin Wang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jia-Hong Dong
- Department of Hepatobiliary and Pancreas Surgery, Beijing Tsinghua Changgung Hospital (BTCH), School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Feng Shen
- Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Kui Qin
- Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, China,**Dr. Shu-Kui Qin, Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing 210002 (China), E-Mail
| | - Jia Fan
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China,*Dr. Jia Fan, Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032 (China), E-Mail
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Wada Y, Takami Y, Matsushima H, Tateishi M, Ryu T, Yoshitomi M, Matsumura T, Saitsu H. The Safety and Efficacy of Combination Therapy of Sorafenib and Radiotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Study. Intern Med 2018; 57:1345-1353. [PMID: 29279513 PMCID: PMC5995712 DOI: 10.2169/internalmedicine.9826-17] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Objective Sorafenib is a standard therapy for advanced hepatocellular carcinoma (HCC), whereas radiotherapy is effective for local control of extrahepatic spread (EHS) or macrovascular invasion (MVI). This study investigated the safety and efficacy of this combined therapy to treat advanced HCC. Methods This retrospective study reviewed 62 patients with advanced-stage HCC with EHS or MVI who received sorafenib therapy, excluding the patients with only lung metastases. Results Of the 62 patients, 15 were treated using the combined therapy of sorafenib and radiotherapy (group RS), and 47 were treated with sorafenib monotherapy (group S). In group RS, patients were treated using three-dimensional conformal radiotherapy with a total irradiation dose of 30-60 Gy (median, 50 Gy). Irradiation was targeted at the bone, lymph nodes, adrenal gland, and MVI in 6, 5, 1, and 4 patients, respectively. The overall incidence of adverse events was 93.3% in group RS and 91.5% in group S (p=N.S.). Incidences of thrombocytopenia, leukopenia, and skin reaction were significantly higher in group RS (73.3%, 40.0%, and 66.7%, respectively) than in group S (36.2%, 10.6%, and 27.7%, respectively, p=0.02, 0.02, and <0.01, respectively). The incidence of severe adverse events, however, was comparable in the 2 groups: 20% in group RS and 19.2% in group S. The median progression-free survival (PFS) of EHS or MVI, PFS of whole lesions, and overall survival were longer in group RS (13.5, 10.6, and 31.2 months, respectively) than in group S (3.3, 3.5, and 12.1 months, respectively) (p<0.01 for all). Conclusion Sorafenib in combination with radiotherapy is a feasible and tolerable treatment option for advanced HCC.
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Affiliation(s)
- Yoshiyuki Wada
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan
| | - Yuko Takami
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan
| | - Hajime Matsushima
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan
| | - Masaki Tateishi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan
| | - Tomoki Ryu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan
| | - Munehiro Yoshitomi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan
| | - Taisei Matsumura
- Department of Radiology, National Hospital Organization Kyushu Medical Center, Japan
| | - Hideki Saitsu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan
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Kim Y, Park HC, Yoon SM, Kim TH, Lee J, Choi J, Yu JI, Park JH, Kim JH, Park JW, Seong J. Prognostic group stratification and nomogram for predicting overall survival in patients who received radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma: a multi-institutional retrospective study (KROG 15-02). Oncotarget 2017; 8:94450-94461. [PMID: 29212241 PMCID: PMC5706887 DOI: 10.18632/oncotarget.21775] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 09/20/2017] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE To develop a prognostic model for overall survival (OS) in hepatocellular carcinoma (HCC) patients receiving radiotherapy (RT) to metastatic abdominal lymph nodes (LNs). MATERIALS AND METHODS Two hundred twenty-eight patients treated with RT to metastatic abdominal LNs were retrospectively reviewed. RESULTS Median OS in all patients was 11.1 months. LN responders had significantly higher median OS than non-responders (14.2 months vs. 7.5 months, p<0.05). On multivariate analysis, Child-Pugh classification, status of intrahepatic tumor, presence of distant metastasis, number and location of metastatic LNs, serum level of alpha fetoprotein (AFP), and the LN response to RT were significant prognostic factors for OS (p < 0.05 each). Based on the results of multivariate analysis, prognostic group stratification according to the number of pre-treatment risk factors was a significant predictor of OS, and median OS in patients with ≥ 4, 3, 2, 1, and 0 risk factors were 2.9, 5.5, 10.3, 13.6, and 27.8 months, respectively (p<0.05). A nomogram was formulated by integrating the different prognostic contribution of each factor, and it showed good accuracy for predicting 2-year OS with a concordance index of 0.72. CONCLUSION Prognostic group stratification and nomogram could be useful prognostic and therapeutic indicators in selecting treatment strategies.
