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Wei H, Jiang H, Yoo J, Kim JH, Kang HJ, Wu Y, Liu R, Kim HC, Lee JM. Temporal evolution of the LI-RADS radiation treatment response assessment on multiphase CT/MRI in patients undergoing selective internal radiation therapy for hepatocellular carcinoma. Eur Radiol 2025:10.1007/s00330-025-11659-1. [PMID: 40382488 DOI: 10.1007/s00330-025-11659-1] [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: 11/23/2024] [Revised: 03/20/2025] [Accepted: 04/11/2025] [Indexed: 05/20/2025]
Abstract
OBJECTIVES To assess the temporal evolution and interobserver agreement of the early categories per the liver imaging reporting and data system (LI-RADS) radiation treatment response assessment (TRA) algorithm in patients receiving selective internal radiation therapy (SIRT) with Yttrium-90 for hepatocellular carcinoma (HCC). MATERIALS AND METHODS This single-center retrospective study included consecutive patients with treatment-naïve HCC who underwent serial contrast-enhanced CT/MRI before and after SIRT. Three masked radiologists independently evaluated response at 3-6 months. Another senior radiologist assessed response at 9, 12, 15, 18, 21, 24, and > 24 months after comprehensive review of available clinical-radiological information. RESULTS 65 patients (mean age, 66.7 ± 11.2 years; 48 men) were included. At 3-6 months after SIRT, 47.7% (31/65) of lesions were assigned to the nonprogressing category, and the remaining 52.3% (34/65) to the nonviable category. Among early nonprogressing lesions, 64.5% (20/31) regressed to the nonviable category, 25.8% (8/31) remained nonprogressing, and 9.7% (3/31) evolved into the viable category at ≥ 12 months. The nonprogressing category decreased in number over time, with 61.3% (19/31) conversion to the nonviable category at 9 months. Among the early nonviable lesions, 91.2% (31/34) remained nonviable at ≥ 12 months, and 8.8% (3/34) evolved into the viable category. Agreement for the 3-6 months LR-TR category assignment was moderate (kappa = 0.46) with CT but almost perfect (kappa = 0.85) with MRI. CONCLUSIONS SIRT induced a delayed and sustained response in the majority of HCC patients after ≥ 12 months. MRI demonstrated superior agreement over CT in assessing response at 3-6 months. KEY POINTS Question Tumor response to SIRT can change; there is limited evidence on the evolution of the imaging appearance of HCC following SIRT. Findings Sixty-four and five-tenths of early nonprogressing lesions regressed to nonviable, and 91.2% of early nonviable lesions remained free of viability. LR-TR category assignment agreement was moderate with CT but almost perfect with MRI. Clinical relevance SIRT induced a delayed and sustained response in HCC, underscoring the necessity of dynamic evaluation of long-term changes in treated lesions. MRI with subtraction imaging may be preferred over CT for long-term monitoring, which may help prevent premature retreatment decisions.
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Affiliation(s)
- Hong Wei
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Hanyu Jiang
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Jeongin Yoo
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jae Hyun Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyo-Jin Kang
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yuanan Wu
- Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, China
| | - Rongbo Liu
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Bucalau AM, Collette B, Tancredi I, Vierasu I, Tannouri F, Pezzullo M, Moreno-Reyes R, Verset G. 166Ho-RadioEmbolizaTiOn Using personalized prediCtive dosimetry in patients with Hepatocellular carcinoma: A prospective, single-centre study (RETOUCH). Liver Int 2025; 45:e15923. [PMID: 39569818 DOI: 10.1111/liv.15923] [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: 10/26/2023] [Revised: 02/28/2024] [Accepted: 03/21/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND AND AIMS Holmium-166 (166Ho) radioembolization could offer a more individualized approach in terms of imaging and dosimetry. We aim to evaluate the feasibility and safety of 166Ho selective internal radiation therapy (SIRT) using a higher tumour dose than previously administered determined by 166Ho-scout as a surrogate marker in HCC patients. METHODS This is an open-label, prospective, non-randomized, single-centre pilot study that included patients with HCC that received 166Ho-SIRT if the work-up using 166Ho-scout showed a tumour-absorbed dose ≥150 Gy, a non-tumoural liver absorbed dose less than 60 Gy and a lung absorbed dose less than 30 Gy. Primary endpoints were feasibility and safety-toxicity profiles at 24-48 h and 1 month. Overall response rates (ORR) at 3 months (mRECIST, RECIST 1.1 and metabolic response by FDG and choline PET CT) and time to progression (TTP) represented the secondary endpoints. RESULTS Fifteen patients with large tumours (mean diameter 55.67 ± 28.42 mm) received 17 166Ho-SIRT treatments between July 2020 and June 2022. All the attempted treatments were accomplished. Mean administered tumour dose was 183.18 ± 71.71 Gy, while non-tumour liver dose was 30.29 ± 14.56 Gy. Median time of follow-up was 12 months (IQR 9-16). Only grade 1-2 clinical and biological AEs were observed. There were no liver decompensations. At 3 months, objective response was achieved for all target lesions (CR 78.57%, PR 21.43% according to mRECIST). Median TTP was 18.8 (range 2.9; n.e.) months. CONCLUSION Personalized 166Ho-SIRT with a tumour delivered dose ≥150 Gy was feasible and safe for HCC patients with promising response rates.
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Affiliation(s)
- Ana-Maria Bucalau
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Benoît Collette
- Department of Nuclear Medicine, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
- Laboratory of Image Synthesis and Analysis, Brussels School of Engineering, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Illario Tancredi
- Department of Radiology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Irina Vierasu
- Department of Nuclear Medicine, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Fadi Tannouri
- Department of Radiology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Martina Pezzullo
- Department of Radiology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Rodrigo Moreno-Reyes
- Department of Nuclear Medicine, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Gontran Verset
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
- Medical Oncology Department, Institut Paoli-Calmettes Marseille, Marseille, France
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Chen K, Tong AK, Moe FN, Ng DC, Lo RH, Gogna A, Yan SX, Thang SP, Loke KS, Venkatanarasimha NK, Huang HL, Too CW, Ong TS, Yeo EX, Peh DYY, Ng AW, Yang L, Chan WY, Chang JP, Goh BK, Toh HC, Chow PK. The Impact of Radiation Dose and Tumour Burden on Outcomes in Hepatocellular Carcinoma: 11-Year Experience in a 413-Patient Cohort Treated with Yttrium-90 Resin Microsphere Radioembolisation. Liver Cancer 2025; 14:158-179. [PMID: 40255874 PMCID: PMC12005707 DOI: 10.1159/000541539] [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: 11/09/2023] [Accepted: 09/16/2024] [Indexed: 04/22/2025] Open
Abstract
Introduction Transarterial radioembolisation (RE) using yttrium-90 (Y-90) microspheres is a widely used locoregional therapy for a broad spectrum of hepatocellular carcinoma (HCC) given its favourable safety profile. We evaluated the real-world outcomes of unresectable HCC treated with resin Y-90 RE and the relationship between tumour absorbed dose and subsequent curative therapy with survival. Methods Included were consecutive patients treated with Y-90 resin microspheres RE for unresectable HCC between January 2008 and May 2019 at the National Cancer Centre Singapore/Singapore General Hospital. The outcomes were stratified by tumour burden, distribution, presence of portal vein invasion (PVI) and liver function to improve prognostication. Results The median overall survival (OS) evaluated on 413 included patients was 20.9 months (95% CI: 18.2-24.0). More than half of the patients (214/413, 51.8%) had HCC beyond up-to-seven criteria, and 37.3% had portal vein invasion (154/413, 37.3%). Majority (71.7%) had dosimetry calculated based on the partition model. Patients who received ≥150 Gy to tumour had significantly better outcomes (OS 32.2 months, 95% CI: 18.3-46.4) than those who did not (OS 17.5 months, 95% CI: 13.7-22.7, p < 0.001). Seventy patients (17%) received curative therapies after tumour was downstaged by Y-90 RE and had better OS of 79.7 months (95% CI: 40.4 - NE) compared to those who did not receive curative therapies (OS 17.1 months; 95% CI: 13.5-20.4, p < 0.001). RE-induced liver injury was observed in 5.08% of the patients while 3.2% of the patients had possible radiation pneumonitis but none developed Grade 3-4 toxicity. For HCC without PVI, OS differed significantly with performance status, albumin-bilirubin grade, tumour distribution, and radiation dose; for HCC with PVI, Child-Pugh class and AFP were significant predictors of survival. Conclusions Treatment outcomes for unresectable HCC using Y-90 RE were favourable. Incorporating tumour burden and distribution improved prognostication. Patients who received tumour absorbed dose above 150 Gy had better OS. Patients who subsequently received curative therapies after being downstaged by Y-90 RE had remarkable clinical outcomes.
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Affiliation(s)
- Kaina Chen
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Medical School Singapore, Singapore, Singapore
| | - Aaron K.T. Tong
- Duke-NUS Medical School Singapore, Singapore, Singapore
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore
| | - Fiona N.N. Moe
- National Cancer Centre Singapore, Program in Translational and Clinical Liver Cancer Research, Singapore, Singapore
| | - David C.E. Ng
- Duke-NUS Medical School Singapore, Singapore, Singapore
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore
| | - Richard H.G. Lo
- Duke-NUS Medical School Singapore, Singapore, Singapore
- Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore, Singapore
| | - Apoorva Gogna
- Duke-NUS Medical School Singapore, Singapore, Singapore
- Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore, Singapore
| | - Sean X. Yan
- Duke-NUS Medical School Singapore, Singapore, Singapore
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore
| | - Sue Ping Thang
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore
| | - Kelvin S.H. Loke
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore
| | | | - Hian Liang Huang
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore
| | - Chow Wei Too
- Duke-NUS Medical School Singapore, Singapore, Singapore
- Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore, Singapore
| | - Timothy S.K. Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Eng Xuan Yeo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Daniel Yang Yao Peh
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore
| | - Ashley W.Y. Ng
- National Cancer Centre Singapore, Program in Translational and Clinical Liver Cancer Research, Singapore, Singapore
| | - Lu Yang
- Duke-NUS Medical School Singapore, Singapore, Singapore
| | - Wan Ying Chan
- National Cancer Centre Singapore, Division of Oncologic Imaging, Singapore, Singapore
| | - Jason P.E. Chang
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Medical School Singapore, Singapore, Singapore
| | - Brian K.P. Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School Singapore, Surgery Academic Clinical Program, Singapore, Singapore
| | - Han Chong Toh
- Duke-NUS Medical School Singapore, Singapore, Singapore
- National Cancer Centre Singapore, Division of Medical Oncology, Singapore, Singapore
| | - Pierce K.H. Chow
- National Cancer Centre Singapore, Program in Translational and Clinical Liver Cancer Research, Singapore, Singapore
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School Singapore, Surgery Academic Clinical Program, Singapore, Singapore
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Muglia R, De Giorgio M, Marra P, Carbone FS, Dulcetta L, Prussia C, Loglio A, Ghirardi A, Grikke LA, Bianchi C, Poli GL, Gerali A, Erba PA, Sironi S, Fagiuoli S, Viganò M. Long-term outcomes of Yttrium-90 transarterial radioembolization for patients with hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2025:10.1007/s00259-025-07185-3. [PMID: 40056213 DOI: 10.1007/s00259-025-07185-3] [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: 12/16/2024] [Accepted: 02/25/2025] [Indexed: 03/10/2025]
Abstract
AIMS We retrospectively assessed the long-term outcomes of Yttrium-90 (90Y) transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC), focusing on overall survival (OS), radiological response, and safety. METHODS We included patients with HCC treated with 90Y TARE at a single center between January 2012 and December 2021 with measurable lesions and a minimum of 2 years of follow-up. Only the former was analyzed for patients with multiple TARE. The primary endpoints were long-term OS, radiological response, and safety; the secondary endpoints included predictors of OS and response, with emphasis on dosimetry. The collected data included demographics, laboratory test results, liver function, and tumor staging. Radiological response was evaluated 3-6 months post-TARE using the modified RECIST (mRECIST) criteria. OS was calculated from TARE until death or censoring. Univariate logistic regression was used to identify the predictors of complete radiological response and OS. Dosimetry was analyzed to determine correlations with mRECIST response. RESULTS Among 142 patients (median age 66.8, cirrhotic 92.3%; M: F = 121:21), a median OS of 16.68 months was achieved, with a complete radiological response in 31% (44/142). OS was strongly correlated with radiological response (p < 0.001). Absorbed dose ≥ 234.6 Gy was associated with complete response (p = 0.017) but not with survival (p = 0.102). Rising alpha-fetoprotein levels (p = 0.017) and worsening Child-Pugh scores post-TARE (p = 0.044) were independent predictors of mortality. CONCLUSION A complete radiological response is crucial for long-term survival, highlighting the need for dosimetry optimization in TARE for HCC.
