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Kwon JH, Jwa EK, Lee JW, Tak E, Hwang S. Development and validation of a dynamic prognostic nomogram for conditional survival in hepatocellular carcinoma: an analysis from the Korea Liver Cancer Registry. Sci Rep 2025; 15:8654. [PMID: 40082572 PMCID: PMC11906733 DOI: 10.1038/s41598-025-92500-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 02/27/2025] [Indexed: 03/16/2025] Open
Abstract
Compared to overall survival, conditional survival is a more relevant measure of prognosis in surviving patients over time. This study developed and validated a nomogram-based dynamic prognostic model to predict the conditional survival estimates of patients with hepatocellular carcinoma (HCC) through an analysis of a nationwide cancer registry. This retrospective cohort study included 2492 patients with HCC registered in the Korea Liver Cancer Registry. Patients underwent hepatic resection (HR) from 2008 to 2017, were followed up until December 2019, and were divided into development and validation cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the risk factors for conditional survival of patients who underwent HR. The patients were scored based on the Cox regression coefficients; the nomogram was predicted by calculating the survival probability with Cox model. Our dynamic prognostic model nomogram for predicting conditional overall survival demonstrated Harrell's C-index of 0.622 and 0.674 in the development and validation sets; for conditional disease-specific survival, it was 0.623 and 0.686 in the development and validation sets. The prediction power of the model is applicable in clinical practice. Factors incorporated in our nomogram included age, albumin, the ADV score, lymph node metastasis, and T stage in American Joint Commission on Cancer staging system. We developed and validated a nomogram to predict conditional survival estimates for overall survival and disease-specific survival. The proposed nomogram incorporating the ADV score presents a more accurate and useful prognostic prediction for patients with HCC who received HR.
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Affiliation(s)
- Jae Hyun Kwon
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14068, South Korea.
| | - Eun-Kyoung Jwa
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jong Woo Lee
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14068, South Korea
| | - Eunyoung Tak
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
- Department of Biochemistry and Molecular Biology, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul, South Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Cumming J, Scott N, Howell J, Flores JE, Pavlyshyn D, Hellard ME, Winata LSH, Ryan M, Sutherland T, Thompson AJ, Doyle JS, Sacks-Davis R. Improving Hepatocellular Carcinoma Surveillance Outcomes in Patients with Cirrhosis after Hepatitis C Cure: A Modelling Study. Cancers (Basel) 2024; 16:2745. [PMID: 39123472 PMCID: PMC11312194 DOI: 10.3390/cancers16152745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. METHODS This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. CONCLUSIONS Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy.
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Affiliation(s)
- Jacob Cumming
- Disease Elimination Program, Burnet Institute, Melbourne, VIC 3004, Australia (J.S.D.); (R.S.-D.)
- Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia
| | - Nick Scott
- Disease Elimination Program, Burnet Institute, Melbourne, VIC 3004, Australia (J.S.D.); (R.S.-D.)
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia
| | - Jessica Howell
- Disease Elimination Program, Burnet Institute, Melbourne, VIC 3004, Australia (J.S.D.); (R.S.-D.)
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC 3065, Australia
- Department of Medicine, University of Melbourne, Melbourne, VIC 3052, Australia
| | - Joan Ericka Flores
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC 3065, Australia
| | - Damian Pavlyshyn
- Disease Elimination Program, Burnet Institute, Melbourne, VIC 3004, Australia (J.S.D.); (R.S.-D.)
| | - Margaret E. Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, VIC 3004, Australia (J.S.D.); (R.S.-D.)
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia
- Department of Infectious Diseases, The Alfred and Monash University, Melbourne, VIC 3004, Australia
- Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, VIC 3052, Australia
| | - Leon Shin-han Winata
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC 3065, Australia
| | - Marno Ryan
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC 3065, Australia
| | - Tom Sutherland
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC 3065, Australia
- Department of Medicine, University of Melbourne, Melbourne, VIC 3052, Australia
| | - Alexander J. Thompson
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC 3065, Australia
- Department of Medicine, University of Melbourne, Melbourne, VIC 3052, Australia
| | - Joseph S. Doyle
- Disease Elimination Program, Burnet Institute, Melbourne, VIC 3004, Australia (J.S.D.); (R.S.-D.)
