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Singh SP, Kumar K, Kulkarni A, Arora V, Choudhury A, Chaubal A, Rathi S, Shah S, Taneja S, Kumar A, Duseja A, Kumar G, Nagaraja Rao P, Saraswat V, Sarin SK. Predictors of Non-response to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma: A Multicentre Real World Study (HCC-AB Study). J Clin Exp Hepatol 2025; 15:102513. [PMID: 40129631 PMCID: PMC11930068 DOI: 10.1016/j.jceh.2025.102513] [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: 09/25/2024] [Accepted: 02/04/2025] [Indexed: 03/26/2025] Open
Abstract
Background The approved immunotherapies for patients with advanced HCC are Atezolizumab and Bevacizumab. However, patients in India present late and healthcare is often available through self-financing. To rationalise the therapy, we conducted a large multicentre study to identify the baseline predictors of non-response to atezolizumab and bevacizumab in advanced unresectable HCC. Methods A dose of atezolizumab 1200 mg and bevacizumab 15 mg/kg was used every 3 weeks from 6 centres across India. A total of 278 patients were screened, and 160 were included in the study. The study included patients with locally advanced metastatic or inoperable hepatocellular carcinoma who were at least 18 years of age and those who received <3 injections were excluded. Fifty-four percent of the included patients were BCLC-B and 46% were BCLC-C. The primary objective was to study overall survival and progression-free survival. While identifying radiological response, objective response rate and adverse effects were secondary objectives. Results The mean age was 61.9 ± 11.7 years, 88% were male, 55% had NASH, 16.3% had hepatitis C, 18.8% had hepatitis B and the rest were alcohol. The mean Model for End-Stage Liver Disease (MELD) is 12.05 ± 4.46, Albumin-Bilirubin Score (ALBI) is -2.04 ± 0.57. Fifty-five percent received first-line and 45% as second/other line therapy. The median overall survival was 10 (95% confidence interval [CI]: 6.1-15.6) months. Progression-free survival was found to be 8 (95%CI: 5.1-14.7) months overall. Eleven (6.9%) achieved complete response, 28 (17.5%) partial response, 33 (20.6%) had stable disease and 88 (55%) had progressive disease. On multivariate analysis, CRP>1 mg/dl (P-0.007), PIVKA-II>400 mAU/mL (P-0.019), AFP>100 ng/ml (P-0.009), presence of diabetes (P-0.042) were associated with non-response to atezolizumab and bevacizumab injection. Fifty-three percent of patients developed any grade of adverse effect, and 20% developed grade 3/4 adverse events amounting to the stoppage of therapy. Conclusion Non-response to atezolizumab and bevacizumab immunotherapy was predicted by CRP>1 mg/dl, PIVKA-II>400mAU/ml, AFP>100 ng/ml and the presence of diabetes.
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Affiliation(s)
- Satender P. Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Karan Kumar
- Department of Hepatology and Liver Transplant, Mahatma Gandhi Hospital, Jaipur, India
| | - Anand Kulkarni
- Department of Hepatology and Liver Transplant, Asian Institute of Gastroenterology, Hyderabad, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Alisha Chaubal
- Department of Hepatology and Liver Intensive Care, Global Hospitals, Mumbai, India
| | - Sahaj Rathi
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Samir Shah
- Department of Hepatology and Liver Intensive Care, Global Hospitals, Mumbai, India
| | - Sunil Taneja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Guresh Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - P. Nagaraja Rao
- Department of Hepatology and Liver Transplant, Asian Institute of Gastroenterology, Hyderabad, India
| | - Vivek Saraswat
- Department of Hepatology and Liver Transplant, Mahatma Gandhi Hospital, Jaipur, India
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
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Tee SR, Hughes H, Ryan ER, McCann J, O'Rourke C, Bourke M, MacNicholas R, Cantwell CP, Healy GM. Outcomes and Complications of Image-Guided Percutaneous Tumour Ablation for Hepatocellular Carcinoma at the Irish National Liver Transplant Centre. Can Assoc Radiol J 2025; 76:333-343. [PMID: 39344072 DOI: 10.1177/08465371241286795] [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] [Indexed: 10/01/2024] Open
Abstract
Background: Image-guided tumour ablation is a minimally invasive treatment for early stage hepatocellular carcinoma (HCC). Our study reviews the complications and long term outcomes in patients treated at a tertiary referral centre. Methods: Retrospective study. All patients with HCC who underwent microwave ablation (MWA) or radiofrequency ablation (RFA) from 1st January 2014 to 31st December 2022 were identified. Treatment response of target lesion, complications, and survival were recorded. Results: One hundred seventy ablations were performed in 118 patients; 70% MWA, 30% RFA. Median radiological follow-up 21 months (range 3-107). Follow-up imaging was reported using LI-RADS and mRECIST. At first follow-up imaging, 94 patients had complete response (primary efficacy rate 80.3%) while 19.7% (n = 23) had residual disease. Fifteen of these had repeat ablation; 10 had complete response (secondary efficacy rate 85.6%). By end of study duration, 70.5% (n = 79) achieved sustained local complete response from single ablation without documented recurrence. 14.3% (n = 16) required more than one ablation of target lesion. Overall, 84.8% (n = 95) demonstrated long term local complete response to ablation. Complication occurred in 5.9% (n = 10); 40.0% Grade I, 40.0% Grade II, 10.0% Grade III, 10.0% Grade IV as per the CIRSE Classification. 1-, 3-, and 5-year overall survival (OS) rate was 97%, 68%, and 61% respectively. Mean OS was 5.3 years (median 4.7). No difference in OS (P = .7) or local progression free survival (P = .5) between patients treated with MWA versus RFA. Conclusion: This study demonstrates excellent long-term response to TA, with acceptable complication profile. No difference in survival between RFA versus MWA.
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Affiliation(s)
- Syer Ree Tee
- Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland
| | - Hannah Hughes
- Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland
| | - Edmund Ronan Ryan
- Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Jeff McCann
- Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Colin O'Rourke
- Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Michele Bourke
- Department of Hepatology, St. Vincent's University Hospital, Dublin, Ireland
| | - Ross MacNicholas
- School of Medicine, University College Dublin, Dublin, Ireland
- Department of Hepatology, St. Vincent's University Hospital, Dublin, Ireland
| | - Colin P Cantwell
- Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Gerard M Healy
- Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
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Zhang X, Zhang X, Luo QK, Fu Q, Liu P, Pan CJ, Liu CJ, Zhang HW, Qin T. Pretreatment radiomic imaging features combined with immunological indicators to predict targeted combination immunotherapy response in advanced hepatocellular carcinoma. World J Clin Oncol 2025; 16:102735. [DOI: 10.5306/wjco.v16.i4.102735] [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: 10/27/2024] [Revised: 12/16/2024] [Accepted: 01/23/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Early symptoms of hepatocellular carcinoma (HCC) are not obvious, and more than 70% of which does not receive radical hepatectomy, when first diagnosed. In recent years, molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC (aHCC). Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.
AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.
METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected. Signal intensity of intrahepatic nodules was measured, and the hepatobiliary relative enhancement ratio (RER) was calculated. Progression-free survival (PFS) of patients with high and low reinforcement of HCC nodules was compared. The model was validated using receiver operating characteristic curves. Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.
RESULTS Univariate and multivariate analyses revealed that the RER, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy (P < 0.05). The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876 (95% confidence interval: 0.781-0.971, P < 0.05), the optimal cutoff value was 0.904, diagnostic sensitivity was 87.5%, and specificity was 79.2%. Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio < 5, platelet-to-lymphocyte ratio < 300, prognostic nutritional index < 45, and RER < 0.9 significantly improved PFS.
CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS. Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.
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Affiliation(s)
- Xu Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Xu Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Qian-Kun Luo
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Qiang Fu
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Pan Liu
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Chang-Jie Pan
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Chuan-Jiang Liu
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Hong-Wei Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Tao Qin
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
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Wang M, Bonne L, Laenen A, Dekervel J, Monbaliu D, Laleman W, Vandecaveye V, Pirenne J, Verslype C, Maleux G. Long-Term Outcome of Liver Transplantation for Hepatocellular Carcinoma After Bridging or Downstaging with Doxorubicin-Eluting Superabsorbent Polymer Microspheres. Cardiovasc Intervent Radiol 2025; 48:472-484. [PMID: 39961859 DOI: 10.1007/s00270-025-03981-4] [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: 04/18/2024] [Accepted: 01/26/2025] [Indexed: 04/01/2025]
Abstract
PURPOSE To retrospectively evaluate the long-term outcomes of patients treated with liver transplantation after neoadjuvant or induction transarterial chemoembolization using doxorubicin-eluting superabsorbent polymer microspheres and to assess risk factors associated with disease recurrence and death after transplantation. MATERIALS AND METHODS Between January 2006 and April 2021, 286 patients underwent liver transplantation related to cirrhosis and early hepatocellular carcinoma (HCC). Demographic, angiographic imaging, and clinical follow-up data were collected from patients' electronic medical records. Kaplan-Meier method was used to estimate disease-free survival. The prognostic effect of patient and disease characteristics on HCC recurrence was analyzed using logistic regression models. RESULTS Fifty-three out of 286 patients (19%) underwent neoadjuvant or induction chemoembolization with doxorubicin-eluting superabsorbent polymer microspheres as bridging (n = 36) or as downstaging (n = 17) treatment. Time between diagnosis and liver transplantation was 311 days (range:225-440). Post-transplant follow-up revealed HCC recurrence in n = 1 (3%) and n = 4 (23.5%) patients in the bridging and downstaging groups, respectively, and disease-free survival at 5 years of 86% and 65% (p < 0.05) in the bridging and downstaging groups, respectively. Prognostic factors for post-transplant HCC recurrence include number of HCC lesions (p = 0.0088) and total tumor size (p = 0.0188) at diagnosis, as well as number of lesions (p = 0.0181) and largest tumor size (p = 0.0179) at explant analysis. CONCLUSION Neoadjuvant or induction chemoembolization with doxorubicin-eluting superabsorbent polymer microspheres is associated with a low incidence of post-transplant HCC recurrence; number and total size of HCC lesions at diagnosis and at explant analysis are risk factors for post-transplant HCC recurrence.
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Affiliation(s)
- Maud Wang
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium
| | - Lawrence Bonne
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium
| | - Annouschka Laenen
- Department of Biostatistics and Statistical Bioinformatics, University Hospitals KU Leuven, Leuven, Belgium
| | - Jeroen Dekervel
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Wim Laleman
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Vincent Vandecaveye
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Chris Verslype
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Geert Maleux
- Department of Radiology and Department of Imaging and Pathology, University Hospitals KU Leuven, Leuven, Belgium.
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Unome S, Imai K, Aiba M, Miwa T, Hanai T, Suetsugu A, Takai K, Shimizu M. Cachexia is an independent predictor of mortality in patients with hepatocellular carcinoma on systemic targeted therapy. Clin Nutr ESPEN 2025; 66:454-459. [PMID: 39993564 DOI: 10.1016/j.clnesp.2025.02.018] [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: 11/15/2024] [Revised: 01/21/2025] [Accepted: 02/08/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND & AIM This study aimed to investigate the prevalence and prognostic impact of cachexia in patients with unresectable hepatocellular carcinoma (HCC) receiving systemic targeted therapy. METHODS This single-center retrospective study included patients with HCC who underwent systemic targeted therapy. Cachexia was defined using novel criteria proposed in 2023. The prognostic impact of cachexia was evaluated using the Cox proportional hazards model. RESULTS Of the 200 patients (160 males [80%]; median age, 73 years), cachexia was identified in 70 patients and associated with higher des-gamma-carboxy prothrombin levels, and extrahepatic spread. Patients with cachexia had significantly shorter overall survival (OS) (median 14.1 vs. 20.9 months, p = 0.002) and post-progression survival (PPS) (4.8 vs. 11.1 months, p = 0.001) compared to patients without cachexia. Multivariable analyses revealed cachexia as an independent adverse factor for OS (hazard ratio 1.54; 95% confidence interval 1.03-2.30, p = 0.035) and PPS (hazard ratio 1.64; 95% confidence interval 1.08-2.47, p = 0.018). No significant differences were observed in Progression-free survival between the two groups. Treatment discontinuation due to general appearance deterioration was more common in cachectic patients. CONCLUSIONS Cachexia was prevalent among patients with HCC receiving systemic targeted therapy and was identified as an independent predictor of poorer OS and PPS. Given the prognostic impact, the evaluation of cachexia is crucial in managing patients with HCC undergoing systemic targeted therapy.
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Affiliation(s)
- Shinji Unome
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Kenji Imai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Masashi Aiba
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Atsushi Suetsugu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Koji Takai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
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Gupta AN, Serhal M, Gordon AC, Gabr A, Kalyan A, Kulik L, Sato KT, Riaz A, Hohlastos ES, Salem R, Lewandowski RJ. Radiation Segmentectomy and Modified Radiation Lobectomy for Unresectable Early-Stage Intrahepatic Cholangiocarcinoma. J Vasc Interv Radiol 2025; 36:650-659. [PMID: 39709122 DOI: 10.1016/j.jvir.2024.12.016] [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: 08/25/2024] [Revised: 11/30/2024] [Accepted: 12/11/2024] [Indexed: 12/23/2024] Open
Abstract
PURPOSE To validate the safety and effectiveness of radiation segmentectomy (RS) and modified radiation lobectomy (mRL) in intrahepatic cholangiocarcinoma (iCCA) and to evaluate long-term outcomes in patients with unresectable, early-stage iCCA. MATERIALS AND METHODS A single-institution, retrospective study of patients with unresectable, solitary iCCA without extrahepatic disease or vascular involvement (Stage I) treated with RS and mRL was performed. Fifteen patients met inclusion criteria (median age, 65.5 years), including 11 (73%) with T1a disease and 4 (27%) with T1b disease. Outcomes included biochemical and clinical toxicities, tumor response by Response Evaluation Criteria in Solid Tumors (RECIST), time to progression, and overall survival (OS). RESULTS Median treatment dose was 308.2 Gy (range, 194.2-879.3 Gy). There were no cases of periprocedural mortality or hepatic deterioration. Grade 3+ clinical toxicities occurred in 1 patient (7%). The 3-month and best objective response rates by RECIST were 47% and 60%, respectively. Three patients went on to surgery with explant pathology revealing complete pathologic necrosis. Target lesion progression occurred in 4 patients at a median of 43.4 months. Median OS was 72 months. The 1-, 3-, and 5-year OS rates were 100%, 73.3%, and 50.3%, respectively. CONCLUSIONS RS and mRL were safe and effective in treating unresectable, early-stage iCCA. Overall progression of 47% and 5-year OS of 50% were comparable with those of surgical resection. RS and mRL may represent viable therapeutic options for patients with early-stage disease deemed surgically unresectable.
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Affiliation(s)
- Aakash N Gupta
- Section of Vascular and Interventional Radiology, Department of Radiology, Stanford University, Stanford, California
| | - Muhamad Serhal
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Andrew C Gordon
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Ahmed Gabr
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Aparna Kalyan
- Division of Hematology and Oncology, Northwestern University, Chicago, Illinois
| | - Laura Kulik
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois; Division of Hematology and Oncology, Northwestern University, Chicago, Illinois; Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, Illinois
| | - Kent T Sato
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Ahsun Riaz
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Elias S Hohlastos
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Riad Salem
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois; Division of Hematology and Oncology, Northwestern University, Chicago, Illinois; Division of Organ Transplantation, Department of Surgery, Northwestern University, Chicago, Illinois
| | - Robert J Lewandowski
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois; Division of Hematology and Oncology, Northwestern University, Chicago, Illinois; Division of Organ Transplantation, Department of Surgery, Northwestern University, Chicago, Illinois.
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Iseda N, Itoh S, Toshima T, Yoshiya S, Bekki Y, Tsutsui Y, Toshida K, Inokuchi S, Utsunomiya T, Tomino T, Sugimachi K, Morita K, Ninomiya M, Harada N, Minagawa R, Yoshizumi T. Outcome of hepatectomy after systemic therapy for hepatocellular carcinoma: a Japanese multicenter study. Surg Today 2025; 55:510-517. [PMID: 39192138 DOI: 10.1007/s00595-024-02930-x] [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: 06/30/2024] [Accepted: 08/03/2024] [Indexed: 08/29/2024]
Abstract
BACKGROUND AND PURPOSE In recent years, new systemic therapies have been developed for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the prognosis of patients with unresectable HCC treated with R0 hepatectomy after systemic therapy. METHODS Data from 27 patients who underwent hepatectomy for HCC after systemic therapy at six facilities were analyzed retrospectively. Cancer-specific survival (CSS) and recurrence-free survival (RFS) after hepatectomy were investigated using Kaplan-Meier curves. We examined the prognostic value of the oncological criteria of resectability for HCC reported by the Japanese Expert Consensus 2023. RESULTS R0 resection was performed in 24 of the 27 patients. Using the Response Evaluation Criteria in Solid Tumors, 0 patient had a complete response, 16 had a partial response, 6 had stable disease, and 2 had progressive disease. Median CSS was not evaluated, but the median RFS was 17.8 months. Patients with resectable and borderline resectable (BR) 1 cancers had a better prognosis than those with BR2 cancers. The group whose oncological criteria were improved by systemic therapy had a lower recurrence rate than the group whose oncological criteria were maintained, but no difference was observed in CSS. CONCLUSIONS The findings of this study suggest that hepatectomy after systemic therapy may improve the prognosis of HCC patients.
