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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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Kennedy AS, Brown DB, Fakih M, Jeyarajah R, Jones S, Liu D, Pinato DJ, Sangro B, Sharma NK, Sze DY, Van Cutsem E, Wasan HS. Multidisciplinary Delphi Consensus on Safety of Combining Transarterial Radioembolization with Yttrium-90 Microspheres with Systemic Anticancer Agents for the Treatment of Liver Malignancy. J Vasc Interv Radiol 2024; 35:1253-1267.e1. [PMID: 38885899 DOI: 10.1016/j.jvir.2024.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 05/31/2024] [Accepted: 06/09/2024] [Indexed: 06/20/2024] Open
Abstract
PURPOSE To provide guidance, via multidisciplinary consensus statements, on the safety interactions between systemic anticancer agents (such as radiosensitizing chemotherapy, immunotherapy, targeted therapy, and peptide receptor radionuclide therapy) and transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled microspheres in the treatment of primary and metastatic liver malignancies. MATERIALS AND METHODS A literature search identified 59 references that informed 26 statements on the safety of 90Y TARE combined with systemic therapies. Modified Delphi method was used to develop consensus on statements through online anonymous surveys of the 12 panel members representing the fields of interventional radiology, medical oncology, surgical oncology, hepatology, and pharmacy, focusing on hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), neuroendocrine tumors, metastatic breast cancer, and intrahepatic cholangiocarcinoma. RESULTS High-level evidence was limited. Level 1 data in patients with mCRC suggest that some radiosensitizing chemotherapies (eg, oxaliplatin) require temporary dose reduction when used concomitantly with 90Y TARE, and some targeted therapies (eg, vascular endothelial growth factor inhibitors and antiangiogenic tyrosine kinase inhibitors) should be avoided for at least 4 weeks before 90Y TARE. In patients with HCC, the feasibility of 90Y TARE and immunotherapy has been demonstrated with Level 4 evidence. Data are more limited for other primary and secondary liver malignancies, and consensus statements were driven by expert opinion (Level 5). CONCLUSIONS Given the absence of evidence-based guidelines on the safety of 90Y TARE in combination with systemic anticancer therapy, these consensus statements provide expert guidance on the potential risks when considering specific combinations.
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Affiliation(s)
- Andrew S Kennedy
- Radiation Oncology, Sarah Cannon Research Institute, Nashville, Tennessee.
| | - Daniel B Brown
- Interventional Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Marwan Fakih
- Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center Duarte, Duarte, California
| | | | - Suzanne Jones
- Drug Development, Sarah Cannon Research Institute, Nashville, Tennessee
| | - David Liu
- Faculty of Medicine, School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - David J Pinato
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra and CIBEREHD, Pamplona-Madrid, Spain
| | - Navesh K Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, New York, Pennsylvania
| | - Daniel Y Sze
- Interventional Radiology, Stanford University, Palo Alto, California
| | - Eric Van Cutsem
- Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium
| | - Harpreet S Wasan
- Department of Cancer Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
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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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Villalobos A, Pisanie JLD, Gandhi RT, Kokabi N. Yttrium-90 Radioembolization Dosimetry: Dose Considerations, Optimization, and Tips. Semin Intervent Radiol 2024; 41:63-78. [PMID: 38495257 PMCID: PMC10940044 DOI: 10.1055/s-0044-1779715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Affiliation(s)
- Alexander Villalobos
- Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Johannes L. du Pisanie
- Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Ripal T. Gandhi
- Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Nima Kokabi
- Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Chung S, Gogna A, Chandramohan S, Lo R, Irani FG, Venkatanarasimha N. Review of outcomes of combination therapy using yttrium 90 radioembolization and sorafenib/nivolumab for HCC with hepatic vein or IVC invasion. PROCEEDINGS OF SINGAPORE HEALTHCARE 2023. [DOI: 10.1177/20101058231154666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Background A systematic review of the outcomes of combination therapy using Yttrium 90 radioembolization (Y90) and sorafenib/nivolumab for patients with hepatocellular carcinoma (HCC), with hepatic vein (HV) or inferior vena cava (IVC) invasion. The aim of this study is to summarise the results of different studies that used the combination therapy for HCC patients with tumor thrombosis involving the HV or IVC. Method A literature search was performed using keywords in Medline and Google Scholar limited to publications from 2010 to 2021. There were 173 articles identified during the initial literature search. During abstract screening, 81 articles were excluded. Another 83 did not contain information on hepatic vein or IVC invasion. Therefore, 9 articles met the eligibility criteria and were included in the synthesis. Results In total, 37 patients with hepatic vein or IVC invasion were identified. There were 31 patients who were given sorafenib, 7 were given nivolumab and 1 was given both sorafenib and nivolumab. Among the 37 patients, 21 had hepatic vein invasion, 22 had IVC invasion and 6 had both HV and IVC invasion. The median OS was 20.55 months and median PFS was 8.18 months. For the results, 23 patients were evaluated via modified RECIST (mRECIST) criteria and 14 were evaluated via RECIST 1.1. Conclusion The combination of local and systemic therapies demonstrated potential results for increased response rates, OS and PFS benefits. Further studies are required to determine the long-term outcomes of the combination therapy for this group of patients.
