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Deng W, Xie J, Wang T, Luo L, Zhu G, Xiao Y, Tao J, Lin L, Ge X, Wen W, Wang M, Yu B, Liu Y, Luo R, Wan R, Hu Z, Shan R. The safety and efficacy of tyrosine kinase inhibitors and programmed cell death protein- 1 inhibitors combined with HAIC/TACE in the treatment of recurrent unresectable hepatocellular carcinoma. BMC Cancer 2025; 25:779. [PMID: 40281460 PMCID: PMC12032721 DOI: 10.1186/s12885-025-14185-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 04/18/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) frequently recurs after surgical treatment, necessitating effective postoperative recurrence management for improved long-term patient outcomes. Currently, no standardized treatment approach exists for recurrent unresectable HCC. This study aims to investigate the safety and efficacy of combining tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors with hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) in the treatment of recurrent unresectable HCC. METHODS A retrospective analysis was conducted on clinical data from 83 patients diagnosed with unresectable recurrent HCC. Patients were categorized into three groups based on their treatment regimens: HAIC combined with TKIs and PD-1 inhibitors (HTP), TACE combined with TKIs and PD-1 inhibitors (TTP), and TACE alone. Treatment efficacy and safety were compared among these groups, and potential risk factors were identified. RESULTS The median progression-free survival (PFS) for patients in the HTP group, TTP group, and TACE alone group was found to be 13.7, 9.2, and 2.5 months (p = 0.001, p = 0.002). According to the mRECIST criteria, the disease control rates (DCR) in the HTP, TTP and TACE groups was 89.7%, 75.0%, 50.0% (p = 0.002); objective response rates (ORR) was 44.8%, 35%, 14.7% (p = 0.037); and complete response (CR) was 17.2%, 0, 0 (p = 0.005). No serious adverse reactions were observed in the HTP and TTP groups. CONCLUSION The HTP and TTP groups were safe and effective compared to TACE alone for the treatment of recurrent unresectable hepatocellular carcinoma, and the HTP group demonstrated a superior CR.
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Affiliation(s)
- Wei Deng
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Jin Xie
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Tao Wang
- Department of Day Surgery Ward, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Laihui Luo
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Guoqing Zhu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Yongqiang Xiao
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Jiahao Tao
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Liucong Lin
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Xian Ge
- Department of Pathology, Jiangxi Province, The First Affiliated Hospital of Nanchang University, Nanchang City, 330006, China
| | - Wu Wen
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Minglong Wang
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Bin Yu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Yu Liu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Rongguang Luo
- Department of Medical Imaging and Interventional Radiology, Jiangxi Province, The First Affiliated Hospital of Nanchang University, Nanchang City, 330006, China
| | - Renhua Wan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China
| | - Zhigao Hu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China.
| | - Renfeng Shan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, China.
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Yang J, Dong X, Jin S, Wang S, Wang Y, Zhang L, Wei Y, Wu Y, Wang L, Zhu L, Feng Y, Gan M, Hu H, Ji W. Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Microvascular Invasion in Hepatocellular Carcinoma. Acad Radiol 2025; 32:146-156. [PMID: 39025700 DOI: 10.1016/j.acra.2024.07.007] [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: 04/16/2024] [Revised: 06/26/2024] [Accepted: 07/02/2024] [Indexed: 07/20/2024]
Abstract
RATIONALE AND OBJECTIVES To develop and validate a clinical-radiomics model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of Vessels encapsulating tumor clusters (VETC)- microvascular invasion (MVI) and prognosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS 219 HCC patients from Institution 1 were split into internal training and validation groups, with 101 patients from Institution 2 assigned to external validation. Histologically confirmed VETC-MVI pattern categorizing HCC into VM-HCC+ (VETC+/MVI+, VETC-/MVI+, VETC+/MVI-) and VM-HCC- (VETC-/MVI-). The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI. Six radiomics models (intratumor and peritumor in AP, PP, and DP of DCE-MRI) and one clinical model were developed for assessing VM-HCC. Establishing intra-tumoral and peri-tumoral models through combining intratumor and peritumor features. The best-performing radiomics model and the clinical model were then integrated to create a Combined model. RESULTS In institution 1, pathological VM-HCC+ were confirmed in 88 patients (training set: 61, validation set: 27). In internal testing, the Combined model had an AUC of 0.85 (95% CI: 0.76-0.93), which reached an AUC of 0.75 (95% CI: 0.66-0.85) in external validation. The model's predictions were associated with early recurrence and progression-free survival in HCC patients. CONCLUSIONS The clinical-radiomics model offers a non-invasive approach to discern VM-HCC and predict HCC patients' prognosis preoperatively, which could offer clinicians valuable insights during the decision-making phase.
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Affiliation(s)
- Jiawen Yang
- Department of Radiology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang 317000, China; Department of Radiology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, China.
| | - Xue Dong
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
| | - Shengze Jin
- Department of Radiology, Taizhou Hospital of Zhejiang Province, Shaoxing University, Taizhou 318000 Zhejiang, China.
| | - Sheng Wang
- Department of Radiology, Taizhou First People's Hospital, Wenzhou Medical College, Taizhou 318020 Zhejiang, China.
| | - Yanna Wang
- Department of Radiology, Taizhou Central Hospital,Wenzhou Medical University, Taizhou 318000 Zhejiang,China.
| | - Limin Zhang
- Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Yuguo Wei
- Precision Health Institution, GE Healthcare, 310000 Xihu District, Hangzhou, China.
| | - Yitian Wu
- Department of Radiology, Taizhou Hospital of Zhejiang Province, Shaoxing University, Taizhou 318000 Zhejiang, China.
| | - Lingxia Wang
- Department of Radiology, Taizhou Hospital, Zhejiang University, Taizhou 318000 Zhejiang, China.
| | - Lingwei Zhu
- Department of Radiology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang 317000, China.
| | - Yuyi Feng
- Department of Radiology, Taizhou Hospital of Zhejiang Province, Shaoxing University, Taizhou 318000 Zhejiang, China.
| | - Meifu Gan
- Department of Pathology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang 317000, China.
| | - Hongjie Hu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016 Hangzhou, People's Republic of China.
| | - Wenbin Ji
- Department of Radiology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang 317000, China; Key Laboratory of evidence-based Radiology of Taizhou, Linhai 317000, Zhejiang, China.
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Fei X, Zhu L, Han P, Jiang B, Li M, Li N, Jiao Z, Clevert DA, Luo Y. Value of high frame rate contrast-enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma. Insights Imaging 2024; 15:273. [PMID: 39546065 PMCID: PMC11568103 DOI: 10.1186/s13244-024-01821-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 09/10/2024] [Indexed: 11/17/2024] Open
Abstract
OBJECTIVES To investigate the value of vascular morphology on high frame rate contrast-enhanced ultrasound (H-CEUS) and CEUS Li-RADS in predicting microvascular invasion (MVI), Ki-67 expression and recurrence of hepatocellular carcinoma (HCC). METHODS This retrospective study enrolled 78 patients with single HCC diagnosed by postoperative pathology between January 1, 2021, and June 30, 2022. All patients underwent ultrasound and H-CEUS examination before operation. H-CEUS image features and CEUS Li-RADS were compared in different MVI status and Ki-67 level. Multiple logistic regression analysis was performed to select independent variables for MVI. Differences in recurrence among different H-CEUS image features, MVI status and Ki-67 level were further analyzed. RESULTS Tumor shape, vascular morphology, LR-M category, necrosis and AFP level were different between the MVI-positive group and MVI-negative group (p < 0.05). Vascular morphology and LR-M category were independent risk factors related to MVI (p < 0.05). Vascular morphology was also different between the high Ki-67 expression group and low Ki-67 expression group (p < 0.05). Vascular morphology, MVI status and Ki-67 expression were different between the recurrence group and no recurrence group (p < 0.05). CONCLUSION The vascular morphology of HCC on H-CEUS can indicate the risk of MVI status, Ki-67 expression and recurrence, which provides a feasible imaging technique for predicting the prognosis before operation. CRITICAL RELEVANCE STATEMENT H-CEUS shows the different vascular morphology of HCC in arterial phase and indicates the risk of MVI, Ki-67 expression and recurrence, which provides a feasible imaging technique for clinician to judge the risk of MVI pre-operation and adopt appropriate treatment. KEY POINTS H-CEUS can clearly show different vascular morphology of HCC in arterial phase. Vascular morphology on H-CEUS is associated with MVI status, Ki-67 expression and HCC recurrence. Preoperative MVI and Ki-67 expression prediction could help surgeons choose a more appropriate treatment plan.
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Affiliation(s)
- Xiang Fei
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Lianhua Zhu
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Peng Han
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Bo Jiang
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Miao Li
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Nan Li
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Ziyu Jiao
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Dirk-André Clevert
- Interdisciplinary Ultrasound-Center University of Munich-Grosshadern Campus, Munich, Germany.
| | - Yukun Luo
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
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Tu S, He Y, Shu X, Bao S, Wu Z, Cui L, Luo L, Li Y, He K. Development and validation of a nomogram for predicting microvascular invasion and evaluating the efficacy of postoperative adjuvant transarterial chemoembolization. Heliyon 2024; 10:e36770. [PMID: 39290260 PMCID: PMC11407026 DOI: 10.1016/j.heliyon.2024.e36770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 04/03/2024] [Accepted: 08/21/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND AND AIM Accurately predicting microvascular invasion (MVI) before surgery is beneficial for surgical decision-making, and some high-risk hepatocellular carcinoma (HCC) patients may benefit from postoperative adjuvant transarterial chemoembolization (PA-TACE). The purpose of this study was to develop and validate a novel nomogram for predicting MVI and assessing the survival benefits of selectively receiving PA-TACE in HCC patients. METHODS The 1372 HCC patients who underwent hepatectomy at four medical institutions were randomly divided into training and validation datasets according to a 7:3 ratio. We developed and validated a nomogram for predicting MVI using preoperative clinical data and further evaluated the survival benefits of selective PA-TACE in different risk subgroups. RESULTS The nomogram for predicting MVI integrated alpha-fetoprotein, tumor diameter, tumor number, and tumor margin, with an area under the curve of 0.724, which was greater than that of any single predictive factor. The calibration curve, decision curve, and clinical impact curve demonstrated that the nomogram had strong predictive performance. Risk stratification based on the nomogram revealed that patients in the low-risk group did not achieve better DFS and OS with PA-TACE (all p > 0.05), while patients in the medium-to-high risk groups could benefit from higher DFS (Medium-risk, p = 0.039; High-risk, p = 0.027) and OS (Medium-risk, p = 0.001; High-risk, p = 0.019) with PA-TACE. CONCLUSIONS The nomogram predicting MVI demonstrated strong predictive performance, and its risk stratification aided in identifying different subgroups of HCC patients who may benefit from PA-TACE with improved survival outcomes.
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Affiliation(s)
- Shuju Tu
- Department of HepatobiliarySurgery, Xiantao First People's Hospital, Xiantao City, Hubei Province, 433000, China
| | - Yongzhu He
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen City, Guangdong Province, 518020, China
| | - Xufeng Shu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University (The First Clinical Medical College of Nanchang University), Nanchang City, Jiangxi Province, 330006, China
| | - Shiyun Bao
- Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen City, Guangdong Province, 518020, China
| | - Zhao Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University (The Second Clinical Medical College of Nanchang University), Nanchang City, Jiangxi Province, 330006, China
| | - Lifeng Cui
- Maoming People's Hospital, Maoming City, Guangdong Province, 525000, China
| | - Laihui Luo
- Department of General Surgery, The First Affiliated Hospital of Nanchang University (The First Clinical Medical College of Nanchang University), Nanchang City, Jiangxi Province, 330006, China
| | - Yong Li
- Department of General Surgery, The First Affiliated Hospital of Nanchang University (The First Clinical Medical College of Nanchang University), Nanchang City, Jiangxi Province, 330006, China
| | - Kun He
- Department of Hepatobiliary Surgery, Zhongshan People's Hospital (Zhongshan Hospital Affiliated to Sun Yat-sen University), ZhongshanCity, Guangdong Province, 528400, China
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Wang G, Ding F, Chen K, Liang Z, Han P, Wang L, Cui F, Zhu Q, Cheng Z, Chen X, Huang C, Cheng H, Wang X, Zhao X. CT-based radiomics nomogram to predict proliferative hepatocellular carcinoma and explore the tumor microenvironment. J Transl Med 2024; 22:683. [PMID: 39218938 PMCID: PMC11367757 DOI: 10.1186/s12967-024-05393-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 06/12/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Proliferative hepatocellular carcinomas (HCCs) is a class of aggressive tumors with poor prognosis. We aimed to construct a computed tomography (CT)-based radiomics nomogram to predict proliferative HCC, stratify clinical outcomes and explore the tumor microenvironment. METHODS Patients with pathologically diagnosed HCC following a hepatectomy were retrospectively collected from two medical centers. A CT-based radiomics nomogram incorporating radiomics model and clinicoradiological features to predict proliferative HCC was constructed using the training cohort (n = 184), and validated using an internal test cohort (n = 80) and an external test cohort (n = 89). The predictive performance of the nomogram for clinical outcomes was evaluated for HCC patients who underwent surgery (n = 201) or received transarterial chemoembolization (TACE, n = 104). RNA sequencing data and histological tissue slides from The Cancer Imaging Archive database were used to perform transcriptomics and pathomics analysis. RESULTS The areas under the receiver operating characteristic curve of the radiomics nomogram to predict proliferative HCC were 0.84, 0.87, and 0.85 in the training, internal test, and external test cohorts, respectively. The radiomics nomogram could stratify early recurrence-free survivals in the surgery outcome cohort (hazard ratio [HR] = 2.25; P < 0.001) and progression-free survivals in the TACE outcome cohort (HR = 2.21; P = 0.03). Transcriptomics and pathomics analysis indicated that the radiomics nomogram was associated with carbon metabolism, immune cells infiltration, TP53 mutation, and heterogeneity of tumor cells. CONCLUSION The CT-based radiomics nomogram could predict proliferative HCC, stratify clinical outcomes, and measure a pro-tumor microenvironment.