- Department of Infectious Diseases, The Alfred and Monash University, Melbourne, VIC 3004, Australia
| | - Rachel Sacks-Davis
- Disease Elimination Program, Burnet Institute, Melbourne, VIC 3004, Australia (J.S.D.); (R.S.-D.)
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia
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Yang YP, Guo CJ, Gu ZX, Hua JJ, Zhang JX, Shi J. Conditional survival probability of distant-metastatic hepatocellular carcinoma: A population-based study. World J Gastrointest Oncol 2023; 15:1874-1890. [DOI: 10.4251/wjgo.v15.i11.1874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/20/2023] [Accepted: 09/06/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND The prognosis of many patients with distant metastatic hepatocellular carcinoma (HCC) improved after they survived for several months. Compared with traditional survival analysis, conditional survival (CS) which takes into account changes in survival risk could be used to describe dynamic survival probabilities.
AIM To evaluate CS of distant metastatic HCC patients.
METHODS Patients diagnosed with distant metastatic HCC between 2010 and 2015 were extracted from the Surveillance, Epidemiology and End Results database. Univariate and multivariate Cox regression analysis were used to identify risk factors for overall survival (OS), while competing risk model was used to identify risk factors for cancer-specific survival (CSS). Six-month CS was used to calculate the probability of survival for an additional 6 mo at a specific time after initial diagnosis, and standardized difference (d) was used to evaluate the survival differences between subgroups. Nomograms were constructed to predict CS.
RESULTS Positive α-fetoprotein expression, higher T stage (T3 and T4), N1 stage, non-primary site surgery, non-chemotherapy, non-radiotherapy, and lung metastasis were independent risk factors for actual OS and CSS through univariate and multivariate analysis. Actual survival rates decreased over time, while CS rates gradually increased. As for the 6-month CS, the survival difference caused by chemotherapy and radiotherapy gradually disappeared over time, and the survival difference caused by lung metastasis reversed. Moreover, the influence of age and gender on survival gradually appeared. Nomograms were fitted for patients who have lived for 2, 4 and 6 mo to predict 6-month conditional OS and CSS, respectively. The area under the curve (AUC) of nomograms for conditional OS decreased as time passed, and the AUC for conditional CSS gradually increased.
CONCLUSION CS for distant metastatic HCC patients substantially increased over time. With dynamic risk factors, nomograms constructed at a specific time could predict more accurate survival rates.
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Affiliation(s)
- Yong-Ping Yang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Cheng-Jun Guo
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Zhao-Xuan Gu
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jun-Jie Hua
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jia-Xuan Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jian Shi
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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Kwon MJ, Chang S, Kim JH, Han JW, Jang JW, Choi JY, Yoon SK, Sung PS. Factors associated with the survival outcomes of patients with untreated hepatocellular carcinoma: An analysis of nationwide data. Front Oncol 2023; 13:1142661. [PMID: 37035191 PMCID: PMC10073541 DOI: 10.3389/fonc.2023.1142661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/13/2023] [Indexed: 04/11/2023] Open
Abstract
Introduction In this study, we examined the natural course of untreated hepatocellular carcinoma (HCC) and identified predictors of survival in an area where hepatitis B is the predominant cause of HCC. Methods We identified 1,045 patients with HCC who did not receive HCC treatment and were registered in the Korean Primary Liver Cancer Registry between 2008 and 2014, and were followed-up up to December 2018. Thereafter, we analyzed the clinical characteristics of patients who survived for <12 or ≥12 months. A Cox proportional regression model was used to identify the variables associated with patient survival. Results and discussion The mean age of the untreated patients at HCC diagnosis was 59.6 years, and 52.1% of patients had hepatitis B. Most untreated patients (94.2%) died during the observation period. The median survival times for each Barcelona Clinic Liver Cancer (BCLC) stage were as follows: 31.0 months for stage 0/A (n = 123), 10.0 months for stage B (n = 96), 3.0 months for stage C (n = 599), and 1.0 month for stage D (n = 227). Multivariate Cox regression analysis demonstrated that BCLC stage D (hazard ratio, 4.282; P < 0.001), model for end-stage liver disease (MELD) score ≥10 (HR, 1.484; P < 0.001), and serum alpha-fetoprotein (AFP) level ≥1,000 ng/mL (HR, 1.506; P < 0.001) were associated with poor survival outcomes in patients with untreated HCC. In untreated patients with HCC, advanced stage BCLC, serum AFP level ≥1,000 ng/mL, and MELD score ≥10 were significantly associated with overall survival.