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Affiliation(s)
| | - Apoorva Gogna
- Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore
| | | | - Richard Lo
- Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore
| | - Farah Gillan Irani
- Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore
| | - Nanda Venkatanarasimha
- Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore
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Patel MV, Davies H, Williams AO, Bromilow T, Baker H, Mealing S, Holmes H, Anderson N, Ahmed O. Transarterial therapies in patients with hepatocellular carcinoma eligible for transarterial embolization: a US cost-effectiveness analysis. J Med Econ 2023; 26:1061-1071. [PMID: 37632520 DOI: 10.1080/13696998.2023.2248840] [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: 05/24/2023] [Revised: 08/10/2023] [Accepted: 08/14/2023] [Indexed: 08/28/2023]
Abstract
OBJECTIVES To assess the cost-effectiveness of transarterial radioembolization (TARE) versus conventional transarterial chemoembolization (cTACE) and drug-eluting beads chemoembolization (DEE-TACE) for patients with unresectable early- to intermediate-stage hepatocellular carcinoma (HCC). DESIGN A cohort-based Markov model with a five-year time horizon was developed to evaluate the cost-effectiveness of the three embolization treatments. Upon entering the model, patients with HCC received either TARE or one of the two other embolization treatments. Patients remained in a "watch and wait" state for tumor downstaging that allowed them to move to health states such as liver transplant, resection, systemic therapies, or cure. Clinical input parameters were retrieved from the published literature, and where values could not be sourced, assumptions were made and validated by clinical experts. Health benefits were quantified using quality-adjusted life years (QALYs). Cost input parameters were obtained from various sources, including the Medicare Cost Report, IBM® Micromedex RED BOOK, and published literature. RESULTS At five years, TARE was found to be cost-saving (saving $15,779 per person compared to cTACE) and produced 0.33 more QALYs per person than cTACE. TARE cost $13,696 more but produced 0.33 more QALYs than DEE-TACE, with an incremental cost-effectiveness ratio of $41,474 per QALY gained at five years. After accounting for parameter uncertainty, the likelihood of TARE being cost-effective was at least 90% against all comparators at a cost-effectiveness threshold of $100,000 per QALY gained. CONCLUSIONS TARE produces more QALYs than cTACE and DEE-TACE, with a high probability of being cost-effective against both comparators.
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Affiliation(s)
- Mikin V Patel
- Section of Interventional Radiology, Department of Radiology, University of Chicago Medicine, Chicago, IL, USA
| | - Heather Davies
- York Health Economics Consortium, University of York, Heslington, UK
| | | | - Tom Bromilow
- York Health Economics Consortium, University of York, Heslington, UK
| | - Hannah Baker
- York Health Economics Consortium, University of York, Heslington, UK
| | - Stuart Mealing
- York Health Economics Consortium, University of York, Heslington, UK
| | - Hayden Holmes
- York Health Economics Consortium, University of York, Heslington, UK
| | | | - Osman Ahmed
- Section of Interventional Radiology, Department of Radiology, University of Chicago Medicine, Chicago, IL, USA
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Salem R, Padia SA, Lam M, Chiesa C, Haste P, Sangro B, Toskich B, Fowers K, Herman JM, Kappadath SC, Leung T, Sze DY, Kim E, Garin E. Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol Imaging 2023; 50:328-343. [PMID: 36114872 PMCID: PMC9816298 DOI: 10.1007/s00259-022-05956-w] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 08/23/2022] [Indexed: 01/11/2023]
Abstract
PURPOSE In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). METHODS The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. RESULTS Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. CONCLUSION Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.