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Affiliation(s)
- Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Shohei Yoshiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuki Bekki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuriko Tsutsui
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Katsuya Toshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Shoichi Inokuchi
- Department of Surgery, Oita Prefectural Hospital, Oita, 870-8511, Japan
| | - Toru Utsunomiya
- Department of Surgery, Oita Prefectural Hospital, Oita, 870-8511, Japan
| | - Takahiro Tomino
- Department of Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, 811-1395, Japan
| | - Keishi Sugimachi
- Department of Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, 811-1395, Japan
| | - Kazutoyo Morita
- Department of Surgery, Fukuoka City Hospital, Fukuoka, 812-0046, Japan
| | - Mizuki Ninomiya
- Department of Surgery, Fukuoka City Hospital, Fukuoka, 812-0046, Japan
| | - Noboru Harada
- Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, 810-0001, Japan
| | - Ryosuke Minagawa
- Department of Surgery, Japanese Red Cross Matsuyama Hospital, Matsuyama, 790-8524, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Lim J, Goh MJ, Song BG, Sinn DH, Kang W, Gwak GY, Choi MS, Lee JH, Cha DI, Gu K, Ha SY, Hwang I, Park WY, Paik YH. Unraveling the immune-activated tumor microenvironment correlated with clinical response to atezolizumab plus bevacizumab in advanced HCC. JHEP Rep 2025; 7:101304. [PMID: 40124166 PMCID: PMC11929055 DOI: 10.1016/j.jhepr.2024.101304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 12/05/2024] [Accepted: 12/10/2024] [Indexed: 03/25/2025] Open
Abstract
Background & Aims Despite atezolizumab plus bevacizumab being a standard treatment for advanced hepatocellular carcinoma (HCC), a significant proportion of patients do not achieve durable benefit. This study aimed to identify predictive biomarkers for this therapy by investigating the role of immune activation within the tumor microenvironment (TME). Methods We characterized the intratumoral TME of patients with advanced HCC treated with atezolizumab plus bevacizumab using single cell transcriptomics on pretreatment tumor biopsies from 12 patients. To complement and support these findings, we integrated our single cell data with publicly available bulk RNA-sequencing data from independent clinical trial cohorts. Results Patients who responded to combination therapy with atezolizumab plus bevacizumab demonstrated an immune-activated TME, marked by enhanced cytotoxicity and a tumor-specific T cell response. These patients also exhibited an increased proportion of inflammatory cytokine-enriched tumor-associated macrophage clusters with stronger interactions with T cells, an increased population of conventional dendritic cells, and activated antigen-presenting function in tumor endothelial cells. When publicly available bulk RNA-sequencing data from independent clinical trial cohorts were analyzed, these immune activation features were associated with improved progression-free survival (median 10.8 months, 95% CI: 7.3-not reached versus 5.5 months, 95% CI: 4.0-6.7; p <0.001). Conclusions These findings suggest that the existence of an activated immune TME before treatment is crucial for a favorable clinical response in patients with HCC treated with atezolizumab plus bevacizumab. Impact and implications Only a subset of patients with HCC benefit from combination therapy with atezolizumab plus bevacizumab, limiting its clinical utility. In this study, we used single cell RNA analysis to identify TME features associated with a clinical response to this therapy. Our findings suggest that a pre-existing immune-activated TME is crucial for predicting the response to atezolizumab plus bevacizumab. Specifically, features such as enhanced T cell cytotoxicity, inflammatory cytokine-enriched macrophage clusters, active antigen presentation in endothelial cells, and an increased presence of dendritic cells may aid patient selection and inform therapeutic strategies.
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Affiliation(s)
- Jinyeong Lim
- Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sunkyunkwan University, Seoul, South Korea
- Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea
| | - Myung Ji Goh
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Byeong Geun Song
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Hyun Sinn
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Moon Seok Choi
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Hyeok Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Ik Cha
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kyowon Gu
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Inwoo Hwang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Woong-Yang Park
- Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sunkyunkwan University, Seoul, South Korea
- Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea
| | - Yong-Han Paik
- Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sunkyunkwan University, Seoul, South Korea
- Division of Gastroenterology and Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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9
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Yu J, Yu J, Chen Y, Yang Y, Yi P. PD-1 inhibitors improve the efficacy of transcatheter arterial chemoembolization combined with apatinib in advanced hepatocellular carcinoma: a meta-analysis and trial sequential analysis. BMC Cancer 2025; 25:564. [PMID: 40155828 PMCID: PMC11951536 DOI: 10.1186/s12885-025-13932-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Accepted: 03/12/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND The efficacy of adding programmed death-1 (PD-1) inhibitors to transcatheter arterial chemoembolization (TACE) combined with apatinib for advanced hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the efficacy of incorporating PD-1 inhibitors into TACE combined with apatinib. METHODS Relevant literature on TACE combined with apatinib plus PD-1 inhibitors for advanced HCC was searched in PubMed, Cochrane Library, Embase, and Web of Science databases. Trial sequential analysis (TSA) was conducted to minimize randomization errors and assess whether the meta-analysis provided conclusive evidence. RESULTS Six studies involving 1,452 patients were included. Compared with the TACE combined with apatinib treatment group (T-A), TACE combined with apatinib plus PD-1 inhibitors (T-A-P) significantly prolonged overall survival (OS) (Hazard Ratio [HR] 2.22, 95% Confidence Interval [CI] 1.93-2.56; p < 0.001) and progression-free survival (PFS) (HR 2.36, 95% CI 2.01-2.77; p < 0.001), while also improving the objective response rate (ORR) (risk ratios [RR] 1.60, 95% CI 1.20-2.14; p < 0.001) and disease control rate (DCR) (RR 1.06, 95% CI 1.00-1.12; p < 0.001). TSA results indicated that additional studies were required to confirm the significance of DCR. Prognostic analysis identified treatment regimen and extrahepatic metastasis as common independent risk factors for OS and PFS. The incidence of adverse events in the T-A-P treatment group was comparable to that in the T-A treatment group. CONCLUSION Adding PD-1 inhibitors to TACE combined with apatinib significantly prolonged OS and PFS, particularly in patients without extrahepatic metastases. It also improved ORR and DCR in patients with HCC.
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Affiliation(s)
- Jiahui Yu
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China
| | - Jinxin Yu
- North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China
| | - Yimiao Chen
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China
| | - Yuting Yang
- Department of Educational Technology, Institute of Education, China West Normal University, Nanchong, Sichuan, 637000, People's Republic of China
- Nanchong Gaoping District Wangcheng Primary School, Nanchong, People's Republic of China
| | - Pengsheng Yi
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China.
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10
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Iizuka Y, Inoue M, Kokubo M, Sakamoto T, Murofushi KN, Imagumbai T, Shimizuguchi T, Hiraoka M, Mizowaki T. Long-term results of dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring using a gimbal-mounted linac for liver tumors: a multicenter observational study. Int J Clin Oncol 2025:10.1007/s10147-025-02740-2. [PMID: 40117082 DOI: 10.1007/s10147-025-02740-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/02/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND Despite advancements in liver tumor treatments, a persistent need remains for minimally invasive therapies with high efficacy and long-term outcomes. In a previous multicenter phase II study, the safety and efficacy of dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors were evaluated using a gimbal-mounted system. Herein, we report the updated long-term results of this technique. METHODS This observational study examined patients with a single liver tumor, respiratory movement of at least 10 mm, performance status of 0-2, and Child-Pugh score of < 9. Patients who agreed to participate in the trial underwent dynamic tumor-tracking stereotactic body radiotherapy (prescribed dose, 40 Gy in five fractions for the planning target volume [D95]; 70% of the maximum dose). The primary endpoint was the 4-year overall survival rate. Secondary endpoints included 4-year local control and progression-free survival rates and the incidence of adverse events. RESULTS Between September 2015 and March 2019, 48 patients (median age, 74 years; median tumor diameter, 17.5 mm) underwent dynamic tumor-tracking stereotactic body radiotherapy. All lesions were successfully treated (hepatocellular carcinoma, 39 patients; liver metastases, 9 patients). The median observation period was 46 months, and the 4-year overall survival, local control, and progression-free survival rates were 67.4%, 97.9%, and 29.1%, respectively. Eight patients had grade 3 hepatobiliary enzyme elevation, hematologic toxicity, or hyponatremia; none had grade ≥ 4 adverse events. CONCLUSION These findings demonstrate the long-term safety and efficacy of dynamic tumor-tracking stereotactic body radiotherapy for liver tumors, with an excellent local control rate.
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Affiliation(s)
- Yusuke Iizuka
- Graduate School of Medicine, Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Kyoto, Japan.
- Department of Radiation Oncology, Shizuoka City Shizuoka Hospital, Shizuoka, Shizuoka, Japan.
| | - Minoru Inoue
- Graduate School of Medicine, Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Kyoto, Japan
| | - Masaki Kokubo
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Takashi Sakamoto
- Department of Radiation Oncology, Kyoto Katsura Hospital, Kyoto, Kyoto, Japan
| | - Keiko Nemoto Murofushi
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo, Tokyo, Japan
| | - Toshiyuki Imagumbai
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Takuya Shimizuguchi
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo, Tokyo, Japan
| | - Masahiro Hiraoka
- Department of Radiation Oncology, Uji-Tokushukai Medical Center, Uji, Kyoto, Japan
| | - Takashi Mizowaki
- Graduate School of Medicine, Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Kyoto, Japan
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Xi M, Yang Z, Hu L, Fu Y, Hu D, Zhou Z, Liu M, Zhao J, Shen J, Li Q, Chen B, Xu L, Fang A, Chen M, Liu S, Zhang Y. Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Recurrent Small Hepatocellular Carcinoma: A Randomized, Open-Label, Controlled Trial. J Clin Oncol 2025; 43:1073-1082. [PMID: 39693584 DOI: 10.1200/jco-24-01532] [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: 07/16/2024] [Revised: 09/18/2024] [Accepted: 10/22/2024] [Indexed: 12/20/2024] Open
Abstract
PURPOSE To assess the efficacy and safety of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) in treating recurrent small hepatocellular carcinoma (HCC). METHODS In this trial, patients with recurrent small HCC (single lesion ≤5 cm) were randomly assigned to receive either SBRT or RFA. The primary end point was local progression-free survival (LPFS), and secondary end points were progression-free survival (PFS), overall survival (OS), local control rate, and safety. RESULTS Between August 2019 and April 2022, 166 patients were assigned to SBRT (n = 83) and RFA (n = 83) groups. After a median follow-up time of 42.8 and 42.9 months in the SBRT and RFA groups, respectively, SBRT demonstrated a significantly better LPFS than that of RFA (hazard ratio [HR], 0.45 [95% CI, 0.24 to 0.87]; P = .014). The 2-year LPFS rates were 92.7% (95% CI, 87.3 to 98.5) with SBRT and 75.8% (95% CI, 67.2 to 85.7) with RFA. The median PFS time of the SBRT and RFA groups was 37.6 (95% CI, 26.0 to 49.2) and 27.6 (95% CI, 20.3 to 34.8) months, respectively (HR, 0.76 [95% CI, 0.50 to 1.15]; P = .190). Nine patients in the SBRT group and 10 in the RFA group died during the follow-up. The 2-year OS rates were 97.6% (95% CI, 94.3 to 100.0) in the SBRT group and 93.9% (95% CI, 88.9 to 99.2) in the RFA group (HR, 0.91 [95% CI, 0.37 to 2.22]; P = .830). The incidences of both acute and late adverse events were comparable between the groups (P = .436 and P = .715, respectively). CONCLUSION SBRT achieved better LPFS than that of RFA in patients with single recurrent HCC ≤5 cm, especially in HCC ≤2 cm, whereas PFS, OS, and safety were comparable between the two treatments.
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Affiliation(s)
- Mian Xi
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhoutian Yang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Li Hu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yizhen Fu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Dandan Hu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhongguo Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Mengzhong Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jing Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jingxian Shen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qiaoqiao Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Baoqing Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Li Xu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Aiping Fang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Minshan Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shiliang Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yaojun Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
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12
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Fan W, Zheng X, Zhang W, Zhu B, Wu Y, Xue M, Tang R, Huang Z, Qiao L, Lu M, Wu J, Tang Y, Chen J, Huang S, Bai M, Li J. Prediction Model of Survival in Unresectable HCC with Central Bile Duct Invasion Receiving TACE After Biliary Drainage: TEMP Score. J Hepatocell Carcinoma 2025; 12:615-628. [PMID: 40130082 PMCID: PMC11932117 DOI: 10.2147/jhc.s505328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 03/07/2025] [Indexed: 03/26/2025] Open
Abstract
Purpose Central bile duct invasion (BDI) by hepatocellular carcinoma (HCC) is rare and associated with poor prognosis, lacking treatment guidelines. While transarterial chemoembolization (TACE) is often used for unresectable cases, determining optimal candidates post-biliary drainage is controversial. We aim to develop a prognostic prediction model for unresectable HCC (uHCC) patients with central BDI receiving sequential TACE after successful biliary drainage. Patients and Methods We retrospectively analyzed 267 uHCC patients with central BDI receiving successful biliary drainage and sequential TACE from seven tertiary centers (2015-2021), divided into training (n=187) and validation (n=80) sets. Using Cox proportional-hazards regression model, we identified key prognostic indicators for overall survival (OS) and constructed a prediction model. Results Pre-TACE total bilirubin (TBil) values, extrahepatic spread (EHS), multiple intrahepatic tumors (MIT), and portal vein tumor thrombus (PVTT) were identified as the significant clinical indicators for OS. These four parameters were included in a novel prediction model, named TEMP score, which could successfully categorize patients in the training set into three distinct risk grades with median OS of 26.9, 9.4, and 5.8 months, respectively. The TEMP score predicted the time-dependent areas under the receiver operating characteristic curves for OS at 6 months, 1 year, and 2 years of 0.813/0.907, 0.833/0.782, and 0.838/0.811 in the training and validation sets, with corresponding C-indices of 0.812/0.929, 0.829/0.761, and 0.818/0.791, respectively, outperforming other currently available models in both cohorts. The calibration curve of the model for predicting OS presented good consistency between observations and predictions in both the training set and validation set. Conclusion The TEMP score effectively stratifies the prognosis of uHCC patients with central BDI who have undergone successful bile drainage and sequential TACE, helping to identify those who may benefit from TACE treatment.