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Affiliation(s)
- Riccardo Muglia
- Radiology Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy.
| | - Massimo De Giorgio
- Gastroenterology Hepatology & Transplantation Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Paolo Marra
- Radiology Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
- School of Medicine, University of Milano-Bicocca, Milano, Italy
| | | | | | | | - Alessandro Loglio
- Gastroenterology Hepatology & Transplantation Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Arianna Ghirardi
- Fondazione per la Ricerca Ospedale di Bergamo (FROM) Ente del Terzo Settore (ETS), Bergamo, Italy
| | | | - Claudia Bianchi
- Medical Physics Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Gian Luca Poli
- Medical Physics Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Alberto Gerali
- Nuclear Medicine Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Paola Anna Erba
- School of Medicine, University of Milano-Bicocca, Milano, Italy
- Nuclear Medicine Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Sandro Sironi
- Radiology Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
- School of Medicine, University of Milano-Bicocca, Milano, Italy
| | - Stefano Fagiuoli
- Gastroenterology Hepatology & Transplantation Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
- School of Medicine, University of Milano-Bicocca, Milano, Italy
| | - Mauro Viganò
- Gastroenterology Hepatology & Transplantation Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
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Ormiston W, Samuelson S, Van Wyk M, Calzadilla-Bertot L, Smith B, Garas G, MacQuillan G, Adams LA, Jeffrey GP, Wallace M, Tibballs J. Safety and Efficacy of Selective Internal Radiation Therapy for Portal Vein Tumour Thrombus in Advanced Hepatocellular Carcinoma: A Single-Centre Experience in Australia. J Med Imaging Radiat Oncol 2025; 69:244-250. [PMID: 39913851 DOI: 10.1111/1754-9485.13837] [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: 09/05/2024] [Revised: 12/12/2024] [Accepted: 01/15/2025] [Indexed: 04/15/2025]
Abstract
INTRODUCTION Portal vein tumour thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a poor prognosis. Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) microspheres is a minimally invasive treatment option that has shown promise in treating PVTT. Studies have suggested a survival advantage of SIRT in this population, but data in the Australasian population are lacking. The aim of this study was to evaluate the safety and efficacy of SIRT in a series of patients at an Australian hospital with advanced HCC and PVTT. METHOD All patients underwent pre-treatment imaging with MRI or CT, and immediate post-treatment imaging with Y90 PET CT and MRIs at 3-, 6-, 9- and 12-months. The primary endpoints were time to progression (TTP) and overall survival (OS) post-SIRT. The secondary endpoint was safety. RESULTS Of the 698 patients who underwent SIRT at our institution between 2007 and 2023, 64 patients had HCC and PVTT. 59/64 (92%) were male, with a median age of 61 years (range 37-86 years). The majority of patients had Child-Pugh a cirrhosis (87%), and the majority were ECOG 0 (91%). The majority had main PVTT at the time of SIRT. All patients underwent SIRT with Y90-coated resin microspheres (SIR-Spheres, Sirtex Medical, Australia). Personalised dosimetry planning was performed by the treating interventional radiologist. SIRT was well tolerated by most patients, with major complications reported in a minority of cases (19/64 patients had an episode of biochemical decompensation within 90 days following treatment). The median TTP was 4.8 months (range 1-48 months). The median OS was 11.5 months (range 1-80 months), with those with a favourable MAAPE score having a median OS of 21.2 months (12.6-29.7 months). CONCLUSIONS Our cohort suggests that SIRT is a safe and effective treatment option for a difficult-to-treat patient population. Our data suggest a longer OS for those with preserved liver function, good functional status and low AFP levels at 21.2 months. Poor pre-treatment liver function and functional status are predictors of decompensation, and decompensation is a predictor of poor survival. These data provide an Australasian perspective and support the expanding role of SIRT in HCC treatment guidelines. Further prospective studies with larger sample sizes and longer follow-up are warranted to confirm these findings.
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Affiliation(s)
- William Ormiston
- Department of Interventional Radiology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Shaun Samuelson
- Department of Interventional Radiology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Matthys Van Wyk
- Department of Interventional Radiology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Luis Calzadilla-Bertot
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Briohny Smith
- Medical School, University of Western Australia, Perth, Australia
| | - George Garas
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
- Medical School, University of Western Australia, Perth, Australia
| | - Gerry MacQuillan
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
- Medical School, University of Western Australia, Perth, Australia
| | - Leon A Adams
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
- Medical School, University of Western Australia, Perth, Australia
| | - Gary P Jeffrey
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
- Medical School, University of Western Australia, Perth, Australia
| | - Michael Wallace
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
- Medical School, University of Western Australia, Perth, Australia
| | - Jonathan Tibballs
- Department of Interventional Radiology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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7
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Finessi M, Cioffi M, Grimaldi S, Fronda M, Rovera G, Passera R, Carucci P, Gaia S, Rolle E, Rizza G, Colli F, Saracco GM, Romagnoli R, Calandri M, Fonio P, Morbelli SD, Doriguzzi Breatta A. Albi score predicts overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with selective internal radiation therapy (SIRT). LA RADIOLOGIA MEDICA 2025; 130:271-279. [PMID: 39681817 DOI: 10.1007/s11547-024-01943-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 12/11/2024] [Indexed: 12/18/2024]
Abstract
PURPOSE We aimed to evaluate the prognostic impact of baseline clinical features and treatment procedure, including liver function measured with albumin-bilirubin (ALBI) formula and dosing methods in HCC patients treated with SIRT. MATERIAL AND METHODS The study includes 82 consecutive patients with liver-dominant HCC treated with SIRT (90Y glass microspheres, TheraSphereTM) between October 2014 and September 2023. Twenty-five patients were treated with standard dosimetry, while for remaining patients, multi-compartment dosimetry was performed using Simplicit90YTM software. Impact of baseline patient's characteristics including presence of portal vein thrombosis (PVT), Child-Pugh score (CP), ALBI score, bilirubin levels, tumor size and prior locoregional liver-directed or systemic treatments was assessed through multivariable Cox proportional hazard model. RESULTS Median follow-up after treatment was 40.0 months (15.2-67.9). At univariable analysis, ALBI score and bilirubin levels were found to be independent prognostic factors for survival after SIRT (p = 0.001, respectively); furthermore, at Cox proportional hazards analysis, HR for death of ALBI 2 versus ALBI 1 was 10.54 (95% CI, 1.42-78.19, p = 0.021), while despite not significant, HR in patients with bilirubin levels over 1.1 mg/dl was 2.67 (0.75-9.44, p = 0.118). Conversely, no significant association was found between OS and cirrhosis, tumor size and PVT. CONCLUSION ALBI score demonstrated to impact OS in HCC patients treated with SIRT thus going beyond a simple prediction of treatment-related toxicity. The present results are relevant for the selection of HCC patients for SIRT in a real-world clinical setting.
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Affiliation(s)
- Monica Finessi
- Nuclear Medicine Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy.
| | - Martina Cioffi
- Nuclear Medicine Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Serena Grimaldi
- Nuclear Medicine Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Marco Fronda
- Interventional Radiology Unit, Department of Diagnostic Imaging and Interventional Radiology, A.O.U. Città Della Salute e della Scienza Di Torino, Turin, Italy
| | - Guido Rovera
- Nuclear Medicine Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Roberto Passera
- Nuclear Medicine Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Patrizia Carucci
- Gastroenterology and Digestive Endoscopy Unit, AOU Città Della Salute e della Scienza, University of Turin, Turin, Italy
| | - Silvia Gaia
- Gastroenterology and Digestive Endoscopy Unit, AOU Città Della Salute e della Scienza, University of Turin, Turin, Italy
| | - Emanuela Rolle
- Gastroenterology and Digestive Endoscopy Unit, AOU Città Della Salute e della Scienza, University of Turin, Turin, Italy
| | - Giorgia Rizza
- General Surgery 2U-Liver Transplant Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Fabio Colli
- General Surgery 2U-Liver Transplant Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Giorgio Maria Saracco
- Gastroenterology and Digestive Endoscopy Unit, AOU Città Della Salute e della Scienza, University of Turin, Turin, Italy
| | - Renato Romagnoli
- General Surgery 2U-Liver Transplant Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Marco Calandri
- Department of Surgical Sciences, University of Torino, Turin, Italy
- Radiology Unit, Department of Diagnostic Imaging and Interventional Radiology, A.O.U. Città Della Salute e della Scienza Di Torino, Turin, Italy
| | - Paolo Fonio
- Department of Surgical Sciences, University of Torino, Turin, Italy
- Radiology Unit, Department of Diagnostic Imaging and Interventional Radiology, A.O.U. Città Della Salute e della Scienza Di Torino, Turin, Italy
| | - Silvia Daniela Morbelli
- Nuclear Medicine Unit, A.O.U. Città Della Salute e della Scienza Di Torino, University of Turin, Turin, Italy
| | - Andrea Doriguzzi Breatta
- Interventional Radiology Unit, Department of Diagnostic Imaging and Interventional Radiology, A.O.U. Città Della Salute e della Scienza Di Torino, Turin, Italy
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8
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Ronot M, Loffroy R, Arnold D, Greget M, Sengel C, Pinaquy JB, Pellerin O, Maleux G, Peynircioglu B, Pelage JP, Schaefer N, Sangro B, de Jong N, Zeka B, Urdaniz M, Helmberger T, Vilgrain V. Transarterial Radioembolisation with Y90 Resin Microspheres and the Effect of Reimbursement Criteria in France: Final Results of the CIRT-FR Prospective Observational Study. Cardiovasc Intervent Radiol 2025; 48:205-220. [PMID: 39809885 PMCID: PMC11790776 DOI: 10.1007/s00270-024-03955-y] [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: 09/04/2024] [Accepted: 12/18/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE This analysis of the CIRSE Registry for SIR-Spheres Therapy in France, CIRT-FR, reports on real-world outcomes of transarterial radioembolisation (TARE) with Y90 resin microspheres for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRLM) patients in France, focusing on safety, effectiveness and health-related quality of life (HRQoL). Results on patients treated based on national reimbursement criteria are discussed here. METHODS Prospective, multicentre, observational study of HCC and CRLM patients treated between August 2017 and July 2020 with TARE Y90 resin microspheres. Patients were assigned to different analysis groups based on reimbursement recommendations. Follow-up period was at least 24 months with patient data collected every 3 months. RESULTS In total, 252 (193 HCC, 59 CRLM) patients of CIRT-FR were included in the analysis. No differences in effectiveness, safety and HRQoL were found between analysis groups based on reimbursement recommendations. Median overall survival for HCC and CRLM was 19.0 (95% CI, 16.1-22.4) and 10.8 (95% CI, 8.0-13.5) months, respectively. Serious procedure-related adverse events occurred in 13% of the patients. HRQoL generally remained stable, with some fluctuations in function scores and symptoms. CONCLUSION In our cohorts, patients performed similarly regarding clinical outcomes irrespective of their analysis group based on reimbursement recommendations. Our results suggest that instead of restrictive reimbursement criteria, more decision-making power in selecting suitable patient groups could be given to multidisciplinary tumour boards. Results confirm that TARE with Y90 resin microspheres is an effective and safe treatment for liver cancer, with maintained HRQoL in most patients.
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Affiliation(s)
- M Ronot
- Department of Radiology, Hôpital Beaujon APHP Nord, Université Paris Cité, Paris, CRI, INSERM, 1149, Clichy, France
| | - R Loffroy
- Department of Vascular and Interventional Radiology, Image-Guided Therapy Center, CHU Dijon Bourgogne, François-Mitterrand University Hospital, 14 Rue Gaffarel, 21000, Dijon, France
| | - D Arnold
- Oncology and Hematology, Asklepios Tumorzentrum Hamburg, AK Altona, Paul-Ehrlich-Str. 1, 22763, Hamburg, Germany
| | - M Greget
- Imagerie Interventionnelle UF 7524 Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 67200, Strasbourg, France
| | - C Sengel
- Interventional Radiology, Centre Hospitalier Universitaire de Grenoble, Boulevard de La Chantourne, 38100, Grenoble, France
| | - J B Pinaquy
- Department of Nuclear Medicine, CHU Bordeaux, 33000, Bordeaux, France
| | - O Pellerin
- Department of Vascular and Oncological Interventional Radiology, AP-HP, Hôpital Européen Georges Pompidou, HEKA INRIA, INSERM PARCC U 970, Université de Paris Cité, 20 Rue LEBLANC, 75015, Paris, France
| | - G Maleux
- Radiology, Universitair Ziekenhuis Leuven, Herestraat 49, 3000, Louvain, Belgium
| | - B Peynircioglu
- Department of Radiology, School of Medicine, Hacettepe University, Sihhiye Campus, 06100, Ankara, Turkey
| | - J P Pelage
- Department of Diagnostic Radiology, McGill University Health Centre (MUHC - Glen) - Royal Victoria Hospital, Montreal, Canada
| | - N Schaefer
- Service de Médecine Nucléaire Et Imagerie Moléculaire, CHUV, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - B Sangro
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Avda. Pio XII 36, 31008, Pamplona, Spain
| | - N de Jong
- P+F Products and Features GmbH, Bösendorferstraße 5/3, 1010, Vienna, Austria
| | - B Zeka
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Neutorgasse 9, 1010, Vienna, Austria
| | - M Urdaniz
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Neutorgasse 9, 1010, Vienna, Austria.
