|
1
|
Wang Q, Ji X, Sun J, Zhang A, Jia J, Zhang T, Li W, Duan X. Stereotactic Body Radiotherapy Combined With Lenvatinib With or Without PD-1 Inhibitors as Initial Treatment for Unresectable Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2024; 120:1363-1376. [PMID: 38583495 DOI: 10.1016/j.ijrobp.2024.03.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 03/07/2024] [Accepted: 03/20/2024] [Indexed: 04/09/2024]
Abstract
PURPOSE The aim of this study was to compare the clinical benefit and safety of the triple combination of stereotactic body radiotherapy (SBRT), lenvatinib, and programmed cell death protein 1 (PD-1) inhibitors with the dual combination of SBRT and lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC). METHODS AND MATERIALS Patients with uHCC who received SBRT in combination with lenvatinib and PD-1 inhibitors or SBRT in combination with lenvatinib alone as first-line treatment from October 2018 to July 2022 were reviewed in this study. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were intrahepatic PFS, extrahepatic PFS, and objective remission rate. In addition, safety profiles were assessed by analyzing treatment-related adverse events between the two groups to assess safety profiles. RESULTS In total, 214 patients with uHCC who received combination therapy were included in this retrospective study. Among them, 146 patients received triple combination therapy of SBRT, lenvatinib, and PD-1 inhibitors (SBRT-L-P group), and 68 patients received dual therapy of SBRT and lenvatinib (SBRT-L group). The median OS times of the 2 groups were 31.2 months and 17.4 months, respectively (P < .001). The median PFS time was significantly longer in the SBRT-L-P group than in the SBRT-L group (15.6 months vs 8.8 months, P < .001). Additionally, the median intrahepatic PFS (17.5 vs 9.9 months, P < .001) and extrahepatic PFS (20.9 vs 11.6 months, P < .001) were significantly longer in the SBRT-L-P group than in the SBRT-L group. The objective remission rate in the SBRT-L-P group was higher than in the SBRT-L group (63.0 vs 39.7%, P = .002). The incidence and severity of treatment-related adverse events in the SBRT-L-P group were comparable to those in the SBRT-L group. CONCLUSION The use of both lenvatinib and PD-1 inhibitors with SBRT in patients with uHCC was associated with improved overall survival compared with lenvatinib and SBRT alone with a manageable safety profile.
Collapse
Affiliation(s)
- Quan Wang
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xiaoquan Ji
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Jing Sun
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Aimin Zhang
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jun Jia
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Teng Zhang
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Wengang Li
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China.
| | - Xuezhang Duan
- Department of Radiation Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
| |
Collapse
|
|
2
|
Ou X, Wu J, Wu J, Fu Y, Zeng Z, Li S, Li Y, Liu D, Li H, Li B, Zhou J, Zhuang S, Cheng S, Zhang Z, Wang K, Qu S, Yan M. Efficacy of Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study. Cancer Res Treat 2024; 56:1207-1218. [PMID: 38697847 PMCID: PMC11491243 DOI: 10.4143/crt.2023.1165] [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: 10/27/2023] [Accepted: 04/29/2024] [Indexed: 05/05/2024] Open
Abstract
PURPOSE The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. MATERIALS AND METHODS This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. RESULTS During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. CONCLUSION Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.
Collapse
Affiliation(s)
- Xiangye Ou
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Junyi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jiayi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Yangkai Fu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Zhenxin Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Shuqun Li
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Yinan Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Deyi Liu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Han Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Bin Li
- Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jianyin Zhou
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Shaowu Zhuang
- Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zhibo Zhang
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Kai Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shuang Qu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hematology, Fujian Provincial Hospital, Fuzhou, China
| | - Maolin Yan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| |
Collapse
|
|
3
|
Kim JH, Kim GH, Gwon DI. Reappraisal of transarterial radioembolization for liver-confined hepatocellular carcinoma with portal vein tumor thrombosis: Editorial on "Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis". Clin Mol Hepatol 2024; 30:659-662. [PMID: 39019082 PMCID: PMC11540354 DOI: 10.3350/cmh.2024.0516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/16/2024] [Accepted: 07/16/2024] [Indexed: 07/19/2024] Open
Affiliation(s)
- Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gun Ha Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
4
|
Dutta D, Yarlagadda S, Kalavagunta S, Nair H, Sasidharan A, Nimmya SK, Kannan R, George S, Edappattu A, Haridas NK, Jose WM, Keechilat P, Valsan A, Koshy A, Gopalakrishna R, Sadasivan S, Gopalakrishnan U, Balakrishnan D, Sudheer OV, Surendran S. Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma. J Clin Exp Hepatol 2024; 14:101404. [PMID: 38680618 PMCID: PMC11053332 DOI: 10.1016/j.jceh.2024.101404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 03/22/2024] [Indexed: 05/01/2024] Open
Abstract
Background/aims The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.
Collapse
Affiliation(s)
- Debnarayan Dutta
- Department of Radiation Oncology, Amrita Institute of Medical Science, Kochi, India
| | - Sreenija Yarlagadda
- Department of Radiation Oncology, Amrita Institute of Medical Science, Kochi, India
| | - Sruthi Kalavagunta
- Department of Radiation Oncology, Amrita Institute of Medical Science, Kochi, India
| | - Haridas Nair
- Department of Radiation Oncology, Amrita Institute of Medical Science, Kochi, India
| | - Ajay Sasidharan
- Department of Radiation Oncology, Amrita Institute of Medical Science, Kochi, India
| | - Sathish Kumar Nimmya
- Department of Radiation Oncology, Amrita Institute of Medical Science, Kochi, India
| | - Rajesh Kannan
- Radiology, Amrita Institute of Medical Science, Kochi, India
| | - Shibu George
- Medical Gastroenterology, Amrita Institute of Medical Science, Kochi, India
| | - Annex Edappattu
- Medical Physics, Amrita Institute of Medical Science, Kochi, India
| | | | - Wesley M. Jose
- Medical Oncology, Amrita Institute of Medical Science, Kochi, India
| | | | - Arun Valsan
- Medical Gastroenterology, Amrita Institute of Medical Science, Kochi, India
| | - Anoop Koshy
- Medical Gastroenterology, Amrita Institute of Medical Science, Kochi, India
| | | | - Shine Sadasivan
- Medical Gastroenterology, Amrita Institute of Medical Science, Kochi, India
| | | | - Dinesh Balakrishnan
- Surgical Gastroenterology, Amrita Institute of Medical Science, Kochi, India
| | | | | |
Collapse
|
|
5
|
Garcia A, Mathew SO. Racial/Ethnic Disparities and Immunotherapeutic Advances in the Treatment of Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:2446. [PMID: 39001508 PMCID: PMC11240753 DOI: 10.3390/cancers16132446] [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: 05/24/2024] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/16/2024] Open
Abstract
Hepatocellular carcinoma (HCC) remains one of the leading causes of death among many associated liver diseases. Various conventional strategies have been utilized for treatment, ranging from invasive surgeries and liver transplants to radiation therapy, but fail due to advanced disease progression, late screening/staging, and the various etiologies of HCC. This is especially evident within racially distinct populations, where incidence rates are higher and treatment outcomes are worse for racial/ethnic minorities than their Caucasian counterparts. However, with the rapid development of genetic engineering and molecular and synthetic biology, many novel strategies have presented promising results and have provided potential treatment options. In this review, we summarize past treatments, how they have shaped current treatments, and potential treatment strategies for HCC that may prove more effective in the future.
Collapse
Affiliation(s)
- Alexsis Garcia
- Department of Microbiology, Immunology & Genetics, UNT Health Science Center, Fort Worth, TX 76107, USA
| | - Stephen O Mathew
- Department of Microbiology, Immunology & Genetics, UNT Health Science Center, Fort Worth, TX 76107, USA
| |
Collapse
|
|
6
|
Liu J, Zhang G, Li X, Zheng C, Kan X. Enhancing the therapeutic impact of sublethal radiofrequency hyperthermia in malignant solid tumor treatment. Heliyon 2024; 10:e29866. [PMID: 38681568 PMCID: PMC11053292 DOI: 10.1016/j.heliyon.2024.e29866] [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: 02/13/2024] [Revised: 04/16/2024] [Accepted: 04/16/2024] [Indexed: 05/01/2024] Open
Abstract
Radiofrequency ablation (RFA) is an effective alternative to surgery for managing some malignant solid tumors. However, for medium-to-large tumors (>3 cm), tumors adjacent to large blood vessels, and certain irregular tumors, sublethal radiofrequency hyperthermia (RFH) often produces a margin of ablated tumor owing to the "heat-sink" effect. This effect typically leaves behind viable residual tumors at the margin. Several studies have reported that a sublethal RFH can significantly enhance the efficacy of chemotherapy, radiotherapy, immunotherapy, and gene therapy for malignant solid tumors. The possible mechanisms by which RFH enhances these therapies include heat-induced tissue fracturing, increased permeability of the cytoplasmic membrane, exaggerated cellular metabolism, blockade of the repair pathways of radiation-damaged tumor cells, and activation of the heat shock protein pathways. Therefore, RFA in combination with chemotherapy, radiotherapy, immunotherapy, or gene therapy may help reduce the rates of residual and recurrent tumors after RFA of malignant solid tumors.
Collapse
Affiliation(s)
- Jiayun Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Guilin Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xinyi Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| |
Collapse
|
|
7
|
Kaneko T, Makishima H, Wakatsuki M, Hiroshima Y, Matsui T, Yasuda S, Okada NN, Nemoto K, Tsuji H, Yamada S, Miyazaki M. Carbon-ion radiotherapy for hepatocellular carcinoma with major vascular invasion: a retrospective cohort study. BMC Cancer 2024; 24:383. [PMID: 38532338 DOI: 10.1186/s12885-024-12154-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 03/20/2024] [Indexed: 03/28/2024] Open
Abstract
BACKGROUND Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. METHODS This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan-Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. RESULTS In total, 76 patients with a median age of 71 years (range, 45-86 years) were evaluated. Among them, 68 had Child-Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5-180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7-79.4%), 32.7% (95% CI: 22.0-43.8%), and 8.9% (95% CI: 1.7-23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. CONCLUSIONS C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.