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Affiliation(s)
- Gongzheng Wang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China
| | - Feier Ding
- Department of Radiology, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China
| | - Kaige Chen
- Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Zhuoshuai Liang
- Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun, 130021, China
| | - Pengxi Han
- Department of Radiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China
| | - Linxiang Wang
- Department of Radiology, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China
| | - Fengyun Cui
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Zhaoping Cheng
- Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China
| | - Xingzhi Chen
- Department of Research Collaboration, R&D Center, Beijing Deepwise & League of PHD Technology Co., Ltd, Beijing, 100080, People's Republic of China
| | - Chencui Huang
- Department of Research Collaboration, R&D Center, Beijing Deepwise & League of PHD Technology Co., Ltd, Beijing, 100080, People's Republic of China
| | - Hongxia Cheng
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China.
| | - Ximing Wang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China.
| | - Xinya Zhao
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China.
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Liang ZN, Wang H, Cui WC, Zhou W, Wang S, Zhang ZY, Wu W, Yan K, Ji YL, Yang W. Multimode Ultrasound Model for Predicting the Early Treatment Response of Anti-VEGF Agents Plus Anti-PD-1 Antibody in Patients with Unresectable Hepatocellular Carcinoma. ULTRASOUND IN MEDICINE & BIOLOGY 2024; 50:1318-1328. [PMID: 38871491 DOI: 10.1016/j.ultrasmedbio.2024.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 04/16/2024] [Accepted: 05/02/2024] [Indexed: 06/15/2024]
Abstract
OBJECTIVE The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. METHODS A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. RESULTS On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. CONCLUSION Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.
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Affiliation(s)
- Zi-Nan Liang
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital, Haidian District, Beijing, China
| | - Hong Wang
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital, Haidian District, Beijing, China
| | - Wen-Chao Cui
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying District, Dongying, Shandong Province, China
| | - Wei Zhou
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying District, Dongying, Shandong Province, China
| | - Song Wang
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital, Haidian District, Beijing, China
| | - Zhong-Yi Zhang
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital, Haidian District, Beijing, China
| | - Wei Wu
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital, Haidian District, Beijing, China
| | - Kun Yan
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital, Haidian District, Beijing, China
| | - Yong-Li Ji
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying District, Dongying, Shandong Province, China
| | - Wei Yang
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital, Haidian District, Beijing, China.
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Fan W, Zhu B, Chen S, Wu Y, Zhao X, Qiao L, Huang Z, Tang R, Chen J, Lau WY, Chen M, Li J, Kuang M, Peng Z. Survival in Patients With Recurrent Intermediate-Stage Hepatocellular Carcinoma: Sorafenib Plus TACE vs TACE Alone Randomized Clinical Trial. JAMA Oncol 2024; 10:1047-1054. [PMID: 38900435 PMCID: PMC11190833 DOI: 10.1001/jamaoncol.2024.1831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 12/29/2023] [Indexed: 06/21/2024]
Abstract
Importance Transarterial chemoembolization (TACE) is commonly used to treat patients with recurrent intermediate-stage hepatocellular carcinoma (HCC) and positive microvascular invasion (MVI); however, TACE alone has demonstrated unsatisfactory survival benefits. A previous retrospective study suggested that TACE plus sorafenib (SOR-TACE) may be a better therapeutic option compared with TACE alone. Objective To investigate the clinical outcomes of SOR-TACE vs TACE alone for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI. Design, Setting, and Participants In this phase 3, open-label, multicenter randomized clinical trial, patients with recurrent intermediate-stage HCC and positive MVI were randomly assigned in a 1:1 ratio via a computerized minimization technique to either SOR-TACE treatment or TACE alone. This trial was conducted at 5 hospitals in China, and enrolled patients from October 2019 to December 2021, with a follow-up period of 24 months. Data were analyzed from June 2023 to September 2023. Interventions Randomization to on-demand TACE (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter: 150-350 μm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 μm or 300-500 μm]) (TACE group) or sorafenib, 400 mg, twice daily plus on-demand TACE (SOR-TACE group) (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter, 150-350 μm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 μm or 300-500 μm]). Main Outcomes and Measures The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. Results A total of 162 patients (median [range] age, 55 [28-75] years; 151 males [93.2%]), were randomly assigned to be treated with either SOR-TACE (n = 81) or TACE alone (n = 81). The median overall survival was significantly longer in the SOR-TACE group than in the TACE group (22.2 months vs 15.1 months; hazard ratio [HR], 0.55; P < .001). SOR-TACE also prolonged progression-free survival (16.2 months vs 11.8 months; HR, 0.54; P < .001), and improved the objective response rate when compared with TACE alone based on the modified Response Evaluation Criteria in Solid Tumors criteria (80.2% vs 58.0%; P = .002). Any grade adverse events were more common in the SOR-TACE group, but all adverse events responded well to treatment. No unexpected adverse events or treatment-related deaths occurred in this study. Conclusions and Relevance The results of this randomized clinical trial demonstrated that SOR-TACE achieved better clinical outcomes than TACE alone. These findings suggest that combined treatment should be used for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI. Trial Registration ClinicalTrials.gov Identifier: NCT04103398.
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Affiliation(s)
- Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bowen Zhu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuling Chen
- Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yanqin Wu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiao Zhao
- Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liangliang Qiao
- Department of Interventional Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhen Huang
- Department of Interventional Angiology, Huizhou First People’s Hospital, Huizhou, China
| | - Rong Tang
- Department of Hepatopancreatobiliary Surgery, Hainan General Hospital, Haikou, China
| | - Jinghua Chen
- Cancer Center, Guangzhou Twelfth People’s Hospital, Guangzhou, China
| | - Wan Yee Lau
- Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wale Hospital, Shatin, New Territories, Hongkong, SAR, China
| | - Minshan Chen
- Department of Liver Surgery, Cancer Center of Sun Yat-sen University, Guangzhou, China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ming Kuang
- Center of Hepato-PancreatoBiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhenwei Peng
- Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Lei Y, Feng B, Wan M, Xu K, Cui J, Ma C, Sun J, Yao C, Gan S, Shi J, Cui E. Predicting microvascular invasion in hepatocellular carcinoma with a CT- and MRI-based multimodal deep learning model. Abdom Radiol (NY) 2024; 49:1397-1410. [PMID: 38433144 DOI: 10.1007/s00261-024-04202-1] [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: 10/29/2023] [Revised: 01/04/2024] [Accepted: 01/12/2024] [Indexed: 03/05/2024]
Abstract
PURPOSE To investigate the value of a multimodal deep learning (MDL) model based on computed tomography (CT) and magnetic resonance imaging (MRI) for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS A total of 287 patients with HCC from our institution and 58 patients from another individual institution were included. Among these, 119 patients with only CT data and 116 patients with only MRI data were selected for single-modality deep learning model development, after which select parameters were migrated for MDL model development with transfer learning (TL). In addition, 110 patients with simultaneous CT and MRI data were divided into a training cohort (n = 66) and a validation cohort (n = 44). We input the features extracted from DenseNet121 into an extreme learning machine (ELM) classifier to construct a classification model. RESULTS The area under the curve (AUC) of the MDL model was 0.844, which was superior to that of the single-phase CT (AUC = 0.706-0.776, P < 0.05), single-sequence MRI (AUC = 0.706-0.717, P < 0.05), single-modality DL model (AUCall-phase CT = 0.722, AUCall-sequence MRI = 0.731; P < 0.05), clinical (AUC = 0.648, P < 0.05), but not to that of the delay phase (DP) and in-phase (IP) MRI and portal venous phase (PVP) CT models. The MDL model achieved better performance than models described above (P < 0.05). When combined with clinical features, the AUC of the MDL model increased from 0.844 to 0.871. A nomogram, combining deep learning signatures (DLS) and clinical indicators for MDL models, demonstrated a greater overall net gain than the MDL models (P < 0.05). CONCLUSION The MDL model is a valuable noninvasive technique for preoperatively predicting MVI in HCC.
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Affiliation(s)
- Yan Lei
- Department of Radiology, Jiangmen Central Hospital, 23 Beijie Haibang Street, Jiangmen, People's Republic of China
- Zunyi Medical University, 1 Xiaoyuan Road, Zunyi, People's Republic of China
| | - Bao Feng
- Laboratory of Intelligent Detection and Information Processing, School of Electronic Information and Automation, Guilin University of Aerospace Technology, 2 Jinji Road, Guilin, People's Republic of China
| | - Meiqi Wan
- Department of Radiology, Jiangmen Central Hospital, 23 Beijie Haibang Street, Jiangmen, People's Republic of China
- Zunyi Medical University, 1 Xiaoyuan Road, Zunyi, People's Republic of China
| | - Kuncai Xu
- Laboratory of Intelligent Detection and Information Processing, School of Electronic Information and Automation, Guilin University of Aerospace Technology, 2 Jinji Road, Guilin, People's Republic of China
| | - Jin Cui
- Department of Radiology, Jiangmen Central Hospital, 23 Beijie Haibang Street, Jiangmen, People's Republic of China
| | - Changyi Ma
- Department of Radiology, Jiangmen Central Hospital, 23 Beijie Haibang Street, Jiangmen, People's Republic of China
| | - Junqi Sun
- Department of Radiology, Yuebei People's Hospital, 133 Huimin Street, Shaoguan, People's Republic of China
| | - Changyin Yao
- Department of Radiology, Jiangmen Central Hospital, 23 Beijie Haibang Street, Jiangmen, People's Republic of China
- Guangdong Medical University, 2 Wenming East Road, Zhanjiang, People's Republic of China
| | - Shiman Gan
- Department of Radiology, Jiangmen Central Hospital, 23 Beijie Haibang Street, Jiangmen, People's Republic of China
- Guangdong Medical University, 2 Wenming East Road, Zhanjiang, People's Republic of China
| | - Jiangfeng Shi
- Laboratory of Intelligent Detection and Information Processing, School of Electronic Information and Automation, Guilin University of Aerospace Technology, 2 Jinji Road, Guilin, People's Republic of China
| | - Enming Cui
- Department of Radiology, Jiangmen Central Hospital, 23 Beijie Haibang Street, Jiangmen, People's Republic of China.
- Zunyi Medical University, 1 Xiaoyuan Road, Zunyi, People's Republic of China.
- Guangdong Medical University, 2 Wenming East Road, Zhanjiang, People's Republic of China.
- Jiangmen Key Laboratory of Artificial Intelligence in Medical Image Computation and Application, 23 Beijie Haibang Street, Jiangmen, People's Republic of China.
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9
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Sun B, Ji WD, Wang WC, Chen L, Ma JY, Tang EJ, Lin MB, Zhang XF. Circulating tumor cells participate in the formation of microvascular invasion and impact on clinical outcomes in hepatocellular carcinoma. Front Genet 2023; 14:1265866. [PMID: 38028589 PMCID: PMC10652898 DOI: 10.3389/fgene.2023.1265866] [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: 07/28/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Although the treatment strategies have been improved in recent years, the long-term prognosis of HCC is far from satisfactory mainly due to high postoperative recurrence and metastasis rate. Vascular tumor thrombus, including microvascular invasion (MVI) and portal vein tumor thrombus (PVTT), affects the outcome of hepatectomy and liver transplantation. If vascular invasion could be found preoperatively, especially the risk of MVI, more reasonable surgical selection will be chosen to reduce the risk of postoperative recurrence and metastasis. However, there is a lack of reliable prediction methods, and the formation mechanism of MVI/PVTT is still unclear. At present, there is no study to explore the possibility of tumor thrombus formation from a single circulating tumor cell (CTC) of HCC, nor any related study to describe the possible leading role and molecular mechanism of HCC CTCs as an important component of MVI/PVTT. In this study, we review the current understanding of MVI and possible mechanisms, discuss the function of CTCs in the formation of MVI and interaction with immune cells in the circulation. In conclusion, we discuss implications for potential therapeutic targets and the prospect of clinical treatment of HCC.
