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Ronot M, Loffroy R, Arnold D, Greget M, Sengel C, Pinaquy JB, Pellerin O, Maleux G, Peynircioglu B, Pelage JP, Schaefer N, Sangro B, de Jong N, Zeka B, Urdaniz M, Helmberger T, Vilgrain V. Transarterial Radioembolisation with Y90 Resin Microspheres and the Effect of Reimbursement Criteria in France: Final Results of the CIRT-FR Prospective Observational Study. Cardiovasc Intervent Radiol 2025; 48:205-220. [PMID: 39809885 PMCID: PMC11790776 DOI: 10.1007/s00270-024-03955-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 12/18/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE This analysis of the CIRSE Registry for SIR-Spheres Therapy in France, CIRT-FR, reports on real-world outcomes of transarterial radioembolisation (TARE) with Y90 resin microspheres for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRLM) patients in France, focusing on safety, effectiveness and health-related quality of life (HRQoL). Results on patients treated based on national reimbursement criteria are discussed here. METHODS Prospective, multicentre, observational study of HCC and CRLM patients treated between August 2017 and July 2020 with TARE Y90 resin microspheres. Patients were assigned to different analysis groups based on reimbursement recommendations. Follow-up period was at least 24 months with patient data collected every 3 months. RESULTS In total, 252 (193 HCC, 59 CRLM) patients of CIRT-FR were included in the analysis. No differences in effectiveness, safety and HRQoL were found between analysis groups based on reimbursement recommendations. Median overall survival for HCC and CRLM was 19.0 (95% CI, 16.1-22.4) and 10.8 (95% CI, 8.0-13.5) months, respectively. Serious procedure-related adverse events occurred in 13% of the patients. HRQoL generally remained stable, with some fluctuations in function scores and symptoms. CONCLUSION In our cohorts, patients performed similarly regarding clinical outcomes irrespective of their analysis group based on reimbursement recommendations. Our results suggest that instead of restrictive reimbursement criteria, more decision-making power in selecting suitable patient groups could be given to multidisciplinary tumour boards. Results confirm that TARE with Y90 resin microspheres is an effective and safe treatment for liver cancer, with maintained HRQoL in most patients.
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Affiliation(s)
- M Ronot
- Department of Radiology, Hôpital Beaujon APHP Nord, Université Paris Cité, Paris, CRI, INSERM, 1149, Clichy, France
| | - R Loffroy
- Department of Vascular and Interventional Radiology, Image-Guided Therapy Center, CHU Dijon Bourgogne, François-Mitterrand University Hospital, 14 Rue Gaffarel, 21000, Dijon, France
| | - D Arnold
- Oncology and Hematology, Asklepios Tumorzentrum Hamburg, AK Altona, Paul-Ehrlich-Str. 1, 22763, Hamburg, Germany
| | - M Greget
- Imagerie Interventionnelle UF 7524 Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 67200, Strasbourg, France
| | - C Sengel
- Interventional Radiology, Centre Hospitalier Universitaire de Grenoble, Boulevard de La Chantourne, 38100, Grenoble, France
| | - J B Pinaquy
- Department of Nuclear Medicine, CHU Bordeaux, 33000, Bordeaux, France
| | - O Pellerin
- Department of Vascular and Oncological Interventional Radiology, AP-HP, Hôpital Européen Georges Pompidou, HEKA INRIA, INSERM PARCC U 970, Université de Paris Cité, 20 Rue LEBLANC, 75015, Paris, France
| | - G Maleux
- Radiology, Universitair Ziekenhuis Leuven, Herestraat 49, 3000, Louvain, Belgium
| | - B Peynircioglu
- Department of Radiology, School of Medicine, Hacettepe University, Sihhiye Campus, 06100, Ankara, Turkey
| | - J P Pelage
- Department of Diagnostic Radiology, McGill University Health Centre (MUHC - Glen) - Royal Victoria Hospital, Montreal, Canada
| | - N Schaefer
- Service de Médecine Nucléaire Et Imagerie Moléculaire, CHUV, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - B Sangro
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Avda. Pio XII 36, 31008, Pamplona, Spain
| | - N de Jong
- P+F Products and Features GmbH, Bösendorferstraße 5/3, 1010, Vienna, Austria
| | - B Zeka
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Neutorgasse 9, 1010, Vienna, Austria
| | - M Urdaniz
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Neutorgasse 9, 1010, Vienna, Austria.
| | - T Helmberger
- Department of Radiology, Neuroradiology and Minimal-Invasive Therapy, Klinikum Bogenhausen, Englschalkinger Str. 77, 81925, Munich, Germany
| | - V Vilgrain
- Department of Radiology, Hôpital Beaujon APHP Nord, Université Paris Cité, Paris, CRI, INSERM, 1149, Clichy, France
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Cutrì E, Morel-Corlu E, Rolland Y, Saint-Jalmes H, Eliat PA, Garin E, Bezy-Wendling J. A microscopic model of the dose distribution in hepatocellular carcinoma after selective internal radiation therapy. Phys Med 2024; 122:103384. [PMID: 38824827 DOI: 10.1016/j.ejmp.2024.103384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 04/03/2024] [Accepted: 05/21/2024] [Indexed: 06/04/2024] Open
Abstract
The dosimetry evaluation for the selective internal radiation therapy is currently performed assuming a uniform activity distribution, which is in contrast with literature findings. A 2D microscopic model of the perfused liver was developed to evaluate the effect of two different 90Y microspheres distributions: i) homogeneous partitioning with the microspheres equally distributed in the perfused liver, and ii) tumor-clustered partitioning where the microspheres distribution is inferred from the patient specific images. METHODS Two subjects diagnosed with liver cancer were included in this study. For each subject, abdominal CT scans acquired prior to the SIRT and post-treatment 90Y positron emission tomography were considered. Two microspheres partitionings were simulated namely homogeneous and tumor-clustered partitioning. The homogeneous and tumor-clustered partitionings were derived starting from CT images. The microspheres radiation is simulated by means of Russell's law. RESULTS In homogenous simulations, the dose delivery is uniform in the whole liver while in the tumor-clustered simulations a heterogeneous distribution of the delivered dose is visible with higher values in the tumor regions. In addition, in the tumor-clustered simulation, the delivered dose is higher in the viable tumor than in the necrotic tumor, for all patients. In the tumor-clustered case, the dose delivered in the non-tumoral tissue (NTT) was considerably lower than in the perfused liver. CONCLUSIONS The model proposed here represents a proof-of-concept for personalized dosimetry assessment based on preoperative CT images.
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Affiliation(s)
- Elena Cutrì
- Univ Rennes, CLCC Eugène Marquis, Inserm, LTSI - UMR 1099, F-35000, Rennes, France; Université de technologie de Compiègne, CNRS, Biomechanics and Bioengineering, 60203 Compiègne Cedex, France; Inria, Saclay Ile-de-France, Palaiseau, 91120, France.
| | - Ewan Morel-Corlu
- Univ Rennes, CLCC Eugène Marquis, Inserm, LTSI - UMR 1099, F-35000, Rennes, France
| | - Yan Rolland
- Univ Rennes, CLCC Eugène Marquis, Inserm, LTSI - UMR 1099, F-35000, Rennes, France
| | - Hervé Saint-Jalmes
- Univ Rennes, CLCC Eugène Marquis, Inserm, LTSI - UMR 1099, F-35000, Rennes, France
| | - Pierre-Antoine Eliat
- INRAE, INSERM, Univ Rennes, Nutrition Metabolisms and Cancer, NuMeCan, St Gilles, Rennes, France; CNRS, INSERM, Biosit UAR 3480 US_S 018, PRISM, Univ Rennes, Rennes, France
| | - Etienne Garin
- INRAE, INSERM, Univ Rennes, Nutrition Metabolisms and Cancer, NuMeCan, St Gilles, Rennes, France; Department of Nuclear Medicine, Centre Eugène Marquis, Rennes, France
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Roll W, Masthoff M, Köhler M, Rahbar K, Stegger L, Ventura D, Morgül H, Trebicka J, Schäfers M, Heindel W, Wildgruber M, Schindler P. Radiomics-Based Prediction Model for Outcome of Radioembolization in Metastatic Colorectal Cancer. Cardiovasc Intervent Radiol 2024; 47:462-471. [PMID: 38416178 DOI: 10.1007/s00270-024-03680-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 01/31/2024] [Indexed: 02/29/2024]
Abstract
PURPOSE To evaluate the benefit of a contrast-enhanced computed tomography (CT) radiomics-based model for predicting response and survival in patients with colorectal liver metastases treated with transarterial Yttrium-90 radioembolization (TARE). MATERIALS AND METHODS Fifty-one patients who underwent TARE were included in this single-center retrospective study. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 3-month follow-up. Patients were stratified as responders (complete/partial response and stable disease, n = 24) or non-responders (progressive disease, n = 27). Radiomic features (RF) were extracted from pre-TARE CT after segmentation of the liver tumor volume. A model was built based on a radiomic signature consisting of reliable RFs that allowed classification of response using multivariate logistic regression. Patients were assigned to high- or low-risk groups for disease progression after TARE according to a cutoff defined in the model. Kaplan-Meier analysis was performed to analyze survival between high- and low-risk groups. RESULTS Two independent RF [Energy, Maximal Correlation Coefficient (MCC)], reflecting tumor heterogeneity, discriminated well between responders and non-responders. In particular, patients with higher magnitude of voxel values in an image (Energy), and texture complexity (MCC), were more likely to fail TARE. For predicting treatment response, the area under the receiver operating characteristic curve of the radiomics-based model was 0.75 (95% CI 0.48-1). The high-risk group had a shorter overall survival than the low-risk group (3.4 vs. 6.4 months, p < 0.001). CONCLUSION Our CT radiomics model may predict the response and survival outcome by quantifying tumor heterogeneity in patients treated with TARE for colorectal liver metastases.
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Affiliation(s)
- Wolfgang Roll
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Max Masthoff
- Clinic for Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Michael Köhler
- Clinic for Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Kambiz Rahbar
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Lars Stegger
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - David Ventura
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Haluk Morgül
- Department for General, Visceral and Transplantation Surgery, University Hospital Münster, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Jonel Trebicka
- Department of Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Michael Schäfers
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Walter Heindel
- Clinic for Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany
| | - Moritz Wildgruber
- Clinic for Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
- Department of Radiology, University Hospital LMU, Munich, Munich, Germany
| | - Philipp Schindler
- Clinic for Radiology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
- West German Cancer Centre (WTZ), Münster Site, Münster, Germany.
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González-Flores E, Zambudio N, Pardo-Moreno P, Gonzalez-Astorga B, de la Rúa JR, Triviño-Ibáñez EM, Navarro P, Espinoza-Cámac N, Casado MÁ, Rodríguez-Fernández A. Recommendations for the management of yttrium-90 radioembolization in the treatment of patients with colorectal cancer liver metastases: a multidisciplinary review. Clin Transl Oncol 2024; 26:851-863. [PMID: 37747636 PMCID: PMC10981623 DOI: 10.1007/s12094-023-03299-y] [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: 05/04/2023] [Accepted: 07/27/2023] [Indexed: 09/26/2023]
Abstract
PURPOSE Strategies for the treatment of liver metastases from colon cancer (lmCRC) are constantly evolving. Radioembolization with yttrium 90 (Y-90 TARE) has made significant advancements in treating liver tumors and is now considered a potential option allowing for future resection. This study reviewed the scientific evidence and developed recommendations for using Y-90 TARE as a treatment strategy for patients with unresectable lmCRC. METHODS A multidisciplinary scientific committee, consisting of experts in medical oncology, hepatobiliary surgery, radiology, and nuclear medicine, all with extensive experience in treating patients with ImCRC with Y-90 TARE, led this project. The committee established the criteria for conducting a comprehensive literature review on Y-90 TARE in the treatment of lmCRC. The data extraction process involved addressing initial preliminary inquiries, which were consolidated into a final set of questions. RESULTS This review offers recommendations for treating patients with lmCRC using Y-90 TARE, addressing four areas covering ten common questions: 1) General issues (multidisciplinary tumor committee, indications for treatment, contraindications); 2) Previous process (predictive biomarkers for patient selection, preintervention tests, published evidence); 3) Procedure (standard procedure); and 4) Post-intervention follow-up (potential toxicity and its management, parameters for evaluation, quality of life). CONCLUSIONS Based on the insights of the multidisciplinary committee, this document offers a comprehensive overview of the technical aspects involved in the management of Y-90 TARE. It synthesizes recommendations for applying Y-90 TARE across various phases of the treatment process.