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Affiliation(s)
- Youngkyong Kim
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Min Yoon
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Jieun Lee
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinhyun Choi
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin-Hong Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joong-Won Park
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea
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Mu L, Sun L, Pan T, Lyu N, Li S, Li X, Wang J, Xie Q, Deng H, Zheng L, Peng J, Shen L, Fan W, Wu P, Zhao M. Percutaneous CT-guided radiofrequency ablation for patients with extrahepatic oligometastases of hepatocellular carcinoma: long-term results. Int J Hyperthermia 2017; 34:59-67. [PMID: 28540809 DOI: 10.1080/02656736.2017.1318332] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The aim of this study was to evaluate the therapeutic outcome of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for extrahepatic oligometastases of hepatocellular carcinoma (HCC). METHODS Institutional review board approval was obtained for this retrospective study, and all patients provided written informed consent. Between April 2004 and December 2015, 116 oligometastases (diameter, 5-50 mm; 20.3 ± 10.4) in 79 consecutive HCC patients (73 men and 6 women; average age, 50.3 years ±13.0) were treated with RFA. We focussed on patients with 1-3 extrahepatic metastases (EHM) confined to 1-2 organs (including the lung, adrenal gland, bone, lymph node and pleura/peritoneum) who were treated naïve with curative intent. Survival, technical success and safety were evaluated. The log-rank test and Cox proportional hazards regression models were used to analyse the survival data. RESULTS No immediate technical failure occurred, and at 1 month, the technique effectiveness rate was determined to be 95.8%. After a median follow-up time of 28.0 months (range, 6-108 months), the 1-, 2- and 3-year overall survival (OS) rates were 91, 70 and 48%, respectively, with a median survival time of 33.5 months. Time to unoligometastatic progression (TTUP) of less than 6 months (p < 0.001) and a Child-Pugh score of more than 5 (p = 0.001) were significant indicators of shorter OS. The 1-, 2- and 3-year disease free survival (DFS) rates were 34, 21 and 8%, respectively, with a median DFS time of 6.8 months. DFS was better for those with lung metastases (p = 0.006). Major complication occurred in nine (9.5%, 9/95) RFA sessions without treatment-related mortality. CONCLUSIONS CT-guided RFA for oligometastatic HCC may provide favourable efficacy and technical success with a minimally invasive approach.
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Affiliation(s)
- Luwen Mu
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China.,c Department of Vascular Interventional Radiology , Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China
| | - Lin Sun
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,d Department of Medical Imaging , Sun Yat-sen University Cancer Center , Guangzhou , PR China.,e Department of Medical Imaging , Guangdong Second Provincial General Hospital, Guangdong Provincial Emergency Hospital , Guangzhou , PR China
| | - Tao Pan
- c Department of Vascular Interventional Radiology , Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China
| | - Ning Lyu
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Shaolong Li
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Xishan Li
- f Department of Interventional Radiology , Guangzhou First People's Hospital Guangzhou Medical University , Guangzhou , PR China
| | - Jianpeng Wang
- g Target and Interventional Therapy Department of Oncology , First People's Hospital of Foshan, Affiliated Foshan Hospital of Sun Yat-sen University , Foshan , PR China
| | - Qiankun Xie
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Haijing Deng
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Lie Zheng
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,d Department of Medical Imaging , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Jianhong Peng
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,h Department of Colorectal Surgery , Sun Yat-sen University Cancer Center, Guangzhou , PR China
| | - Lujun Shen
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Weijun Fan
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Peihong Wu
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
| | - Ming Zhao
- a State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou , PR China.,b Minimally Invasive Interventional Division , Sun Yat-sen University Cancer Center , Guangzhou , PR China
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Pan T, Xie QK, Lv N, Li XS, Mu LW, Wu PH, Zhao M. Percutaneous CT-guided Radiofrequency Ablation for Lymph Node Oligometastases from Hepatocellular Carcinoma: A Propensity Score–matching Analysis. Radiology 2017; 282:259-270. [DOI: 10.1148/radiol.2016151807] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Zhang L, Xiang ZL, Zeng ZC, Fan J, Tang ZY, Zhao XM. A microRNA-based prediction model for lymph node metastasis in hepatocellular carcinoma. Oncotarget 2016; 7:3587-98. [PMID: 26657296 PMCID: PMC4823129 DOI: 10.18632/oncotarget.6534] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Accepted: 11/22/2015] [Indexed: 12/17/2022] Open