| | - T Helmberger
- Department of Radiology, Neuroradiology and Minimal-Invasive Therapy, Klinikum Bogenhausen, Englschalkinger Str. 77, 81925, Munich, Germany
| | - V Vilgrain
- Department of Radiology, Hôpital Beaujon APHP Nord, Université Paris Cité, Paris, CRI, INSERM, 1149, Clichy, France
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9
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Berardi G, Guglielmo N, Cucchetti A, Usai S, Colasanti M, Meniconi RL, Ferretti S, Mariano G, Angrisani M, Sciuto R, Di Stefano F, Ventroni G, Riu P, Giannelli V, Pellicelli A, Lionetti R, D'Offizi G, Vennarecci G, Maritti M, Tritapepe L, Cianni R, Ettorre GM. Transarterial Radioembolization Can Downstage Intermediate and Advanced Hepatocellular Carcinoma to Liver Transplantation. Transplantation 2025; 109:e54-e63. [PMID: 39285520 DOI: 10.1097/tp.0000000000005204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2024]
Abstract
BACKGROUND Transarterial radioembolization (TARE) is an effective treatment to control tumor growth and improve survival in hepatocellular carcinoma (HCC). The role of TARE in downstaging patients to liver transplantation (LT) is unclear. The aim of this study was to investigate the downstaging efficacy of TARE for intermediate and advanced HCC. METHODS Intention-to-treat analysis with multistate modeling was performed. Patients moved through 5 health states: (1) from TARE to listing, (2) from TARE to death without listing, (3) from listing to LT, (4) from listing to death without LT, and (5) from transplant to death. Factors affecting the chance of death after TARE were considered to stratify outcomes. RESULTS Two hundred fourteen patients underwent TARE. Of those, 43.9% had radiological response, 29.9% were listed, and 22.8% were transplanted. The probability of being alive without LT was 40.5% 1 y after TARE and 11.5% at 5 y. The chance of being listed was 9.4% at 1 y and 0.9% at 5 y. The probability of dying after TARE without LT was 38% at 1 y and 73% at 5 y. The overall survival of patients receiving LT was 61% at 5 y after transplant. Tumor beyond up-to-seven criteria, alfafetoprotein >400 ng/mL, and albumin-bilirubin ≥2 were associated with death. Three risk groups were associated with different response, chances of being listed, and receiving LT. Median survival was 3 y for low-risk, 1.9 y for intermediate-risk, and 9 mo for high-risk patients ( P < 0.001). CONCLUSIONS In intermediate and advanced HCC, TARE allows for a 44% chance of response, 30% downstaging, and 23% probability of permitting LT. Patient's and tumor's characteristics allow for risk stratification and predict survival from TARE.
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Affiliation(s)
- Giammauro Berardi
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Nicola Guglielmo
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
- Department of Medical Surgical Science and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences-DIME, Alma Mater Studiorum, University of Bologna, Italy
- Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Ausl Romagna, Forlì, Italy
| | - Sofia Usai
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Marco Colasanti
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Roberto Luca Meniconi
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Stefano Ferretti
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Germano Mariano
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Marco Angrisani
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Rosa Sciuto
- Nuclear Medicine Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy
| | - Federica Di Stefano
- Department of Radiology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy
| | - Guido Ventroni
- Nuclear Medicine Department, San Camillo Forlanini Hospital, Rome, Italy
| | - Pascale Riu
- Department of Interventional Radiology, San Camillo Forlanini Hospital, Rome, Italy
| | - Valerio Giannelli
- Department of Hepatology and Transplant Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Adriano Pellicelli
- Department of Hepatology and Transplant Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Raffaella Lionetti
- Infectious Diseases and Hepatology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy
| | - Giampiero D'Offizi
- Infectious Diseases and Hepatology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy
| | - Giovanni Vennarecci
- Department of Hepatobiliary Surgery and Transplantation, Aorn Cardarelli Hospital, Naples, Italy
| | - Micaela Maritti
- Department of Anesthesiology, San Camillo Forlanini Hospital, Rome, Italy
| | - Luigi Tritapepe
- Department of Anesthesiology, San Camillo Forlanini Hospital, Rome, Italy
| | - Roberto Cianni
- Department of Interventional Radiology, San Camillo Forlanini Hospital, Rome, Italy
| | - Giuseppe Maria Ettorre
- Department of General Surgery and Transplantation Unit, San Camillo Forlanini Hospital, Rome, Italy
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10
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Arar A, Heglin A, Veluri S, Alnablsi MW, Benjamin JL, Choudhary M, Pillai A. Radioembolization of HCC and secondary hepatic tumors: a comprehensive review. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2024; 68:270-287. [PMID: 39088238 DOI: 10.23736/s1824-4785.24.03572-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.
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Affiliation(s)
- Ahmad Arar
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA -
| | - Alex Heglin
- Division of Nuclear Medicine, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Shriya Veluri
- The University of Texas Health Science Center, San Antonio, TX, USA
| | - Mhd Wisam Alnablsi
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jamaal L Benjamin
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Moaz Choudhary
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Anil Pillai
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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11
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Mansouri Z, Salimi Y, Hajianfar G, Wolf NB, Knappe L, Xhepa G, Gleyzolle A, Ricoeur A, Garibotto V, Mainta I, Zaidi H. The role of biomarkers and dosimetry parameters in overall and progression free survival prediction for patients treated with personalized 90Y glass microspheres SIRT: a preliminary machine learning study. Eur J Nucl Med Mol Imaging 2024; 51:4111-4126. [PMID: 38981950 PMCID: PMC11639191 DOI: 10.1007/s00259-024-06805-8] [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: 03/13/2024] [Accepted: 06/17/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND Overall Survival (OS) and Progression-Free Survival (PFS) analyses are crucial metrics for evaluating the efficacy and impact of treatment. This study evaluated the role of clinical biomarkers and dosimetry parameters on survival outcomes of patients undergoing 90Y selective internal radiation therapy (SIRT). MATERIALS/METHODS This preliminary and retrospective analysis included 17 patients with hepatocellular carcinoma (HCC) treated with 90Y SIRT. The patients underwent personalized treatment planning and voxel-wise dosimetry. After the procedure, the OS and PFS were evaluated. Three structures were delineated including tumoral liver (TL), normal perfused liver (NPL), and whole normal liver (WNL). 289 dose-volume constraints (DVCs) were extracted from dose-volume histograms of physical and biological effective dose (BED) maps calculated on 99mTc-MAA and 90Y SPECT/CT images. Subsequently, the DVCs and 16 clinical biomarkers were used as features for univariate and multivariate analysis. Cox proportional hazard ratio (HR) was employed for univariate analysis. HR and the concordance index (C-Index) were calculated for each feature. Using eight different strategies, a cross-combination of various models and feature selection (FS) methods was applied for multivariate analysis. The performance of each model was assessed using an averaged C-Index on a three-fold nested cross-validation framework. The Kaplan-Meier (KM) curve was employed for univariate and machine learning (ML) model performance assessment. RESULTS The median OS was 11 months [95% CI: 8.5, 13.09], whereas the PFS was seven months [95% CI: 5.6, 10.98]. Univariate analysis demonstrated the presence of Ascites (HR: 9.2[1.8,47]) and the aim of SIRT (segmentectomy, lobectomy, palliative) (HR: 0.066 [0.0057, 0.78]), Aspartate aminotransferase (AST) level (HR:0.1 [0.012-0.86]), and MAA-Dose-V205(%)-TL (HR:8.5[1,72]) as predictors for OS. 90Y-derived parameters were associated with PFS but not with OS. MAA-Dose-V205(%)-WNL, MAA-BED-V400(%)-WNL with (HR:13 [1.5-120]) and 90Y-Dose-mean-TL, 90Y-D50-TL-Gy, 90Y-Dose-V205(%)-TL, 90Y-Dose- D50-TL-Gy, and 90Y-BED-V400(%)-TL (HR:15 [1.8-120]) were highly associated with PFS among dosimetry parameters. The highest C-index observed in multivariate analysis using ML was 0.94 ± 0.13 obtained from Variable Hunting-variable-importance (VH.VIMP) FS and Cox Proportional Hazard model predicting OS, using clinical features. However, the combination of VH. VIMP FS method with a Generalized Linear Model Network model predicting OS using Therapy strategy features outperformed the other models in terms of both C-index and stratification of KM curves (C-Index: 0.93 ± 0.14 and log-rank p-value of 0.023 for KM curve stratification). CONCLUSION This preliminary study confirmed the role played by baseline clinical biomarkers and dosimetry parameters in predicting the treatment outcome, paving the way for the establishment of a dose-effect relationship. In addition, the feasibility of using ML along with these features was demonstrated as a helpful tool in the clinical management of patients, both prior to and following 90Y-SIRT.
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Affiliation(s)
- Zahra Mansouri
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Yazdan Salimi
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Ghasem Hajianfar
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Nicola Bianchetto Wolf
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Luisa Knappe
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Genti Xhepa
- Service of Radiology, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Adrien Gleyzolle
- Service of Radiology, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Alexis Ricoeur
- Service of Radiology, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Valentina Garibotto
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland
- Centre for Biomedical Imaging (CIBM), Geneva, Switzerland
| | - Ismini Mainta
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland
| | - Habib Zaidi
- Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospital, CH-1211, Geneva, Switzerland.
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
- Department of Nuclear Medicine, University of Southern Denmark, Odense, Denmark.
- University Research and Innovation Center, Óbuda University, Budapest, Hungary.
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12
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Hao K, Paik AJ, Han LH, Makary MS. Yttrium-90 radioembolization treatment strategies for management of hepatocellular carcinoma. World J Radiol 2024; 16:512-527. [PMID: 39494134 PMCID: PMC11525828 DOI: 10.4329/wjr.v16.i10.512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 10/14/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024] Open
Abstract
As the third leading cause of cancer-related deaths worldwide, hepatocellular carcinoma (HCC) represents a significant global health challenge. This paper provides an introduction and comprehensive review of transarterial radioembolization (TARE) with Yttrium-90 (Y90), a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery. TARE involves the targeted delivery of radioactive microspheres to liver tumors, offering a promising treatment option for managing HCC across various stages of the disease. By evaluating Y90 TARE outcomes across early, intermediate, and advanced stages of HCC, the review aims to present a thorough understanding of its efficacy and safety. Additionally, this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies, as well as personalized treatments. The exploration of these innovative approaches aims to improve treatment outcomes, reduce adverse events, and provide new therapeutic opportunities for HCC patients. The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.
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Affiliation(s)
- Kelly Hao
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Andrew J Paik
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Lauren H Han
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Mina S Makary
- Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, United States
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13
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Kim GM, Kim DY, Won JY, Moon S, Kim SU, Kim BK. Outcome of Transarterial Radioembolization in the Treatment of Hepatocellular Carcinoma: Glass Versus Resin Microsphere. Cardiovasc Intervent Radiol 2024; 47:1210-1221. [PMID: 38744685 DOI: 10.1007/s00270-024-03726-9] [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: 11/24/2023] [Accepted: 04/01/2024] [Indexed: 05/16/2024]
Abstract
PURPOSE To compare the treatment outcomes of glass and resin microspheres for the treatment of hepatocellular carcinoma (HCC) and evaluate the prognostic factors that influence the outcomes. MATERIALS AND METHODS We retrospectively reviewed 251 consecutive patients who underwent radioembolization for the treatment of HCC at a single tertiary center. Imaging responses after radioembolization were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors. RESULTS A total of 195 patients were included in this study (glass microsphere, n = 75; resin microsphere, n = 120). The complete and objective response rates were 16.0% and 50.7% in the glass microsphere group and 17.5% and 58.3% in the resin microsphere group, respectively. Median PFS was 241 days in the glass microsphere group and 268 days in the resin microsphere group (p = 0.871). Median OS was 29 months in the glass microsphere group and 40 months in the resin microsphere group (p = 0.669). The only significant prognostic factor was bilobar tumor distribution, which favored resin microspheres (p = 0.023). Procedure-related adverse events occurred more frequently in the resin microsphere group (glass, 2.7% vs. resin, 5.0%; p < 0.001). CONCLUSION Glass and resin microspheres for the treatment of HCC did not show a significant difference in survival, though major adverse events occurred more frequently with the use of resin microspheres.
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Affiliation(s)
- Gyoung Min Kim
- Department of Radiology, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1, Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
| | - Jong Yun Won
- Department of Radiology, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Sungmo Moon
- Department of Radiology, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1, Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1, Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
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14
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Franzè MS, Vigneron P, Sessa A, Saitta C, Chalaye J, Tacher V, Luciani A, Regnault H, Bejan A, Rhaiem R, Sommacale D, Leroy V, Brustia R, Raimondo G, Amaddeo G. Prognostic factors influencing outcomes in hepatocellular carcinoma patients undergoing selective internal radiation therapy. Ann Hepatol 2024; 30:101539. [PMID: 39179159 DOI: 10.1016/j.aohep.2024.101539] [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: 06/17/2024] [Accepted: 07/06/2024] [Indexed: 08/26/2024]
Abstract
Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.