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Affiliation(s)
- Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Xinlin Zheng
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Weihong Zhang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Bowen Zhu
- Department of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Yanqin Wu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Miao Xue
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Rong Tang
- Department of Hepatopancreatobiliary Surgery, Hainan General Hospital, Haikou, People’s Republic of China
| | - Zhen Huang
- Department of Interventional Angiology, Huizhou First People’s Hospital, Huizhou, People’s Republic of China
| | - Liangliang Qiao
- Department of Interventional Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Mingjian Lu
- Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Jian Wu
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Yiyang Tang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Jinghua Chen
- Cancer Center, Guangzhou Twelfth People’s Hospital, Guangzhou, People’s Republic of China
| | - Shugui Huang
- Department of General Surgery I, The First Affiliated Hospital of Guangzhou Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Mingjun Bai
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
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Guha S, Ibrahim A, Geng P, Wu Q, Chou Y, Akin O, Schwartz LH, Xie CM, Zhao B. Variability of HCC Tumor Diameter and Density Measurements on Dynamic Contrast-Enhanced Computed Tomography. Tomography 2025; 11:36. [PMID: 40137576 PMCID: PMC11946049 DOI: 10.3390/tomography11030036] [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: 01/23/2025] [Revised: 03/13/2025] [Accepted: 03/16/2025] [Indexed: 03/29/2025] Open
Abstract
PURPOSE In cancers imaged using contrast-enhanced protocols, such as hepatocellular carcinoma (HCC), formal guidelines rely on measurements of lesion size (in mm) and radiographic density (in Hounsfield units [HU]) to evaluate response to treatment. However, the variability of these measurements across different contrast enhancement phases remains poorly understood. This limits the ability of clinicians to discern whether measurement changes are accurate. METHODS In this study, we investigated the variability of maximal lesion diameter and mean lesion density of HCC lesions on CT scans across four different contrast enhancement phases: non-contrast-enhanced phase (NCE), early arterial phase (E-AP), late arterial phase (L-AP), and portal venous phase (PVP). HCC lesions were independently segmented by two expert radiologists. For each pair of a lesion's scan timepoints, one was selected randomly as the baseline measurement and the other as the repeat measurement. Both absolute and relative differences in measurements were calculated, as were the coefficients of variance (CVs). Analysis was further stratified by both contrast enhancement phase and lesion diameter. RESULTS Lesion diameter was found to have a CV of 5.11% (95% CI: 4.20-6.01%). About a fifth of the measurement's relative changes were greater than 10%. Although there was no significant difference in diameter measurements across different phases, there was a significant negative correlation (R = -0.303, p-value = 0.030) between lesion diameter and percent difference in diameter measurement. Lesion density measurements varied significantly across all phases, with the greatest relative difference of 47% in the late arterial phase and a CV of 22.84% (21.48-24.20%). The overall CV for lesion density measurements was 26.19% (24.66-27.72%). CONCLUSIONS Changes in tumor diameter measurements within 10% may simply be due to variability, and lesion density is highly sensitive to contrast timing. This highlights the importance of paying attention to these two variables when evaluating tumor response in both clinical trials and practice.
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Affiliation(s)
- Siddharth Guha
- Department of Radiology, Columbia University Irving Medical Center, New York, NY 10032, USA; (S.G.); (Y.C.)
| | - Abdalla Ibrahim
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (A.I.); (P.G.); (Q.W.); (O.A.); (L.H.S.)
| | - Pengfei Geng
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (A.I.); (P.G.); (Q.W.); (O.A.); (L.H.S.)
| | - Qian Wu
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (A.I.); (P.G.); (Q.W.); (O.A.); (L.H.S.)
| | - Yen Chou
- Department of Radiology, Columbia University Irving Medical Center, New York, NY 10032, USA; (S.G.); (Y.C.)
| | - Oguz Akin
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (A.I.); (P.G.); (Q.W.); (O.A.); (L.H.S.)
| | - Lawrence H. Schwartz
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (A.I.); (P.G.); (Q.W.); (O.A.); (L.H.S.)
| | - Chuan-Miao Xie
- Sun Yat-sen University Cancer Center, Guangzhou 510060, China;
| | - Binsheng Zhao
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (A.I.); (P.G.); (Q.W.); (O.A.); (L.H.S.)
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14
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Shen Y, Bai X, Zhang Q, Liang X, Jin X, Zhao Z, Song W, Tan Q, Zhao R, Jia W, Gu S, Shi G, Zheng Z, Wei G, Wang Y, Fang T, Li Y, Wang Z, Yang Z, Guo S, Lin D, Wei F, Wang L, Sun X, Qin A, Xie L, Qiu Y, Bao W, Rahimian S, Singh M, Murad Y, Shang J, Chu M, Huang M, Ding J, Chen W, Ye Y, Chen Y, Li X, Liang T. Oncolytic virus VG161 in refractory hepatocellular carcinoma. Nature 2025:10.1038/s41586-025-08717-5. [PMID: 40108464 DOI: 10.1038/s41586-025-08717-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 01/30/2025] [Indexed: 03/22/2025]
Abstract
Hepatocellular carcinoma remains a life-threatening malignancy with limited therapeutic options following the failure of second-line treatments1,2. Oncolytic viruses selectively replicate in and lyse cancer cells, releasing neoantigens and stimulating systemic antitumour immunity3, offering a potential therapeutic option. Here we present the results of a multicentre phase 1 clinical trial evaluating VG161, an engineered oncolytic herpes simplex virus that expresses IL-12, IL-15, IL-15Rα and a PD-1-PD-L1-blocking fusion protein4, for safety and efficacy in patients with advanced liver cancer. VG161 was well tolerated, with no dose-limiting toxicities observed, and it demonstrated promising efficacy by reshaping the tumour immune microenvironment and re-sensitizing tumours that were previously resistant to systemic treatments. Notably, we also found that patients who had previously been sensitive to checkpoint inhibitor therapy showed enhanced efficacy with VG161 treatment. Furthermore, we developed an efficacy-prediction model based on differentially expressed genes, which successfully identified patients who were likely to benefit from VG161 and predicted prolonged overall survival. These findings position VG161 as a promising third-line therapeutic option for refractory hepatocellular carcinoma. This provides a new avenue for treatment and advances the field of oncolytic virus-based immunotherapies. ClinicalTrials.gov registration: NCT04806464 .
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Affiliation(s)
- Yinan Shen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Xingmei Liang
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinyan Jin
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zeda Zhao
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Wei Song
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Qian Tan
- Shanghai Virogin Biotech, Shanghai, China
| | | | - William Jia
- Shanghai Virogin Biotech, Shanghai, China
- Virogin Biotech Canada, Richmond, British Columbia, Canada
- CNBG-Virogin Biotech (Shanghai), Shanghai, China
| | - Shanzhi Gu
- Department of Interventional Radiology, Hunan Cancer Hospital, Changsha, China
| | - Guoming Shi
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | - Guyue Wei
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Youlei Wang
- Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian Fang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuwei Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Zijun Wang
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Zifan Yang
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Sida Guo
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Danni Lin
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Fang Wei
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Lei Wang
- Department of Radiotherapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoli Sun
- Department of Radiotherapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Aijun Qin
- Shanghai Virogin Biotech, Shanghai, China
| | - Longshen Xie
- CNBG-Virogin Biotech (Shanghai), Shanghai, China
| | - Yeting Qiu
- Shanghai Virogin Biotech, Shanghai, China
| | | | - Shah Rahimian
- Virogin Biotech Canada, Richmond, British Columbia, Canada
| | - Manu Singh
- Virogin Biotech Canada, Richmond, British Columbia, Canada
| | - Yanal Murad
- Virogin Biotech Canada, Richmond, British Columbia, Canada
| | | | - Min Chu
- Shanghai Virogin Biotech, Shanghai, China
| | | | - Jun Ding
- Shanghai Virogin Biotech, Shanghai, China
- Virogin Biotech Canada, Richmond, British Columbia, Canada
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yufu Ye
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiwen Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Xiang Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China.
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Wu G, Chen X, Luo R, Koh YX, Lim TKH, Chew V, Zhou J, Fan J, Gao Q, Zhu K, Shi R. Histopathologic Grading of Residual Tumor Predicts Survival of Intrahepatic Cholangiocarcinoma Patients Treated With Neoadjuvant Therapy: Major Pathologic Response and Its Clinical Significance. Am J Surg Pathol 2025:00000478-990000000-00491. [PMID: 40103370 DOI: 10.1097/pas.0000000000002359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2025]
Abstract
Neoadjuvant therapy (NAT) is increasingly used to treat patients with initially unresectable intrahepatic cholangiocarcinoma (iCCA). A histopathologic grading system for residual tumors that can predict patient survival is lacking in the literature. This retrospective study enrolled 151 iCCA patients who received NAT. The percentage of residual viable tumor (%RVT) extent was calculated by RVT surface area/total tumor bed area ×100 and scored in 5% increments. Kaplan-Meier and Cox regression analyses were used to investigate its correlations with recurrence-free survival (RFS) and overall survival (OS). Tumor regression grading by the College of American Pathologists (CAP) and MD Anderson (MDA) methodologies were also validated. A 10% RVT-based tumor regression score (TRS) showed a significant correlation with both OS and RFS. TRS and major pathologic response (mPR) were therefore defined as follows: TRS 1/mPR, tumor with 0 to 10% RVT; TRS 2, more than 10% RVT. Patients graded as TRS 1/mPR had superior OS (P=0.006) and RFS (P<0.001) compared with those with TRS 2 in univariate analysis. In a multivariate analysis including ypTNM stages, lymphovascular invasion, and perineural invasion, TRS 1/mPR was also found to be an independent prognostic factor for both OS (hazard ratio [HR]: 0.226; 95% CI: 0.053-0.966, P=0.045) and RFS (HR: 0.474; 95% CI: 0.231-0.974, P=0.042). As for the CAP and MDA grading methodologies, they were found to correlate with RFS (CAP: P=0.002; MDA: P=0.001), but not with OS (CAP: P=0.181; MDA: P=0.09). Our study revealed that a TRS of ≤10% RVT significantly correlates with longer OS and RFS and can be suggested as an mPR in iCCA. This indicator is easily applicable, prognostically relevant, and could be further validated in future prospective clinical trials.
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Affiliation(s)
- Gaohua Wu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Xiufen Chen
- Department of Anatomical Pathology, Singapore General Hospital
| | - Rongkui Luo
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre
| | | | - Valerie Chew
- Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Qiang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Kai Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Ruoyu Shi
- Department of Pathology and Laboratory Medicine, Kandang Kerbau Women's and Children's Hospital, Singapore
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Zhou S, Song C, Liu P, Ju S, Wang YC. A nationwide investigation on imaging follow-up after Locoregional therapy for hepatocellular carcinoma in China: Current practices and challenges. Eur J Radiol 2025; 186:112057. [PMID: 40132470 DOI: 10.1016/j.ejrad.2025.112057] [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: 01/11/2025] [Revised: 02/22/2025] [Accepted: 03/17/2025] [Indexed: 03/27/2025]
Abstract
PURPOSE To investigate the perspectives of interventional radiologists in China on imaging follow-up protocols and adherence to treatment response criteria for hepatocellular carcinoma (HCC) following locoregional therapies (LRT), with a particular focus on identifying gaps and proposing strategies to bridge the discrepancy between clinical guidelines and real-world practice. MATERIALS AND METHODS The web-based survey was conducted among members of Chinese Society of Radiology and Zhongda Radiology Alliance between 1st October 2024 to 30th November 2024, via WPS Office survey tool. The frequencies and percentages of responses were summarized as n (%), and a chi-squared test was employed to compare the responses among diagnostic radiologists, interventional radiologists, and interventional physicians. RESULTS A total of 604 respondents from 325 hospitals in 31 provinces were analyzed. Of the respondents, 72.7 % (439/604) believed that the same imaging modality should be used for follow-up after conventional transarterial chemoembolization (cTACE) and other LRT for HCC. Among these respondents, contrast-enhanced computed tomography (CE-CT) (57.2 %, 251/439) was the most preferred imaging modality for initial follow-up, and hepatobiliary contrast-enhanced MRI (63.1 %, 277/439) for subsequent follow-up examinations. For respondents (27.3 %, 165/604) who believed that follow-up strategies should be tailored to the type of LRT, CE-CT was most commonly recommended for post-cTACE HCC, both for initial (64.2 %, 106/165) and subsequent (60.6 %, 100/165) follow-up. For HCC treated with other LRT, the majority of respondents preferred extracellular contrast-enhanced MRI for initial follow-up (55.8 %, 92/165) and hepatobiliary contrast-enhanced MRI for subsequent follow-up (61.2 %, 101/165). The most recommended time frame for initial follow-up was "within 1-2 months" among all respondents. However, significant differences in the recommended time frame were observed among diagnostic radiologists, interventional radiologists, and interventional physicians (P < 0.001). Notably, more than 95 % of the respondents who selected 'unclear' were diagnostic radiologists. The most recommended monitoring frequency was every 3-4 months (46.0 %, 278/604) for viable lesions and every 5-6 months (32.9 %, 199/604) for nonviable lesions. Regarding adherence to treatment response criteria, mRECIST (32.0 %, 193/604) and LR-TRA (v2017/v2024) (24.2 %, 146/604) were commonly adopted in clinical practice. Nevertheless, a significant proportion of respondents (25.2 %, 152/604) indicated that none of these criteria were applied in their clinical practice. CONCLUSION CE-CT performed within 1-2 months was the most preferred modality and time frame for initial follow-up. Significant variability remains in follow-up frequency and treatment response criteria for post-LRT HCC, highlighting the need for further standardization of imaging follow-up protocols and structured treatment response assessment to optimize post-LRT management in clinical practice.
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Affiliation(s)
- Shuwei Zhou
- Department of Radiology, Zhongda Hospital, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, School of Medicine, Southeast University, Nanjing 210009, China.
| | - Chenxin Song
- Department of Radiology, Zhongda Hospital, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, School of Medicine, Southeast University, Nanjing 210009, China.
| | - Pei Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Shenghong Ju
- Department of Radiology, Zhongda Hospital, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, School of Medicine, Southeast University, Nanjing 210009, China.
| | - Yuan-Cheng Wang
- Department of Radiology, Zhongda Hospital, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, School of Medicine, Southeast University, Nanjing 210009, China.
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Garrou F, Sacchetti GM, Leva L, Andreatta P, Brambilla M, Morbelli S, Carriero A. Transarterial radioembolization in neuroendocrine liver metastases 25 years later: A systematic review. Crit Rev Oncol Hematol 2025; 210:104697. [PMID: 40096872 DOI: 10.1016/j.critrevonc.2025.104697] [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: 09/16/2024] [Revised: 03/05/2025] [Accepted: 03/06/2025] [Indexed: 03/19/2025] Open
Abstract
Transarterial Radioembolization (TARE) currently lacks a defined role in treating neuroendocrine liver metastases (NELM). This systematic review aims to clarify TARE's role based on its prognostic impact. A search identified 138 studies onPubMed/MEDLINE over the past 25 years, focusing on TARE for NELM patients. Of these, 46 studies met eligibility criteria, and 11 were selected for their similar settings, populations, and outcomes. These were grouped into three clusters based on survival outcomes: overall survival (OS), hepatic progression-free survival (HPFS), and imaging response (IR) per RECIST 1.1 criteria. Statistical analyses showed a median OS of 33 months for 809 patients, a median HPFS of 24 months for 414 patients, and an IR of 28.6 % complete or partial response, 57.8 % stable disease, and 13.6 % disease progression in 581 patients. This evidence supports TARE as a viable treatment option, but further studies are needed to optimize its use and dosimetric procedures.
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Affiliation(s)
- Federico Garrou
- Nuclear Medicine Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Nuclear Medicine Unit, AOU Maggiore della Carità, Novara, Italy.
| | | | - Lucia Leva
- Nuclear Medicine Unit, AOU Maggiore della Carità, Novara, Italy
| | - Paolo Andreatta
- Medical Physics Department, AOU Maggiore della Carità, Novara, Italy
| | - Marco Brambilla
- Medical Physics Department, AOU Maggiore della Carità, Novara, Italy
| | - Silvia Morbelli
- Nuclear Medicine Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Nuclear Medicine Unit, AOU Città della Salute e della Scienza di Torino, Turin, Italy
| | - Alessandro Carriero
- Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
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18
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Sanuki N, Kimura T, Takeda A, Ariyoshi K, Oyamada S, Yamaguchi T, Tsurugai Y, Doi Y, Kokubo M, Imagumbai T, Katoh N, Eriguchi T, Ishikura S. Final Results of a Multicenter Prospective Study of Stereotactic Body Radiation Therapy for Previously Untreated Solitary Primary Hepatocellular Carcinoma (The STRSPH Study). Int J Radiat Oncol Biol Phys 2025; 121:942-950. [PMID: 39706374 DOI: 10.1016/j.ijrobp.2024.10.040] [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: 05/06/2024] [Revised: 09/19/2024] [Accepted: 10/11/2024] [Indexed: 12/23/2024]
Abstract
PURPOSE To report final results of a prospective study of stereotactic body radiation therapy (SBRT) in patients with previously untreated solitary primary hepatocellular carcinoma (HCC). METHODS AND MATERIALS This prospective, single-arm, multicenter phase 2 trial recruited patients with HCC who were unsuitable for, or refused, surgery and radiofrequency ablation, with 3-year overall survival rates as the primary endpoint and survival outcomes and adverse events as secondary endpoints. The prescribed SBRT dose was 40 Gy in 5 fractions. The final data were analyzed in November 2022. RESULTS Between 2014 and 2018, 36 patients (median age, 73.5 years) were registered; enrollment was closed before full recruitment due to slow accrual. Overall, 34 patients were analyzed for efficacy evaluation after excluding 2 patients. The median tumor size was 2.3 cm. The median follow-up times for all patients and for survivors were 49 and 56 months, respectively. The 3-year overall survival rate was 82% (95% confidence interval, 65%-92%). The 3-year local control rate was 93% (95% confidence interval, 76%-98%). Grade 3 or higher SBRT-related nonlaboratory toxicities were observed in 4 patients (11%). No grade 5 adverse events were observed. CONCLUSIONS Final results of this phase 2 trial suggest the efficacy and safety of SBRT for newly diagnosed early-stage HCC that is unfit for other local therapies. Although this study was underpowered by the small number of registrations, the excellent results indicate that SBRT may be an alternative option for the management of early-stage HCC.