Abstract
We developed an efficient microRNA (miRNA) model that could predict the risk of lymph node metastasis (LNM) in hepatocellular carcinoma (HCC). We first evaluated a training cohort of 192 HCC patients after hepatectomy and found five LNM associated predictive factors: vascular invasion, Barcelona Clinic Liver Cancer stage, miR-145, miR-31, and miR-92a. The five statistically independent factors were used to develop a predictive model. The predictive value of the miRNA-based model was confirmed in a validation cohort of 209 consecutive HCC patients. The prediction model was scored for LNM risk from 0 to 8. The cutoff value 4 was used to distinguish high-risk and low-risk groups. The model sensitivity and specificity was 69.6 and 80.2 %, respectively, during 5 years in the validation cohort. And the area under the curve (AUC) for the miRNA-based prognostic model was 0.860. The 5-year positive and negative predictive values of the model in the validation cohort were 30.3 and 95.5 %, respectively. Cox regression analysis revealed that the LNM hazard ratio of the high-risk versus low-risk groups was 11.751 (95 % CI, 5.110–27.021; P < 0.001) in the validation cohort. In conclusion, the miRNA-based model is reliable and accurate for the early prediction of LNM in patients with HCC.
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Affiliation(s)
- Li Zhang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zuo-Lin Xiang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhao-Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhao-You Tang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Xiao-Mei Zhao
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Abstract
Global incidence and mortality of hepatocellular carcinoma (HCC) has increased over the past two decades. Although transplantation and surgical resection offer a chance for cure and long-term survival, most patients present with more advanced tumor stage when these therapies are not possible. Although rarely curative, locoregional therapy with transarterial chemoembolization or radioembolization offers a survival benefit for those with liver-isolated HCC who are not amenable to curative therapies. Patients with metastatic disease or macrovascular invasion are treated with systemic therapy; however, median survival remains below 1 year. Patients with severe liver dysfunction or poor performance status should be treated with best supportive care given poor prognosis and no survival benefit for treatment. Lack of predictive and prognostic biomarkers in intermediate and advanced HCC tumors has hampered integration of clinical and molecular data to aid tailoring treatment decisions. However, with increasingly complex treatment decisions, optimal outcomes are achieved through multidisciplinary care.
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Wee CW, Kim K, Chie EK, Yu SJ, Kim YJ, Yoon JH. Prognostic stratification and nomogram for survival prediction in hepatocellular carcinoma patients treated with radiotherapy for lymph node metastasis. Br J Radiol 2016; 89:20160383. [PMID: 27416997 DOI: 10.1259/bjr.20160383] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVE To establish a prognostic model for overall survival prediction in patients with hepatocellular carcinoma (HCC) treated with external beam radiotherapy (RT) for lymph node (LN) metastasis. METHODS 105 patients with HCC underwent RT for LN metastasis. The median age, biologically effective RT dose and follow-up period were 60 years, 59 Gy10 and 5.7 months, respectively. 51 patients had symptoms related to LN metastasis. RESULTS The median survival (MS) was 5.8 months for all patients. For patients with LN-related symptoms, MS was 3.8 months compared with 10.7 months for those without LN-related symptoms. On multivariate analysis of pre-RT factors, symptoms related to LN metastasis [hazard ratio (HR) 2.93], Child-Pugh Class B-C (HR 2.77), uncontrolled intrahepatic disease (HR 2.74) and non-nodal distant metastasis (HR 1.62) were significantly poor prognostic factors for survival (all p < 0.05). Prognostic grouping into three groups by the number of risk factors also had a significant predictive value for survival, with patients having 0, 1, 2 and 3-4 risk factors demonstrating MS of 18.0, 11.7, 5.7 and 3.0 months, respectively (p < 0.001). A clinical nomogram based on the four prognostic factors was formulated and demonstrated good accuracy for predicting 6-month survival with a concordance index of 0.77. CONCLUSION In a heterogeneous group of patients with HCC treated with RT for LN metastasis, the presence of LN-related symptoms was highly associated with poor survival. The prognostic grouping and nomogram developed by the present study can be effectively used for the prediction of survival. ADVANCES IN KNOWLEDGE Patients treated with RT for LN metastases harbour various clinical features. Prognostic model and nomogram can help in predicting survival in these patients.
