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Mortezaei A, Taghlabi KM, Al-Saidi N, Amasa S, Whitehead RE, Hoang A, Yaeger K, Faraji AH, Kadirvel R, Ghozy S. Advanced targeted microsphere embolization for arteriovenous malformations: state-of-the-art and future directions. Neuroradiology 2025; 67:1009-1022. [PMID: 40088307 DOI: 10.1007/s00234-025-03584-3] [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: 12/06/2024] [Accepted: 03/04/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Arteriovenous malformations (AVMs) present a significant therapeutic challenge, as current treatment modalities frequently fail to achieve complete and rapid obliteration and are associated with substantial morbidity in both the short and long term. This underscores the critical need for innovative therapeutic strategies that enable efficient AVM obliteration while minimizing patient risk. The current review aims to comprehensively assess the role of ATME in AVM management, examining its clinical efficacy, associated risks and benefits, and the economic and ethical implications to provide valuable foundation for future studies and guiding development in treatment strategies for AVMs. RESULTS Advanced targeted microsphere embolization (ATME) has emerged as a promising therapeutic option, initially developed for the localized treatment of AVMs and unresectable tumors, including liver cancer. By providing targeted delivery, ATME offers potential advantages over conventional approaches in achieving effective local control. CONCLUSIONS ATME are safe and effective for vascular disease and cancer. Although evidence for microspheres in AVMs is scarce, results are promising. Future research could refine eligibility criteria, evaluate treatment techniques, and optimize ATME.
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Affiliation(s)
- Ali Mortezaei
- Gonabad University of Medical Sciences, Gonabad, Iran
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
| | - Khaled M Taghlabi
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA.
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA.
| | - Nadir Al-Saidi
- College of Medicine, Central Michigan University, Mt Pleasant, MI, USA.
| | - Saketh Amasa
- Department of Neurosurgery, The University of Texas Medical Branch, Galveston, TX, USA
| | - Rachael E Whitehead
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Alex Hoang
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Kurt Yaeger
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Amir H Faraji
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ramanathan Kadirvel
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Sherief Ghozy
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
- Department of Radiology, Mayo Clinic, Rochester, MN, USA.
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Braat MN, Braat AJ, Lam MG. Toxicity comparison of yttrium-90 resin and glass microspheres radioembolization. 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; 68:133-142. [PMID: 35762664 DOI: 10.23736/s1824-4785.22.03452-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
BACKGROUND To investigate the clinical, hematological and biochemical toxicity differences between glass and resin yttrium-90 (90Y)-microspheres radioembolization treatment of primary and metastatic liver disease. METHODS Between May 2014 and November 2016 all consecutive glass and resin 90Y microspheres radioembolization treatments were retrospectively analyzed. Biochemical, hematological and clinical data were collected at treatment day, two weeks, one month and three months follow-up. Post-treatment 90Y PET/CTs were assessed for the absorbed doses in non-tumorous liver volume (DNTLV) and tumor volume (DTV). Biochemical, hematological and clinical toxicity were compared between glass and resin using chi square tests and repeated ANOVA measures. Biochemical and clinical toxicity was correlated with DNTLV,total by means of Pearson correlation and independent t-tests. RESULTS A total of 85 patients were included (N.=44 glass, N.=41 resin). Clinical toxicity the day after treatment (i.e. abdominal pain [P=0.000], nausea [P=0.000] and vomiting [P=0.003]) was more prevalent for resin. Biochemical and hematological toxicities were similar for both microspheres. The DNTLV,total was significantly higher in patients with REILD grade ≥3 in the resin group (43.5 versus 33.3 Gy [P=0.050]). A similar non-significant trend was seen in the glass group: 95.0 versus 69.0 Gy [P=0.144]. CONCLUSIONS The clinical, hematological and biochemical toxicity of radioembolization treatment with glass and resin is comparable, however, post-embolization syndrome related complaints are more common for resin.
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Affiliation(s)
- Manon N Braat
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands -
| | - Arthur J Braat
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Marnix G Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
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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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Sogbe M, Rodríguez-Fraile M, de la Cuesta AM, Rotellar F, Iñarrairaegui M. Partial Radiation Nephrectomy Using 90 Y Resin Microspheres: A Treatment Option for Renal Tumors With Malignant Characteristics in Patients Not Candidates for Surgery. Clin Nucl Med 2023; 48:960-962. [PMID: 37756468 DOI: 10.1097/rlu.0000000000004792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2023]
Abstract
ABSTRACT Contrast-enhancing renal masses are likely to be malignant in over 90% of cases due to the high diagnostic accuracy of abdominal imaging. In this situation, tumor biopsy is unnecessary and should be managed as a renal cell carcinoma. Resection remains the only potentially curative treatment. However, as in the case herein presented, comorbidities can prevent surgical resection. Radioembolization with 90 Y microspheres is an intra-arterial procedure capable of delivering high doses of radiation to tumors. The present case demonstrates the concept of partial radiation nephrectomy in treating renal tumors with malignant characteristics in patients not amenable to surgery.
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Affiliation(s)
| | | | | | - Fernando Rotellar
- HPB and Liver Transplant Unit, Department of General Surgery, Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain
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Pollock RF, Shergill S, Carion PL, von Oppen N, Agirrezabal I, Brennan VK. Advances in Delivery of Selective Internal Radiation Therapy (SIRT): Economic and Logistical Effects of Same-Stay Work-Up and Procedure in the Treatment of Unresectable Liver Tumors in England. Adv Ther 2023; 40:294-309. [PMID: 36318388 PMCID: PMC9628427 DOI: 10.1007/s12325-022-02323-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 09/14/2022] [Indexed: 11/07/2022]
Abstract
INTRODUCTION Selective internal radiation therapy (SIRT) is a targeted method of treatment for unresectable liver tumors in which radiation therapy is directly delivered to the tumor(s) via the hepatic vasculature. Successful outcomes with SIRT are dependent on the specific vasculature of the liver and tumor, and the patient therefore needs to attend a "work-up" to map the hepatic vasculature prior to the SIRT procedure. Recent advances in SIRT delivery have enabled same-day or same-stay work-up and procedure, requiring only one hospital visit rather than two. We aimed to evaluate the economic, travel time, and transport-related environmental impact of a new brachytherapy device delivery program, the order-map-treat (OMT) program, in patients with unresectable hepatocellular carcinoma (HCC) in England. METHODS A healthcare resource group (HRG)-based analysis of costs from a national payer (Department of Health and Social Care, DHSC) perspective was conducted assuming that, with OMT, patients would have to attend hospital only once for both the SIRT work-up and procedure versus twice without OMT. Patient travel time and CO2 emissions were then estimated by identifying the SIRT center closest to the centroid of each clinical commissioning group (CCG) and calculating straight-line distances with a "detour index" to capture the effect of indirect routes via road or rail. RESULTS It was estimated that 856 patients per annum would be eligible for SIRT treatment for unresectable HCC in England. OMT would be anticipated to save GBP 2842 per patient versus performing SIRT without OMT. Furthermore, across all patients with HCC eligible for SIRT in England, OMT would avoid 74,500 km of travel, 2299 h of travel time, and 13.9 metric tons of patient transport-related CO2 emissions annually. CONCLUSION OMT reduces the number of hospital visits required for SIRT by 50%, resulting in financial savings from the DHSC perspective, time savings from the patient perspective, and reduced CO2 emissions arising from patient transport.
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Affiliation(s)
- Richard F. Pollock
- Covalence Research Ltd, Rivers Lodge, West Common, Harpenden, AL5 2JD UK
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Miller SR, Jernigan SR, Abraham RJ, Buckner GD. Comparison of Bolus Versus Dual-Syringe Administration Systems on Glass Yttrium-90 Microsphere Deposition in an In Vitro Microvascular Hepatic Tumor Model. J Vasc Interv Radiol 2023; 34:11-20. [PMID: 36108898 DOI: 10.1016/j.jvir.2022.07.032] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 07/12/2022] [Accepted: 07/17/2022] [Indexed: 01/04/2023] Open
Abstract
PURPOSE To utilize an in vitro microvascular hepatic tumor model to compare the deposition characteristics of glass yttrium-90 microspheres using the dual-syringe (DS) and traditional bolus administration methods. MATERIALS AND METHODS The microvascular tumor model represented a 3.5-cm tumor in a 1,400-cm3 liver with a total hepatic flow of 160 mL/min and was dynamically perfused. A microcatheter was placed in a 2-mm artery feeding the tumor model and 2 additional nontarget arteries. Glass microspheres with a diameter of 20-30 μm were administered using 2 methods: (a) DS delivery at a concentration of 50 mg/mL in either a single, continuous 2-mL infusion or two 1-mL infusions and (b) bolus delivery (BD) of 100 mg of microspheres in a single 3-mL infusion. RESULTS Overall, the degree of on-target deposition of the microspheres was 85% ± 11%, with no significant differences between the administration methods. Although the distal penetration into the tumor arterioles was approximately 15 mm (from the second microvascular bifurcation of the tumor model) for all the cases, the distal peak particle counts were significantly higher for the DS delivery case (approximately 5 × 105 microspheres achieving distal deposition vs 2 × 105 for the BD case). This resulted in significantly higher deposition uniformity within the tumor model (90% for the DS delivery case vs 80% for the BD case, α = 0.05). CONCLUSIONS The use of this new in vitro microvascular hepatic tumor model demonstrated that the administration method can affect the deposition of yttrium-90 microspheres within a tumor, with greater distal deposition and more uniform tumor coverage when the microspheres are delivered at consistent concentrations using a DS delivery device. The BD administration method was associated with less favorable deposition characteristics of the microspheres.