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Affiliation(s)
- Riad Salem
- Department of Radiology, Northwestern Feinberg School of Medicine, 676 N. St. Clair, Suite 800, Chicago, IL, USA.
| | - Siddharth A Padia
- Department of Radiology, University of California-Los Angeles, Los Angeles, CA, USA
| | - Marnix Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Carlo Chiesa
- Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Paul Haste
- Department of Interventional Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain
| | - Beau Toskich
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA
| | - Kirk Fowers
- Boston Scientific Corporation, Marlborough, MA, USA
| | - Joseph M Herman
- Department of Radiation Medicine, Northwell Health, New Hyde Park, NY, USA
| | - S Cheenu Kappadath
- Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thomas Leung
- Comprehensive Oncology Centre, Hong Kong Sanatorium and Hospital, Hong Kong, Hong Kong
| | - Daniel Y Sze
- Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Edward Kim
- Department of Interventional Radiology, Mount Sinai, New York City, NY, USA
| | - Etienne Garin
- INSERM, INRA, Centre de Lutte Contre Le Cancer Eugène Marquis, Institut NUMECAN (Nutrition Metabolisms and Cancer), Univ Rennes, 35000, Rennes, France
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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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Goyal P, Salem R, Mouli SK. Role of interventional oncology in hepatocellular carcinoma: Future best practice beyond current guidelines. Br J Radiol 2022; 95:20220379. [PMID: 35867889 PMCID: PMC9815732 DOI: 10.1259/bjr.20220379] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Liver transplant remains the goal of curative treatment, but limited supply of organs decreases accessibility and prolongs waiting time to transplantation. Therefore, interventional oncology therapies have been used to treat the majority of HCC patients, including those awaiting transplant. The Barcelona Clinic Liver Cancer (BCLC) classification is the most widely used staging system in management of HCC that helps allocate treatments. Since its inception in 1999, it was updated for the fifth time in November 2021 and for the first time shaped by expert opinions outside the core BCLC group. The most recent version includes additional options for early-stage disease, substratifies intermediate disease into three groups, and lists alternates to Sorafenib that can double the expected survival of advanced-stage disease. The group also proposed a new BCLC staging schema for disease progression, and endorsed treatment stage migration (TSM) directly into the main staging and treatment algorithm. This article reviews the recent developments underlying the current BCLC guidelines and highlights ongoing research, particularly involving radioembolization, that will shape future best practice.
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Affiliation(s)
- Piyush Goyal
- Department of Radiology, Section of Interventional Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois, United States
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois, United States
| | - Samdeep K. Mouli
- Department of Radiology, Section of Interventional Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois, United States
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Sharma NK, Kappadath SC, Chuong M, Folkert M, Gibbs P, Jabbour SK, Jeyarajah DR, Kennedy A, Liu D, Meyer JE, Mikell J, Patel RS, Yang G, Mourtada F. The American Brachytherapy Society consensus statement for permanent implant brachytherapy using Yttrium-90 microsphere radioembolization for liver tumors. Brachytherapy 2022; 21:569-591. [PMID: 35599080 PMCID: PMC10868645 DOI: 10.1016/j.brachy.2022.04.004] [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: 12/20/2021] [Revised: 03/25/2022] [Accepted: 04/14/2022] [Indexed: 11/02/2022]
Abstract
PURPOSE To develop a multidisciplinary consensus for high quality multidisciplinary implementation of brachytherapy using Yttrium-90 (90Y) microspheres transarterial radioembolization (90Y TARE) for primary and metastatic cancers in the liver. METHODS AND MATERIALS Members of the American Brachytherapy Society (ABS) and colleagues with multidisciplinary expertise in liver tumor therapy formulated guidelines for 90Y TARE for unresectable primary liver malignancies and unresectable metastatic cancer to the liver. The consensus is provided on the most recent literature and clinical experience. RESULTS The ABS strongly recommends the use of 90Y microsphere brachytherapy for the definitive/palliative treatment of unresectable liver cancer when recommended by the multidisciplinary team. A quality management program must be implemented at the start of 90Y TARE program development and follow-up data should be tracked for efficacy and toxicity. Patient-specific dosimetry optimized for treatment intent is recommended when conducting 90Y TARE. Implementation in patients on systemic therapy should account for factors that may enhance treatment related toxicity without delaying treatment inappropriately. Further management and salvage therapy options including retreatment with 90Y TARE should be carefully considered. CONCLUSIONS ABS consensus for implementing a safe 90Y TARE program for liver cancer in the multidisciplinary setting is presented. It builds on previous guidelines to include recommendations for appropriate implementation based on current literature and practices in experienced centers. Practitioners and cooperative groups are encouraged to use this document as a guide to formulate their clinical practices and to adopt the most recent dose reporting policies that are critical for a unified outcome analysis of future effectiveness studies.
