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1
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Dimopoulos PM, Sotirchos VS, Dunne-Jaffe C, Petre EN, Gonen M, Zhao K, Kirov AS, Crane C, D'Angelica M, Connell LC, Sofocleous CT. Voxel-Based Dosimetry Predicts Local Tumor Progression Post 90 Y Radiation Segmentectomy of Colorectal Liver Metastases. Clin Nucl Med 2025; 50:133-142. [PMID: 39745670 DOI: 10.1097/rlu.0000000000005565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
BACKGROUND Radiation segmentectomy (RS) is an alternative potential local curative treatment for selected colorectal liver metastases (CLMs) not amenable to ablation or limited resection. PURPOSE The aim of this study was to evaluate the dosimetric response of low volume CLMs to RS in heavily pretreated patients who are not candidates for resection or percutaneous ablation. PATIENTS AND METHODS This single-center retrospective study evaluated CLMs patients treated with RS (prescribed tumor dose >190 Gy) from 2015 to 2023. RS doses to tumor(s) and margins were calculated from SPECT/CT and PET/CT images. Response and local tumor progression (LTP) were assessed using anatomic (RECIST 1.1) and metabolic (PERCIST) criteria. LTP-free survival (LTPFS) and overall survival were estimated with Kaplan-Meier methodology. Variables were assessed as predictors of LTPFS using the Cox proportional hazards model. RESULTS Thirty-six patients underwent 38 RS procedures to treat 57 tumors. Median time from initial diagnosis to detection of liver metastases and RS were 16.4 (interquartile range: 6.5-32.2) and 26.8 (interquartile range: 12.5-40.0) months, respectively. Median overall survival after RS was 14.3 (95% confidence interval [CI]: 10.8-30.7) months. Predictors of LTPFS included tumor number(s), mean tumor dose (MTD), and margin mean absorbed dose (MMAD). Complete radiographic (hazards ratio [HR]: 1.29e-16, 95% CI: 4.06e-17-4.07e-16, P < 0.001) and metabolic response (HR: 0.38, 95% CI: 0.15-0.95, P = 0.038) correlated with prolonged LTPFS. One-year LTPFS rate was 83.3% for tumors receiving MTD ≥400 Gy and a 5-mm surrounding MMAD ≥350 Gy ( P = 0.006). No instances of LTP were observed when tumors received stereotactic irradiation over 300 Gy (at least 95% of the tumor volume received ≥300 Gy). One-year LTPFS rate for tumors receiving MTD ≥400 Gy was 68.6% versus 14.3% for those that did not reach this threshold ( P = 0.013). In multivariate analysis, MTD ≥400 Gy and 5-mm MMAD ≥350 Gy were independent predictors of LTPFS (HR: 0.11; 95% CI: 0.01-0.81; P = 0.03). CONCLUSIONS MTD ≥400 Gy, MMAD ≥350 Gy, and stereotactic tumor irradiation ≥300 Gy are associated with prolonged LTPFS after RS for CLMs.
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Affiliation(s)
| | - Vlasios S Sotirchos
- From the Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Elena N Petre
- From the Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ken Zhao
- From the Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Assen S Kirov
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Christopher Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Louise C Connell
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Constantinos T Sofocleous
- From the Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
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Das S, Berlin J. Systemic Therapy Improvements Will Render Locoregional Treatments Obsolete for Patients with Cancer with Liver Metastases. Hematol Oncol Clin North Am 2025; 39:191-206. [PMID: 39510673 DOI: 10.1016/j.hoc.2024.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Hepatic metastases are a major cause of morbidity and mortality for patients with cancer. Apart from curative resection, which offers patients the potential for long-term survival, an array of locoregional therapies, with limited evidence of improving survival, are used to treat them. The authors use examples from the realm of gastrointestinal cancer, largely focusing on the experience of patients with neuroendocrine cancer, hepatobiliary cancer, and colorectal cancer, to suggest that current systemic therapies offer, at minimum, similar survival outcomes for patients compared with these locoregional approaches.
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Affiliation(s)
- Satya Das
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232, USA.
| | - Jordan Berlin
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232, USA. https://twitter.com/jordanberlin5
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Gebauer B, Collettini F, Pfob CH, Lapa C. [Modern TARE 2023 - from palliative care to a curative treatment alternative]. Nuklearmedizin 2024; 63:328-336. [PMID: 39013456 PMCID: PMC11614522 DOI: 10.1055/a-2353-5819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 05/13/2024] [Indexed: 07/18/2024]
Abstract
Selective internal radiotherapy (SIRT) or transarterial radioembolisation (TARE) is an alternative treatment for hepatocellular carcinoma (HCC) or hepatic metastatic colorectal carcinoma (mCRC) and is now anchored in many guidelines. The article summarises the current guidelines on SIRT/TARE in HCC and mCRC.