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Affiliation(s)
- Encarna González-Flores
- Medical Oncology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
- Instituto de Investigación Biosanitaria IBS, Granada, Spain
| | - Natalia Zambudio
- Surgery Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - Pedro Pardo-Moreno
- Radiodiagnostic Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | | | | | - Eva M Triviño-Ibáñez
- Nuclear Medicine Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - Pablo Navarro
- Radiodiagnostic Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - Nataly Espinoza-Cámac
- Pharmacoeconomics and Outcomes Research Iberia (PORIB), Paseo Joaquín Rodrigo 4-I, Pozuelo de Alarcón, 28224, Madrid, Spain.
| | - Miguel Ángel Casado
- Pharmacoeconomics and Outcomes Research Iberia (PORIB), Paseo Joaquín Rodrigo 4-I, Pozuelo de Alarcón, 28224, Madrid, Spain
| | - Antonio Rodríguez-Fernández
- Instituto de Investigación Biosanitaria IBS, Granada, Spain
- Nuclear Medicine Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
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He J, Li M, Xu Y, Fan N, Tian C, Lv T, Xing W, Yu H. In vitro characteristics of Epirubicin-loaded thermosensitive liquid embolic agent. J Cancer Res Ther 2023; 19:1597-1602. [PMID: 38156927 DOI: 10.4103/jcrt.jcrt_334_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 08/01/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVE To investigate the drug loading and release rate of epirubicin-loaded thermosensitive liquid embolic agents in vitro. MATERIALS AND METHODS The drug loading and stability of epirubicin-loaded thermosensitive liquid embolic agents with or without iopromide were determined by high-performance liquid chromatography, and the same method was used to determine the drug release rate of thermosensitive liquid embolic agents at different time points. RESULTS For epirubicin-loaded thermosensitive liquid embolic agents without iopromide, the average drug loading after filtration by membrane was (0.78 ± 0.02) mg and the drug loading rate was (16.1 ± 0.35)%, while the average drug loading without membrane was (0.73 ± 0.06) mg and the drug loading rate was (15.07 ± 1.17)%. After adding iopromide, the drug loading capacity was measured from 0 h-24 h solution and the drug loading was calculated indirectly and conclude that the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared. The sustained release rate of epirubicin from 0 to 48 hours was 42.65% in 48 hours. CONCLUSION Epirubicin can be successfully loaded into the thermosensitive liquid embolic agents with good stability and sustained release. After adding iopromide, the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared.
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Affiliation(s)
- Ji'an He
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
- Department of General Surgery, Tianjin Beichen Traditional Chinese Medicine Hospital, Tianjin, China
| | - Mei Li
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Yan Xu
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Ning Fan
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
- Department of General Surgery, Tianjin Beichen Traditional Chinese Medicine Hospital, Tianjin, China
| | - Chong Tian
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
- Department of Oncology, Tianjin Beichen Hospital, Tianjin, China
| | - Tianye Lv
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
- Department of Oncology, The 983 Hospital of Joint Logistics Support Force of PLA, Tianjin, China
| | - Wenge Xing
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Haipeng Yu
- Department of Interventional Therapy, Tianjin Medical University Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
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Boshell D, Bester L. Radioembolisation of liver metastases. J Med Imaging Radiat Oncol 2023; 67:842-852. [PMID: 37343147 DOI: 10.1111/1754-9485.13549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 06/05/2023] [Indexed: 06/23/2023]
Abstract
This review aims to present contemporary data for SIRT in the treatment of secondary hepatic malignancies including colorectal, neuroendocrine, breast and uveal melanoma.
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Affiliation(s)
- David Boshell
- Department of Radiology, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Lourens Bester
- Department of Radiology, University of Notre Dame, Sydney, New South Wales, Australia
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Vulasala SSR, Sutphin PD, Kethu S, Onteddu NK, Kalva SP. Interventional radiological therapies in colorectal hepatic metastases. Front Oncol 2023; 13:963966. [PMID: 37324012 PMCID: PMC10266282 DOI: 10.3389/fonc.2023.963966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 05/19/2023] [Indexed: 06/17/2023] Open
Abstract
Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases.
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Affiliation(s)
- Sai Swarupa R. Vulasala
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL, United States
| | - Patrick D. Sutphin
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Samira Kethu
- Department of Microbiology and Immunology, College of Arts and Sciences, University of Miami, Coral Gables, FL, United States
| | - Nirmal K. Onteddu
- Department of Hospital Medicine, Flowers Hospital, Dothan, AL, United States
| | - Sanjeeva P. Kalva
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
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Schmid BP, Silva Cunha MJ, Moreira Valle LG, Galastri FL, Affonso BB, Falsarella PM, Kaliks Guendelmann RA, Garcia RG, Nasser F. Transarterial Selective Internal Radiation Therapy with Yttrium-90 for Liver Metastatic Urothelial Carcinoma of the Ureter as a Bridging Therapy to Immunotherapy: A Case Report with a 10-Year Follow-Up. Case Rep Oncol 2023; 16:711-717. [PMID: 37933309 PMCID: PMC10625822 DOI: 10.1159/000531787] [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: 09/26/2022] [Accepted: 06/16/2023] [Indexed: 11/08/2023] Open
Abstract
Primary transitional cell carcinoma of the ureter is a rare type of cancer with metastasis presented in approximately 25% at diagnosis. Due to its rarity and poor prognosis, the management of this neoplasm is still controversial, and the development of new therapies is of uttermost importance. Herein, we describe a case of a 54-year-old patient diagnosed with transitional cell carcinoma of the left ureter submitted to left nephroureterectomy (pT3N2M0) and methotrexate, vinblastine, doxorubicin, and cisplatin adjuvant chemotherapy. A single liver metastasis was detected and combination chemotherapy with gemcitabine and carboplatin was initiated along with stereotactic body radiation therapy. Despite these 2 previous chemotherapy regimens, the patient presented disease progression and transarterial selective internal radiation therapy (SIRT) with yttrium-90 was indicated. This locoregional treatment was performed with the administration of 1.2 GBq yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, NSW, Australia) into the right hepatic artery. Another systemic treatment was immunotherapy using nivolumab with excellent tolerability. After 10 years of follow-up, at the last clinical evaluation, the patient had no clinical symptoms and the last imaging follow-up using positron emission tomography-computed tomography scan showed complete response. This report introduces upper urinary tract urothelial carcinoma as a distinct type of malignancy in which SIRT can be safely implemented. As a transition method to nivolumab, it was successful. There might be a potential therapeutic synergism between these 2 treatment modalities.
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Affiliation(s)
- Bruno Pagnin Schmid
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | | | | | | | - Breno Boueri Affonso
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | | | | | - Rodrigo Gobbo Garcia
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Felipe Nasser
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
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Alexander HC, Nguyen CH, Chu MJJ, Tarr GP, Han CH, Thomas RH, Holden AH, Bartlett ASJR. Transarterial Radioembolization for Hepatic Metastases of Pancreatic Adenocarcinoma: A Systematic Review. J Vasc Interv Radiol 2022; 33:1559-1569.e2. [PMID: 36084842 DOI: 10.1016/j.jvir.2022.08.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 08/19/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
PURPOSE To assess the safety and effectiveness of transarterial radioembolization (TARE) in the treatment of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS A systematic search of the Embase and MEDLINE databases was conducted using keywords and Medical Subject Headings terms related to TARE and hepatic metastases from PDAC. Observational studies and clinical trials reporting overall survival (OS), hepatic progression-free survival (hPFS), or tumor response after TARE were included. RESULTS Eight studies, comprising 145 patients with metastatic PDAC, met the inclusion criteria. No randomized controlled trials were identified, and 4 studies were prospective. Forty-four (30.3%) patients underwent previous pancreatic resection, and 66 (45.5%) had extrahepatic metastases at the time of TARE. Most studies (n = 6) used resin microspheres for TARE. The pooled disease control rate was 69.4% at a median of 3 months. The median OS from the time of TARE ranged from 3.7 to 9 months. The median hPFS ranged from 2.4 to 5.2 months. There were 31 Grade 3-4 biochemical toxicities and 4 treatment-related deaths. CONCLUSIONS The role of TARE in patients with hepatic metastases from PDAC remains unclear owing to low patient numbers, limited prospective data, and heterogeneity in the study design. Further prospective studies are required to evaluate the role of TARE in carefully selected patients with liver-only metastatic disease.
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Affiliation(s)
- Harry C Alexander
- Department of Radiology, Auckland District Health Board, Auckland, New Zealand.
| | - Cindy H Nguyen
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Michael J J Chu
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Gregory P Tarr
- Department of Radiology, Auckland District Health Board, Auckland, New Zealand
| | - Catherine H Han
- Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Robert H Thomas
- Department of Radiology, Imperial College London, London, United Kingdom
| | - Andrew H Holden
- Department of Radiology, Auckland District Health Board, Auckland, New Zealand
| | - Adam S J R Bartlett
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
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Messmer F, Zgraggen J, Kobe A, Chaykovska L, Puippe G, Reiner CS, Pfammatter T. Quantitative and qualitative evaluation of liver metastases with intraprocedural cone beam CT prior to transarterial radioembolization as a predictor of treatment response. RESEARCH IN DIAGNOSTIC AND INTERVENTIONAL IMAGING 2022; 1:100005. [PMID: 39077371 PMCID: PMC11265323 DOI: 10.1016/j.redii.2022.100005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 03/21/2022] [Indexed: 07/31/2024]
Abstract
Purpose To investigate, by quantitative and qualitative enhancement measurements, the correlation between tumor enhancement on cone beam computed tomography (CBCT) images and treatment response at 6 months in patients undergoing transarterial radioembolization (TARE) for liver metastases. Materials and Methods 36 patients (56% male; median age 62.5 years) with 104 metastases were retrospectively included. Quantitative and qualitative enhancement of liver metastases were evaluated on CBCT images before TARE. Quantitative analysis consisted of lesion enhancement measurements (ROI HU lesion - ROI HU relative to inferior vena cava). Qualitative analysis consisted of subjective enhancement pattern analysis (diffuse, sparse, rim-like or non-enhancing). Morphologic tumor response was evaluated according to RECIST 1.1 criteria on follow-up CT or MR imaging. Results At a mean follow up of 6.5 ± 3.7 months, progressive disease (PD) was found in 4 patients, partial response (PR) in 11 and stable disease (SD) in 21. Relative lesion enhancement was significantly different between these groups (-37.5±154.2 HU vs. 103.8±93.4 vs. 181±144 HU in PD vs. SD vs. PR group, respectively; p<0.01). ROC analysis of relative lesion enhancement to predict progressive disease showed an area under the curve of 0.86 (p<0.01). For qualitative lesion enhancement analysis, no difference between groups was found. Conclusion Quantitative enhancement measurements derived from intraprocedural contrast enhanced CBCT may identify responders to TARE in patients with liver metastases.
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Affiliation(s)
- Florian Messmer
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Juliana Zgraggen
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Adrian Kobe
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | | | - Gilbert Puippe
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Caecilia S. Reiner
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Thomas Pfammatter
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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11
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Bartoli F, Eckelman WC, Boyd M, Mairs RJ, Erba PA. Principles of Molecular Targeting for Radionuclide Therapy. NUCLEAR ONCOLOGY 2022:41-93. [DOI: 10.1007/978-3-031-05494-5_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Alexander H, Wen D, Chu M, Han C, Hadden P, Thomas R, Bartlett A. Selective internal radiation therapy for hepatic metastases of uveal melanoma: a systematic review. Br J Radiol 2022; 95:20210200. [PMID: 34757824 PMCID: PMC8722257 DOI: 10.1259/bjr.20210200] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE Uveal melanoma (UM) commonly metastasizes to the liver. Treatment usually consists of liver-directed therapies, such as selective internal radiation therapy (SIRT). This review aimed to assess the effectiveness and safety of SIRT for hepatic metastases from UM. METHODS The study protocol is available at OSF (https://osf.io/vhyct/). EMBASE and MEDLINE were searched until July 2020, using terms related to SIRT and hepatic metastases from UM. Studies reporting outcomes of SIRT in patients with UM and at least one hepatic metastasis were included. Data on overall survival (OS), hepatic progression free survival (hPFS) or tumor response were collected. The Newcastle-Ottawa Scale (NOS) was used to assess risk of bias. RESULTS 11 studies were included, reporting outcomes for 268 patients with hepatic metastases from UM. Most studies (n = 9, 81.8%) were retrospective. Disease control was achieved in 170 patients (67.5%) and the median OS from time of SIRT was 12.3 months. Median hPFS was 5.4 months. Low-grade side-effects were common but serious complications were infrequent. There were two treatment-related deaths. The median NOS score was 6 (moderate risk of bias). CONCLUSION SIRT appears to be a safe and effective treatment for patients with unresectable hepatic metastases from UM. The certainty of our results is unclear due to predominantly retrospective data with moderate risk of bias. Further prospective studies are required to explore the role of SIRT in UM. ADVANCES IN KNOWLEDGE SIRT appears to be a safe treatment for patients with unresectable hepatic metastases from UM. Further prospective work is required.