Collapse
Affiliation(s)
- Takashi Kaneko
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
- Department of Radiology, Division of Radiation Oncology, Yamagata University, Faculty of Medicine, Yamagata, Japan
| | - Hirokazu Makishima
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
- Department of Radiation Oncology, University of Tsukuba, Tsukuba, Japan
| | - Masaru Wakatsuki
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan.
| | - Yuichi Hiroshima
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
- Department of Radiation Oncology, University of Tsukuba, Tsukuba, Japan
- Department of Radiation Oncology, Ibaraki Prefectural Central Hospital, Ibaraki Cancer Center, Kasama, Japan
| | - Toshiaki Matsui
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
- Department of Radiation Oncology, Saitama Cancer Center, Saitama, Japan
| | - Shigeo Yasuda
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
- Department of Radiation Oncology, Chiba Rosai Hospital, Chiba, Japan
| | - Naomi Nagatake Okada
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
| | - Kenji Nemoto
- Department of Radiology, Division of Radiation Oncology, Yamagata University, Faculty of Medicine, Yamagata, Japan
| | - Hiroshi Tsuji
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
| | - Shigeru Yamada
- QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan
| | - Masaru Miyazaki
- Mita Hospital, International University of Health and Welfare, Tokyo, Japan
| |
Collapse
|
|
8
|
Kim J, Jeong WK, Kim JM, Ha SY, Kim K. Refining MRI-based criteria for portal vein invasion in hepatocellular carcinoma: improving sensitivity beyond portal vein tumor thrombosis. Abdom Radiol (NY) 2024; 49:437-446. [PMID: 37989897 DOI: 10.1007/s00261-023-04106-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/11/2023] [Accepted: 10/18/2023] [Indexed: 11/23/2023]
Abstract
PURPOSE To investigate the imaging features indicating portal vein invasion (PVI) of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI and to create more accurate diagnostic criteria than the presence of portal vein tumor thrombosis (PVTT) on MRI. METHODS This retrospective study included patients with surgically resected HCC larger than 5 cm, and the presence of PVI was investigated. On MRI, we evaluated the image findings of portal vein occlusion, the parenchymal signal change caused by hemodynamic alterations of the portal vein, and their combination showing the highest odds ratio (OR) to define the diagnostic criteria for radiological PVI detection (rPVI criteria). The diagnostic performance and recurrence-free survival were compared between the rPVI criteria and the presence of PVTT using McNemar's test and Kaplan-Meier method, respectively. Interobserver agreement was evaluated using Cohen's weighted ĸ statistics. RESULTS Of 189 enrolled patients, 25 (13.2%) had PVI on histology. To diagnose PVI on MRI, either peripheral wedge-shaped arterial peritumoral hyperemia with an abrupt cut-off of a portal vein or the presence of PVTT had the highest OR (41.67, p < 0.001). The sensitivity of PVI was significantly increased under this diagnostic criterion (64.0% to 88.0%; p = 0.031) with comparable accuracy (95.2% vs. 94.7%; p > 0.999). In terms of recurrence-free survival, the patient group with rPVI was significantly worse (p = 0.017) compared with the patients without rPVI. Interobserver agreement of radiologic findings was substantial (ĸ = 0.64). CONCLUSION Diagnostic criteria for radiologically PVI detection increase the sensitivity more than the only presence of PVTT.
Collapse
Affiliation(s)
- Jeongju Kim
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
- Department of Digital Health, SAIHST, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Data Convergence & Future Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
9
|
Dong A, Zhu M, Zhang Z, Fan W, Wu Z, Chen Y, Tu J, Zhang Y, Zhuang W, He X, Peng Z. Efficacy of radiation plus transarterial chemoembolization and lenvatinib in hepatocellular carcinoma with portal vein tumor thrombus. Front Oncol 2023; 13:1320818. [PMID: 38173836 PMCID: PMC10763235 DOI: 10.3389/fonc.2023.1320818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 12/04/2023] [Indexed: 01/05/2024] Open
Abstract
Background We aimed to investigate the efficacy of a novel regimen, external beam radiation (RT) combined with trans arterial chemoembolization (TACE) and lenvatinib (LEN), in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus. Methods We prospectively observed 102 participants from three tertiary medical centers in China between October 2018 and October 2020, who chose either RT plus TACE and LEN (RT-TACE-LEN) or TACE and LEN (TACE-LEN). LEN (12 mg or 8 mg daily) was administrated orally and continued until progression or intolerable side effects were noted. TACE was given one day after administration of LEN, and RT began within 4 weeks after the first TACE. The median dose/fraction of RT was 50 Gy/25 fractions (range: 45-60 Gy/25 fractions). Overall survival and progression free survival were compared between two groups, and complications were assessed. Results Both 51 patients received RT-TACE-LEN and TACE-LEN, respectively. Most patients had tumor size> 5 cm (73.8%) and tumor number≥ 2 (69.9%). The overall incidence of toxicities was significantly higher in RT-TACE-LEN group than TACE-LEN group (100% vs. 64.7%, p< 0.001), but incidences of grade 3-4 toxicities were comparable (54.9% vs. 49.0%, p= 0.552). Both median overall survival (22.8 vs. 17.1 months, p= 0.031) and median progression-free survival (12.8 vs. 10.5 months, p= 0.035) were significantly longer after RT-TACE-LEN treatment than TACE-LEN. Conclusions The addition of RT to TACE and LEN was safe, and might improve clinical outcomes of patients with advanced HCC, which needs conformation from further studies.
Collapse
Affiliation(s)
- Aoran Dong
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Meiyan Zhu
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zeyu Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Zhiqiang Wu
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yong Chen
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jianfei Tu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, Lishui, China
| | - Yaojun Zhang
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wenquan Zhuang
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaofang He
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
10
|
Lin YM, Fellman BM, Taiji R, Paolucci I, Silva JAM, Koay EJ, Avritscher R, Mahvash A, Holliday EB, Lee SS, Kaseb AO, Das P, Vauthey JN, Odisio BC. Salvage Locoregional Therapy Following Progression After Radiotherapy for Hepatocellular Carcinoma Is Associated with Improved Outcomes. J Gastrointest Surg 2023; 27:1867-1875. [PMID: 37268830 DOI: 10.1007/s11605-023-05712-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 05/13/2023] [Indexed: 06/04/2023]
Abstract
PURPOSE To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following radiotherapy. METHODS This single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015-2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors. RESULTS A total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (n = 33), ablation (n = 11), selective internal radiotherapy (n = 7), and external beam radiotherapy (n = 8). At a median follow-up of 15.1 months (range, 3.4-54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child-Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months; p = 0.03). CONCLUSIONS Salvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy.
Collapse
Affiliation(s)
- Yuan-Mao Lin
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Bryan M Fellman
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Ryosuke Taiji
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Iwan Paolucci
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Jessica Albuquerque Marques Silva
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Eugene J Koay
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Rony Avritscher
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Armeen Mahvash
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Emma B Holliday
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Sunyoung S Lee
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Prajnan Das
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Bruno C Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
| |
Collapse
|
|
11
|
Kim N, Yu JI, Park HC, Hong JY, Lim HY, Goh MJ, Paik YH. Nomogram for predicting overall survival in patients with large (>5 cm) hepatocellular carcinoma based on real-world practice. JOURNAL OF LIVER CANCER 2023; 23:350-361. [PMID: 37670423 PMCID: PMC10565549 DOI: 10.17998/jlc.2023.08.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/02/2023] [Accepted: 08/10/2023] [Indexed: 09/07/2023]
Abstract
BACKGROUND/AIM Patients with large (>5 cm) hepatocellular carcinoma (HCC) have limited treatment options, thus necessitating the identification of prognostic factors and the development of predictive tools. This study aimed to identify prognostic factors and to construct a nomogram to predict survival outcomes in patients with large HCC. METHODS A cohort of 438 patients, who were diagnosed with large HCC at a tertiary hospital between 2015 and 2018, was analyzed. Cox proportional hazards models were used to identify key prognosticators of overall survival (OS), and an independent set of prognostic factors was used to develop a nomogram. The discrimination and calibration abilities of the nomogram were assessed and internal validation was performed using cross-validation and bootstrapping methods. RESULTS During a median follow-up of 9.3 months, the median OS was 9.9 months, and the 1-year OS rate was 43.9%. Multivariable Cox regression analysis revealed that performance status, modified albumin-bilirubin grade, tumor size, extent of portal vein tumor thrombosis, and initial treatment significantly affected OS. The newly developed nomogram incorporating these variables demonstrated favorable accuracy (Harrell's concordance index, 0.807). CONCLUSIONS The newly developed nomogram facilitated the estimation of individual survival outcomes in patients with large HCC, providing an acceptable level of accuracy.
Collapse
Affiliation(s)
- Nalee Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Yong Hong
- Department of Intenal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ho Yeong Lim
- Department of Intenal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Myung Ji Goh
- Department of Intenal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Intenal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
12
|
Lee HA, Lee S, Lee HL, Song JE, Lee DH, Han S, Shim JH, Kim BH, Choi JY, Rhim H, Kim DY. The efficacy of treatment for hepatocellular carcinoma in elderly patients. JOURNAL OF LIVER CANCER 2023; 23:362-376. [PMID: 37705145 PMCID: PMC10565541 DOI: 10.17998/jlc.2023.08.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/22/2023] [Accepted: 08/03/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND/AIM Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. METHODS Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. RESULTS Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P<0.001). In early-stage HCC, surgery yielded significantly lower OS in elderly patients compared to non-elderly patients (median, 97.4 vs. 138.0 months; P<0.001), however, local ablation (median, 82.2 vs. 105.5 months) and transarterial therapy (median, 42.6 vs. 56.9 months) each provided comparable OS between the two groups after inverse probability of treatment weighting (IPTW) analysis (all P>0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). CONCLUSIONS Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.