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Affiliation(s)
- Chan Woo Wee
- 1 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyubo Kim
- 2 Department of Radiation Oncology, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Eui Kyu Chie
- 1 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Su Jong Yu
- 3 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Jun Kim
- 3 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung Hwan Yoon
- 3 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Radiotherapy for Adrenal Metastasis from Hepatocellular Carcinoma: A Multi-Institutional Retrospective Study (KROG 13-05). PLoS One 2016; 11:e0152642. [PMID: 27022932 PMCID: PMC4811532 DOI: 10.1371/journal.pone.0152642] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 03/17/2016] [Indexed: 12/30/2022] Open
Abstract
Although the adrenal glands are not common sites of metastasis from hepatocellular carcinoma (HCC), this metastasis can be met in patients with advanced HCC in some clinical settings. However, the effectiveness of radiotherapy against such metastases is unclear. Therefore, we performed the present multi-institutional study to investigate tumor response, overall survival (OS), treatment-related toxicity, and prognostic factors after radiotherapy. We retrospectively reviewed 134 patients who completed a planned radiotherapy for their adrenal metastases. Complete response was noted in 6 (4.3%), partial response in 48 (34.0%), and stable disease in 78 patients (55.3%). The median OS was 12.8 months, and the 1-, 2-, and 5-year OS rates were 53.1%, 23.9%, and 9.3%, respectively. Grade 3 anorexia occurred in 2 patients, grade 3 diarrhea in 1, and grade 3 fatigue in 1. Multivariate analyses revealed that the following factors had significant effects on OS: controlled intrahepatic tumor; controlled extrahepatic metastasis; and Child-Pugh class A. Although patients with adrenal metastasis from HCC had poor OS, radiotherapy provided an objective response rate of 38.3% and disease stability of 93.6%, with minimal adverse events. Therefore, radiotherapy for these patients could represent a good treatment modality, especially for patients with controlled intrahepatic tumors, controlled extrahepatic metastasis, and good hepatic function.
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Lee DY, Park JW, Kim TH, Lee JH, Kim BH, Woo SM, Kim SS, Lee WJ, Kim DY, Kim CM. Prognostic indicators for radiotherapy of abdominal lymph node metastases from hepatocellular carcinoma. Strahlenther Onkol 2015; 191:835-44. [PMID: 26174506 DOI: 10.1007/s00066-015-0873-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 06/23/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE To identify prognostic indicators in patients treated with radiotherapy (RT) for metastases from hepatocellular carcinoma (HCC) in abdominal lymph nodes (LNs). PATIENTS AND METHODS RT was used to treat 65 patients for metastases from HCC in abdominal LNs. Total radiation dose was 30-60 Gy (median 52.8 Gy), with fraction size 1.8-3 Gy. RT was administered five times per week to an equivalent dose in 2-Gy fractions (EQD2; Gy10) of 32.5-65 Gy10 (median 54 Gy10) and an α/βratio for tumor and acute effects of normal tissue of 10. RESULTS Median overall survival (OS) in all patients was 8.1 months. LN responders had significantly higher median OS than nonresponders (14.5 vs. 3.7 months, p < 0.05). Multivariate analysis showed that Child-Pugh classification, status of intrahepatic tumor, number of metastatic LNs, and LN response were independently predictive of OS (p < 0.05 each). Based on results of multivariate analysis, patients were prognostically stratified according to pretreatment risk factors, including Child-Pugh classification, intrahepatic tumor status, and number of metastatic LNs; with the expected median OS in patients with ≥ 2, 1, and 0 risk factors being 2.9, 9.8, and 27.6 months, respectively (p < 0.05). CONCLUSION Our data showed that LN response to RT was an independent prognostic factor for OS in advanced HCC patients with abdominal LN metastases, and suggested that RT for metastatic LNs might improve OS in these patients. In addition, our data suggest that Child-Pugh classification, intrahepatic tumor status, and number of metastatic LNs may be useful prognostic and therapeutic indicators for selecting treatment strategies.