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Affiliation(s)
- Bin Sun
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wei-Dan Ji
- Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital and National Center for Liver Cancer, Navy Military Medical University, Shanghai, China
| | - Wen-Chao Wang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lei Chen
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jun-Yong Ma
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, China
| | - Er-Jiang Tang
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Mou-Bin Lin
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiao-Feng Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, China
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10
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Xu Y, Li Z, Zhou Y, Yang Y, Ouyang J, Li L, Huang Z, Ye F, Ying J, Zhao H, Zhou J, Zhao X. Using immunovascular characteristics to predict very early recurrence and prognosis of resectable intrahepatic cholangiocarcinoma. BMC Cancer 2023; 23:1009. [PMID: 37858111 PMCID: PMC10588260 DOI: 10.1186/s12885-023-11476-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: 02/02/2023] [Accepted: 10/03/2023] [Indexed: 10/21/2023] Open
Abstract
OBJECTIVE To predict the very early recurrence (VER) of patients with intrahepatic cholangiocarcinoma (ICC) based on TLSs and MVI status, and further perform prognosis stratifications. METHODS A total of 160, 51 ICC patients from two institutions between May 2012 and July 2022 were retrospectively included as training, external validation cohort. Clinical, radiological and pathological variables were evaluated and collected. Univariate and multivariate analysis were applied to select the significant factors related to VER of ICC. The factors selected were combined to perform stratification of overall survival (OS) using the Kaplan-Meier method with the log-rank test. RESULTS Overall, 39 patients (24.4%) had VER, whereas 121 (75.6%) did not (non-VER group). In the training cohort, the median OS was 40.5 months (95% CIs: 33.2-47.7 months). The VER group showed significantly worse OS than the non-VER group (median OS: 14.8, 95% CI:11.6-18.0 months vs. 53.4, 34.3-72.6 months; p<0.001), and it was confirmed in the validation cohort (median OS: 22.1, 95% CI: 8.8-35.4 months vs. 40.1, 21.2-59.0 months; p = 0.003). According to the univariate analysis, four variables were significantly different between the VER group and non-VER group (TLSs status, p = 0.028; differentiation, p = 0.023; MVI status, p = 0.012; diameter, p = 0.028). According to the multivariate analysis, MVI-positive status was independently associated with a higher probability of VER (odds ratio [OR], 2.5; 95% CIs,1.16-5.18; p = 0.018), whereas intra-tumoral TLSs-positive status was associated with lower odds of VER (OR, 0.43; 95% CIs, 0.19-0.97; p = 0.041). Based on the TLSs and MVI status, patients of ICC were categorized into four groups: TLSs-positive and MVI-negative (TP/MN); TLSs-negative and MVI-negative (TN/MN); TLSs-positive and MVI-positive (TP/MP), TLSs-negative and MVI-positive groups (TN/MP). In the training cohort, the four groups could be correlated with OS significantly (p<0.001), and it was confirmed in the validation cohort (p<0.001). CONCLUSION Intra-tumoral TLSs and MVI status are independent predictive factors of VER after surgery, based on which immunovascular stratifications are constructed and associated with OS significantly of resectable intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Ying Xu
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhuo Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanzhao Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Yi Yang
- 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
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingzhong Ouyang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Lu Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- 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
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Ye
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Hong Zhao
- 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.
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China.
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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11
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Liu Y, Fu S, Yu X, Zhang J, Zhu S, Yang Y, Huang J, Luo H, Tang K, Zheng Y, Zhao Y, Chen X, Zhan M, He X, Li Q, Duan C, Chen Y, Lu L. Model containing sarcopenia and visceral adiposity can better predict the prognosis of hepatocellular carcinoma: a multicenter study. BMC Cancer 2023; 23:969. [PMID: 37828461 PMCID: PMC10568831 DOI: 10.1186/s12885-023-11357-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 08/31/2023] [Indexed: 10/14/2023] Open
Abstract
AIM This study aimed to explore whether the addition of sarcopenia and visceral adiposity could improve the accuracy of model predicting progression-free survival (PFS) in hepatocellular carcinoma (HCC). METHODS In total, 394 patients with HCC from five hospitals were divided into the training and external validation datasets. Patients were initially treated by liver resection or transarterial chemoembolization. We evaluated adipose and skeletal muscle using preoperative computed tomography imaging and then constructed three predictive models, including metabolic (ModelMA), clinical-imaging (ModelCI), and combined (ModelMA-CI) models. Their discrimination, calibration, and decision curves were compared, to identify the best model. Nomogram and subgroup analysis was performed for the best model. RESULTS ModelMA-CI containing sarcopenia and visceral adiposity had good discrimination and calibrations (integrate area under the curve for PFS was 0.708 in the training dataset and 0.706 in the validation dataset). ModelMA-CI had better accuracy than ModelCI and ModelMA. The performance of ModelMA-CI was not affected by treatments or disease stages. The high-risk subgroup (scored > 198) had a significantly shorter PFS (p < 0.001) and poorer OS (p < 0.001). CONCLUSIONS The addition of sarcopenia and visceral adiposity improved accuracy in predicting PFS in HCC, which may provide additional insights in prognosis for HCC in subsequent studies.
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Affiliation(s)
- Yao Liu
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Sirui Fu
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Xiangrong Yu
- Department of Radiology, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, 519000, Guangdong Province, China
| | - Jinxiong Zhang
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Siyu Zhu
- Department of Biostatistics, School of Public Health, Southern Medical University, No. 1023-1063 Shatai South Road, Guangzhou, 510515, Guangdong Province, China
| | - Yang Yang
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Jianwen Huang
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Hanlin Luo
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Kai Tang
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Youbing Zheng
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Yujie Zhao
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Xiaoqiong Chen
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China
| | - Meixiao Zhan
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, 519000, Guangdong, China
| | - Xiaofeng He
- Interventional Diagnosis and Treatment Department, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qiyang Li
- Department of Radiology, Shenzhen People's Hospital, Shenzhen, China
| | - Chongyang Duan
- Department of Biostatistics, School of Public Health, Southern Medical University, No. 1023-1063 Shatai South Road, Guangzhou, 510515, Guangdong Province, China.
| | - Yuan Chen
- Department of Interventional Treatment, Zhongshan City People's Hospital, No. 2, Sunwen East Road, Zhongshan, 528400, Guangdong Province, China.
| | - Ligong Lu
- Zhuhai Interventional Medical Centre, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, China.
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Qin X, Zhu J, Tu Z, Ma Q, Tang J, Zhang C. Contrast-Enhanced Ultrasound with Deep Learning with Attention Mechanisms for Predicting Microvascular Invasion in Single Hepatocellular Carcinoma. Acad Radiol 2023; 30 Suppl 1:S73-S80. [PMID: 36567144 DOI: 10.1016/j.acra.2022.12.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/29/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022]
Abstract
RATIONALE AND OBJECTIVES Prediction of microvascular invasion (MVI) status of hepatocellular carcinoma (HCC) holds clinical significance for decision-making regarding the treatment strategy and evaluation of patient prognosis. We developed a deep learning (DL) model based on contrast-enhanced ultrasound (CEUS) to predict MVI of HCC. MATERIALS AND METHODS We retrospectively analyzed the data for single primary HCCs that were evaluated with CEUS 1 week before surgical resection from December 2014 to February 2022. The study population was divided into training (n = 198) and test (n = 54) cohorts. In this study, three DL models (Resnet50, Resnet50+BAM, Resnet50+SE) were trained using the training cohort and tested in the test cohort. Tumor characteristics were also evaluated by radiologists, and multivariate regression analysis was performed to determine independent indicators for the development of predictive nomogram models. The performance of the three DL models was compared to that of the MVI prediction model based on radiologist evaluations. RESULTS The best-performing model, ResNet50+SE model achieved the ROC of 0.856, accuracy of 77.2, specificity of 93.9%, and sensitivity of 52.4% in the test group. The MVI prediction model based on a combination of three independent predictors showed a C-index of 0.729, accuracy of 69.4, specificity of 73.8%, and sensitivity of 62%. CONCLUSION The DL algorithm can accurately predict MVI of HCC on the basis of CEUS images, to help identify high-risk patients for the assist treatment.
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Affiliation(s)
- Xiachuan Qin
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, AH, China, 230022; Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, China
| | - Jianhui Zhu
- Anhui Provincial Key Laboratory of Multimodal Cognitive Computation, School of Computer Science and Technology, Anhui University, Hefei, Anhui, China
| | - Zhengzheng Tu
- Anhui Provincial Key Laboratory of Multimodal Cognitive Computation, School of Computer Science and Technology, Anhui University, Hefei, Anhui, China
| | - Qianqing Ma
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, AH, China, 230022
| | - Jin Tang
- Anhui Provincial Key Laboratory of Multimodal Cognitive Computation, School of Computer Science and Technology, Anhui University, Hefei, Anhui, China
| | - Chaoxue Zhang
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, AH, China, 230022.
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Huang H, Qiao H, Jiang J, Yan J, Wen Q, Gen D, Wu Q. T1 relaxation time analysis in predicting hepatic dysfunction and prognosis in patients with HCC undergoing transarterial chemoembolization. Eur J Radiol 2023; 165:110938. [PMID: 37392548 DOI: 10.1016/j.ejrad.2023.110938] [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: 04/27/2023] [Revised: 06/04/2023] [Accepted: 06/17/2023] [Indexed: 07/03/2023]
Abstract
OBJECTIVE To evaluate the value of T1 mapping in predicting hepatic dysfunction and prognosis in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). MATERIAL AND METHODS 100 consecutive patients with treatment-naive HCC treated with TACE were prospectively analyzed. Clinical, laboratory, and MRI parameters (liver and tumor T1 relaxation times (T1L, T1T)) before and/or following TACE were measured and calculated. Clinical parameters included the Child-Turcotte-Pugh (CTP) classification, Barcelona Clinic Liver Cancer Classification (BCLC) criteria, and albumin-bilirubin (ALBI) score. Laboratory parameters were the gold standard for hepatic dysfunction. T1L and T1T were combined by stepwise multivariate logistic regression to yield a T1-related probability index (T1com) for further analysis. Study endpoints included hepatic dysfunction and progression-free survival (PFS) rate. RESULTS 38 patients (38%) were diagnosed with hepatic dysfunction following TACE. There was no significant difference in clinical parameters between the groups with and without hepatic dysfunction. Logistic regression analysis showed that T1L and T1T were independent risk factors for assessing hepatic dysfunction. T1com showed a better AUC than T1L and T1T (0.81 vs. 0.76 and 0.69, P = 0.007 and 0.006). Patients with low T1com (≤0.42) showed a better median PFS than patients with high T1com (>0.42) (167.0 vs. 215.9 days, P = 0.010). In comparison, CTP, BCLC, and ALBI scores were not statistically significant in predicting PFS in HCC patients treated with TACE (P > 0.05). CONCLUSION Compared with widely used clinical parameters, T1 was more capable of predicting hepatic dysfunction after TACE. Stratification of patients with HCC undergoing TACE according to T1 may help clinicians to develop treatment strategies in preventing the occurrence of hepatic dysfunction and improving individual prognoses.
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Affiliation(s)
- Hong Huang
- Department of Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Hongyan Qiao
- Department of Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jianwei Jiang
- Department of Interventional Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jian Yan
- Department of Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Qingqing Wen
- GE Healthcare, MR Research China, Beijing, China
| | - Da Gen
- Department of Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Qinghua Wu
- Department of Interventional Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China.
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Zhou J, Yang D. Prognostic Significance of Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:821-831. [PMID: 37288141 PMCID: PMC10243610 DOI: 10.2147/jhc.s411521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 05/24/2023] [Indexed: 06/09/2023] Open
Abstract
Purpose HALP score consisting of hemoglobin content, albumin content, lymphocyte count, and platelet count can comprehensively evaluate the inflammatory response and nutritional status. Many researchers have indicated that the HALP score is an effective predictor of the overall prognosis of various tumors. However, there is no relevant research to suggest whether the HALP score can predict the prognosis of patients with hepatocellular carcinoma (HCC). Patients and Methods We retrospectively analyzed 273 HCC patients who underwent surgical resection. Hemoglobin content, albumin content, lymphocyte count, and platelet count in peripheral blood were measured for each patient. The relationship between the HALP score and overall survival (OS) was investigated. Results With a mean of 56.69 ± 1.25 months follow-up, the 1-, 3-, and 5-year OS was 98.9%, 76.9%, and 55.3% for all patients, respectively. HALP scores (HR=1.708, 95% CI=1.192-2.448, P=0.004) were significant independent risk factors of OS. The 1-, 3-, and 5-year OS were 99.3%, 84.3%, and 63.4% for patients with high HALP scores; and 98.6%, 69.8%, and 47.5% for patients with low HALP scores, respectively (P=0.018). In TNM I-II stage patients, compared with high HALP scores, low HALP scores have worse OS (P=0.039). In AFP positive patients, compared with high HALP scores, low HALP scores have worse OS (P=0.042). Conclusion Our research showed the preoperative HALP score is an independent predictive factor of overall prognosis, and a low HALP score indicates a worse prognosis in HCC patients who underwent surgical resection.
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Affiliation(s)
- Jing Zhou
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Daofeng Yang
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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Gao YX, Ning QQ, Yang PX, Guan YY, Liu PX, Liu ML, Qiao LX, Guo XH, Yang TW, Chen DX. Recent advances in recurrent hepatocellular carcinoma therapy. World J Hepatol 2023; 15:460-476. [PMID: 37206651 PMCID: PMC10190692 DOI: 10.4254/wjh.v15.i4.460] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 12/20/2022] [Accepted: 03/24/2023] [Indexed: 04/20/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, accounting for 75%-85% of cases. Although treatments are given to cure early-stage HCC, up to 50%-70% of individuals may experience a relapse of the illness in the liver after 5 years. Research on the fundamental treatment modalities for recurrent HCC is moving significantly further. The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcomes. These strategies aim to minimize substantial morbidity, support good life quality, and enhance survival for patients with recurrent HCC. For individuals with recurring HCC after curative treatment, no approved therapeutic regimen is currently available. A recent study presented novel approaches, like immunotherapy and antiviral medication, to improve the prognosis of patients with recurring HCC with the apparent lack of data to guide the clinical treatment. The data supporting several neoadjuvant and adjuvant therapies for patients with recurring HCC are outlined in this review. We also discuss the potential for future clinical and translational investigations.
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Affiliation(s)
- Yu-Xue Gao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Qi-Qi Ning
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Yuan-Yue Guan
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Peng-Xiang Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Meng-Lu Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Lu-Xin Qiao
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Xiang-Hua Guo
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Tong-Wang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Academician Workstation, Changsha Medical University, Changsha 410219, Hunan Province, China
- Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, Hunan Province, China
| | - De-Xi Chen
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
- Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
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Duan R, Gong F, Wang Y, Huang C, Wu J, Hu L, Liu M, Qiu S, Lu L, Lin Y. Transarterial chemoembolization (TACE) plus tyrosine kinase inhibitors versus TACE in patients with hepatocellular carcinoma: a systematic review and meta-analysis. World J Surg Oncol 2023; 21:120. [PMID: 37004052 PMCID: PMC10064711 DOI: 10.1186/s12957-023-02961-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 02/22/2023] [Indexed: 04/03/2023] Open
Abstract
PURPOSE Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC. METHODS We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio's random-effects model. Quality assessments were performed using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs). RESULTS The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65-0.80), OS (combined HR 0.57, 95% CI 0.49-0.67), and objective response rate (OR 2.13, 95% CI 1.23-3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88-177.23), diarrhea (OR 18.13%, 95%CI 9.32-35.27), and hypertension (OR 12.24%, 95%CI 5.89-25.42). CONCLUSIONS Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings. TRIAL REGISTRATION PROSPERO registration number: CRD42022298003.