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Affiliation(s)
- Maria Stella Franzè
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Paul Vigneron
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Anna Sessa
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Carlo Saitta
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Julia Chalaye
- Department of Nuclear Medicine, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Vania Tacher
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Medical Imaging, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Alain Luciani
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Medical Imaging, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Hélène Regnault
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Ancuta Bejan
- Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Rami Rhaiem
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatobiliary, Pancreatic and Digestive Surgery, Robert Debré University Hospital, Reims, France; University Reims Champagne-Ardenne, France
| | - Daniele Sommacale
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Digestive and Hepatobiliary Surgery, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Vincent Leroy
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Raffaele Brustia
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Digestive and Hepatobiliary Surgery, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giuliana Amaddeo
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France.
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15
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Lee RC, Liang PC, Liang HL, Chen YF, Yu CY, Cheng PN, Hung CF, Hsia CY, Lai HC, Ho MC, Cheng YF, Liu YS, Chao Y, Chen CH. Multicenter evaluation of the safety and efficacy of selective internal radiation therapy with yttrium-90 resin microspheres in Taiwan: data from the RESIN registry. J Gastroenterol Hepatol 2024; 39:1318-1327. [PMID: 38615197 DOI: 10.1111/jgh.16556] [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: 01/18/2023] [Revised: 02/17/2024] [Accepted: 03/20/2024] [Indexed: 04/15/2024]
Abstract
BACKGROUND AND AIM The REgistry of Selective Internal radiation therapy in AsiaNs (RESIN) was a multicenter, single-arm, prospective, observational study of 90Y resin microspheres in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) from Taiwan. RESIN is the first real-life clinical study of this therapy in an Asian cohort. Study objectives were to evaluate the safety and efficacy of 90Y resin microspheres. METHODS Adults with HCC or mCRC scheduled to receive SIRT with 90Y resin microspheres were included. Primary endpoints were best overall response rate (ORR), adverse events, and changes from baseline in liver function. Secondary efficacy endpoints included overall survival (OS). RESULTS Of 107 enrolled patients, 83 had HCC, and 24 had mCRC. ORR was 55.41% (HCC) and 33.33% (mCRC). Of 58 HCC patients with 6-month post-SIRT data, 13.79% (n = 8) had resection, transplantation, transarterial chemoembolization, or radiofrequency ablation as the result of down-staging or down-sizing of their lesions. One hundred and ten treatment emergent adverse events (TEAEs) were reported in 51 patients, and five serious adverse events (SAEs) were reported in five patients. The most frequent TEAEs were abdominal pain, nausea and decreased appetite (HCC), and abdominal pain, decreased appetite, fatigue, and vomiting (mCRC). Two deaths due to SAEs (probably related to SIRT) were reported, both in patients with extensive HCC, active hepatitis infection, and other comorbidities. Median OS was 24.07 (HCC) and 12.66 (mCRC) months. CONCLUSIONS Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.
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Affiliation(s)
- Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
- Department of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yung-Fang Chen
- Department of Radiology, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Yen Yu
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chien-Fu Hung
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Medical Imaging and Intervention, New Taipei City Tucheng Hospital, Taoyuan, Taiwan
| | - Cheng-Yuan Hsia
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsueh-Chou Lai
- Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imaging, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yee Chao
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
- Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
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16
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Regnault H, Chalaye J, Galetto-Pregliasco A, Perrin C, Derbel H, Amaddeo G, Mulé S, Lequoy M, Kobeiter H, Reizine E, Itti E, Duvoux C, Laurent A, Leroy V, Sommacale D, Rasolonirina D, Luciani A, Calderaro J, Tacher V, Brustia R. Selective internal radiation therapy for unresectable HCC: The SIRT downstaging study. Hepatol Commun 2024; 8:e0475. [PMID: 38934702 PMCID: PMC11213600 DOI: 10.1097/hc9.0000000000000475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 05/02/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. METHODS We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. RESULTS One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). CONCLUSIONS These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.
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Affiliation(s)
- Hélène Regnault
- Hepatology Department, Henri Mondor Hospital (AP-HP), Créteil, France
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
| | - Julia Chalaye
- Nuclear Medicine Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | | | - Clara Perrin
- Hepatology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Haytham Derbel
- Radiology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Giuliana Amaddeo
- Hepatology Department, Henri Mondor Hospital (AP-HP), Créteil, France
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
| | - Sébastien Mulé
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Radiology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Marie Lequoy
- Hepatology Department, Saint Antoine Hospital (AP-HP), Paris, France
| | - Hicham Kobeiter
- Radiology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Edouard Reizine
- Radiology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Emmanuel Itti
- Nuclear Medicine Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Christophe Duvoux
- Hepatology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Alexis Laurent
- Hepatobiliary Surgery, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Vincent Leroy
- Hepatology Department, Henri Mondor Hospital (AP-HP), Créteil, France
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
| | - Daniele Sommacale
- Hepatobiliary Surgery, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Diana Rasolonirina
- Nuclear Medicine Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Alain Luciani
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Radiology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Julien Calderaro
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Department of Pathology, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Vania Tacher
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Radiology Department, Henri Mondor Hospital (AP-HP), Créteil, France
| | - Raffaele Brustia
- Team “Viruses, Hepatology, Cancer”, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Hepatobiliary Surgery, Henri Mondor Hospital (AP-HP), Créteil, France
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17
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Tang Z, Bai T, Wei T, Wang X, Chen J, Ye J, Li S, Wei M, Li X, Lin Y, Tang J, Li L, Wu F. TACE combined Lenvatinib plus Camrelizumab versus TACE alone in efficacy and safety for unresectable hepatocellular carcinoma: a propensity score-matching study. BMC Cancer 2024; 24:717. [PMID: 38862932 PMCID: PMC11165855 DOI: 10.1186/s12885-024-12484-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 06/06/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUNDS To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . METHODS A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. RESULTS After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. CONCLUSION TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/therapy
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/pathology
- Liver Neoplasms/therapy
- Liver Neoplasms/drug therapy
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- Quinolines/therapeutic use
- Quinolines/administration & dosage
- Quinolines/adverse effects
- Male
- Female
- Chemoembolization, Therapeutic/methods
- Chemoembolization, Therapeutic/adverse effects
- Middle Aged
- Retrospective Studies
- Propensity Score
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/administration & dosage
- Phenylurea Compounds/therapeutic use
- Phenylurea Compounds/administration & dosage
- Phenylurea Compounds/adverse effects
- Aged
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Treatment Outcome
- Combined Modality Therapy
- Adult
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Affiliation(s)
- Zhihong Tang
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Tao Bai
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Tao Wei
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Hepatobiliary Surgery Department, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China
| | - Xiaobo Wang
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jie Chen
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jiazhou Ye
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Shangqi Li
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Meng Wei
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xingzhi Li
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Youzhi Lin
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Juan Tang
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Lequn Li
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Feixiang Wu
- Department of Hepatobiliarypancreatic-Splenic Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.
- Key Laboratory of High-Incidence Cancer Prevention & Treatment, Ministry of Education, Nanning, China.
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18
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Zhao K, Son S, Karimi A, Marinelli B, Erinjeri JP, Alexander ES, Sotirchos VS, Harding JJ, Soares KC, Ziv E, Covey A, Sofocleous CT, Yarmohammadi H. Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma in Patients Previously Treated with Transarterial Embolization. Curr Oncol 2024; 31:2650-2661. [PMID: 38785481 PMCID: PMC11120081 DOI: 10.3390/curroncol31050200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 04/29/2024] [Accepted: 05/06/2024] [Indexed: 05/25/2024] Open
Abstract
The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.
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Affiliation(s)
- Ken Zhao
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - Sam Son
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - Anita Karimi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - Brett Marinelli
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - Joseph P. Erinjeri
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - Erica S. Alexander
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - Vlasios S. Sotirchos
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - James J. Harding
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Kevin C. Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Etay Ziv
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | - Anne Covey
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
| | | | - Hooman Yarmohammadi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (J.P.E.)
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19
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Baloji A, Kalra N, Chaluvashetty S, Bhujade H, Chandel K, Duseja A, Taneja S, Gorsi U, Kumar R, Singh H, Sood A, Bhattacharya A, Singh B, Mittal BR, Singh V, Sandhu MS. Efficacy of Yttrium-90 Transarterial Radioembolisation in Advanced Hepatocellular Carcinoma: An Experience With Hybrid Angio-Computed Tomography and Glass Microspheres. J Clin Exp Hepatol 2024; 14:101342. [PMID: 38283702 PMCID: PMC10819781 DOI: 10.1016/j.jceh.2023.101342] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 12/23/2023] [Indexed: 01/30/2024] Open
Abstract
Background Hepatocellular carcinoma is one of the most common malignancies worldwide. Transarterial radioembolisation (TARE) involves selective intra-arterial administration of microspheres loaded with a radioactive compound like Yttrium-90 (Y-90). Conventionally, C-arm-based cone-beam computed tomography has been extensively used during TARE. However, angio-computed tomography (CT) is a relatively new modality which combines the advantages of both fluoroscopy and fCT. There is scarce literature detailing the use of angio-CT in Y90 TARE. Methods This was a retrospective study of primary liver cancer cases in which the TARE procedure was done from November 2017 to December 2021. Glass-based Y-90 microspheres were used in all these cases. All the cases were performed in the hybrid angio-CT suite. A single photon emission computed tomography-computed comography (SPECT-CT) done postplanning session determined the lung shunt fraction and confirmed the accurate targeting of the lesion. Postdrug delivery, positron emission tomography-computed tomography (PET-CT) was obtained to confirm the distribution of the Y-90 particles. The technical success, median follow-up, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were recorded. Results A total of 56 hepatocellular carcinoma patients underwent TARE during this period, out of which 36 patients (30 males and 6 females) underwent Y90 TARE. The aetiology of cirrhosis included non-alcoholic steatohepatitis (NASH) (11), hepatitis C (HCV) (11), hepatitis B (HBV) (9), metabolic dysfunction and alcohol-associated liver disease (MetALD) (2), alcoholic liver disease (ALD) (1), cryptogenic (1), and autoimmune hepatitis (AIH) (1). The technical success was 100 % and the median follow-up was 7 months (range: 1-32 months). The median OS was 15 months (range 10.73-19.27 months; 95 % CI) and the median local PFS was 4 months (range 3.03-4.97 months; 95 % CI). The ORR (best response, CR + PR) was 58 %. No major complications were seen in this study. Conclusion TARE is a viable option for liver cancer in all stages, but more so in the advanced stages. The use of angio-CT in TARE aids in the precise delivery of the particles to the tumour and avoids non-target embolisation.
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Affiliation(s)
- Abhiman Baloji
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Naveen Kalra
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sreedhara Chaluvashetty
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Harish Bhujade
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Karamvir Chandel
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ujjwal Gorsi
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajender Kumar
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Harmandeep Singh
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani Sood
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Anish Bhattacharya
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Baljinder Singh
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Bhagwant R. Mittal
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Manavjit S. Sandhu
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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20
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Piñero F, Mauro E, Casciato P, Forner A. From evidence to clinical practice: Bridging the gap of new liver cancer therapies in Latin America. Ann Hepatol 2024; 29:101185. [PMID: 38042481 DOI: 10.1016/j.aohep.2023.101185] [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: 10/15/2023] [Accepted: 10/26/2023] [Indexed: 12/04/2023]
Abstract
The most common primary liver tumors are hepatocellular carcinoma and cholangiocarcinoma. They constitute the sixth most common neoplasia and the third cause of cancer-related deaths worldwide. Although both tumors may share etiologic factors, diagnosis, prognostic factors, and treatments, they differ substantially in determining distinctive clinical management. In recent years, significant advances have been made in the management of these neoplasms, particularly in advanced stages. In this review, we focus on the most relevant diagnostic, prognostic, and treatment aspects of both, hepatocellular carcinoma and cholangiocarcinoma, underlying their applicability in Latin America.
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Affiliation(s)
- Federico Piñero
- Hospital Universitario Austral, Austral University, School of Medicine, Buenos Aires, Argentina.
| | - Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | | | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain; University of Barcelona, Barcelona, Spain.
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21
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Bracco C, Gallarate M, Badinella Martini M, Magnino C, D'Agnano S, Canta R, Racca G, Melchio R, Serraino C, Polla Mattiot V, Gollè G, Fenoglio L. Epidemiology, therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont, Italy. World J Gastrointest Oncol 2024; 16:761-772. [PMID: 38577451 PMCID: PMC10989369 DOI: 10.4251/wjgo.v16.i3.761] [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: 10/19/2023] [Revised: 12/19/2023] [Accepted: 12/28/2023] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental.
AIM To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.
METHODS In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019).
RESULTS Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis (P < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology (P < 0.05) and alpha-fetoprotein (AFP) levels (P < 0.01).
CONCLUSION In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology (P < 0.05) and AFP levels (P < 0.01).
