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Zhang Y, Numata K, Imajo K, Uojima H, Funaoka A, Komiyama S, Ogushi K, Chuma M, Irie K, Kokubu S, Yoneda M, Kobayashi T, Hidaka H, Fukushima T, Kobayashi S, Morimoto M, Kagawa T, Hattori N, Watanabe T, Iwase S, Maeda S. Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study. Hepatol Res 2024; 54:1174-1192. [PMID: 38953838 DOI: 10.1111/hepr.14089] [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: 03/06/2024] [Revised: 06/07/2024] [Accepted: 06/09/2024] [Indexed: 07/04/2024]
Abstract
AIM This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.
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Affiliation(s)
- Ying Zhang
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Medical Ultrasound, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kento Imajo
- Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan
- Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akihiro Funaoka
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Satoshi Komiyama
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Katsuaki Ogushi
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kuniyasu Irie
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Shigehiro Kokubu
- Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Taito Fukushima
- Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Satoshi Kobayashi
- Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Manabu Morimoto
- Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Tatehiro Kagawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Nobuhiro Hattori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tsunamasa Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Shigeru Iwase
- Department of Gastroenterology, Fujisawa City Hospital, Fujisawa, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Yang Q, Dong L, Zhang L, Zhang W, Zhang Y, Huang Y, Jin H, Yang H, Liu X, Zhao Y. Analytical and Diagnostic Performance of a Dual-Target Blood Detection Test for Hepatocellular Carcinoma. Cancer Rep (Hoboken) 2024; 7:e70017. [PMID: 39324668 PMCID: PMC11425738 DOI: 10.1002/cnr2.70017] [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: 04/25/2024] [Revised: 08/14/2024] [Accepted: 09/06/2024] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND Surveillance approaches with high sensitivity and specificity for hepatocellular carcinoma (HCC) are still urgently needed. Previous studies have shown that methylation of GNB4 and Riplet can effectively diagnose HCC. AIMS This study plan to analyze the performance of a blood test for detecting HCC using GNB4 and Riplet methylation. METHODS AND RESULTS This study mainly investigated the analytical performance of the dual-target HCC blood test (DT-HBT), including cut-off value, limit of detection (LOD), precision, analytical specificity, and coincidence rate. In addition, the detection performance for HCC was validated in 1030 clinical plasma samples (214 HCC and 816 non-HCC). Plasma samples from 25 HCC patients after hepatectomy were collected to assess the feasibility of the kit for postoperative recurrence monitoring. All analytical performance of the DT-HBT met prespecified requirements. The LOD for GNB4, Riplet, and β-actin was 1% methylation/100 copies/μL with cut-offs of 43, 43, and 35, respectively. The DT-HBT showed excellent precision, within 5% CV. It had a specificity of 91.5% for detecting other cancers, and 100% for breast, lung, and bladder cancer. No cross-reactions were observed with 9 potential interfering substances. The DT-HBT achieved a 100% coincidence rate in detecting reference and clinical samples. The clinical performance study found that the kit showed a sensitivity of 81.7% for stage I HCC, and an overall sensitivity and specificity of 87.4% and 92.3%, respectively. The detection sensitivity for postoperative recurrent patients was 95.8%, with a specificity of 100%. CONCLUSION The analytical performance of the DT-HBT met prespecified criteria. It provided HCC patients with a reliable and high-performing new blood test for the HCC diagnosis and surveillance. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT05685524.