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Affiliation(s)
- Samuel R Miller
- Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina
| | - Shaphan R Jernigan
- Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina
| | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada; ABK Biomedical Inc., Halifax, Nova Scotia, Canada.
| | - Gregory D Buckner
- Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina
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Radioembolization-Induced Changes in Hepatic [ 18F]FDG Metabolism in Non-Tumorous Liver Parenchyma. Diagnostics (Basel) 2022; 12:diagnostics12102518. [PMID: 36292207 PMCID: PMC9600277 DOI: 10.3390/diagnostics12102518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/07/2022] [Accepted: 10/13/2022] [Indexed: 11/17/2022] Open
Abstract
Background: [18F]FDG-PET/CT is increasingly used for response assessments after oncologic treatment. The known response criteria for [18F]FDG-PET/CT use healthy liver parenchyma as the reference standard. However, the [18F]FDG liver metabolism results may change as a result of the given therapy. The aim of this study was to assess changes in [18F]FDG liver metabolism after hepatic 90Y resin radioembolization. Methods: [18F]FDG-PET/CT scans prior to radioembolization and one and three months after radioembolization (consistent with the PERCIST comparability criteria), as well as 90Y-PET/CT scans, were analyzed using 3 cm VOIs. The FDG activity concentration and absorbed dose were measured. A linear mixed-effects logistic regression model and logistic mixed-effects model were used to assess the correlation between the FDG-activity concentration, absorbed dose, and biochemical changes. Results: The median SULVOI,liver at baseline was 1.8 (range = 1.2−2.8). The mean change in SULVOI,liver per month with an increase in time was 0.05 (95%CI 0.02−0.09) at p < 0.001. The median absorbed dose per VOI was 31.3 Gy (range = 0.1−82.3 Gy). The mean percent change in ΔSULVOI,liver for every Gy increase in the absorbed dose was −0.04 (95%CI −0.22−0.14) at p = 0.67. The SULblood and SULspleen results showed no increase. Conclusions: The [18F]FDG metabolism in the normal liver parenchyma is significantly but mildly increased after radioembolization, which can interfere with its use as a threshold for therapy response.
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Páramo M, Santamaría E, Idoate MA, Rodríguez-Fraile M, Benito A, Collantes M, Quincoces G, Peñuelas I, Berasain C, Argemi J, Quiroga J, Sangro B, Bilbao JI, Iñarrairaegui M. A new animal model of atrophy-hypertrophy complex and liver damage following Yttrium-90 lobar selective internal radiation therapy in rabbits. Sci Rep 2022; 12:1777. [PMID: 35110610 PMCID: PMC8810801 DOI: 10.1038/s41598-022-05672-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 01/17/2022] [Indexed: 11/30/2022] Open
Abstract
Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy–hypertrophy complex after SIRT. Three groups of 5–8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with different activities (0.3, 0.6 and 1.2 GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2 GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6 GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced significant toxicity. Cranial SIRT with 0.3 GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2 GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3 GBq groups developed moderate damage with inflammation and portal fibrosis at 15 days, partially recovering at 30 days. There was no difference in the expression of hepatocyte function and differentiation genes between 0.3 GBq and control groups. Cranial SIRT with 0.3 GBq of 90Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy–hypertrophy complex and liver damage without toxicity.
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Affiliation(s)
- María Páramo
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain
| | - Eva Santamaría
- Hepatology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Miguel A Idoate
- Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain
| | - Macarena Rodríguez-Fraile
- Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain
| | - Alberto Benito
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain
| | - Maria Collantes
- Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.,Radiopharmacy, Radionanopharmacology and Translational Molecular Imaging Research Group, Clínica Universidad de Navarra, Pamplona, Spain
| | - Gemma Quincoces
- Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.,Radiopharmacy, Radionanopharmacology and Translational Molecular Imaging Research Group, Clínica Universidad de Navarra, Pamplona, Spain.,Radiopharmacy Unit, Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain
| | - Iván Peñuelas
- Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.,Radiopharmacy, Radionanopharmacology and Translational Molecular Imaging Research Group, Clínica Universidad de Navarra, Pamplona, Spain.,Radiopharmacy Unit, Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain
| | - Carmen Berasain
- Hepatology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain
| | - Josepmaria Argemi
- Hepatology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain
| | - Jorge Quiroga
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.,Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain
| | - Bruno Sangro
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain.,Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain
| | - José I Bilbao
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain
| | - Mercedes Iñarrairaegui
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain. .,Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain. .,Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain.
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d’Abadie P, Hesse M, Louppe A, Lhommel R, Walrand S, Jamar F. Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects. Molecules 2021; 26:3966. [PMID: 34209590 PMCID: PMC8271370 DOI: 10.3390/molecules26133966] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 01/31/2023] Open
Abstract
Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, 90Y and 166Ho. The relationship between the microspheres' properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.
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Affiliation(s)
- Philippe d’Abadie
- Department of Nuclear Medicine, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, 1200 Brussels, Belgium; (M.H.); (A.L.); (R.L.); (S.W.); (F.J.)
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10
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Determination of Tumor Dose Response Thresholds in Patients with Chemorefractory Intrahepatic Cholangiocarcinoma Treated with Resin and Glass-based Y90 Radioembolization. Cardiovasc Intervent Radiol 2021; 44:1194-1203. [PMID: 33890170 DOI: 10.1007/s00270-021-02834-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Accepted: 03/30/2021] [Indexed: 01/03/2023]
Abstract
PURPOSE To compare the efficacies of glass and resin-based Yttrium-90 microspheres by comparing absorbed tumor dose (TD) with both tumor response (TR) and overall survival (OS) in patients with chemorefractory intrahepatic cholangiocarcinoma (ICC). METHODS Post-Y90 treatment bremsstrahlung SPECT/CT of 38 consecutive patients receiving 45 treatments (21 resin microspheres, 24 glass microspheres) were analyzed retrospectively. MIM software v6.9.4 (MIM Software Inc, Cleveland, OH) was used to calculate targeted tumors' dose volume histogram. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response 3 months post-treatment. Kaplan Meier estimation was used for survival analysis. T-test was used to compare the devices on various dosimetric parameters. RESULTS Thresholds for TD to predict TR with ≥ 80% specificity were as follows: mean TD (Resin: 78.9 Gy; Glass: 254.7 Gy), maximum TD (Resin: 162.9 Gy; Glass: 591 Gy), minimum TD (Resin: 53.7 Gy; Glass: 149.1 Gy). Microsphere type had no effect on survival from first Y90 (Resin: 11.2 mo; Glass 10.9 mo [p = 0.548]). In patients receiving resin microspheres, mean TD ≥ 75 Gy or maximum TD ≥ 150 Gy was associated with median OS of 20.2 mo compared to 6.5 mo for those receiving less (p = 0.001, 0.002, respectively). For patients treated with glass microspheres, those receiving a mean TD ≥ 150 Gy had a median OS of 14.6 mo vs. 2.6 mo for those receiving less (p = 0.031). CONCLUSION TD thresholds predictive of TR and OS differ significantly between glass and resin microspheres. However, microsphere type has no impact on survival in patients with chemorefractory ICC. LEVEL OF EVIDENCE Level 3, Retrospective Study.
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Grisanti F, Prieto E, Bastidas JF, Sancho L, Rodrigo P, Beorlegui C, Iñarrairaegui M, Bilbao JI, Sangro B, Rodríguez-Fraile M. 3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization. Eur J Nucl Med Mol Imaging 2021; 48:3048-3057. [PMID: 33674893 DOI: 10.1007/s00259-021-05272-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 02/17/2021] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. MATERIALS AND METHODS Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2-5 (T2), and 6-12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. RESULTS Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). CONCLUSION NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.
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Affiliation(s)
- Fabiana Grisanti
- Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
| | - Elena Prieto
- Department of Medical Physics, Clínica Universidad de Navarra, Pamplona, Spain
| | | | - Lidia Sancho
- Department of Nuclear Medicine, Clínica Universidad de Navarra, Madrid, Spain
| | - Pablo Rodrigo
- Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain
| | | | | | | | - Bruno Sangro
- Liver Unit, Clínica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain
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12
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"Primum Non Nocere" in Interventional Oncology for Liver Cancer: How to Reduce the Risk for Complications? Life (Basel) 2020; 10:life10090180. [PMID: 32899925 PMCID: PMC7555139 DOI: 10.3390/life10090180] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/28/2020] [Accepted: 09/02/2020] [Indexed: 12/12/2022] Open
Abstract
Interventional oncology represents a relatively new clinical discipline based upon minimally invasive therapies applicable to almost every human organ and disease. Over the last several decades, rapidly evolving research developments have introduced a newer generation of treatment devices, reagents, and image-guidance systems to expand the armamentarium of interventional oncology across a wide spectrum of disease sites, offering potential cure, control, or palliative care for many types of cancer patients. Due to the widespread use of locoregional procedures, a comprehensive review of the methodologic and technical considerations to optimize patient selection with the aim of performing a safe procedure is mandatory. This article summarizes the expert discussion and report from the Mediterranean Interventional Oncology Live Congress (MIOLive 2020) held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions as a means for providing guidance on prudent ways to reduce complications. The aim of the paper is to provide an updated guiding tool not only to residents and fellows but also to colleagues approaching locoregional treatments.