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Affiliation(s)
- Ruihua Duan
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fen Gong
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yan Wang
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Caixia Huang
- Medical Examination Center, Huizhou Central People's Hospital, Huizhou, Guangdong, China
| | - Jiaming Wu
- Zhongshan Affiliated Hospital, Guangzhou University of Chinese Medicine, Zhongshan, China
| | - Leihao Hu
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Min Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 16 Jichang Road, Guangzhou, China
| | - Shijun Qiu
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Liming Lu
- Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Yisheng Lin
- Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, China.
- Department of Interventional Radiology, Huizhou Municipal Central Hospital, Huizhou Guangdong, China.
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17
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Cao L, Wang Q, Hong J, Han Y, Zhang W, Zhong X, Che Y, Ma Y, Du K, Wu D, Pang T, Wu J, Liang K. MVI-TR: A Transformer-Based Deep Learning Model with Contrast-Enhanced CT for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:1538. [PMID: 36900327 PMCID: PMC10001339 DOI: 10.3390/cancers15051538] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/21/2023] [Accepted: 02/24/2023] [Indexed: 03/05/2023] Open
Abstract
In this study, we considered preoperative prediction of microvascular invasion (MVI) status with deep learning (DL) models for patients with early-stage hepatocellular carcinoma (HCC) (tumor size ≤ 5 cm). Two types of DL models based only on venous phase (VP) of contrast-enhanced computed tomography (CECT) were constructed and validated. From our hospital (First Affiliated Hospital of Zhejiang University, Zhejiang, P.R. China), 559 patients, who had histopathological confirmed MVI status, participated in this study. All preoperative CECT were collected, and the patients were randomly divided into training and validation cohorts at a ratio of 4:1. We proposed a novel transformer-based end-to-end DL model, named MVI-TR, which is a supervised learning method. MVI-TR can capture features automatically from radiomics and perform MVI preoperative assessments. In addition, a popular self-supervised learning method, the contrastive learning model, and the widely used residual networks (ResNets family) were constructed for fair comparisons. With an accuracy of 99.1%, a precision of 99.3%, an area under the curve (AUC) of 0.98, a recalling rate of 98.8%, and an F1-score of 99.1% in the training cohort, MVI-TR achieved superior outcomes. Additionally, the validation cohort's MVI status prediction had the best accuracy (97.2%), precision (97.3%), AUC (0.935), recalling rate (93.1%), and F1-score (95.2%). MVI-TR outperformed other models for predicting MVI status, and showed great preoperative predictive value for early-stage HCC patients.
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Affiliation(s)
- Linping Cao
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Qing Wang
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jiawei Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Yuzhe Han
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Weichen Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Xun Zhong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Yongqian Che
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yaqi Ma
- Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Keyi Du
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Dongyan Wu
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Tianxiao Pang
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Kewei Liang
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310058, China
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Yang YQ, Wen ZY, Liu XY, Ma ZH, Liu YE, Cao XY, Hou L, Xie H. Current status and prospect of treatments for recurrent hepatocellular carcinoma. World J Hepatol 2023; 15:129-150. [PMID: 36926237 PMCID: PMC10011906 DOI: 10.4254/wjh.v15.i2.129] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/13/2022] [Accepted: 01/23/2023] [Indexed: 02/24/2023] Open
Abstract
Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.
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Affiliation(s)
- Yu-Qing Yang
- Department of Epidemiology and Biostatistics, Jilin University, Changchun 130021, Jilin Province, China
| | - Zhen-Yu Wen
- Department of Occupational and Environmental Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Xiao-Yan Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhen-Hu Ma
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yan-E Liu
- Department of Epidemiology and Biostatistics, Jilin University, Changchun 130021, Jilin Province, China
| | - Xue-Ying Cao
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Li Hou
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hui Xie
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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Yang J, Dong X, Wang G, Chen J, Zhang B, Pan W, Zhang H, Jin S, Ji W. Preoperative MRI features for characterization of vessels encapsulating tumor clusters and microvascular invasion in hepatocellular carcinoma. Abdom Radiol (NY) 2023; 48:554-566. [PMID: 36385192 DOI: 10.1007/s00261-022-03740-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/31/2022] [Accepted: 11/01/2022] [Indexed: 11/17/2022]
Abstract
PURPOSE This study aimed to analyze imaging features based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the identification of vessels encapsulating tumor clusters (VETC)-microvascular invasion (MVI) in hepatocellular carcinoma (HCC), VM-HCC pattern. METHODS Patients who underwent hepatectomy and preoperative DCE-MRI between January 2015 and March 2021 were retrospectively analyzed. Clinical and imaging features related to VM-HCC (VETC + /MVI-, VETC-/MVI +, VETC + /MVI +) and Non-VM-HCC (VETC-/MVI-) were determined by multivariable logistic regression analyses. Early and overall recurrence were determined using the Kaplan-Meier survival curve. Indicators of early and overall recurrence were identified using the Cox proportional hazard regression model. RESULTS In total, 221 patients (177 men, 44 women; median age, 60 years; interquartile range, 52-66 years) were evaluated. The multivariable logistic regression analyses revealed fetoprotein > 400 ng/mL (odds ratio [OR] = 2.17, 95% confidence interval [CI] 1.07, 4.41, p = 0.033), intratumor vascularity (OR 2.15, 95% CI 1.07, 4.31, p = 0.031), and enhancement pattern (OR 2.71, 95% CI 1.17, 6.03, p = 0.019) as independent predictors of VM-HCC. In Kaplan-Meier survival analysis, intratumor vascularity was associated with early and overall recurrence (p < 0.05). CONCLUSION Based on DCE-MRI, intratumor vascularity can be used to characterize VM-HCC and is of prognostic significance for recurrence in patients with HCC.
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Affiliation(s)
- Jiawen Yang
- Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen St, Linhai, Taizhou, 317000, Zhejiang, China
| | - Xue Dong
- Department of Radiology, Taizhou Hospital, Zhejiang University, Taizhou, 318000, Zhejiang, China
| | - Guanliang Wang
- Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen St, Linhai, Taizhou, 317000, Zhejiang, China
| | - Jinyao Chen
- Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen St, Linhai, Taizhou, 317000, Zhejiang, China
| | - Binhao Zhang
- Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen St, Linhai, Taizhou, 317000, Zhejiang, China
| | - Wenting Pan
- Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen St, Linhai, Taizhou, 317000, Zhejiang, China
| | - Huangqi Zhang
- Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen St, Linhai, Taizhou, 317000, Zhejiang, China
| | - Shengze Jin
- Department of Radiology, Taizhou Hospital of Zhejiang Province, Shaoxing University, Taizhou, 318000, Zhejiang, China
| | - Wenbin Ji
- Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen St, Linhai, Taizhou, 317000, Zhejiang, China.
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Wang XH, Duan WB, Liang W, Li H, Xie XY, Li SQ, Chen MS, Liang P, Mao XH, Zhou QF. Efficacy of radiofrequency ablation following transarterial chemoembolisation combined with sorafenib for intermediate stage recurrent hepatocellular carcinoma: a retrospective, multicentre, cohort study. EClinicalMedicine 2023; 56:101816. [PMID: 36703645 PMCID: PMC9871741 DOI: 10.1016/j.eclinm.2022.101816] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND The evidence of radiofrequency ablation (RFA) following transarterial chemoembolisation (TACE) combined with sorafenib for intermediate-stage recurrent hepatocellular carcinoma (RHCC) is limited. Patient responses to this treatment vary because of the heterogeneous nature of RHCC, making it important to identify patients who are most likely to benefit from this combination therapy. The aim of this study was to evaluate the efficacy of RFA following TACE and sorafenib for the intermediate-stage RHCC. METHODS This retrospective, multicentre, cohort study included 363 patients with intermediate-stage RHCC underwent TACE combined with sorafenib (TACE-sorafenib group) or RFA following TACE and sorafenib (TACE-sorafenib + RFA group) between January 01, 2009 to December 31, 2015 from four institutions in China. Overall survival (OS), progression-free survival (PFS) and efficacy of patients were compared between the two groups by propensity score-matching (PSM). FINDINGS The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% in TACE-sorafenib + RFA group, and 93.3%, 57.0%, 32.7% in TACE-sorafenib group. The 1-, 2-, and 3-year PFS rates were 85.3%, 58.0%, 26.9% in TACE-sorafenib + RFA group, and 55.3%, 30.7%, 15.3% in TACE-sorafenib group. Compared with the TACE-sorafenib group, the TACE-sorafenib + RFA group had significantly longer OS (HR, 0.54; 95%CI, 0.40-0.73; P < 0.001) and PFS (HR, 0.52; 95% CI, 0.41-0.66; P < 0.001). Subgroup analysis was conducted to precisely screen out the beneficial population from RFA treatment. INTERPRETATION Our findings suggest that addition of RFA following TACE and sorafenib combination was superior to TACE combined with sorafenib for intermediate-stage RHCC, resulting in longer OS and PFS. Patients who had good response to TACE and achieved downstaging successfully could not benefit from the RFA therapy. FUNDING This research was funded by National Natural Science Foundation of China (No. 81627803), Chen Xiao-Ping Science and Technology Development Fund (CXPJJH1200009-06).
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Affiliation(s)
- Xiao-Hui Wang
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
| | - Wen-Bin Duan
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
| | - Wei Liang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
| | - Hui Li
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510060, China
| | - Shao-Qiang Li
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 510060, China
| | - Min-Shan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
- Corresponding author.
| | - Xian-Hai Mao
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
- Corresponding author.
| | - Qun-Fang Zhou
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
- Corresponding author.
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Liang J, Bai Y, Ha FS, Luo Y, Deng HT, Gao YT. Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:1-18. [PMID: 36684055 PMCID: PMC9850755 DOI: 10.4251/wjgo.v15.i1.1] [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: 09/24/2022] [Revised: 12/06/2022] [Accepted: 12/27/2022] [Indexed: 01/10/2023] Open
Abstract
Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.
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Affiliation(s)
- Jing Liang
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Yi Bai
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
| | - Fu-Shuang Ha
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying Luo
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Hui-Ting Deng
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying-Tang Gao
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
- Tianjin Institute of Hepatobiliary Disease, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
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22
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Si Y, Xu P, Xu A, Wang P, Zhao K. Geriatric nutritional risk index as a prognostic factor in patients with hepatocellular carcinoma following transarterial chemoembolization: A retrospective study. Medicine (Baltimore) 2022; 101:e32322. [PMID: 36595771 PMCID: PMC9794247 DOI: 10.1097/md.0000000000032322] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The geriatric nutritional risk index (GNRI) has been shown to be associated with the prognosis of cancer patients except for hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE). Our aim is to examine the association between the GNRI and long-term prognosis in patients with HCC who underwent TACE. Patients with HCC who underwent TACE were enrolled. The relationship between the patient characteristics and GNRI were compared, and the independent prognostic factors were investigated. Nomogram performance was assessed via the concordance index (C-index) and calibration plots. Decision curve analysis (DCA) was performed to evaluate the net benefit of the nomogram. A total of 235 patients met the inclusion criteria. Compared with the parameters of the high GNRI group, low GNRI was significantly associated with hypertension, ascites, body mass index, tumor size, anemia, Child-Turcotte-Pugh class. The univariate analysis demonstrated that overall survival (OS) was inferior when GNRI < 98, tumor size ≥ 5cm, vascular invasion, alpha-fetoprotein level ≥ 400, Barcelona clinical liver cancer stage B to C and TACE times < 3. The multivariate analysis revealed that GNRI < 98, tumor size ≥ 5cm, tumor number ≥ 2, alpha-fetoprotein level ≥ 400 and TACE times < 3 were independent predictors of a poor OS. In the validation step, OS was shown to be well calibrated (C-index = 0.724), and a satisfactory clinical utility was proven by DCA. Low GNRI score was associated with a shorter OS in patients undergoing TACE.
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Affiliation(s)
- Youjiao Si
- Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Peng Xu
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Aihua Xu
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Peiyuan Wang
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Kaikai Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
- * Correspondence: Kaikai Zhao, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China (e-mail: )
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Yi PS, Liu JN, Li Y, Wu B, Li JS. The priority of liver resection compared with transarterial chemoembolization in hepatocellular carcinoma at BCLC B1 stage: A single-center experience. Front Surg 2022; 9:920976. [PMID: 36439533 PMCID: PMC9681909 DOI: 10.3389/fsurg.2022.920976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 10/17/2022] [Indexed: 08/30/2023] Open
Abstract
BACKGROUND This study aimed to compare the efficacy of liver resection (LR) and transarterial chemoembolization (TACE) in the treatment of Barcelona Clinic Liver Cancer B1 (BCLC B1) hepatocellular carcinoma. METHODS A total of 65 patients with BCLC B1 were divided into the radical (LR group) and TACE groups. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were carried out, and the prognostic factors for survival outcomes were identified using Cox proportional analysis. RESULTS The 1-, 3-, and 5-year survival rates and the 1-, 3-, and 5-year progression-free survival (PFS) rates in the LR group (P = 0.036) were significantly higher than those in the TACE group (P = 0.027). Results of the multivariate analysis demonstrated that tumor distribution (both lobes vs. semi-liver) and treatment strategy (LR vs. TACE) were independent risk factors for the overall survival (OS) [hazard ratios (HRs): 3.926 and 0.479; P < 0.05] and PFS (HR: 3.336 and 0.465, P < 0.05). LR was associated with increased OS and PFS compared with TACE in patients with BCLC B1 hepatocellular carcinoma.