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Affiliation(s)
- Qiankun Yang
- Department of TransfusionThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Lanlan Dong
- Academic DepartmentWuhan Ammunition Life‐Tech Company, Ltd.WuhanChina
| | - Lianglu Zhang
- Academic DepartmentWuhan Ammunition Life‐Tech Company, Ltd.WuhanChina
| | - Wei Zhang
- Academic DepartmentWuhan Ammunition Life‐Tech Company, Ltd.WuhanChina
| | - Yan Zhang
- Academic DepartmentWuhan Ammunition Life‐Tech Company, Ltd.WuhanChina
| | - Yue Huang
- Academic DepartmentWuhan Ammunition Life‐Tech Company, Ltd.WuhanChina
| | - Huifang Jin
- Department of TransfusionThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Hao Yang
- Department of TransfusionThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Xing Liu
- Department of Infectious Disease and Liver Disease, the Second Hospital of NanjingAffiliated to Nanjing University of Chinese MedicineNanjingChina
| | - Yanteng Zhao
- Department of TransfusionThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
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Lee JH, Kim KY, Lee CH, Kim M, Yoon CJ. Superselective ablative chemo-ethanol embolization for recurrent single hepatocellular carcinoma: a 6-month outcome analysis. JOURNAL OF LIVER CANCER 2024; 24:217-223. [PMID: 38741422 PMCID: PMC11449584 DOI: 10.17998/jlc.2024.05.08] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/08/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUNDS/AIMS To evaluate the safety and effectiveness of superselective ablative chemo-ethanol embolization (SACE) for the treatment of patients with recurrent single hepatocellular carcinoma (rHCC). METHODS This retrospective study included 22 patients (19 men; median age, 63 years [range, 38-86]) with Child-Pugh class of A/ B/C (16/3/3) that underwent SACE between January and June 2023 for recurrent single HCCs measuring ≤5 cm in diameter using a mixture of 99% ethanol and ethiodized oil/doxorubicin emulsion. The primary endpoint was the 6-month tumor response, and the secondary endpoints were the 1-month tumor response and treatment-related safety. This study was approved by our institutional review board, and the requirement for informed consent was waived. RESULTS SACE was successfully performed in 22 patients (95.2%). The complete response rates at 1-month and 6-month after treatment were 100.0% and 83.3%, respectively. At 6-month, local tumor progression occurred in one patient and intrahepatic distant metastasis was found in six patients (30.0%). No 6-month mortalities were reported. No adverse events greater than grade 2 or laboratory deteriorations were observed. Biliary complications or liver abscesses were not observed. CONCLUSIONS SACE for a single rHCC was highly effective in achieving a favorable 6-month tumor response and showed acceptable adverse events. However, further prospective studies are required to verify these findings.
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Affiliation(s)
- Jae Hwan Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kun Yung Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Chong-Ho Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Minuk Kim
- Department of Radiology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
| | - Chang Jin Yoon
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea
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Guo JY, Zhao LL, Cai HJ, Zeng H, Mei WD. Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer. World J Gastrointest Surg 2024; 16:1756-1764. [PMID: 38983320 PMCID: PMC11230010 DOI: 10.4240/wjgs.v16.i6.1756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/29/2024] [Accepted: 05/23/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND The recurrence rate of liver cancer after surgery is high. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is an effective treatment for liver cancer; however, its efficacy in recurrent liver cancer remains unclear. AIM To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer. METHODS Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan: Control (RFA alone); and experimental [TACE combined with RFA (TACE + RFA)]. The incidence of increased alanine aminotransferase levels, complications, and other indices were compared between the two groups before and after the procedures. RESULTS One month after the procedures, the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group (P < 0.05). Alpha-fetoprotein (AFP) and total bilirubin levels were lower than those in the control group (P < 0.05); The overall response rate was 82.22% and 66.67% in the experimental and control groups, respectively; The disease control rate was 93.33% and 82.22% in the experimental and control groups, respectively, the differences are statistically significant (P < 0.05). And there were no statistical differences in complications between the two groups (P > 0.05). CONCLUSION TACE + RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.
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Affiliation(s)
- Jin-You Guo
- Department of Oncology, The Second People's Hospital of Zhejiang Province Taizhou Yuhuan City, Taizhou 317605, Zhejiang Province, China
| | - Li-Li Zhao
- Department of Oncology, The Second People's Hospital of Zhejiang Province Taizhou Yuhuan City, Taizhou 317605, Zhejiang Province, China
| | - Hui-Jun Cai
- Department of Oncology, The Second People's Hospital of Zhejiang Province Taizhou Yuhuan City, Taizhou 317605, Zhejiang Province, China
| | - Hui Zeng
- Department of Interventional, China's Zhejiang Province Tumor Hospital, Hangzhou 310000, Zhejiang Province, China
| | - Wei-Dong Mei
- Department of Oncology, The Second People's Hospital of Zhejiang Province Taizhou Yuhuan City, Taizhou 317605, Zhejiang Province, China
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Ippolito D, Maino C, Gatti M, Marra P, Faletti R, Cortese F, Inchingolo R, Sironi S. Radiological findings in non-surgical recurrent hepatocellular carcinoma: From locoregional treatments to immunotherapy. World J Gastroenterol 2023; 29:1669-1684. [PMID: 37077517 PMCID: PMC10107213 DOI: 10.3748/wjg.v29.i11.1669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/10/2023] [Accepted: 03/02/2023] [Indexed: 03/17/2023] Open
Abstract
Since hepatocellular carcinoma (HCC) represents an important cause of mortality and morbidity all over the world. Currently, it is fundamental not only to achieve a curative treatment but also to manage in the best way any possible recurrence. Even if the latest update of the Barcelona Clinic Liver Cancer guidelines for HCC treatment has introduced new locoregional techniques and confirmed others as well-established clinical practices, there is still no consensus about the treatment of recurrent HCC (RHCC). Locoregional treatments and medical therapy represent two of the most widely accepted approaches for disease control, especially in the advanced stage of liver disease. Different medical treatments are now approved, and others are under investigation. On this basis, radiology plays a central role in the diagnosis of RHCC and the assessment of response to locoregional treatments and medical therapy for RHCC. This review summarized the actual clinical practice by underlining the importance of the radiological approach both in the diagnosis and treatment of RHCC.