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Affiliation(s)
- Navesh K Sharma
- Department of Radiation Oncology, Penn State Hershey School of Medicine, Hershey, PA
| | - S Cheenu Kappadath
- Department of Imaging Physics, UT MD Anderson Cancer Center, Houston, TX
| | - Michael Chuong
- Department of Radiation Oncology, Miami Cancer Institute, Miami, FL
| | - Michael Folkert
- Northwell Health Cancer Institute, Radiation Medicine at the Center for Advanced Medicine, New Hyde Park, NY
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
| | - Salma K Jabbour
- Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ
| | | | | | - David Liu
- Vancouver General Hospital, Vancouver, British Columbia, Canada
| | | | | | - Rahul S Patel
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Gary Yang
- Loma Linda University, Loma Linda, CA
| | - Firas Mourtada
- Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE; Department of Radiation Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA.
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11
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Facciorusso A, Paolillo R, Tartaglia N, Ramai D, Mohan BP, Cotsoglou C, Chandan S, Ambrosi A, Bargellini I, Renzulli M, Sacco R. Efficacy of combined transarterial radioembolization and sorafenib in the treatment of hepatocarcinoma: A meta-analysis. Dig Liver Dis 2022; 54:316-323. [PMID: 34193367 DOI: 10.1016/j.dld.2021.06.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/04/2021] [Accepted: 06/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Adjuvant sorafenib may further enhance the efficacy of transarterial radioembolization for the treatment of hepatocellular carcinoma. AIMS To evaluate the efficacy and safety of radioembolization plus sorafenib in hepatocellular carcinoma patients. METHODS With a literature search through October 2020, we identified 9 studies (632 patients). Primary outcome was overall survival. Results were expressed as pooled median, odds ratio, or hazard ratio and 95% confidence intervals. RESULTS Pooled overall survival after radioembolization plus sorafenib was 10.79 months (95% confidence interval 9.19-12.39) and it was longer in Barcelona Clinic Liver Cancer (BCLC) B (14.47 months, 9.07-19.86) as compared to BCLC C patients (10.22 months, 7.53-12.9). No difference between combined therapy versus radioembolization alone was observed in terms of overall survival (hazard ratio 1.07, 0.89-1.30). Pooled median progression-free survival was 6.32 months (5.68-6.98), with 1-year progression-free survival pooled rate of 38.5% (12.7%-44.2%). No difference in progression-free survival (hazard ratio 0.94, 0.79-1.12) between the two treatments was observed. Pooled rate of severe adverse events was 48.9% (26.7%-71.2%), again with no difference between the two treatment regimens (odds ratio 1.52, 0.15-15.02). CONCLUSIONS The association of sorafenib does not seem to prolong survival nor delay disease progression in patients treated with radioembolization.
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Affiliation(s)
- Antonio Facciorusso
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy.