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Affiliation(s)
| | - Federico Collettini
- Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health at Charite, Berlin, Germany
| | | | - Constantin Lapa
- Nuklearmedizin, Universitätsklinikum Augsburg, Augsburg, Germany
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Arar A, Heglin A, Veluri S, Alnablsi MW, Benjamin JL, Choudhary M, Pillai A. Radioembolization of HCC and secondary hepatic tumors: a comprehensive review. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2024; 68:270-287. [PMID: 39088238 DOI: 10.23736/s1824-4785.24.03572-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.
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Affiliation(s)
- Ahmad Arar
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA -
| | - Alex Heglin
- Division of Nuclear Medicine, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Shriya Veluri
- The University of Texas Health Science Center, San Antonio, TX, USA
| | - Mhd Wisam Alnablsi
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jamaal L Benjamin
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Moaz Choudhary
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Anil Pillai
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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5
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Badran O, Dereza S, Mireb L, Neeman Z, Bar-Sela G. Case Report: Successful Treatment of Solitary Fibrous Tumor with Selective Internal Radiation Therapy (SIRT). Diseases 2024; 12:290. [PMID: 39589964 PMCID: PMC11592958 DOI: 10.3390/diseases12110290] [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: 10/03/2024] [Revised: 11/05/2024] [Accepted: 11/05/2024] [Indexed: 11/28/2024] Open
Abstract
Background: This case report details the innovative use of selective internal radiation therapy (SIRT) with Yttrium-90 resin microspheres to treat a 73-year-old woman with a solitary fibrous tumor (SFT), a rare and challenging tumor type. SFTs often present significant treatment difficulties, especially in cases of recurrence or metastasis, as systemic therapies typically show limited effectiveness. This report explores SIRT as an alternative therapeutic approach for SFTs with liver metastasis. Methods: The patient initially presented with a pelvic mass, which was surgically resected. However, metastatic disease later developed in the liver. After experiencing severe side effects from targeted therapy with sunitinib, the patient was selected for treatment with SIRT as an alternative. Results: Following the SIRT intervention, the patient demonstrated a substantial reduction in tumor size and significant relief from symptoms. This outcome suggests SIRT's effectiveness as a targeted treatment for metastatic SFT. Conclusions: To our knowledge, and based on an extensive literature review, this is the first reported instance of treating SFT with SIRT. This case provides new insights into SIRT's potential as a therapeutic strategy, particularly for patients for whom conventional treatments are either ineffective or intolerable. The success observed here underscores SIRT's potential as a less invasive, locally targeted treatment option, offering hope for similar cases.
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Affiliation(s)
- Omar Badran
- Department of Oncology, Emek Medical Center, Yitzhak Rabin Boulevard 21, Afula 1834111, Israel;
- Technion Integrated Cancer Center, Faculty of Medicine, Technion, Haifa 1834111, Israel;
| | - Sergey Dereza
- Diagnostic Imaging Department, Emek Medical Center, Yitzhak Rabin Boulevard 21, Afula 1834111, Israel; (S.D.); (L.M.)
| | - Labib Mireb
- Diagnostic Imaging Department, Emek Medical Center, Yitzhak Rabin Boulevard 21, Afula 1834111, Israel; (S.D.); (L.M.)
| | - Ziv Neeman
- Technion Integrated Cancer Center, Faculty of Medicine, Technion, Haifa 1834111, Israel;
- Diagnostic Imaging Department, Emek Medical Center, Yitzhak Rabin Boulevard 21, Afula 1834111, Israel; (S.D.); (L.M.)
| | - Gil Bar-Sela
- Department of Oncology, Emek Medical Center, Yitzhak Rabin Boulevard 21, Afula 1834111, Israel;
- Technion Integrated Cancer Center, Faculty of Medicine, Technion, Haifa 1834111, Israel;
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Mansur A, Habibollahi P, Fang A, Mahvash A, Etezadi V, Liddell RP, Camacho JC, Cohen EI, Kokabi N, Arepally A, Georgiades C, Nezami N. New frontiers in radioembolization. Ther Adv Med Oncol 2024; 16:17588359241280692. [PMID: 39371617 PMCID: PMC11456171 DOI: 10.1177/17588359241280692] [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: 01/17/2024] [Accepted: 08/19/2024] [Indexed: 10/08/2024] Open
Abstract
Radioembolization is a locoregional transarterial therapy that combines radionuclide and micron-sized beads to deliver radiation internally to the target tumors based on the arterial blood flow. While initially developed as a palliative treatment option, radioembolization is now used for curative intent treatment, neoadjuvant therapy, and method to downstage or bridge for liver transplant. Radioembolization has become increasingly utilized and is an important therapeutic option for the management of hepatocellular carcinoma and liver metastasis. This article provides an overview of the techniques, challenges, and novel developments in radioembolization, including new dosimetry techniques, radionuclides, and new target tumors.