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Affiliation(s)
- Peng-Sheng Yi
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Zhang Y, Wei Q, Huang Y, Yao Z, Yan C, Zou X, Han J, Li Q, Mao R, Liao Y, Cao L, Lin M, Zhou X, Tang X, Hu Y, Li L, Wang Y, Yu J, Zhou J. Deep Learning of Liver Contrast-Enhanced Ultrasound to Predict Microvascular Invasion and Prognosis in Hepatocellular Carcinoma. Front Oncol 2022; 12:878061. [PMID: 35875110 PMCID: PMC9300962 DOI: 10.3389/fonc.2022.878061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/14/2022] [Indexed: 12/24/2022] Open
Abstract
Background and Aims Microvascular invasion (MVI) is a well-known risk factor for poor prognosis in hepatocellular carcinoma (HCC). This study aimed to develop a deep convolutional neural network (DCNN) model based on contrast-enhanced ultrasound (CEUS) to predict MVI, and thus to predict prognosis in patients with HCC. Methods A total of 436 patients with surgically resected HCC who underwent preoperative CEUS were retrospectively enrolled. Patients were divided into training (n = 301), validation (n = 102), and test (n = 33) sets. A clinical model (Clinical model), a CEUS video-based DCNN model (CEUS-DCNN model), and a fusion model based on CEUS video and clinical variables (CECL-DCNN model) were built to predict MVI. Survival analysis was used to evaluate the clinical performance of the predicted MVI. Results Compared with the Clinical model, the CEUS-DCNN model exhibited similar sensitivity, but higher specificity (71.4% vs. 38.1%, p = 0.03) in the test group. The CECL-DCNN model showed significantly higher specificity (81.0% vs. 38.1%, p = 0.005) and accuracy (78.8% vs. 51.5%, p = 0.009) than the Clinical model, with an AUC of 0.865. The Clinical predicted MVI could not significantly distinguish OS or RFS (both p > 0.05), while the CEUS-DCNN predicted MVI could only predict the earlier recurrence (hazard ratio [HR] with 95% confidence interval [CI 2.92 [1.1–7.75], p = 0.024). However, the CECL-DCNN predicted MVI was a significant prognostic factor for both OS (HR with 95% CI: 6.03 [1.7–21.39], p = 0.009) and RFS (HR with 95% CI: 3.3 [1.23–8.91], p = 0.011) in the test group. Conclusions The proposed CECL-DCNN model based on preoperative CEUS video can serve as a noninvasive tool to predict MVI status in HCC, thereby predicting poor prognosis.
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Affiliation(s)
- Yafang Zhang
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qingyue Wei
- School of Information Science and Technology, Fudan University, Shanghai, China
| | - Yini Huang
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhao Yao
- School of Information Science and Technology, Fudan University, Shanghai, China
| | - Cuiju Yan
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xuebin Zou
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jing Han
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qing Li
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Rushuang Mao
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying Liao
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Lan Cao
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Min Lin
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiaoshuang Zhou
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiaofeng Tang
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yixin Hu
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Lingling Li
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yuanyuan Wang
- School of Information Science and Technology, Fudan University, Shanghai, China
| | - Jinhua Yu
- School of Information Science and Technology, Fudan University, Shanghai, China
- *Correspondence: Jinhua Yu, ; Jianhua Zhou,
| | - Jianhua Zhou
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- *Correspondence: Jinhua Yu, ; Jianhua Zhou,
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Liao J, Yi Y, Yue X, Wu X, Zhu M, Chen Y, Peng S, Kuang M, Lin S, Peng Z. Methyltransferase 1 is required for nonhomologous end-joining repair and renders hepatocellular carcinoma resistant to radiotherapy. Hepatology 2022; 77:1896-1910. [PMID: 35698894 DOI: 10.1002/hep.32615] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 06/08/2022] [Accepted: 06/09/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Radiotherapy is an increasingly essential therapeutic strategy in the management of hepatocellular carcinoma (HCC). Nevertheless, resistance to radiotherapy is one of the primary obstacles to successful treatment outcomes. Hence, we aim to elucidate the mechanisms underlying radioresistance and identify reliable biotargets that would be inhibited to enhance the efficacy of radiotherapy in HCC. APPROACH AND RESULTS From a label-free quantitative proteome screening, we identified transfer RNA (tRNA; guanine-N [7]-) methyltransferase 1 (METTL1), a key enzyme for N7-methylguanosine (m7 G) tRNA modification, as an essential driver for HCC cells radioresistance. We reveal that METTL1 promotes DNA double-strand break (DSB) repair and renders HCC cells resistant to ionizing radiation (IR) using loss-of-function and gain-of-function assays in vitro and in vivo. Mechanistically, METTL1-mediated m7 G tRNA modification selectively regulates the translation of DNA-dependent protein kinase catalytic subunit or DNA ligase IV with higher frequencies of m7 G-related codons after IR treatment, thereby resulting in the enhancement of nonhomologous end-joining (NHEJ)-mediated DNA DSB repair efficiency. Clinically, high METTL1 expression in tumor tissue is significantly correlated with poor prognosis in radiotherapy-treated patients with HCC. CONCLUSIONS Our findings show that METTL1 is a critical enhancer for HCC cell NHEJ-based DNA repair following IR therapy. These findings give insight into the role of tRNA modification in messenger RNA translation control in HCC radioresistance.
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Affiliation(s)
- Junbin Liao
- Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yang Yi
- Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xin Yue
- Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoxue Wu
- Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Meiyan Zhu
- Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yong Chen
- Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Sui Peng
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ming Kuang
- Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shuibin Lin
- Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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26
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Chen Q, Xiao H, Gu Y, Weng Z, Wei L, Li B, Liao B, Li J, Lin J, Hei M, Peng S, Wang W, Kuang M, Chen S. Deep learning for evaluation of microvascular invasion in hepatocellular carcinoma from tumor areas of histology images. Hepatol Int 2022; 16:590-602. [PMID: 35349075 PMCID: PMC9174315 DOI: 10.1007/s12072-022-10323-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 02/16/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Microvascular invasion (MVI) is essential for the management of hepatocellular carcinoma (HCC). However, MVI is hard to evaluate in patients without sufficient peri-tumoral tissue samples, which account for over a half of HCC patients. METHODS We established an MVI deep-learning (MVI-DL) model with a weakly supervised multiple-instance learning framework, to evaluate MVI status using only tumor tissues from the histological whole slide images (WSIs). A total of 350 HCC patients (2917 WSIs) from the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU cohort) were divided into a training and test set. One hundred and twenty patients (504 WSIs) from Dongguan People's Hospital and Shunde Hospital of Southern Medical University (DG-SD cohort) formed an external test set. Unsupervised clustering and class activation mapping were applied to visualize the key histological features. RESULTS In the FAHSYSU and DG-SD test set, the MVI-DL model achieved an AUC of 0.904 (95% CI 0.888-0.920) and 0.871 (95% CI 0.837-0.905), respectively. Visualization results showed that macrotrabecular architecture with rich blood sinus, rich tumor stroma and high intratumor heterogeneity were identified as the key features associated with MVI ( +), whereas severe immune infiltration and highly differentiated tumor cells were associated with MVI (-). In the simulation of patients with only one WSI or biopsies only, the AUC of the MVI-DL model reached 0.875 (95% CI 0.855-0.895) and 0.879 (95% CI 0.853-0.906), respectively. CONCLUSION The effective, interpretable MVI-DL model has potential as an important tool with practical clinical applicability in evaluating MVI status from the tumor areas on the histological slides.
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Affiliation(s)
- Qiaofeng Chen
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Han Xiao
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Yunquan Gu
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zongpeng Weng
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Lihong Wei
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Bin Li
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Bing Liao
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jiali Li
- Department of Liver and Pancreatobiliary Surgery, Dongguan People's Hospital, Dongguan, Guangdong, China
| | - Jie Lin
- Department of Liver and Pancreatobiliary Surgery, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Mengying Hei
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Sui Peng
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
| | - Ming Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
- Department of Liver Surgery, Cancer Center, Institute of Precision Medicine, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
| | - Shuling Chen
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
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27
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Ren Q, Zhu P, Li C, Yan M, Liu S, Zheng C, Xia X. Pretreatment Computed Tomography-Based Machine Learning Models to Predict Outcomes in Hepatocellular Carcinoma Patients who Received Combined Treatment of Trans-Arterial Chemoembolization and Tyrosine Kinase Inhibitor. Front Bioeng Biotechnol 2022; 10:872044. [PMID: 35677305 PMCID: PMC9168370 DOI: 10.3389/fbioe.2022.872044] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/22/2022] [Indexed: 11/15/2022] Open
Abstract
Aim: Trans-arterial chemoembolization (TACE) in combination with tyrosine kinase inhibitor (TKI) has been evidenced to improve outcomes in a portion of patients with hepatocellular carcinoma (HCC). Developing biomarkers to identify patients who might benefit from the combined treatment is needed. This study aims to investigate the efficacy of radiomics/deep learning features-based models in predicting short-term disease control and overall survival (OS) in HCC patients who received the combined treatment. Materials and Methods: A total of 103 HCC patients who received the combined treatment from Sep. 2015 to Dec. 2019 were enrolled in the study. We exacted radiomics features and deep learning features of six pre-trained convolutional neural networks (CNNs) from pretreatment computed tomography (CT) images. The robustness of features was evaluated, and those with excellent stability were used to construct predictive models by combining each of the seven feature exactors, 13 feature selection methods and 12 classifiers. The models were evaluated for predicting short-term disease by using the area under the receiver operating characteristics curve (AUC) and relative standard deviation (RSD). The optimal models were further analyzed for predictive performance on overall survival. Results: A total of the 1,092 models (156 with radiomics features and 936 with deep learning features) were constructed. Radiomics_GINI_Nearest Neighbors (RGNN) and Resnet50_MIM_Nearest Neighbors (RMNN) were identified as optimal models, with the AUC of 0.87 and 0.94, accuracy of 0.89 and 0.92, sensitivity of 0.88 and 0.97, specificity of 0.90 and 0.90, precision of 0.87 and 0.83, F1 score of 0.89 and 0.92, and RSD of 1.30 and 0.26, respectively. Kaplan-Meier survival analysis showed that RGNN and RMNN were associated with better OS (p = 0.006 for RGNN and p = 0.033 for RMNN). Conclusion: Pretreatment CT-based radiomics/deep learning models could non-invasively and efficiently predict outcomes in HCC patients who received combined therapy of TACE and TKI.
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Affiliation(s)
- Qianqian Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Peng Zhu
- Department of Hepatobiliary Surgery, Wuhan No.1 Hospital, Wuhan, China
| | - Changde Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Meijun Yan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Song Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
- *Correspondence: Xiangwen Xia,
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Hu HT, Luo JP, Cao GS, Li Z, Jiang M, Guo CY, Yuan H, Yao QJ, Geng X, Park JH, Cheng HT, Jiang L, Ma JL, Zhao Y, Li HL. Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Transarterial Chemoembolization and Sorafenib vs. 125Iodine Implantation. Front Oncol 2022; 11:806907. [PMID: 35004330 PMCID: PMC8733476 DOI: 10.3389/fonc.2021.806907] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 12/06/2021] [Indexed: 01/15/2023] Open
Abstract
Background and Aims This study investigated the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) combined with CT-guided 125iodine seed implantation for treatment of hepatocellular carcinoma (HCC) with first-branch portal vein tumor thrombosis (PVTT). Methods This prospective, controlled, multicenter study included HCC patients with Barcelona Clinic Liver Cancer stage C disease and PVTT in the right and/or left portal veins. Patients were treated with either TACE and sorafenib or TACE and CT-guided 125iodine seed implantation and regularly evaluated for clinical response and adverse events, with treatment termination resulting from declining clinical status, loss to follow-up, or death. Results This study demonstrated a significant between-group difference in median overall survival (OS); therefore, it was terminated early. A total of 123 patients were included in this study, with 52 patients in the TACE-sorafenib group and 71 patients in the TACE-125iodine group, without significant differences in baseline characteristics between groups. The median OS was 8.3 months (95% CI: 6.105–10.495) in the TACE-sorafenib group and 13.8 months (95% CI: 9.519–18.081) in the TACE-125iodine group. In a subgroup analysis of type IIa versus type IIb PVTT, the median OS was 17.5 months for type IIa and 7.1 months for IIb in the TACE-125iodine group. The median OS was 9.3 months for IIa and 4.0 months for IIb in the TACE-sorafenib group. Univariate and multivariate analyses confirmed that the PVTT type and treatment strategy were significant independent factors affecting OS. The objective response rates (ORR) for intrahepatic lesions and PVTT showed significant differences between groups. Most patients in both groups experienced minor adverse events related to TACE. The overall incidence of sorafenib-related adverse events or toxic effects was 90.4% in TACE-sorafenib group. In the TACE-125iodine group, the incidence of pneumothorax and minor hepatic subcapsular hemorrhage were 7.04% and 9.86%, respectively. Conclusions This study showed that TACE-125iodine treatment significantly enhanced survival of patients with HCC and type II PVTT, especially subtype IIa, with minimal adverse events. Clinical Trial Registration Chinese Clinical Trials Database, identifier ChiCTR-ONN-16007929.