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Stechele M, Wittgenstein H, Stolzenburg N, Schnorr J, Neumann J, Schmidt C, Günther RW, Streitparth F. Novel MR-Visible, Biodegradable Microspheres for Transcatheter Arterial Embolization: Experimental Study in a Rabbit Renal Model. Cardiovasc Intervent Radiol 2020; 43:1515-1527. [PMID: 32514611 DOI: 10.1007/s00270-020-02534-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 05/18/2020] [Indexed: 12/17/2022]
Abstract
PURPOSE To assess feasibility, embolization success, biodegradability, reperfusion, biocompatibility and in vivo visibility of novel temporary microspheres (MS) for transcatheter arterial embolization. MATERIAL AND METHODS In 9 New Zealand white rabbits unilateral superselective embolization of the lower kidney pole was performed with biodegradable MS made of polydioxanone (PDO) (size range 90-300 and 200-500 µm) impregnated with super-paramagnetic iron oxide (SPIO). Magnetic resonance imaging (MRI) was performed post-interventionally to assess in vivo visibility. Embolization success was assessed on digital subtraction angiography, MRI and gross pathology. One animal was killed immediately after embolization to assess original particle appearance. 8 animals were randomly assigned to different observation periods (1, 4, 8, 12 and 16 weeks), after which control angiography and MRI were obtained to determine recanalization. Histopathological analysis was performed to determine biodegradability and biocompatibility by using dedicated quantitative assessment analysis. RESULTS Ease of injection was moderate. Embolization was technically successful in 7 of 8 animals, one rabbit received non-selective embolization of the whole kidney and abdominal off-target embolization. Arterial occlusion was achieved in all kidneys, infarct areas in macro- and microscopic analysis confirmed embolization success. Control angiograms showed evidence of partial reperfusion. The microspheres showed extensive degradation over the course of time along with increasing inflammatory response and giant cell formation. SPIO-loaded MS were visible on MRI at all time points. CONCLUSIONS SPIO-impregnated biodegradable PDO-MS achieved effective embolization with in vivo visibility on MRI and increasing biodegradation over time while demonstrating good biocompatibility, i.e., a physiologically immune response without transformation into chronic inflammation. Further studies are needed to provide clinical applicability.
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Affiliation(s)
- Matthias Stechele
- Department of Radiology, University Hospital, Ludwig Maximilians University, Marchioninistraße 15, 81377, Munich, Germany
| | - Helena Wittgenstein
- Evidensia Veterinary Clinic for Small Animals GmbH, Kabels Stieg 41, 22850, Norderstedt, Germany
| | - Nicola Stolzenburg
- Department of Radiology, Charité School of Medicine and University Hospital Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Jörg Schnorr
- Department of Radiology, Charité School of Medicine and University Hospital Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Jens Neumann
- University Hospital, Institute of Pathology, Ludwig Maximilians University, Marchioninistraße 15, 81377, Munich, Germany
| | | | - Rolf W Günther
- Department of Radiology, Charité School of Medicine and University Hospital Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Florian Streitparth
- Department of Radiology, University Hospital, Ludwig Maximilians University, Marchioninistraße 15, 81377, Munich, Germany.
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Ezponda A, Rodríguez-Fraile M, Morales M, Vivas I, De La Torre M, Sangro B, Bilbao JI. Hepatic Flow Redistribution is Feasible in Patients with Hepatic Malignancies Undergoing Same-Day Work-Up Angiography and Yttrium-90 Microsphere Radioembolization. Cardiovasc Intervent Radiol 2019; 43:987-995. [PMID: 31848672 DOI: 10.1007/s00270-019-02371-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 10/31/2019] [Indexed: 12/16/2022]
Abstract
PURPOSE To assess the feasibility of performing same-day vascular flow redistribution and Yttrium-90 radioembolization (90Y-RE) for hepatic malignancies. MATERIALS AND METHODS From November 2015 to February 2019, patients undergoing same-day hepatic flow redistribution during work-up angiography, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA) SPECT/CT and 90Y microsphere-RE, were recruited. Within 18 h following the delivery of 90Y resin microspheres, an 90Y-PET/CT study was performed. According to patients' vascular anatomy, flow redistribution was performed by microcoil embolization of extrahepatic branches (group A), intrahepatic non-tumoral vessels (group B) and intrahepatic tumoral arteries (group C). The accumulation of 99mTc-MAA particles and microspheres in the redistributed areas was qualitatively evaluated using a 5-point visual scale (grade 1 = < 25% accumulation; grade 5 = 100% accumulation). Differences in the distribution of microspheres among groups were assessed with Mann-Whitney U test. RESULTS Twenty-two patients were treated for primary (n = 17) and secondary (n = 5) hepatic malignancies. The MAA-SPECT/CT showed uptake in all the redistributed areas. Regarding the accumulation of microspheres within the redistributed segments in all the groups, perfusion patterns were classified as 2 in 1 case, 4 in 6 cases and 5 in 15 cases. No statistically significant differences were observed between groups A and B-C (U value = 34, p = 0.32) and between groups B and C (U value = 26, p = 0.7). Mean predicted absorbed doses by the tumoral and normal hepatic tissues were 163.5 ± 131.2 Gy and 60.4 ± 69.3 Gy, respectively. Mean total procedure time (from work-up angiography to 90Y delivery) was 401 ± 0.055 min. CONCLUSION Performing same-day redistribution of the arterial hepatic flow to the target and 90Y-microsphere delivery is feasible in the treatment of liver tumors. Clinical Trials Registry NCT03380130.
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Affiliation(s)
- A Ezponda
- Department of Radiology, Clínica Universitaria de Navarra, Universidad de Navarra, Avenida de Pio XII n°36, 31008, Pamplona, Spain.
| | - M Rodríguez-Fraile
- Department of Nuclear Medicine, Clínica Universitaria de Navarra, Universidad de Navarra, Avenida de Pio XII n°36, 31008, Pamplona, Spain
| | - M Morales
- Department of Nuclear Medicine, Clínica Universitaria de Navarra, Universidad de Navarra, Avenida de Pio XII n°36, 31008, Pamplona, Spain
| | - I Vivas
- Department of Radiology, Clínica Universitaria de Navarra, Universidad de Navarra, Avenida de Pio XII n°36, 31008, Pamplona, Spain
| | - M De La Torre
- Department of Internal Medicine-Hepatology, Clínica Universidad de Navarra, Universidad de Navarra, Avenida de Pio XII n°36, 31008, Pamplona, Spain.,Clínica Universidad de Navarra, Calle Marquesado de Sta Marta n°1, 28027, Madrid, Spain
| | - B Sangro
- Department of Internal Medicine-Hepatology, Clínica Universidad de Navarra, Universidad de Navarra, Avenida de Pio XII n°36, 31008, Pamplona, Spain.,Clínica Universidad de Navarra, Calle Marquesado de Sta Marta n°1, 28027, Madrid, Spain
| | - J I Bilbao
- Department of Radiology, Clínica Universitaria de Navarra, Universidad de Navarra, Avenida de Pio XII n°36, 31008, Pamplona, Spain
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Toskich BB, Liu DM. Y90 Radioembolization Dosimetry: Concepts for the Interventional Radiologist. Tech Vasc Interv Radiol 2019; 22:100-111. [PMID: 31079706 DOI: 10.1053/j.tvir.2019.02.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Transarterial radioembolization (TARE) with beta particle emitting microspheres via Yttrium-90 decay has become a fundamental component of the contemporary Interventional Oncology practice. TARE continues to advance as a result of increased utilization, clinical study, technological improvements, and evolving applications. To maximize TARE safety and efficacy, a core understanding of dosimetry is essential. The intent of this overview is to provide the reader with a general survey of radiation physics and biology, device differentiation, patient selection, anatomic assessment, activity administration models, and procedural techniques involved with TARE dosimetry.
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Affiliation(s)
| | - David M Liu
- University of British Columbia, Vancouver, BC, Canada
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16
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Sommer CM, Do TD, Schlett CL, Flechsig P, Gockner TL, Kuthning A, Vollherbst DF, Pereira PL, Kauczor HU, Macher-Göppinger S. In vivo characterization of a new type of biodegradable starch microsphere for transarterial embolization. J Biomater Appl 2017; 32:932-944. [DOI: 10.1177/0885328217746674] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Christof M Sommer
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
- Clinic for Diagnostic and Interventional Radiology, Klinikum Stuttgart, Stuttgart, Germany
| | - Thuy D Do
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christopher L Schlett
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Paul Flechsig
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
- Clinic for Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
| | - Theresa L Gockner
- Clinic for Diagnostic and Interventional Radiology, University Hospital Mainz, Mainz, Germany
| | | | - Dominik F Vollherbst
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
- Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Philippe L Pereira
- Clinic for Radiology, Minimally-invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Heilbronn, Germany
| | - Hans U Kauczor
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
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Luo SH, Song SL, Zheng CS, Li WY, Wang Y, Xia XW, Feng GS. Embolic effects of Bletilla striata microspheres in renal artery and transplanted VX2 liver tumor model in rabbits. Chin J Integr Med 2017; 25:431-438. [PMID: 28497394 DOI: 10.1007/s11655-017-2953-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model. METHODS BSMs were prepared with an emulsification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 μm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 μm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining. RESULTS The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more difficult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcification. There were no significant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no significant difference between groups B and C (P>0.05). CONCLUSIONS The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.