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Affiliation(s)
| | - Peiman Habibollahi
- Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Adam Fang
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Armeen Mahvash
- Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Vahid Etezadi
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Robert P. Liddell
- Division of Vascular and Interventional Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Juan C. Camacho
- Department of Clinical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA
- Vascular and Interventional Radiology, Radiology Associates of Florida, Sarasota, FL, USA
| | - Emil I. Cohen
- Division of Vascular and Interventional Radiology, Department of Radiology, Georgetown University School of Medicine, Washington, DC, USA
| | - Nima Kokabi
- Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Aravind Arepally
- Radiology Associates of Atlanta, Atlanta, GA, USA
- ABK Biomedical Inc., Atlanta, GA, USA
| | - Christos Georgiades
- Division of Vascular and Interventional Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Radiology, Georgetown University School of Medicine, 3800 Reservoir Road, NW, CCC Bldg., Room CG225, Washington, DC 20007, USA
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7
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Buscombe J, Cwikla J, Quigley AM, Navalkissoor S, Yu D. Selective Internal Radiotherapy in Liver Tumors: Early Promise Yet to be Fulfilled. Semin Nucl Med 2024; 54:530-536. [PMID: 38627159 DOI: 10.1053/j.semnuclmed.2024.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 03/25/2024] [Indexed: 08/05/2024]
Abstract
Selective intra-arterial radiotherapy (SIRT) is a technique which has evolved over the past 30 years. In present this is primarily used to treat primary and secondary tumors in the liver. The technique normally depends on the delivery of a therapeutic radiopharmaceutical or radiolabeled particulate via a radiologically placed intra-arterial catheter in the hepatic artery. This is because most of these tumors have a single arterial blood supply but normal hepatocytes are supplied by both the hepatic artery and portal vein. Initially, this was done with I-131 labelled poppy seed oil but this technique was only used in a few centers. The technique became more popular when Y-90 particulates become widely available. Early results were promising but in phase 3 randomized controlled trials resulted in disappointing results compared to systemic chemotherapy. More recent work however, have shown that increasing the radiation dose to the tumor to at least 60Gy and combining with more effective systemic therapies are starting to produce better clinical results. There have also been advances in the angiographic methods used to make this into a day-case technique and the use of new radionuclides such as Ho-166 and Re-188 provides a wider range of possible SIRT techniques.
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Affiliation(s)
- John Buscombe
- Department of Nuclear Medicine, Cambridge University Hospitals, Cambridge, UK.
| | - Jaroslaw Cwikla
- Nuclear Medicine, University of Warmia and Mazury, Olsztyn, Poland
| | | | | | - Dominic Yu
- Department of Radiology, Royal Free Hospital, London, UK
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8
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Pollock RF, Shergill S, Carion PL, von Oppen N, Agirrezabal I, Brennan VK. Advances in Delivery of Selective Internal Radiation Therapy (SIRT): Economic and Logistical Effects of Same-Stay Work-Up and Procedure in the Treatment of Unresectable Liver Tumors in England. Adv Ther 2023; 40:294-309. [PMID: 36318388 PMCID: PMC9628427 DOI: 10.1007/s12325-022-02323-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 09/14/2022] [Indexed: 11/07/2022]
Abstract
INTRODUCTION Selective internal radiation therapy (SIRT) is a targeted method of treatment for unresectable liver tumors in which radiation therapy is directly delivered to the tumor(s) via the hepatic vasculature. Successful outcomes with SIRT are dependent on the specific vasculature of the liver and tumor, and the patient therefore needs to attend a "work-up" to map the hepatic vasculature prior to the SIRT procedure. Recent advances in SIRT delivery have enabled same-day or same-stay work-up and procedure, requiring only one hospital visit rather than two. We aimed to evaluate the economic, travel time, and transport-related environmental impact of a new brachytherapy device delivery program, the order-map-treat (OMT) program, in patients with unresectable hepatocellular carcinoma (HCC) in England. METHODS A healthcare resource group (HRG)-based analysis of costs from a national payer (Department of Health and Social Care, DHSC) perspective was conducted assuming that, with OMT, patients would have to attend hospital only once for both the SIRT work-up and procedure versus twice without OMT. Patient travel time and CO2 emissions were then estimated by identifying the SIRT center closest to the centroid of each clinical commissioning group (CCG) and calculating straight-line distances with a "detour index" to capture the effect of indirect routes via road or rail. RESULTS It was estimated that 856 patients per annum would be eligible for SIRT treatment for unresectable HCC in England. OMT would be anticipated to save GBP 2842 per patient versus performing SIRT without OMT. Furthermore, across all patients with HCC eligible for SIRT in England, OMT would avoid 74,500 km of travel, 2299 h of travel time, and 13.9 metric tons of patient transport-related CO2 emissions annually. CONCLUSION OMT reduces the number of hospital visits required for SIRT by 50%, resulting in financial savings from the DHSC perspective, time savings from the patient perspective, and reduced CO2 emissions arising from patient transport.