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Affiliation(s)
- Doo Yeul Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea.
| | - Ju Hee Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Bo Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Sang Myung Woo
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Sang Soo Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Woo Jin Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Dae Yong Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
| | - Chang-Min Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea, Goyang, Korea
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2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver 2015; 9:267-317. [PMID: 25918260 PMCID: PMC4413964 DOI: 10.5009/gnl14460] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 03/09/2015] [Indexed: 12/23/2022] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015; 16:465-522. [PMID: 25995680 PMCID: PMC4435981 DOI: 10.3348/kjr.2015.16.3.465] [Citation(s) in RCA: 151] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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Saito Y, Abiko R, Kishida A, Kuwahara Y, Yamamoto Y, Yamamoto F, Fukumoto M, Ohkubo Y. Loss of EGF-dependent cell proliferation ability on radioresistant cell HepG2-8960-R. Cell Biochem Funct 2015; 33:73-9. [PMID: 25663666 DOI: 10.1002/cbf.3090] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 12/10/2014] [Accepted: 12/11/2014] [Indexed: 01/29/2023]
Abstract
Acquired radioresistance of cancer cells interferes with radiotherapy and increases the probability of cancer recurrence. HepG2-8960-R, which is one of several clinically relevant radioresistant (CRR) cell lines, has a high tolerance to the repeated clinically relevant doses of X-ray radiation. In this study, HepG2-8960-R had slightly lower cell proliferation ability than HepG2 in the presence of FBS. In particular, epidermal growth factor (EGF) hardly enhanced cell proliferation and DNA synthesis in HepG2-8960-R. Additionally, EGF could not induce the activation of Erk1/2, because the expression of EGF receptor (EGFR) protein decreased in HepG2-8960-R in accordance with the methylation of the EGFR promoter region. Therefore, cetuximab did not inhibit HepG2-8960-R cell proliferation. Our study showed that HepG2-8960-R had radioresistant and cetuximab-resistant abilities.
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Affiliation(s)
- Yohei Saito
- Department of Radiopharmacy, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan
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Kalogeridi MA, Zygogianni A, Kyrgias G, Kouvaris J, Chatziioannou S, Kelekis N, Kouloulias V. Role of radiotherapy in the management of hepatocellular carcinoma: A systematic review. World J Hepatol 2015; 7:101-112. [PMID: 25625001 PMCID: PMC4295187 DOI: 10.4254/wjh.v7.i1.101] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 10/26/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
Many patients with hepatocellular carcinoma (HCC) present with advanced disease, not amenable to curative therapies such as surgery, transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization (TACE) and radiation therapy. Especially TACE, delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy, has given favorable results on local control and survival. Radiotherapy, as a therapeutic modality of internal radiation therapy with radioisotopes, has also achieved efficacious tumor control in advanced disease. On the contrary, the role of external beam radiotherapy for HCC has been limited in the past, due to the low tolerance of surrounding normal liver parenchyma. However, technological innovations in the field of radiotherapy treatment planning and delivery, have provided the means of delivering radical doses to the tumor, while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy, evaluated for efficacy and safety for HCC, report encouraging results. In this review, we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment.
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Zhou LY, Zeng ZC, Fan J, Chen B, Rao SX, He J, Yang P, Hou JZ, Wu ZF, Zhang JY, Hu Y. Radiotherapy treatment of adrenal gland metastases from hepatocellular carcinoma: clinical features and prognostic factors. BMC Cancer 2014; 14:878. [PMID: 25421498 PMCID: PMC4289365 DOI: 10.1186/1471-2407-14-878] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 11/18/2014] [Indexed: 12/30/2022] Open
Abstract
Background The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. Methods We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were treated by surgical resection, transarterial chemoembolization (TACE), liver transplantation, and/or RT. RT was conducted to adrenal lesions after their intrahepatic lesions were controlled more than 2 months. The parameters studied included survival rates and tumor responses to RT. The Kaplan-Meier method was used to evaluate survival rate and the Cox regression model was used to identify potential predictors of outcome. Results The patients treated by RT had adrenal metastasis on the right side (41), the left (6), or on both sides (8). In all 55 patients, the median survival duration was 13.6 months and there was 100% pain relief after completion of RT. Adverse effects were mild to moderate. Unfavorable pretreatment predictors determined by univariate analysis were associated with multiple intrahepatic foci, metastases to additional organs, high γ-glutamyltransferase and alpha-fetoprotein levels, liver function of Child-Pugh classification B and uncontrolled primary HCC. By multivariate analysis, unfavorable predictors were multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC. Conclusions Radiotherapy as treatment for adrenal metastases in HCC is a good palliative therapy that is associated with reasonable safety. It appears reasonable that such patients should be considered to be treated with radiotherapy. Multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC were unfavorable predictors.