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Affiliation(s)
- Harry Alexander
- Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Daniel Wen
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Michael Chu
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Catherine Han
- Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Peter Hadden
- Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Robert Thomas
- Department of Radiology, Imperial College London, London, UK
| | - Adam Bartlett
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
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Lentz RW, Messersmith WA. Transarterial Radioembolization in Patients With Unresectable Colorectal Cancer Liver Metastases. J Clin Oncol 2021; 39:3887-3889. [PMID: 34541862 DOI: 10.1200/jco.21.01993] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Robert W Lentz
- Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO
| | - Wells A Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO
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Torres-Jiménez J, Esteban-Villarrubia J, Ferreiro-Monteagudo R, Carrato A. Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist. Cancers (Basel) 2021; 13:5938. [PMID: 34885047 PMCID: PMC8656541 DOI: 10.3390/cancers13235938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/18/2021] [Accepted: 11/21/2021] [Indexed: 12/12/2022] Open
Abstract
For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.
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Affiliation(s)
- Javier Torres-Jiménez
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Jorge Esteban-Villarrubia
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Reyes Ferreiro-Monteagudo
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Alfredo Carrato
- Medical Oncology Department, Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcalá University, University Hospital Ramon y Cajal, 28034 Madrid, Spain;
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15
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Triviño-Ibáñez EM, Pardo Moreno P, Ciampi Dopazo JJ, Ramos-Font C, Ruiz Villaverde G, González-Flores E, Navarro Vergara PF, Rashki M, Gómez-Río M, Rodríguez-Fernández A. Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience. Rev Esp Med Nucl Imagen Mol 2021; 41:231-238. [PMID: 34454892 DOI: 10.1016/j.remnie.2021.08.001] [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: 04/07/2021] [Accepted: 05/22/2021] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. MATERIAL AND METHODS This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). RESULTS Thirty TAREs were performed in 23 patients (mean age, 61.61 ± 9.13 years; 56.5% male). At three months, the objective response rate (ORR) was 16.7% and the disease control rate (DCR) 53.3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P = 0.047), previous bevacizumab treatment (P = 0.008), pre-TARE haemoglobin (P = 0.008), NLR (P = 0.040), pre-TARE albumin (P = 0.012), pre-TARE ALT (P = 0.023) and tumour-absorbed dose > 115 Gy (P = 0.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P = 0.019), KRAS mutation (HR: 5.15; P = 0.024), pre-TARE haemoglobin (HR: 0.50; p = 0.009), pre-TARE NLR (HR: 1.65; P = 0.005) and PLR (HR: 1.01; P = 0.042). CONCLUSION TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics.
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Affiliation(s)
- E M Triviño-Ibáñez
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain; IBS, Granada Bio-Health Research Institute, Granada, Spain.
| | - P Pardo Moreno
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - J J Ciampi Dopazo
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - C Ramos-Font
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain; IBS, Granada Bio-Health Research Institute, Granada, Spain
| | - G Ruiz Villaverde
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - E González-Flores
- Servicio de Oncología Médica, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - P F Navarro Vergara
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - M Rashki
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - M Gómez-Río
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain; IBS, Granada Bio-Health Research Institute, Granada, Spain
| | - A Rodríguez-Fernández
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain; IBS, Granada Bio-Health Research Institute, Granada, Spain
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16
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Triviño-Ibáñez EM, Pardo Moreno P, Ciampi Dopazo JJ, Ramos-Font C, Ruiz Villaverde G, González-Flores E, Navarro Vergara PF, Rashki M, Gómez-Río M, Rodríguez-Fernández A. Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience. Rev Esp Med Nucl Imagen Mol 2021; 41:S2253-654X(21)00129-3. [PMID: 34294586 DOI: 10.1016/j.remn.2021.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 11/30/2022]
Abstract
OBJETIVE To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. MATERIAL AND METHODS This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). RESULTS Thirty TAREs were performed in 23 patients (mean age, 61,61±9,13 years; 56,5% male). At three months, the objective response rate (ORR) was 16,7% and the disease control rate (DCR) 53,3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P=.047), previous bevacizumab treatment (P=.008), pre-TARE haemoglobin (P=.008), NLR (P=.040), pre-TARE albumin (P=.012), pre-TARE ALT (P=.023) and tumour-absorbed dose>115Gy (P=.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P=.019), KRAS mutation (HR: 5.15; P=.024), pre-TARE haemoglobin (HR: .50; p=.009), pre-TARE NLR (HR: 1.65; P=.005) and PLR (HR: 1.01; P=.042). CONCLUSION TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics.
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Affiliation(s)
- E M Triviño-Ibáñez
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, España; IBS, Granada Bio-Health Research Institute, Granada, España.
| | - P Pardo Moreno
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, España
| | - J J Ciampi Dopazo
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, España
| | - C Ramos-Font
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, España; IBS, Granada Bio-Health Research Institute, Granada, España
| | - G Ruiz Villaverde
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, España
| | - E González-Flores
- Servicio de Oncología Médica, Hospital Universitario Virgen de las Nieves, Granada, España
| | - P F Navarro Vergara
- Servicio de Radiodiagnóstico, Hospital Universitario Virgen de las Nieves, Granada, España
| | - M Rashki
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, España
| | - M Gómez-Río
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, España; IBS, Granada Bio-Health Research Institute, Granada, España
| | - A Rodríguez-Fernández
- Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, España; IBS, Granada Bio-Health Research Institute, Granada, España
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17
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Yttrium-90 Hepatic Radioembolization for Advanced Chemorefractory Metastatic Colorectal Cancer: Survival Outcomes Based on Right- Versus Left-Sided Primary Tumor Location. AJR Am J Roentgenol 2021; 217:1141-1152. [PMID: 33594907 DOI: 10.2214/ajr.20.25315] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND. Primary colon cancer location affects survival of patients with metastatic colorectal cancer (mCRC). Outcomes based on primary tumor location after salvage hepatic radioembolization with 90Y resin microspheres are not well studied. OBJECTIVE. The objectives of this study are to assess the survival outcomes of patients with advanced chemorefractory mCRC treated with 90Y radioembolization, as stratified by primary tumor location, and to explore potential factors that are predictive of survival. METHODS. A total of 99 patients who had progressive mCRC liver metastases while receiving systemic therapy and who were treated with 90Y radioembolization at a single center were retrospectively analyzed. For 89 patients, tumor response on the first imaging follow-up examination (CT or MRI performed at a mean [± SD] of 1.9 ± 0.9 months after 90Y radioembolization) was evaluated using RECIST. Overall survival (OS), OS after 90Y radioembolization, and hepatic progression-free survival (PFS) were calculated using the Kaplan-Meier method. Outcomes and associations of outcomes with tumor response were compared between patients with left- and right-sided tumors. RESULTS. A total of 74 patients had left-sided colon cancer, and 25 patients had right-sided colon cancer. Median OS from the time of mCRC diagnosis was 37.2 months, median OS after 90Y radioembolization was 5.8 months, and median hepatic PFS was 3.3 months. Based on RECIST, progressive disease on first imaging follow-up was observed in 38 patients (43%) after 90Y radioembolization and was associated with shorter OS after 90Y radioembolization compared with observation of disease control on first imaging follow-up (4.0 vs 10.5 months; p < .001). Patients with right-sided primary tumors showed decreased median OS after 90Y radioembolization compared with patients with left-sided primary tumors (5.4 vs 6.2 months; p = .03). Right- and left-sided primary tumors showed no significant difference in RECIST tumor response, hepatic PFS, or extrahepatic disease progression (p > .05). Median survival after 90Y radioembolization was significantly lower among patients with progressive disease than among those with disease control in the group with left-sided primary tumors (4.2 vs 13.9 months; p < .001); however, this finding was not observed in the group with right-sided primary tumors (3.3 vs 7.2 months; p = .05). CONCLUSION. Right-sided primary tumors were independently associated with decreased survival among patients with chemorefractory mCRC after 90Y radioembolization, despite these patients having a similar RECIST tumor response, hepatic PFS, and extrahepatic disease progression compared with patients with left-sided primary tumors. CLINICAL IMPACT. Primary colon cancer location impacts outcomes after salvage 90Y radioembolization and may help guide patient selection.
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18
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Cortesi E, Caponnetto S, Masi G, Urbano F, Mezi S, Gelibter A, Pelle G, Filippi L, Cianni R. Efficacy and Tolerability of Selective Internal Radiotherapy With Yttrium-90 as Consolidation Treatment After Chemotherapy in Metastatic Colorectal Cancer. Clin Colorectal Cancer 2020; 19:e272-e276. [PMID: 32768271 DOI: 10.1016/j.clcc.2020.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 06/09/2020] [Accepted: 06/18/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Selective internal radiotherapy (SIRT) with yttrium-90 (Y-90)-labeled resin microspheres may have a role in consolidating the response to chemotherapy in patients with metastatic colorectal cancer unamenable to resection after assessment of the best response to first-line chemotherapy. PATIENTS AND METHODS This was a retrospective analysis of outcomes in patients who had received SIRT as consolidation therapy after one or more lines of chemotherapy. Eligible patients were 18 years or older, had confirmed colorectal liver metastases, and had disease unsuitable for surgical resection or local ablation with curative intent. The primary endpoint was progression-free survival. RESULTS Sixty-eight patients with colorectal liver metastases were treated with at least one SIRT procedure after receiving one or more lines of chemotherapy. Median progression-free survival was significantly longer in patients who received SIRT after prior first-line chemotherapy compared to those who received SIRT after two or more lines of chemotherapy (9 vs. 3 months, respectively; hazard ratio = 0.07; 95% confidence interval, 0.02854‒0.2039; P < .001), and in patients with liver-only disease compared to those who had extrahepatic metastases (6.4 vs. 4.1 months, respectively; hazard ratio = 0.57; 95% confidence interval, 0.34-0.95; P = .0318). There were no grade 3 or higher adverse events. CONCLUSION SIRT represents a valid option for the treatment of colorectal liver metastases. Earlier use of SIRT may provide a greater survival benefit compared to that afforded by the procedure when used in salvage settings.
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Affiliation(s)
- Enrico Cortesi
- Medical Oncology Department, "La Sapienza" University, Rome, Italy
| | | | - Gianluca Masi
- Azienda Ospedaliero-Universitaria Pisana and Università di Pisa, Pisa, Italy
| | - Federica Urbano
- Medical Oncology Department, "La Sapienza" University, Rome, Italy
| | - Silvia Mezi
- Medical Oncology Department, "La Sapienza" University, Rome, Italy
| | - Alain Gelibter
- Medical Oncology Department, "La Sapienza" University, Rome, Italy
| | | | - Luca Filippi
- Santa Maria Goretti General Hospital, Latina, Italy
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Nance ME, Biedermann GB, Bhat AP, Davis RM. Chemorefractory liver metastasis from cervical cancer successfully treated with a combination of yttrium-90 and immunotherapy. Radiol Case Rep 2020; 15:1359-1365. [PMID: 32636973 PMCID: PMC7327429 DOI: 10.1016/j.radcr.2020.06.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 06/01/2020] [Accepted: 06/02/2020] [Indexed: 12/24/2022] Open
Abstract
Liver metastases in cervical cancer is rare and can be difficult-to-treat. The current guidelines established by the Gynecologic Oncology Group recommend platinum-based systemic chemotherapy in combination with an anti-angiogenic agent such as bevacizumab, however, overall survival remains poor following diagnosis and options for patients who fail chemotherapy are limited. Yttrium-90 (Y90) radioembolization (RE) has shown great promise in the treatment of chemo-refractory colorectal liver metastases. We describe a 30-year-old female with a history of stage IB endocervical adenocarcinoma who later developed metastases to the liver, that were unresponsive to multiple chemotherapeutics and chemoembolization, and was successfully treated with Y90 RE with concurrent systemic Pembrolizumab. The Y90 RE treatment resulted in positive clinical and imaging responses with improvement in her quality of life, all of which continue to persist at the time of writing this manuscript about 8-months into her RE treatment.