| | - Rosa Paolillo
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
| | - Nicola Tartaglia
- Surgical Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
| | - Daryl Ramai
- Gastroenterology and Hepatology, Brooklyn Hospital Center, Brooklyn, NY, United States
| | - Babu P Mohan
- Gastroenterology & Hepatology, University of Utah Health, Salt Lake City, UT, United States
| | | | - Saurabh Chandan
- Division of Gastroenterology, CHI Creighton University Medical Center, Omaha, NE, United States
| | - Antonio Ambrosi
- Surgical Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
| | - Irene Bargellini
- Department of Interventional Radiology, Pisa University Hospital, Pisa 56124, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy
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12
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Yttrium-90 radioembolization for unresectable hepatocellular carcinoma: predictive modeling strategies to anticipate tumor response and improve patient selection. Eur Radiol 2022; 32:4687-4698. [PMID: 35230518 PMCID: PMC9213379 DOI: 10.1007/s00330-022-08585-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/12/2022] [Accepted: 01/18/2022] [Indexed: 12/24/2022]
Abstract
Objectives This study aims to better characterize potential responders of Y-90-radioembolization at baseline through analysis of clinical variables and contrast enhanced (CE) MRI tumor volumetry in order to adjust therapeutic regimens early on and to improve treatment outcomes. Methods Fifty-eight HCC patients who underwent Y-90-radioembolization at our center between 10/2008 and 02/2017 were retrospectively included. Pre- and post-treatment target lesion volumes were measured as total tumor volume (TTV) and enhancing tumor volume (ETV). Survival analysis was performed with Cox regression models to evaluate 65% ETV reduction as surrogate endpoint for treatment efficacy. Univariable and multivariable logistic regression analyses were used to evaluate the combination of baseline clinical variables and tumor volumetry as predictors of ≥ 65% ETV reduction. Results Mean patients’ age was 66 (SD 8.7) years, and 12 were female (21%). Sixty-seven percent of patients suffered from liver cirrhosis. Median survival was 11 months. A threshold of ≥ 65% in ETV reduction allowed for a significant (p = 0.04) separation of the survival curves with a median survival of 11 months in non-responders and 17 months in responders. Administered activity per tumor volume did predict neither survival nor ETV reduction. A baseline ETV/TTV ratio greater than 50% was the most important predictor of arterial devascularization (odds ratio 6.3) in a statistically significant (p = 0.001) multivariable logistic regression model. The effect size was strong with a Cohen’s f of 0.89. Conclusion We present a novel approach to identify promising candidates for Y-90 radioembolization at pre-treatment baseline MRI using tumor volumetry and clinical baseline variables. Key Points • A decrease of 65% enhancing tumor volume (ETV) on follow-up imaging 2–3 months after Y-90 radioembolization of HCC enables the early prediction of significantly improved median overall survival (11 months vs. 17 months, p = 0.04). • Said decrease in vascularization is predictable at baseline: an ETV greater than 50% is the most important variable in a multivariable logistic regression model that predicts responders at a high level of significance (p = 0.001) with an area under the curve of 87%. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-022-08585-x.
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13
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Teyateeti A, Mahvash A, Long J, Abdelsalam M, Avritscher R, Kaseb A, Odisio B, Ravizzini G, Surasi D, Teyateeti A, Macapinlac H, Kappadath SC. Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib. World J Gastroenterol 2021; 27:8166-8181. [PMID: 35068861 PMCID: PMC8704272 DOI: 10.3748/wjg.v27.i47.8166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 07/28/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Impressive survival outcome of our previous study in unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass microspheres transarterial radioembolization (TARE) with/without sorafenib according to individuals' disease burden, i.e., intrahepatic tumor load (IHT) and adverse disease features (ADFs) might partly be confounded by other treatments and underlying hepatic function. Therefore, a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden. AIM To assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients. METHODS This retrospective study was conducted in successful TARE procedures with available pre- and post-treatment imaging studies (n = 169). Three treatment subgroups were (1) TARE only (TARE_alone) for IHT ≤ 50% without ADFs, i.e., macrovascular invasion, extrahepatic disease (EHD) and infiltrative/ill-defined HCC (n = 63); (2) TARE with sorafenib (TARE_sorafenib) for IHT > 50% and/or presence of ADFs (n = 81); and (3) TARE only for patients who could not receive sorafenib due to contraindication or intolerance (TARE_no_sorafenib) (n = 25). Objective response rate (ORR; consisted of complete response (CR) and partial response (PR)), disease control rate (DCR; consisted of CR, PR and stable disease) and failure patterns of treated, intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors. Time to progression (TTP) was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method. Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups, TARE_alone and TARE_sorafenib. RESULTS The median radiologic follow-up time was 4.4 mo (range 0.5-48.8). In treated area, ORR was highest in TARE_sorafenib (53.1%), followed by TARE_alone (41.3%) and TARE_no_sorafenib (16%). In intrahepatic area, DCR remained highest in TARE_sorafenib (84%), followed by TARE_alone (79.4%) and TARE_no_sorafenib (44%). The overall DCR was highest in TARE_alone (79.4%), followed by TARE_sorafenib (71.6%) and TARE_no_sorafenib (40%). Dominant failure patterns were intrahepatic for both TARE_alone (44.5%) and TARE_sorafenib (38.4%). Extrahepatic progression was more common in TARE_sorafenib (32%) and TARE_no_sorafenib (40%) than in TARE_alone (12.7%). TTP was longest in TARE_alone (8.6 mo; 95%CI: 3.4-13.8), followed by TARE_sorafenib (5.1 mo; 95%CI: 4.0-6.2) and TARE_no_sorafenib (2.7 mo; 95%CI: 2.2-3.1). Pre-existing EHD (HR: 0.37, 95%CI: 0.24-0.56, P < 0.001) was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone. CONCLUSION TARE with/without sorafenib according to individuals' disease burden provided DCR approximately 70% with intrahepatic progression as dominant failure pattern. Extrahepatic progression was more common in procedures with initially high disease burden.