Collapse
Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Sangheun Lee
- Department of Internal Medicine, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Hae Lim Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Eun Song
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Dong Hyeon Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Sojung Han
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University, Eulji University School of Medicine, Uijeongbu, Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Jong Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyunchul Rhim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Cancer Center, Severance Hospital, Seoul, Korea
| |
Collapse
|
|
13
|
Li X, Ding X, Liu M, Wang J, Sun W, Teng Y, Xu Y, Wu H, Li W, Zhou L, Chen J. A multicenter prospective study of TACE combined with lenvatinib and camrelizumab for hepatocellular carcinoma with portal vein tumor thrombus. Cancer Med 2023; 12:16805-16814. [PMID: 37387602 PMCID: PMC10501288 DOI: 10.1002/cam4.6302] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 03/25/2023] [Accepted: 06/20/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) predicts a poor prognosis. The aim of the present study was to evaluate the efficacy and safety of using lenvatinib and camrelizumab combined with transarterial chemoembolization (TACE) to treat HCC with PVTT. METHODS This was a single-arm, open-label, multicenter, and prospective study. Eligible patients with advanced HCC accompanied by PVTT were enrolled to receive TACE combined with lenvatinib and camrelizumab. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS Between April 2020 and April 2022, 69 patients were successfully enrolled. With a median follow-up time of 17.3 months, the median age of the patient cohort was 57 years (range: 49-64 years). According to modified Response Evaluation Criteria in Solid Tumors, the ORR was 26.1% (18 partial responses [PRs]) and the DCR was 78.3% (18 PRs, 36 stable diseases [SDs]). The median PFS (mPFS) and median OS (mOS) were 9.3 and 18.2 months, respectively. And tumor number >3 was identified as an adverse risk factor for both PFS and OS. The most common adverse events across all grades included fatigue (50.7%), hypertension (46.4%), and diarrhea (43.5%). Twenty-four patients (34.8%) experienced Grade 3 toxicity that was relieved by dose adjustment and symptomatic treatment. No treatment-related deaths occurred. CONCLUSIONS TACE combined with lenvatinib and camrelizumab is a well-tolerated modality treatment with promising efficacy for advanced HCC with PVTT.
Collapse
Affiliation(s)
- Xiaomi Li
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| | - Xiaoyan Ding
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| | - Mei Liu
- Department of Oncology, Beijing You'an HospitalCapital Medical UniversityBeijingChina
| | - Jingyan Wang
- Department of Interventional Radiology, The Fifth Medical CenterChinese PLA General HospitalBeijingChina
| | - Wei Sun
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| | - Ying Teng
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| | - Yawen Xu
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| | - Hongxiao Wu
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| | - Wendong Li
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| | - Lin Zhou
- Department of Interventional Radiology, The Fifth Medical CenterChinese PLA General HospitalBeijingChina
| | - Jinglong Chen
- Department of Cancer Center, Beijing Ditan HospitalCapital Medical UniversityBeijingChina
| |
Collapse
|
|
14
|
Chang PY, Lee RC, Liang PC, Liu YS, Chuang VP, Wu DK, Cheng YF, Huang JI, Tseng HS, Hung CF, Wu RH, Chern MC, Cheng HM, Wu CH, Cheng SM, Chiang CL, Liang HL. Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment. Front Oncol 2023; 13:1186674. [PMID: 37427137 PMCID: PMC10328116 DOI: 10.3389/fonc.2023.1186674] [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: 03/15/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
Collapse
Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imagine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Vicent P. Chuang
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jen-I. Huang
- Department of Radiology, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan
| | - Hsiuo-Shan Tseng
- Department of Radiology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Radiology, Chang−Gung Memorial Hospital, Taoyuan, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Chih Chern
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Hua-Ming Cheng
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Horng Wu
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - She-Meng Cheng
- Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| |
Collapse
|
|
15
|
Kim SH, Moon DB, Park YH, Lee SG, Kim KH, Hwang S, Ahn CS, Ha TY, Song GW, Jung DH, Park GC, Kim M, Na BG, Yang G, Kim SM, Oh RK. Favorable Prognostic Factors for Survival Outcomes of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis After Hepatectomy. Ann Surg Oncol 2023:10.1245/s10434-023-13316-7. [PMID: 37043034 DOI: 10.1245/s10434-023-13316-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 02/17/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND This study aimed to investigate prognostic factors of recurrence and survival associated with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). PATIENTS AND METHODS This retrospective study included 161 patients with HCC with PVTT who underwent hepatectomy between January 2003 and January 2014 at the Asan Medical Center. Regression analyses were conducted to identify favorable predictive factors for overall survival (OS) and recurrence-free survival (RFS). RESULTS The median follow-up was 15.9 months, while 1-, 3-, and 5-year OS was 65.0%, 38.4%, and 36.0%, respectively, and 1-year RFS was 25.5%. There were no significant differences in OS and RFS between the patients with portal vein invasion (Vp) 1-2 and Vp3-4 PVTT. Patients with intrahepatic recurrence had significantly better overall survival than patients with extrahepatic recurrence. Transcatheter arterial chemoembolization and radiofrequency ablation were the most effective treatments for intrahepatic metastasis, and surgery was the most effective treatment for extrahepatic metastasis. On multivariate analysis, absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection were favorable prognostic factors for OS and R0 resection, and absence of microvascular invasion was a favorable prognostic factor for RFS. CONCLUSION The long-term outcome of patients with HCC with PVTT can be improved under consideration of favorable prognostic factors including absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection, R0 resection, and absence of microvascular invasion. In addition, recurrent HCC required aggressive management to prolong overall survival.
Collapse
Affiliation(s)
- Sang-Hoon Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Yo-Han Park
- Division of Hepatobiliary Surgery, Department of Surgery, On Hospital, Busan, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Minjae Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byeong-Gon Na
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Geunhyeok Yang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Min Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Rak-Kyun Oh
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
16
|
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
| |
Collapse
|
|
17
|
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: 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: 09/18/2022] [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.
Collapse
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
| |
Collapse
|
|
18
|
Wang K, Xiang YJ, Yu HM, Cheng YQ, Liu ZH, Zhong JY, Feng S, Ni QZ, Zhu HF, Pan WW, Li JJ, Liang C, Zhou HK, Meng Y, Lau WY, Cheng SQ. Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study. Front Immunol 2023; 14:1107542. [PMID: 36875125 PMCID: PMC9978499 DOI: 10.3389/fimmu.2023.1107542] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 02/08/2023] [Indexed: 02/18/2023] Open
Abstract
Background and aims The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients. Methods This multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety. Results Of 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths. Conclusions IMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study. Clinical trial registration http://www.chictr.org.cn, Identifier ChiCTR2200061793.
Collapse
Affiliation(s)
- Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Yan-Jun Xiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Hong-Ming Yu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Yu-Qiang Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Zong-Han Liu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Jing-Ya Zhong
- Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China
| | - Shuang Feng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Naval Medical University Shanghai, Shanghai, China
| | - Qian-Zhi Ni
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.,CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Hong-Fei Zhu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Wei-Wei Pan
- Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.,G60 STI Valley Industry & Innovation Institute, Jiaxing University, Jiaxing, China
| | - Jing-Jing Li
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Chao Liang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hong-Kun Zhou
- The First Hospital of Jiaxing Affiliated Hospital of Jiaxing University, Jiaxing University, Jiaxing, China
| | - Yan Meng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Naval Medical University Shanghai, Shanghai, China
| | - Wan Yee Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.,Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.,Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, China.,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,The First Hospital of Jiaxing Affiliated Hospital of Jiaxing University, Jiaxing University, Jiaxing, China
| |
Collapse
|
|
19
|
2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
|
|
20
|
Guo L, Wei X, Feng S, Zhai J, Guo W, Shi J, Lau WY, Meng Y, Cheng S. Radiotherapy prior to or after transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus: a randomized controlled trial. Hepatol Int 2022; 16:1368-1378. [PMID: 36271176 DOI: 10.1007/s12072-022-10423-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 09/09/2022] [Indexed: 11/24/2022]
Abstract
INTRODUCTION To compare survival outcomes of radiotherapy (RT) prior to transcatheter arterial chemoembolization (TACE) (RT + TACE) with TACE followed with RT (TACE + RT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). METHODS A randomized controlled study was conducted from August 2016 to December 2019 on patients with unresectable HCC and PVTT. The patients were randomly assigned to RT + TACE group or TACE + RT group in a 1:1 ratio. Evaluation of therapeutic effects on the primary tumor was based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while that on PVTT was based on the changing of Cheng's PVTT classification. The primary end-point was overall survival (OS). RESULTS The 120 patients who entered this study were evenly assigned to two groups. In the intention-to-treat (ITT) population, the OS rates for RT + TACE group at 1, 2 and 3 years were 61.7%, 27.4% and 15.6%, compared with 45.0%, 16.1% and 4.7% in TACE + RT group. The median OS was increased in patients with RT + TACE compared with those who had TACE + RT with a marginally significance (15.4 versus 11.5 months, HR = 0.68, 95% CI 0.46-1.01, p = 0.054). The median progression-free survival (PFS) in RT + TACE group was 6.6 months versus 4.2 months in TACE + RT group (HR = 0.66, 95% CI 0.46-0.96, p = 0.030). The corresponding disease control rate (DCR) at 3 months was 86.7% versus 66.7% (p = 0.017) and 61.7% versus 46.7% (p = 0.099) at 6 months. In subgroup analyses, RT + TACE was associated with better OS (HR, 0.48; 95% CI 0.33-0.99, p = 0.048) and PFS (HR, 0.55; 95% CI 0.33-0.93, p = 0.026) versus TACE + RT among patients with type III/IV PVTT. There were 3 patients in RT + TACE group and 2 in TACE + RT group had adverse events ≥ grade 3. CONCLUSION Applying RT prior to TACE provided better survival outcomes than TACE followed by RT for patients with HCC and PVTT, which may act as an optimized regional modality to further improve local control rates (Trial registration: ChiCTR ChiCTR2000033573.).
Collapse
Affiliation(s)
- Lei Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China
| | - Xubiao Wei
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China
| | - Shuang Feng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China
| | - Jian Zhai
- Department of Intervention, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai, 200438, China
| | - Weixing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China
| | - Wan Yee Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China.,Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Yan Meng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China.