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Affiliation(s)
- Michael E. Nance
- School of Medicine, University of Missouri, Columbia, MO, USA
- Department of Radiology, Section of Vascular and Interventional Radiology, University of Missouri, One Hospital drive, Columbia, MO 65212, USA
| | - Gregory B. Biedermann
- Department of Radiology, Section of Radiation Oncology, University of Missouri, Columbia, Columbia, MO, USA
| | - Ambarish P. Bhat
- Department of Radiology, Section of Vascular and Interventional Radiology, University of Missouri, One Hospital drive, Columbia, MO 65212, USA
| | - Ryan M. Davis
- Department of Radiology, Section of Vascular and Interventional Radiology, University of Missouri, One Hospital drive, Columbia, MO 65212, USA
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20
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Dabrowiecki A, Sankhla T, Shinn K, Bercu ZL, Ermentrout M, Shaib W, Cardona K, Newsome J, Kokabi N. Impact of Genomic Mutation and Timing of Y90 Radioembolization in Colorectal Liver Metastases. Cardiovasc Intervent Radiol 2020; 43:1006-1014. [PMID: 32367230 DOI: 10.1007/s00270-020-02463-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 03/21/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE To investigate timing of Yttrium-90 radioembolization (Y90) during treatment course, genomics, and other clinical factors as predictors of overall survival (OS) in colorectal liver metastasis (CRLM) that have progressed on at least one line of chemotherapy. MATERIALS AND METHODS This was a retrospective study from 2013 to 2018 of patients with CRLM and genomic analysis prior to Y90 at a multihospital tertiary referral center. OS from liver metastasis diagnosis and predictors of OS were analyzed using Kaplan-Meier estimation with log-rank and Cox regression analyses. RESULTS Overall, 58 patients with CRLM who progressed on at least one line of chemotherapy who had genomic analysis prior to Y90 were identified. Median OS after hepatic metastasis was 29.9 months. Of these, 16 (28%) patients received Y90 after failure of the first-line systemic chemotherapy. There was significantly prolonged OS in patients receiving Y90 immediately following failure of the first-line chemotherapy folinic acid, fluorouracil, oxaliplatin ((FOLFOX) ± bevacizumab) versus following multiple lines of chemotherapy (median OS of 46.3 vs. 26.6 months, P = 0.005). The presence of genetic mutation in tumor, MAPK pathway wild type, left-sided primary tumor, low MELD score, and non-diffuse unilobar disease were also found to be predictors prolonged survival on log-rank analysis (P's < 0.05). On multivariate analysis, receiving Y90 after failure of the first line of chemotherapy, low baseline MELD score, and baseline ECOG performance score of 0 were all found to be independent predictors of prolonged OS from the time of metastatic disease diagnosis (P's < 0.05). CONCLUSION In patients with CRLM, receiving Y90 after failing the first line of chemotherapy, lack of genetic mutation, low MELD score, and lower tumor burden appear to be independent predictors of prolonged OS. LEVEL OF EVIDENCE Level 4, case-control study.
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Affiliation(s)
- Alexander Dabrowiecki
- Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA.
| | - Tina Sankhla
- Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA
| | - Kaitlin Shinn
- Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA
| | - Zachary L Bercu
- Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA
| | - Mitchell Ermentrout
- Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA
| | - Walid Shaib
- Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, 1364 Clifton Rd. NE, Atlanta, GA, 30322, USA
| | - Janice Newsome
- Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA
| | - Nima Kokabi
- Department of Radiology and Imaging Sciences, Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Suite #D112, Atlanta, GA, USA
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21
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Lau DK, Burge M, Roy A, Chau I, Haller DG, Shapiro JD, Peeters M, Pavlakis N, Karapetis CS, Tebbutt NC, Segelov E, Price TJ. Update on optimal treatment for metastatic colorectal cancer from the AGITG expert meeting: ESMO congress 2019. Expert Rev Anticancer Ther 2020; 20:251-270. [PMID: 32186929 DOI: 10.1080/14737140.2020.1744439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Outcomes in metastatic colorectal cancer are improving, due to the tailoring of therapy enabled by better understanding of clinical behavior according to molecular subtype.Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of systemic treatment of metastatic colorectal cancer. This review summarizes expert discussion of the current evidence for therapies in metastatic colorectal cancer (mCRC) based on molecular subgrouping.Expert opinion: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for mCRC. EGFR-targeted antibodies are restricted to patients with extended RAS wild-type profiles, with evidence that they should be further restricted to patients with left-sided tumors. Clinically distinct treatment pathways based on tumor RAS, BRAF, HER2 and MMR status, are now clinically applicable. Evidence suggests therapy for additional subgroups will soon be defined; the most advanced being for patients with KRAS G12 C mutation and gene TRK fusion defects.
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Affiliation(s)
- David K Lau
- GI and Lymphoma Unit, Royal Marsden NHS Foundation Trust, London and Surrey, UK
| | - Matthew Burge
- Medical Oncology, Royal Brisbane Hospital, Brisbane, Australia.,University of Queensland, Brisbane, Australia
| | - Amitesh Roy
- Medical Oncology, Flinders Centre for Innovation in Cancer, Bedford Park, Australia
| | - Ian Chau
- GI and Lymphoma Unit, Royal Marsden NHS Foundation Trust, London and Surrey, UK
| | - Daniel G Haller
- Abramson Cancer Center at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jeremy D Shapiro
- Monash University, Melbourne, Australia.,Medical Oncology, Cabrini Medical Centre, Melbourne, Australia
| | - Marc Peeters
- Medical Oncology, University Hospital Antwerp, Edegem, Belgium
| | - Nick Pavlakis
- Medical Oncology, Royal North Shore Hospital, St Leonards, Australia.,Sydney University, Camperdown, Sydney, Australia
| | | | - Niall C Tebbutt
- Medical Oncology, Austin Health, Heidelberg, Australia.,Department of Surgery, University of Melbourne, Melbourne, Australia
| | - Eva Segelov
- Monash University, Melbourne, Australia.,Medical Oncology, Monash Medical Centre, Clayton, Australia
| | - Timothy J Price
- Medical Oncology, The Queen Elizabeth Hospital, Woodville, Australia
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22
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Aramburu J, Antón R, Rivas A, Ramos JC, Sangro B, Bilbao JI. Liver Radioembolization: An Analysis of Parameters that Influence the Catheter-Based Particle-Delivery via CFD. Curr Med Chem 2020; 27:1600-1615. [DOI: 10.2174/0929867325666180622145647] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 05/18/2017] [Accepted: 05/25/2017] [Indexed: 12/13/2022]
Abstract
Radioembolization (RE) is a valuable treatment for liver cancer. It consists of administering
radioactive microspheres by an intra-arterially placed catheter with the aim of
lodging these microspheres, which are driven by the bloodstream, in the tumoral bed. Even
though it is a safe treatment, some radiation-induced complications may arise. In trying to
detect or solve the possible incidences that cause nontarget irradiation, simulating the particle-
hemodynamics in hepatic arteries during RE by computational fluid dynamics (CFD)
tools has become a valuable approach. This paper reviews the parameters that influence the
outcome of RE and that have been studied via numerical simulations. In this numerical approach,
the outcome of RE is regarded as successful if particles reach the artery branches that
feed tumor-bearing liver segments. Up to 10 parameters have been reviewed. The variation
of each parameter actually alters the hemodynamic pattern in the vicinities of the catheter tip
and locally alters the incorporation of the particles into the bloodstream. Therefore, in general,
the local influences of these parameters should result in global differences in terms of
particle distribution in the hepatic artery branches. However, it has been observed that under
some (qualitatively described) appropriate conditions where particles align with blood
streamlines, the local influence resulting from a variation of a given parameter vanishes and
no global differences are observed. Furthermore, the increasing number of CFD studies on
RE suggests that numerical simulations have become an invaluable research tool in the study
of RE.
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Affiliation(s)
- Jorge Aramburu
- Universidad de Navarra, TECNUN Escuela de Ingenieros, 20018 Donostia-San Sebastian, Spain
| | - Raúl Antón
- Universidad de Navarra, TECNUN Escuela de Ingenieros, 20018 Donostia-San Sebastian, Spain
| | - Alejandro Rivas
- Universidad de Navarra, TECNUN Escuela de Ingenieros, 20018 Donostia-San Sebastian, Spain
| | - Juan C. Ramos
- Universidad de Navarra, TECNUN Escuela de Ingenieros, 20018 Donostia-San Sebastian, Spain
| | - Bruno Sangro
- IdiSNA, Instituto de Investigacion Sanitaria de Navarra, 31008 Pamplona, Spain
| | - José I. Bilbao
- IdiSNA, Instituto de Investigacion Sanitaria de Navarra, 31008 Pamplona, Spain
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Palmer DH, Hawkins NS, Vilgrain V, Pereira H, Chatellier G, Ross PJ. Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study. Future Oncol 2019; 16:4315-4325. [PMID: 31797680 DOI: 10.2217/fon-2019-0658] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.
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Affiliation(s)
- Daniel H Palmer
- Liverpool CR UK/NIHR Experimental Cancer Medicine Centre, University of Liverpool, Liverpool, L69 3BX, United Kingdom
| | - Neil S Hawkins
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, G12 8RZ, United Kingdom
| | - Valérie Vilgrain
- Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, 92118 Clichy, France.,Centre de Recherche de l'Inflammation, INSERM U1149, Université Paris Sorbonne Cité, Paris, France
| | - Helena Pereira
- Assistance Publique - Hôpitaux de Paris, Hôpital européen Georges-Pompidou, Unité d'épidémiologie et de Recherche Clinique, Paris, 75015 France.,Module Épidémiologie Clinique, Centre d'Investigation Clinique 1418, INSERM, Paris, France
| | - Gilles Chatellier
- Assistance Publique - Hôpitaux de Paris, Hôpital européen Georges-Pompidou, Unité d'épidémiologie et de Recherche Clinique, Paris, 75015 France.,Module Épidémiologie Clinique, Centre d'Investigation Clinique 1418, INSERM, Paris, France
| | - Paul J Ross
- Department of Medical Oncology, Guy's & St Thomas' NHS Foundation Trust, London, SE1 9RT, United Kingdom.,Department of Oncology, King's College Hospital NHS Foundation Trust, London, SE5 9RS, United Kingdom
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24
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Jadoul A, Bernard C, Lovinfosse P, Gérard L, Lilet H, Cornet O, Hustinx R. Comparative dosimetry between 99mTc-MAA SPECT/CT and 90Y PET/CT in primary and metastatic liver tumors. Eur J Nucl Med Mol Imaging 2019; 47:828-837. [PMID: 31388721 DOI: 10.1007/s00259-019-04465-7] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 07/26/2019] [Indexed: 12/22/2022]
Abstract
INTRODUCTION The aim of this study is to determine whether 99mTc-MAA SPECT/CT-based dosimetry could predict the actual absorbed dose in hepatocellular carcinoma (HCC) or liver metastases, treated by glass or resin microspheres. MATERIAL AND METHODS Fifty-seven patients who underwent selective internal radiation therapy (SIRT) were retrospectively included in the study, for a total of 59 treatments. Nineteen HCC were treated by resin microspheres (HCC-SIR), 20 HCC with glass microspheres (HCC-Thera), and 20 liver metastases with resin microspheres (Metastases-SIR). The mean absorbed doses in tumoral liver (Dm) and non-tumoral liver (DmNTL) were determined on the 99mTc-MAA SPECT/CT and the 90Y PET/CT, and compared with each other. RESULTS DmNTL was < 50 Gy in the 3 groups, with a strong correlation in all population, albeit slightly lower in Metastases-SIR than HCC-SIR and HCC-Thera (CCC 0.8, 0.94 and 0.96, respectively). In tumoral liver, Dm was higher in HCC than metastases (159 ± 117 Gy versus 63 ± 31 Gy). 99mTc-MAA SPECT/CT proved to be a better indicator of Dm in HCC compared with metastases, with similar 99mTc-MAA-90Y concordance in resin and glass microspheres (CCC HCC-SIR 0.82, CCC HCC-Thera 0.82, and CCC Metastases-SIR 0.52). CONCLUSION 99mTc-MAA SPECT/CT is a reasonably reliable tool for predicting the dose to the non-tumoral liver in both HCC and metastases, regardless of the type of microspheres. It is also fairly reliable for predicting the tumor dose in HCC, again regardless of the type of spheres, although individual variations are observed.