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Affiliation(s)
- Ajalaya Teyateeti
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Armeen Mahvash
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - James Long
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Mohamed Abdelsalam
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Rony Avritscher
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Bruno Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Gregory Ravizzini
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Devaki Surasi
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Achiraya Teyateeti
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Homer Macapinlac
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Srinivas Cheenu Kappadath
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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Advances in locoregional therapy for hepatocellular carcinoma combined with immunotherapy and targeted therapy. J Interv Med 2021; 4:105-113. [PMID: 34805958 PMCID: PMC8562181 DOI: 10.1016/j.jimed.2021.05.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 05/11/2021] [Accepted: 05/13/2021] [Indexed: 12/11/2022] Open
Abstract
Locoregional therapies (LRTs) of hepatocellular carcinoma (HCC) represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC. Among these, TACE is used throughout the stage Ib to IIIb of HCC treatment. In recent years, immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research. At the same time, targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC, and their clinical application has been quite mature. HCC is the sixth most common malignant tumor in the world. When it comes to its treatment, different therapies have different indications, and their individual efficacies are not satisfactory, which makes the exploration of the use of combination therapy in HCC treatment become a new trend. In this paper, the status of the three therapies and the progress of their combined application are briefly reviewed.
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15
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Kaseb AO, Kappadath SC, Lee SS, Raghav KP, Mohamed YI, Xiao L, Morris JS, Ohaji C, Avritscher R, Odisio BC, Kuban J, Abdelsalam ME, Chasen B, Elsayes KM, Elbanan M, Wolff RA, Yao JC, Mahvash A. A Prospective Phase II Study of Safety and Efficacy of Sorafenib Followed by 90Y Glass Microspheres for Patients with Advanced or Metastatic Hepatocellular Carcinoma. J Hepatocell Carcinoma 2021; 8:1129-1145. [PMID: 34527608 PMCID: PMC8437411 DOI: 10.2147/jhc.s318865] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 08/13/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose The most common cause of death in advanced/metastatic hepatocellular carcinoma (HCC) is liver failure due to tumor progression. While retrospective studies and meta-analyses of systemic therapy combined with liver-directed therapy have been performed, prospective studies of safety/efficacy of antiangiogenesis followed by intra-arterial therapies are lacking. We tested our hypothesis that sorafenib followed by yttrium 90 glass microspheres (90Y GMs) is safe and that survival outcomes may improve by controlling hepatic tumors. Methods We enrolled 38 Child–Pugh A patients with advanced/metastatic HCC. In sum, 34 received sorafenib, followed after 4 weeks by 90Y GMs. Analysis of safety and survival outcomes was performed to assess adverse events, median progression-free survival, and overall survival. Results A total of 34 patients were evaluable: 14 (41.2%) with chronic hepatitis, nine (26.5%) with vascular invasion, and eleven (32.4%) with extrahepatic diseases. Safety analysis revealed that the combination therapy was well tolerated. Grade III–IV adverse events comprised fatigue (n=3), diarrhea (n=2), nausea (n=1), vomiting (n=2), hypertension (n=4), thrombocytopenia (n=1), hyperbilirubinemia (n=1), proteinuria (n=1), hyponatremia (n=1), and elevated alanine or aspartate aminotransferase (n=5). Median progression-free and overall survival were 10.4 months (95% CI 5.8–14.4) and 13.2 months (95% CI 7.9–18.9), respectively. Twelve patients (35.3%) achieved partial responses and 16 (47.0%) stable disease. Median duration of sorafenib was 20 (3–90) weeks, and average dose was 622 (466–800) mg daily. Dosimetry showed similar mean doses between planned and delivered calculations to normal liver and tumor:normal liver uptake ratio, with no significant correlation with adverse events at 3 and 6 months post-90Y treatment. Conclusion This is the first prospective study to evaluate sorafenib followed by 90Y in patients with advanced HCC. The study validated our hypothesis of safety with encouraging efficacy signals of the sequencing treatment, and provides proof of concept for future combination modalities for patients with advanced or metastatic HCC. Clinical Trial Registration Number NCT01900002.