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Affiliation(s)
- Richard F. Pollock
- Covalence Research Ltd, Rivers Lodge, West Common, Harpenden, AL5 2JD UK
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Schaefer N, Grözinger G, Pech M, Pfammatter T, Soydal C, Arnold D, Kolligs F, Maleux G, Munneke G, Peynircioglu B, Sangro B, Pereira H, Zeka B, de Jong N, Helmberger T. Prognostic Factors for Effectiveness Outcomes After Transarterial Radioembolization in Metastatic Colorectal Cancer: Results From the Multicentre Observational Study CIRT. Clin Colorectal Cancer 2022; 21:285-296. [PMID: 36270925 DOI: 10.1016/j.clcc.2022.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/31/2022] [Accepted: 09/14/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND Transarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treatment application can improve survival outcomes. METHODS We analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for independent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. RESULTS The median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease (P= .0391), prior locoregional procedures (P= .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of ≤0.40 (P< .0001) and International Normalized Ratio (INR) ≤1 (P= .0078). Partition model dosimetry resulted in improved OS outcomes compared to the body surface area model (P = .0120). Independent predictors for PFS were APRI >0.40 (P = .0416) and prior ablation (P = .0323), and for hPFS these were 2 to 5 tumor nodules (P = .0148), Albumin-bilirubin (ALBI) grade 3 (P = .0075) and APRI >0.40 (P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. CONCLUSION Including easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.
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Affiliation(s)
- Niklaus Schaefer
- Service de médecine nucléaire et imagerie moléculaire, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - Gerd Grözinger
- Eberhard Karls University, Department of Diagnostic and Interventional Radiology, Tübingen, Germany
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany
| | - Thomas Pfammatter
- Institute of Diagnostic and Interventional Radiology, UniversitätsSpital Zürich, Zürich, Switzerland
| | - Cigdem Soydal
- Ankara University, Medical School, Department of Nuclear Medicine, Cebeci, Ankara, Turkey
| | - Dirk Arnold
- Oncology and Hematology, Asklepios Tumorzentrum Hamburg, Hamburg, Germany
| | - Frank Kolligs
- Department of Internal Medicine and Gastroenterology, Helios Klinikum Berlin-Buch, Berlin, Germany
| | - Geert Maleux
- Radiology, Universitair Ziekenhuis Leuven, Leuven, Belgium
| | - Graham Munneke
- Interventional Oncology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Bora Peynircioglu
- Department of Radiology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Bruno Sangro
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain
| | - Helena Pereira
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Unité de Recherche Clinique, Paris, France; INSERM, Centre d'Investigation Clinique 1418 (CIC1418), Paris, France
| | - Bleranda Zeka
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Vienna Austria
| | - Niels de Jong
- Clinical Research Department, Cardiovascular and Interventional Radiological Society of Europe, Vienna Austria.