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Affiliation(s)
- Naoko Sanuki
- Department of Radiology, Keio University School of Medicine, Sinjuku-ku, Tokyo, Japan; Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Tomoki Kimura
- Department of Radiation Oncology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
| | - Atsuya Takeda
- Department of Radiology, Keio University School of Medicine, Sinjuku-ku, Tokyo, Japan; Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Keisuke Ariyoshi
- Department of Biostatistics, JORTC Data Center, Arakawa-ku, Tokyo, Japan
| | - Shunsuke Oyamada
- Department of Biostatistics, JORTC Data Center, Arakawa-ku, Tokyo, Japan
| | - Takuhiro Yamaguchi
- Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Yuichiro Tsurugai
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Yoshiko Doi
- Department of Radiation Oncology, Hiroshima Prefectural Hospital, Hiroshima, Hiroshima, Japan
| | - Masaki Kokubo
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Toshiyuki Imagumbai
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Norio Katoh
- Department of Radiation Oncology, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan
| | - Takahisa Eriguchi
- Department of Radiation Oncology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Kanagawa, Japan
| | - Satoshi Ishikura
- Department of Radiation Oncology, St. Luke's International Hospital, St. Luke's International University, Chuo-ku, Tokyo, Japan
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Xu J, Wang X, Jia Z, Sun G. Effectiveness and safety of angiogenesis inhibitors combined with PD-1/PD-L1 blockades in the first-line treatment of patients with advanced hepatocellular carcinoma: A single-center retrospective study. Medicine (Baltimore) 2025; 104:e41814. [PMID: 40101095 PMCID: PMC11922473 DOI: 10.1097/md.0000000000041814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/20/2025] Open
Abstract
The combination of immune checkpoint inhibitors targeting anti-programmed cell death-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) with antiangiogenic agents has emerged as a revolutionary therapy for advanced hepatocellular carcinoma (aHCC). Key antiangiogenic medications encompass monoclonal antibodies targeting vascular endothelial growth factor (anti-VEGF mAbs) and multiple kinase inhibitors (MKIs). The aim of this study is to assess the difference of efficacy and safety between 2 combination therapies. This study retrospectively examined the outcomes of 57 patients with aHCC who underwent first-line treatment with a combination of immune checkpoint inhibitors and antiangiogenic therapy at the First Affiliated Hospital of Anhui Medical University, from September 2018 to July 2023. The analysis, conducted using SPSS software, focused on patient outcomes such as tumor response (assessed according to modified Response Evaluation Criteria in Solid Tumors criteria), objective response rate, disease control rate, progression-free survival, overall survival, and safety. Comparisons among different groups were also made. The anti-PD-1/anti-PD-L1-anti-VEGF mAbs group showed a trend of higher partial response rate (37.50% vs 22.45%), objective response rate (37.50% vs 24.49%), disease control rate (62.50% vs 59.18%), and seemed to achieve longer median progression-free survival (14.93 vs 14.90 months) and median overall survival (15.80 vs 11.10 months) without higher grade 3 or higher adverse events comparing to anti-PD-1/anti-PD-L1-MKIs group. Subgroup analysis showed that the anti-PD-1-lenvatinib group achieved longer median progression-free survival (23.97 months), while the anti-PD-1-regorafenib group achieved longer median overall survival (37.97 months). The anti-PD-1/anti-PD-L1 combined with anti-VEGF mAbs was effective and tolerable compared to anti-PD-1/anti-PD-L1-MKIs in aHCC. The addition of lenvatinib or regorafenib may provide promising incremental benefit for patients with aHCC.
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Affiliation(s)
- Jing Xu
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
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D'Alessio A, Rimassa L. A new standard for HCC: The high stakes of TACE-immunotherapy combinations. MED 2025; 6:100635. [PMID: 40088884 DOI: 10.1016/j.medj.2025.100635] [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: 02/10/2025] [Revised: 02/11/2025] [Accepted: 02/11/2025] [Indexed: 03/17/2025]
Abstract
Transarterial chemoembolization (TACE) has long been the standard for intermediate-stage hepatocellular carcinoma (HCC), but two recent phase 3 trials have redefined treatment paradigms. The EMERALD-11 and LEAP-0122 trials demonstrated significant progression-free survival improvement with TACE combined with durvalumab/bevacizumab or pembrolizumab/lenvatinib, respectively, but doubts remain regarding the patient selection and the toxicity of these novel combinations.
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Affiliation(s)
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
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21
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Luo C, Xiang H, Tan J. The efficacy of transcatheter arterial chemoembolization for hepatocellular carcinoma: is the alteration of the inflammation index important? Front Med (Lausanne) 2025; 12:1543903. [PMID: 40160321 PMCID: PMC11949957 DOI: 10.3389/fmed.2025.1543903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 03/03/2025] [Indexed: 04/02/2025] Open
Abstract
Introduction Transcatheter arterial chemoembolization (TACE) is widely applied for locoregional malignant lesions control in intermediate and selected advanced hepatocellular carcinoma (HCC). Various inflammation indices, such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammatory index (SII), and Lymphocyte-to-C Reactive Protein Ratio (LCR) have been explored as tools for predicting the efficacy of TACE. However, the role and predictive value for dynamic changes of peripheral inflammatory indicators pre- and post-TACE remains unclear. Objective To explore the association between the alteration in inflammatory index and the efficacy and prognosis of TACE and to provide more evidence for early prediction of the efficacy of TACE. Methods This was a retrospective single-center study. HCC patients who received TACE as initial treatment were enrolled. The relationship between the alteration of inflammation indices (calculated as post-TACE minus pre-TACE measurements) and TACE efficacy and prognosis was investigated. Progression-free survival (PFS) was the primary endpoint, and treatment efficacy was evaluated based on mRECIST criteria. Results Before propensity score matching (PSM), the change in LMR was significantly associated with treatment effective rate, with the unelevated ΔLMR group achieving a 79.4% treatment effective rate compared to 36.4% in the elevated group (p < 0.001). The estimated median PFS was 9.7 months and 4.5 months in the unelevated and elevated group, with a significant difference (p = 0.016). After PSM, the treatment effective rate was 48.7 and 38.5% (p = 0.214), and the estimated median PFS was 8.9 and 5.5 months (p = 0.173) for the unelevated and elevated group, respectively. Conclusion Our study demonstrated that alteration of indices of peripheral inflammation, including ΔNLR, ΔLMR, ΔSII, and ΔPLR, may not be valuable prognostic markers for HCC patients who received TACE.
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Affiliation(s)
- Chao Luo
- Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Hua Xiang
- Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
- Department of Interventional Vascular Surgery, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jie Tan
- Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
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22
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Odisio BC, Albuquerque J, Lin YM, Anderson BM, O'Connor CS, Rigaud B, Briones-Dimayuga M, Jones AK, Fellman BM, Huang SY, Kuban J, Metwalli ZA, Sheth R, Habibollahi P, Patel M, Shah KY, Cox VL, Kang HC, Morris VK, Kopetz S, Javle MM, Kaseb A, Tzeng CW, Cao HT, Newhook T, Chun YS, Vauthey JN, Gupta S, Paolucci I, Brock KK. Software-based versus visual assessment of the minimal ablative margin in patients with liver tumours undergoing percutaneous thermal ablation (COVER-ALL): a randomised phase 2 trial. Lancet Gastroenterol Hepatol 2025:S2468-1253(25)00024-X. [PMID: 40090348 DOI: 10.1016/s2468-1253(25)00024-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 01/30/2025] [Accepted: 01/31/2025] [Indexed: 03/18/2025]
Abstract
BACKGROUND Tumour coverage with an optimal minimal ablative margin is crucial for improving local control of liver tumours following thermal ablation. The minimal ablative margin has traditionally been assessed through visual inspection of co-registered CT images. However, rates of local tumour control after thermal ablation are highly variable with visual assessment. We aimed to assess the use of a novel software-based method for minimal ablative margin assessment that incorporates biomechanical deformable image registration and artificial intelligence (AI)-based autosegmentation. METHODS The COVER-ALL randomised, phase 2, superiority trial was conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with up to three histology-agnostic liver tumours measuring 1-5 cm and undergoing CT-guided thermal ablation were enrolled. Thermal ablation was performed with the aim of achieving a minimal ablative margin of 5 mm or greater. Patients were randomly assigned (1:1) to the experimental group (software-based assessment) or the control group (visual assessment) by use of dynamic minimisation to balance covariates. Randomisation was performed intraprocedurally after placement of the ablation applicator. Assessment of oncological outcomes and adverse events were masked to treatment allocation. All analyses were conducted on an intention-to-treat basis. The primary endpoint was the minimal ablative margin on post-ablation intraprocedural CT. A preplanned interim analysis for superiority was done at 50% patient enrolment. Adverse events were recorded with the Common Terminology Criteria for Adverse Events. This trial is registered with ClinicalTrials.gov (NCT04083378), and recruitment is complete. FINDINGS Patients were enrolled and treated with thermal ablation between June 15, 2020, and Oct 5, 2023. 26 patients were randomly assigned to the control group (mean age 58·1 [SD 14·8] years; 18 [69%] male and eight [31%] female; 11 [42%] colorectal cancer liver metastasis; median tumour diameter 1·7 cm [IQR 1·3-2·3]) and 24 to the experimental group (mean age 60·5 [14·4] years; 16 [67%] male and eight [33%] female; ten [42%] colorectal cancer liver metastasis; median tumour diameter 1·8 cm [1·5-2·5]). The interim analysis showed a mean minimal ablative margin of 2·2 mm (SD 2·8) in the control group and 5·9 mm (2·7) in the experimental group (p<0·0001), prompting halting of enrolment in the control group. A further 50 patients were enrolled to a non-randomised experimental group (mean age 56·5 [SD 11·7] years; 27 [54%] male and 23 [46%] female; 30 [60%] colorectal cancer liver metastasis; median tumour diameter 1·5 cm [IQR 1·3-2·2]); among these patients, the mean minimal ablative margin was 7·2 mm (SD 2·8). Grade 1-3 adverse events were reported in five (5%) of 100 patients: three (12%) of 26 in the control group and two (3%) of 74 in the experimental groups. No grade 4-5 adverse events or treatment-related deaths were reported. INTERPRETATION Software-based assessment during CT-guided thermal ablation of liver tumours is safe and significantly improves the minimal ablative margin compared to visual assessment. Adoption of software-based assessment as a standard component of thermal ablation should be considered to achieve the intended minimal ablative margin. FUNDING US National Institutes of Health and US National Cancer Institute.
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Affiliation(s)
- Bruno C Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Jessica Albuquerque
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yuan-Mao Lin
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Brian M Anderson
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Caleb S O'Connor
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bastien Rigaud
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Maria Briones-Dimayuga
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aaron K Jones
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bryan M Fellman
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Steven Y Huang
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Joshua Kuban
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zeyad A Metwalli
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rahul Sheth
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Peiman Habibollahi
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Milan Patel
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ketan Y Shah
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Veronica L Cox
- Department of Abdominal Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - HyunSeon C Kang
- Department of Abdominal Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Van K Morris
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Milind M Javle
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei Tzeng
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hop-Tran Cao
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Timothy Newhook
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sanjay Gupta
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Iwan Paolucci
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kristy K Brock
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Pan S, Wang J, Tian J, Wang Y, Wang S, Yu Y, Li F, Jiao YM, Shen Y, Yang L, Liu X, Qiu Q, Luan J, Wang FS, Meng F. Safety and efficacy of PD-1 inhibitors plus tyrosine kinase inhibitors combination therapy in patients with advanced hepatocellular carcinoma combined with hyperbilirubinemia: a retrospective cohort study. Front Immunol 2025; 16:1530477. [PMID: 40134422 PMCID: PMC11932989 DOI: 10.3389/fimmu.2025.1530477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/21/2025] [Indexed: 03/27/2025] Open
Abstract
Background Programmed death-1 (PD-1) inhibitors plus tyrosine kinase inhibitors (TKIs) combination therapy are considered as a first-line treatment recommendation for advanced hepatocellular carcinoma (HCC). However, patients with hyperbilirubinemia are excluded from this therapeutic option due to limitations in indications. There is a notable absence of published studies evaluating the safety and efficacy of the PD-1 inhibitors plus TKIs combination therapy in patients with HCC combined with hyperbilirubinemia. Methods Patients with HCC complicated with hyperbilirubinemia who received combination therapy with PD-1 inhibitors and TKIs were retrospectively analyzed. Adverse events, tumor response, and laboratory parameters were recorded to assess the safety and efficacy of the treatment, as well as to identify potential risk factors influencing survival. Results A total of 108 participants were included in the study, with 56 patients (51.9%) reporting at least one adverse event, the majority of which were mild. The objective response rate (ORR) for the enrolled participants was 11.9%, and the disease control rate(DCR) reached 61.2%. The median overall survival (OS) for the entire cohort was 5.03 months, while the median progression-free survival (PFS) was 3.63 months. Multifactorial analysis showed that MELD score >18 and increased total bilirubin (TBIL) levels within one week were significant risk factors for OS. Patients with a decrease in TBIL levels within one week had significantly prolonged median OS (not reached vs 3.3months, P =0.013) and median PFS (7.03 months vs 2.77 months, P =0.010). Conclusion Combination therapy demonstrated favorable safety and tolerability among patients with HCC combined with hyperbilirubinemia. Patients who experienced a rapid decline in TBIL levels during the early phase of treatment with PD-1 inhibitors and TKIs were observed to derive clinical benefits. Early initiation of aggressive interventions aimed at reducing TBIL levels is recommended to optimize treatment outcomes.
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Affiliation(s)
- Shida Pan
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Jianing Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
| | - Jiahe Tian
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
| | - Yilin Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- Chinese People's Liberation Army (PLA) Medical School, Beijing, China
| | - Siyu Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yingying Yu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- 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
| | - Fengyi Li
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yan-Mei Jiao
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yingjuan Shen
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Luo Yang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Xiaomeng Liu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Qin Qiu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Junqing Luan
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Fu-Sheng Wang
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
- Chinese People's Liberation Army (PLA) Medical School, Beijing, China
| | - Fanping Meng
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
- Chinese People's Liberation Army (PLA) Medical School, Beijing, China
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Yang C, Zhu F, Yang J, Wang M, Zhang S, Zhao Z. DCE-MRI quantitative analysis and MRI-based radiomics for predicting the early efficacy of microwave ablation in lung cancers. Cancer Imaging 2025; 25:26. [PMID: 40065426 PMCID: PMC11892232 DOI: 10.1186/s40644-025-00851-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
OBJECTIVES To evaluate the feasibility and value of dynamic contrast-enhanced MRI (DCE-MRI) quantitative analysis and MRI-based radiomics in predicting the efficacy of microwave ablation (MWA) in lung cancers (LCs). METHODS Forty-three patients with LCs who underwent DCE-MRI within 24 h of receiving MWA were enrolled in the study and divided into two groups according to the modified response evaluation criteria in solid tumors (m-RECIST) criteria: the effective treatment (complete response + partial response + stable disease, n = 28) and the ineffective treatment (progressive disease, n = 15). DCE-MRI datasets were processed by Omni. Kinetics software, using the extended tofts model (ETM) and exchange model (ECM) to yield pharmacokinetic parameters and their histogram features. Changes in quantitative perfusion parameters were compared between the two groups. Scientific research platform ( https://medresearch.shukun.net/ ) was used for radiomics analysis. A total of 1874 radiomic features were extracted for each tumor by manually segmentation of T1WI and Contrast-enhanced of T1WI (Ce-T1WI) fat inhibition sequence. The performances of radiomics models were evaluated by the receiver operating characteristic curve. Based on radiomics features, survival curves were generated by Kaplan-Meier survival analysis to evaluate patient outcomes. P < 0.05 was set for the significance threshold. RESULTS The Vp value of ECM was significantly higher in the ineffective group compared to the effective group (p = 0.027). Additionally, the skewness, and kurtosis of Vp (p = 0.020 and 0.013, respectively) derived from ETM and Fp (p = 0.027 and 0.030, respectively) from ECM as well as the quantiles were higher in the ineffective group than in the effective group. Significant statistical differences were observed in the energy and entropy of Ve (p = 0.044 and 0.025, respectively) and Vp (p = 0.025 and 0.026, respectively) between the two groups. In the process of model construction, seven features from T1WI, five features from Ce-T1WI, and ten features from combined sequences were ultimately selected. The area under the curve (AUC) values for the T1WI model, Ce-T1WI model, and combined model were 0.910, 0.890, 0.965 in the training group, and 0.850, 0.700, 0.850 in the test group, respectively. CONCLUSIONS DCE-MRI quantitative analysis and MRI-based radiomics may be helpful in assessing the early response to MWA in patients with LCs.