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Affiliation(s)
- Christian Bracco
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | - Marta Gallarate
- Department of Medical Sciences, "City of Health and Science" University Hospital, Torino 10100, Italy
| | | | - Corrado Magnino
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | - Salvatore D'Agnano
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | - Roberta Canta
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | - Giulia Racca
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | - Remo Melchio
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | - Cristina Serraino
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | | | - Giovanni Gollè
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
| | - Luigi Fenoglio
- Department of Internal Medicine, Santa Croce e Carle General Hospital, Cuneo 12100, Italy
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22
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Chen JJ, Jin ZC, Zhong BY, Fan W, Zhang WH, Luo B, Wang YQ, Teng GJ, Zhu HD. Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives. United European Gastroenterol J 2024; 12:226-239. [PMID: 38372444 PMCID: PMC10954431 DOI: 10.1002/ueg2.12554] [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: 06/29/2023] [Accepted: 01/07/2024] [Indexed: 02/20/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.
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Affiliation(s)
- Jian-Jian Chen
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Zhi-Cheng Jin
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei-Hua Zhang
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Biao Luo
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Yu-Qing Wang
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Gao-Jun Teng
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Hai-Dong Zhu
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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23
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e213-e282. [PMID: 38364849 DOI: 10.1055/a-2189-8567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein, Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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24
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Patel M, Pillai A. Management of Intermediate-Stage Hepatocellular Carcinoma: Systemic Versus Locoregional Therapy. Surg Oncol Clin N Am 2024; 33:159-172. [PMID: 37945141 DOI: 10.1016/j.soc.2023.06.008] [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: 11/12/2023]
Abstract
Intermediate-stage hepatocellular carcinoma (HCC) comprises a heterogeneous group of patients with varying levels of tumor burden. Transarterial chemoembolization was traditionally the mainstay of treatment for intermediate-stage HCC for almost 2 decades. New and emerging treatment options have revolutionized HCC therapy, allowing for broader application to patients with intermediate- and advanced-stage disease. Accordingly, new guidelines acknowledge these options, and intermediate stage HCC can now be treated with surgical, locoregional or systemic therapies, or a combination thereof. Patients will continue to benefit from the development of complex treatment strategies in a multidisciplinary setting to optimize individual outcomes.
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Affiliation(s)
- Mikin Patel
- Department of Radiology, University of Chicago Medicine, Chicago, IL, USA
| | - Anjana Pillai
- Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
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25
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Kaufmann NC, Zeka B, Pereira PL. Research in interventional oncology: How sound is the evidence base? J Med Imaging Radiat Oncol 2023; 67:903-914. [PMID: 37170844 DOI: 10.1111/1754-9485.13529] [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: 01/09/2023] [Accepted: 03/26/2023] [Indexed: 05/13/2023]
Abstract
INTRODUCTION Interventional oncology (IO) is an essential component of cancer care, which has gained substantial recognition in recent years. The aim of this review is to evaluate the level of evidence supporting IO and its inclusion in cancer treatment guidelines. METHODS A literature search of the PubMed database was performed to identify publication numbers and types for IO treatments published between 2012 and 2022. Selected cancer treatment guidelines and recommendations were reviewed for their inclusion of IO treatments. RESULTS With 68%, the majority of studies on IO treatments are case reports while randomised controlled trials (RCTs) amount only to 7% of studies. Despite this, IO studies have generated sufficient data to support the inclusion of IO treatments in cancer treatment guidelines and recommendations. This was frequently based on large prospective patient cohorts that corresponded to 24% (20% non-randomised studies and 4% observational studies) of all analysed studies rather than RCTs. CONCLUSION The level of evidence underpinning IO, as well as inclusion of IO in treatment guidelines and recommendations have increased substantially in recent years, indicating the growing importance and acceptance of IO in cancer care. The difficulty in conducting RCTs in IO is mitigated by the observation that they are not necessary to achieve guideline-inclusion. Nevertheless, it is crucial to conduct well-designed research projects to further consolidate the position of IO in the field of oncology. This will ensure that IO continues to evolve and meet the needs of cancer patients worldwide.
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Affiliation(s)
- Nathalie C Kaufmann
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Vienna, Austria
- Next Research GmbH, Contract Research Organisation, Vienna, Austria
| | - Bleranda Zeka
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Vienna, Austria
- Next Research GmbH, Contract Research Organisation, Vienna, Austria
| | - Philippe L Pereira
- SLK-Kliniken Heilbronn GmbH, Zentrum für Radiologie, Minimal-Invasive Therapien und Nuklearmedizin, Heilbronn, Germany
- Academic Hospital Karls-Ruprecht University, Heidelberg, Germany
- Eberhard-Karls-University, Tübingen, Germany
- Danube Private University, Krems, Austria
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26
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Yeo YH, Liang J, Lauzon M, Luu M, Noureddin M, Ayoub W, Kuo A, Sankar K, Gong J, Hendifar A, Osipov A, Friedman ML, Lipshutz HG, Steinberger J, Kosari K, Nissen N, Abou-Alfa GK, Singal AG, Yang JD. Immunotherapy and Transarterial Radioembolization Combination Treatment for Advanced Hepatocellular Carcinoma. Am J Gastroenterol 2023; 118:2201-2211. [PMID: 37561061 DOI: 10.14309/ajg.0000000000002467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 05/25/2023] [Indexed: 08/11/2023]
Abstract
INTRODUCTION The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.
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Affiliation(s)
- Yee Hui Yeo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Jeff Liang
- Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Marie Lauzon
- Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Michael Luu
- Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Mazen Noureddin
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Walid Ayoub
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Alexander Kuo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Kamya Sankar
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Jun Gong
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Andrew Hendifar
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Arsen Osipov
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Marc L Friedman
- Division of Interventional Radiology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - H Gabriel Lipshutz
- Division of Interventional Radiology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Jonathan Steinberger
- Division of Interventional Radiology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Kambiz Kosari
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Nicholas Nissen
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Ghassan K Abou-Alfa
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
- Department of Population & Data Sciences, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Tzedakis S, Sebai A, Jeddou H, Garin E, Rolland Y, Bourien H, Uguen T, Sulpice L, Robin F, Edeline J, Boudjema K. Resection Postradioembolization in Patients With Single Large Hepatocellular Carcinoma. Ann Surg 2023; 278:756-762. [PMID: 37539588 DOI: 10.1097/sla.0000000000006061] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
OBJECTIVE The aim of this study was to evaluate the efficacy of yttrium-90 transarterial radioembolization (TARE) to convert to resection initially unresectable, single, large (≥5 cm) hepatocellular carcinoma (HCC). BACKGROUND TARE can downsize cholangiocarcinoma to resection but its role in HCC resectability remains debatable. METHODS All consecutive patients with a single large HCC treated between 2015 and 2020 in a single tertiary center were reviewed. When indicated, patients were either readily resected (upfront surgery) or underwent TARE. TARE patients were converted to resection (TARE surgery) or not (TARE-only). To further assess the effect of TARE on the long-term and short-term outcomes, a propensity score matching analysis was performed. RESULTS Among 216 patients, 144 (66.7%) underwent upfront surgery. Among 72 TARE patients, 20 (27.7%) were converted to resection. TARE-surgery patients received a higher mean yttrium-90 dose that the 52 remaining TARE-only patients (211.89±107.98 vs 128.7±36.52 Gy, P <0.001). Postoperative outcomes between upfront-surgery and TARE-surgery patients were similar. In the unmatched population, overall survival at 1, 3, and 5 years was similar between upfront-surgery and TARE-surgery patients (83.0%, 60.0%, 47% vs 94.0%, 86.0%, 55.0%, P =0.43) and compared favorably with TARE-only patients (61.0%, 16.0% and 9.0%, P <0.0001). After propensity score matching, TARE-surgery patients had significantly better overall survival than upfront-surgery patients ( P =0.021), while disease-free survival was similar ( P =0.29). CONCLUSION TARE may be a useful downstaging treatment for unresectable localized single large HCC providing comparable short-term and long-term outcomes with readily resectable tumors.
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Affiliation(s)
- Stylianos Tzedakis
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, University of Rennes 1, Rennes, France
| | - Amine Sebai
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, University of Rennes 1, Rennes, France
| | - Heithem Jeddou
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, University of Rennes 1, Rennes, France
| | - Etienne Garin
- Department of Nuclear Medicine, Centre Eugène Marquis, Rennes, France
| | - Yan Rolland
- Department of Interventional Radiology, Centre Eugène Marquis, Rennes, France
| | - Heloise Bourien
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Thomas Uguen
- Department of Hepatology, Pontchaillou University Hospital, University of Rennes 1, Rennes, France
| | - Laurent Sulpice
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, University of Rennes 1, Rennes, France
| | - Fabien Robin
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, University of Rennes 1, Rennes, France
| | - Julien Edeline
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Karim Boudjema
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, University of Rennes 1, Rennes, France
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Hu Z, Yang Z, Wang J, Fu Y, Hu Z, Zhou Z, Chen M, Zhang Y. Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus. Front Pharmacol 2023; 14:1223632. [PMID: 37799969 PMCID: PMC10549930 DOI: 10.3389/fphar.2023.1223632] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/06/2023] [Indexed: 10/07/2023] Open
Abstract
Background/purpose: The prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is generally poor and hepatectomy is optional for these patients. This study aims to explore the survival benefits of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) for resectable HCC with PVTT. Methods: This retrospective study included 120 resectable HCC patients with PVTT who underwent hepatectomy, from January 2017 to January 2021 at Sun Yat-sen University Cancer Center. Of these patients, the overall survival (OS) and recurrence-free survival (RFS) of 55 patients who received hepatectomy alone (Surgery group) and 65 patients who received neoadjuvant HAIC followed by hepatectomy (HAIC-Surgery group) were compared. Logistic regression analysis was conducted to develop a model predicting the response to neoadjuvant HAIC. Results: The OS rates for the HAIC-Surgery group at 1, 3, and 5 years were 94.9%, 78%, and 66.4%, respectively, compared with 84.6%, 47.6%, and 37.2% in the Surgery group (p < 0.001). The RFS rates were 88.7%, 56.2%, and 38.6% versus 84.9%, 38.3%, and 22.6% (p = 0.002). The subgroup analysis revealed that the survival benefit of neoadjuvant HAIC was limited to patients who responded to it. The logistic model, consisting of AFP and CRP, that predicted the response to neoadjuvant HAIC performed well, with an area under the ROC curve (AUC) of 0.756. Conclusion: Neoadjuvant HAIC followed by hepatectomy is associated with a longer survival outcome than hepatectomy alone for HCC patients with PVTT and the survival benefit is limited to patients who respond to neoadjuvant FOLFOX-HAIC.
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Affiliation(s)
- Zili Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhenyun Yang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jiongliang Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yizhen Fu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhiwen Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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Elnawasany S, Haggag YA, Shalaby SM, Soliman NA, EL Saadany AA, Ibrahim MAA, Badria F. Anti-cancer effect of nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line. BMC Complement Med Ther 2023; 23:270. [PMID: 37516826 PMCID: PMC10386659 DOI: 10.1186/s12906-023-04096-4] [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: 06/25/2022] [Accepted: 07/18/2023] [Indexed: 07/31/2023] Open
Abstract
BACKGROUND liver cancer is one of the most common cancers in the world. So far, there is no gold standard treatment for hepatocellular carcinoma. We conducted this in vitro study to assess the effect of three natural products: Boswellic acids, curcumin and naringin versus corresponding nanoparticles (NPs) on Hep G2 cells proliferation. METHODS Boswellic acid, curcumin, naringin-loaded NPs were prepared using nanoprecipitation method. Human liver (HepG2) cell line was cultured in Dulbecco's modified Eagle's medium (DMEM). The cell growth inhibition and cytotoxicity were evaluated by MTT assay. RESULTS Boswellic acid, curcumin, naringin were able to inhibit HepG2 cells proliferation. IC50 at 24 h, 48 h showed significant lower values in NPs versus Free herbs. IC50 values of free Boswellic acids and NPs at 24 h were (24.60 ± 1.89 and 7.78 ± 0.54, P < 0.001), at 48 h were (22.45 ± 1.13 and 5.58 ± 0.27, P < 0.001) respectively. IC50 values of free curcumin and NPs at 24 h were (5.89 ± 0.8 and 3.46 ± 0.23, P < 0.05), at 48 h were (5.57 ± 0.94 and 2.51 ± 0.11, P < 0.05), respectively. For free and naringenin NPs, IC50 values at 24 h were (14.57 ± 1.78 and 7.25 ± 0.17, P < 0.01), at 48 h were (11.37 ± 1.45 and 5.21 ± 0.18, P < 0.01) respectively. CONCLUSION Boswellic acid, curcumin, naringin and their nanoprecipitation prepared nanoparticles suppressed Hep G2 cells proliferation.