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Affiliation(s)
- Min Jung Kwon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soy Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Won Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Young Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Kew Yoon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Pil Soo Sung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Kong J, Huang T, Zhang J, Tang S, Liu H, Liu J, Zeng Y. Analysis of conditional survival in primary hepatocellular carcinoma after narrow-margin hepatectomy: a large-sample, dual-centre, retrospective study. HPB (Oxford) 2023; 25:179-188. [PMID: 36443197 DOI: 10.1016/j.hpb.2022.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 06/21/2022] [Accepted: 08/15/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Overall survival (OS) reflects the constant hazard and survival probabilities calculated from the initial follow-up. Conditional survival (CS) dynamically estimates prognosis based on survival time after treatment. This study aimed to estimate CS in patients who had undergone narrow-margin hepatectomy for primary hepatocellular carcinoma. METHODS The clinical data of 1010 eligible patients between 2012 and 2017 were retrospectively analysed. The equation CS1=OS(x+1)/OS(x) was used to calculate the probability of an additional 1-year survival in patients who had survived for x years. RESULTS Tumour differentiation, microvascular invasion, and tumour emboli were independent risk factors for OS. Actuarial survival decreased from 91.53% at 1 year after hepatectomy to 48.92% at 4 years, whereas CS1 increased from 69.45% at 1 year to 94.62% at 4 years. The difference was more obvious in the tumour-emboli subgroup, with an OS of 26.38% at 5 years versus a CS1 of 88.91% at 4 years following narrow-margin hepatectomy (Δ62.53%). CONCLUSION CS is potentially useful in providing a dynamic evaluation of survival, predicting prognosis more accurately than OS during follow-up, and formulating more appropriate treatment measures based on disease progression.
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Affiliation(s)
- Jie Kong
- The First Clinical Medical College of Fujian Medical University, Fuzhou, 350025, China; Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Tingfeng Huang
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China; Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Jianxi Zhang
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China; Department of Hepatobiliary Surgery, Xiamen Hospital, Beijing University of Chinese Medicine, Xiamen, Fujian, 361000, China
| | - Shichuan Tang
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China; Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Hongzhi Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China; Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Jingfeng Liu
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China; Fujian Provincial Cancer Hospital, Fuzhou, 350025, China
| | - Yongyi Zeng
- The First Clinical Medical College of Fujian Medical University, Fuzhou, 350025, China; Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China; Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
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Yan L, Chen F, Chen L, Lin J, Chen Q, Bao X, Qiu Y, Lin L, Zheng X, Pan L, Wang J, Hu Z, Liu F, He B, Shi B. Dynamic evaluation of conditional survival in patients with oral squamous cell carcinoma after surgical resection: A large-scale prospective study. Oral Oncol 2020; 104:104639. [PMID: 32220811 DOI: 10.1016/j.oraloncology.2020.104639] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 03/01/2020] [Accepted: 03/08/2020] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To dynamically estimate conditional survival (CS) probabilities for patients with oral squamous cell carcinoma (OSCC) after surgical resection. METHOD A large-scale prospective study was performed involving 1147 eligible OSCC patients from December 2002 to June 2018. Follow-up was completed on January 8, 2019. Cox proportional hazards models were utilized to assess prognostic factors related to overall survival (OS). Three-year CS (CS3) of patients who had already survived x years was calculated as the formula CS3 = OS(x+3)/OS(x). RESULTS CS3 estimates at the time of 0, 1, 3, 5-year survival demonstrated a tendency increase over time, and improved from 78.47% to 82.25%, while the postoperative actuarial OS decreased from 78.47% at 3 years to 57.12% at 8 years. Moreover, the differences between CS3 and actuarial OS were more obvious among patients with unfavorable tumor characteristics. Disparities in CS3 across all subgroups of tumor features illustrated more prominent at baseline (d range: 0.24 to 0.40), while the gaps would narrow if those patients have already survived 5 years (d range: -0.01 to 0.18). CONCLUSION Our findings suggest that survival profiles of OSCC patients evolve and increase over time following resection, especially for those with unfavorable tumor features at initial diagnosis. CS estimates may provide more accurate prediction and guide surveillance schedules.