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, 225 Changhai Road, Yangpu District, Shanghai, 200438, China.
| |
Collapse
|
|
21
|
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 161] [Impact Index Per Article: 53.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
|
|
22
|
Li W, Pei Y, Wang Z, Liu J. Efficacy of transarterial chemoembolization monotherapy or combination conversion therapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis. Front Oncol 2022; 12:930868. [PMID: 35978834 PMCID: PMC9377519 DOI: 10.3389/fonc.2022.930868] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a highly malignant disease with poor prognosis, and most cases were already considered unresectable at the time of presentation. Conversion therapy, as an emerging treatment, is designed to provide patients with initially unresectable hepatocellular carcinoma (uHCC) the opportunity to undergo radical resection. At present, conversion therapy for patients with uHCC remains controversial. Transarterial chemoembolization (TACE) is currently the most widely selected treatment for uHCC, but its efficacy as a conversion therapy remains controversial. Methods We compared and evaluated the conversion rate for and tumor response to TACE monotherapy or combination therapy. Meanwhile, postoperative complications and overall survival (OS) in uHCC patients who underwent conversion therapy were also analyzed. Results A total of 18 studies were included in this meta-analysis. The conversion rate for triple therapy [TACE in combination with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs)] was 42% [95% confidence interval (CI), 0.29-0.56], higher than any other group [TACE monotherapy: 10% (95% CI, 0.08-0.12), bigeminy therapy: 19% (95% CI, 0.06-0.36)]. Meanwhile, triple therapy yielded a better tumor response than TACE monotherapy or bigeminy therapy. Among the patients with successful surgical resection after conversion therapy, the pooled postoperative OS rates at 1, 2, and 5 years were 90% (95% CI, 0.81-0.97), 58% (95% CI, 0.42-0.73), and 42% (95% CI, 0.26-0.60), respectively, and the major postoperative complications were biliary leakage (7%; 95% CI, 0.03-0.12) and liver failure (3%; 95% CI, 0.00-0.07). Conclusion TACE conversion therapies showed good conversion rates, especially the triple therapy of TACE in combination with TKIs and ICIs. Surgical resection after successful conversion therapy could maximize the outcome of patients with uHCC.
Collapse
Affiliation(s)
| | | | | | - Jinlong Liu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| |
Collapse
|
|
23
|
Lee HA, Seo YS, Shin IS, Yoon WS, Lee HY, Rim CH. Efficacy and feasibility of surgery and external radiotherapy for hepatocellular carcinoma with portal invasion: A meta-analysis. Int J Surg 2022; 104:106753. [DOI: 10.1016/j.ijsu.2022.106753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/18/2022] [Accepted: 06/20/2022] [Indexed: 11/28/2022]
|
|
24
|
Hou JP, Shi YB, Fu YF, Li H. I-125 seeds insertion with TACE for advanced HCC: a meta-analysis of randomized controlled trials. MINIM INVASIV THER 2022; 31:848-855. [PMID: 35107390 DOI: 10.1080/13645706.2022.2033786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE To assess the effectiveness of I-125 seeds (IS) insertion with transcatheter arterial chemoembolization (TACE) in treating patients with advanced hepatocellular carcinoma (HCC). MATERIAL AND METHODS An extensive search was conducted for relevant randomized controlled trials (RCTs) from the establishment date of each database to November 2020. RESULTS A total of nine RCTs were included in this study. Our analysis showed no significant changes in the pooled Δalpha-fetoprotein values (p = .06), incident rates of myelosuppression (p = .46), vomit occurrence (p = .27), and abnormal liver function (p = .42) between the two treatment groups. However, the complete response (p < .00001), total response (p < .00001), and disease control (p < .00001) rates were significantly higher in patients who underwent TACE with IS insertion, as opposed to patients who received TACE alone. Furthermore, patients who underwent TACE with IS insertion experienced markedly longer pooled overall survival (OS) time (p < .0001), with better OS rates at the six-month (p = .0002), one-year (p < .0001), and three-year (p = .0003) follow-ups than patients who received TACE alone. CONCLUSION TACE with IS insertion can significantly improve clinical response and prolong the survival of advanced HCC patients.
Collapse
Affiliation(s)
- Ju-Pan Hou
- Department of Radiology, Xuzhou Central Hospital, Xuzhou, China
| | - Yi-Bing Shi
- Department of Radiology, Xuzhou Central Hospital, Xuzhou, China
| | - Yu-Fei Fu
- Department of Radiology, Xuzhou Central Hospital, Xuzhou, China
| | - Hao Li
- Department of Interventional Radiology, Xuzhou Central Hospital, Xuzhou, China
| |
Collapse
|
|
25
|
Yang SB, Zhang JH, Fu YF, Wang R. TACE with portal vein radioactive seeds for HCC with portal vein tumor thrombus: a meta-analysis. MINIM INVASIV THER 2022; 31:856-864. [PMID: 35238280 DOI: 10.1080/13645706.2022.2045326] [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] [Indexed: 01/27/2023]
Abstract
PURPOSE To assess the efficacy and safety of transarterial chemoembolization (TACE) and portal vein radioactive seed insertion (RSI) combination in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). MATERIAL AND METHODS The relevant databases were searched from the earliest to January 2021. The endpoints included treatment response, treatment side effects, and overall survival (OS). RESULTS Nine studies were included in this meta-analysis. The pooled total response (TR, p = 0.55) and disease control (DC, p = 0.13) rates for HCC were similar between the two treatment groups. The pooled TR (p = 0.0004) and DC (p < 0.0001) rates for PVTT were both significantly higher in the TACE with portal vein RSI group than in the TACE without portal vein RSI group. The pooled HR for OS was significantly better in the TACE with portal vein RSI group than in the TACE without portal vein RSI group (p < 0.00001). The pooled rates of fever (p = 0.97), vomiting (p = 0.64), and myelosuppression (p = 0.65) were similar between the two groups. CONCLUSION Compared to traditional TACE, TACE combined with portal vein RSI can effectively prolong the patients' OS and decrease PVTT disease progression.
Collapse
Affiliation(s)
- Song-Bo Yang
- Department of Nuclear Medicine, Southwest Hospital of The Army Medical University, Chongqing, China
| | - Jian-Hua Zhang
- Department of Interventional Radiology, Fengjie People's Hospital, Chongqing, China
| | - Yu-Fei Fu
- Department of Radiology, Xuzhou Central Hospital, Xuzhou, China
| | - Ru Wang
- Department of Radiology, Xuzhou Central Hospital, Xuzhou, China
| |
Collapse
|
|
26
|
Gao FL, Wang Y, Huang XZ, Pan TF, Guo JH. I-125 seeds brachytherapy with transcatheter arterial chemoembolization for subcapsular hepatocellular carcinoma. BMC Gastroenterol 2022; 22:273. [PMID: 35650532 PMCID: PMC9158176 DOI: 10.1186/s12876-022-02356-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 05/26/2022] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND I-125 seeds brachytherapy (ISB) has been used to improve the clinical effectiveness of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We aim to appraise the safety and clinical efficacy of combined ISB and TACE for the treatment of subcapsular HCC. MATERIALS AND METHODS A retrospective investigative study extending from January 2017 to December 2020, involved individuals suffering from subcapsular HCC, who were subjected to TACE treatment with or without ISB in our center. The clinical effectiveness was compared between 2 groups. RESULTS Sixty-four patients, in total, with subcapsular HCC had to undergo TACE with (n = 32) or without (n = 32) ISB in our center. After CT-guided ISB, only 2 (6.3%) patients experienced a self-limited pneumothorax. Combined treatment resulted in a significantly higher complete response (56.3% vs. 18.8%, P = 0.002) and total response (90.7% vs. 59.4%, P = 0.004) rates than that of TACE alone. In comparison to the TACE alone group, the median progression-free survival was substantially longer in the combined treatment group (11 months vs. 5 months, P = 0.016). Further, 15 and 28 patients in combined and TACE alone groups respectively died within the follow-up. The median OS was comparable between combined and TACE alone groups (22 months vs. 18 months, P = 0.529). CONCLUSIONS Combined TACE and ISB therapy is a safe treatment method for individuals suffering from subcapsular HCC. When compared, combined treatment had significantly enhanced clinical efficacy as a subcapsular HCC therapy, in comparison to TACE alone.
Collapse
Affiliation(s)
- Fu-Lei Gao
- Department of Interventional Radiology, Affiliated Jiangyin Hospital, Medical College of Southeast University, Jiangyin, China
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Yong Wang
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Xiang-Zhong Huang
- Department of Interventional Radiology, Affiliated Jiangyin Hospital, Medical College of Southeast University, Jiangyin, China
| | - Tian-Fan Pan
- Department of Interventional Radiology, Affiliated Jiangyin Hospital, Medical College of Southeast University, Jiangyin, China
| | - Jin-He Guo
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| |
Collapse
|
|
27
|
Fang F, Qiu B, Zhen P, Wang J. Hypofractionated Radiotherapy for Palliation of Main Portal Vein Tumor Thrombosis. Front Oncol 2022; 12:882272. [PMID: 35574374 PMCID: PMC9092647 DOI: 10.3389/fonc.2022.882272] [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: 02/23/2022] [Accepted: 03/30/2022] [Indexed: 12/03/2022] Open
Abstract
Background Hypofractionated radiotherapy delivered for portal vein tumor thrombosis (PVTT) located in the main portal vein is rarely exploited. The study aimed to evaluate the efficacy and safety of hypofractionated radiotherapy as palliative treatment for PVTT in cirrhotic patients with hepatocellular carcinoma. Methods From March 2016 to July 2020, 16 patients (mean age, 59.1 ± 6.3 years; 15 men) with hepatocellular carcinoma and hepatitis virus-related cirrhosis who underwent hypofractionated radiotherapy for PVTT (located in the main portal vein) in our institute were retrospectively reviewed. Results Complete response of the PVTT was observed in 4 cases (25%) with partial response in 7 cases (43.75%) and stable disease in 5 cases (31.25%). Symptom relief was observed in all 7 patients suffering from ventosity. The median time to progression was 6 months (interquartile range, IQR: 6–12 months). Eight patients (50%) failed due to primary cancer progression, 7 patients failed due to extrahepatic metastasis, and only 1 patient failed due to PVTT progression. The median overall survival was 17.4 months (IQR: 8–25 months). Grade I/II anorexia/nausea was observed in 14 patients (87.5%) and Grade I/II leukopenia was observed in 14 patients (87.5%). No complications ≥ Grade III were observed. Conclusions Hypofractionated radiotherapy as palliative treatment appears effective and safe for PVTT located in the main portal vein in cirrhotic patients with advanced hepatocellular carcinoma, yielding a high rate of tumor response. Further study is warranted.