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Affiliation(s)
| | - Zhao-Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
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Suh YG, Lee EJ, Cha H, Yang SH, Seong J. Prognostic values of vascular endothelial growth factor and matrix metalloproteinase-2 in hepatocellular carcinoma after radiotherapy. Dig Dis 2014; 32:725-32. [PMID: 25376290 DOI: 10.1159/000368010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Hepatocellular carcinoma (HCC) is a highly vascularized tumor. In this study, we investigated the prognostic and predictive values of proangiogenic factors in HCC patients receiving radiotherapy. METHODS Between September 2008 and December 2009, a total of 50 patients treated with radiotherapy were prospectively enrolled in this study. Serum and urine samples were collected <1 week before and after radiotherapy. RESULTS After completion of radiotherapy, serum vascular endothelial growth factor (VEGF)/platelet (Plt) levels were significantly increased (p < 0.01). Patients who experienced hepatic tumor recurrence outside the radiation field showed higher VEGF-A/Plt levels before and after radiotherapy than patients who did not (p = 0.04), whereas patients who had hepatic tumor recurrence inside the radiation field showed significantly higher matrix metalloproteinase (MMP)-2 levels after radiotherapy (p = 0.04). On multivariate analyses, a high level of either VEGF/Plt or MMP-2 (≥median) before radiotherapy was a significant independent prognostic factor for a worse progression-free survival (p = 0.04). CONCLUSIONS In HCC patients receiving radiotherapy, levels of VEGF/Plt and MMP-2 before radiotherapy can be useful to predict treatment outcome. This study also suggests the necessity of anti-angiogenic therapy, such as sorafenib, since radiotherapy increases VEGF/Plt levels, and higher levels of VEGF/Plt are associated with a poor outcome.
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Affiliation(s)
- Yang-Gun Suh
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
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Clinical significance of surgical resection of metastatic lymph nodes from hepatocellular carcinoma. Surg Today 2014; 45:1112-20. [PMID: 25205550 DOI: 10.1007/s00595-014-1028-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 08/20/2014] [Indexed: 01/24/2023]
Abstract
PURPOSE The clinical significance of the surgical resection of metastatic lymph nodes (LN) from patients with hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to evaluate the significance of the surgical resection of LN metastasis of HCC. METHODS Among 961 patients who underwent surgical resection for HCC in our hospital, LN metastasis was identified in 38 patients. In these patients, the metastatic LN were removed completely in 22 patients (complete removal group), and incompletely or not removed in 16 patients (control group). The long-term prognosis after LN metastasis was compared between the two groups. RESULTS The overall survival rate after LN metastasis was significantly better in the complete removal group (1-, 3- and 5-year: 71.2, 58.0 and 49.7%, respectively) than in the control group (45.9, 23.0 and 15.3%, respectively, p = 0.0477). LN metastasis was not the cause of death in any of the patients in the complete removal group, whereas it was a cause in some patients in the control group. No local LN recurrence was identified in the complete removal group. CONCLUSIONS The present results suggest that the complete removal of metastatic LN from HCC is clinically beneficial in selected patients.
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Kumar M, Panda D. Role of supportive care for terminal stage hepatocellular carcinoma. J Clin Exp Hepatol 2014; 4:S130-9. [PMID: 25755605 PMCID: PMC4284220 DOI: 10.1016/j.jceh.2014.03.049] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Accepted: 03/03/2014] [Indexed: 02/07/2023] Open
Abstract
Patients with end stage or terminal HCC are those presenting with tumors leading to a very poor Performance Status (ECOG 3-4) or Child-Pugh C patients with tumors beyond the transplantation threshold. Among HCC patients, 15-20% present with end stage or terminal stage HCC. Their median survival is less than 3-4 months. The management of end stage or terminal HCC is only symptomatic and no definitive tumor directed treatment is indicated. Patients with end stage or terminal HCC should receive palliative support including management of pain, nutrition and psychological support. In general, they should not be considered for participating in clinical trials. This review focuses on palliative care of terminal stage HCC.