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Affiliation(s)
- Alexandre Jadoul
- Division of Nuclear Medicine and Oncological Imaging, University Hospital of Liege, B35 Domaine Universitaire du Sart-Tilman, 4000, Liege, Belgium.
| | - Claire Bernard
- Division of Nuclear Medicine and Oncological Imaging, University Hospital of Liege, B35 Domaine Universitaire du Sart-Tilman, 4000, Liege, Belgium
| | - Pierre Lovinfosse
- Division of Nuclear Medicine and Oncological Imaging, University Hospital of Liege, B35 Domaine Universitaire du Sart-Tilman, 4000, Liege, Belgium
| | - Laurent Gérard
- Division of Radiology, University Hospital of Liege, Liege, Belgium
| | - Henri Lilet
- Division of Nuclear Medicine and Oncological Imaging, University Hospital of Liege, B35 Domaine Universitaire du Sart-Tilman, 4000, Liege, Belgium
| | - Olivier Cornet
- Division of Radiology, University Hospital of Liege, Liege, Belgium
| | - Roland Hustinx
- Division of Nuclear Medicine and Oncological Imaging, University Hospital of Liege, B35 Domaine Universitaire du Sart-Tilman, 4000, Liege, Belgium
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25
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When oncologic treatment options outpace the existing evidence: Contributing factors and a path forward. J Cancer Policy 2019. [DOI: 10.1016/j.jcpo.2019.100188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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26
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Petrelli F, Comito T, Barni S, Pancera G, Scorsetti M, Ghidini A. Stereotactic body radiotherapy for colorectal cancer liver metastases: A systematic review. Radiother Oncol 2018; 129:427-434. [PMID: 29997034 DOI: 10.1016/j.radonc.2018.06.035] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 06/07/2018] [Accepted: 06/25/2018] [Indexed: 12/18/2022]
Abstract
INTRODUCTION While surgery is the preferred option for isolated, operable liver metastases from colorectal cancer (CRC), ablative techniques are endorsed for medically or technically inoperable lesions. Stereotactic body radiotherapy (SBRT) is an alternative ablative local therapy that delivers high RT doses in a few fractions to the cancer, sparing surrounding critical tissue. We have performed a systematic review of published trials to evaluate the efficacy of SBRT as a primary modality therapy for CRC liver oligometastases. MATERIALS AND METHODS We searched the Cochrane Central Register of Controlled Trials, Pubmed, and EMBASE for publications regarding SBRT for CRC liver metastases. Overall survival (OS: median, 1- and 2-year OS %) was the primary endpoint, and median PFS and one- and two-year local control (LC) were the secondary endpoints. A random-effect model pooled-analysis was performed to calculate the aggregated OS rates at 1 and 2 years as well as the one- and two-year LC. RESULTS A total of 18 studies, encompassing 656 patients, were included in the analysis. The pooled one- and two-year OS were 67.18% (95% CI, 42.1-92.2) and 56.5% (95% CI, 36.7-76.2), respectively. Median PFS and OS were 11.5 and 31.5 months. The pooled one-year LC was 67% (95% CI, 43.8-90.2), while the pooled two-year LC was 59.3% (95% CI, 37.2-81.5). Correlation analysis revealed a moderate/poor linear relationship between the SBRT (BED10) dose and LC (p = 0.001, R = 0.47)/OS (p = 0.001, R = 0.29) at 2 years. Mild-moderate and severe liver toxicity were 30.7% and 8.7%. CONCLUSION SBRT for liver oligometastases is an effective option for patients with advanced CRC, with encouraging local control and survival. However, a definitive validation in large randomised studies is required, due to the retrospective or non-randomised nature of the included studies and the limitations of series with different doses/schedules of treatment.
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Affiliation(s)
| | - Tiziana Comito
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Sandro Barni
- Oncology Unit, ASST Bergamo Ovest, Treviglio, Italy
| | | | - Marta Scorsetti
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
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27
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White J, Carolan-Rees G, Dale M, Morgan HE, Patrick HE, See TC, Beeton EL, Swinson DEB, Bell JK, Manas DM, Crellin A, Slevin NJ, Sharma RA. Analysis of a National Programme for Selective Internal Radiation Therapy for Colorectal Cancer Liver Metastases. Clin Oncol (R Coll Radiol) 2018; 31:58-66. [PMID: 30297164 DOI: 10.1016/j.clon.2018.09.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Revised: 07/31/2018] [Accepted: 08/01/2018] [Indexed: 12/20/2022]
Abstract
AIMS Patients with chemotherapy-refractory colorectal cancer liver metastases have limited therapeutic options. Selective internal radiation therapy (SIRT) delivers yttrium 90 microspheres as a minimally invasive procedure. This prospective, single-arm, observational, service-evaluation study was part of National Health Service England Commissioning through Evaluation. METHODS Patients eligible for treatment had histologically confirmed carcinoma with liver-only/liver-dominant metastases with clinical progression during or following oxaliplatin-based and irinotecan-based chemotherapy. All patients received SIRT plus standard of care. The primary outcome was overall survival; secondary outcomes included safety, progression-free survival (PFS) and liver-specific PFS (LPFS). RESULTS Between December 2013 and March 2017, 399 patients were treated in 10 centres with a median follow-up of 14.3 months (95% confidence interval 9.2-19.4). The median overall survival was 7.6 months (95% confidence interval 6.9-8.3). The median PFS and LPFS were 3.0 months (95% confidence interval 2.8-3.1) and 3.7 months (95% confidence interval 3.2-4.3), respectively. During the follow-up period, 143 patients experienced an adverse event and 8% of the events were grade 3. CONCLUSION Survival estimates from this pragmatic study show clinical outcomes attainable in the National Health Service comparable with previously published data. This study shows the value of a registry-based commissioning model to aid national commissioning decisions for highly specialist cancer treatments.
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Affiliation(s)
- J White
- Cedar, Cardiff & Vale University Health Board, Cardiff Medicentre, Cardiff, UK
| | - G Carolan-Rees
- Cedar, Cardiff & Vale University Health Board, Cardiff Medicentre, Cardiff, UK
| | - M Dale
- Cedar, Cardiff & Vale University Health Board, Cardiff Medicentre, Cardiff, UK
| | - H E Morgan
- Cedar, Cardiff University, Cardiff Medicentre, Cardiff, UK
| | - H E Patrick
- Centre for Health Technology Evaluation, National Institute for Health and Care Excellence, London, UK
| | - T C See
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
| | - E L Beeton
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - D E B Swinson
- Leeds Teaching Hospitals NHS Trust, St James's Hospital, Leeds, UK
| | - J K Bell
- Department of Radiology, The Christie NHS Foundation Trust, Manchester, UK
| | - D M Manas
- The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - A Crellin
- NHS England, Institute of Oncology, St James's University Hospital, Leeds, UK
| | - N J Slevin
- The Christie NHS Foundation Trust, Withington, Manchester, UK
| | - R A Sharma
- NIHR University College London Hospitals Biomedical Research Centre, UCL Cancer Institute, University College London, London, UK.
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28
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Tan HL, Lee M, Vellayappan BA, Neo WT, Yong WP. The Role of Liver-Directed Therapy in Metastatic Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2018; 14:129-137. [PMID: 30294248 PMCID: PMC6153585 DOI: 10.1007/s11888-018-0409-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Purpose of Review Colorectal cancer liver metastasis is a major clinical problem, and surgical resection is the only potentially curative treatment. We seek to discuss various liver-directed therapy modalities and explore their roles in the evolving realm of treatment strategies for metastatic colorectal cancer. Recent Findings Clinical outcomes for patients with colorectal cancer liver metastases have improved as more patients undergo potentially curative resection and as the armamentarium of systemic treatment and liver-directed therapies continues to expand. Liver-directed therapies have been developed as adjuncts to improve resectability, employed in the adjuvant setting to potentially reduce local recurrence rates, and utilized in the palliative setting with the aim to improve overall survival. Summary Ongoing research is expected to validate the role of these evolving therapeutic options, and determine how best to sequence and when to apply these therapies.
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Affiliation(s)
- Hon Lyn Tan
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 1E Kent Ridge Road, Singapore, 119228 Singapore
| | - Matilda Lee
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 1E Kent Ridge Road, Singapore, 119228 Singapore
| | - Balamurugan A Vellayappan
- Department of Radiation Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 1E Kent Ridge Road, Singapore, 119228 Singapore
| | - Wee Thong Neo
- 3Department of Diagnostic Imaging, National University Health System, 1E Kent Ridge Road, Singapore, 119228 Singapore
| | - Wei Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 1E Kent Ridge Road, Singapore, 119228 Singapore
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29
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Price TJ, Tang M, Gibbs P, Haller DG, Peeters M, Arnold D, Segelov E, Roy A, Tebbutt N, Pavlakis N, Karapetis C, Burge M, Shapiro J. Targeted therapy for metastatic colorectal cancer. Expert Rev Anticancer Ther 2018; 18:991-1006. [PMID: 30019590 DOI: 10.1080/14737140.2018.1502664] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Outcomes in metastatic colorectal cancer are improving, with better understanding and use of targeted therapies. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of systemic treatment of metastatic colorectal cancer. This article reviews the current evidence for targeted therapies in advanced colorectal cancer, including up-to-date data regarding anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF) agents, the relevance of primary tumor location and novel subgroups such as BRAF mutated, HER2 amplified, and mismatch-repair-deficient cancers. Expert commentary: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for metastatic colorectal cancer (mCRC). The use of EGFR-targeted antibodies should be restricted to patients with extended RAS wild-type profiles, and there is evidence that they should be further restricted to patients with left-sided tumors. Clinically, mCRC can be divided into subgroups based on RAS, BRAF, HER2, and MMR status, each of which have distinct treatment pathways.
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Affiliation(s)
- Timothy J Price
- a Medical Oncology , The Queen Elizabeth Hospital, Woodville, and University of Adelaide , Adelaide , Australia
| | - Monica Tang
- b Medical Oncology , NHMRC Clinical Trials Centre, University of Sydney , Sydney , Australia
| | - Peter Gibbs
- c Medical Oncology , Western Hospital , Melbourne , Australia.,d Medical Oncology , Walter and Eliza Hall Institute , Melbourne , Australia
| | - Daniel G Haller
- e Medical Oncology , Abrahamson Cancer Centre at the Perelman School of Medicine, University of Pennsylvania , Philadelphia , USA
| | - Marc Peeters
- f Medical Oncology , University Hospital Antwerp, Edegem, Belgiumg Asklepios Tumorzentrum Hamburg , Hamburg , Germany
| | - Dirk Arnold
- g Medical Oncology , Asklepios Tumorzentrum Hamburg , Germany
| | - Eva Segelov
- h Medical Oncology , Monash University School of Clinical Sciences at Monash Health, Monash Medical Centre , Clayton , Australia
| | - Amitesh Roy
- i Medical Oncology , Flinders Centre for Innovation in Cancer , Bedford Park , Australia.,j Medical Oncology , Flinders University , Bedford Park , Australia
| | - Niall Tebbutt
- k Medical Oncology , Austin Health , Heidelberg , Australia
| | - Nick Pavlakis
- l Medical Oncology , Royal North Shore Hospital , St Leonards , Australia
| | - Chris Karapetis
- i Medical Oncology , Flinders Centre for Innovation in Cancer , Bedford Park , Australia
| | - Matthew Burge
- m Medical Oncology , Royal Brisbane Hospital , Brisbane , Australia
| | - Jeremy Shapiro
- n Medical Oncology , Cabrini Hospital and Monash University , Melbourne , Australia
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30
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Kinetic analysis of contralateral liver hypertrophy after radioembolization of primary and metastatic liver tumors. Surgery 2018; 163:1020-1027. [PMID: 29325784 DOI: 10.1016/j.surg.2017.11.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 11/02/2017] [Accepted: 11/20/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Radioembolization induces liver hypertrophy, although the extent and rate of hypertrophy are unknown. Our goal was to examine the kinetics of contralateral liver hypertrophy after transarterial radioembolization. METHODS A retrospective study (2010-2014) of treatment-naïve patients with primary/secondary liver malignancies undergoing right lobe radioembolization was performed. Computed tomography volumetry was performed before and 1, 3, and 6 months after radioembolization. Outcomes of interest were left lobe (standardized future liver remnant) degree of hypertrophy, kinetic growth rate, and ability to reach goal standardized future liver remnant ≥40%. Medians were compared with the Kruskall-Wallis test. Time to event analysis was used to estimate time to reach goal standardized future liver remnant. RESULTS In the study, 25 patients were included. At 1, 3, and 6 months, median degree of hypertrophy was 4%, 8%, and 12% (P < .001), degree of hypertrophy relative to baseline future liver remnants was 11%, 17%, and 31% (P = .015), and kinetic growth rate was 0.8%, 0.5%, and 0.4%/week (P = .002). In patients with baseline standardized future liver remnant <40% (N= 16), median time to reach standardized future liver remnant ≥40% was 7.3 months, with 75% accomplishing standardized future liver remnant ≥40% at 8.2 months. CONCLUSION Radioembolization induces hypertrophy of the contralateral lobe to a similar extent as existing methods, although at a lower rate. The role of radioembolization as a dual therapy (neoadjuvant and hypetrophy-inducing) for selected patients needs to be studied. (Surgery 2017;160:XXX-XXX.).