Collapse
Affiliation(s)
- Fang Fang
- Department of Radiation Oncology, Chifeng Tumor Hospital, Chifeng, China
| | - Bin Qiu
- Department of Radiation Oncology, Peking University Third Hospital, Beijing, China
| | - Peng Zhen
- Department of Radiation Oncology, Chifeng Tumor Hospital, Chifeng, China
| | - Junjie Wang
- Department of Radiation Oncology, Peking University Third Hospital, Beijing, China
| |
Collapse
|
|
28
|
Srivastava A, Parambath HK, Ramdulari AV, Saxena H, Kumar R, Pandey S, Shalimar, Gupta S, Jee B. Is hepatocellular carcinoma complicated with portal vein tumor thrombosis potentially curable by radiotherapy in the form of stereotactic body radiation therapy? Int J Radiat Biol 2022; 98:1495-1509. [PMID: 35311612 DOI: 10.1080/09553002.2022.2055800] [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] [Indexed: 01/27/2023]
Abstract
PURPOSE The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal. Despite best treatment and care, the patients with this malignancy only showed 2.7-4 months of overall survival. It is debatable whether liver transplantation helps PVTT sufferers. The effectiveness of radiation therapy in treating HCC patients with PVTT should not be undervalued. By limiting the high dosage region to a small planning target volume, stereotactic radiation delivery has shifted toward hypofractionation, limiting the radiation exposure to healthy organs and tissues. Stereotactic body radiotherapy (SBRT) has a local control rate of 75-100%, depending on the treatment. The major limitation in SBRT for hepatocellular carcinoma with PVTT is the paucity of prospective evidence for longer periods beyond the first two years after treatment. More prospective studies/randomized clinical trials with a longer follow-up, larger sample size, and adequate statistical power are the dire need of the present situation to ascertain the curative effect of SBRT as primary therapy for advanced HCC with PVTT. CONCLUSION SBRT can improve survival, particularly for patients receiving multidisciplinary treatment. This review sums up our most current understanding of how radiation therapy, notably SBRT, can be used to treat hepatocellular carcinoma when combined with PVTT. Recent research has led us to believe that irradiation in the form of SBRT may cure hepatocellular carcinoma complicated by PVTT.
Collapse
Affiliation(s)
- Astha Srivastava
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Haresh Kunhi Parambath
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Anjali V Ramdulari
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Harsh Saxena
- Department of Medicine Trauma, All India Institute of Medical Sciences, New Delhi, India
| | - Rishabh Kumar
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Suyash Pandey
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Subhash Gupta
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Babban Jee
- Department of Health Research, Ministry of Health and Family Welfare, Government of India, New Delhi, India
| |
Collapse
|
|
29
|
Wu G, Huang G, Huang J, Lu L, Peng S, Li Y, Zhao W. Comparison of External Beam Radiation Therapy Modalities for Hepatocellular Carcinoma With Macrovascular Invasion: A Meta-Analysis and Systematic Review. Front Oncol 2022; 12:829708. [PMID: 35242713 PMCID: PMC8887617 DOI: 10.3389/fonc.2022.829708] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
Purpose We performed a systematic review and meta-analysis to compare external beam radiation therapy modalities for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI). Methods Studies were selected from online databases from the date of inception to November 2021. The outcomes of interest were overall survival (OS), objective response rate (ORR), and local control rate (LCR). Results Forty-four studies (n = 3730) were selected from 1050 articles. The pooled 1-year OS were 60.9%, 45.3%, and 44.9 for particle radiotherapy (PRT) group, conventional radiotherapy (CRT), and stereotactic body radiotherapy (SBRT) group, respectively; p = 0.005 and 0.002 for PRT vs. CRT and SBRT, respectively. Both the PRT group and the SBRT group have the advantage over the CRT group in the pooled ORR. The PRT group showed significantly higher than the CRT group (p = 0.007) in LCR. For combination therapy, CRT plus transarterial chemoembolization can prolong survival than CRT alone (p = 0.006 for 1-year OS; p = 0.014 for 2-year OS). Among grade ≥ 3 complications, the most frequent type of toxicity in CRT, SBRT, PRT group was hematological toxicity, hepatotoxicity, dermatological toxicity, respectively. Conclusions Among patients with HCC with MVI, the 1-year OS and the 2-year OS were both higher in the PRT group than in the CRT, SBRT groups. The ORR was similar between the PRT and SBRT groups. The combination therapy based on radiotherapy is expectable. PRT is associated with less complications than photon radiotherapy.
Collapse
Affiliation(s)
- Guanheng Wu
- Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Guomin Huang
- Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Jianwen Huang
- Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Ligong Lu
- Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Shaojun Peng
- Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Yong Li
- Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Wei Zhao
- Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| |
Collapse
|
|
30
|
Lee S, Jung J, Park JH, Kim SY, Choi J, Lee D, Shim JH, Kim KM, Lim YS, Lee HC, Park HH, Kim JH, Yoon SM. Stereotactic body radiation therapy as a salvage treatment for single viable hepatocellular carcinoma at the site of incomplete transarterial chemoembolization: a retrospective analysis of 302 patients. BMC Cancer 2022; 22:175. [PMID: 35172769 PMCID: PMC8848650 DOI: 10.1186/s12885-022-09263-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 01/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND To evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE). METHODS Patients treated with SBRT for single viable HCC after incomplete TACE between 2012 and 2017 at Asan Medical Center (Seoul, South Korea) were included. Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up dynamic computed tomography (CT) or magnetic resonance imaging following one or more consecutive TACEs, (2) no definite tumor staining on superselective hepatic angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or CT. Doses of 10-15 Gy per fraction were given over 3-4 consecutive days. The primary outcome was local control rate at 3 years and secondary outcome included tumor response, overall survival rate, out-of-field intrahepatic recurrence-free survival, distant metastasis-free survival and treatment-related toxicities. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03. RESULTS A total of 302 patients were analyzed. The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6-41.7) and the median tumor size was 2.0 cm (range, 0.7-6.9). The local control (LC) and overall survival rates at 3 years were 91.2 and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9-4.7), and 39.9 and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field. CONCLUSION SBRT could be considered a feasible salvage treatment option for HCC after incomplete TACE.
Collapse
Affiliation(s)
- Sumin Lee
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jinhong Jung
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Jin-Hong Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - So Yeon Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jonggi Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Danbi Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kang Mo Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hee Hyun Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sang Min Yoon
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| |
Collapse
|
|
31
|
Liu S, Liu KC, Lv WF, Lu D, Zhu XH, Jiang B, Tan YL, Wang GX. The Efficacy and Prognostic Factors of the Combination of TACE and Apatinib for the Treatment of BCLC Stage C Hepatocellular Carcinoma. Front Med (Lausanne) 2022; 8:774345. [PMID: 34970563 PMCID: PMC8713136 DOI: 10.3389/fmed.2021.774345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 11/08/2021] [Indexed: 12/28/2022] Open
Abstract
Objective: Apatinib is a inhibitor of vascular endothelial growth factor receptor-2. To explore the efficacy and prognostic factors of transarterial chemoembolization (TACE) combined with apatinib in the treatment of Barcelona Clinic Liver Cancer stage C (BCLC C) hepatocellular carcinoma (HCC). Methods: Clinical data of 146 HCC patients with BCLC stage C admitted to our hospital were collected and analyzed retrospectively, of which 76 cases were treated with TACE combined with apatinib (TACE-apatinib) and 70 with TACE alone. The tumor response, survival time, and adverse events were compared between the two groups, and the factors affecting the prognosis were analyzed. Results: The objective response rate (ORR) and disease control rate (DCR) in the TACE-apatinib group were higher than in the TACE-alone group (ORR: 42.10 vs. 25.71%, P = 0.03; DCR: 84.21 vs. 55.71%, P = 0.001). The median time to progression (TTP) and overall survival (OS) in the TACE-apatinib group were longer than in the TACE-alone group (TTP: 5.5 vs. 3.7 months, P = 0.02; OS: 10.0 vs. 6.2 months, P = 0.01). Univariate and multivariate Cox regression analysis showed that tumor size, Child-Pugh class, and the presence of the portal vein tumor thrombus affect the prognosis of patients. Subgroup analysis revealed that TACE-apatinib therapy resulted in a higher OS in patients with tumor size <10 cm, without portal vein tumor thrombus, and with Child-Pugh class A (P < 0.05). The likelihood of adverse events (hand-foot syndrome, hypertension, oral ulcer) was significantly higher in the increased in the TACE-apatinib group than in the TACE alone group (P < 0.05). Conclusion: TACE-apatinib is an effective and safe method for the treatment of BCLC stage C HCC. Tumor size, Child-Pugh class, and portal vein tumor thrombus affect survival time in HCC patients with BCLC stage C.
Collapse
Affiliation(s)
- Shun Liu
- Department of Radiology, Anhui Provincial Hospital of Anhui Medical University, Hefei, China.,Department of Radiology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Kai-Cai Liu
- Infection Hospital, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Wei-Fu Lv
- Department of Radiology, Anhui Provincial Hospital of Anhui Medical University, Hefei, China.,Department of Radiology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Dong Lu
- Department of Radiology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Xian-Hai Zhu
- Department of Radiology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Bo Jiang
- Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, China
| | - Yu-Lin Tan
- Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Guo-Xiang Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
| |
Collapse
|
|
32
|
Lam T, Wong W, Lee C, Cheung C. Transarterial chemoembolisation plus stereotactic body radiotherapy as conversion therapy for large right lobe hepatocecullar carcinoma. SURGICAL PRACTICE 2021. [DOI: 10.1111/1744-1633.12530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Tang‐yu Lam
- Department of Surgery Tuen Mun Hospital Hong Kong China
| | - Wai‐man Wong
- Department of Surgery Tuen Mun Hospital Hong Kong China
| | | | | |
Collapse
|
|
33
|
Luo J, Xu L, Li L, Zhang J, Zhang M, Xu M. Comparison of treatments for hepatocellular carcinoma patients with portal vein thrombosis: a systematic review and network meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1450. [PMID: 34734002 PMCID: PMC8506756 DOI: 10.21037/atm-21-3937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 08/26/2021] [Indexed: 02/05/2023]
Abstract
Background Sorafenib, hepatectomy, and transarterial chemoembolization (TACE) are the recommended treatment for portal vein tumor thrombosis (PVTT) patients. Therefore, the aim of the present study was to conduct a multi-treatment meta-analysis. The aim of the present study was to analyze the survival benefit of different treatments options on PVTT patients. Methods We systematically analyzed 12 randomized controlled trials (4,265 participants) from 2012 to 2019, which compared any of the following treatment options on PVTT patients: TACE, sorafenib, hepatectomy, sorafenib + TACE, hepatectomy + TACE, and sorafenib + hepatectomy. The main outcome was the 1-year survival rate of patients. Results The results of the rank probability of effectiveness showed that sorafenib + TACE was more likely to be the most effective treatment, sorafenib + TACE group was ranged rank 1 when compared with the others [hepatectomy group: odds ratio (OR): 0.79, 95% confidence interval (CI): 0.03–18.26; hepatectomy + TACE group: OR: 0.51, 95% CI: 0.01–13.59; sorafenib group: OR: 0.14, 95% CI 0.01–2.29, sorafenib + hepatectomy group: OR: 0.15, 95% CI: 0.00–24.88; and TACE group: OR: 0.51, 95% CI: 0.02–9.88]. The second most effect treatment option was hepatectomy alone. Discussion Sorafenib + TACE is more likely to be the most effective treatment option, while hepatectomy alone is the second effective treatment option.