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Affiliation(s)
- Manoj Kumar
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, India
| | - Dipanjan Panda
- Department of Medical Oncology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, India
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Sareo T, Devi YS, Singh LJ. Hepatocellular carcinoma in situs inversus totalis-a case report. MEDICAL JOURNAL OF INDONESIA 2014. [DOI: 10.13181/mji.v23i1.690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Brochard C, Hamy A, Michalak S, Aubé C, Picquet J, Nebout N, Caroli-Bosc FX, Oberti F, Calès P, Boursier J. Metastatic hepatocellular carcinoma: when surgery and successive palliative treatments lead to remission. Clin Res Hepatol Gastroenterol 2014; 38:e19-22. [PMID: 23608740 DOI: 10.1016/j.clinre.2013.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2012] [Revised: 02/04/2013] [Accepted: 02/19/2013] [Indexed: 02/04/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of death by cancer worldwide. The prognosis of patients with metastatic HCC remains limited, with an expected median survival lower than 50% at 1 year. Here, we report the case of a 63-year-old man who suffered from a small HCC in the liver and a large unique metastasis in the right adrenal gland. A surgical resection of both lesions was performed. Seven months later, HCC recurred with an isolated right renal metastatic lymphadenopathy and a high alpha-fetoprotein level. HCC was brought under control by sorafenib; the alpha-fetoprotein level was greatly reduced but remained moderately elevated and stable over 2 years after the onset of chemotherapy. Additional external radiotherapy on the metastatic lymphadenopathy led to a normalization of the alpha-fetoprotein level and discontinuation of sorafenib treatment. One year after the end of radiotherapy, a second isolated metastasis occurred in the right lung. This tumor was surgically removed. Twenty-one months after this second surgical procedure, i.e., more than 5.5 years after the initial diagnosis of metastatic HCC, the patient was asymptomatic and tumor free.
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Affiliation(s)
- Charlène Brochard
- Department of Hepato-Gastroenterology, University Hospital, Angers, France
| | - Antoine Hamy
- Department of Visceral Surgery, University Hospital, Angers, France
| | - Sophie Michalak
- Department of Pathology, University Hospital, Angers, France
| | - Christophe Aubé
- Department of Radiology, University Hospital, Angers, France
| | - Jean Picquet
- Department of Vascular and Thoracic Surgery, University Hospital, Angers, France
| | - Nathalie Nebout
- Department of Radiotherapy, Centre Paul-Papin, Angers, France
| | | | - Frédéric Oberti
- Department of Hepato-Gastroenterology, University Hospital, Angers, France
| | - Paul Calès
- Department of Hepato-Gastroenterology, University Hospital, Angers, France
| | - Jérôme Boursier
- Department of Hepato-Gastroenterology, University Hospital, Angers, France.
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Imada S, Ishiyama K, Ide K, Kobayashi T, Amano H, Tashiro H, Arihiro K, Aikata H, Chayama K, Ohdan H. Inferior vena cava tumor thrombus that directly infiltrated from paracaval lymph node metastases in a patient with recurrent hepatocellular carcinoma. World J Surg Oncol 2013; 11:177. [PMID: 23915104 PMCID: PMC3751697 DOI: 10.1186/1477-7819-11-177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Accepted: 07/27/2013] [Indexed: 01/24/2023] Open
Abstract
Herein, we present the case of a patient with recurrent hepatocellular carcinoma (HCC) who had paracaval lymph node (LN) metastases with an inferior vena cava (IVC) tumor thrombus after a hepatectomy. A 65-year-old man with chronic hepatitis B virus infection received an extended anterior segmentectomy because of two hepatic tumors, located in segments 7 and 8. Histological examination of both resected specimens showed mostly moderately differentiated HCC with some poorly differentiated areas, and liver cirrhosis (A2/F4). Because the patient had an elevated α-fetoprotein serum level, abdominal computed tomography (CT) was performed. Abdominal CT revealed a 9-mm-diameter recurrent tumor in hepatic segment 3 and paracaval LN metastases with an IVC tumor thrombus at 8 months after the first operation. The patient received transcatheter arterial chemoembolization as treatment for the intrahepatic recurrence, following resection of the paracaval LN metastases and removal of the IVC tumor thrombus. In this case, the paracaval LN metastases had directly infiltrated the IVC via the lumbar veins, resulting in an IVC tumor thrombus, which usually develops from an intrahepatic tumor via the hepatic vein. The development of an IVC tumor thrombus with HCC recurrence, as in this case, is very rare, and based on a PubMed search, we believe this report may be the first to describe this condition.