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31
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Church C, Mawko G, Archambault JP, Lewandowski R, Liu D, Kehoe S, Boyd D, Abraham R, Syme A. Absorbed dose kernel and self-shielding calculations for a novel radiopaque glass microsphere for transarterial radioembolization. Med Phys 2017; 45:934-942. [PMID: 29206288 DOI: 10.1002/mp.12717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 11/22/2017] [Accepted: 11/27/2017] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Radiopaque microspheres may provide intraprocedural and postprocedural feedback during transarterial radioembolization (TARE). Furthermore, the potential to use higher resolution x-ray imaging techniques as opposed to nuclear medicine imaging suggests that significant improvements in the accuracy and precision of radiation dosimetry calculations could be realized for this type of therapy. This study investigates the absorbed dose kernel for novel radiopaque microspheres including contributions of both short and long-lived contaminant radionuclides while concurrently quantifying the self-shielding of the glass network. METHODS Monte Carlo simulations using EGSnrc were performed to determine the dose kernels for all monoenergetic electron emissions and all beta spectra for radionuclides reported in a neutron activation study of the microspheres. Simulations were benchmarked against an accepted 90 Y dose point kernel. Self-shielding was quantified for the microspheres by simulating an isotropically emitting, uniformly distributed source, in glass and in water. The ratio of the absorbed doses was scored as a function of distance from a microsphere. The absorbed dose kernel for the microspheres was calculated for (a) two bead formulations following (b) two different durations of neutron activation, at (c) various time points following activation. RESULTS Self-shielding varies with time postremoval from the reactor. At early time points, it is less pronounced due to the higher energies of the emissions. It is on the order of 0.4-2.8% at a radial distance of 5.43 mm with increased size from 10 to 50 μm in diameter during the time that the microspheres would be administered to a patient. At long time points, self-shielding is more pronounced and can reach values in excess of 20% near the end of the range of the emissions. Absorbed dose kernels for 90 Y, 90m Y, 85m Sr, 85 Sr, 87m Sr, 89 Sr, 70 Ga, 72 Ga, and 31 Si are presented and used to determine an overall kernel for the microspheres based on weighted activities. The shapes of the absorbed dose kernels are dominated at short times postactivation by the contributions of 70 Ga and 72 Ga. Following decay of the short-lived contaminants, the absorbed dose kernel is effectively that of 90 Y. After approximately 1000 h postactivation, the contributions of 85 Sr and 89 Sr become increasingly dominant, though the absorbed dose-rate around the beads drops by roughly four orders of magnitude. CONCLUSIONS The introduction of high atomic number elements for the purpose of increasing radiopacity necessarily leads to the production of radionuclides other than 90 Y in the microspheres. Most of the radionuclides in this study are short-lived and are likely not of any significant concern for this therapeutic agent. The presence of small quantities of longer lived radionuclides will change the shape of the absorbed dose kernel around a microsphere at long time points postadministration when activity levels are significantly reduced.
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Affiliation(s)
- Cody Church
- Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, Canada
| | - George Mawko
- Department of Diagnostic Imaging, Dalhousie University, Halifax, Nova Scotia, Canada.,Department of Medical Physics, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
| | | | - Robert Lewandowski
- Interventional Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - David Liu
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Sharon Kehoe
- ABK Biomedical Inc., Halifax, Nova Scotia, Canada.,Department of Applied Oral Sciences, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Daniel Boyd
- ABK Biomedical Inc., Halifax, Nova Scotia, Canada.,Department of Applied Oral Sciences, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Robert Abraham
- Department of Diagnostic Imaging, Dalhousie University, Halifax, Nova Scotia, Canada.,ABK Biomedical Inc., Halifax, Nova Scotia, Canada
| | - Alasdair Syme
- Department of Medical Physics, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada.,Department of Radiation Oncology, Dalhousie University, Halifax, Nova Scotia, Canada
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Orwat KP, Beckham TH, Cooper SL, Ashenafi MS, Anderson MB, Guimaraes M, Yamada R, Marshall DT. Pretreatment albumin may aid in patient selection for intrahepatic Y-90 microsphere transarterial radioembolization (TARE) for malignancies of the liver. J Gastrointest Oncol 2017; 8:1072-1078. [PMID: 29299369 DOI: 10.21037/jgo.2017.06.18] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Hepatic malignancies are common including primary malignancies and metastases. Transarterial radioembolization (TARE) is an important treatment option. We reviewed safety and efficacy of (TARE) in our patients to identify factors that may impact treatment outcomes in a heterogeneous population. Methods All patients that received TARE at the Medical University of South Carolina from March 2006 through May of 2014 were included. Kaplan-Meier estimates on overall survival (OS) from date of first procedure are reported. Potential prognostic factors for OS were evaluated using log rank tests and Cox proportional hazards models. Results In the 114 patients that received TARE at our institution, median follow-up was 6.4 months (range, 0-86 months) with the following histologies: colorectal (CR) n=55, hepatocellular (HC) n=20, cholangiocarcinoma (CC) n=16, neuroendocrine (NE) n=12, breast (BR) n=6, other n=5. At least 1 line of prior systemic therapy was noted in 79% of patients. Median OS was significantly better with NE and BR histology, and in those with normal albumin levels. With an albumin >3.4 median OS was 10.3 months, but was only 3.1 months with an albumin <3 g/dL. Grade ≥2 toxicity was observed in 22 patients (19.3%) including 9 (7.9%) with Grade 3 and 1 (0.9%) with Grade 4 toxicity. Conclusions TARE is a relatively safe and effective treatment for intrahepatic malignancies. Patients with NE and BR histology as well as those with better hepatic synthetic function were associated with significantly better survival. Our data suggest that patients with albumin below 3 g/dL may not derive significant benefit from TARE.
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Affiliation(s)
- Kelly P Orwat
- Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA
| | - Thomas H Beckham
- Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA
| | - Samuel Lewis Cooper
- Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA
| | - Michael S Ashenafi
- Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA
| | | | - Marcelo Guimaraes
- Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Ricardo Yamada
- Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - David T Marshall
- Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA
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Abstract
OBJECTIVE The outcome for patients with unresectable hepatic sarcoma is poor with a median survival period of 12-16 months. The purpose of this study was to evaluate liver-directed transcatheter therapies for the treatment of hepatic sarcomas. MATERIALS AND METHODS In a retrospective study, the cases of patients with primary and metastatic hepatic sarcoma treated by transcatheter embolization, chemoembolization, and 90Y radioembolization between 2004 and 2015 were identified. Response Evaluation Criteria in Solid Tumors version 1.1 response was assessed for the target tumor. Survival was assessed by means of Kaplan-Meier analysis. RESULTS Twenty-eight patients (17 [61%] men, 11 [39%] women; median age, 47 years) were included. Eighteen patients were treated electively. Two of the electively treated patients underwent embolization; eight, chemoembolization; six, radioembolization; and two, a combination of transcatheter treatments. Treatment was well tolerated; only one patient had grade 3 hepatic toxicity. The objective response rate of the index tumor was 61%, and the median overall survival period was 26.7 months. Ten patients underwent emergency embolization to control acute hemorrhage from tumor rupture. The median overall survival periods were 611 days for the patients with ruptured gastrointestinal stromal tumors (GIST) (n = 3) and 19 days for the patients with ruptured angiosarcoma (n = 7). CONCLUSION Liver-directed transcatheter therapies are safe and may have a role in the elective management of unresectable primary and metastatic liver sarcomas. Emergency embolization for ruptured GIST may be effective for stabilizing the patient's condition and allowing more definitive therapy in the future. However, emergency embolization has limited efficacy in treating patients with ruptured angiosarcoma, likely because of substantial venous bleeding at rupture and the aggressive behavior of this lesion.
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Sangha BS, Nimeiri H, Hickey R, Salem R, Lewandowski RJ. Radioembolization as a Treatment Strategy for Metastatic Colorectal Cancer to the Liver: What Can We Learn from the SIRFLOX Trial? Curr Treat Options Oncol 2017; 17:26. [PMID: 27098532 DOI: 10.1007/s11864-016-0402-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OPINION STATEMENT In the setting of liver metastases from colorectal cancer (CRC), radioembolization with yttrium-90 has been used to treat chemotherapy refractory disease with a growing interest to establish its efficacy in prospective trials combined with first- and second-line chemotherapy. SIRFLOX is an ongoing, multi-center, phase 3 randomized trial comparing first-line chemotherapy alone or in combination with yttrium-90 radioembolization in patients with CRC who have isolated liver metastases or liver-dominant metastases. Preliminary results from SIRFLOX demonstrate that radioembolization combined with first-line chemotherapy is safe and feasible. There was no significant difference in median overall progression-free survival (PFS) between the combined radioembolization-chemotherapy and chemotherapy-only arms (10.7 versus 10.2 months). Although the trial did not meet its primary endpoint of improved median PFS, there was a significant increase in the median hepatic PFS (20.5 versus 12.6 months; p = 0.02) favoring the combination arm. Thus, combining radioembolization with chemotherapy in the first-line setting may be most effective for liver-limited metastatic CRC. Since radioembolization targets liver disease, it is plausible that the trial failed to achieve an improvement in PFS given that 40 % of the SIRFLOX population had extra-hepatic disease. It is also possible that the overall median PFS may be a poor surrogate endpoint, and other endpoints like overall survival still needs to be delineated in this setting. In addition, it is crucial to document improvement or delay in time to deterioration in quality of life symptom endpoints in this population. SIRFLOX is the first of three prospective studies that assess the efficacy of adding radioembolization to first-line chemotherapy, and the combined data from these trials will provide the necessary power for an overall survival analysis. The final results of SIRFLOX will be eagerly awaited to determine if the increased hepatic PFS in preliminary data will translate to increased overall survival benefit.
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Affiliation(s)
- Bippan Singh Sangha
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA
| | - Halla Nimeiri
- Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Ryan Hickey
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA
- Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
- Division of Hepatology, Department of Medicine, Northwestern University, Chicago, IL, USA
| | - Robert J Lewandowski
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA.
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Aranda E, Aparicio J, Bilbao JI, García-Alfonso P, Maurel J, Rodríguez J, Sangro B, Vieitez JM, Feliu J. Recommendations for SIR-Spheres Y-90 resin microspheres in chemotherapy-refractory/intolerant colorectal liver metastases. Future Oncol 2017; 13:2065-2082. [PMID: 28703622 DOI: 10.2217/fon-2017-0220] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
A Spanish expert panel reviewed current evidence for the use of SIR-Spheres Y-90 resin microspheres in patients with chemotherapy refractory/intolerant unresectable colorectal liver metastases. Substantial evidence for its efficacy and safety is available from a randomized controlled study, retrospective comparative studies and several single arm studies. Clinical evidence data obtained from more than 1500 patients have led to the inclusion of selective internal radiation therapy in the 2016 ESMO Clinical Guidelines as third-line treatment. This publication results from an expert panel meeting, where published evidence and author's experiences were shared to position SIR-Spheres Y-90 resin microspheres in Spain for the treatment of chemotherapy refractory/intolerant unresectable colorectal liver metastases, and second, to define the patient subgroup that will benefit the most with this treatment.