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Affiliation(s)
- Ahmed Omar Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - S Cheenu Kappadath
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sunyoung S Lee
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kanwal Pratap Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yehia I Mohamed
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lianchun Xiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey S Morris
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Chimela Ohaji
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rony Avritscher
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruno C Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Joshua Kuban
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mohamed E Abdelsalam
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Beth Chasen
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Khaled M Elsayes
- Department of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mohamed Elbanan
- Department of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - James C Yao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Armeen Mahvash
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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16
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De la Garza-Ramos C, Overfield CJ, Montazeri SA, Liou H, Paz-Fumagalli R, Frey GT, McKinney JM, Ritchie CA, Devcic Z, Lewis AR, Harnois DM, Patel T, Toskich BB. Biochemical Safety of Ablative Yttrium-90 Radioembolization for Hepatocellular Carcinoma as a Function of Percent Liver Treated. J Hepatocell Carcinoma 2021; 8:861-870. [PMID: 34368021 PMCID: PMC8335548 DOI: 10.2147/jhc.s319215] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 07/06/2021] [Indexed: 12/20/2022] Open
Abstract
Purpose Transarterial radioembolization can serve as an ablative therapy for early-stage hepatocellular carcinoma (HCC). Given the volumetric variability of liver segments, this study aimed to characterize the safety of ablative radioembolization by determining percent liver treated (%LT) thresholds associated with biochemical toxicity. Patients and Methods Patients with HCC receiving a single ablative radioembolization treatment using glass microspheres from 2017 through 2020 were reviewed. %LT was calculated as treatment angiosome volume divided by whole liver volume. Biochemical toxicities were defined as increases in Albumin-Bilirubin (ALBI) grade or Child-Pugh (CP) class compared to baseline and albumin or bilirubin adverse events (AEs) per the Common Terminology Criteria for Adverse Events. Receiver operating characteristic curves and multivariate logistic regression analyses were performed to assess the impact of %LT on toxicities. Results Of 141 patients analyzed, 53% (n=75) were ALBI 1, 45% (n=64) ALBI 2, 79% (n=111) CP-A, and 21% (n=30) CP-B. A %LT ≥14.5% was associated with grade/class increases in ALBI 2 (p≤0.01) and CP-B patients (p=0.026). In multivariate analysis, a %LT ≥14.5% was an independent predictor of increases in the ALBI 2 and CP-B groups (p<0.01). No significant %LT threshold was found for ALBI 1 and CP-A patients. No grade 3/4 albumin or bilirubin AEs were reported, while grade 2 AEs were related to an initial whole liver volume <1.3 L (p≤0.01). Conclusion Patients with ALBI 2 and CP-B liver function are less likely to have an increase in their respective grade/class when treating <14.5% of the liver using glass microspheres. ALBI 1 and CP-A patients showed no definitive %LT threshold for biochemical toxicity within the range of this study.
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Affiliation(s)
| | - Cameron J Overfield
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - S Ali Montazeri
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Harris Liou
- Alix School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | | | - Gregory T Frey
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - J Mark McKinney
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Charles A Ritchie
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Zlatko Devcic
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Andrew R Lewis
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Denise M Harnois
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Tushar Patel
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Beau B Toskich
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
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