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Affiliation(s)
- Chen Yang
- Department of Radiology, Shaoxing People's Hosipital, Shaoxing, China
| | - Fandong Zhu
- Department of Radiology, Shaoxing People's Hosipital, Shaoxing, China
| | - Jing Yang
- Department of Radiology, Shaoxing People's Hosipital, Shaoxing, China
| | - Min Wang
- Department of Pathology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Shijun Zhang
- Department of Pathology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
| | - Zhenhua Zhao
- Department of Radiology, Shaoxing People's Hosipital, Shaoxing, China.
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25
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Akula V, Chen L, Acikgoz Y, Klein K, Yavuz BG, Cevik L, Demir T, Manne A, Sahin I, Kaseb A, Hasanov E. Neoadjuvant immune checkpoint inhibitors for hepatocellular carcinoma. NPJ Precis Oncol 2025; 9:60. [PMID: 40050446 PMCID: PMC11885445 DOI: 10.1038/s41698-025-00846-4] [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: 09/23/2024] [Accepted: 02/24/2025] [Indexed: 03/09/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC treatment is challenging; surgical resection is the primary curative treatment for early-stage disease, but recurrence rates are high. Immune checkpoint inhibitors (ICIs) are a promising neoadjuvant treatment that can reduce recurrence rates and mortality after surgery and achieve complete/partial responses. Clinical trials provide strong evidence for the efficacy and safety of ICI monotherapy for neoadjuvant HCC treatment.
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Affiliation(s)
- Vinita Akula
- Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Lily Chen
- Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Yusuf Acikgoz
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Katherine Klein
- Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Betul Gok Yavuz
- Department of Medicine, University of Missouri, Columbia, MO, USA
| | - Lokman Cevik
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Tarik Demir
- Division of Hematology and Oncology Developmental Therapeutics Institute, Northwestern University, Chicago, IL, USA
| | - Ashish Manne
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Ilyas Sahin
- Division of Hematology & Oncology, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elshad Hasanov
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
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Kim J, Kim JH, Ko E, Kim JY, Im BS, Kim GH, Chu HH, Ko HK, Gwon DI, Shin JH, Alrashidi I. Model Predicting Survival in Intermediate-Stage HCC Patients Reclassified for TACE Based on the 2022 BCLC Criteria. Cancers (Basel) 2025; 17:894. [PMID: 40075741 PMCID: PMC11898427 DOI: 10.3390/cancers17050894] [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: 02/08/2025] [Revised: 02/25/2025] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
Background/Objectives: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) was updated in 2022 to refine patient stratification, particularly in patients with intermediate-stage (BCLC B) HCC. Although transarterial chemoembolization (TACE) remains a key treatment for these patients, there is no prognostic model for survival outcomes based on the pretreatment factors of patients who meet the updated 2022 BCLC indications for TACE. The aim of this study was to develop a pretreatment risk model predicting overall survival (OS) in patients with intermediate-stage HCC and reclassified as candidates for TACE according to the updated 2022 BCLC criteria. Methods: This retrospective study included 658 HCC patients treated with first-line TACE according to the updated BCLC 2022 guidelines. Pretreatment factors such as the Child-Pugh score, tumor burden (up-to-11 criteria), bilobar tumor involvement, and serum alpha-fetoprotein (AFP) levels were analyzed. Cox proportional hazards models were used to identify significant predictors of OS, with these factors subsequently incorporated into a risk prediction model. Results: Significant predictors of OS included Child-Pugh score ≥ 7, bilobar tumor involvement, beyond up-to-11 criteria, and AFP ≥ 400 ng/mL. A risk model was developed using these factors, stratifying patients into low-, intermediate-, and high-risk groups. The median OS in the low-, intermediate-, and high-risk groups was 53, 35, and 21 months, respectively. Conclusions: The proposed pretreatment risk prediction model may be useful for predicting OS and guiding TACE candidacy in intermediate-stage HCC patients based on the updated 2022 BCLC guidelines.
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Affiliation(s)
- Jihoon Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Jin-Hyoung Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Eunbyul Ko
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Jeong-Yeon Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Byung Soo Im
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Gun Ha Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Hee Ho Chu
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Heung-Kyu Ko
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Dong Il Gwon
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Ji Hoon Shin
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Ibrahim Alrashidi
- Department of Radiology, Prince Sultan Military Hospital, Madinah 42375, Saudi Arabia;
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27
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Chen J, Huang X, Wei Q, Liu S, Song W, Liu M. The relationship between systemic therapies and low skeletal muscle mass in patients with intermediate and advanced hepatocellular carcinoma. Front Immunol 2025; 16:1557839. [PMID: 40109345 PMCID: PMC11919905 DOI: 10.3389/fimmu.2025.1557839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
Background Low skeletal muscle mass (LSMM) has been associated with poor prognosis in hepatocellular carcinoma (HCC) patients receiving systemic therapy. However, its impact across different treatment regimens remains unclear. Methods A retrospective study analyzed 714 patients with intermediate and advanced HCC, divided into immunotherapy (I, n=85), target-immunotherapy combination (I+T, n=545), and targeted therapy (T, n=84) groups based on treatment. Skeletal muscle was assessed via computed tomography (CT) at the third lumbar vertebral level (L3) before and after 3 months of treatment. LSMM was evaluated by the third lumbar skeletal muscle index (L3-SMI) using a predefined threshold. Patients were stratified by baseline values and treatment changes. Kaplan-Meier and Cox models were used to compare overall survival (OS) and progression-free survival (PFS). Results There was no significant difference in the loss of muscle mass among the three groups of LSMM patients; whereas, non-LSMM(NLSMM) patients in group T lost more muscle mass than those in group I (P=0.040).In the I+T group, patients who achieved an objective response (ORR) had less muscle mass loss than those without (P=0.013), while the changes in muscle mass for patients in the I group and T group were unrelated to treatment response. Baseline or post-treatment LSMM was associated with poorer median OS, especially in the I+T group. Progressive LSMM was linked to shorter median PFS (4.9 vs 5.7 months) and OS (9.8 vs 16.5 months), with similar results in the I+T group (mPFS, 4.2 vs. 5.8 months; mOS, 9.7 vs 16.1 months). Patients with LSMM had a higher incidence of treatment-related SAEs, particularly ascites and fatigue. Conclusion In patients with combined LSMM in hepatocellular carcinoma, muscle loss did not significantly differ between those treated with I, I+T, and T; however, T treatment contributed to muscle mass loss in NLSMM patients. Greater muscle loss correlated with poorer treatment outcomes and increased SAEs, and baseline, post-treatment, and progressive LSMM were linked to significantly worse prognoses, particularly with combined treatment regimens.
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Affiliation(s)
- Jingjing Chen
- Department of Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Xueying Huang
- Department of Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Qiaoxin Wei
- Department of Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Songtao Liu
- Department of Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Wenyan Song
- Department of Imaging, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Mei Liu
- Department of Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, China
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Masthoff M, Irle M, Kaldewey D, Rennebaum F, Morgül H, Pöhler GH, Trebicka J, Wildgruber M, Köhler M, Schindler P. Integrating CT Radiomics and Clinical Features to Optimize TACE Technique Decision-Making in Hepatocellular Carcinoma. Cancers (Basel) 2025; 17:893. [PMID: 40075740 PMCID: PMC11899091 DOI: 10.3390/cancers17050893] [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: 01/29/2025] [Revised: 02/28/2025] [Accepted: 03/02/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND/OBJECTIVES To develop a decision framework integrating computed tomography (CT) radiomics and clinical factors to guide the selection of transarterial chemoembolization (TACE) technique for optimizing treatment response in non-resectable hepatocellular carcinoma (HCC). METHODS A retrospective analysis was performed on 151 patients [33 conventional TACE (cTACE), 69 drug-eluting bead TACE (DEB-TACE), 49 degradable starch microsphere TACE (DSM-TACE)] who underwent TACE for HCC at a single tertiary center. Pre-TACE contrast-enhanced CT images were used to extract radiomic features of the TACE-treated liver tumor volume. Patient clinical and laboratory data were combined with radiomics-derived predictors in an elastic net regularized logistic regression model to identify independent factors associated with early response at 4-6 weeks post-TACE. Predicted response probabilities under each TACE technique were compared with the actual techniques performed. RESULTS Elastic net modeling identified three independent predictors of response: radiomic feature "Contrast" (OR = 5.80), BCLC stage B (OR = 0.92), and viral hepatitis etiology (OR = 0.74). Interaction models indicated that the relative benefit of each TACE technique depended on the identified patient-specific predictors. Model-based recommendations differed from the actual treatment selected in 66.2% of cases, suggesting potential for improved patient-technique matching. CONCLUSIONS Integrating CT radiomics with clinical variables may help identify the optimal TACE technique for individual HCC patients. This approach holds promise for a more personalized therapy selection and improved response rates beyond standard clinical decision-making.
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Affiliation(s)
- Max Masthoff
- Clinic for Radiology, University of Münster, 48149 Münster, Germany
| | - Maximilian Irle
- Clinic for Radiology, University of Münster, 48149 Münster, Germany
| | - Daniel Kaldewey
- Clinic for Radiology, University of Münster, 48149 Münster, Germany
| | - Florian Rennebaum
- Department of Internal Medicine B, University of Münster, 48149 Münster, Germany
| | - Haluk Morgül
- Department of General, Visceral and Transplant Surgery, University of Münster, 48149 Münster, Germany
| | | | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, 48149 Münster, Germany
| | | | - Michael Köhler
- Clinic for Radiology, University of Münster, 48149 Münster, Germany
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Hosseini Shabanan S, Shobeiri P, Behnoush AH, Haghshomar M, Fowler KJ, Lewandowski RJ. 90Y-Transarterial Radioembolization Combined with Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: A Systematic Review. J Gastrointest Cancer 2025; 56:73. [PMID: 40025380 DOI: 10.1007/s12029-025-01189-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Transarterial radioembolization with yttrium-90 (90Yt-TARE) and immune checkpoint inhibitors (ICIs) are emerging as treatment modalities for intermediate to advanced hepatocellular carcinoma (HCC) based on randomized controlled trials. Herein, we systematically reviewed the published literature on the effects of 90Yt-TARE and ICIs combined on clinical outcomes of HCC. METHODS Medical databases of PubMed, Embase, and Cochrane Library were systematically searched for all studies assessing the use of concomitant immunotherapy of ICI with TARE in patients with HCC. Patient characteristics, treatment protocols, treatment outcomes, treatment adverse events, and survival outcomes were extracted after the screening phase. The primary outcomes were overall survival (OS) and patient-free survival (PFS), while the secondary outcomes were imaging objective response (OR) and adverse events. RESULTS Among 3432 reviewed, ten studies were included in this systematic review, including four randomized controlled trials and six retrospective studies. These consisted of 413 patients with HCC, and seven studies included patients with Child-Pugh A or B7 scores. Most studies allowed advanced or intermediate HCC stages, but only two specified BCLC stages (B and C). Median tumor sizes ranged from 56 to 78.5 mm. Various agents with different administration schedules were used as ICIs for immunotherapy by different studies for the combination of 90Yt-TARE with ICIs. Median OS ranged from 16.2 to 27 months between different studies while the PFS also ranged from 5.6 to 13.3 months. The OR rates according to imaging-based response assessments were reported between 31 and 89%, and the incidence rate of any grade toxicities was between 50 and 80%. CONCLUSION Concomitant treatment with 90Yt-TARE and ICIs has shown promising results in the treatment of patients with HCC. Further studies are required to reach a consensus on the optimal treatment protocol and the outcome of these treatments for patients with intermediate to advanced HCC.
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Affiliation(s)
| | - Parnian Shobeiri
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Amir Hossein Behnoush
- Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Maryam Haghshomar
- Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N. Saint Clair Street, Arkes Family Pavilion, Suite 800, Chicago, IL, 60611, USA
| | - Kathryn J Fowler
- Department of Radiology, University of California, San Diego, CA, USA
| | - Robert J Lewandowski
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
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30
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Keshavarz P, Nezami N, Yazdanpanah F, Khojaste-Sarakhsi M, Mohammadigoldar Z, Azami M, Hajati A, Ebrahimian Sadabad F, Chiang J, McWilliams JP, Lu DSK, Raman SS. Prediction of treatment response and outcome of transarterial chemoembolization in patients with hepatocellular carcinoma using artificial intelligence: A systematic review of efficacy. Eur J Radiol 2025; 184:111948. [PMID: 39892373 DOI: 10.1016/j.ejrad.2025.111948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 01/10/2025] [Accepted: 01/22/2025] [Indexed: 02/03/2025]
Abstract
PURPOSE To perform a systematic literature review of the efficacy of different AI models to predict HCC treatment response to transarterial chemoembolization (TACE), including overall survival (OS) and time to progression (TTP). METHODS This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines until May 2, 2024. RESULTS The systematic review included 23 studies with 4,486 HCC patients. The AI algorithm receiver operator characteristic (ROC) area under the curve (AUC) for predicting HCC response to TACE based on mRECIST criteria ranged from 0.55 to 0.97. Radiomics-models outperformed non-radiomics models (AUCs: 0.79, 95 %CI: 0.75-0.82 vs. 0.73, 0.61-0.77, respectively). The best ML methods used for the prediction of TACE response for HCC patients were CNN, GB, SVM, and RF with AUCs of 0.88 (0.79-0.97), 0.82 (0.71-0.89), 0.8 (0.60-0.87) and 0.8 (0.55-0.96), respectively. Of all predictive feature models, those combining clinic-radiologic features (ALBI grade, BCLC stage, AFP level, tumor diameter, distribution, and peritumoral arterial enhancement) had higher AUCs compared with models based on clinical characteristics alone (0.79, 0.73-0.89; p = 0.04 for CT + clinical, 0.81, 0.75-0.88; p = 0.017 for MRI + clinical versus 0.6, 0.55-0.75 in clinical characteristics alone). CONCLUSION Integrating clinic-radiologic features enhances AI models' predictive performance for HCC patient response to TACE, with CNN, GB, SVM, and RF methods outperforming others. Key predictive clinic-radiologic features include ALBI grade, BCLC stage, AFP level, tumor diameter, distribution, and peritumoral arterial enhancement. Multi-institutional studies are needed to improve AI model accuracy, address heterogeneity, and resolve validation issues.
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Affiliation(s)
- Pedram Keshavarz
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
| | - Nariman Nezami
- Department of Radiology, MedStar Georgetown University Hospital, Washington, DC 20007, USA; Georgetown University School of Medicine, Washington, DC 20007, USA; Lombardi Comprehensive Cancer Center, Washington, DC 20007, USA
| | | | | | - Zahra Mohammadigoldar
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Mobin Azami
- Department of Diagnostic & Interventional Radiology, New Hospitals Ltd., Tbilisi 0114, Georgia
| | - Azadeh Hajati
- Department of Radiology, Division of Abdominal Imaging, Harvard Medical School, Boston, MA 02114, USA
| | | | - Jason Chiang
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Justin P McWilliams
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - David S K Lu
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Steven S Raman
- Department of Radiological Sciences, David Geffen School of Medicine at The University of California, Los Angeles (UCLA), Los Angeles, CA, USA
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31
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Zhao J, Bera K, Mohamed A, Li Q, Ramaiya N, Tirumani SH. Comparison of RECIST 1.1, mRECIST and PERCIST for assessment of peptide receptor radionuclide therapy treatment response in metastatic neuroendocrine tumors. Curr Probl Diagn Radiol 2025; 54:228-232. [PMID: 39389807 DOI: 10.1067/j.cpradiol.2024.10.003] [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: 08/09/2024] [Accepted: 10/02/2024] [Indexed: 10/12/2024]
Abstract
PURPOSE To compare RECIST 1.1, modified RECIST (mRECIST) and PERCIST for assessment of Peptide Receptor Radionuclide Therapy (PRRT) treatment response in metastatic neuroendocrine tumors. MATERIALS In this IRB-approved, HIPAA compliant retrospective study, patients treated with PRRT between July 2019 and Dec 2022 were identified. Inclusion criteria were presence of at least one pre-and one post-treatment imaging (CT, MRI, Ga 68 or Cu64 DOTATATE PET/CT) within one year of the start and end of PRRT respectively. The imaging was reviewed independently by two radiologists using RECIST 1.1, modified RECIST (mRECIST) and PERCIST criteria. Response of first post treatment scan and presence of disease progression during follow-up were recorded along with the date of best response and disease progression. Statistical analysis was performed to determine inter-reader agreement and agreement between the various response criteria using kappa statistics. RESULTS Best response by RECIST 1.1 was recorded in 26 patients (PR-7, SD- 13, PD- 6), by mRECIST in 22 patients (PR-7, SD- 10, PD- 5), by PERCIST in 14 patients (PR-4, SD- 3, PD- 7). Inter-reader agreement was highest for PERCIST (weighted kappa 0.921, standard error 0.078 95% CI 0.769 to 1.000) followed by RECIST 1.1 (weighted kappa 0.897, standard error 0.071 95% CI 0.758 to 1.000) and mRECIST (weighted kappa 0.883, standard error 0.079 95% CI 0.727 to 1.000).