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Affiliation(s)
- Hong-Tao Hu
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Jun-Peng Luo
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, Guangzhou, China
| | - Guang-Shao Cao
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhen Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ming Jiang
- Department of Minimal-Invasive Intervention, Anyang Tumor Hospital/The Forth Affiliated Hospital of Henan University of Science and Technology, Anyang, China
| | - Chen-Yang Guo
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Hang Yuan
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Quan-Jun Yao
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Xiang Geng
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Jung-Hoon Park
- Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea
| | - Hong-Tao Cheng
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Li Jiang
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Jun-Li Ma
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Yan Zhao
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Hai-Liang Li
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
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Zhou Q, Wang X, Li R, Wang C, Wang J, Xie X, Li Y, Li S, Mao X, Liang P. Sorafenib as adjuvant therapy following radiofrequency ablation for recurrent hepatocellular carcinoma within Milan criteria: a multicenter analysis. J Gastroenterol 2022; 57:684-694. [PMID: 35816221 PMCID: PMC9392709 DOI: 10.1007/s00535-022-01895-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 06/12/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Radiofrequency ablation (RFA) is considered as a convenient treatment with mild damage in treating recurrent hepatocellular carcinoma (RHCC). However, for patients with high risk of progression after RFA still needs new strategies to decrease the repeat recurrence. METHODS A total of 460 patients with RHCC within Milan criteria in four institutions were enrolled. 174 pairs were enrolled after propensity score matching (PSM). Overall survival (OS) and tumor-free survival (TFS) were compared between the two groups. A quantitative score system was established to screen out the beneficial population from RFA-sorafenib treatment. RESULTS The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% for RFA-sorafenib group, and 93.1%, 61.3%, 30.9% for RFA group after PSM, respectively. Compared with the RFA group, the RFA-sorafenib group had significantly better OS (P < 0.001). The 1-, 3-, and 5-year TFS rates were 90.8%, 49.0%, 20.4% for RFA-sorafenib group, and 67.8%, 28.0%, 14.5% for RFA group after PSM. The difference was observed significantly between RFA-sorafenib group and RFA group (P < 0.001). A quantitative risk score system was established to precisely screen out the beneficial population from RFA-sorafenib treatment. CONCLUSIONS Adjuvant sorafenib after RFA was superior to RFA alone in improving survival outcomes in patients with recurrent HCC within Milan criteria after initial hepatectomy. Subgroup analyses concluded that patients with high risk score had significantly longer survival from sorafenib administration.
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Affiliation(s)
- Qunfang Zhou
- grid.414252.40000 0004 1761 8894Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 China
| | - Xiaohui Wang
- grid.477407.70000 0004 1806 9292Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410002 Hunan Province China
| | - Ruixia Li
- grid.414252.40000 0004 1761 8894Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 China
| | - Chenmeng Wang
- grid.414252.40000 0004 1761 8894Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 China
| | - Juncheng Wang
- grid.488530.20000 0004 1803 6191Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060 Guangdong China
| | - Xiaoyan Xie
- grid.412615.50000 0004 1803 6239Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510060 China
| | - Yali Li
- grid.414252.40000 0004 1761 8894Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 China
| | - Shaoqiang Li
- grid.412615.50000 0004 1803 6239Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510060 Guangdong Province China
| | - Xianhai Mao
- grid.477407.70000 0004 1806 9292Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410002 Hunan Province China
| | - Ping Liang
- grid.414252.40000 0004 1761 8894Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 China
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Zheng Z, Guan R, Jianxi W, Zhao Z, Peng T, Liu C, Lin Y, Jian Z. Microvascular Invasion in Hepatocellular Carcinoma: A Review of Its Definition, Clinical Significance, and Comprehensive Management. JOURNAL OF ONCOLOGY 2022; 2022:9567041. [PMID: 35401743 PMCID: PMC8986383 DOI: 10.1155/2022/9567041] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 02/28/2022] [Accepted: 03/14/2022] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of malignancies in the world, and most HCC patients undergoing liver resection relapse within five years. Microvascular invasion (MVI) is an independent factor for both the disease-free survival and overall survival of HCC patients. At present, the definition of MVI is still controversial, and a global consensus on how to evaluate MVI precisely is needed. Moreover, this review summarizes the current knowledge and clinical significance of MVI for HCC patients. In terms of management, antiviral therapy, wide surgical margins, and postoperative transcatheter arterial chemoembolization (TACE) could effectively reduce the incidence of MVI or improve the disease-free survival and overall survival of HCC patients with MVI. However, other perioperative management practices, such as anatomical resection, radiotherapy, targeted therapy and immune therapy, should be clarified in future investigations.
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Affiliation(s)
- Zehao Zheng
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Renguo Guan
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Wang Jianxi
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zhen Zhao
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of General Surgery, School of Medicine, Southern China University of Technology, Guangzhou, China
| | - Tianyi Peng
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Chunsheng Liu
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ye Lin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Wang K, Xiang YJ, Yu HM, Cheng YQ, Qin YY, Wang WJ, Zhang XP, Zheng YT, Shan YF, Cong WM, Dong H, Lau WY, Cheng SQ. A novel classification in predicting prognosis and guiding postoperative management after R0 liver resection for patients with hepatocellular carcinoma and microvascular invasion. Eur J Surg Oncol 2021; 48:1348-1355. [PMID: 34996665 DOI: 10.1016/j.ejso.2021.12.466] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 12/13/2021] [Accepted: 12/25/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). The current classification of MVI is not refined enough to prognosticate long-term survival of these patients, and a new MVI classification is needed. METHODS Patients with HCC who underwent R0 LR at the Eastern Hepatobiliary Surgery Hospital from January 2013 to December 2013 and with resected specimens showing MVI were included in this study with an aim to establish a novel MVI classification. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS There were 180 patients in the derivation cohort and 131 patients in the external validation cohort. The following factors were used for scoring: α-fetoprotein level (AFP), liver cirrhosis, tumor number, tumor diameter, MVI number, and distance between MVI and HCC. Three classes of patients could be distinguished by using the total score: class A, ≤3 points; class B, 3.5-5 points and class C, >5 points with distinct long-term survival outcomes (median recurrence free survival (mRFS), 22.6, 10.2, and 1.9 months, P < 0.001). The predictive accuracy of this classification was more accurate than the other commonly used classifications for HCC patients with MVI. In addition, the mRFS of class C patients was significantly prolonged (1.9 months vs. 6.2 months, P < 0.001) after adjuvant transcatheter arterial chemoembolization (TACE). CONCLUSIONS A novel MVI classification was established in predicting prognosis of HCC patients with MVI after R0 LR. Adjuvant TACE was useful for class C patients.
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Affiliation(s)
- Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yan-Jun Xiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Hong-Ming Yu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Qiang Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ying-Yi Qin
- Department of Health Statistics, Second Military Medical University, Shanghai, China
| | - Wei-Jun Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiu-Ping Zhang
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yi-Tao Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Yun-Feng Shan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Hui Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
| | - Wan Yee 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, Hong Kong, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
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A Novel Four-Gene Signature as a Potential Prognostic Biomarker for Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2021; 2021:1452801. [PMID: 34950206 PMCID: PMC8691992 DOI: 10.1155/2021/1452801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 11/23/2021] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor with high incidence and mortality rates. However, a reliable prognostic signature has not yet been confirmed. Thus, the purpose of the present study was to develop a biomarker with high specificity and sensitivity for the diagnosis and prognosis of patients with HCC. The mRNA expression profiles of HCC were obtained from the GSE19665, GSE41804, and TCGA databases. Subsequently, 193 differentially expressed genes (DEGs) were identified from the intersection of the data from the three datasets. Bioinformatics analysis showed that the identified DEGs are related to the cell cycle, oocyte meiosis, and p53 signaling pathway, among other factors, in cancers. A protein-protein interaction (PPI) and a functional analysis were performed to investigate the biological function of the DEGs and obtain the candidate genes using the MCODE of Cytoscape. The candidate genes were introduced into the TCGA database for survival analysis, and the four candidate genes that were hub genes and meaningful for survival were retained for further verification. We validated the gene and protein expression and determined the prognosis of our patient cohort. In addition, we evaluated the biological functions regulating tumor cell proliferation and metastasis in vitro. According to the ROC curve analysis of gene expression in clinical samples, it was found that the four genes can be used to predict the diagnosis. A survival analysis based on data from the TCGA database and clinical samples showed that the four genes may be used as biomarkers for providing prognoses for patients. The cell functional experiments revealed that these four genes were related to tumor proliferation, migration, and invasion. In conclusion, the genes identified in the present study could be used as markers to diagnose and predict the prognosis of patients with HCC and guide targeted therapy.
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Wang LZ, Hu XX, Shen XC, Wang TC, Zhou S. Intraarterial Lidocaine Administration for Pain Control by Water-in-Oil Technique in Transarterial Chemoembolization: in vivo and Randomized Clinical Trial. J Hepatocell Carcinoma 2021; 8:1221-1232. [PMID: 34676180 PMCID: PMC8502067 DOI: 10.2147/jhc.s331779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/23/2021] [Indexed: 11/23/2022] Open
Abstract
Objective To investigate the sustained release of lidocaine from a lidocaine–epirubicin–lipiodol emulsion created by water-in-oil (W/O) technique in vivo and evaluate the efficacy and safety of intraarterial lidocaine administration for intra- and postoperative pain control in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods The in vivo concentrations of lidocaine were determined in tumor tissues after VX2 rabbit models for hepatic tumor were administered with intra-arterial lidocaine–epirubicin–lipiodol emulsion. A prospective randomized controlled clinical trial was performed, enrolling 70 consecutive patients who underwent TACE. Patients were randomized into two groups: Group A received an immediate bolus intraarterial lidocaine injection before TACE, and Group B received a lidocaine–epirubicin–lipiodol emulsion during TACE. Pain intensity was compared between the two groups using a visual analog scale (VAS) score before (Tbefore) and at 0 h (T0), 4 h (T4), 8 h (T8), 24 h (T24), 48 h (T48), and 72 h (T72) after the procedure. Adverse events and intake of analgesics were evaluated and compared between the two groups. Results The concentrations of lidocaine in tumor tissues were higher in experimental group than in control group at T0.5 (P=0.004), T1 (P=0.038), T4 (P=0.036), and T8 (P=0.029). In the clinical trial, VAS scores in Group B were significantly lower than in Group A at T0 (P=0.006), T4 (P=0.001), T8 (P=0.002), and T24 (P=0.005). The tramadol intake in Group B was significantly lower than in Group A (P=0.021). No significant difference was observed regarding the incidence of adverse events between the two groups. Conclusion This study demonstrated the effectiveness and safety of intraarterial lidocaine administration using the W/O technique in controlling intra- and post-TACE pain.
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Affiliation(s)
- Li-Zhou Wang
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China
| | - Xiao-Xia Hu
- The State Laboratory of Functions and Application of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China
| | - Xiang-Chun Shen
- The State Laboratory of Functions and Application of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.,School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China
| | - Tian-Cheng Wang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China
| | - Shi Zhou
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China
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Fu S, Pan M, Zhang J, Zhang H, Tang Z, Li Y, Mu W, Huang J, Dong D, Duan C, Li X, Wang S, Chen X, He X, Yan J, Lu L, Tian J. Deep Learning-Based Prediction of Future Extrahepatic Metastasis and Macrovascular Invasion in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2021; 8:1065-1076. [PMID: 34513748 PMCID: PMC8427842 DOI: 10.2147/jhc.s319639] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 08/18/2021] [Indexed: 12/24/2022] Open
Abstract
PURPOSE For timely treatment of extrahepatic metastasis and macrovascular invasion (aggressive progressive disease [PD]) in hepatocellular carcinoma, models aimed at stratifying the risks of subsequent aggressive PD should be constructed. PATIENTS AND METHODS After dividing 332 patients from five hospitals into training (n = 236) and validation (n = 96) datasets, non-invasive models, including clinical/semantic factors (ModelCS), deep learning radiomics (ModelD), and both (ModelCSD), were constructed to stratify patients according to the risk of aggressive PD. We examined the discrimination and calibration; similarly, we plotted a decision curve and devised a nomogram. Furthermore, we performed analyses of subgroups who received different treatments or those in different disease stages and compared time to aggressive PD and overall survival in the high- and low-risk subgroups. RESULTS Among the constructed models, ModelCSD, combining clinical/semantic factors and deep learning radiomics, outperformed ModelCS and ModelD (areas under the curve [AUCs] for the training dataset: 0.741, 0.815, and 0.856; validation dataset: 0.780, 0.836, and 0.862), with statistical difference per the net reclassification improvement, the integrated discrimination improvement, and/or the DeLong test in both datasets. Besides, ModelCSD had the best calibration and decision curves. The performance of ModelCSD was not affected by treatment types (AUC: resection = 0.839; transarterial chemoembolization = 0.895; p = 0.183) or disease stages (AUC: BCLC [Barcelona Clinic Liver Cancer] stage 0 and A = 0.827; BCLC stage AB &B = 0.861; p = 0.537). Moreover, the high-risk group had a significantly shorter median time to aggressive PD than the low-risk group (training dataset hazard ratio [HR] = 0.108, p < 0.001; validation dataset HR = 0.058, p < 0.001) and poorer overall survival (training dataset HR = 0.357, p < 0.001; validation dataset HR = 0.204, p < 0.001). CONCLUSION Our deep learning-based model successfully stratified the risks of aggressive PD. In the high-risk population, current guideline indicates that first-line treatments are insufficient to prevent extrahepatic metastasis and macrovascular invasion and ensure survival benefits, so more therapies may be explored for these patients.