| | - Thomas Helmberger
- Department of Radiology, Neuroradiology and Minimal-Invasive Therapy, Klinikum Bogenhausen, Munich, Germany
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Role of Transhepatic Arterial Radioembolization in Metastatic Colorectal Cancer. Cardiovasc Intervent Radiol 2022; 45:1579-1589. [PMID: 36104632 DOI: 10.1007/s00270-022-03268-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 08/25/2022] [Indexed: 11/28/2022]
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Sharma NK, Kappadath SC, Chuong M, Folkert M, Gibbs P, Jabbour SK, Jeyarajah DR, Kennedy A, Liu D, Meyer JE, Mikell J, Patel RS, Yang G, Mourtada F. The American Brachytherapy Society consensus statement for permanent implant brachytherapy using Yttrium-90 microsphere radioembolization for liver tumors. Brachytherapy 2022; 21:569-591. [PMID: 35599080 PMCID: PMC10868645 DOI: 10.1016/j.brachy.2022.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/25/2022] [Accepted: 04/14/2022] [Indexed: 11/02/2022]
Abstract
PURPOSE To develop a multidisciplinary consensus for high quality multidisciplinary implementation of brachytherapy using Yttrium-90 (90Y) microspheres transarterial radioembolization (90Y TARE) for primary and metastatic cancers in the liver. METHODS AND MATERIALS Members of the American Brachytherapy Society (ABS) and colleagues with multidisciplinary expertise in liver tumor therapy formulated guidelines for 90Y TARE for unresectable primary liver malignancies and unresectable metastatic cancer to the liver. The consensus is provided on the most recent literature and clinical experience. RESULTS The ABS strongly recommends the use of 90Y microsphere brachytherapy for the definitive/palliative treatment of unresectable liver cancer when recommended by the multidisciplinary team. A quality management program must be implemented at the start of 90Y TARE program development and follow-up data should be tracked for efficacy and toxicity. Patient-specific dosimetry optimized for treatment intent is recommended when conducting 90Y TARE. Implementation in patients on systemic therapy should account for factors that may enhance treatment related toxicity without delaying treatment inappropriately. Further management and salvage therapy options including retreatment with 90Y TARE should be carefully considered. CONCLUSIONS ABS consensus for implementing a safe 90Y TARE program for liver cancer in the multidisciplinary setting is presented. It builds on previous guidelines to include recommendations for appropriate implementation based on current literature and practices in experienced centers. Practitioners and cooperative groups are encouraged to use this document as a guide to formulate their clinical practices and to adopt the most recent dose reporting policies that are critical for a unified outcome analysis of future effectiveness studies.
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Affiliation(s)
- Navesh K Sharma
- Department of Radiation Oncology, Penn State Hershey School of Medicine, Hershey, PA
| | - S Cheenu Kappadath
- Department of Imaging Physics, UT MD Anderson Cancer Center, Houston, TX
| | - Michael Chuong
- Department of Radiation Oncology, Miami Cancer Institute, Miami, FL
| | - Michael Folkert
- Northwell Health Cancer Institute, Radiation Medicine at the Center for Advanced Medicine, New Hyde Park, NY
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
| | - Salma K Jabbour
- Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ
| | | | | | - David Liu
- Vancouver General Hospital, Vancouver, British Columbia, Canada
| | | | | | - Rahul S Patel
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Gary Yang
- Loma Linda University, Loma Linda, CA
| | - Firas Mourtada
- Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE; Department of Radiation Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA.
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12
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Ytrrium-90 transarterial radioembolization in patients with gastrointestinal malignancies. Clin Transl Oncol 2022; 24:796-808. [PMID: 35013882 DOI: 10.1007/s12094-021-02745-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 11/29/2021] [Indexed: 10/19/2022]
Abstract
Transarterial radioembolization (TARE) with yttrium-90 (Y90) is a promising alternative strategy to treat liver tumors and liver metastasis from colorectal cancer (CRC), as it selectively delivers radioactive isotopes to the tumor via the hepatic artery, sparring surrounding liver tissue. The landscape of TARE indications is constantly evolving. This strategy is considered for patients with hepatocellular carcinoma (HCC) with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible. In patients with liver metastases from CRC, TARE is advised when other chemotherapeutic options have failed. Recent phase III trials have not succeeded to prove benefit in overall survival; however, it has helped to better understand the patients that may benefit from TARE based on subgroup analysis. New strategies and treatment combinations are being investigated in ongoing clinical trials. The aim of this review is to summarize the clinical applications of TARE in patients with gastrointestinal malignancies.
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13
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Entezari P, Gabr A, Salem R, Lewandowski RJ. Yttrium-90 for colorectal liver metastasis - the promising role of radiation segmentectomy as an alternative local cure. Int J Hyperthermia 2022; 39:620-626. [DOI: 10.1080/02656736.2021.1933215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Pouya Entezari
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL, USA
| | - Ahmed Gabr
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL, USA
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL, USA
- Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA
| | - Robert J. Lewandowski
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL, USA
- Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA
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14
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Weber M, Lam M, Chiesa C, Konijnenberg M, Cremonesi M, Flamen P, Gnesin S, Bodei L, Kracmerova T, Luster M, Garin E, Herrmann K. EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. Eur J Nucl Med Mol Imaging 2022; 49:1682-1699. [PMID: 35146577 PMCID: PMC8940802 DOI: 10.1007/s00259-021-05600-z] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 10/19/2021] [Indexed: 12/15/2022]
Abstract
Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.