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Affiliation(s)
- Davide Ippolito
- Department of Radiology, IRCCS San Gerardo dei Tintori, Monza 20900, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Milano 20121, Italy
| | - Cesare Maino
- Department of Radiology, IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Marco Gatti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Paolo Marra
- Department of Diagnostic and Interventional Radiology, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Francesco Cortese
- Interventional Radiology Unit, “F. Miulli” Regional General Hospital, Bari 70121, Italy
| | - Riccardo Inchingolo
- Interventional Radiology Unit, “F. Miulli” Regional General Hospital, Bari 70121, Italy
| | - Sandro Sironi
- School of Medicine and Surgery, University of Milano-Bicocca, Milano 20121, Italy
- Department of Diagnostic and Interventional Radiology, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
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Liang J, Bai Y, Ha FS, Luo Y, Deng HT, Gao YT. Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:1-18. [PMID: 36684055 PMCID: PMC9850755 DOI: 10.4251/wjgo.v15.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 12/06/2022] [Accepted: 12/27/2022] [Indexed: 01/10/2023] Open
Abstract
Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.
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Affiliation(s)
- Jing Liang
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Yi Bai
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
| | - Fu-Shuang Ha
- Department of Hepatology, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying Luo
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Hui-Ting Deng
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
| | - Ying-Tang Gao
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
- Tianjin Institute of Hepatobiliary Disease, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
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Papaconstantinou D, Tsilimigras DI, Pawlik TM. Recurrent Hepatocellular Carcinoma: Patterns, Detection, Staging and Treatment. J Hepatocell Carcinoma 2022; 9:947-957. [PMID: 36090786 PMCID: PMC9450909 DOI: 10.2147/jhc.s342266] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 08/29/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with the incidence of recurrence being as high as 88% even among patients who have undergone curative-intent treatment. Despite improvements in overall survival, recurrence remains a challenge necessitating accurate reappraisal of patient and disease status. To that end, accurate staging of recurrent HCC is a necessity to provide better care for these patients. Risk factors for poor survival after HCC recurrence have been identified and include characteristics of the primary disease, such as tumor multifocality, large size (≥5 cm), macroscopic vascular or microscopic lymphovascular invasion, preoperative a-fetoprotein (AFP) levels, R0 resection, and the presence of impaired liver function. Close surveillance with imaging is warranted following curative-intent therapy, with magnetic resonance imaging (MRI) being the preferred approach to identify small, early recurrent HCCs. Treatment decisions at the time of recurrence involve ruling out extrahepatic disease and identifying candidates for potentially curative-intent repeat treatment options. Patients with recurrent disease are, however, very diverse in terms of tumor morphology and biologic behavior, as well as residual hepatic functional reserve. Patients with preserved liver function may benefit from repeat liver resection or ablation. Patients with recurrence within the Milan criteria may even be candidates for salvage liver transplantation, while multimodality treatment with combination of liver-directed therapies appears to enhance oncologic outcomes for individuals with advanced recurrent disease. A “one-size-fits-all” approach in staging recurrent HCC does not exist. Rather, individualized and evidence-based decision-making is necessary in order to optimize outcomes for patients with recurrent HCC.
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Affiliation(s)
- Dimitrios Papaconstantinou
- Third Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
- Correspondence: Timothy M Pawlik, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA, Tel +1 614 293 8701, Fax +1 614 293 4063, Email
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