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Affiliation(s)
- Sirui Fu
- Zhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China
- Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China
| | - Meiqing Pan
- Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Jie Zhang
- Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China
| | - Hui Zhang
- Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, People’s Republic of China
| | - Zhenchao Tang
- Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, People’s Republic of China
| | - Yong Li
- Zhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China
| | - Wei Mu
- Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, People’s Republic of China
| | - Jianwen Huang
- Zhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China
| | - Di Dong
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Chongyang Duan
- Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China
| | - Xiaoqun Li
- Department of Interventional Treatment, Zhongshan City People’s Hospital, Zhongshan, People’s Republic of China
| | - Shuo Wang
- Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Xudong Chen
- Department of Radiology, Shenzhen People’s Hospital, Shenzhen, People’s Republic of China
| | - Xiaofeng He
- Interventional Diagnosis and Treatment Department, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Jianfeng Yan
- Department of Radiology, Yangjiang People’s Hospital, Yangjiang, People’s Republic of China
| | - Ligong Lu
- Zhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China
| | - Jie Tian
- Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, People’s Republic of China
- University of Chinese Academy of Sciences, Beijing, People’s Republic of China
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Feng B, Ma XH, Wang S, Cai W, Liu XB, Zhao XM. Application of artificial intelligence in preoperative imaging of hepatocellular carcinoma: Current status and future perspectives. World J Gastroenterol 2021; 27:5341-5350. [PMID: 34539136 PMCID: PMC8409162 DOI: 10.3748/wjg.v27.i32.5341] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/15/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor in China. Preoperative diagnosis of HCC is challenging because of atypical imaging manifestations and the diversity of focal liver lesions. Artificial intelligence (AI), such as machine learning (ML) and deep learning, has recently gained attention for its capability to reveal quantitative information on images. Currently, AI is used throughout the entire radiomics process and plays a critical role in multiple fields of medicine. This review summarizes the applications of AI in various aspects of preoperative imaging of HCC, including segmentation, differential diagnosis, prediction of histopathology, early detection of recurrence after curative treatment, and evaluation of treatment response. We also review the limitations of previous studies and discuss future directions for diagnostic imaging of HCC.
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Affiliation(s)
- Bing Feng
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao-Hong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shuang Wang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wei Cai
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xia-Bi Liu
- Beijing Laboratory of Intelligent Information Technology, School of Computer Science and Technology, Beijing Institute of Technology, Beijing 100081, China
| | - Xin-Ming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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HCC: role of pre- and post-treatment tumor biology in driving adverse outcomes and rare responses to therapy. Abdom Radiol (NY) 2021; 46:3686-3697. [PMID: 34195886 DOI: 10.1007/s00261-021-03192-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 06/19/2021] [Accepted: 06/21/2021] [Indexed: 12/12/2022]
Abstract
Liver cancer is the fastest-growing cause of cancer deaths in the United States and is a complex disease. The response of hepatocellular carcinoma (HCC) to treatment can be variable. Predicting response to determine the most effective therapy is an active area of research. Our understanding of underlying factors which drive response to therapy is continually increasing. As more therapies for the treatment of this disease evolve, it is crucial to identify and match the ideal therapy for a particular tumor and patient. The potential predicative imaging features of tumor behavior, while of research interest, have not been validated for clinical use and do not currently inform treatment planning. If further validated though, prognostic features may be used in the future to personalize treatment plans according to individual patients and tumors. Unexpected post-treatment responses such as potential tumor biology changes and abscopal effect which are important to be aware of. This review is intended for radiologists who routinely interpret post treatment HCC imaging and is designed to increase their cognizance about how HCC tumor biology drives response to therapy and explore rare responses to therapy.
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Wang TC, An TZ, Li JX, Pang PF. Systemic Inflammation Response Index is a Prognostic Risk Factor in Patients with Hepatocellular Carcinoma Undergoing TACE. Risk Manag Healthc Policy 2021; 14:2589-2600. [PMID: 34188570 PMCID: PMC8232961 DOI: 10.2147/rmhp.s316740] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 06/02/2021] [Indexed: 12/12/2022] Open
Abstract
Background Mounting evidence has shown that systemic inflammation response index (SIRI), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil and monocyte counts, is associated with poor prognosis for several tumors. However, the prognostic value of SIRI in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is elusive. Herein, we aimed to evaluate the correlation between SIRI and clinical outcomes in these patients. Methods A total of 194 consecutive patients who underwent TACE were included in this study. Patients were stratified into high and low SIRI groups based on the cut-off value using receiver operating characteristic (ROC) analysis. Independent risk factors for tumor response were analyzed using forward stepwise logistic regression. A one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) and overall survival (OS) between low and high SIRI patients. The discriminatory power of the combination of number of tumors and SIRI in predicting initial TACE response was evaluated by ROC analysis. Results Patients were divided into high SIRI (> 0.88) and low SIRI (≤ 0.88) groups. High SIRI (p = 0.003) and more than three tumors (p = 0.002) were significantly related to poorer tumor response. Moreover, the low SIRI group had longer PFS and OS than the high SIRI group (both P < 0.05) before and after PSM. Combination of SIRI and number of tumors can improve the predictive ability to predict initial TACE response with an area under the curve (AUC) of 0.678. Conclusion Pretreatment peripheral blood SIRI was found to be an independent predictor of tumor response and clinical outcomes in patients with HCC undergoing TACE. Patients with high SIRI may have a poor prognosis.
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Affiliation(s)
- Tian-Cheng Wang
- Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China.,Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China
| | - Tian-Zhi An
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China
| | - Jun-Xiang Li
- Department of Interventional Radiology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China
| | - Peng-Fei Pang
- Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
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High HBV Load Weakens Predictive Effect of Serum miR-122 on Response to Sorafenib in Hepatocellular Carcinoma Patients. JOURNAL OF ONCOLOGY 2021; 2021:9938207. [PMID: 34194500 PMCID: PMC8214498 DOI: 10.1155/2021/9938207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/26/2021] [Accepted: 06/03/2021] [Indexed: 11/17/2022]
Abstract
Background MiR-122 is a liver-specific microRNA. The aim of the study was to explore the association of serum miR-122 with response to sorafenib in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) patients and to further reveal the effect of the virus load on such potential relationship. Methods A total of 588 patients with HCC were retrospectively included. All of them were diagnosed with HBV-related locally advanced HCC and were treated with sorafenib. Therapeutic and prognostic information and other information were collected from medical records. Stored blood specimens that were obtained before sorafenib treatment were adopted to detect miR-122. Results The patients were divided into high-level group and low-level group according to the median of serum miR-122 level, and each group contained 294 patients. During the first 24 weeks after sorafenib treatment, the patients in the high-level group had more opportunities to experience progression-free survival (PFS) and overall survival (OS) than those in the low-level group (HR: 2.47, 95%CI: 1.24∼4.88; HR: 1.20, 95%CI: 1.09∼1.32). In the subgroup analysis, the relationship between serum miR-122 level and overall survival still existed in the patients with relatively lower HBV load (HR: 1.22, 95%CI: 1.09∼1.36), but not in the patients with higher HBV load (HR: 1.12, 95%CI: 0.93∼1.35). Conclusion Higher serum level of miR-122 at baseline was associated with a better response to sorafenib in HBV-related locally advanced HCC patients, and relatively high HBV load weakened such predictive effect mentioned above.
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Li X, Wang Y, Ye X, Liang P. Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development. Front Mol Biosci 2021; 8:635243. [PMID: 33928118 PMCID: PMC8076864 DOI: 10.3389/fmolb.2021.635243] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 02/09/2021] [Indexed: 12/12/2022] Open
Abstract
Despite the application of antiviral drugs and improved surveillance tools, the number of patients diagnosed with hepatocellular carcinoma (HCC) at an advanced stage and with a dismal prognosis is still on the rise. Systemic treatment with multiple multitargeted tyrosine kinase inhibitors (TKIs), such as sorafenib, has been a widely utilized approach for a decade. In addition, the use of a combination of TKIs with other types of compounds, including immune checkpoint inhibitors (ICIs) and antiangiogenic inhibitors, has shown efficacy in treating advanced HCC. However, the presence of intolerable adverse events, low disease response and control rates, and relative short overall survival of such combinatory therapies makes novel or optimized therapies for advance HCC urgently needed. Locoregional therapy (transarterial chemoembolization, and thermal ablation) can destroy primary tumors and decrease tumor burden and is widely used for HCC management. This type of treatment modality can result in local hypoxia and increased vascular permeability, inducing immunogenic effects by releasing tumor antigens from dying cancer cells and producing damage-associated molecular patterns that facilitate antiangiogenic therapy and antitumor immunity. The combination of systemic and locoregional therapies may further produce synergistic effects without overlapping toxicity that can improve prognoses for advanced HCC. In preliminary studies, several combinations of therapeutic modes exhibited promising levels of safety, feasibility, and antitumor effects in a clinical setting and have, thus, garnered much attention. This review aims to provide a comprehensive, up-to-date overview of the underlying mechanisms of combined systemic and locoregional therapies in the treatment of advanced HCC, commenting on both their current status and future direction.
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Affiliation(s)
- Xin Li
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Yaxi Wang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
- Department of Ultrasound, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Xin Ye
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
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Wang TC, An TZ, Li JX, Zhang ZS, Xiao YD. Development and Validation of a Predictive Model for Early Refractoriness of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma. Front Mol Biosci 2021; 8:633590. [PMID: 33816555 PMCID: PMC8012485 DOI: 10.3389/fmolb.2021.633590] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 01/07/2021] [Indexed: 01/03/2023] Open
Abstract
Objectives: To develop and validate a predictive model for early refractoriness of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: In this multicenter retrospective study, a total of 204 consecutive patients who initially underwent TACE were included. Early TACE refractoriness was defined as patients presented with TACE refractoriness after initial two consecutive TACE procedures. Of all patients, 147 patients (approximately 70%) were assigned to a training set, and the remaining 57 patients (approximately 30%) were assigned to a validation set. Predictive model was established using forward stepwise logistic regression and nomogram. Based on factors selected by logistic regression, a one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) between patients who were present or absent of early TACE refractoriness. PFS curve was estimated by Kaplan-Meier method and compared by log-rank test. Results: Logistic regression revealed that bilobar tumor distribution (p = 0.002), more than three tumors (p = 0.005) and beyond up-to-seven criteria (p = 0.001) were significantly related to early TACE refractoriness. The discriminative abilities, as determined by the area under the receiver operating characteristic (ROC) curve, were 0.788 in the training cohort and 0.706 in the validation cohort. After PSM, the result showed that patients who were absent of early TACE refractoriness had a significantly higher PFS rate than those of patients who were present (p < 0.001). Conclusion: This study presents a predictive model with moderate accuracy to identify patients with high risk of early TACE refractoriness, and patients with early TACE refractoriness may have a poor prognosis.
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Affiliation(s)
- Tian-Cheng Wang
- Department of Radiology, Secong Xiangya Hospital, Central South University, Changsha, China
| | - Tian-Zhi An
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Jun-Xiang Li
- Department of Interventional Radiology, Guizhou Medical University Affiliated Cancer Hospital, Guiyang, China
| | - Zi-Shu Zhang
- Department of Radiology, Secong Xiangya Hospital, Central South University, Changsha, China
| | - Yu-Dong Xiao
- Department of Radiology, Secong Xiangya Hospital, Central South University, Changsha, China
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Cao J, Dong Y, Fan P, Mao F, Chen K, Chen R, Huang B, Cheng Y, Wang WP. Early evaluation of treatment response to transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The role of dynamic three-dimensional contrast-enhanced ultrasound. Clin Hemorheol Microcirc 2021; 78:365-377. [PMID: 33682701 DOI: 10.3233/ch-201086] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. OBJECTIVE To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. METHODS In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1-3 days (T1) after treatment. Tumor microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. RESULTS Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. CONCLUSION Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients.
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Affiliation(s)
- Jiaying Cao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peili Fan
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Feng Mao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kailing Chen
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rongxin Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Beijian Huang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yaqing Cheng
- Department of Ultrasound in Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
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Qiu Z, Shen L, Jiang Y, Qiu J, Xu Z, Shi M, Yu Z, Ma Y, He W, Zheng Y, Li B, Wang G, Yuan Y. Transarterial chemoembolization (TACE) combined with apatinib versus TACE combined with sorafenib in advanced hepatocellular carcinoma patients: a multicenter retrospective study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:283. [PMID: 33708910 PMCID: PMC7944263 DOI: 10.21037/atm-20-5360] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background The combination of transarterial chemoembolization (TACE) with sorafenib has demonstrated superior efficacy over sorafenib and TACE monotherapy in hepatocellular carcinoma (HCC). Apatinib, a new targeted agent, has been recently reported to prolong the survival of HCC patients, either alone or in combination with TACE. However, the superior regimen between TACE-apatinib and TACE-sorafenib in HCC patients has not been determined. In this study, we compared the efficacy and safety of TACE-apatinib versus TACE-sorafenib in advanced stage HCC patients. Methods The data of 201 HCC patients who had received TACE-sorafenib or TACE-apatinib between January 2016 and June 2018 in three hospitals were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and adverse effects (AEs) between the two treatment groups were compared. A subgroup analysis based on the doses of targeted agents was also performed. Results No significant differences in baseline clinicopathological features were found between the two groups except for dose reduction. The TACE-apatinib group had higher incidences of hypertension, oral or anal ulcer and proteinuria, while the TACE-sorafenib group had higher incidences of diarrhea and alopecia. Grade 3/4 AEs occurred more frequently in the TACE-apatinib group than in the TACE-sorafenib group (52.3% vs. 22.6%, P<0.001). The TACE-sorafenib group had better PFS than the TACE-apatinib group (median PFS: 5.0 vs. 6.0 months, P=0.002) while the two groups showed no difference in OS (median OS: 13.0 vs. 13.0 months, P=0.448). The TACE-apatinib group had a higher rate of targeted agent dose reduction than the TACE-sorafenib group (53.5% vs. 17.4%, P<0.001). When the patients were stratified into normal and reduced-dose subgroups, those who received TACE-sorafenib exhibited improved PFS but similar OS compared with the patients who received TACE-apatinib in the reduced-dose subgroup (median OS: 12.0 vs. 13.3 months, P=0.614; median PFS: 3.0 vs. 7.0 months, P<0.001). Multivariable analysis validated that treatments and dose reduction were independent prognostic factors for PFS among all patients. Conclusions Compared with TACE-sorafenib, the strategy of TACE-apatinib yielded shorter PFS in advanced HCC patients while no difference in OS was observed. A high rate of AE-related dose reduction of apatinib could account for the observed differences.