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Affiliation(s)
- Enrique Aranda
- Department of Medical Oncology, Hospital Universitario Reina Sofía, CIBERONC, IMIBIC, UCO, Córdoba, Spain
| | - Jorge Aparicio
- Department of Medical Oncology, Hospital Universitari I Politecnic La Fe, Valencia, Spain
| | - José Ignacio Bilbao
- Department of Vascular & Interventional Radiology, Clínica Universidad de Navarra, Navarra, Spain
| | - Pilar García-Alfonso
- Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Joan Maurel
- Department of Medical Oncology, Hospital Clinic, Barcelona, Spain
| | - Javier Rodríguez
- Department of Medical Oncology, Clínica Universitaria de Navarra, Navarra, Spain
| | - Bruno Sangro
- Liver Unit & HPB Oncology Area, Clínica Universitaria de Navarra-IDISNA-CIBEREHD, Pamplona, Spain
| | - José María Vieitez
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Asturias, Spain
| | - Jaime Feliu
- Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC, Madrid, Spain
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Fairchild AH, White SB. Decision Making in Interventional Oncology: Intra-arterial Therapies for Metastatic Colorectal Cancer-Y90 and Chemoembolization. Semin Intervent Radiol 2017; 34:87-91. [PMID: 28579675 DOI: 10.1055/s-0037-1601854] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Colorectal cancer is the third most common cancer in the United States and the liver is the most common site of metastatic disease. The presence and extent of hepatic metastases are a major prognostic indicator. Although surgical resection is the accepted first-line therapy for colorectal liver metastasis, only 20 to 25% of patients are eligible for resection due to the extent and location of disease. This article discusses the current role of transarterial therapies in the treatment of colorectal liver metastases.
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Affiliation(s)
- Alexandra H Fairchild
- Division of Vascular and Interventional Radiology, Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Sarah B White
- Division of Vascular and Interventional Radiology, Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin
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Akinwande O, Dendy M, Ludwig JM, Kim HS. Hepatic intra-arterial injection of irinotecan drug eluting beads (DEBIRI) for patients with unresectable colorectal liver metastases: A systematic review. Surg Oncol 2017; 26:268-275. [PMID: 28807246 DOI: 10.1016/j.suronc.2017.05.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Revised: 04/30/2017] [Accepted: 05/19/2017] [Indexed: 12/22/2022]
Abstract
PURPOSE To systematically review the safety and efficacy of transarterial drug-eluting beads, irinotecan (DEBIRI) for the treatment of pretreated patients with unresectable colorectal liver metastases (CRLM). METHODS A systematic search of the current literature was conducted to extract publications reporting on the use of DEBIRI for CRLM. Data on the safety and efficacy was extracted and tabulated. Weighted average values (WAV) were calculated for each variable to provide a single value representing the pooled safety and efficacy data. RESULTS 13 studies (15 treatment arms) were evaluated, comprising a total of 850 patients. There were 6 prospective phase I/II trials, 5 retrospective trials and 2 randomized control trials. All papers involved patients previously treated with systemic chemotherapy. The weighted average all-grade toxicity rate was 35.2% (range; 6-100%). The high-grade WAV toxicity rate was 10.1% (range; 0-32%). Weighted average response rates were 56.2% and 51.1% according to RECIST (Response Evaluation Criteria in Solid Tumors) and modified RECIST/EASL (European Association for the Study of the Liver) response criteria respectively. The weighted average progression-free survival and overall survival were 8.1 months and 16.8 months, respectively. CONCLUSION Transarterial DEBIRI is safe and effective in the treatment of unresectable CRLM to the liver. Further studies are warranted to better define its role in the treatment algorithm of this patient subset.
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Affiliation(s)
- Olaguoke Akinwande
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, United States
| | - Meaghan Dendy
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States
| | - Johannes M Ludwig
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States
| | - Hyun S Kim
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States; Yale Cancer Center, Yale University, New Haven, CT, United States.
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Di Noia V, Basso M, Marsico V, Cerchiaro E, Rossi S, D'Argento E, Strippoli A, Schinzari G, Iezzi R, Cassano A, Barone C. DEBIRI plus capecitabine: a treatment option for refractory liver-dominant metastases from colorectal cancer. Future Oncol 2017; 15:2349-2360. [PMID: 28440086 DOI: 10.2217/fon-2017-0025] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: This single institution Phase II study evaluated drug-eluting beads loaded with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal cancer liver metastases. Patients & methods: Forty patients with liver-limited or liver-dominant disease, who have failed at least two previous lines of chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every 4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was given at 1000 mg/m2 twice-daily on days 1-14 every 3 weeks. Results: Seven partial responses and 12 stable diseases were observed, achieving a disease control rate of 47.5%. Median progression-free survival and overall survival resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40 points (15%) of patients. Conclusion: DEBIRI plus capecitabine is a valid treatment option for heavily pretreated patients with colorectal cancer liver metastases.
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Affiliation(s)
- Vincenzo Di Noia
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Michele Basso
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Valentina Marsico
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Eleonora Cerchiaro
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Sabrina Rossi
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Ettore D'Argento
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Antonia Strippoli
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Giovanni Schinzari
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Roberto Iezzi
- Institute of Radiology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Alessandra Cassano
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
| | - Carlo Barone
- Division of Medical Oncology, Università cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli, Rome, Italy
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Qian Y, Kumar KA, Dudley SA, Koong AC, Chang DT. Radiation Therapy for Colorectal Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2017. [DOI: 10.1007/s11888-017-0368-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Obrzut S, McCammack K, Badran KW, Balistreri A, Ou E, Nguyen BJ, Hoh CK, Rose SC. Prognostic value of post-Yttrium 90 radioembolization therapy 18F-fluorodeoxyglucose positron emission tomography in patients with liver tumors. Clin Imaging 2017; 42:43-49. [DOI: 10.1016/j.clinimag.2016.11.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 10/31/2016] [Accepted: 11/15/2016] [Indexed: 12/23/2022]
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Aramburu J, Antón R, Rivas A, Ramos JC, Sangro B, Bilbao JI. Computational particle-haemodynamics analysis of liver radioembolization pretreatment as an actual treatment surrogate. INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING 2017; 33:e02791. [PMID: 27038438 DOI: 10.1002/cnm.2791] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 03/23/2016] [Accepted: 03/24/2016] [Indexed: 06/05/2023]
Abstract
Liver radioembolization (RE) is a treatment option for patients with unresectable and chemorefractory primary and metastatic liver tumours. RE consists of intra-arterially administering via catheter radioactive microspheres that locally attack the tumours, sparing healthy tissue. Prior to RE, the standard practice is to conduct a treatment-mimicking pretreatment assessment via the infusion of 99m Tc-labelled macroaggregated albumin microparticles. The usefulness of this pretreatment has been debated in the literature, and thus, the aim of the present study is to shed light on this issue by numerically simulating the liver RE pretreatment and actual treatment particle-haemodynamics in a patient-specific hepatic artery under two different literature-based cancer scenarios and two different placements of a realistic end-hole microcatheter in the proper hepatic artery. The parameters that are analysed are the following: microagent quantity and size (accounting for RE pretreatment and treatment), catheter-tip position (near the proper hepatic artery bifurcation and away from it), and cancer burden (10% and 30% liver involvement). The conclusion that can be reached from the simulations is that when it comes to mimicking RE in terms of delivering particles to tumour-bearing segments, the catheter-tip position is much more important (because of the importance of local haemodynamic pattern alteration) than the infused microagents (i.e. quantity and size). Cancer burden is another important feature because the increase in blood flow rate to tumour-bearing segments increases the power to drag particles. These numerical simulation-based conclusions are in agreement with clinically observed events reported in the literature. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Jorge Aramburu
- Thermal and Fluids Engineering Division, Mechanical Department, Tecnun-University of Navarra, P° Manuel Lardizabal 13, 20018, Donostia-San Sebastián, Spain
| | - Raúl Antón
- Thermal and Fluids Engineering Division, Mechanical Department, Tecnun-University of Navarra, P° Manuel Lardizabal 13, 20018, Donostia-San Sebastián, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Av. Pío XII 36, 31008, Pamplona, Spain
| | - Alejandro Rivas
- Thermal and Fluids Engineering Division, Mechanical Department, Tecnun-University of Navarra, P° Manuel Lardizabal 13, 20018, Donostia-San Sebastián, Spain
| | - Juan Carlos Ramos
- Thermal and Fluids Engineering Division, Mechanical Department, Tecnun-University of Navarra, P° Manuel Lardizabal 13, 20018, Donostia-San Sebastián, Spain
| | - Bruno Sangro
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Av. Pío XII 36, 31008, Pamplona, Spain
- Clínica Universidad de Navarra, Av. Pío XII 36, 31008, Pamplona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Av. Pío XII 36, 31008, Pamplona, Spain
| | - José Ignacio Bilbao
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Av. Pío XII 36, 31008, Pamplona, Spain
- Clínica Universidad de Navarra, Av. Pío XII 36, 31008, Pamplona, Spain
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Wright GP, Marsh JW, Varma MK, Doherty MG, Bartlett DL, Chung MH. Liver Resection After Selective Internal Radiation Therapy with Yttrium-90 is Safe and Feasible: A Bi-institutional Analysis. Ann Surg Oncol 2016; 24:906-913. [PMID: 27878478 DOI: 10.1245/s10434-016-5697-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Treatment with yttrium-90 (Y90) microspheres has emerged as a viable liver-directed therapy for patients with unresectable tumors and those outside transplantation criteria. A select number of patients demonstrate a favorable response and become candidates for surgical resection. METHODS Patients who underwent selective internal radiation therapy (SIRT) with Y90 microspheres at two institutions were reviewed. Patients who underwent liver resection were included in the study. The data gathered included demographics, tumor characteristics, response to Y90, surgical details, perioperative outcomes, and survival. RESULTS The inclusion criteria were met by 12 patients. The diagnoses included metastatic disease from colorectal adenocarcinoma (n = 6), neuroendocrine tumor (n = 1), and ocular melanoma (n = 1) in addition to hepatocellular carcinoma (n = 4). The median time from liver disease diagnosis to Y90 treatment was 5.5 months (range 2-92 months). The median time from Y90 treatment to surgery was 9.5 months (range 3-20 months). The surgical approach included right hepatectomy (n = 3), extended right hepatectomy (n = 5), extended left hepatectomy (n = 1), segmentectomy with ablation (n = 2), and segmentectomy with isolated liver perfusion (n = 1). The hospital stay was 7 days (range 4-31 days), and 67% of the patients were discharged home. The readmission rate was 42%. The 90-day morbidity and mortality rates were respectively 42 and 8%. At this writing, the median overall survival has not been reached at 25 months. CONCLUSION Liver resection after Y90 SIRT is a challenging surgical procedure with high rates of perioperative morbidity and hospital readmission. However, for properly selected patients, potential exists for extending disease-free and overall survival in the current era of multimodal therapy for malignant liver disease.