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Affiliation(s)
- Sally Elnawasany
- Tropical Medicine Department, Faculty of Medicine, Tanta University, Tanta, Gharbia, 31111 Egypt
| | - Yusuf A. Haggag
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Gharbia, Egypt
| | - Shahinaz M. Shalaby
- Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt
| | - Nema A. Soliman
- Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt
| | - Amira A. EL Saadany
- Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt
| | - Marwa A. A. Ibrahim
- Histology Department, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt
| | - Farid Badria
- Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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Hu L, Lin J, Shi X, Wang A. Efficacy of transarterial therapy combined with first-line tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a network meta-analysis. World J Surg Oncol 2023; 21:208. [PMID: 37475030 PMCID: PMC10360255 DOI: 10.1186/s12957-023-03098-3] [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: 03/11/2023] [Accepted: 07/12/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Transarterial therapies, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and selective internal radiation therapy, combined with first-line tyrosine kinase inhibitors (TKIs) are considered the standard therapy for unresectable hepatocellular carcinoma. However, inconsistent results have been reported in various studies assessing different combinations of targeted agents. METHODS A network meta-analysis (NMA) was performed by including 23 randomized controlled trials (RCTs) with 6175 patients to investigate the efficiency of transarterial therapies in combination with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), time to progression (TTP), and tumor objective response rate (ORR). A random-effects consistency model was used in this Bayesian NMA. Hazard ratio and odd risks with a 95% credible interval were calculated and agents were ranked based on ranking probability. RESULTS HAIC showed maximal OS and TTP and TACE plus lenvatinib showed maximal PFS, ORR, and disease control rate (DCR). HAIC and TACE plus lenvatinib were ranked highest based on their respective parameters, which were OS for HAIC and PFS, ORR, and DCR for TACE plus lenvatinib. CONCLUSION HAIC and TACE plus lenvatinib were relatively better choice for unresectable hepatocellular carcinoma. However, owing to the lack of statistically significant OS benefits among most agents, other agents should be considered as potential alternatives for unresectable hepatocellular carcinoma.
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Affiliation(s)
- Lingbo Hu
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Zhejiang, China
| | - Jiangying Lin
- Department of Blood Purification, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
| | - Xingpeng Shi
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Zhejiang, China
| | - Aidong Wang
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China.
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Zhejiang, China.
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Hur MH, Cho Y, Kim DY, Lee JS, Kim GM, Kim HC, Sinn DH, Hyun D, Lee HA, Seo YS, Lee IJ, Park JW, Kim YJ. Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol 2023; 29:763-778. [PMID: 37254488 PMCID: PMC10366806 DOI: 10.3350/cmh.2023.0076] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/24/2023] [Accepted: 05/24/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND/AIMS Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. METHODS This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). RESULTS In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28-0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0-56.7%, whereas that of the TKI group was 12.3-15.0%. CONCLUSION For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.
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Affiliation(s)
- Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Do Young Kim
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Seung Lee
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Gyoung Min Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dongho Hyun
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - In Joon Lee
- Department of Radiology, National Cancer Center, Goyang, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Brandi N, Renzulli M. The Synergistic Effect of Interventional Locoregional Treatments and Immunotherapy for the Treatment of Hepatocellular Carcinoma. Int J Mol Sci 2023; 24:ijms24108598. [PMID: 37239941 DOI: 10.3390/ijms24108598] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Immunotherapy has remarkably revolutionized the management of advanced HCC and prompted clinical trials, with therapeutic agents being used to selectively target immune cells rather than cancer cells. Currently, there is great interest in the possibility of combining locoregional treatments with immunotherapy for HCC, as this combination is emerging as an effective and synergistic tool for enhancing immunity. On the one hand, immunotherapy could amplify and prolong the antitumoral immune response of locoregional treatments, improving patients' outcomes and reducing recurrence rates. On the other hand, locoregional therapies have been shown to positively alter the tumor immune microenvironment and could therefore enhance the efficacy of immunotherapy. Despite the encouraging results, many unanswered questions still remain, including which immunotherapy and locoregional treatment can guarantee the best survival and clinical outcomes; the most effective timing and sequence to obtain the most effective therapeutic response; and which biological and/or genetic biomarkers can be used to identify patients likely to benefit from this combined approach. Based on the current reported evidence and ongoing trials, the present review summarizes the current application of immunotherapy in combination with locoregional therapies for the treatment of HCC, and provides a critical evaluation of the current status and future directions.
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Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
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Luu MH, Mai HS, Pham XL, Le QA, Le QK, Walsum TV, Le NH, Franklin D, Le VH, Moelker A, Chu DT, Trung NL. Quantification of liver-Lung shunt fraction on 3D SPECT/CT images for selective internal radiation therapy of liver cancer using CNN-based segmentations and non-rigid registration. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2023; 233:107453. [PMID: 36921463 DOI: 10.1016/j.cmpb.2023.107453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 01/25/2023] [Accepted: 02/27/2023] [Indexed: 06/18/2023]
Abstract
PURPOSE Selective internal radiation therapy (SIRT) has been proven to be an effective treatment for hepatocellular carcinoma (HCC) patients. In clinical practice, the treatment planning for SIRT using 90Y microspheres requires estimation of the liver-lung shunt fraction (LSF) to avoid radiation pneumonitis. Currently, the manual segmentation method to draw a region of interest (ROI) of the liver and lung in 2D planar imaging of 99mTc-MAA and 3D SPECT/CT images is inconvenient, time-consuming and observer-dependent. In this study, we propose and evaluate a nearly automatic method for LSF quantification using 3D SPECT/CT images, offering improved performance compared with the current manual segmentation method. METHODS We retrospectively acquired 3D SPECT with non-contrast-enhanced CT images (nCECT) of 60 HCC patients from a SPECT/CT scanning machine, along with the corresponding diagnostic contrast-enhanced CT images (CECT). Our approach for LSF quantification is to use CNN-based methods for liver and lung segmentations in the nCECT image. We first apply 3D ResUnet to coarsely segment the liver. If the liver segmentation contains a large error, we dilate the coarse liver segmentation into the liver mask as a ROI in the nCECT image. Subsequently, non-rigid registration is applied to deform the liver in the CECT image to fit that obtained in the nCECT image. The final liver segmentation is obtained by segmenting the liver in the deformed CECT image using nnU-Net. In addition, the lung segmentations are obtained using 2D ResUnet. Finally, LSF quantitation is performed based on the number of counts in the SPECT image inside the segmentations. Evaluations and Results: To evaluate the liver segmentation accuracy, we used Dice similarity coefficient (DSC), asymmetric surface distance (ASSD), and max surface distance (MSD) and compared the proposed method to five well-known CNN-based methods for liver segmentation. Furthermore, the LSF error obtained by the proposed method was compared to a state-of-the-art method, modified Deepmedic, and the LSF quantifications obtained by manual segmentation. The results show that the proposed method achieved a DSC score for the liver segmentation that is comparable to other state-of-the-art methods, with an average of 0.93, and the highest consistency in segmentation accuracy, yielding a standard deviation of the DSC score of 0.01. The proposed method also obtains the lowest ASSD and MSD scores on average (2.6 mm and 31.5 mm, respectively). Moreover, for the proposed method, a median LSF error of 0.14% is obtained, which is a statically significant improvement to the state-of-the-art-method (p=0.004), and is much smaller than the median error in LSF manual determination by the medical experts using 2D planar image (1.74% and p<0.001). CONCLUSIONS A method for LSF quantification using 3D SPECT/CT images based on CNNs and non-rigid registration was proposed, evaluated and compared to state-of-the-art techniques. The proposed method can quantitatively determine the LSF with high accuracy and has the potential to be applied in clinical practice.
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Affiliation(s)
- Manh Ha Luu
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam; FET, VNU University of Engineering and Technology, Hanoi, Vietnam; Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands.
| | - Hong Son Mai
- Department of Nuclear Medicine, Hospital 108, Hanoi, Vietnam
| | - Xuan Loc Pham
- FET, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Quoc Anh Le
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Quoc Khanh Le
- Department of Nuclear Medicine, Hospital 108, Hanoi, Vietnam
| | - Theo van Walsum
- Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands
| | - Ngoc Ha Le
- Department of Nuclear Medicine, Hospital 108, Hanoi, Vietnam
| | - Daniel Franklin
- School of Electrical and Data Engineering, University of Technology Sydney, Sydney, Australia
| | - Vu Ha Le
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam; FET, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Adriaan Moelker
- Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands
| | - Duc Trinh Chu
- FET, VNU University of Engineering and Technology, Hanoi, Vietnam
| | - Nguyen Linh Trung
- AVITECH, VNU University of Engineering and Technology, Hanoi, Vietnam
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Chami P, Jarnagin W, Abou-Alfa GK, Harding J, Kim N, Lin H, El Homsi M, Crane C, Hajj C. Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:1748. [PMID: 36980634 PMCID: PMC10046599 DOI: 10.3390/cancers15061748] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/09/2023] [Accepted: 03/11/2023] [Indexed: 03/16/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials.
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Affiliation(s)
- Perla Chami
- Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107, Lebanon
| | - William Jarnagin
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Surgery, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Ghassan K. Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - James Harding
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Neal Kim
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Haibo Lin
- New York Proton Center, New York, NY 10035, USA
| | - Maria El Homsi
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | | | - Carla Hajj
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- New York Proton Center, New York, NY 10035, USA
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Wong JK, Lim HJ, Tam VC, Burak KW, Dawson LA, Chaudhury P, Abraham RJ, Meyers BM, Sapisochin G, Valenti D, Samimi S, Ramjeesingh R, Mujoomdar A, Martins I, Dixon E, Segedi M, Liu DM. Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada. Cancer Treat Rev 2023; 115:102526. [PMID: 36924644 DOI: 10.1016/j.ctrv.2023.102526] [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: 12/09/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Affiliation(s)
- Jason K Wong
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Howard J Lim
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | - Vincent C Tam
- Tom Baker Cancer Centre, University of Calgary, 1331 29 St NW, Calgary, AB T2N 4N2, Canada.
| | - Kelly W Burak
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Laura A Dawson
- Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C1, Canada.
| | | | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Brandon M Meyers
- Juravinski Cancer Centre, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
| | | | - David Valenti
- McGill University, 845 Rue Sherbrooke O, Montréal, QC H3A 0G4, Canada.
| | - Setareh Samimi
- Hopital Sacre-Coeur de Montreal, University of Montreal, 5400 Boul Gouin O, Montréal, QC H4J 1C5, Canada.
| | - Ravi Ramjeesingh
- Department of Medicine, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Amol Mujoomdar
- Western University, 1151 Richmond Street, London, ON N6A 5B9, Canada.
| | - Ilidio Martins
- Kaleidoscope Strategic, Inc. 1 King Street W, Suite 4800 - 117, Toronto, ON M5H 1A1, Canada.
| | - Elijah Dixon
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Maja Segedi
- Department of Surgery, Vancouver General Hospital, Jim Pattison Pavilion, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada.
| | - David M Liu
- School of Biomedical Engineering, University of British Columbia, 2329 West Mall Vancouver, BC V6T 1Z4, Canada.
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Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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Sangro B, Argemí J. Transarterial Radioembolization Ought Not to Borrow Future Liver Function from Patients with Hepatocellular Carcinoma. But Does It? J Vasc Interv Radiol 2023; 34:976-977. [PMID: 36787816 DOI: 10.1016/j.jvir.2023.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 02/07/2023] [Indexed: 02/16/2023] Open
Affiliation(s)
- Bruno Sangro
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
| | - Josepmaria Argemí
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain; Hepatology Program, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Spain
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38
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Welling MM, Duszenko N, van Meerbeek MP, Molenaar TJM, Buckle T, van Leeuwen FWB, Rietbergen DDD. Microspheres as a Carrier System for Therapeutic Embolization Procedures: Achievements and Advances. J Clin Med 2023; 12:918. [PMID: 36769566 PMCID: PMC9917963 DOI: 10.3390/jcm12030918] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/17/2023] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
The targeted delivery of anti-cancer drugs and isotopes is one of the most pursued goals in anti-cancer therapy. One of the prime examples of such an application is the intra-arterial injection of microspheres containing cytostatic drugs or radioisotopes during hepatic embolization procedures. Therapy based on the application of microspheres revolves around vascular occlusion, complemented with local therapy in the form of trans-arterial chemoembolization (TACE) or radioembolization (TARE). The broadest implementation of these embolization strategies currently lies within the treatment of untreatable hepatocellular cancer (HCC) and metastatic colorectal cancer. This review aims to describe the state-of-the-art TACE and TARE technologies investigated in the clinical setting for HCC and addresses current trials and new developments. In addition, chemical properties and advancements in microsphere carrier systems are evaluated, and possible improvements in embolization therapy based on the modification of and functionalization with therapeutical loads are explored.