Collapse
Affiliation(s)
- Jianchen Luo
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Liangliang Xu
- Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Lian Li
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jingfu Zhang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ming Zhang
- Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Mingqing Xu
- Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
34
|
Khorprasert C, Thonglert K, Alisanant P, Amornwichet N. Advanced radiotherapy technique in hepatocellular carcinoma with portal vein thrombosis: Feasibility and clinical outcomes. PLoS One 2021; 16:e0257556. [PMID: 34555075 PMCID: PMC8460041 DOI: 10.1371/journal.pone.0257556] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 09/06/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND In Thailand, individuals with hepatocellular carcinoma (HCC) who develop portal vein tumor thrombosis (PVTT) have a restricted treatment option because to the extent of the disease, poor underlying liver function, and non-coverage of immuno/targeted therapy. Radiotherapy (RT) plays an increasingly important function in these patients. To investigate the feasibility, efficacy, and adverse event rates, we performed a retrospective analysis of patients with HCC with PVTT who underwent 3-dimensional conformal radiation (3DCRT), intensity-modulated radiation (IMRT), volumetric-modulated radiotherapy (VMAT), and stereotactic body radiotherapy (SBRT) in a single-institution. OBJECTIVES To examine clinical results in terms of overall survival (OS), local control (LC), response of primary tumor and PVTT, hepatic and gastrointestinal adverse reaction, and prognosis variables for OS and LC. MATERIALS AND METHODS Between July 2007 and August 2019, non-metastatic HCC with PVTT patients treated with RT were retrospectively reviewed and evaluated. RESULTS The analysis included data from 160 patients. The mean age of the patients was 60.8 years ((95% CI 58.2-62.0). The median diameter of the tumor was 7.7 cm (range: 1-24.5). 85 (54.5%) individuals had PVTT in the main or first branch. At 1.8-10 Gy per fraction, the mean biologically effective dose (BED) as α/β ratio of 10 was 49.6 (95% CI 46.7-52.5) Gy10. The median survival time was 8.3 (95% CI 6.1-10.3) months. Survival rates at one and two years were 39.6% and 17.1%, respectively. Estimated incidence of local failure using competing risk analysis were 24% and 60% at 1 and 2 years, respectively. The overall response rate was 74%, with an 18.5 percent complete response rate. In multivariate analysis, tumor size, overall response, and radiation dose were all significant prognostic variables for OS. Hepatic unfavorable events of grade 3 and 4 were for 14.1% of the total. There was no occurrences of grade 3-4 gastrointestinal toxicity, either acute or late. Additionally, there were no treatment-related mortality. CONCLUSIONS Advanced RT is regarded as a safe and effective therapeutic option for HCC with PVTT. Overall survival was clearly related to tumor size, radiation dose, and tumor/PVTT response. Individuals with BED 56 Gy10 had significantly better overall survival than patients with BED 56 Gy10. A prospective randomized trial is required to validate these outcomes in order to corroborate these findings.
Collapse
Affiliation(s)
- Chonlakiet Khorprasert
- Faculty of Medicine, Division of Radiation Oncology, Department of Radiology, Chulalongkorn University, Bangkok, Thailand
| | - Kanokphorn Thonglert
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Petch Alisanant
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Napapat Amornwichet
- Faculty of Medicine, Division of Radiation Oncology, Department of Radiology, Chulalongkorn University, Bangkok, Thailand
| |
Collapse
|
|
35
|
Hong D, Zhou Y, Wan X, Su H, Shao H. Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma. BMC Cancer 2021; 21:1020. [PMID: 34521375 PMCID: PMC8439081 DOI: 10.1186/s12885-021-08680-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 08/13/2021] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT). METHODS Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival. RESULTS No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p's ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3. CONCLUSIONS The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.
Collapse
Affiliation(s)
- Duo Hong
- Department of Interventional Radiology, The First Hospital of China Medical University, No.155 Nanjing Road, Heping District, Shenyang, 110000 Liaoning China
| | - Yi Zhou
- Vascular Surgery and Interventional Department, Changzhou No.2 People’s Hospital, 29 Xinglong Lane, Tianning District, Changzhou, 213000 Jiangsu China
| | - Xiaoting Wan
- Department of Nuclear Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510000 China
| | - Hongying Su
- Department of Interventional Radiology, The First Hospital of China Medical University, No.155 Nanjing Road, Heping District, Shenyang, 110000 Liaoning China
| | - Haibo Shao
- Department of Interventional Radiology, The First Hospital of China Medical University, No.155 Nanjing Road, Heping District, Shenyang, 110000 Liaoning China
| |
Collapse
|
|
36
|
Tsai HM, Han MZ, Lin YJ, Chang TT, Chen CY, Cheng PN, Chuang CH, Wu IC, Chen PJ, Kang JW, Chiu YC, Chiu HC, Chien SC, Kuo HY. Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis. Cancer Immunol Immunother 2021; 70:1929-1937. [PMID: 33409737 PMCID: PMC8195886 DOI: 10.1007/s00262-020-02845-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/28/2020] [Indexed: 02/08/2023]
Abstract
Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2-12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child-Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes.
Collapse
Affiliation(s)
- Hong-Ming Tsai
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Zhi Han
- Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Chiung-Yu Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - I-Chin Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Po-Jun Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Jui-Wen Kang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Shih-Chieh Chien
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Hsin-Yu Kuo
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan.
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| |
Collapse
|
|
37
|
Hwang S, Moon DB, Kim KH, Ahn CS, Song GW, Jung DH, Park GC, Lee SG. Prognostic Accuracy of the ADV Score Following Resection of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis. J Gastrointest Surg 2021; 25:1745-1759. [PMID: 32948961 DOI: 10.1007/s11605-020-04800-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 09/06/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND We assessed the prognostic accuracy of ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) following resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS This was a retrospective observational study. This study included 147 patients who underwent hepatic resection for HCC with PVTT. They were followed up for ≥ 66 months or until patient death. RESULTS The grades of PVTT were Vp1 in 121 (14.3%), Vp2 in 41 (27.9%), Vp3 in 71 (48.3%), and Vp4 in14 (9.5%) cases. Preoperative HCC treatment was performed in 48 (32.7%) patients. R0 and R1 resections were performed in 119 (81.0%) and 28 (19.0%) cases, respectively. The 5-year tumor recurrence, HCC-specific survival, and post-recurrence survival rates were 79.2%, 43.5%, and 25.4%, respectively. Neither PVTT grade nor history of preoperative HCC treatment was a significant prognostic indicator. Stratification in accordance with ADV scores of 1log- and 3log-intervals resulted in high prognostic accuracy in predicting tumor recurrence and patient survival. Following cluster analysis, the cutoff for ADV score was determined at 9log and was more prognostically significant in terms of tumor recurrence and patient survival than surgical curability or microvascular invasion. Further comparisons revealed that prognostic prediction with an ADV score cutoff at 9log was more accurate than that using the Eastern Hepatobiliary Surgery Hospital-PVTT score. CONCLUSIONS ADV score is an integrated surrogate biomarker for post-resection prognosis in HCC with PVTT. Our prognostic prediction model using ADV scores provides reliable post-resection prognosis for patients with various grades of these tumors.
Collapse
Affiliation(s)
- Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| |
Collapse
|
|
38
|
Zhou TY, Chen SQ, Wang HL, Weng SM, Zhou GH, Zhang YL, Nie CH, Zhu TY, Wang BQ, Yu ZN, Jing L, Chen F, Sun JH. Safety and efficacy of drug-eluting bead transarterial chemoembolization with CalliSpheres® microsphere for hepatocellular carcinoma with portal vein tumor thrombus: a preliminary study. J Cancer 2021; 12:4522-4529. [PMID: 34149916 PMCID: PMC8210571 DOI: 10.7150/jca.54650] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 05/18/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: To prospectively evaluate the safety and therapeutic effectiveness of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) with CalliSpheres® microsphere (CSM) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to analyze the prognostic factors. Method: Between November 2015 and November 2017, consecutive 58 HCC patients with PVTT who received DEB-TACE with CSM treatment were prospectively enrolled in this study. The demographic characteristics, adverse events (AEs) and treatment response were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the independent factors correlated with OS. Results: The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh classification (HR=2.279; 95%CI, 1.042-4.985, p = 0.039) and tumor burden (p = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. The most common clinical AEs were postembolization syndrome (PES) and the most prevalent laboratory toxicity was transient liver function damage. Conclusion: DEB-TACE with CSM is safe and well-tolerated in HCC patients with PVTT, and reveals a favorable preliminary clinical outcome. The higher Child-Pugh classification and liver tumor burden are independent prognostic factors associated with poor survival for HCC patients with PVTT treated by DEB-TACE with CSM.