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Affiliation(s)
- G Paul Wright
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| | - J Wallis Marsh
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | | | | | - David L Bartlett
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mathew H Chung
- Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, MI, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, MI, USA
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Harrold EC, Nicholson PJ, Tuite DJ, Power DG. Selective Internal Radiation Therapy/Yttrium-90: Have We Found Its Place? J Clin Oncol 2016; 34:4193. [PMID: 27621399 DOI: 10.1200/jco.2016.68.6782] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Emily C Harrold
- Emily C. Harrold, Patrick J. Nicholson, David J. Tuite, and Derek G. Power, Cork University Hospital, Wilton, County Cork, Ireland
| | - Patrick J Nicholson
- Emily C. Harrold, Patrick J. Nicholson, David J. Tuite, and Derek G. Power, Cork University Hospital, Wilton, County Cork, Ireland
| | - David J Tuite
- Emily C. Harrold, Patrick J. Nicholson, David J. Tuite, and Derek G. Power, Cork University Hospital, Wilton, County Cork, Ireland
| | - Derek G Power
- Emily C. Harrold, Patrick J. Nicholson, David J. Tuite, and Derek G. Power, Cork University Hospital, Wilton, County Cork, Ireland
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Cercek A, Boucher TM, Gluskin JS, Aguiló A, Chou JF, Connell LC, Capanu M, Reidy-Lagunes D, D'Angelica M, Kemeny NE. Response rates of hepatic arterial infusion pump therapy in patients with metastatic colorectal cancer liver metastases refractory to all standard chemotherapies. J Surg Oncol 2016; 114:655-663. [PMID: 27566258 DOI: 10.1002/jso.24399] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 07/21/2016] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND OBJECTIVES To evaluate the role of hepatic arterial infusion (HAI) in patients with metastatic colorectal cancer (mCRC) liver metastases (LM) refractory to oxaliplatin, irinotecan, and fluorouracil-based treatments. METHODS A search identified patients with mCRC treated after tumor progression on at least three standard systemic therapies. RESULTS One hundred and ten patients met criteria for inclusion (i.e., progression on at least three standard agents). Fifty seven patients had LM-only and 53 patients had LM and low volume extrahepatic metastases (LME). Patients with LM-only and LME had a response rate (RR) of 33% and 36%, median survival of 20 months and 11.4 months, respectively. Patients with LM-only had progression free survival of 6 months and hepatic progression free survival of 7.56 months. In a secondary analysis, 46 patients were RECIST-refractory to all standard therapies: LM-only (n = 24) and LME (n = 22). LM-only and LME had a RR of 29% and 36%, and median survival 17.2 months and 9.1 months, respectively. CONCLUSIONS Patients with refractory mCRC LM can achieve a response to HAI resulting in antitumor activity and improvement in survival. Responses are rarely seen in such heavily treated patients with systemic therapy alone, suggesting a regional directed approach is useful. J. Surg. Oncol. 2016;114:655-663. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
| | - Taryn M Boucher
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jill S Gluskin
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ariel Aguiló
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joanne F Chou
- Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Louise C Connell
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marinela Capanu
- Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Diane Reidy-Lagunes
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
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Mahnken AH. Current status of transarterial radioembolization. World J Radiol 2016; 8:449-459. [PMID: 27247711 PMCID: PMC4882402 DOI: 10.4329/wjr.v8.i5.449] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Revised: 10/17/2015] [Accepted: 03/14/2016] [Indexed: 02/07/2023] Open
Abstract
Unresectable primary and secondary liver malignancies present a major problem in the treatment of solid tumors. Transarterial radioembolization (TARE) is an increasingly used technique for treating various types of malignant liver tumors. This approach is appealing, as the mechanism of action is independent from other loco-regional treatments and potentially complementary to systemic therapies. There are two commercially available products in use for TARE: 90Y-resin and 90Y-glass microspheres. Currently available data indicates TARE so be safe and effective in hepatocellular carcinoma (HCC) and metastatic liver disease. In HCC the results compare well with chemoembolization, while the role of TARE in combination with kinase inhibitors has yet to be established. Current data on TARE in metastatic liver disease is promising, but there is a strong need for prospective randomized trials comparing TARE and modern chemotherapeutic regimen to support the growing role of TARE in metastatic liver disease.
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Kousik V, Promila P, Verma R, Gupta A. Role of yttrium-90 in the management of unresectable hepatocellular carcinoma and hepatic metastases. Indian J Gastroenterol 2016; 35:179-85. [PMID: 27185180 DOI: 10.1007/s12664-016-0657-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 03/27/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The management of unresectable HCC and hepatic metastases from various solid tumors is a clinical dilemma. There is paucity of data on the treatment of unresectable HCC and hepatic metastases with yttrium-90 (90Y) radioembolization. METHODS Thirty patients (mean age; 55.2 years; range 43-82 years) comprising 21 patients with HCC (12 patients have cirrhosis of which 3 patients belong to Child-Pugh class A and 9 patients belong to Child-Pugh class B), 7 patients with metastasis from colorectal cancer, 1 patient with metastasis from melanoma, and 1 patient with metastasis from ovarian carcinoma underwent resin-based 90Y radioembolization between 2013 and 2015 in our study. In all the patients, after embolization of non-target vasculature, SPECT and planar scintigraphy were done with the injection of 5-6 mCi (185-222 MBq) of 99mTc-labeled macroaggregated albumin (MAA) into the hepatic artery. Then, lung shunt fraction was assessed and dose was calculated based on body surface area (BSA) method for SIR-Spheres. Post therapeutic 90Y bremsstrahlung SPECT and 90Y PET was performed within 30 hours following therapy to see the hepatic and extrahepatic distribution of spheres. Side effects following therapy were noted in all the patients. All patients were followed up with triphasic CT liver 3 months following therapy. Therapeutic response was evaluated with necrosis criteria used for therapy response assessment in solid tumors. RESULTS On follow up, 14 patients (46 %) developed minor side effects following treatment and resolved without active intervention. The most common side effects include mild abdominal pain in 11 patients (36 %), nausea in 8 patients (26 %), and fatigue in 6 patients (20 %). On follow up imaging at 3 months following treatment, a complete response was observed in two patients (7 %), partial response in seven patients (23 %), stable disease in 15 patients (50 %), and progressive disease in six patients (20 %). CONCLUSION This study provides supportive evidence of the safety and efficacy on 90Y radioembolization for the treatment of unresectable HCC and hepatic metastases from various solid tumors. 90Y PET is a better radionuclide technique for assessing the hepatic and extrahepatic distribution of spheres following therapy compared to 90Y Bremsstrahlung SPECT. Thus, 90Y radioembolization is proving to be promising treatment with average disease control rates around 80 % and should be widely utilized.
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Affiliation(s)
- Vankadari Kousik
- Department of Nuclear Medicine and PET CT, Ganga Ram Institute for Postgraduate Medical Education and Research, Rajinder Nagar, New Delhi, 110 060, India.
| | - Pankaj Promila
- Department of Nuclear Medicine and PET CT, Ganga Ram Institute for Postgraduate Medical Education and Research, Rajinder Nagar, New Delhi, 110 060, India
| | - Ritu Verma
- Department of Nuclear Medicine and PET CT, Ganga Ram Institute for Postgraduate Medical Education and Research, Rajinder Nagar, New Delhi, 110 060, India
| | - Arun Gupta
- Department of Interventional Radiology, Sir Ganga Ram Hospital, Ganga Ram Institute for Postgraduate Medical Education and Research, Rajinder Nagar, New Delhi, 110 060, India
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Choi H, Lee YS, Hwang DW, Lee DS. Translational radionanomedicine: a clinical perspective. EUROPEAN JOURNAL OF NANOMEDICINE 2016. [DOI: 10.1515/ejnm-2015-0052] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AbstractMany nanomaterials were developed for the anticipated in vivo theranostic use exploiting their unique characteristics as a multifunctional platform. Nevertheless, only a few nanomaterials are under investigation for human use, most of which have not entered clinical trials yet. Radionanomedicine, a convergent discipline of radiotracer technology and use of nanomaterials in vivo, can facilitate clinical nanomedicine because of its advantages of radionuclide imaging and internal radiation therapy. In this review, we focuse on how radionanomedicine would impact profoundly on clinical translation of nanomaterial theranostics. Up-to-date advances and future challenges are critically reviewed regarding the issues of how to radiolabel and engineer radionanomaterials, in vivo behavior tracing of radionanomaterials and then the desired clinical radiation dosimetry. Radiolabeled extracellular vesicles were further discussed as endogenous nanomaterials radiolabeled for possible clinical use.
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Maleux G, Deroose C, Laenen A, Verslype C, Heye S, Haustermans K, De Hertogh G, Sagaert X, Topal B, Aerts R, Prenen H, Vanbeckevoort D, Vandecaveye V, Van Cutsem E. Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival. Acta Oncol 2015; 55:486-95. [PMID: 26625262 DOI: 10.3109/0284186x.2015.1101151] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The purpose of this study was to retrospectively assess the technical and clinical outcomes, overall survival and prognostic factors for prolonged survival after yttrium-90 ((90)Y) radioembolization as a salvage therapy for patients with chemorefractory liver-only or liver-dominant colorectal metastases. MATERIAL AND METHODS From January 2005 to January 2014, all the patients selected for (90)Y radioembolization to treat chemorefractory colorectal liver metastases were identified. Demographic, laboratory, imaging and dosimetry data were collected. Post-treatment technical and clinical outcomes were analyzed as well as overall survival; finally several factors potentially influencing survival were analyzed. RESULTS In total 88 patients were selected for angiographic workup; 71 patients (81%) finally underwent catheter-directed (90)Y microsphere infusion into the hepatic artery 25 days (standard deviation 13 days) after angiographic workup. Median infused activity was 1809 MBq; 30-day toxicity included: fatigue (n = 39; 55%), abdominal discomfort (n = 33; 47%), nausea (n = 5; 7%), fever (n = 14; 20%), diarrhea (n = 6; 9%), liver function abnormalities and elevated bilirubin (transient) (n = 3; 4%). Gastric ulcer was found in five patients (7%). A late complication was radioembolization-induced portal hypertension (REIPH) in three patients (4%). Median time to progression in the liver was 4.4 months. Estimated survival at six and 12 months was 65% and 30%, respectively, with a 50% estimated survival after 8.0 months in this group of chemorefractory patients. Prognostic factors for worse survival were high preprocedural bilirubin, alkaline phosphatase and tumor volume levels. CONCLUSION (90)Y microsphere radioembolization for chemorefractory colorectal liver metastases has an acceptable safety profile with a 50% estimated survival after 8.0 months. Pretreatment high bilirubin, alkaline phosphatase and tumor volume levels were associated with early death.
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Affiliation(s)
- Geert Maleux
- Department of Radiology, University Hospitals Leuven, Department of Imaging & Pathology, KU Leuven, Belgium
| | | | - Annouschka Laenen
- Interuniversity Centre for Biostatistics and Statistical Bioinformatics, Catholic University of Leuven and University Hasselt, Belgium
| | - Chris Verslype
- Department of Gastroenterology, University Hospitals Leuven, Belgium
| | - Sam Heye
- Department of Radiology, University Hospitals Leuven, Department of Imaging & Pathology, KU Leuven, Belgium
| | - Karin Haustermans
- Department of Radiation Oncology, University Hospitals Leuven, Belgium
| | - Gert De Hertogh
- Department of Pathology, University Hospitals Leuven, Belgium
| | - Xavier Sagaert
- Department of Pathology, University Hospitals Leuven, Belgium
| | - Baki Topal
- Department of Abdominal Surgery, University Hospitals Leuven, Belgium
| | - Raymond Aerts
- Department of Abdominal Surgery, University Hospitals Leuven, Belgium
| | - Hans Prenen
- Department of Gastroenterology, University Hospitals Leuven, Belgium
| | - Dirk Vanbeckevoort
- Department of Radiology, University Hospitals Leuven, Department of Imaging & Pathology, KU Leuven, Belgium
| | - Vincent Vandecaveye
- Department of Radiology, University Hospitals Leuven, Department of Imaging & Pathology, KU Leuven, Belgium
| | - Eric Van Cutsem
- Department of Gastroenterology, University Hospitals Leuven, Belgium
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Orsi F, Varano G. Minimal invasive treatments for liver malignancies. ULTRASONICS SONOCHEMISTRY 2015; 27:659-667. [PMID: 26050603 DOI: 10.1016/j.ultsonch.2015.05.030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 05/13/2015] [Indexed: 06/04/2023]
Abstract
Minimal invasive therapies have proved useful in the management of primary and secondary hepatic malignancies. The most relevant aspects of all these therapies are their minimal toxicity profiles and highly effective tumor responses without affecting the normal hepatic parenchyma. These unique characteristics coupled with their minimally invasive nature provide an attractive therapeutic option for patients who previously may have had few alternatives. Combination of these therapies might extend indications to bring curative treatment to a wider selected population. The results of various ongoing combination trials of intraarterial therapies with targeted therapies are awaited to further improve survival in this patient group. This review focuses on the application of ablative and intra-arterial therapies in the management of hepatocellular carcinoma and hepatic colorectal metastasis.
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Affiliation(s)
- Franco Orsi
- European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
| | - Gianluca Varano
- European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
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Groote KD, Prenen H. Intrahepatic therapy for liver-dominant metastatic colorectal cancer. World J Gastrointest Oncol 2015; 7:148-152. [PMID: 26380058 PMCID: PMC4569592 DOI: 10.4251/wjgo.v7.i9.148] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Revised: 07/06/2015] [Accepted: 08/03/2015] [Indexed: 02/05/2023] Open
Abstract
In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer.
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