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Affiliation(s)
- Mick. M. Welling
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Nikolas Duszenko
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Departments of Parasitology and Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Maarten P. van Meerbeek
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Tom J. M. Molenaar
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Radiochemistry Facility, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Tessa Buckle
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Fijs W. B. van Leeuwen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Daphne D. D. Rietbergen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Section of Nuclear Medicine, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
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Taswell CS, Studenski M, Pennix T, Stover B, Georgiou M, Venkat S, Jones P, Zikria J, Thornton L, Yechieli R, Mohan P, Portelance L, Spieler B. For Hepatocellular Carcinoma Treated with Yttrium-90 Microspheres, Dose Volumetrics on Post-Treatment Bremsstrahlung SPECT/CT Predict Clinical Outcomes. Cancers (Basel) 2023; 15:cancers15030645. [PMID: 36765603 PMCID: PMC9913422 DOI: 10.3390/cancers15030645] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 01/11/2023] [Accepted: 01/17/2023] [Indexed: 01/22/2023] Open
Abstract
In transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) with Yttrium-90 (Y-90) microspheres, recent studies correlate dosimetry from bremsstrahlung single photon emission tomography (SPECT/CT) with treatment outcomes; however, these studies focus on measures of central tendency rather than volumetric coverage metrics commonly used in radiation oncology. We hypothesized that three-dimensional (3D) isodose coverage of gross tumor volume (GTV) is the driving factor in HCC treatment response to TARE and is best assessed using advanced dosimetry techniques applied to nuclear imaging of actual Y-90 biodistribution. We reviewed 51 lobar TARE Y-90 treatments of 43 HCC patients. Dose prescriptions were 120 Gy for TheraSpheres and 85 Gy for SIR-Spheres. All patients underwent post-TARE Y-90 bremsstrahlung SPECT/CT imaging. Commercial software was used to contour gross tumor volume (GTV) and liver on post-TARE SPECT/CT. Y-90 dose distributions were calculated using the Local Deposition Model based on post-TARE SPECT/CT activity maps. Median gross tumor volume (GTV) dose; GTV receiving less than 100 Gy, 70 Gy and 50 Gy; minimum dose covering the hottest 70%, 95%, and 98% of the GTV (D70, D95, D98); mean dose to nontumorous liver, and disease burden (GTV/liver volume) were obtained. Clinical outcomes were collected for all patients by chart and imaging review. HCC treatment response was assessed according to the modified response criteria in solid tumors (mRECIST) guidelines. Kaplan-Meier (KM) survival estimates and multivariate regression analyses (MVA) were performed using STATA. Median survival was 22.5 months for patients achieving objective response (OR) in targeted lesions (complete response (CR) or partial response (PR) per mRECIST) vs. 7.6 months for non-responders (NR, stable disease or disease progression per mRECIST). On MVA, the volume of underdosed tumor (GTV receiving less than 100 Gy) was the only significant dosimetric predictor for CR (p = 0.0004) and overall survival (OS, p = 0.003). All targets with less than CR (n = 39) had more than 20 cc of underdosed tumor. D70 (p = 0.038) correlated with OR, with mean D70 of 95 Gy for responders and 60 Gy for non-responders (p = 0.042). On MVA, mean dose to nontumorous liver trended toward significant association with grade 3+ toxicity (p = 0.09) and correlated with delivered activity (p < 0.001) and burden of disease (p = 0.05). Dosimetric models supplied area under the curve estimates of > 0.80 predicting CR, OR, and ≥grade 3 acute toxicity. Dosimetric parameters derived from the retrospective analysis of post-TARE Y-90 bremsstrahlung SPECT/CT after lobar treatment of HCC suggest that volumetric coverage of GTV, not a high mean or median dose, is the driving factor in treatment response and that this is best assessed through the analysis of actual Y-90 biodistribution.
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Affiliation(s)
- Crystal Seldon Taswell
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Matthew Studenski
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Thomas Pennix
- Miller School of Medicine, University of Miami, 1600 NW 10th Ave, Miami, FL 33136, USA
| | - Bryan Stover
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Mike Georgiou
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Shree Venkat
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Patricia Jones
- Department of Medicine, Division of Digestive Health and Liver Diseases, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Joseph Zikria
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Lindsay Thornton
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Raphael Yechieli
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Prasoon Mohan
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Lorraine Portelance
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
| | - Benjamin Spieler
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA
- Correspondence:
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Oliván-Sasot P, Pérez-Enguix D, Bello-Arques P, Torres-Espallardo I, Falgás-Lacueva M, Yepes-Agudelo AM, Olivas-Arroyo C. Radioembolization in patients with hepatocellular carcinoma: a series of 53 cases. RADIOLOGIA 2023; 65:12-21. [PMID: 36842781 DOI: 10.1016/j.rxeng.2021.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 09/30/2020] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To contribute our results to increase the scientific evidence about the use of radioembolization in the management of patients with hepatocellular carcinoma. MATERIAL AND METHODS This retrospective review included 53 patients with hepatocellular carcinoma treated with radioembolization at our center. Patients were classified according to the BCLC algorithm in detail according to their Child-Pugh functional status. We analyzed survival using the Kaplan-Meier method. We used Cox regression analysis to determine clinically significant parameters, including the doses administered in the parameters studied. RESULTS Patients ranged in age from 28 to 86 years (mean, 60 years). A total of 61 procedures were done. The mean activity administered was 2.8GBq (0.7-6.4GBq), with a mean dose of 229.9Gy (74-425.9Gy) administered in the tumor. Progression-free survival was 6.7 months and overall survival was 12.8 months. Differences in disease-free survival according to BCLC and Child-Pugh classification were not significant (p=0.848 and p=0.252, respectively). The clinical parameters that were significantly different with respect to overall survival were bilirubin levels (p<0.001), pretreatment transaminase levels (AST) (p=0.022), Child-Pugh subclassification (p=0.003), and dose administered in the tumor (p=0.001). Only one patient had a severe adverse reaction, developing posttreatment liver failure resulting in death. CONCLUSIONS Radioembolization is safe and efficacious in the treatment of patients with hepatocellular carcinoma. Liver function and the doses received by the tumor are key parameters for the efficacy of treatment. The increase in the scientific evidence supports the inclusion of this technique in treatment guidelines.
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Affiliation(s)
- P Oliván-Sasot
- Medicina Nuclear, Hospital de La Ribera, Alzira, Valencia, Spain.
| | - D Pérez-Enguix
- Radiología Intervencionista, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - P Bello-Arques
- Medicina Nuclear, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | | | - M Falgás-Lacueva
- Medicina Nuclear, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - A M Yepes-Agudelo
- Medicina Nuclear, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - C Olivas-Arroyo
- Radiofarmacia, Hospital Universitario y Politécnico La Fe, Valencia, Spain
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Arrichiello A, Di Meglio L, Angileri SA, Duka E, Gurgitano M, Rodà GM, Ierardi AM, Carrafiello G. Liver Cancer Interventions. MULTIMODALITY IMAGING AND INTERVENTION IN ONCOLOGY 2023:189-199. [DOI: 10.1007/978-3-031-28524-0_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Yttrium-90 Radioembolization: Current Indications and Outcomes. J Gastrointest Surg 2022; 27:604-614. [PMID: 36547759 DOI: 10.1007/s11605-022-05559-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 12/06/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND Radioembolization (RE) with 90Yttrium (Y90) has generally been used to treat patients with advanced disease. Recent data suggest, however, that RE is also safe and feasible to treat patients with early or intermediate stage disease. We herein review the current evidence regarding the use of RE with Y90 for patients with HCC. METHODS A comprehensive review of the literature was performed using MEDLINE/PubMed and Web of Science databases with a search end date of August 1, 2022. RESULTS Patients with HCC are often treated according to the BCLC staging system. Among patients with early-stage HCC (BCLC A), intermediate-stage HCC (BCLC B), and advanced-stage HCC (BCLC C), RE with Y90 has demonstrated promising results with comparable overall survival, time to disease progression, and radiological response compared with other standard of care treatment modalities. Moreover, Y90 RE can be used as a downstaging treatment modality for patients with advanced HCC who have a disease burden that is initially outside LT criteria. Radiation lobectomy (RL) has been described as a treatment modality with the intent of treating the ipsilateral liver that harbors the HCC, while also causing compensatory hypertrophy of the future liver remnant (FLR). CONCLUSION While initially considered as a palliative option for HCC patients, Y90 RE has emerged as an important part of the multi-modality care of patients with HCC across a wide spectrum of clinical indications.
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Mosconi C, Cappelli A, Pettinato C, Cocozza MA, Vara G, Terzi E, Morelli MC, Lodi Rizzini E, Renzulli M, Modestino F, Serenari M, Bonfiglioli R, Calderoni L, Tabacchi E, Cescon M, Morganti AG, Trevisani F, Piscaglia F, Fanti S, Strigari L, Cucchetti A, Golfieri R. Improved Survival after Transarterial Radioembolisation for Hepatocellular Carcinoma Gives the Procedure Added Value. J Clin Med 2022; 11:jcm11247469. [PMID: 36556085 PMCID: PMC9781303 DOI: 10.3390/jcm11247469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/09/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Transarterial Radioembolisation (TARE) requires multidisciplinary experience and skill to be effective. The aim of this study was to identify determinants of survival in patients with hepatocellular carcinoma (HCC), focusing on learning curves, technical advancements, patient selection and subsequent therapies. METHODS From 2005 to 2020, 253 patients were treated. TARE results achieved in an initial period (2005-2011) were compared to those obtained in a more recent period (2012-2020). To isolate the effect of the treatment period, differences between the two periods were balanced using "entropy balance". RESULTS Of the 253 patients, 68 were treated before 2012 and 185 after 2012. In the second period, patients had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 1 (p = 0.025) less frequently, less liver involvement (p = 0.006) and a lesser degree of vascular invasion (p = 0.019). The median overall survival (OS) of patients treated before 2012 was 11.2 months and that of patients treated beginning in 2012 was 25.7 months. After reweighting to isolate the effect of the treatment period, the median OS of patients before 2012 increased to 16 months. CONCLUSIONS Better patient selection, refinement of technique and adoption of personalised dosimetry improved survival after TARE. Conversely, sorafenib after TARE did not impact life expectancy.
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Affiliation(s)
- Cristina Mosconi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Cinzia Pettinato
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Maria Adriana Cocozza
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Correspondence: ; Tel.: +39-051-6362-311
| | - Giulio Vara
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Eleonora Terzi
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Maria Cristina Morelli
- Division of Internal Medicine for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Elisa Lodi Rizzini
- Radiation Oncology, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Francesco Modestino
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Matteo Serenari
- General Surgery and Transplantation Unit, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Rachele Bonfiglioli
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Letizia Calderoni
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Elena Tabacchi
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Matteo Cescon
- General Surgery and Transplantation Unit, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | | | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotica Medica, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Stefano Fanti
- Nuclear Medicine Unit, IRCCS, Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Lidia Strigari
- Department of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy
- Department of General Surgery, Morgagni—Pierantoni Hospital, 47121 Forlì, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Alma Mater Studiorum, Università Degli Studi Di Bologna, 40138 Bologna, Italy
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Kolligs F, Arnold D, Golfieri R, Pech M, Peynircioglu B, Pfammatter T, Ronot M, Sangro B, Schaefer N, Maleux G, Munneke G, Pereira H, Zeka B, de Jong N, Helmberger T, CIRT Principal Investigators AlbrechtThomasD’ArchambeauOlivierBalliTugsanBilgicSadikBloomAllanCioniRobertoFischbachRomanFlamenPatrickGerardLaurentGrözingerGerdKatohMarcusKoehlerMichaelKrögerJan RobertKuhlChristianeOrsiFrancoÖzgünMuratReimerPeterRonotMaximeSchmidAxelVitAlessandro, Neukölln VK, D’Archambeau O, Balli T, Bilgic S, Bloom A, Cioni R, Fischbach R, Altona AK, Flamen P, Gerard L, Grözinger G, Katoh M, Koehler M, Kröger JR, Kuhl C, Orsi F, Özgün M, Reimer P, Ronot M, Schmid A, Vit A. Factors impacting survival after transarterial radioembolization in patients with hepatocellular carcinoma: Results from the prospective CIRT study. JHEP Rep 2022; 5:100633. [PMID: 36593888 PMCID: PMC9804139 DOI: 10.1016/j.jhepr.2022.100633] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 11/14/2022] [Accepted: 11/16/2022] [Indexed: 11/27/2022] Open
Abstract
Background & Aims Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study. Methods We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes. Results The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events. Conclusions This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes. Impact and implications Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE. Clinical trial number NCT02305459.