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Affiliation(s)
- Jack Zhao
- Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Kaustav Bera
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States.
| | - Amr Mohamed
- Medical Oncology, Department of Hematology and Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Qiubai Li
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Nikhil Ramaiya
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Sree Harsha Tirumani
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
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Xu M, Xie P, Liu S, Gao X, Yang S, Hu Z, Zhao Y, Yi Y, Dong Q, Bruns C, Kong X, Hung MC, Ren N, Zhou C. LCAT deficiency promotes hepatocellular carcinoma progression and lenvatinib resistance by promoting triglyceride catabolism and fatty acid oxidation. Cancer Lett 2025; 612:217469. [PMID: 39842501 DOI: 10.1016/j.canlet.2025.217469] [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: 09/22/2024] [Revised: 01/12/2025] [Accepted: 01/15/2025] [Indexed: 01/24/2025]
Abstract
Lecithin cholesterol acyltransferase (LCAT), a crucial enzyme in lipid metabolism, plays important yet poorly understood roles in tumours, especially in hepatocellular carcinoma (HCC). In this study, our investigation revealed that LCAT is a key downregulated metabolic gene and an independent risk factor for poor prognosis in patients with HCC. Functional experiments showed that LCAT inhibited HCC cell proliferation, migration and invasion. Mechanistically, LCAT interacts with caveolin-1 (CAV1) to promote the binding of CAV1 to PRKACA and inhibit its phosphorylation, thereby inhibiting triglyceride (TAG) catabolism. On the other hand, LCAT inhibits fatty acid oxidation (FAO) by interacting with CPT1A to promote its ubiquitination and degradation. These events result in an inadequate supply of raw materials and energy and inhibit the malignant behaviours of HCC cells. In addition, LCAT is a reliable predictive biomarker for the efficacy of lenvatinib treatment in HCC patients, and the inhibition of FAO can increase lenvatinib sensitivity in patients with LCATlow HCC. This study revealed that LCAT plays a critical role in the regulation of lipid metabolic reprogramming and is a reliable predictive biomarker for the efficacy of lenvatinib treatment in HCC patients.
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Affiliation(s)
- Min Xu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Peiyi Xie
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Shaoqing Liu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China; Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, P.R. China
| | - Xukang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Shiguang Yang
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, PR China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, PR China; Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, PR China
| | - Zhiqiu Hu
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, PR China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, PR China; Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, PR China
| | - Yue Zhao
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Kerpener Straße 62, 50937, Cologne, Germany
| | - Yong Yi
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Qiongzhu Dong
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, PR China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, PR China
| | - Christiane Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Kerpener Straße 62, 50937, Cologne, Germany
| | - Xiaoni Kong
- Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China.
| | - Mien-Chie Hung
- Graduate Institute of Biomedical Sciences, Institute of Biochemistry and Molecular Biology, Research Center for Cancer Biology, Cancer Biology and Precision Therapeutics Center, and Center for Molecular Medicine, China Medical University, Taichung, 40402, Taiwan.
| | - Ning Ren
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China.
| | - Chenhao Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China.
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Chen S, Liu J, Zhang S, Zhao L, Zhang J, Han P, Zhang Q, Liu Y, Wang F, Li J. Deciphering m6A signatures in hepatocellular carcinoma: Single-cell insights, immune landscape, and the protective role of IGFBP3. ENVIRONMENTAL TOXICOLOGY 2025; 40:367-383. [PMID: 38366283 DOI: 10.1002/tox.24177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 01/23/2024] [Accepted: 01/26/2024] [Indexed: 02/18/2024]
Abstract
RNA m6 methyladenosine (m6A) modifications impact tumor biology and immune processes, particularly in hepatocellular malignant tumors. Using a consensus clustering algorithm on 371 hepatocellular carcinoma (HCC) samples, we identified three m6A-modified subtypes and correlated them with positive tumor microenvironment (TME) markers for distinct immune phenotypes. Stratifying patients based on m6A scores revealed a low presentation group with better immune penetration, lower tumor mutation load, and increased expression of immune checkpoint markers like CTLA-4 and PD-1, suggesting enhanced responsiveness to immunization therapy. A machine-learning model of 23 m6A genes was constructed. Single-cell analysis revealed a surprising enrichment of IGFBP3 in astrocytes, prompting the exploration of associated signaling pathways. Experimental verification shows that IGFBP3 is significantly enhanced in normal tissues, while immunohistochemical analysis shows that its expression is lower in tumor tissues, indicating its protective effect in HCC and a good prognosis. Importantly, high IGFBP3 expression is associated with better outcomes in patients receiving immunotherapy. Moreover, cytotoxic T lymphocyte (CTL) experiments have confirmed that high expression of IGFBP3 is associated with stronger T cell-killing ability. In summary, the comprehensive evaluation of m6A modification, immune characteristics, and single-cell analysis in this study not only revealed the TME of HCC but also made significant contributions to the progress of personalized HCC immunotherapy targeting IGFBP3. This study provides a solid theoretical foundation for clinical translation and emphasizes its potential impact on developing effective treatment strategies.
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Affiliation(s)
- Shujia Chen
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
| | - Jie Liu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Shuting Zhang
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
| | - Lili Zhao
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Jindong Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Ping Han
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
| | - Qian Zhang
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
| | - Yao Liu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
| | - Fengmei Wang
- Department of Hepatology and Gastroenterology, Tianjin First Center Hospital, Tianjin, China
| | - Jia Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
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34
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Yang TS, Gong XH, Wang L, Zhang S, Shi YP, Ren HN, Yan YQ, Zhu L, Lv L, Dai YM, Qian LJ, Xu JR, Zhou Y. Comparison of automated with manual 3D qEASL assessment based on MR imaging in hepatocellular carcinoma treated with conventional TACE. Abdom Radiol (NY) 2025; 50:1180-1188. [PMID: 39297930 DOI: 10.1007/s00261-024-04571-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 09/01/2024] [Accepted: 09/04/2024] [Indexed: 09/21/2024]
Affiliation(s)
- Tian Shu Yang
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Xu Hua Gong
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Li Wang
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Shan Zhang
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yao Ping Shi
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Interventional Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Hai Nan Ren
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yun Qi Yan
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Li Zhu
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Lei Lv
- ShuKun (Beijing) Technology Co. Ltd, Beijing, China
| | | | - Li Jun Qian
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
| | - Jian Rong Xu
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
| | - Yan Zhou
- Diagnostic Radiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
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Choi JW, Kim GM, Hyun D, Jang MJ, Kim HC. Radioembolization as a Spearhead Treatment of Hepatocellular Carcinoma with Localized Portal Vein Tumor Thrombosis (RESOLVE): Protocol for an Open-label, Multi-center, Single-arm Trial. Cardiovasc Intervent Radiol 2025; 48:398-404. [PMID: 39948248 DOI: 10.1007/s00270-024-03935-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 11/27/2024] [Indexed: 03/08/2025]
Abstract
PURPOSE To evaluate the efficacy, safety, and clinical course following ablative radioembolization with glass microspheres for hepatocellular carcinoma (HCC) with localized portal vein tumor thrombosis (PVTT) in patients with well-preserved liver function. MATERIALS AND METHODS This is a prospective, open-label, multi-center, single-arm, phase II trial. Key inclusion criteria are unilobar HCC, PVTT confined to the ipsilateral lobe (Vp1-3), no extrahepatic spread, Child-Pugh class A, and a performance status of ≤ 1. Main exclusion criteria are hepatic venous tumor thrombus, bile duct invasion, and massive arterioportal shunting. Depending on the extent of the tumor and PVTT, patients will undergo radiation segmentectomy, modified radiation lobectomy, or ablative lobar treatment, while adhering to dose limits for the non-tumorous liver and lung. The primary outcome measure is overall survival, with the overall survival rate at two years provided as the summary measurement. STATISTICS This study will enroll 30 patients to explore the efficacy and safety of ablative radioembolization for HCC with localized PVTT. Efficacy will be evaluated by intention-to-treat and per-protocol populations. Safety will be assessed for all patients who received radioembolization at any dose. EXPECTED GAIN OF KNOWLEDGE This study aims to address the potential of ablative radioembolization as a definitive or effective downstaging treatment for HCC with localized PVTT, where locoregional treatments may be more beneficial than systemic treatments. The results will help establish treatment outcomes that can serve as a standard for future comparative studies and contribute to the standardization of radioembolization approaches for HCC with localized PVTT. TRIAL REGISTRATION ClinicalTrials.gov ( https://classic. CLINICALTRIALS gov/ct2/show/NCT06166576 ). Identifier: NCT06166576.
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Affiliation(s)
- Jin Woo Choi
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
| | - Gyoung Min Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dongho Hyun
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Myoung-Jin Jang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
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Inoue M, Ogasawara S, Kobayashi K, Okubo T, Itokawa N, Obu M, Fujimoto K, Unozawa H, Yumita S, Fujiwara K, Nakagawa M, Kanzaki H, Koroki K, Kiyono S, Nakamura M, Kanogawa N, Kondo T, Nakamoto S, Nagashima K, Itobayashi E, Atsukawa M, Koma Y, Azemoto R, Kato N. Assessment of Macrovascular Invasion in Advanced Hepatocellular Carcinoma: Clinical Implications and Treatment Outcomes with Systemic Therapy. Liver Cancer 2025; 14:8-18. [PMID: 40144472 PMCID: PMC11936442 DOI: 10.1159/000539380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 04/12/2024] [Indexed: 03/28/2025] Open
Abstract
Introduction Macrovascular invasion (MVI) is a strong prognostic factor for advanced hepatocellular carcinoma (HCC). The current criteria for radiological assessment are unclear in evaluating the impact of MVI on systemic therapy. In this study, we standardized the assessment of MVI and validated its clinical relevance. Methods Clinical data were collected from patients with advanced HCC and MVI who received first-line systemic therapy at four medical centers in Japan. First, we used MVI progressive disease (MVI-PD) to track MVI progression and Response Evaluation Criteria in Solid Tumors version 1.1 progressive disease (RECIST v1.1-PD) to evaluate tumor enlargement other than MVI and the appearance of new lesions. Next, we assessed the prognostic value of MVI-PD and RECIST v1.1-PD. Results Of the 207 advanced HCC patients with MVI, 189 received appropriate imaging evaluation. Forty (21.2%) patients had MVI-PD and RECIST v1.1-PD, 51 (27.0%) had prior MVI-PD, and 61 (32.3%) had prior RECIST v1.1-PD. In a landmark analysis, the prognosis of 163 patients who survived more than 3 months was analyzed based on the assessment of imaging response during the first 3 months. The median overall survival (OS) was 5.4 months in those who had MVI-PD and RECIST v1.1-PD, 7.4 months in those who had RECIST v1.1-PD only, 7.2 months in those who had MVI-PD only, and 19.7 months in patients who had neither (p < 0.001). The correlation coefficients between progression-free survival and OS in patients with appropriate imaging assessments were similar for MVI-PD (0.515) and RECIST v1.1-PD (0.498). Conclusion Our findings demonstrate the link between MVI progression and poor OS in systemic therapy for advanced HCC, emphasizing the importance of an accurate method for assessing MVI progression.
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Affiliation(s)
- Masanori Inoue
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kazufumi Kobayashi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tomomi Okubo
- Department of Gastroenterology, Nippon Medical School Chibahokusoh Hospital, Chiba, Japan
| | - Norio Itokawa
- Department of Gastroenterology, Nippon Medical School Chibahokusoh Hospital, Chiba, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Masamichi Obu
- Department of Gastroenterology, Kimitsu Chuo Hospital, Chiba, Japan
| | - Kentaro Fujimoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hidemi Unozawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Sae Yumita
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kisako Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Miyuki Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroaki Kanzaki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Keisuke Koroki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Soichiro Kiyono
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kanogawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takayuki Kondo
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kengo Nagashima
- Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Chiba, Japan
| | - Masanori Atsukawa
- Department of Gastroenterology, Nippon Medical School Chibahokusoh Hospital, Chiba, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Yoshihiro Koma
- Department of Gastroenterology, Kimitsu Chuo Hospital, Chiba, Japan
| | - Ryosaku Azemoto
- Department of Gastroenterology, Kimitsu Chuo Hospital, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Pahwa P, Sharma D, Yadav P, Thomas SS, Hora S, Preedia Babu E, Ramakrishna G, Sarin SK, Trehanpati N. Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma. J Clin Exp Hepatol 2025; 15:102444. [PMID: 39654812 PMCID: PMC11625295 DOI: 10.1016/j.jceh.2024.102444] [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: 08/05/2024] [Accepted: 10/17/2024] [Indexed: 12/12/2024] Open
Abstract
Background/Aims Stereotactic body radiation therapy (SBRT) has evolved as a treatment alternative for advanced hepatocellular carcinoma (HCC) patients who are ineligible for other local therapies. Posttreatment responses are assessed by imaging modalities, serum AFP, and protein induced by vitamin K absence-II (PIVKA) II levels. Despite good specificity, both AFP and PIVKA-II have low to medium sensitivity. The study aimed to find more effective biomarkers that have an impact on the survival outcomes of the patients. Methods We have prospectively collected blood samples from 18 patients undergoing SBRT. Serum levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) were analyzed kinetically pre-SBRT following day 5 and day 30 post-SBRT. Local control (LC), overall survival (OS), progression free survival (PFS), and postprocedure adverse events were recorded. Results The cohort had a median follow-up duration of 12.5 months (range 4-30 months). In the entire cohort, the estimated mean OS was 21.2 months (95% confidence interval [CI], 15.9-26.4), and the median progression free survival (mPFS) was 8 months (95% CI, 1.7-14.2). Patients with higher PIVKA-II levels (pre- and post-SBRT) also showed increased concentrations of VEGF-A and HGF. Patients with metastasis at presentation had higher HGF (P = 0.028) and VEGF-A (P = 0.027) concentrations compared to the nonmetastatic group. Patients with increased levels of VEGF-A and HGF at day 30 post-SBRT compared to day 5 had poor PFS. Indeed, the mPFS was 22 months vs 6 months (P = 0.301) in patients with low VEGF-A post SBRT on day 30 compared to day 5. Similarly, mPFS in patients with increase in HGF was 6 months as compared to 22 months (P = 0.326) in patients in whom HGF was reduced post-SBRT. Conclusion We conclude that in addition to PIVKA-II, HGF, and VEGF-A can be used as prognostic and predictive markers for early progression of disease post-SBRT. However, further prospective trials are warranted in the future to validate the results.
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Affiliation(s)
- Prabhjyoti Pahwa
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Deepti Sharma
- Department of Radiation Oncology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Pushpa Yadav
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sherin S. Thomas
- Department of Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sandhya Hora
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - E. Preedia Babu
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Gayatri Ramakrishna
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nirupama Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
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Yu J, Li Y, Yu J, Yang Y, Chen Y, Yi P. Hepatic arterial infusion chemotherapy enhances the efficacy of lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma: A meta-analysis and trial sequential analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109573. [PMID: 39793379 DOI: 10.1016/j.ejso.2025.109573] [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: 12/18/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025]
Abstract
BACKGROUND Hepatic arterial infusion chemotherapy (HAIC) was an effective treatment for advanced hepatocellular carcinoma (HCC), and its effectiveness in combination with targeted immunotherapy regimens was controversial. This meta-analysis was performed to evaluate the efficacy of adding HAIC to lenvatinib in combination with programmed death-1 (PD-1) inhibitors. METHODS Literature related to the efficacy of HAIC in combination with lenvatinib plus PD-1 inhibitors in the treatment of advanced HCC was searched through PubMed, Cochrane Library, Embase, and Web of Science databases. TSA was used to control for the risk of random error and assess whether the meta-analysis evidence was conclusive. RESULTS Eight relevant papers with a total of 1244 patients. Compared with the L-P treatment group, the H-L-P treatment group significantly prolonged OS (hazard ratio [HR] 2.11 [95 % confidence interval (CI) 1.82-2.44]; p < 0.001) and PFS (HR 1.91 [95 % CI 1.67-2.17]; p < 0.001) and improved ORR (risk ratio [RR] 2.20 [95 % CI 1.74-2.78]; p < 0.001) and DCR (RR 1.28 [95 % CI 1.15-1.42]; p < 0.001) in patients with advanced HCC. TSA analysis indicated that further trials were unnecessary, preliminary positive results were promptly obtained. Prognostic factor analysis demonstrated that extrahepatic metastasis were common independent risk factor for OS and PFS. The rate of adverse events (AEs) was higher in the H-L-P treatment group than in the L-P treatment group. CONCLUSION HAIC combined with lenvatinib plus PD-1 inhibitors markedly extended OS and PFS, particularly in patients without extrahepatic metastases. Furthermore, it markedly enhanced ORR and DCR in patients with HCC.