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Affiliation(s)
- Shi-Hua Luo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Song-Lin Song
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chuan-Sheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Wei-Yong Li
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yong Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiang-Wen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Gan-Sheng Feng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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Sommer C, Pallwein-Prettner L, Vollherbst D, Seidel R, Rieder C, Radeleff B, Kauczor H, Wacker F, Richter G, Bücker A, Rodt T, Massmann A, Pereira P. Transarterial embolization (TAE) as add-on to percutaneous radiofrequency ablation (RFA) for the treatment of renal tumors: Review of the literature, overview of state-of-the-art embolization materials and further perspective of advanced image-guided tumor ablation. Eur J Radiol 2017; 86:143-162. [DOI: 10.1016/j.ejrad.2016.10.024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 10/17/2016] [Accepted: 10/21/2016] [Indexed: 02/08/2023]
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Sommer CM, Richter G, Vollherbst D, Macher-Göppinger S, Gnutzmann D, Pereira P, Radeleff B, Kauczor H, Stampfl U. ETHIBLOC_Reloaded: First in-vivo results of the re-designed zein-based fluid embolic agent. COGENT MEDICINE 2017. [DOI: 10.1080/2331205x.2017.1287644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Affiliation(s)
- Christof M. Sommer
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
- Clinic for Diagnostic and Interventional Radiology, Klinikum Stuttgart, Stuttgart, Germany
| | - G.M. Richter
- Clinic for Diagnostic and Interventional Radiology, Klinikum Stuttgart, Stuttgart, Germany
| | - D.F. Vollherbst
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
- Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
| | - S. Macher-Göppinger
- Department of General Pathology, University Hospital Heidelberg, Heidelberg, Germany
- Department of General Pathology, University Hospital Mainz, Mainz, Germany
| | - D. Gnutzmann
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - P.L. Pereira
- Clinic for Radiology, Minimally-Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Heilbronn, Germany
| | - B.A. Radeleff
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - H.U. Kauczor
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - U. Stampfl
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
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de Silva S, Mackie S, Aslan P, Cade D, Delprado W. Histological Comparison of Kidney Tissue Following Radioembolization with Yttrium-90 Resin Microspheres and Embolization with Bland Microspheres. Cardiovasc Intervent Radiol 2016; 39:1743-1749. [PMID: 27743088 DOI: 10.1007/s00270-016-1482-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 10/03/2016] [Indexed: 11/27/2022]
Abstract
BACKGROUND Intra-arterial brachytherapy with yttrium-90 (90Y) resin microspheres (radioembolization) is a procedure to selectively deliver high-dose radiation to tumors. The purpose of this research was to compare the radioembolic effect of 90Y-radioembolization versus the embolic effect of bland microspheres in the porcine kidney model. METHODS In each of six pigs, ~25-33 % of the kidney volume was embolized with 90Y resin microspheres and an equivalent number of bland microspheres in the contralateral kidney. Kidney volume was estimated visually from contrast-enhanced fluoroscopy imaging. Morphologic and histologic analysis was performed 8-9 weeks after the procedure to assess the locations of the microspheres and extent of tissue necrosis from 90Y-radioembolization and bland embolization. A semi-quantified evaluation of the non-acute peri-particle and perivascular tissue reaction was conducted. All guidelines for the care and use of animals were followed. RESULTS Kidneys embolized with 90Y-radioembolization decreased in mass by 30-70 % versus the contralateral kidney embolized with bland microspheres. These kidneys showed significant necrosis/fibrosis, avascularization, and glomerular atrophy in the immediate vicinity of the 90Y resin microspheres. By contrast, glomerular changes were not observed, even with clusters of bland microspheres in afferent arterioles. Evidence of a foreign body reaction was recorded in some kidneys with bland microspheres, and subcapsular scarring/infarction only with the highest load (4.96 × 106) of bland microspheres. CONCLUSION This study showed that radioembolization with 90Y resin microspheres produces localized necrosis/fibrosis and loss of kidney mass in a porcine kidney model. This result supports the study of 90Y resin microspheres for the localized treatment of kidney tumors.
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Affiliation(s)
- Suresh de Silva
- Radiology Department Sutherland Hospital, Southern Radiology Group, The Kingsway Caringbah, Sydney, NSW, 2229, Australia.
| | - Simon Mackie
- Department of Urology, Western General Hospital, Crewe Road, Edinburgh, Scotland, EH42XU, UK
| | - Peter Aslan
- Department of Urology, St George Hospital, South Street, Kogarah, NSW, Australia
| | - David Cade
- Sirtex Technology Pty Ltd, Level 33, 101 Miller Street, North Sydney, NSW, 2060, Australia
| | - Warick Delprado
- Douglass Hanly Moir Pathology, 14 Giffnock Ave, Macquarie Park, NSW, 2113, Australia
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Westcott MA, Coldwell DM, Liu DM, Zikria JF. The development, commercialization, and clinical context of yttrium-90 radiolabeled resin and glass microspheres. Adv Radiat Oncol 2016; 1:351-364. [PMID: 28740906 PMCID: PMC5514171 DOI: 10.1016/j.adro.2016.08.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 08/02/2016] [Accepted: 08/03/2016] [Indexed: 12/14/2022] Open
Abstract
Selective internal radiation therapy has emerged as a well-accepted therapeutic for primary and metastatic hepatic malignancies. This therapeutic modality requires the combined efforts of multiple medical disciplines to ensure the safe delivery of yttrium-90 (90Y)-labeled microspheres. The development of this therapy followed decades of clinical research involving tumor vascularity and microsphere development. Today, it is essential that treating physicians have a thorough understanding of hepatic tumor vascularity and 90Y microsphere characteristics before undertaking this complex intervention. This review explores the contributions of early investigators of this therapy, as well as the development, US Food and Drug Administration approval, manufacturing process, and attributes of the 2 commercially available 90Y radiolabeled microsphere device to clarify the key physical differences between the products.
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Affiliation(s)
- Mark A. Westcott
- Department of Radiology, Lenox Hill Hospital, New York, New York
| | | | - David M. Liu
- Department of Radiology, University of British Columbia, Vancouver, British Columbia
| | - Joseph F. Zikria
- Department of Radiology, Memorial Regional Hospital, Hollywood, Florida
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Irie T, Kuramochi M, Takahashi N. Diameter of main tumor feeding artery of a hepatocellular carcinoma: Measurement at the entry site into the nodule. Hepatol Res 2016; 46:E100-4. [PMID: 25988271 DOI: 10.1111/hepr.12534] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2015] [Revised: 05/06/2015] [Accepted: 05/12/2015] [Indexed: 02/08/2023]
Abstract
AIM To measure the diameter of the main tumor feeding artery (TFA) of a hepatocellular carcinoma (HCC) nodule at the entry site into the nodule. METHODS Fifty-seven HCC nodules in 43 patients were analyzed using a 3-D workstation and picture archiving system (PACS). TFA was defined as an artery connected to a HCC nodule on catheter-assisted multidetector computed tomography angiography (CAMDCTA). The entry site of the main TFA into the nodule was identified on CAMDCTA, and the corresponding portion was measured on digital angiography (DA) or digital subtracted angiography (DSA). The measuring scale of the PACS was calibrated using the platinum tip of microballoon catheters 0.68 mm in diameter. We investigated the relationship between diameters of the nodule and its main TFA. RESULTS The diameters of the nodule and its main TFA ranged 7-63 mm (20.3 ± 12.7) and 0.12-1.79 mm (0.41 ± 0.32), respectively. Simple regression analysis revealed a relationship between diameters of the nodule and its main TFA (P < 0.0001). The diameter of the main TFA was less than 1 mm in 53 of 57 nodules (93.0%), and less than 0.5 mm in 42 (73.7%). CONCLUSION The diameter of main TFA was thicker in the larger nodule. The size of commercially available porous gelatin particles (1 or 2 mm in diameter) seems too large for embolization of most of HCC nodules.
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Affiliation(s)
- Toshiyuki Irie
- Department of Radiology, Hitachi General Hospital, Hitachi, Japan
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Thakur V, Kush P, Pandey RS, Jain UK, Chandra R, Madan J. Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo study. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2015; 61:113-22. [PMID: 26838831 DOI: 10.1016/j.msec.2015.12.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 12/01/2015] [Accepted: 12/10/2015] [Indexed: 12/22/2022]
Abstract
Vincristine sulfate (VCS) is a drug of choice for the treatment of childhood and adult acute lymphocytic leukemia, Hodgkin's, non-Hodgkin's lymphoma as well as solid tumors including sarcomas. However, poor biopharmaceutical and pharmacokinetic traits of VCS like short serum half-life (12 min), high dosing frequency (1.4 mg/m(2) per week for 4 weeks) and extensive protein binding (75%) limit the clinical potential of VCS in cancer therapy. In present investigation, injectable vincristine sulfate loaded dextran microspheres (VCS-Dextran-MSs) were prepared and amalgamated with chitosan-β-glycerophosphate gel (VCS-Dextran-MSs-Gel) to surmount the biopharmaceutical and pharmacokinetic limitations of VCS that consequently induced synergistic sustained release pattern of the drug. Particle size and zeta-potential of VCS-Dextran-MSs were measured to be 6.8 ± 2.4 μm and -18.3 ± 0.11 mV along with the encapsulation efficiency of about 60.4 ± 4.5%. Furthermore, VCS-Dextran-MSs and VCS-Dextran-MSs-Gel exhibited slow release pattern and 94.7% and 95.8% of the drug was released in 72 h and 720 h, respectively. Results from cell viability assay and pharmacokinetic as well as histopathological analysis in mice indicated that VCS-Dextran-MSs-Gel offers superior therapeutic potential and higher AUClast than VCS-Dextran-MSs and drug solution. In conclusion, VCS-Dextran-MSs-Gel warrants further preclinical tumor growth study to scale up the technology.