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Key Words
- ALBI, albumin-bilirubin
- BCLC, Barcelona Clinic Liver Cancer
- BSA, body surface area
- CIRSE, Cardiovascular and Interventional Radiological Society of Europe
- CIRT, CIRSE Registry for SIR-Spheres Therapy
- ECOG, Eastern Cooperative Oncology Group
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- INR, international normalized ratio
- IPTW, inverse probability of treatment weighting
- OS, overall survival
- PFS, progression-free survival
- PVT, portal vein thrombosis
- REILD, radioembolization-induced liver disease
- SIRT
- TACE, transcatheter arterial chemoembolization
- TARE, transarterial radioembolization
- Y90, Yttrium-90
- dosimetry
- hPFS, hepatic progression-free survival
- liver
- mBSA, modified body surface area
- observational
- radioembolization
- registry
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Affiliation(s)
- Frank Kolligs
- Department of Internal Medicine and Gastroenterology, Helios Klinikum Berlin-Buch, Berlin, Germany
| | - Dirk Arnold
- Oncology and Hematology, Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany
| | - Bora Peynircioglu
- Department of Radiology, School of Medicine, Hacettepe University, Sihhiye Campus, Ankara, Turkey
| | - Thomas Pfammatter
- Institute of Diagnostic and Interventional Radiology, Universitätsspital Zürich, Zürich, Switzerland
| | - Maxime Ronot
- Université Paris Cité, Paris & Service de Radiologie, APHP Nord, Hôpital Beaujon, Clichy, France
| | - Bruno Sangro
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain
| | - Niklaus Schaefer
- Service de médecine nucléaire et imagerie moléculaire, CHUV, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Geert Maleux
- Radiology, Universitair Ziekenhuis Leuven, Leuven, Belgium
| | - Graham Munneke
- Interventional Oncology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Helena Pereira
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Unité de Recherche Clinique, Paris, France,INSERM, Centre d'Investigation Clinique 1418 (CIC1418), Paris, France
| | - Bleranda Zeka
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Vienna, Austria
| | - Niels de Jong
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Vienna, Austria,Corresponding author. Address: Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Neutorgasse 9, 1010, Vienna Austria; Tel.: +43 1904200347
| | - Thomas Helmberger
- Department of Radiology, Neuroradiology and Minimal-Invasive Therapy, Klinikum Bogenhausen, Munich, Germany
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Knavel Koepsel EM, Smolock AR, Pinchot JW, Kim CY, Ahmed O, Chamarthy MRK, Hecht EM, Hwang GL, Kaplan DE, Luh JY, Marrero JA, Monroe EJ, Poultsides GA, Scheidt MJ, Hohenwalter EJ. ACR Appropriateness Criteria® Management of Liver Cancer: 2022 Update. J Am Coll Radiol 2022; 19:S390-S408. [PMID: 36436965 DOI: 10.1016/j.jacr.2022.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/27/2022]
Abstract
The treatment and management of hepatic malignancies can be complex because it encompasses a variety of primary and metastatic malignancies and an assortment of local and systemic treatment options. When to use each of these treatments is critical to ensure the most appropriate care for patients. Interventional radiologists have a key role to play in the delivery of a variety of liver directed treatments including percutaneous ablation, transarterial embolization with bland embolic particles alone, transarterial chemoembolization (TACE) with injection of a chemotherapeutic emulsion, and transarterial radioembolization (TARE). Based on 9 clinical variants, the appropriateness of each treatment is described in this document. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Affiliation(s)
| | - Amanda R Smolock
- Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | - Charles Y Kim
- Panel Vice-Chair, Duke University Medical Center, Durham, North Carolina
| | - Osmanuddin Ahmed
- Vice-Chair of Wellness, Director of Venous Interventions, University of Chicago, Chicago, Illinois
| | - Murthy R K Chamarthy
- Vascular Institute of North Texas, Dallas, Texas; Commission on Nuclear Medicine and Molecular Imaging
| | - Elizabeth M Hecht
- Vice-Chair of Academic Affairs, Professor of Radiology, Weill Cornell Medicine, New York, New York; RADS Committee; Member of Appropriateness Subcommittees on Hepatobiliary Topics; Member of LI-RADS
| | - Gloria L Hwang
- Associate Chair of Clinical Performance Improvement, Stanford Radiology, Stanford Medical Center, Stanford, California
| | - David E Kaplan
- Section Chief of Hepatology at the University of Pennsylvania Division of Gastroenterology and Hepatology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; American Association for the Study of Liver Diseases
| | - Join Y Luh
- Providence Health Radiation Oncology Focus Group Chair, Providence St. Joseph Health, Eureka, California; Commission on Radiation Oncology; ACR CARROS President; ACR Council Steering Committee; California Radiological Society Councilor to ACR
| | - Jorge A Marrero
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; American Gastroenterological Association
| | | | - George A Poultsides
- Chief of Surgical Oncology and Professor of Surgery, Stanford University School of Medicine, Stanford, California; Society of Surgical Oncology
| | - Matthew J Scheidt
- Program Director of Independent IR Residency, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Eric J Hohenwalter
- Specialty Chair; Chief, MCW VIR, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
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Prince DS, Schlaphoff G, Davison SA, Huo YR, Xiang H, Chan MV, Lee AU, Thailakanathan C, Jebeili H, Rogan C, Al-Omary A, Gupta S, Lockart I, Tiwari N, Clark-Dickson M, Hillhouse JW, Laube R, Chang J, Nguyen V, Danta M, Cheng R, Strasser SI, Zekry A, Levy MT, Chan C, Liu K. Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study. J Gastroenterol Hepatol 2022; 37:2173-2181. [PMID: 36031345 DOI: 10.1111/jgh.15986] [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: 05/17/2022] [Revised: 07/27/2022] [Accepted: 08/17/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND AIM The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.
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Affiliation(s)
- David Stephen Prince
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.,Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Glen Schlaphoff
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Scott Anthony Davison
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Ya Ruth Huo
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Hao Xiang
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Michael Vinchill Chan
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia.,Sydney Adventist Hospital, Sydney, New South Wales, Australia
| | - Alice Unah Lee
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Cynthuja Thailakanathan
- Department of Gastroenterology and Hepatology, St George Hospital, Sydney, New South Wales, Australia
| | - Hazem Jebeili
- Department of Gastroenterology and Hepatology, St George Hospital, Sydney, New South Wales, Australia
| | - Christopher Rogan
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.,Sydney Adventist Hospital, Sydney, New South Wales, Australia
| | - Ahmed Al-Omary
- Gastroenterology Department, Westmead Hospital, Sydney, New South Wales, Australia
| | - Sidhartha Gupta
- Gastroenterology Department, Westmead Hospital, Sydney, New South Wales, Australia
| | - Ian Lockart
- Gastroenterology Department, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Neha Tiwari
- Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, New South Wales, Australia
| | | | | | - Robyn Laube
- Macquarie University Hospital, Sydney, New South Wales, Australia
| | - Jeff Chang
- Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, New South Wales, Australia.,Macquarie University Hospital, Sydney, New South Wales, Australia
| | - Vi Nguyen
- Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Mark Danta
- Gastroenterology Department, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Robert Cheng
- Gastroenterology Department, Westmead Hospital, Sydney, New South Wales, Australia
| | - Simone Irene Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Amany Zekry
- Department of Gastroenterology and Hepatology, St George Hospital, Sydney, New South Wales, Australia
| | - Miriam Tania Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Christine Chan
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
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de la Torre-Aláez M, Matilla A, Varela M, Iñarrairaegui M, Reig M, Lledó JL, Arenas JI, Lorente S, Testillano M, Márquez L, Da Fonseca L, Argemí J, Gómez-Martin C, Rodriguez-Fraile M, Bilbao JI, Sangro B. Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study. J Immunother Cancer 2022; 10:jitc-2022-005457. [PMID: 36450386 PMCID: PMC9716796 DOI: 10.1136/jitc-2022-005457] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2022] [Indexed: 12/03/2022] Open
Abstract
PURPOSE To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in combination with a PD-1 inhibitor in patients with unresectable hepatocellular carcinoma (uHCC) and liver-only disease ineligible for chemoembolization. PATIENTS AND METHODS NASIR-HCC is a single-arm, multicenter, open-label, phase 2 trial that recruited from 2017 to 2019 patients who were naïve to immunotherapy and had tumors in the BCLC B2 substage (single or multiple tumors beyond the up-to-7 rule), or unilobar tumors with segmental or lobar portal vein invasion (PVI); no extrahepatic spread; and preserved liver function. Patients received SIRT followed 3 weeks later by nivolumab (240 mg every 2 weeks) for up to 24 doses or until disease progression or unacceptable toxicity. Safety was the primary endpoint. Secondary objectives included objective response rate (ORR), time to progression (TTP), and overall survival (OS). RESULTS 42 patients received SIRT (31 BCLC-B2, 11 with PVI) and were followed for a median of 22.2 months. 27 patients discontinued and 1 never received Nivolumab. 41 patients had any-grade adverse events (AE) and 21 had serious AEs (SAE). Treatment-related AEs and SAEs grade 3-4 occurred in 8 and 5 patients, respectively. Using RECIST 1.1 criteria, ORR reported by investigators was 41.5% (95% CI 26.3% to 57.9%). Four patients were downstaged to partial hepatectomy. Median TTP was 8.8 months (95% CI 7.0 to 10.5) and median OS was 20.9 months (95% CI 17.7 to 24.1). CONCLUSIONS The combination of SIRT and nivolumab has shown an acceptable safety profile and signs of antitumor activity in the treatment of patients with uHCC that were fit for SIRT. TRIAL REGISTRATION NUMBER NCT03380130.
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Affiliation(s)
| | - Ana Matilla
- Digestive Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Maria Varela
- Liver Unit, Hospital Universitario Central de Asturias, IUOPA, ISPA, FINBA, Universidad de Oviedo, Oviedo, Spain
| | - Mercedes Iñarrairaegui
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.,Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Maria Reig
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.,BCLC group, Liver Unit, Hospital Clinic, ICMDM, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Jose Luis Lledó
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.,Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
| | | | - Sara Lorente
- Liver Unit, Hospital Clínico Lozano Blesa, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain
| | | | - Laura Márquez
- Digestive Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Leonardo Da Fonseca
- BCLC group, Liver Unit, Hospital Clinic, ICMDM, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Josepmaria Argemí
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.,Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | | | | | - Jose I Bilbao
- Interventional Radiology, Clínica Universidad de Navarra, Pamplona, Spain
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain .,Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
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Öcal O, Schütte K, Zech CJ, Loewe C, van Delden O, Vandecaveye V, Verslype C, Gebauer B, Sengel C, Bargellini I, Iezzi R, Philipp A, Berg T, Klümpen HJ, Benckert J, Pech M, Gasbarrini A, Amthauer H, Bartenstein P, Sangro B, Malfertheiner P, Ricke J, Seidensticker M. Addition of Y-90 radioembolization increases tumor response and local disease control in hepatocellular carcinoma patients receiving sorafenib. Eur J Nucl Med Mol Imaging 2022; 49:4716-4726. [PMID: 35916920 PMCID: PMC9606085 DOI: 10.1007/s00259-022-05920-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/16/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE To compare the treatment response and progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients who received sorafenib treatment either alone or combined with radioembolization (RE). METHODS Follow-up images of the patients treated within a multicenter phase II trial (SORAMIC) were assessed by mRECIST. A total of 177 patients (73 combination arm [RE + sorafenib] and 104 sorafenib arm) were included in this post-hoc analysis. Response and progression characteristics were compared between treatment arms. Survival analyses were done to compare PFS and post-progression survival between treatment arms. Multivariate Cox regression analysis was used to compare survival with factors known to influence PFS in patients with HCC. RESULTS The combination arm had significantly higher objective response rate (61.6% vs. 29.8%, p < 0.001), complete response rate (13.7% vs. 3.8%, p = 0.022), and a trend for higher disease control rate (79.2% vs. 72.1%, p = 0.075). Progression was encountered in 116 (65.5%) patients and was more common in the sorafenib arm (75% vs. 52.0%, p = 0.001). PFS (median 8.9 vs. 5.4 months, p = 0.022) and hepatic PFS were significantly better in the combination arm (9.0 vs. 5.7 months, p = 0.014). Multivariate analysis confirmed the treatment arm as an independent predictor of PFS. CONCLUSION In advanced HCC patients receiving sorafenib, combination with RE has an additive anticancer effect on sorafenib treatment resulting in a higher and longer tumor response. However, the enhanced response did not translate into prolonged survival. Better patient selection and superselective treatment could improve outcomes after combination therapy.
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Affiliation(s)
- Osman Öcal
- Department of Radiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Kerstin Schütte
- Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken Marienhospital, Osnabrück, Germany
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Carl-Neuberg-Straße 1, 30625, Hannover, Deutschland
| | - Christoph J Zech
- Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Christian Loewe
- Section of Cardiovascular and Interventional Radiology, Department of Bioimaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Otto van Delden
- Department of Radiology and Nuclear Medicine, Academic University Medical Centers, Amsterdam, The Netherlands
| | | | - Chris Verslype
- Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium
| | - Bernhard Gebauer
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| | - Christian Sengel
- Radiology Department, Grenoble University Hospital, La Tronche, France
| | - Irene Bargellini
- Department of Vascular and Interventional Radiology, University Hospital of Pisa, Pisa, Italy
| | - Roberto Iezzi
- UOC di Radiologia, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alexander Philipp
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie, Sektion Hepatologie, Universitätsklinikum Leipzig, Leipzig, Germany
| | - Heinz J Klümpen
- Department of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Julia Benckert
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - Maciej Pech
- Departments of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany
| | - Antonio Gasbarrini
- Fondazione Policlinico Universitario Gemelli IRCCS, Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Holger Amthauer
- Corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Peter Bartenstein
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Bruno Sangro
- Liver Unit, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain
| | | | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany.
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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