Collapse
Affiliation(s)
- Tan-Yang Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Sheng-Qun Chen
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Hong-Liang Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Sheng-Ming Weng
- Department of Radiology, Jingning County People's Hospital, Lishui, Zhejiang Province, China
| | - Guan-Hui Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Yue-Lin Zhang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Chun-Hui Nie
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Tong-Yin Zhu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Bao-Quan Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Zi-Niu Yu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Li Jing
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China
| | - Feng Chen
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun-Hui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, Zhejiang Province, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
| |
Collapse
|
|
39
|
Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med 2021; 15:155-169. [PMID: 33754281 DOI: 10.1007/s11684-021-0848-3] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/20/2021] [Indexed: 01/27/2023]
Abstract
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
Collapse
Affiliation(s)
- Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| |
Collapse
|
|
40
|
Yoon SM. External Beam Radiotherapy for Hepatocellular Carcinoma: a Review of the Current Guidelines in the East and the West. JOURNAL OF LIVER CANCER 2021; 21:25-33. [PMID: 37384266 PMCID: PMC10035720 DOI: 10.17998/jlc.21.1.25] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/11/2021] [Accepted: 01/20/2021] [Indexed: 06/30/2023]
Abstract
The incidence of hepatocellular carcinoma (HCC) is geographically heterogeneous depending on the underlying liver disease. Moreover, the decisions and recommendations about standard treatments differ between countries, especially between the East and the West. Because of the complexity of treatment decisions for the management of HCC, a multidisciplinary approach is recommended to maximize the therapeutic efficacy. External beam radiotherapy (RT) has been increasingly used to manage HCC when recommended treatments cannot be applied in real-world clinical practice. However, Western guidelines for the management of HCC do not recommend RT as a treatment option due to the lack of clinical evidence. RT has often been used more in Eastern countries than in Western countries; hence, it is necessary to review both Eastern and Western guidelines for HCC treatment regarding the recommendations about RT. In this study, the comments and potential roles of external beam RT are summarized from several treatment guidelines for the management of HCC.
Collapse
Affiliation(s)
- Sang Min Yoon
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
41
|
Lim J, Kim HI, Kim E, Kim J, An J, Chang S, Kim SO, Lee HC, Lee YS, Shim JH. Variceal bleeding is aggravated by portal venous invasion of hepatocellular carcinoma: a matched nested case-control study. BMC Cancer 2021; 21:11. [PMID: 33402105 PMCID: PMC7786454 DOI: 10.1186/s12885-020-07708-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 12/03/2020] [Indexed: 02/07/2023] Open
Abstract
Background We hypothesized that portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) increases portal pressure and causes esophageal varices and variceal bleedings. We examined the incidence of high-risk varices and variceal bleeding and determined the indications for variceal screening and prophylaxis. Methods This study included 1709 asymptomatic patients without any prior history of variceal hemorrhage or endoscopic prophylaxis who underwent upper endoscopy within 30 days before or after initial anti-HCC treatment. Of these patients, 206 had PVTT, and after 1:2 individual matching, 161 of them were matched with 309 patients without PVTT. High-risk varices were defined as large/medium varices or small varices with red-color signs and variceal bleeding. Bleeding rates from the varices were compared between matched pairs. Risk factors for variceal bleeding in the entire set of patients with PVTT were also explored. Results In the matched-pair analysis, the proportion of high-risk varices at screening (23.0% vs. 13.3%; P = 0.003) and the cumulative rate of variceal bleeding (4.5% vs. 0.4% at 1 year; P = 0.009) were significantly greater in the PVTT group. Prolonged prothrombin time, lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to high-risk varices in the total set of 206 patients with PVTT (Adjusted odds ratios [95% CIs], 1.662 [1.151–2.401]; 0.985 [0.978–0.993]; 4.240 [1.783–10.084]; and 3.345 [1.457–7.680], respectively; Ps < 0.05). During a median follow-up of 43.2 months, 10 patients with PVTT experienced variceal bleeding episodes, 9 of whom (90%) had high-risk varices. Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of patients with PVTT (Adjusted hazard ratios [95% CIs], 26.432 [3.230–216.289]; and 5.676 [1.273–25.300], respectively; Ps < 0.05). Conclusions PVTT in HCC appears to increase the likelihood of high-risk varices and variceal bleeding. In HCC patients with PVTT, endoscopic prevention could be considered, at least in high-risk variceal carriers taking sorafenib.
Collapse
Affiliation(s)
- Jihye Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Ha Il Kim
- Gastroenterology, Kyung Hee University Hospital, Seoul, Republic of Korea
| | - Eunju Kim
- Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea
| | - Jiyoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Jihyun An
- Gastroenterology, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea
| | - Seheon Chang
- Internal Medicine, Myongji St. Mary's Hospital, Seoul, Republic of Korea
| | - Seon-Ok Kim
- Biostatistics and Clinical Epidemiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.,Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yung Sang Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.,Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea. .,Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
42
|
Tanaka H, Okamoto K, Sato Y, Tanaka T, Tomonari T, Nakamura F, Fujino Y, Mitsui Y, Miyamoto H, Muguruma N, Morita A, Ikushima H, Takayama T. Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma. J Gastroenterol 2020; 55:1072-1086. [PMID: 32666201 DOI: 10.1007/s00535-020-01705-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 06/29/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND The prognosis for patients with unresectable advanced hepatocellular carcinoma (HCC) is poor. Miriplatin is a hydrophobic platinum compound that has a long retention time in lesions after transarterial chemoembolization (TACE). We investigated anti-tumor activity of miriplatin combined with irradiation on HCC cells, and its underlying mechanism of apoptosis. We also analyzed the effectiveness of miriplatin-TACE and radiotherapy for locally advanced HCC. METHODS Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of miriplatin) and radiation, and synergy was evaluated using a combination index (CI). Apoptosis-related proteins and cell cycles were analyzed by western blotting and flowcytometry. We retrospectively analyzed treatment outcomes in 10 unresectable HCC patients with vascular/bile duct invasion treated with miriplatin-TACE and radiotherapy. RESULTS DPC or X-ray irradiation decreased cell viability dose-dependently. DPC plus irradiation decreased cell viability synergistically in both cell lines (CI < 1, respectively). Cleaved PARP expression was induced much more strongly by DPC plus irradiation than by each treatment alone. Expression of p53 up-regulated modulator of apoptosis (PUMA) was significantly induced by the combination, and knockdown of PUMA with siRNA significantly decreased apoptosis in both cell lines. DPC plus irradiation caused sub-G1, G2/M, and S phase cell arrest in those cells. The combination of miriplatin-TACE and radiotherapy showed a high response rate for patients with locally advanced HCC despite small number of patients. CONCLUSIONS Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC.
Collapse
Affiliation(s)
- Hironori Tanaka
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yasushi Sato
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Takahiro Tanaka
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tetsu Tomonari
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Fumika Nakamura
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yasuteru Fujino
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yasuhiro Mitsui
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Naoki Muguruma
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Akinori Morita
- Department of Biomedical Science and Technology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hitoshi Ikushima
- Department of Therapeutic Radiology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
| |
Collapse
|
|
43
|
Chang Y, Jeong SW, Young Jang J, Jae Kim Y. Recent Updates of Transarterial Chemoembolilzation in Hepatocellular Carcinoma. Int J Mol Sci 2020; 21:E8165. [PMID: 33142892 PMCID: PMC7662786 DOI: 10.3390/ijms21218165] [Citation(s) in RCA: 179] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/28/2020] [Accepted: 10/28/2020] [Indexed: 12/24/2022] Open
Abstract
Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). In this review, we summarize recent updates on the use of TACE for HCC. TACE can be performed using two techniques; conventional TACE (cTACE) and drug-eluting beads using TACE (DEB-TACE). The anti-tumor effect of the two has been reported to be similar; however, DEB-TACE carries a higher risk of hepatic artery and biliary injuries and a relatively lower risk of post-procedural pain than cTACE. TACE can be used for early stage HCC if other curative treatments are not feasible or as a neoadjuvant treatment before liver transplantation. TACE can also be considered for selected patients with limited portal vein thrombosis and preserved liver function. When deciding to repeat TACE, the ART (Assessment for Retreatment with TACE) score and ABCR (AFP, BCLC, Child-Pugh, and Response) score can guide the decision process, and TACE refractoriness needs to be considered. Studies on the combination therapy of TACE with other treatment modalities, such as local ablation, radiation therapy, or systemic therapy, have been actively conducted and are still ongoing. Recently, new prognostic models, including analysis of the neutrophil-lymphocyte ratio, radiomics, and deep learning, have been developed to help predict survival after TACE.
Collapse
Affiliation(s)
- Young Chang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Soung Won Jeong
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Jae Young Jang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Yong Jae Kim
- Department of Radiology, Soonchunhyang University College of Medicine, Seoul 04401, Korea;
| |
Collapse
|
|
44
|
Que J, Lin CH, Lin LC, Ho CH. Challenges of BCLC stage C hepatocellular carcinoma: Results of a single-institutional experience on stereotactic body radiation therapy. Medicine (Baltimore) 2020; 99:e21561. [PMID: 32769898 PMCID: PMC7593074 DOI: 10.1097/md.0000000000021561] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
In this study, we evaluated the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).This retrospective study evaluated 139 patients with BCLC stage C HCC who underwent CyberKnife SBRT between January 2009 and September 2017. All patients had BCLC-C, Child-Turcotte-Pugh score A-B. In-field control, overall survival (OS), progression free survival (PFS), and prognostic factors were evaluated.An objective response rate was achieved in 81.5% patients (complete response, 36.2%, partial response, 45.3%). The median survival was 15.44 months, and the 1-, 3-, 5-year OS rates were 56%, 28%, and 20%, respectively. The median PFS was 6 months, the PFS rate at 1-, 3-, and 5-year were 35%, 14%, and 10%, respectively. In-field control of 1 to 2 years was achieved in 85.1% of patients. The major pattern of failure was out-field intrahepatic failure which comprised 42.9% of patients. Multivariate analysis revealed that the Child-Turcotte-Pugh score, macrovascular invasion, advance stage (III-IV), and tumor response rate were independent predictors of OS.The result of our study shows that SBRT is a safe and effective therapeutic option for BCLC stage C HCC lesions that are unsuitable for standard loco-regional therapies, Moreover, SBRT has acceptable local control rates and low-treatment toxicity.