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Affiliation(s)
- Vivek Thakur
- Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India
| | - Preeti Kush
- Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India
| | - Ravi Shankar Pandey
- SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India
| | - Upendra Kumar Jain
- Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India
| | - Ramesh Chandra
- Department of Chemistry, University of Delhi, Delhi, India
| | - Jitender Madan
- Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India.
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Ahmadzadehfar H, Meyer C, Pieper CC, Bundschuh R, Muckle M, Gärtner F, Schild HH, Essler M. Evaluation of the delivered activity of yttrium-90 resin microspheres using sterile water and 5 % glucose during administration. EJNMMI Res 2015; 5:54. [PMID: 26463848 PMCID: PMC4604161 DOI: 10.1186/s13550-015-0133-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 10/06/2015] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The purpose of this study is to evaluate the impact of switching from sterile water to 5 % glucose (G5W) for the administration of yttrium-90 ((90)Y)-resin microspheres on the total activity of (90)Y administered (expressed as a proportion of the prescribed/calculated activity), as well as the number of cases of stasis and the reported incidence of discomfort during the selective internal radiation therapy (SIRT) procedure. METHODS In December 2013, we switched from sterile water to G5W for the administration of SIRT using (90)Y resin microspheres in all patients. This retrospective observational single-center case series describes our experience in the months preceding and after the switch. Apart from the change in administration medium, the protocol for SIRT was otherwise identical. RESULTS One hundred and four SIRT procedures were performed on 78 patients (45 male, mean age: 63 years, range: 31-87 years) with either unresectable hepatocellular carcinoma, cholangiocarcinoma, or chemorefractory liver-dominant metastatic cancer. Compared with sterile water, the whole prescribed activity was administered in significantly more procedures with G5W: 85 vs. 22 %; p < 0.0001. A significantly higher proportion of the calculated activity was administered with G5W: 96.1 ± 11.0 % vs. 77.4 ± 24.3 % (p < 0.0001). G5W procedures were also associated with a significantly lower incidence of stasis (28 vs. 11 % procedures; p = 0.02) and mild-to-moderate upper abdominal pain during the procedure (1.8 vs. 44 % procedures; p < 0.0001). CONCLUSIONS Replacing sterile water with isotonic G5W during administration favorably impacts on the safety of SIRT, eliminates and/or minimizes flow reductions and stasis/reflux during administration of (90)Y resin microspheres, improves percentage activity delivered, and reduces peri-procedural pain.
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Affiliation(s)
- Hojjat Ahmadzadehfar
- Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Carsten Meyer
- Department of Radiology, University Hospital Bonn, Bonn, Germany
| | | | - Ralph Bundschuh
- Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - Marianne Muckle
- Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - Florian Gärtner
- Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | | | - Markus Essler
- Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
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Galun D, Basaric D, Zuvela M, Bulajic P, Bogdanovic A, Bidzic N, Milicevic M. Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols. World J Hepatol 2015; 7:2274-91. [PMID: 26380652 PMCID: PMC4568488 DOI: 10.4254/wjh.v7.i20.2274] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 07/06/2015] [Accepted: 08/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome.
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Affiliation(s)
- Danijel Galun
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Dragan Basaric
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Marinko Zuvela
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Predrag Bulajic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Aleksandar Bogdanovic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Nemanja Bidzic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Miroslav Milicevic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
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Biocompatibility of Bletilla striata Microspheres as a Novel Embolic Agent. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:840896. [PMID: 26472985 PMCID: PMC4579312 DOI: 10.1155/2015/840896] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Revised: 08/17/2015] [Accepted: 08/25/2015] [Indexed: 11/24/2022]
Abstract
We have prepared Chinese traditional herb Bletilla striata into microspheres as a novel embolic agent for decades. The aim of this study was to evaluate the biocompatibility of Bletilla striata microspheres (BSMs). After a thermal test of BSMs in vitro, the cell biocompatibility of BSMs was investigated in mouse fibroblasts and human umbilical vein endothelial cells using the methyl tetrazolium (MTT) assay. In addition, blood biocompatibility was evaluated. In vivo intramuscular implantation and renal artery embolization in rabbits with BSMs were used to examine the inflammatory response. The experimental rabbits did not develop any fever symptoms after injection of BSMs, and BSMs exhibited no cytotoxicity in cultured mouse fibroblasts and human umbilical vein endothelial cells. Additionally, BSMs exhibited high compatibility with red blood cells and no hemolysis activity. Intramuscular implantation with BSMs resulted in a gradually lessened mild inflammatory reaction that disappeared after eight weeks. The occlusion of small renal vessels was associated with a mild perivascular inflammatory reaction without significant renal and liver function damage. In conclusion, we believe that BSMs exhibit high biocompatibility and are a promising embolic agent.
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Garin E, Rolland Y, Laffont S, Edeline J. Clinical impact of (99m)Tc-MAA SPECT/CT-based dosimetry in the radioembolization of liver malignancies with (90)Y-loaded microspheres. Eur J Nucl Med Mol Imaging 2015; 43:559-75. [PMID: 26338177 PMCID: PMC4731431 DOI: 10.1007/s00259-015-3157-8] [Citation(s) in RCA: 112] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Accepted: 07/30/2015] [Indexed: 12/16/2022]
Abstract
Radioembolization with (90)Y-loaded microspheres is increasingly used in the treatment of primary and secondary liver cancer. Technetium-99 m macroaggregated albumin (MAA) scintigraphy is used as a surrogate of microsphere distribution to assess lung or digestive shunting prior to therapy, based on tumoral targeting and dosimetry. To date, this has been the sole pre-therapeutic tool available for such evaluation. Several dosimetric approaches have been described using both glass and resin microspheres in hepatocellular carcinoma (HCC) and liver metastasis. Given that each product offers different specific activities and numbers of spheres injected, their radiobiological properties are believed to lightly differ. This paper summarizes and discusses the available studies focused on MAA-based dosimetry, particularly concentrating on potential confounding factors like clinical context, tumor size, cirrhosis, previous or concomitant therapy, and product used. In terms of the impact of tumoral dose in HCC, the results were concordant and a response relationship and tumoral threshold dose was clearly identified, especially in studies using glass microspheres. Tumoral dose has also been found to influence survival. The concept of treatment intensification has recently been introduced, yet despite several studies publishing interesting findings on the tumor dose-metastasis relationship, no consensus has been reached, and further clarification is thus required. Nor has the maximal tolerated dose to the liver been well documented, requiring more accurate evaluation. Lung dose was well described, despite recently identified factors influencing its evaluation, requiring further assessment. Conclusion: MAA SPECT/CT dosimetry is accurate in HCC and can now be used in order to achieve a fully customized approach, including treatment intensification. Yet further studies are warranted for the metastasis setting and evaluating the maximal tolerated liver dose.
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Affiliation(s)
- Etienne Garin
- Department of Nuclear Medicine, Cancer Institute Eugène Marquis, CS 44229, F-35042, Rennes, France. .,University of Rennes 1, F-35043, Rennes, France. .,INSERM, U-991, Liver Metabolisms and Cancer, F-35033, Rennes, France.
| | - Yan Rolland
- Department of Medical Imaging, Cancer Institute Eugène Marquis, CS 44229, F-35042, Rennes, France
| | | | - Julien Edeline
- University of Rennes 1, F-35043, Rennes, France.,INSERM, U-991, Liver Metabolisms and Cancer, F-35033, Rennes, France.,Department of Medical Oncology, Cancer Institute Eugène Marquis, CS 44229, F-35042, Rennes, France
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Abbott AM, Kim R, Hoffe SE, Arslan B, Biebel B, Choi J, El-Haddad G, Kis B, Sweeney J, Meredith KL, Almhanna K, Strosberg J, Shibata D, Fulp WJ, Shridhar R. Outcomes of Therasphere Radioembolization for Colorectal Metastases. Clin Colorectal Cancer 2015; 14:146-53. [DOI: 10.1016/j.clcc.2015.02.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 01/21/2015] [Accepted: 02/06/2015] [Indexed: 01/05/2023]
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Sangro B. Evidence-based integration of selective internal radiation therapy into hepatocellular carcinoma management. Future Oncol 2015; 10:7-11. [PMID: 25478760 DOI: 10.2217/fon.14.216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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Kao YH, Goodwin M, Lee ST, Lichtenstein M, Scott AM. Scientific basis of personalised tomographic radiation planning for radioembolisation: A form of brachytherapy planning. J Med Imaging Radiat Oncol 2015; 59:617-8. [DOI: 10.1111/1754-9485.12346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 06/27/2015] [Indexed: 11/30/2022]
Affiliation(s)
- Yung Hsiang Kao
- Department of Nuclear Medicine; The Royal Melbourne Hospital; Melbourne Victoria Australia
| | - Mark Goodwin
- Department of Radiology, Department of Molecular Imaging and Therapy; University of Melbourne, Austin Health; Melbourne Victoria Australia
| | - Sze Ting Lee
- Department of Radiology, Department of Molecular Imaging and Therapy; University of Melbourne, Austin Health; Melbourne Victoria Australia
- Olivia Newton-John Cancer Research Institute; La Trobe University; Melbourne Victoria Australia
| | - Meir Lichtenstein
- Department of Nuclear Medicine; The Royal Melbourne Hospital; Melbourne Victoria Australia
| | - Andrew Mark Scott
- Department of Radiology, Department of Molecular Imaging and Therapy; University of Melbourne, Austin Health; Melbourne Victoria Australia
- Olivia Newton-John Cancer Research Institute; La Trobe University; Melbourne Victoria Australia
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Rodríguez-Fraile M, Iñarrairaegui M. Radioembolization with 90Y-microspheres for liver tumors. Rev Esp Med Nucl Imagen Mol 2015. [DOI: 10.1016/j.remnie.2015.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Huang SY, Philip A, Richter MD, Gupta S, Lessne ML, Kim CY. Prevention and management of infectious complications of percutaneous interventions. Semin Intervent Radiol 2015; 32:78-88. [PMID: 26038616 DOI: 10.1055/s-0035-1549372] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Infectious complications following interventional radiology (IR) procedures can cause significant patient morbidity and, potentially, mortality. As the number and breadth of IR procedures grow, it becomes increasingly evident that interventional radiologists must possess a thorough understanding of these potential infectious complications. Furthermore, given the increasing incidence of antibiotic-resistant bacteria, emphasis on cost containment, and attention to quality of care, it is critical to have infection control strategies to maximize patient safety. This article reviews infectious complications associated with percutaneous ablation of liver tumors, transarterial embolization of liver tumors, uterine fibroid embolization, percutaneous nephrostomy, percutaneous biliary interventions, central venous catheters, and intravascular stents. Emphasis is placed on incidence, risk factors, prevention, and management. With the use of these strategies, IR procedures can be performed with reduced risk of infectious complications.