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Affiliation(s)
- M Weber
- Department of Nuclear medicine, University clinic Essen, Essen, Germany.
| | - M Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - C Chiesa
- Nuclear Medicine, Foundation IRCCS National Tumour Institute, Milan, Italy
| | - M Konijnenberg
- Nuclear Medicine Department, Erasmus MC, Rotterdam, The Netherlands
| | - M Cremonesi
- Radiation Research Unit, IEO European Institute of Oncology IRCCS, Via Giuseppe Ripamonti, 435, 20141, Milan, MI, Italy
| | - P Flamen
- Department of Nuclear Medicine, Institut Jules Bordet-Université Libre de Bruxelles (ULB), 1000, Brussels, Belgium
| | - S Gnesin
- Institute of Radiation physics, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - L Bodei
- Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - T Kracmerova
- Department of Medical Physics, Motol University Hospital, Prague, Czech Republic
| | - M Luster
- Department of Nuclear medicine, University hospital Marburg, Marburg, Germany
| | - E Garin
- Department of Nuclear Medicine, Cancer, Institute Eugène Marquis, Rennes, France
| | - K Herrmann
- Department of Nuclear medicine, University clinic Essen, Essen, Germany
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15
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Polverari G, Penna D, Cassalia L, Deandreis D, Pelosi E. Diagnostic Applications of Nuclear Medicine: Colorectal Cancer. NUCLEAR ONCOLOGY 2022:919-932. [DOI: 10.1007/978-3-031-05494-5_19] [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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16
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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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18
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Moslim MA, Jeyarajah DR. Narrative review of the role of yttrium-90 selective internal radiation therapy in the surgical management of colorectal liver metastases. J Gastrointest Oncol 2021; 12:2438-2446. [PMID: 34790404 DOI: 10.21037/jgo-21-96] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 06/08/2021] [Indexed: 11/06/2022] Open
Abstract
The management of colorectal liver metastasis (CRLM) is complicated and benefits from a multidisciplinary team approach. Liver-directed therapy has been emerging as a modality for better progression-free control. In its early years, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) was confined as an end-of-line therapy. However, literature has supported other roles including: a first-line treatment for CRLM alone or in combination with systemic chemotherapy; an adjunct to second or third-line chemotherapy; and a salvage treatment for chemo-refractory disease. Although future liver remnant (FLR) hypertrophy may take 3-12 months, the SIRT effect on loco-regional disease control has rendered it to be a useful tool in some pathologies with certain strategic goals. This paper reviews the use of SIRT with Y-90 in a surgical treatment pathway. This includes: (I) an element of multidisciplinary treatment of low-volume CRLMs, (II) convert an R1 to R0 resection by sterilizing the margins of tumor near critical structures, and (III) radiation lobectomy to induce contralateral hypertrophy in order to aid in a safer resection. There are many opportunities to validate the role of SIRT as a first-line therapy along with surgical resection including an umbrella clinical trial design.
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Abstract
90 Yttrium (Y90) radioembolization has been shown to improve outcomes for primary and metastatic liver cancers, but there is limited understanding of the optimal timing and safety of combining systemic therapies with Y90 treatment. Both therapeutic effects and toxicities could be synergistic depending on the timing and dosing of different coadministration paradigms. In particular, patients with liver-only or liver-dominant metastatic disease progression are often on systemic therapy when referred to interventional radiology for consideration of Y90 treatment. Interventional radiologists are frequently asked to offer insight into whether or not to hold systemic therapy, and for how long, prior to and following transarterial therapy. This study reviews the current evidence regarding the timing and safety of systemic therapy with Y90 treatment for hepatocellular carcinoma, metastatic colorectal carcinoma, intrahepatic cholangiocarcinoma, metastatic neuroendocrine tumors, and other hepatic metastases. A particular focus is placed on the timing, dosing, and toxicities of combined therapy.