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Affiliation(s)
- Zhiyu Qiu
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lujun Shen
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yiquan Jiang
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiliang Qiu
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zining Xu
- Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Mengting Shi
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Zhentao Yu
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Yanping Ma
- Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei He
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yun Zheng
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Binkui Li
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Guoying Wang
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yunfei Yuan
- State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China.,Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
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Wang W, Guo Y, Zhong J, Wang Q, Wang X, Wei H, Li J, Xiu P. The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma. Sci Rep 2021; 11:2415. [PMID: 33510294 PMCID: PMC7843639 DOI: 10.1038/s41598-021-82058-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.
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Affiliation(s)
- Wentao Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Yaxun Guo
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jingtao Zhong
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qi Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
| | - Xin Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Honglong Wei
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jie Li
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Peng Xiu
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China.
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China.
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Mikrovaskuläre Invasion als Marker für die Therapieeffektivität von TACE plus Sorafenib. ROFO-FORTSCHR RONTG 2020. [DOI: 10.1055/a-0999-7447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Lin PT, Teng W, Jeng WJ, Hsieh YC, Hung CF, Huang CH, Lui KW, Chen YC, Lin CC, Lin CY, Sheen IS, Lin SM. Add-on sorafenib is beneficial for hepatocellular carcinoma patients with transarterial chemoembolization refractoriness: a real-world experience. Eur J Gastroenterol Hepatol 2020; 32:1192-1199. [PMID: 31851084 DOI: 10.1097/meg.0000000000001637] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Sorafenib is the first proved target therapy that shows significant survival benefit in advanced hepatocellular carcinoma. This study was aimed to investigate whether add-on sorafenib be beneficial for those experienced transarterial chemoembolization refractoriness. METHODS From 2005 to 2016, a total of 656 treatment-naive hepatocellular carcinoma patients receiving transarterial chemoembolization treatment were recruited. Transarterial chemoembolization refractoriness was defined as progressive disease after two consecutive of transarterial chemoembolization treatment within 6 months. Patient's baseline characteristics, tumor burden, and parameters for liver function evaluation during treatment were analyzed. All the variables were compared between patients with and without transarterial chemoembolization refractoriness, as well as with and without add-on sorafenib. RESULTS Among the 656 patients, the median age was 62.5 (range 27.3-91.5) years old, and 74.5% were male. Transarterial chemoembolization refractoriness events were documented in 202 patients (30.8%). After multivariate logistic regression analysis, tumor size ≧5 cm, baseline alpha-fetoprotein level ≧200 mg/dl, elevation of alpha-fetoprotein ≧20%, and elevation of Child-Turcotte-Pugh score ≧2 points after first transarterial chemoembolization were the independent predictive factors for transarterial chemoembolization refractoriness. Twenty-two patients (10.9%) received add-on sorafenib treatment and 146 (72.3%) patients continued transarterial chemoembolization treatment alone. After 1:2 propensity score matching, patients with add-on sorafenib therapy had significantly longer median overall survival than transarterial chemoembolization treatment alone (23.1 vs. 11.0 months, log-rank P = 0.001). CONCLUSION The tumor size, baseline alpha-fetoprotein, and elevation of alpha-fetoprotein and Child-Turcotte-Pugh score after first transarterial chemoembolization were the predictors for transarterial chemoembolization refractoriness. For patients with transarterial chemoembolization refractoriness, add-on sorafenib achieved better survival benefit than transarterial chemoembolization treatment alone.
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Affiliation(s)
- Po-Ting Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
| | - Wei Teng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - Yi-Chung Hsieh
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - Chen-Fu Hung
- Chang Gung University College of Medicine
- Department of Radiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Chien-Hao Huang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - Kar-Wai Lui
- Chang Gung University College of Medicine
- Department of Radiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Yi-Cheng Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch
- Chang Gung University College of Medicine
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Liu KC, Hao YH, Lv WF, Jia WD, Ji CS, Zhou CZ, Cheng DL, Xu SB, Gao ZG, Su MX, Shi CS. Transarterial Chemoembolization Combined with Sorafenib in Patients with BCLC Stage C Hepatocellular Carcinoma. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:3461-3468. [PMID: 32904650 PMCID: PMC7457560 DOI: 10.2147/dddt.s248850] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 07/31/2020] [Indexed: 01/10/2023]
Abstract
Purpose Transcatheter arterial chemoembolization (TACE) and targeted therapy have become common methods in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of TACE combined with sorafenib (TACE-sorafenib) and TACE alone for the treatment of Barcelona clinical stage C HCC. Methods The clinical data of 75 patients with BCLC stage C HCC who received TACE-sorafenib or TACE as the initial treatment were retrospectively analyzed. Tumor response, time to progression (TTP), overall survival (OS), and adverse events were compared at 1 month after surgery in the two groups. Results One month after treatment, the disease control rate in the TACE-sorafenib group was higher than that in the TACE group alone (82.76% and 57.50%, respectively, P = 0.018). The median values of TTP and OS in the TACE-sorafenib group were longer than those in the TACE group (TTP was 7.6 and 3.4 months, respectively, P = 0.002; OS was 13.6 and 6.3 months, respectively, P = 0.041). The cumulative survival time at 3 months, 6 months, and 1 year was higher in the TACE-sorafenib group than in the TACE group (83.5%, 71.2%, 45.7% vs 57.4%, 40.6%, 21.2%). Sorafenib-related side effects such as hypertension, hand-foot syndrome, and oral ulcers were more common than those in the TACE group alone (P<0.05). Conclusion Compared with TACE treatment alone, TACE combined with sorafenib in BCLC-C stage HCC significantly improved disease control rate, TTP, and OS, and no significant increase in adverse reactions was observed.
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Affiliation(s)
- Kai-Cai Liu
- Infection Hospital, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, People's Republic of China
| | - Ying-Hong Hao
- Department of Radiology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230022, People's Republic of China
| | - Wei-Fu Lv
- Department of Radiology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230022, People's Republic of China
| | - Wei-Dong Jia
- Department of General Surgery, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230022, People's Republic of China
| | - Chu-Shu Ji
- Medical Oncology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230022, People's Republic of China
| | - Chun-Ze Zhou
- Department of Radiology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230022, People's Republic of China
| | - De-Lei Cheng
- Department of Radiology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230022, People's Republic of China
| | - Shao-Bao Xu
- Infection Hospital, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, People's Republic of China
| | - Zong-Gen Gao
- Infection Hospital, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, People's Republic of China
| | - Ming-Xue Su
- Infection Hospital, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, People's Republic of China
| | - Chang-Sheng Shi
- Infection Hospital, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, People's Republic of China
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Gu W, Tong Z. Sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) and microvascular infiltration: a systematic review and meta-analysis. J Int Med Res 2020; 48:300060520946872. [PMID: 32815430 PMCID: PMC7444130 DOI: 10.1177/0300060520946872] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 07/09/2020] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE Microvascular invasion is shown to be an independent risk factor for liver cancer recurrence. Timely treatment may reduce the recurrence rate and prolong total survival time. The aim of this study was to investigate the effectiveness of sorafenib in treating patients with hepatocellular carcinoma (HCC) and microvascular invasion. METHODS A comprehensive literature search was conducted in PubMed, EMBASE, MEDLINE, web of science and Cochrane Library databases for articles published up to December 2019. Two researchers independently reviewed and cross-checked independent reports with sufficient information. A meta-analysis was conducted to assess the impact of sorafenib on mortality in patients with HCC and microvascular involvement. RESULTS Four studies were included in the qualitative and quantitative analyses, comprising 955 cancer events and 505 cancer deaths. Meta-analyses showed that sorafenib treatment was associated with an improved survival rate versus no sorafenib treatment in patients with HCC and microvascular invasion (relative risk 1.369, 95% confidence interval 1.193, 1.570). CONCLUSIONS Sorafenib treatment may improve survival in patients with HCC and microvascular invasion. However, due to the potential for residual confounding, the results should be interpreted with caution.
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Affiliation(s)
- Wang Gu
- Anhui Medical University Third Affiliated Hospital, Hefei, Anhui Province, China
| | - Zhong Tong
- Anhui Medical University Third Affiliated Hospital, Hefei, Anhui Province, China
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Zhang T, Huang W, Dong H, Chen Y. Trans-catheter arterial chemoembolization plus Sorafenib, an unsuccessful therapy in the treatment of hepatocellular carcinoma?: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e20962. [PMID: 32702836 PMCID: PMC7373552 DOI: 10.1097/md.0000000000020962] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Trans-catheter arterial chemoembolization (TACE) plus Sorafenib is recommended as one of the primary means for treating hepatocellular carcinoma (HCC). This updated meta-analysis focuses on identifying the efficacy and safety of TACE plus Sorafenib versus TACE, which remains controversial despite years of exploration. METHOD PubMed, Medline, Embase, China Journal Full-text Database, Wanfang Database, and Weipu Database were used to retrieve the studies which are about comparing the clinical efficacy and safety of TACE+Sorafenib with TACE alone. The Review Manager (Version 5. 3) software was used to perform a meta-analysis of the results of studies which met the inclusion criteria recommended by the Cochrane Collaboration. RESULT Compared with TACE for treating primary HCC, TACE combined with Sorafenib can improve the 1 year, 2 years, 3 years, and 5 years overall survival rate (OS) of patients, respectively, and also improve disease control rate (DCR) and objective response rate (ORR). In terms of adverse reactions, the treatment group can lead to more complications significantly, such as hand-foot skin reaction, hypertension, diarrhea, rash, hair loss, and so on, most of which are relevant to Sorafenib related adverse reactions, but most patients have a good prognosis after symptomatic treatment. CONCLUSION The clinical efficacy of TACE combined with Sorafenib in treating primary hepatocellular carcinoma is better than TACE, and the safety is acceptable.
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Affiliation(s)
- Tao Zhang
- Nanshan School, Guangzhou Medical University
| | - Weisen Huang
- School of Pharmaceutical Sciences, Guangzhou Medical University
| | | | - Yijun Chen
- National Research Center of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
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Cheng Z, Wei-Qi J, Jin D. New insights on sorafenib resistance in liver cancer with correlation of individualized therapy. Biochim Biophys Acta Rev Cancer 2020; 1874:188382. [PMID: 32522600 DOI: 10.1016/j.bbcan.2020.188382] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 05/11/2020] [Accepted: 05/28/2020] [Indexed: 12/19/2022]
Abstract
Liver cancer is highly malignant and insensitive to cytotoxic chemotherapy and is associated with very poor patient prognosis. In 2007, the small-molecule targeted drug sorafenib was approved for the treatment of advanced liver cancer. In the subsequent ten years, sorafenib has been the only first-line therapeutic targeted drug for advanced hepatocellular carcinoma (HCC). However, a number of clinical studies show that a considerable percentage of patients with liver cancer are insensitive to sorafenib. The number of patients who actually benefit significantly from sorafenib treatment is very limited, and the overall efficacy of sorafenib is far from satisfactory, which has attracted the attention of researchers. Based on previous studies and reports, this article reviews the potential mechanisms of sorafenib resistance (SR) and summarizes the biomarkers and clinicopathological indicators that might be used for predicting sorafenib response and developing personalized therapy.
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Affiliation(s)
- Zhang Cheng
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital/Institute, Second Military Medical University, Shanghai 200433, China; National Center for Liver Cancer, Shanghai 200433, China
| | - Jiang Wei-Qi
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital/Institute, Second Military Medical University, Shanghai 200433, China
| | - Ding Jin
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital/Institute, Second Military Medical University, Shanghai 200433, China; National Center for Liver Cancer, Shanghai 200433, China.
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Transcatheter arterial chemoembolization alone or combined with ablation for recurrent intermediate-stage hepatocellular carcinoma: a propensity score matching study. J Cancer Res Clin Oncol 2020; 146:2669-2680. [PMID: 32449005 DOI: 10.1007/s00432-020-03254-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/12/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE The recurrence after curative hepatectomy is common. Limited data have investigated the effect of transcatheter arterial chemoembolization (TACE) combined with ablation in treating recurrent intermediate-stage hepatocellular carcinoma (HCC) after hepatectomy. We aim to compare the efficacy of TACE combined with ablation versus TACE alone in treating recurrent intermediate-stage HCC after hepatectomy. METHODS A total of 183 patients with recurrent intermediate-stage HCC after hepatectomy were enrolled at Sun Yat-sen University Cancer Centre, including 111 patients who underwent TACE alone and 72 patients who underwent TACE combined with ablation (TACE-Ablation). Overall survival (OS) and progression-free survival (PFS) were compared by the log-rank test. Propensity score matching (PSM) was used to reduce the confounding bias. RESULTS Before PSM, the 5-year OS rates were 43.3% vs. 27.9% (P = 0.001), and the 5-year PFS rates were 21.7% vs. 13.0% (P < 0.001) for TACE-Ablation and TACE-alone groups, respectively. After PSM, TACE-Ablation still resulted in better 5-year OS (41.6% vs. 30.2%, P = 0.028) and 5-year PFS rate (21.3% vs. 15.8%, P = 0.024) than that of TACE alone. Patients in TACE-Ablation group exhibited similar major complication rates to TACE-alone group but higher minor complication rates both before and after PSM. Cox regression analysis identified TACE-alone modality as an independently unfavourable predictor for OS and PFS (both P < 0.05). CONCLUSION TACE combined with ablation is safe and superior to TACE alone in tumour control and prolonging overall survival in recurrent intermediate-stage HCC after hepatectomy.
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