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Affiliation(s)
- Steven Y Huang
- Department of Interventional Radiology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Asher Philip
- Department of Interventional Radiology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Michael D Richter
- Department of Interventional Radiology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Sanjay Gupta
- Department of Interventional Radiology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Mark L Lessne
- Vascular and Interventional Specialists of Charlotte Radiology, Charlotte, North Carolina
| | - Charles Y Kim
- Division of Vascular and Interventional Radiology, Duke University Medical Center, Durham, North Carolina
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Prince JF, van Rooij R, Bol GH, de Jong HWAM, van den Bosch MAAJ, Lam MGEH. Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres. J Nucl Med 2015; 56:817-23. [PMID: 25931477 DOI: 10.2967/jnumed.115.155564] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Accepted: 04/15/2015] [Indexed: 12/11/2022] Open
Abstract
UNLABELLED Before (166)Ho radioembolization, a small batch of the same type of microspheres is administered as a scout dose instead of the conventional (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). The (166)Ho scout dose provides a more accurate and precise lung shunt assessment. However, in contrast to (99m)Tc-MAA, an unintended extrahepatic deposition of this β-emitting scout dose could inflict radiation damage, the extent of which we aimed to quantify in this study. METHODS All patients eligible for radioembolization in our institute between January 2011 and March 2014 were reviewed. Of the extrahepatic depositions of (99m)Tc-MAA on SPECT, the amount and volume were measured. These were used to calculate the theoretic absorbed dose in the case a (166)Ho scout dose had been used. The extrahepatic activity was measured as the sum of all voxels of the deposition. Volumes were measured using a threshold technique including all voxels from the maximum voxel intensity up to a certain percentage. The threshold needed to obtain the true volume was studied in a phantom study. RESULTS In the phantom study, a threshold of 40% was found to overestimate the volume, with the consequence of underestimating the absorbed dose. Of 160 patients, 32 patients (34 cases) of extrahepatic deposition were identified. The depositions contained a median of 1.3% (range, 0.1%-19.5%) of the administered activity in a median volume of 6.8 mL (range, 1.1-42 mL). The use of a scout dose of 250 MBq of (166)Ho microspheres in these cases would theoretically have resulted in a median absorbed dose of 6.0 Gy (range, 0.9-374 Gy). The dose exceeded a limit of 49 Gy (reported in 2013) in 2 of 34 cases (5.9%; 95% confidence interval, 0.7%-20.1%) or 2 of 160 (1.3%; 95% confidence interval, 0.1%-4.7%) of all patients. In these 2 patients with a large absorbed dose (112 and 374 Gy), the culprit vessel was identified in 1 case. CONCLUSION Extrahepatic deposition of a (166)Ho scout dose seems to be theoretically safe in most patients. Its safety in clinical practice is being evaluated in ongoing clinical trials.
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Affiliation(s)
- Jip F Prince
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Rob van Rooij
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Gijsbert H Bol
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Hugo W A M de Jong
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
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Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives. World J Hepatol 2015. [PMID: 25914774 DOI: 10.4254/wjh.v7.i5.738].] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Transarterial radioembolization (TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes. On the average, it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma (HCC); however, current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway. The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization (TACE). First-line TARE is best indicated for both intermediate-stage patients (staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden, and for locally advanced-stage patients with solitary tumors, and segmental or lobar portal vein tumor thrombosis. In addition, emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes. As a second-line treatment, TARE can also be applied in patients progressing to TACE or sorafenib; a large number of phase II/III trials are ongoing with the purpose of evaluating the best association with systemic therapies. Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation, including the surrounding liver parenchyma. The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy. Since a correct treatment algorithm for potential TARE candidates is not clear and standardized, this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy, which can be a very important weapon against HCC.
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Rodríguez-Fraile M, Iñarrairaegui M. [Radioembolization with (90)Y-microspheres for liver tumors]. Rev Esp Med Nucl Imagen Mol 2015; 34:244-57. [PMID: 25911062 DOI: 10.1016/j.remn.2015.03.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Revised: 03/12/2015] [Accepted: 03/13/2015] [Indexed: 12/16/2022]
Affiliation(s)
- M Rodríguez-Fraile
- Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Navarra; Área de Oncología Hepatobiliopancreática, Clínica Universidad de Navarra, Pamplona, Navarra, España; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), España.
| | - M Iñarrairaegui
- Unidad de Hepatología, Clínica Universidad de Navarra, Pamplona, Navarra, España; Área de Oncología Hepatobiliopancreática, Clínica Universidad de Navarra, Pamplona, Navarra, España; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, España
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Mosconi C, Cappelli A, Pettinato C, Golfieri R. Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives. World J Hepatol 2015; 7:738-52. [PMID: 25914774 PMCID: PMC4404379 DOI: 10.4254/wjh.v7.i5.738] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 12/09/2014] [Accepted: 01/15/2015] [Indexed: 02/06/2023] Open
Abstract
Transarterial radioembolization (TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes. On the average, it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma (HCC); however, current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway. The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization (TACE). First-line TARE is best indicated for both intermediate-stage patients (staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden, and for locally advanced-stage patients with solitary tumors, and segmental or lobar portal vein tumor thrombosis. In addition, emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes. As a second-line treatment, TARE can also be applied in patients progressing to TACE or sorafenib; a large number of phase II/III trials are ongoing with the purpose of evaluating the best association with systemic therapies. Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation, including the surrounding liver parenchyma. The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy. Since a correct treatment algorithm for potential TARE candidates is not clear and standardized, this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy, which can be a very important weapon against HCC.
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Affiliation(s)
- Cristina Mosconi
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
| | - Alberta Cappelli
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
| | - Cinzia Pettinato
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
| | - Rita Golfieri
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
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Mosconi C, Cappelli A, Pettinato C, Golfieri R. Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives. World J Hepatol 2015. [PMID: 25914774 DOI: 10.4254/wjh.v7.i5.738]] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Transarterial radioembolization (TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes. On the average, it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma (HCC); however, current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway. The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization (TACE). First-line TARE is best indicated for both intermediate-stage patients (staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden, and for locally advanced-stage patients with solitary tumors, and segmental or lobar portal vein tumor thrombosis. In addition, emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes. As a second-line treatment, TARE can also be applied in patients progressing to TACE or sorafenib; a large number of phase II/III trials are ongoing with the purpose of evaluating the best association with systemic therapies. Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation, including the surrounding liver parenchyma. The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy. Since a correct treatment algorithm for potential TARE candidates is not clear and standardized, this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy, which can be a very important weapon against HCC.