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Affiliation(s)
- Jiahui Yu
- Department of Hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, PR China
| | - Yong Li
- Department of Hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, PR China
| | - Jinxin Yu
- North Sichuan Medical College, Nanchong, Sichuan, 637000, PR China
| | - Yuting Yang
- Department of Educational Technology, Institute of Education, China West Normal University, Nanchong, Sichuan, 637000, PR China; Nanchong Gaoping District Wangcheng Primary School, Nanchong, Sichuan, 637100, PR China
| | - Yimiao Chen
- Department of Hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, PR China
| | - Pengsheng Yi
- Department of Hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, PR China.
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Nishikawa D, Shimabukuro T, Suzuki H, Beppu S, Terada H, Kobayashi Y, Hanai N. Predictive Factors for the Efficacy of Head and Neck Photoimmunotherapy and Optimization of Treatment Schedules. CANCER DIAGNOSIS & PROGNOSIS 2025; 5:179-188. [PMID: 40034957 PMCID: PMC11871859 DOI: 10.21873/cdp.10428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/01/2025] [Accepted: 02/03/2025] [Indexed: 03/05/2025]
Abstract
Background/Aim Head and neck photoimmunotherapy (HN-PIT) is a promising treatment for unresectable locally advanced or recurrent head and neck cancers. However, the optimal tumor characteristics and treatment schedules remain unclear. This study aimed to identify factors associated with treatment efficacy and assess the effectiveness of treatment schedules. Patients and Methods A retrospective cohort study of patients treated with HN-PIT at Aichi Cancer Center Hospital from January 2021 to October 2024 was conducted. Tumor characteristics, treatment cycles, and outcomes were analyzed. The thickness and longest diameter of the tumors were evaluated, and treatment intervals were assessed for their association with complete response (CR). Results Among the 19 patients (30 cycles), CR was observed exclusively in local lesions. Smaller and thinner lesions showed significantly better treatment responses. Thinner lesions were more likely to achieve CR after a single cycle, whereas intermediate-thickness tumors often required multiple cycles with shorter intervals. The regional lesions did not achieve CR, even with multiple cycles and shorter intervals. Age was a significant factor influencing CR. Conclusion HN-PIT demonstrated promising efficacy for local lesions, particularly for smaller and thinner lesions. Optimizing treatment schedules, including shorter intervals for intermediate lesions, is critical for improving outcomes. Further research is needed to enhance the efficacy for regional lesions and refine treatment schedules.
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Affiliation(s)
- Daisuke Nishikawa
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takuya Shimabukuro
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hidenori Suzuki
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Shintaro Beppu
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hoshino Terada
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yoshiaki Kobayashi
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Nobuhiro Hanai
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
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Zhai Y, Wang L, Zhao H, Wu F, Xin L, Ye F, Sun W, Song Y, Niu L, Zeng H, Wang J, Tang Y, Song Y, Liu Y, Fang H, Lu N, Jing H, Qi S, Zhang W, Wang S, Li YX, Wu J, Chen B. Phase II study with sorafenib plus radiotherapy for advanced HCC with portal and/or hepatic vein tumor thrombosis. JHEP Rep 2025; 7:101287. [PMID: 39980754 PMCID: PMC11840495 DOI: 10.1016/j.jhepr.2024.101287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/01/2024] [Accepted: 11/20/2024] [Indexed: 02/22/2025] Open
Abstract
Background & Aims Portal and hepatic vein tumor thrombosis is associated with inferior outcomes in patients with hepatocellular carcinoma (HCC), and systemic treatment alone is often insufficient. This phase II trial evaluated the efficacy and safety of combining sorafenib with radiotherapy in advanced HCC with thrombosis. Methods Registered at ClinicalTrials.gov (NCT03535259), this phase II single-arm prospective trial targeted patients with HCC with portal or hepatic vein tumor thrombosis, liver minus gross tumor volume >700 ml, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1. Participants underwent 40-66 Gy radiotherapy for the hepatic primary tumor and vein tumor thrombosis, with concurrent oral sorafenib (400 mg twice daily) until disease progression or unacceptable adverse events. The primary endpoint was median overall survival (mOS) and the secondary endpoints included overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), median progression-free survival (mPFS), time to tumor progression (TTP), tumor thrombosis control, and grade ≥3 adverse events. Results Between May 2018 and January 2020, 86 patients were enrolled with a median radiotherapy dose of 54 Gy (40-65 Gy). At a median follow-up of 17.2 months, mOS, mPFS, and TTP stood at 16.5, 6.1, and 6.8 months, respectively. ORR reached 47.7% and 52.3% per RECIST and mRECIST, respectively. For the tumor thrombosis, 2-year control rates per mRECIST were 93.1%. No grade 5 adverse events were noted, whereas thrombocytopenia (22.1%) and leukopenia (14.0%) were the main grade 3 adverse events. Conclusions Concurrent sorafenib and radiotherapy is an effective and well-tolerated treatment for patients with HCC with portal or hepatic vein tumor thrombosis. Impact and implications Treatment options for patients with hepatocellular carcinoma (HCC) and vascular tumor thrombus are limited. The efficacy and safety of concurrent sorafenib and radiation for HCC with portal or hepatic vein tumor thrombosis has not been elucidated. This phase II trial shows that concurrent sorafenib and radiotherapy is effective and well-tolerated in the treatment of advanced HCC with portal vein or hepatic vein tumor thrombosis. Clinical trials registration This study is registered at ClinicalTrials.gov (NCT03535259).
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Affiliation(s)
- Yirui Zhai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingxia Xin
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Ye
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Sun
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Song
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lijuan Niu
- Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huiying Zeng
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingbo Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Tang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongwen Song
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yueping Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Fang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ningning Lu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hao Jing
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shunan Qi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenwen Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shulian Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Akgun E, Erdim C, Ibicioglu B, Guzelbey T, Akkas BE, Kılıckesmez O. Is there any effect of hcc location on selective internal radiation therapy with 90yttrium response? Ann Nucl Med 2025:10.1007/s12149-025-02028-5. [PMID: 40014290 DOI: 10.1007/s12149-025-02028-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 02/12/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND We planned this retrospective study to evaluate the effect of the central vs peripheral location effect on the success of selective internal radiation therapy (SIRT) with 90Yttrium-90 (90Y) glass microspheres in hepatocellular carcinomas (HCC). MATERIAL AND METHODS Thirty-eight patients diagnosed with HCC who were eligible for SIRT with 90Y glass microspheres were included in this study. The location being central versus peripheral was defined as explained: Straight lines through the bifurcation of the right and left branches of the portal vein to the center of the HCC and the peripheral surface of the liver were traced on the same plane. The coefficient was determined as a ratio of the center of the HCC to the distance from the hilum of the liver at the portal vein bifurcation. Value under ½ accepted as central location (Group 1, n = 17), over ½ values are accepted as peripheral location (Group 2, n = 21). Treatment responses were analyzed after 2 months of the treatment with magnetic resonance imaging, and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) for FDG-avid ones. Differences in treatment responses rates, treatment approach, the absorbed doses and the volumes of each liver segments between groups were investigated. RESULTS In Group 1; mean age was 67. In 5 cases split infusion, in 10 cases tumor selective treatment approach were applied. According to PERCIST/mRECIST criteria treatment responses categories: complete response in 2/1 cases, partial response in 7/9 cases, stable disease in 3/4 cases, progressive diseases in 2/3 cases; respectively. AFP value decreased in 2 cases, increased in 7 cases, and was stable in 1 case. Mean absorbed doses were 347.9 Gy for tumor, 140.6 Gy for perfused normal tissue, and 26.1 Gy for the normal liver. In Group 2; the mean age was 71.5. In 5 cases split infusion, and in 1 case non-selective treatment approach were applied. According to PERCIST/mRECIST criteria treatment responses categories: complete response in 7/6 cases, partial response in 7/10 cases, stable disease in 2/2 cases, and progressive diseases in 3/3 cases; respectively. AFP value decreased in 9 cases, increased in 2 cases, and was stable in 2 cases. Mean absorbed doses were 495.9 Gy for tumor, 134 Gy for perfused normal tissue, and 17.3 Gy for the normal liver.There is no statistically significant difference in terms of gender, treatment response rates, tumor volumes, perfuse tissue volumes between 2 groups. However, tumor-selective approach and absorbed doses of the perfused normal tissue and the tumor were significantly higher in Group 2 (p = 0.007, 0.04, and 0.02; respectively). CONCLUSION Contrary to expectation, centrally located HCCs could be treated as successfully as peripherally located HCCs. However, the complete response rate in the peripheral located tumor is more frequent than centrally located ones.
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Affiliation(s)
- Elife Akgun
- Department of Nuclear Medicine, University of Health Sciences Türkiye, Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye.
| | - Cagrı Erdim
- Department of Radiology Division of Interventional Radiology, University of Health Sciences Türkiye, Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye
| | - Burcu Ibicioglu
- Department of Nuclear Medicine, University of Health Sciences Türkiye, Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye
| | - Tevfik Guzelbey
- Department of Radiology Division of Interventional Radiology, University of Health Sciences Türkiye, Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye
| | - Burcu Esen Akkas
- Department of Nuclear Medicine, University of Health Sciences Türkiye, Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye
| | - Ozgur Kılıckesmez
- Department of Radiology Division of Interventional Radiology, University of Health Sciences Türkiye, Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye
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Iezzi R, Posa A, Bargellini I, Spreafico C. Transarterial Chemoembolization with BioPearls for the Treatment of Hepatocellular Carcinoma: A Preliminary Experience. Pharmaceuticals (Basel) 2025; 18:307. [PMID: 40143086 PMCID: PMC11944499 DOI: 10.3390/ph18030307] [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: 01/07/2025] [Revised: 02/21/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: Transarterial chemoembolization (TACE) is a widely accepted and minimally invasive treatment for primary and metastatic liver cancer. Performing TACE with drug-eluting beads helps obtain a greater drug concentration in the target lesion, significantly reducing systemic drug leakage, liver toxicity, and adverse events. The aim of this study is to describe the safety and feasibility of TACE performed with BioPearlTM, the first biodegradable drug-eluting microspheres. Methods: This was a retrospective observational study on 13 consecutive patients affected by hepatocellular carcinoma (HCC) treated with doxorubicin-loaded-BioPearlTM-TACE. Data on safety, feasibility, and tumor response were collected. Results: One intra-procedural catheter blockage was registered, as well as two post-treatment bilomas that required additional treatment. No severe general drug-related side effects were detected at the follow-up. The 1-month overall disease control was 90.9%, with six complete responses. Conclusions: Data suggest that chemoembolization with BioPearlTM is feasible and safe for the treatment of HCC as indicated by good tolerability.
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Affiliation(s)
- Roberto Iezzi
- Emergency and Interventional Radiology Unit, Department of Diagnostic Imaging and Oncologic Radiotherapy, Fondazione Policlinico Universitario “Agostino Gemelli”-IRCCS, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Alessandro Posa
- Emergency and Interventional Radiology Unit, Department of Diagnostic Imaging and Oncologic Radiotherapy, Fondazione Policlinico Universitario “Agostino Gemelli”-IRCCS, 00168 Rome, Italy
| | - Irene Bargellini
- Division of Diagnostics and Interventional Radiology, Candiolo Cancer Institute FPO-IRCCS, 10060 Candiolo, Italy;
- Department of Surgical Sciences, University of Turin, 10126 Turin, Italy
| | - Carlo Spreafico
- Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, 20133 Milan, Italy;
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Dong R, Fei Y, He Y, Gao P, Zhang B, Zhu M, Wang Z, Wu L, Wu S, Wang X, Cai J, Chen Z, Zuo X. Lactylation-Driven HECTD2 Limits the Response of Hepatocellular Carcinoma to Lenvatinib. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025:e2412559. [PMID: 39976163 DOI: 10.1002/advs.202412559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 02/09/2025] [Indexed: 02/21/2025]
Abstract
Drug resistance remains a major hurdle for the therapeutic efficacy of lenvatinib in hepatocellular carcinoma (HCC). However, the underlying mechanisms remain largely undetermined. Unbiased proteomic screening is performed to identify the potential regulators of lenvatinib resistance in HCC. Patient-derived organoids, patient-derived xenograft mouse models, and DEN/CCl4 induced HCC models are constructed to evaluate the effects of HECTD2 both in vitro and in vivo. HECTD2 is found to be highly expressed in lenvatinib-resistant HCC cell lines, patient tissues, and patient-derived organoids and xenografts. In vitro and in vivo experiments demonstrated that overexpression of HECTD2 limits the response of HCC to lenvatinib treatment. Mechanistically, HECTD2 functions as an E3 ubiquitin ligase of KEAP1, which contributes to the degradation of KEAP1 protein. Subsequently, the KEAP1/NRF2 signaling pathway initiates the antioxidative response of HCC cells. Lactylation of histone 3 on lysine residue 18 facilitates the transcription of HECTD2. Notably, a PLGA-PEG nanoparticle-based drug delivery system is synthesized, effectively targeting HECTD2 in vivo. The NPs achieved tumor-targeting, controlled-release, and biocompatibility, making them a promising therapeutic strategy for mitigating lenvatinib resistance. This study identifies HECTD2 as a nanotherapeutic target for overcoming lenvatinib resistance, providing a theoretical basis and translational application for HCC treatment.
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Affiliation(s)
- Runyu Dong
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Yao Fei
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Yiren He
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China
| | - Peng Gao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Bo Zhang
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China
| | - Menglin Zhu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Zhixiong Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Longfei Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Shuai Wu
- Department of Oncology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Xiaoming Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
| | - Juan Cai
- Department of Oncology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
- Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wannan Medical College, Wuhu, 241000, China
- Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China
| | - Zhiqiang Chen
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary Cancers, Nanjing, 210000, China
| | - Xueliang Zuo
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China
- Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wannan Medical College, Wuhu, 241000, China
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Huang JT, Hu D, Hong X, Zhou WJ, Shen J, Lv PH, Zhu XL. Effectiveness and safety of transarterial chemoembolization combined with PD-1 inhibitors and lenvatinib for unresectable intrahepatic cholangiocarcinoma. Eur Radiol Exp 2025; 9:21. [PMID: 39966235 PMCID: PMC11836246 DOI: 10.1186/s41747-025-00563-4] [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: 09/14/2024] [Accepted: 01/24/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND The objective of this study was to evaluate the therapeutic effectiveness and safety of transarterial chemoembolization (TACE) combined with programmed cell death-1 (PD-1) inhibitors and lenvatinib in the treatment of unresectable intrahepatic cholangiocarcinoma (uICC). METHODS This multicenter retrospective study screened patients with uICC who underwent TACE in combination with PD-1 inhibitors and lenvatinib between January 2019 and June 2023. Tislelizumab or camrelizumab (200 mg) was intravenously administered every three weeks. The daily dose of lenvatinib was 8 mg for patients weighing < 60 kg and 12 mg for those weighing ≥ 60 kg. In cases of disease progression, the therapeutic strategy was adjusted based on the clinical condition and individual patient's treatment preferences. Options included transitioning to standard or supportive care or continuing treatment with TACE in combination with PD-1 inhibitors and lenvatinib. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events (AEs). RESULTS A total of 59 patients with uICC were included. Over a median follow-up period of 32.3 months, the median OS and PFS were 25.8 months (95% confidence interval [CI]: 17.9-33.7) and 9.5 months (95% CI: 7.9-11.0), respectively. The ORR was 55.9%, and the DCR was 96.6%. Grade 3 or four AEs were observed in 15 of 59 patients (25.4%). CONCLUSION TACE combined with PD-1 inhibitors and lenvatinib demonstrated a promising therapeutic potential with a manageable safety profile for patients with uICC. RELEVANCE STATEMENT The combination of TACE, PD-1 inhibitors, and lenvatinib represents a novel therapeutic option for patients with uICC. KEY POINTS TACE plus PD-1 inhibitors and lenvatinib represent a promising therapeutic strategy for uICC. The safety profile of TACE plus PD-1 inhibitors and lenvatinib was manageable. This study demonstrated improved outcomes compared to prior standard-of-care treatments.