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Affiliation(s)
- Tarub S Mabud
- Division of Vascular Interventional Radiology, Department of Radiology, NYU Langone Health, New York, New York
| | - Ryan Hickey
- Division of Vascular Interventional Radiology, Department of Radiology, NYU Langone Health, New York, New York
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20
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Tchelebi LT, Goodman KA. Mature Experiences Using Local Therapy for Oligometastases. Semin Radiat Oncol 2021; 31:180-185. [PMID: 34090644 DOI: 10.1016/j.semradonc.2021.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Cancer is a heterogeneous disease, consisting of a spectrum of disorders ranging from local-only disease to those that are widely metastatic from their onset. The oligometastatic state, in which tumors harbor a limited number of metastases, may be curable in a subset of patients. The early success of surgical resection of hepatic metastases from colorectal cancer led to investigations into metastatectomy of other sites and, more recently, into the use of stereotactic ablative radiotherapy (SABR) for oligometastatic disease. This article reviews the data establishing the role of surgery for managing limited metastatic disease. Further, we review recent experiences using alternative local therapies, such as SABR, for oligometastases. This review also discusses ongoing trials evaluating local therapies for patients with a limited burden of metastatic cancer.
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Affiliation(s)
- Leila T Tchelebi
- Department of Radiation Oncology, Penn State College of Medicine, Hershey, PA.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
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Ghani MA, Fereydooni A, Chen E, Letzen B, Laage-Gaupp F, Nezami N, Deng Y, Gan G, Thakur V, Lin M, Papademetris X, Schernthaner RE, Huber S, Chapiro J, Hong K, Georgiades C. Identifying enhancement-based staging markers on baseline MRI in patients with colorectal cancer liver metastases undergoing intra-arterial tumor therapy. Eur Radiol 2021; 31:8858-8867. [PMID: 34061209 DOI: 10.1007/s00330-021-08058-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/07/2021] [Accepted: 05/06/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To determine if three-dimensional whole liver and baseline tumor enhancement features on MRI can serve as staging biomarkers and help predict survival of patients with colorectal cancer liver metastases (CRCLM) more accurately than one-dimensional and non-enhancement-based features. METHODS This retrospective study included 88 patients with CRCLM, treated with transarterial chemoembolization or Y90 transarterial radioembolization between 2001 and 2014. Semi-automated segmentations of up to three dominant lesions were performed on pre-treatment MRI to calculate total tumor volume (TTV) and total liver volumes (TLV). Quantitative 3D analysis was performed to calculate enhancing tumor volume (ETV), enhancing tumor burden (ETB, calculated as ETV/TLV), enhancing liver volume (ELV), and enhancing liver burden (ELB, calculated as ELV/TLV). Overall and enhancing tumor diameters were also measured. A modified Kaplan-Meier method was used to determine appropriate cutoff values for each metric. The predictive value of each parameter was assessed by Kaplan-Meier survival curves and univariable and multivariable cox proportional hazard models. RESULTS All methods except whole liver (ELB, ELV) and one-dimensional/non-enhancement-based methods were independent predictors of survival. Multivariable analysis showed a HR of 2.1 (95% CI 1.3-3.4, p = 0.004) for enhancing tumor diameter, HR 1.7 (95% CI 1.1-2.8, p = 0.04) for TTV, HR 2.3 (95% CI 1.4-3.9, p < 0.001) for ETV, and HR 2.4 (95% CI 1.4-4.0, p = 0.001) for ETB. CONCLUSIONS Tumor enhancement of CRCLM on baseline MRI is strongly associated with patient survival after intra-arterial therapy, suggesting that enhancing tumor volume and enhancing tumor burden are better prognostic indicators than non-enhancement-based and one-dimensional-based markers. KEY POINTS • Tumor enhancement of colorectal cancer liver metastases on MRI prior to treatment with intra-arterial therapies is strongly associated with patient survival. • Three-dimensional, enhancement-based imaging biomarkers such as enhancing tumor volume and enhancing tumor burden may serve as the basis of a novel prognostic staging system for patients with liver-dominant colorectal cancer metastases.