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Affiliation(s)
- Cristina Mosconi
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
| | - Alberta Cappelli
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
| | - Cinzia Pettinato
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
| | - Rita Golfieri
- Cristina Mosconi, Alberta Cappelli, Rita Golfieri, Radiology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
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Cappelli A, Pettinato C, Golfieri R. Transarterial radioembolization using yttrium-90 microspheres in the treatment of hepatocellular carcinoma: a review on clinical utility and developments. J Hepatocell Carcinoma 2014; 1:163-82. [PMID: 27508185 PMCID: PMC4918277 DOI: 10.2147/jhc.s50472] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
A selective intra-arterial liver injection using yttrium-90-loaded microspheres as sources for internal radiation therapy is a form of transarterial radioembolization (TARE). Current data from the literature suggest that TARE is effective in hepatocellular carcinoma (HCC) and is associated with a low rate of adverse events; however, they are all based on retrospective series or non-controlled prospective studies, since randomized controlled trials comparing the other liver-directed therapies for intermediate and locally advanced stages HCC are still ongoing. The available data show that TARE provides similar or even better survival rates. TARE is very well tolerated and has a low rate of complications; these complications do not result from the embolic effects but mainly from the unintended irradiation to non-target tissue, including the liver parenchyma. The complications can be further reduced by accurate patient selection and a strict pre-treatment evaluation, including dosimetry and assessment of the vascular anatomy. First-line TARE is best indicated for intermediate-stage patients (according to the Barcelona Clinic Liver Cancer [BCLC] staging classification) who are poor candidates for transarterial chemoembolization or patients having locally advanced disease with segmental or lobar branch portal vein thrombosis. Moreover, data are emerging regarding the use of TARE in patients classified slightly above the criteria for liver transplantation with the purpose of downstaging them. TARE can also be applied as a second-line treatment in patients progressing to transarterial chemoembolization or sorafenib; a large number of Phase II/III trials are in progress in order to evaluate the best association with systemic therapies. Given the complexity of a correct treatment algorithm for potential TARE candidates and the need for clinical guidance, a comprehensive review was carried out analyzing both the best selection criteria of patients who really benefit from TARE and the new advances of this therapy which add significant value to the therapeutic weaponry against HCC.
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Affiliation(s)
| | - Cinzia Pettinato
- Medical Physics Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
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Sangro B. Chemoembolization and radioembolization. Best Pract Res Clin Gastroenterol 2014; 28:909-19. [PMID: 25260317 DOI: 10.1016/j.bpg.2014.08.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 08/15/2014] [Indexed: 01/31/2023]
Abstract
Chemoembolization and radioembolization are at the core of the treatment of patients with hepatocellular carcinoma who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. They differ in the mechanism of action (ischaemia and increase cytotoxic drug exposure for chemoembolization, internal irradiation for radioembolization) and may target different patient populations. Chemoembolization with cytotoxic drug-eluting beads is a more standardized although not necessarily more effective way of performing chemoembolization. Cytoreduction is achieved in most patients but complete tumor ablation may be achieved and lead to extended survival. Grade 1 level of evidence support the use of chemoembolization for the treatment of patients in the early and intermediate stages while grade 2 evidence supports the use of radioembolization for the treatment of patients in intermediate to advanced stages. Selecting the best candidates for both techniques is still a work in progress that ongoing clinical trials are trying to address.
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Affiliation(s)
- Bruno Sangro
- Clinica Universidad de Navarra, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Avda, Pio XII 36, 31008 Pamplona, Spain.
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Abstract
The most common non-surgical approaches for the treatment of localized hepatocellular carcinoma remain hepatic artery-delivered particles laden with chemotherapy (TACE), or radioactive microparticles (TARE). External beam radiotherapy has been an effective option in many parts of the world for selected HCC patients, but now has an expanded role with stereotactic and proton beam technologies. This review focuses on existing evidence and current guidance for utilizing these modalities for localized, but unresectable, non-transplantable HCC patients.x.
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Affiliation(s)
- Andrew S Kennedy
- Radiation Oncology Research, Sarah Cannon Research Institute, 3322 West End Avenue, Suite 800, Nashville, TN, 37203, USA,
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Golfieri R. SIR-Spheres yttrium-90 radioembolization for the treatment of unresectable liver cancers. Hepat Oncol 2014; 1:265-283. [PMID: 30190962 DOI: 10.2217/hep.14.6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Transarterial radioembolization with yttrium-90 resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) is a liver-directed therapy that is gaining recognition as a treatment option for liver-dominant primary and metastatic cancers. The incidence of complications is low and can be further reduced by patient selection and rigorous pretreatment assessment. Ideal candidates for radioembolization have preserved liver function without ascites or encephalopathy, Child-Pugh score <7 and limited lung shunting. Phase III randomized controlled trials (RCTs) against other liver-directed therapies are lacking for intermediate-stage hepatocellular carcinoma. However, preliminary data from a recent RCT has suggested that radioembolization has a similar time-to-progression and comparable toxicity to selective chemoembolization. Phase II/III RCTs are now ongoing to evaluate the combination of radioembolization with systemic therapies in advanced-stage hepatocellular carcinoma and metastatic liver-dominant colorectal cancer in order to expand the treatment opportunities for patients with cancers in the liver.
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Affiliation(s)
- Rita Golfieri
- Radiology Unit, Department of Digestive Diseases & Internal Medicine, Azienda Ospedaliero-Universitaria, Policlinico S. Orsola-Malpighi, Via Massarenti 9, Bologna, Italy
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Cremonesi M, Chiesa C, Strigari L, Ferrari M, Botta F, Guerriero F, De Cicco C, Bonomo G, Orsi F, Bodei L, Di Dia A, Grana CM, Orecchia R. Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective. Front Oncol 2014; 4:210. [PMID: 25191640 PMCID: PMC4137387 DOI: 10.3389/fonc.2014.00210] [Citation(s) in RCA: 125] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Accepted: 07/23/2014] [Indexed: 12/18/2022] Open
Abstract
Radioembolization (RE) of liver cancer with 90Y-microspheres has been applied in the last two decades with notable responses and acceptable toxicity. Two types of microspheres are available, glass and resin, the main difference being the activity/sphere. Generally, administered activities are established by empirical methods and differ for the two types. Treatment planning based on dosimetry is a prerogative of few centers, but has notably gained interest, with evidence of predictive power of dosimetry on toxicity, lesion response, and overall survival (OS). Radiobiological correlations between absorbed doses and toxicity to organs at risk, and tumor response, have been obtained in many clinical studies. Dosimetry methods have evolved from the macroscopic approach at the organ level to voxel analysis, providing absorbed dose spatial distributions and dose–volume histograms (DVH). The well-known effects of the external beam radiation therapy (EBRT), such as the volume effect, underlying disease influence, cumulative damage in parallel organs, and different tolerability of re-treatment, have been observed also in RE, identifying in EBRT a foremost reference to compare with. The radiobiological models – normal tissue complication probability and tumor control probability – and/or the style (DVH concepts) used in EBRT are introduced in RE. Moreover, attention has been paid to the intrinsic different activity distribution of resin and glass spheres at the microscopic scale, with dosimetric and radiobiological consequences. Dedicated studies and mathematical models have developed this issue and explain some clinical evidences, e.g., the shift of dose to higher toxicity thresholds using glass as compared to resin spheres. This paper offers a comprehensive review of the literature incident to dosimetry and radiobiological issues in RE, with the aim to summarize the results and to identify the most useful methods and information that should accompany future studies.
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Affiliation(s)
| | | | - Lidia Strigari
- Istituto Nazionale dei Tumori Regina Elena , Rome , Italy
| | | | | | | | | | | | - Franco Orsi
- Istituto Europeo di Oncologia , Milan , Italy
| | - Lisa Bodei
- Istituto Europeo di Oncologia , Milan , Italy
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Gibbs P, Tie J, Bester L. Radioembolization for colorectal cancer liver metastases: current role and future opportunities – the medical oncologist’s perspective. COLORECTAL CANCER 2014. [DOI: 10.2217/crc.14.24] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
SUMMARY The liver is the most common and often the only site of metastatic disease in patients with metastatic colorectal cancer. For patients who do not have resectable disease, a number of liver-directed therapies are increasingly being used in routine clinical practice, including yttrium-90 radioembolization. The challenge for the medical oncologist is how best to integrate this promising new option into routine practice in the setting of ever-evolving standard systemic therapy options. Here we review the most recent data on the efficacy and safety of yttrium-90, considerations when selecting patients for treatment and we examine the potential impact of current clinical trials.
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Affiliation(s)
- Peter Gibbs
- Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Melbourne, Australia
| | - Jeanne Tie
- Systems Biology Division, Walter and Eliza Hall Institute, Parkville, Melbourne, Australia
| | - Lourens Bester
- Interventional Radiology, Department of Medical Imaging, St Vincent’s Hospital, Sydney, Australia
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Cholapranee A, van Houten D, Deitrick G, Dagli M, Sudheendra D, Mondschein JI, Soulen MC. Risk of liver abscess formation in patients with prior biliary intervention following yttrium-90 radioembolization. Cardiovasc Intervent Radiol 2014; 38:397-400. [PMID: 24989145 DOI: 10.1007/s00270-014-0947-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 06/08/2014] [Indexed: 01/14/2023]
Abstract
PURPOSE Patients without a competent sphincter of Oddi due to prior surgical or endoscopic therapy are at high risk for liver abscess following chemoembolization despite aggressive antimicrobial prophylaxis. We examined a cohort of such patients undergoing Y-90 resin radioembolization and compared them to a cohort of chemoembolized patients. METHODS Review of our quality-assurance database identified 24 radioembolizations performed in 16 patients with prior biliary intervention. An aggressive prophylactic regimen of oral levofloxacin and metronidazole 2 days pre-procedure continuing for 14 days after, oral neomycin/erythromycin bowel prep the day before, and IV levofloxacin/metronidazole the day of treatment was prescribed. Patients underwent resin microsphere radioembolization dosed according to the BSA method. Patients had clinical, imaging, and laboratory assessment 1 month after each treatment, and then every 3 months. The chemoembolization cohort consisted of 13 patients with prior biliary intervention who had undergone 24 chemoembolization procedures. RESULTS No radioembolization patient developed an abscess. In the cohort of chemoembolized patients who received the same prophylaxis, liver abscess occurred following 3 of 24 (12.5 %) procedures in 3 of 13 (23 %) patients, one fatal. CONCLUSIONS This preliminary experience suggests that the risk of liver abscess among patients with prior biliary intervention may be lower following radioembolization than chemoembolization, which could potentially expand treatment options in this high-risk population.