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Affiliation(s)
- Lingjun Yan
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Fa Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Lin Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Jing Lin
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Qing Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Xiaodan Bao
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Yu Qiu
- Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Lisong Lin
- Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Xiaoyan Zheng
- Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Lizhen Pan
- Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Jing Wang
- Laboratory Center, The Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Fujian, China
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Fengqiong Liu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China
| | - Baochang He
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fujian, China.
| | - Bin Shi
- Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University, Fujian, China.
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Kim J, Chang JW, Park JY. Nivolumab for Advanced Hepatocellular Carcinoma with Multiple Lung Metastases after Sorafenib Failure. JOURNAL OF LIVER CANCER 2020; 20:72-77. [PMID: 37383058 PMCID: PMC10035702 DOI: 10.17998/jlc.20.1.72] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 06/30/2023]
Abstract
Over the past decade, standard first-line systemic treatment of advanced hepatocellular carcinoma (HCC) has been based on sorafenib, a multi-kinase inhibitor. Regorafenib, another tyrosine kinase inhibitor, is the only second-line therapy that has been globally approved after progression under sorafenib treatment. Recently, immunotherapeutic agents have emerged as promising treatment options in many different malignancies, including advanced HCC. Nivolumab is the first immunotherapy approved by the Food and Drug Administration for use in HCC patients with advanced-stage second-line after sorafenib failure. In this report, a case of advanced HCC with multiple lung metastases in which a complete response and maintained progression-free status was achieved with nivolumab, following the failure of transarterial chemoembolization and sorafenib is presented. We hope this report may help expand the clinical application of second-line treatment.
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Affiliation(s)
- Jaewoong Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Won Chang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Yonsei University Health System, Seoul, Korea
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Lee HW, Cho KJ, Park JY. Current Status and Future Direction of Immunotherapy in Hepatocellular Carcinoma: What Do the Data Suggest? Immune Netw 2020; 20:e11. [PMID: 32158599 PMCID: PMC7049588 DOI: 10.4110/in.2020.20.e11] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/07/2020] [Accepted: 02/08/2020] [Indexed: 02/07/2023] Open
Abstract
Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.
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Affiliation(s)
- Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institue of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
| | - Kyung Joo Cho
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
- BK21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institue of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
- BK21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
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Development of a New Nomogram Including Neutrophil-to-Lymphocyte Ratio to Predict Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Cancers (Basel) 2019; 11:cancers11040509. [PMID: 30974843 PMCID: PMC6520830 DOI: 10.3390/cancers11040509] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/29/2019] [Accepted: 04/08/2019] [Indexed: 12/11/2022] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) has recently been reported to predict the prognosis of hepatocellular carcinoma (HCC). We explored whether NLR predicted the survival of patients with HCC undergoing transarterial chemoembolization (TACE), and developed a predictive model. In total, 1697 patients with HCC undergoing TACE as first-line therapy at two university hospitals were enrolled (derivation set n = 921, internal validation set n = 395, external validation set n = 381). The tumor size, tumor number, AFP level, vascular invasion, Child–Pugh score, objective response after TACE, and NLR, selected as predictors of overall survival (OS) via multivariate Cox’s regression model, were incorporated into a 14-point risk prediction model (SNAVCORN score). The time-dependent areas under the receiver-operating characteristic curves for OS at 1, 3, and 5 years predicted by the SNAVCORN score were 0.812, 0.734, and 0.700 in the derivation set. Patients were stratified into three risk groups by SNAVCORN score (low, 0–4; intermediate, 5–9; high, 10–14). Compared with the low-risk group, the intermediate-risk (HR 3.10, p < 0.001) and high-risk (HR 7.37, p < 0.001) groups exhibited significantly greater mortality. The prognostic performance of the SNAVCORN score including NLR in patients with HCC treated with TACE was remarkable, much better than those of the conventional scores. The SNAVCORN score will guide future HCC treatment decisions.
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