Collapse
Affiliation(s)
- Jenny Que
- Department of Radiation Oncology, Chi Mei Medical Center
- Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science
| | - Chia-Hui Lin
- Department of Radiation Oncology, Chi Mei Medical Center
- Department of Pharmacy, Chia Nan University of Pharmacy and Science
| | - Li-Ching Lin
- Department of Radiation Oncology, Chi Mei Medical Center
| | - Chung-Han Ho
- Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| |
Collapse
|
|
45
|
Choi HS, Kang KM, Jeong BK, Jeong H, Lee YH, Ha IB, Song JH. Effectiveness of stereotactic body radiotherapy for portal vein tumor thrombosis in patients with hepatocellular carcinoma and underlying chronic liver disease. Asia Pac J Clin Oncol 2020; 17:209-215. [PMID: 32757461 DOI: 10.1111/ajco.13361] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 04/14/2020] [Indexed: 01/14/2023]
Abstract
AIM Stereotactic-body radiotherapy (SBRT) is a treatment option for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Here, we report on our experience of treating PVTT using SBRT in patients with concomitant underlying chronic liver disease. METHODS This study included 24 patients. The initial prescription dose was 45 Gy in three fractions in 17 (70.8%) patients, but it was modified in the remaining seven (29.2%) patients, with the dose ranging from 39 to 42 Gy in 3-4 fractions. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients. RESULTS Of the 24 patients, 2 (8.3%) showed complete response, while 11 (45.8%) showed partial response. After a median follow-up of 8.4 months (range: 2.6-56.5 months), the 1-year overall survival (OS) and the median survival were 67.5% and 20.8 months, respectively. Both combined SBRT and TACE and grade ≥3 hepatic toxicity affected the 1-year OS (SBRT alone vs SBRT + TACE: 14.6% vs 71.4%, P < .001; presence of hepatic toxicity vs absence: 0% vs 81.1%, P = .002). CONCLUSIONS Overall, SBRT, especially in combination with TACE, is an effective treatment for patients with HCC and PVTT. An optimal dose schedule must be followed to reduce hepatic toxicity while maintaining tumor response.
Collapse
Affiliation(s)
- Hoon Sik Choi
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.,Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea
| | - Ki Mun Kang
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.,Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea
| | - Bae Kwon Jeong
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea.,Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Hojin Jeong
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea.,Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Yun Hee Lee
- Department of Radiation Oncology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea
| | - In Bong Ha
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea.,Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Jin Ho Song
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| |
Collapse
|
|
46
|
Su TS, Li LQ, Meng WW, Wang YD, Chen YT, Li JX, Du YQ, Qu S, Zhao C, Huang DJ, Liang SX, Li LQ. Long-Term Survival Analysis of Transarterial Chemoembolization Plus Radiotherapy vs. Radiotherapy for Hepatocellular Carcinoma With Macroscopic Vascular Invasion. Front Oncol 2020; 10:1205. [PMID: 32850352 PMCID: PMC7416768 DOI: 10.3389/fonc.2020.01205] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 06/15/2020] [Indexed: 12/13/2022] Open
Abstract
Background: Macroscopic vascular invasion (MVI) is a terminal manifestation of hepatocellular carcinoma (HCC) and carries an extremely poor prognosis. In Chinese and Korean HCC guidelines, transarterial chemoembolization (TACE), or/and radiotherapy (RT) is adopted for treatment of MVI. In the current study, we aimed to compare the long-term outcome of TACE + RT to that of RT alone in patients with local advanced HCC with MVI. Methods: In this retrospective study, 148 treatment-naive patients of HCC with MVI were enrolled. Of the patients enrolled, 49 received TACE + RT treatment, whereas 99 patients received RT alone as a monotherapy. Overall survival (OS), progression-free survival (PFS), and intrahepatic control were evaluated using univariable and propensity score–matched analyses. Results: During follow-up, 126 patients (85.1%) died. The median follow-up time was 55.0 months in the RT group and 57.0 months in the TACE + RT group. The TACE + RT group showed better OS and PFS than the RT group, but intrahepatic control was comparable in these two groups. Of 41 cases well-pairs after propensity score matching, the associations between TACE + RT and better OS and PFS remained (15.0 vs. 8.0 months, and 8.0 vs. 4.0 months, all P < 0.05). The 1-, 2-, 3-, and 5-years OS rates in the TACE + RT group were 56.1, 28.6, 20.8, and 15.7 vs. 31.5%, 13.1%, 9.8%, and 6.7% in the RT group, respectively (P = 0.017). The 6-, 12-, and 24-months rates in the TACE + RT group were 51.2, 39.0, and 23.1% vs. 36.6%, 13.9%, and 11.1% in the RT group, respectively (P = 0.04). Two patients (4.1%) experienced radiation-induced liver disease (RILD), and one (2.0%) experienced RT-related gastrointestinal (GI) bleed in the TACE + RT groups. Nine patients (9.1%) experienced RILD, and two (2.0%) experienced RT-related GI bleed in the RT groups. Conclusion: Transarterial chemoembolization + RT had well-complementarity with no more complications than RT alone, providing a better PFS and OS compared with RT-alone treatment for HCC with MVI.
Collapse
Affiliation(s)
- Ting-Shi Su
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Li-Qing Li
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Wan-Wan Meng
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yu-Dan Wang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yi-Tian Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jian-Xu Li
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - You-Qin Du
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Song Qu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Chang Zhao
- Department of Interventional Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - De-Jia Huang
- Department of Interventional Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Shi-Xiong Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| |
Collapse
|
|
47
|
Sebastian NT, Miller ED, Yang X, Diaz DA, Tan Y, Dowell J, Spain J, Rikabi A, Elliott E, Knopp M, Williams TM. A Pilot Trial Evaluating Stereotactic Body Radiation Therapy to Induce Hyperemia in Combination With Transarterial Chemoembolization for Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2020; 108:1276-1283. [PMID: 32712254 DOI: 10.1016/j.ijrobp.2020.07.033] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 07/12/2020] [Accepted: 07/17/2020] [Indexed: 01/14/2023]
Abstract
PURPOSE Despite the survival benefit of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), a majority of tumors recur, attributed to hypovascularity and treatment resistance. Preclinical studies show that moderate radiation doses induce changes in tumor permeability and perfusion, suggesting an opportunity for TACE sensitization by radiation. In this prospective phase 1 trial, we evaluated the feasibility, safety, tolerability, response, and functional magnetic resonance imaging (MRI) changes associated with single-fraction stereotactic body radiation therapy (SBRT) followed by TACE within 24 hours. METHODS AND MATERIALS Patients with HCC, 1 to 3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hours. Secondary endpoints included safety, tolerability, perfusional changes via functional MRI, overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression, progression-free survival, and overall survival. RESULTS Sixteen patients were enrolled, and 13 received SBRT and TACE. Median follow-up was 15.3 months. Best overall ORR and CBR were 76.9% and 92.3%, respectively. The 1- and 3-month ORR was 76.9% and 69.2%, respectively, and 1- and 3-month CBR was 92.3% and 69.2%, respectively. Median overall survival, progression-free survival, and freedom from local progression were 14.0, 5.2, and 5.9 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity were 85% and 38%, respectively. No grade 3 to 4 toxicities were recorded. One grade 5 toxicity occurred due to hemorrhage 4 days after TACE. On dynamic contrast-enhanced MRI, the transfer rate constant from blood plasma to extracellular extravascular space (kpe) increased within 6 hours post-SBRT but decreased by 24 hours. CONCLUSIONS We hypothesized a strategy of SBRT preceding TACE for the purpose of enhancing TACE delivery and efficacy and tested this strategy in a small pilot study. We found that single-dose SBRT followed by TACE within 24 hours is feasible and tolerable. Dynamic contrast-enhanced MRI revealed acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination and the effects of SBRT on the HCC microenvironment.
Collapse
Affiliation(s)
- Nikhil T Sebastian
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio
| | - Xiangyu Yang
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Dayssy Alexandra Diaz
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio
| | - Yubo Tan
- Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio
| | - Joshua Dowell
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - James Spain
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Ali Rikabi
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Eric Elliott
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Michael Knopp
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Terence M Williams
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio.
| |
Collapse
|
|
48
|
Locoregional Therapy Approaches for Hepatocellular Carcinoma: Recent Advances and Management Strategies. Cancers (Basel) 2020; 12:cancers12071914. [PMID: 32679897 PMCID: PMC7409274 DOI: 10.3390/cancers12071914] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/12/2020] [Accepted: 07/14/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and third leading cause of cancer-related mortality worldwide. While surgical resection and transplantation are the standard first-line treatments for early-stage HCC, most patients do not fulfill criteria for surgery. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable HCC. Improved outcomes have been achieved with novel techniques which can be employed for diverse applications ranging from curative-intent for small localized tumors, to downstaging or bridging to resection and transplantation for early and intermediate disease, and locoregional control and palliation for advanced disease. This review explores recent advances in liver-directed techniques for HCC including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on patient selection, procedural technique, periprocedural management, and outcomes.
Collapse
|
|
49
|
Bansal A, Chaturvedi A. Interventional Radiological Management of Hepatocellular Carcinoma. Indian J Med Paediatr Oncol 2020. [DOI: 10.4103/ijmpo.ijmpo_256_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Abhishek Bansal
- Department of Radiology and Interventional Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Arvind Chaturvedi
- Department of Radiology and Interventional Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| |
Collapse
|
|
50
|
Chemoembolization Plus Radiotherapy Versus Chemoembolization Plus Sorafenib for the Treatment of Hepatocellular Carcinoma Invading the Portal Vein: A Propensity Score Matching Analysis. Cancers (Basel) 2020; 12:cancers12051116. [PMID: 32365655 PMCID: PMC7281632 DOI: 10.3390/cancers12051116] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 04/27/2020] [Accepted: 04/27/2020] [Indexed: 12/16/2022] Open
Abstract
A combination of transarterial chemoembolization (TACE) plus sorafenib or radiotherapy (RT) has demonstrated efficacy in patients with advanced hepatocellular carcinoma (HCC). Here, the two combined treatment approaches were compared in patients with HCC and portal vein tumor thrombus (PVTT). Data from 307 patients treated with TACE plus RT (n = 203) or TACE plus sorafenib (n = 104) as first-line treatment for HCC with PVTT were retrospectively evaluated. Using the propensity model to correct selection bias, 87 patients were included from each treatment group. During follow up (median, 12 months) in the entire study population, the median progression-free survival (PFS) and overall survival (OS) were significantly longer in the TACE plus RT group than in the TACE plus sorafenib group (6.5 vs. 4.3 months, respectively; p = 0.017 and 16.4 vs. 12 months, respectively; p = 0.007). Following propensity score matching, the median PFS and OS in the two groups showed no statistically significant difference. Multivariable analysis found no significant association between PFS or OS and the treatment type. In conclusion, this retrospective study of data from patients with advanced HCC with PVTT shows that PFS and OS did not differ significantly in patients treated with TACE plus RT and TACE plus sorafenib.
Collapse
|