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Affiliation(s)
- Aurada Cholapranee
- Division of Interventional Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
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Cohen SJ, Konski AA, Putnam S, Ball DS, Meyer JE, Yu JQ, Astsaturov I, Marlow C, Dickens A, Cade DN, Meropol NJ. Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer. Br J Cancer 2014; 111:265-71. [PMID: 24983373 PMCID: PMC4102951 DOI: 10.1038/bjc.2014.344] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Revised: 05/16/2014] [Accepted: 05/27/2014] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. METHODS Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine. RESULTS Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively. CONCLUSIONS This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.
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Affiliation(s)
- S J Cohen
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - A A Konski
- Department of Radiation Oncology, Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - S Putnam
- Department of Radiology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - D S Ball
- Department of Radiology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - J E Meyer
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - J Q Yu
- Department of Radiology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - I Astsaturov
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - C Marlow
- Clinical Trials Office, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - A Dickens
- Clinical Trials Office, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - D N Cade
- Sirtex Medical Ltd, Sydney, New South Wales, Australia
| | - N J Meropol
- Division of Hematology and Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA
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Molla N, AlMenieir N, Simoneau E, Aljiffry M, Valenti D, Metrakos P, Boucher LM, Hassanain M. The role of interventional radiology in the management of hepatocellular carcinoma. ACTA ACUST UNITED AC 2014; 21:e480-92. [PMID: 24940108 DOI: 10.3747/co.21.1829] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (hcc) is one of the most common causes of cancer-related death worldwide. Overall, liver transplantation and resection are the only available treatments with potential for cure. Various locoregional therapies are widely used to manage patients with advanced hcc or as a bridging therapy for patients with early and intermediate disease. This article reviews and evaluates the role of interventional radiology in the management of such cases by assessing various aspects of each method, such as effect on rates of survival, recurrence, tumour response, and complications. METHODS A systemic search of PubMed, medline, Ovid Medline In-Process, and the Cochrane Database of Systematic Reviews retrieved all related scientific papers for review. RESULTS Needle core biopsy is a highly sensitive, specific, and accurate method for hcc grading. Portal-vein embolization provides adequate expansion of the future liver remnant, making more patients eligible for resection. In focal or multifocal unresectable early-stage disease, radiofrequency ablation tops all other thermoablative methods. However, microwave ablation is preferred in large tumours and in patients with Child-Pugh B disease. Cryoablation is preferred in recurrent disease and in patients who are poor candidates for anesthesia. Of the various transarterial modalities-transarterial chemoembolization (tace), drug-eluting beads, and transarterial radio-embolization (tare)-tace is the method of choice in Child-Pugh A disease, and tare is the method of choice in hcc cases with portal vein thrombosis. CONCLUSIONS The existing data support the importance of a multidisciplinary approach in hcc management. Large randomized controlled studies are needed to provide clear indication guidelines for each method.
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Affiliation(s)
- N Molla
- Department of Radiology, King Saud University, Riyadh, Saudi Arabia. ; Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC
| | - N AlMenieir
- Department of Radiology, King Saud University, Riyadh, Saudi Arabia
| | - E Simoneau
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC
| | - M Aljiffry
- Department of Surgery, King Abdulaziz University, Jeddah, Saudi Arabia
| | - D Valenti
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - P Metrakos
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC. ; Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - L M Boucher
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - M Hassanain
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC. ; Department of Surgery, King Saud University, Riyadh, Saudi Arabia
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Chiesa C, Lambert B, Maccauro M, Ezziddin S, Ahmadzadehfar H, Dieudonné A, Cremonesi M, Konijnenberg M, Lassmann M, Pettinato C, Strigari L, Vanderlinden B, Crippa F, Flamen P, Garin E. Pretreatment Dosimetry in HCC Radioembolization with (90)Y Glass Microspheres Cannot Be Invalidated with a Bare Visual Evaluation of (99m)Tc-MAA Uptake of Colorectal Metastases Treated with Resin Microspheres. J Nucl Med 2014; 55:1215-6. [PMID: 24898027 DOI: 10.2967/jnumed.113.129361] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Carlo Chiesa
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Bieke Lambert
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Marco Maccauro
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Samer Ezziddin
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Hojjat Ahmadzadehfar
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Arnaud Dieudonné
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Marta Cremonesi
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Mark Konijnenberg
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Michael Lassmann
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Cinzia Pettinato
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Lidia Strigari
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Bruno Vanderlinden
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Flavio Crippa
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Patrick Flamen
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
| | - Etienne Garin
- Foundation IRCCS Istituto Nazionale Tumori Via Giacomo Venezian 1 I-20133 Milan, Italy E-mail:
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Abstract
Unresectable primary and metastatic liver tumors are a leading cause of cancer mortality and morbidity. This remains a challenging and key task for every oncologist despite significant advances that have been made with selective targeted systemic agents and in technology advances with radiotherapy delivery. Radioembolization (RE) is a technique of permanently implanting microspheres containing Yttrium-90 ((90)Y), a beta-emitting isotope with a treatment range of 2 mm, into hepatic tumors. This form of brachytherapy utilizes the unique dual vascular anatomy of the liver to preferentially deliver radioactive particles via the hepatic artery to tumor, sparing normal liver parenchyma. The main treatment inclusion criteria are patients with solid tumors, compensated liver functions, life expectancy of at least three months, and ECOG performance status 0-2. Benefit of RE has been proven in patients that have low-to-moderate extrahepatic disease burden, prior liver radiotherapy, heavy prior chemotherapy and biologic agent exposure, and history of hepatic surgery or ablation. Most of the clinical evidence is reported in metastatic colorectal, and neuroendocrine tumors (NET), and primary hepatocellular cancer. A growing body of data supports the use of RE in hepatic metastatic breast cancer, intrahepatic cholangiocarinoma, and many other metastatic tumor types. Side effects are typically mild constitutional and GI issues limited to the first 7-14 days post treatment, with only 6% grade 3 toxicity reported in large series. Potentially serious or fatal radiation induced liver disease is extremely rare, reported in only 1% or fewer in major series of both metastatic and primary tumors treated with RE. Currently, high priority prospective clinical trials are testing RE combined with chemotherapy in first line therapy for colorectal hepatic metastases, and combined with sorafenib for hepatocellular carcinomas (HCCs). Fortunately, this beneficial and now widely available therapy is being increasingly incorporated into the standard therapy algorithms of multidisciplinary GI cancer teams worldwide. This form of radiotherapy differs significantly from daily external beam radiotherapy in many ways, particularly in dose rate, dosimetric coverage and duration of radiation delivery, side effects, and patient selection factors. A wealth of experience using RE in solid tumors exists and ongoing major prospective clinical trials will soon clarify the role of RE in the management of metastatic colorectal liver metastases.
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Affiliation(s)
- Andrew Kennedy
- Radiation Oncology Research, Sarah Cannon Research Institute, 3322 West End Ave., Suite 800 Nashville, TN 37203, USA
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Pellerin O, Lin M, Bhagat N, Shao W, Geschwind JF. Can C-arm cone-beam CT detect a micro-embolic effect after TheraSphere radioembolization of neuroendocrine and carcinoid liver metastasis? Cancer Biother Radiopharm 2014; 28:459-65. [PMID: 23484809 DOI: 10.1089/cbr.2012.1390] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
RATIONAL AND OBJECTIVE Radioembolization with yttrium-90 microspheres is a therapy that is used for hepatic tumors. 20-30 μm microspheres loaded with Y90 are supposedly occluding tumor vessels at the capillary level. Then, these spheres deliver high-dose radiation to the tumor. However, this theoretical embolic effect has never been appreciated in imaging. Dual-Phase cone-beam computed tomography (DPCBCT) is a multi-phasic intra-procedural scan that uses only one contrast media injection to visualize early (feeding vessel) and delayed (capillary level) tumor enhancement. The purpose of this study was to determine whether there is a micro-embolic effect induced by TheraSpheres® (MDS Nordion, Ottawa, Ontario, Canada) at the capillary level by using DPCBCT imaging. MATERIALS AND METHODS 14 patients with 72 carcinoid or neuroendocrine tumors were treated with radioembolization, and all underwent DPCBCT (Allura Xper, Philips Healthcare) imaging before and immediately after radioembolization with TheraSpheres®. Tumor enhancement was measured in each phase by drawing a region of interest within the tumors. RESULTS 72 tumors were evaluated: average tumor density in the early arterial phase was 241 and 230 Hounsfield units (HU) (p<0.001) before and after radioembolization, respectively; the average density in the delayed arterial phase was 226 and 161 HU (p<0.001) before and after radioembolization, respectively. Average difference in tumor attenuation before and after radioembolization in early arterial and delayed phase was 11 HU and 64 HU (p<0.001), respectively. CONCLUSION The significant decrease in tumor enhancement in the DPCBCT delayed phase after TheraSpheres® injection indicates that there is an appreciable microembolic effect at the tumor capillary bed level.
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Affiliation(s)
- Olivier Pellerin
- Division of Vascular and Interventional Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA
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50
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The dosimetric importance of the number of 90Y microspheres in liver transarterial radioembolization (TARE). Eur J Nucl Med Mol Imaging 2014; 41:634-8. [DOI: 10.1007/s00259-013-2674-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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