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Affiliation(s)
- Jin-Tao Huang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Di Hu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xin Hong
- Department of Interventional Radiology, Affiliated Hospital 2 of Nantong University, Nantong, China
| | - Wen-Jie Zhou
- Department of Interventional Radiology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Jian Shen
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Peng-Hua Lv
- Department of Interventional Radiology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China.
| | - Xiao-Li Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
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Scolozzi V, Nicoletti A, Capotosti A, Ponziani FR, Taralli S, Genco E, Leccisotti L, Moretti R, Indovina L, Pompili M, Calcagni ML. 13N-Ammonia PET-CT for Evaluating Response to Antiangiogenic Therapy and Prognosis in Patients with Advanced Hepatocellular Carcinoma: A Pilot Study. Cancers (Basel) 2025; 17:656. [PMID: 40002251 PMCID: PMC11853641 DOI: 10.3390/cancers17040656] [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: 12/24/2024] [Revised: 02/11/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025] Open
Abstract
PURPOSE To prospectively investigate dynamic 13N-ammonia PET-CT for evaluating early treatment response and predicting prognosis in advanced hepatocellular carcinoma (HCC) patients who have undergone antiangiogenic therapy. METHODS Dynamic 13N-ammonia PET-CT was performed in 23 advanced HCC patients before antiangiogenic therapy (baseline) and in 18/23 patients after 8-10 weeks of treatment (post-therapy). At kinetic PET-CT analysis, mean, maximum, and peak values of K1 (mL/cm3/min) and k2 (min-1) were estimated in HCC lesions and non-neoplastic liver using cardiologic 13N-ammonia PET-CT in 15 patients without any liver diseases as normal controls. Outcome endpoints were treatment response after 8-10 weeks assessed by contrast-enhanced CT, progression-free survival (PFS), and overall survival (OS). RESULTS At both baseline and post-therapy PET-CT, all kinetic PET parameters were significantly higher (p < 0.05) in HCC lesions than in non-neoplastic and healthy liver of HCC patients and controls. According to mRECIST criteria, 13/18 patients (72.2%) were responders (1 CR, 1 PR, and 11 SD), and 5/18 patients (27.8%) were non-responders (PD), with no significant differences in baseline and post-therapy PET parameters between the two groups. At follow-up (median: 14.2 months), 15/18 patients (83.3%) experienced radiological progression, and 14/18 (77.8%) died (7/14 within 12 months from treatment). The nine earlier-progression patients (within 6 months from treatment) showed significantly lower baseline K1mean in HCC lesions than all nine patients with later or no-progression (p = 0.03). Patients still alive 12 months after treatment (n = 11) showed significantly lower post-therapy K1mean (p = 0.05), K1max (p = 0.05), and K1peak (p = 0.03) in non-neoplastic liver than patients with shorter OS (n = 7). CONCLUSIONS In advanced HCC patients treated with antiangiogenic agents, kinetic parameters from baseline and post-therapy 13N-ammonia PET-CT may predict early disease progression and survival. PET-CT seems not able to discriminate responders and non-responders after 8-10 weeks of treatment, suggesting the need for future and larger studies after a longer treatment period.
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Affiliation(s)
- Valentina Scolozzi
- Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Alberto Nicoletti
- Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Amedeo Capotosti
- Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Silvia Taralli
- Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Enza Genco
- Radiologia Addomino-Pelvica, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Lucia Leccisotti
- Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Istituto di Medicina Nucleare, Dipartimento Universitario di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Roberto Moretti
- Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Luca Indovina
- Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Maurizio Pompili
- Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Lucia Calcagni
- Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Istituto di Medicina Nucleare, Dipartimento Universitario di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Wang HY, Zhang GX, Fan WZ, Li JW, Hao SF, Ouyang YS, Li JP, Liu WD. Simultaneous versus sequential transcatheter arterial chemoembolization combined with microwave ablation for hepatocellular carcinoma: A retrospective propensity score-matched analysis. Hepatobiliary Pancreat Dis Int 2025:S1499-3872(25)00030-X. [PMID: 40000294 DOI: 10.1016/j.hbpd.2025.02.001] [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: 08/27/2024] [Accepted: 02/05/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND Transcatheter arterial chemoembolization (TACE) combined with ablation has better clinical outcomes than monotherapy in patients with hepatocellular carcinoma (HCC). However, prolonged time intervals can lead to recanalization and neoangiogenesis, which may interfere with the synergistic effects of combination therapy. This study aimed to investigate whether TACE simultaneously combined with microwave ablation (MWA) is more effective than sequential therapy in patients with HCC. METHODS A total of 129 HCC patients who underwent TACE combined with MWA were included in this study. Based on the time interval between the first combination therapy of TACE and MWA, patients were divided into the simultaneous and sequential groups. Propensity score matching (PSM) was performed to reduce bias between the groups. Overall survival (OS), time-to-progression (TTP), tumor response, and liver function were compared. RESULTS Before PSM, the simultaneous group had a higher tumor load. Following PSM, 36 and 40 patients remained in the simultaneous and sequential groups, respectively. The median TTP and OS were 12.9 vs. 10.6 months (P = 0.262) and 44.0 vs. 26.5 months (P = 0.313) for the simultaneous and sequential groups, respectively. After 4-8 weeks, there were 16 complete responders and 17 partial responders in the simultaneous group and 15 and 22 patients in the sequential group, respectively (P = 0.504). The median complete response duration was 11.3 and 9.2 months for the simultaneous and sequential groups, respectively (P = 0.882). These results did not differ in BCLC stratified subgroups. Patients with small tumor sizes (≤ 5 cm), tumor nodules ≤ 3, well-defined boundaries, and early-stage tumors were more likely to achieve complete response (all P < 0.05). After 4-8 weeks, the liver function was significantly improved compared to that before or one day after treatment. CONCLUSIONS TACE simultaneously combined with MWA is safe and effective but not superior to sequential therapy.
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Affiliation(s)
- Hong-Yu Wang
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Gui-Xiong Zhang
- Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Wen-Zhe Fan
- Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Jin-Wei Li
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Shu-Fang Hao
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Yu-Shu Ouyang
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Jia-Ping Li
- Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Wen-Dao Liu
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
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Steinberg-Vorhoff HL, Tropotel A, Theysohn JM, Schaarschmidt B, Haubold J, Jeschke M, Jochheim L, Ludwig JM. Evaluation of Inflammatory Markers as Prognostic Factors in the Treatment of Hepatocellular Carcinoma (HCC) with Degradable Starch Microspheres by Transarterial Chemoembolization (DSM-TACE). Cancers (Basel) 2025; 17:647. [PMID: 40002242 PMCID: PMC11853491 DOI: 10.3390/cancers17040647] [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: 12/21/2024] [Revised: 02/02/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Objective: To evaluate the prognostic value of pre-therapeutic inflammatory markers before transarterial chemoembolization with degradable starch microspheres (DSM-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: A total of 155 patients (81% male, median age: 68 years) who underwent first-time DSM-TACE between 07/13 and 06/22 were included in the study. Inflammatory indices were dichotomized using median values. Cox proportional hazard model for univariate (UVA) and multivariate (MVA) analyses (hazard ratio; 95% CI, p-value) and Kaplan-Meier analyses (overall survival (OS) in months; 95% CI; log-rank test) were performed. Results: The median OS of the study cohort was 15.9 (12.9-20) months with a median survival according to BCLC stages A (12%), B (41%), and C (47%) of median not reached, 19.3 (15.3-27), and 7.2 (4.5-9.0) months, respectively (p < 0.0001). In the UVA, several inflammatory markers on OS were statistically significant with the systemic inflammatory response index (SIRI; ≤median (2.04) HR: 0.41 (0.19-0.89); p = 0.024) and the lymphocyte to monocyte ratio (LMR; >median (1.82) HR: 0.44 (0.2-0.9); p = 0.025) remaining statistically significant in MVA together with the BCLC stage (p = 0.0001), ALBI grade (p = 0.016), hepatic tumor burden (≤25% vs. >25%; p = 0.006), and largest HCC lesion (≤5.5 cm vs. >5.5 cm; p = 0.008). In subgroup analysis, patients with elevated LMR and reduced SIRI exhibited significantly prolonged overall survival (OS) in both BCLC B (p < 0.0001) and Child-Pugh A (p = 0.021) subgroups. Conclusion: The findings suggest that SIRI and LMR may serve as valuable tools in identifying BCLC B and Child-Pugh A patients who could potentially benefit better from DSM-TACE treatment. Nevertheless, further research is recommended to confirm these findings and to provide more comprehensive insights.
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Affiliation(s)
- Hannah L. Steinberg-Vorhoff
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (H.L.S.-V.); (J.M.T.); (B.S.); (J.H.)
| | - Andriana Tropotel
- Institute of Diagnostic Radiology, Interventional Radiology and Nuclear Medicine, BG Clinics Bergmannsheil, Ruhr-University of Bochum, Buerkle-de-la-Camp Platz 1, 44789 Bochum, Germany;
| | - Jens M. Theysohn
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (H.L.S.-V.); (J.M.T.); (B.S.); (J.H.)
- Institute of Diagnostic Radiology, Interventional Radiology and Nuclear Medicine, BG Clinics Bergmannsheil, Ruhr-University of Bochum, Buerkle-de-la-Camp Platz 1, 44789 Bochum, Germany;
| | - Benedikt Schaarschmidt
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (H.L.S.-V.); (J.M.T.); (B.S.); (J.H.)
| | - Johannes Haubold
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (H.L.S.-V.); (J.M.T.); (B.S.); (J.H.)
| | - Matthias Jeschke
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (M.J.); (L.J.)
| | - Leonie Jochheim
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (M.J.); (L.J.)
| | - Johannes M. Ludwig
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
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Komatsu S, Yano Y, Terashima K, Fujishima Y, Ishida J, Ishihara N, Matsuura T, Okimoto T, Kodama Y, Fukumoto T. The potential efficacy of atezolizumab plus bevacizumab treatment for hepatocellular carcinoma patients with macroscopic portal vein tumor thrombus. Surg Today 2025:10.1007/s00595-025-03009-x. [PMID: 39934306 DOI: 10.1007/s00595-025-03009-x] [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: 09/30/2024] [Accepted: 10/28/2024] [Indexed: 02/13/2025]
Abstract
PURPOSE The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the first-order or main trunk/contralateral branches (Vp3/4) is poor. The present study aimed to clarify the real-world data of atezolizumab plus bevacizumab treatment (Ate/bev) for HCC patients with Vp3/4 PVTT. METHODS The subjects of this study were 22 consecutive HCC patients with Vp3/4 PVTT, who were treated with Ate/bev. Survival rates and radiological responses were evaluated based on the modified albumin-bilirubin (mALBI) grade [mALBI 1 + 2a (1/2a) versus 2b + 3 (2b/3)] using the modified Response Evaluation Criteria in Solid Tumors. RESULTS The median survival time of the 22 patients was 15.0 months, with 1- and 2-year survival rates of 62.7% and 49.3%, respectively. The objective response (OR) rates of patients with mALBI 1/2a and 2b/3 were 91.7% (11/12) and 10.0% (1/10), respectively, with a significant difference (p < 0.001). The 2-year survival rates of patients with mALBI 1/2a and 2b/3 were 78.6% and 20.0%, respectively, with a significant difference (p = 0.0041). CONCLUSION Ate/bev was effective for treating HCC patients with Vp3/4 PVTT. OR rate and MST were favorable, particularly for patients with preserved liver function (mALBI 1/2a), suggesting its great potential for the treatment of HCC in patients with Vp3/4 PVTT.
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Affiliation(s)
- Shohei Komatsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
| | - Yoshihiko Yano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kazuki Terashima
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Yoshimi Fujishima
- Division of Medical Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan
| | - Jun Ishida
- Division of Radiology, Kobe Minimally Invasive Cancer Center, Kobe, Japan
| | - Nobuaki Ishihara
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Takanori Matsuura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tomoaki Okimoto
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
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Zhong S, Yi J, Chen S, Mo X, Chen Q, Guo W, Jiang X, Mu L, Hu Y, Wang J, Song Y, Xu J, Tan G, Shi M, Chen M, Lyu N, Zhao M. Combining immune checkpoint inhibitors and molecular-targeted agents with hepatic arterial infusion chemotherapy for hepatocellular carcinoma with inferior vena cava and/or right atrium tumor thrombus. Hepatol Int 2025:10.1007/s12072-025-10777-8. [PMID: 39934618 DOI: 10.1007/s12072-025-10777-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 01/09/2025] [Indexed: 02/13/2025]
Abstract
BACKGROUND Hepatocellular carcinoma with inferior vena cava and/or right atrium tumor thrombus (HCC-IVC/RATT) has a poor prognosis and lacks evidence for standard first-line systemic therapy. This study aims to evaluate the effectiveness and safety of three therapeutic regimens in HCC-IVC/RATT: immune checkpoint inhibitors plus molecular-targeted agents (ICI-MTA), hepatic arterial infusion chemotherapy (HAIC), and their combination (ICI-MTA-HAIC). METHODS This multicenter retrospective cohort study included consecutive HCC-IVC/RATT who received ICI-MTA-HAIC, ICI-MTA, or HAIC from June 2015 to December 2023. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS A total of 355 patients were included: 209 received ICI-MTA-HAIC, 66 received ICI-MTA, and 80 received HAIC. After PSM, the ICI-MTA-HAIC group showed superior median overall survival (OS) to both the ICI-MTA (18.0 vs. 7.5 months, p < 0.001) and HAIC (18.5 vs. 7.1 months, p < 0.001) groups. The ICI-MTA-HAIC group demonstrated better median progression-free survival (PFS) and objective response rate (ORR) compared to the ICI-MTA (PFS: 9.5 vs. 4.4 months; ORR: 47.0% vs. 21.3%, all p < 0.001) and HAIC (PFS: 9.5 vs. 4.4 months; ORR: 48.8% vs. 21.6%, all p < 0.001) groups. There was no significant difference in OS, PFS, or ORR between the ICI-MTA and HAIC groups (all p > 0.05). Grade 3-4 adverse event rates were 49.8%, 33.3%, and 35.0% for the ICI-MTA-HAIC, ICI-MTA, and HAIC groups, respectively. No unexpected events or treatment-related deaths were observed. CONCLUSION ICI-MTA-HAIC was a safe and effective therapy that prolonged the survival of HCC-IVC/RATT compared to ICI-MTA or HAIC.
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Affiliation(s)
- Suixing Zhong
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Junzhe Yi
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Song Chen
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Xiaoyan Mo
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Qifeng Chen
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Wenbo Guo
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Xiongying Jiang
- Interventional Radiology Division, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China
| | - Luwen Mu
- Department of Vascular Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China
| | - Yue Hu
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Jiongliang Wang
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Yujia Song
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Jie Xu
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Genjun Tan
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Ming Shi
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China
| | - Ning Lyu
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.
| | - Ming Zhao
- Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.
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Magyar CTJ, O'Kane GM, Aceituno L, Li Z, Vogel A, Bruix J, Mazzaferro V, Sapisochin G. Liver Transplantation for Hepatocellular Carcinoma: An Expanding Cornerstone of Care in the Era of Immunotherapy. J Clin Oncol 2025; 43:589-604. [PMID: 39680821 DOI: 10.1200/jco.24.00857] [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: 04/21/2024] [Revised: 09/20/2024] [Accepted: 10/19/2024] [Indexed: 12/18/2024] Open
Abstract
Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.
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Affiliation(s)
- Christian Tibor Josef Magyar
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Grainne Mary O'Kane
- University of Toronto, Toronto, ON, Canada
- St Vincent's University Hospital and School of Medicine, University College Dublin, Dublin, Ireland
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
| | - Laia Aceituno
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
- Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Zhihao Li
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Arndt Vogel
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada
- Department of Hepatology, Gastroenterology, Endocrinology & Infectious Diseases, Hannover Medical School, Hannover, Germany
| | - Jordi Bruix
- BCLC Group, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Vincenzo Mazzaferro
- Istituto Nazionale Tumori IRCCS, Hepato Pancreatic Biliary Surgery & Liver Transplantation Unit, Milano, Italy
- Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy
| | - Gonzalo Sapisochin
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
- Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
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