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Collettini F, Schippers AC, Schnapauff D, Denecke T, Hamm B, Riess H, Wust P, Gebauer B. Percutaneous ablation of lymph node metastases using CT-guided high-dose-rate brachytherapy. Br J Radiol 2013; 86:20130088. [PMID: 23659925 DOI: 10.1259/bjr.20130088] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE To assess the technical feasibility, safety and clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) for achieving local tumour control (LTC) in isolated lymph node metastases. METHODS From January 2008 to December 2011, 10 patients (six males and four females) with isolated nodal metastases were treated with CT-HDRBT. Five lymph node metastases were para-aortic, three were at the liver hilum, one at the coeliac trunk and one was a left iliac nodal metastasis. The mean lesion diameter was 36.5 mm (range 12.0-67.0 mm). Patients were followed up by either contrast-enhanced CT or MRI 6 weeks and then every 3 months after the end of treatment. The primary end point was LTC. Secondary end points included primary technical effectiveness rate, adverse events and progression-free survival. RESULTS The first follow-up examination after 6 weeks revealed complete coverage of all nodal metastases treated. There was no peri-interventional mortality or major complications. The mean follow-up period was 13.2 months (range 4-20 months). 2 out of 10 patients (20%) showed local tumour progression 9 and 10 months after ablation. 5 out of 10 patients (50%) showed systemic tumour progression. The mean progression-free interval was 9.2 months (range 2-20 months). CONCLUSION CT-HDRBT is a safe and effective technique for minimally invasive ablation of nodal metastases. ADVANCES IN KNOWLEDGE CT-HDRBT of lymph node metastases is feasible and safe. CT-HDRBT might be a viable therapeutic alternative to obtain LTC in selected patients with isolated lymph node metastases.
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Affiliation(s)
- F Collettini
- Department of Diagnostic and Interventional Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
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Jiang W, Zeng ZC. Is it time to adopt external beam radiotherapy in the NCCN guidelines as a therapeutic strategy for intermediate/advanced hepatocellular carcinoma? Oncology 2013; 84 Suppl 1:69-74. [PMID: 23428862 DOI: 10.1159/000345893] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE External beam radiotherapy (EBRT) is recommended as a therapeutic strategy for stage III hepatocellular carcinoma (HCC) in national guidelines of the Chinese Society of Liver Disease and in Korea Liver Cancer Study Group practice guidelines, but has not been considered a therapeutic option for HCC in Western countries. In this study, we review evidence supporting EBRT as an option for HCC treatment. METHODS Retrospective investigation was made of 775 patient records of intermediate/advanced HCC treated in our hospital during the last 10 years, including 98 patients with confined intrahepatic tumor, 181 with portal vein (PV) or inferior vena cava (IVC) tumor thrombi, 191 with lymph node metastases, 55 with adrenal gland metastases, 205 with bone metastases, 13 with lung metastases and 32 with brain metastases. RESULTS Transcatheter arterial chemoembolization combined with radiotherapy was found to constitute an improved therapeutic strategy for unresectable but confined intrahepatic HCC with poor lipid accumulation. Survival of HCC patients with PV/IVC tumor thrombi was prolonged to 10.7 months by radiotherapy, and it was 8.0 months in patients with abdominal lymph node metastasis. Radiotherapy also shrinks adrenal and lung metastatic HCC lesions, resulting in median survival times of 13.6 and progression-free survival of 13.4 months, respectively. In bone metastatic HCC, radiotherapy significantly relieved symptoms, although median survival time was only 7.4 months. Radiotherapy is effective for treatment of intermediate/advanced stages of HCC. Although our finding is based only on retrospective analysis, no therapeutic option that provides better treatment than EBRT in this indication has thus far been identified. Because sorafenib has been recommended as a treatment strategy by the National Comprehensive Cancer Network (NCCN) for HCC, we compared the survival after EBRT with sorafenib treatment on the basis of published clinical data. From this comparison, we found that EBRT treatment was more effective than sorafenib for improving patient survival when tested on tumors of comparable metastatic size. CONCLUSION Based on the evidence reviewed, we propose that EBRT be included in the NCCN guideline as a treatment strategy for intermediate/advanced HCC.
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Affiliation(s)
- Wei Jiang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, PR China
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