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Affiliation(s)
- Mansur A Ghani
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - Arash Fereydooni
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - Evan Chen
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - Brian Letzen
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - Fabian Laage-Gaupp
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - Nariman Nezami
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA.,Russel H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, USA.,Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Yanhong Deng
- Yale Center for Analytical Science, Yale School of Public Health, New Haven, CT, USA
| | - Geliang Gan
- Yale Center for Analytical Science, Yale School of Public Health, New Haven, CT, USA
| | - Vinayak Thakur
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - MingDe Lin
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - Xenophon Papademetris
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA.,Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | - Ruediger E Schernthaner
- Russel H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, USA.,Department of Diagnostic and Interventional Radiology, Hospital Landstraße, Vienna, Austria
| | - Steffen Huber
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar St, New Haven, CT, USA. .,Russel H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, USA.
| | - Kelvin Hong
- Russel H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Christos Georgiades
- Russel H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, USA
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22
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Mauri G, Monfardini L, Garnero A, Zampino MG, Orsi F, Della Vigna P, Bonomo G, Varano GM, Busso M, Gazzera C, Fonio P, Veltri A, Calandri M. Optimizing Loco Regional Management of Oligometastatic Colorectal Cancer: Technical Aspects and Biomarkers, Two Sides of the Same Coin. Cancers (Basel) 2021; 13:2617. [PMID: 34073585 PMCID: PMC8198296 DOI: 10.3390/cancers13112617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 11/23/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and has a high rate of metastatic disease which is the main cause of CRC-related death. Oligometastatic disease is a clinical condition recently included in ESMO guidelines that can benefit from a more aggressive locoregional approach. This review focuses the attention on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic locoregional strategies drawn from the current literature and consensus conferences. The different percutaneous therapies (radiofrequency ablation, microwave ablation, irreversible electroporation) as well as trans-arterial approaches (chemoembolization and radioembolization) are discussed. Ablation margins, the choice of the imaging guidance as well as characteristics of the different ablation techniques and other technical aspects are analyzed. A specific attention is then paid to the increasing role of biomarkers (in particular molecular profiling) and their role in the selection of the proper treatment for the right patient. In conclusion, in this review an up-to-date state of the art of the application of locoregional treatments on CRLM is provided, highlighting both technical aspects and the role of biomarkers, two sides of the same coin.
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Affiliation(s)
- Giovanni Mauri
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
- Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, 20122 Milan, Italy
| | | | - Andrea Garnero
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
| | - Maria Giulia Zampino
- Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy;
| | - Franco Orsi
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Paolo Della Vigna
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Guido Bonomo
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Gianluca Maria Varano
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Marco Busso
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
| | - Carlo Gazzera
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Paolo Fonio
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Andrea Veltri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
| | - Marco Calandri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
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23
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Walrand S, Hesse M, d’Abadie P, Jamar F. Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy. Cancers (Basel) 2021; 13:cancers13071537. [PMID: 33810511 PMCID: PMC8036746 DOI: 10.3390/cancers13071537] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/22/2021] [Accepted: 03/23/2021] [Indexed: 02/08/2023] Open
Abstract
Simple Summary Radioembolization of hepatic tumors is performed by injecting 90Y or 166Ho loaded spheres into the hepatic artery. A twofold tumor to normal liver absorbed dose ratio is commonly obtained. In order to improve tumoral cell killing while preserving lobule function, co-injection of arterial vasoconstrictor has been proposed, but without success: the hepatic arterial buffer response quickly inhibits the arterioles vasoconstriction. The aim of the study is to investigate whether it is possible to take benefit from this buffer response, by co-infusing a mesenteric arterial vasodilator in order to dump the hepatic lobules arterial flow. Animal studies evidencing such mechanism are reviewed. Some potential mesenteric vasodilators are identified and their safety profile discussed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in hepatocellular carcinoma (HCC), more frequent in obese subjects, and where ultra-selective spheres delivery is often not possible. Abstract Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.
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24
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Kwan J, Pua U. Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis. Cancers (Basel) 2021; 13:cancers13061371. [PMID: 33803606 PMCID: PMC8003062 DOI: 10.3390/cancers13061371] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/14/2021] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. Abstract The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.
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Abstract
The fundamental premise of yttrium-90 radioembolisation is to balance safety with efficacy. To achieve this, dose-response guidance must be provided. This is a tabulation of published data of key dose-response metrics for yttrium-90 resin microsphere radioembolisation of liver malignancies. Metrics are expressed in terms of mean radiation absorbed doses (Gy), dose-volume histograms, Biologically Effective Doses, Normal Tissue Complication Probability and Tumour Control Probability.
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Affiliation(s)
- Yung Hsiang Kao
- Department of Nuclear Medicine, The Royal Melbourne Hospital, Victoria, Australia
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Piasecki P, Majewska A, Narloch J, Maciak M, Brodaczewska K, Kuc M, Was H, Wierzbicki M, Brzozowski K, Ziecina P, Mazurek A, Dziuk M, Iller E, Kieda C. A new in vitro model applied 90Y microspheres to study the effects of low dose beta radiation on colorectal cancer cell line in various oxygenation conditions. Sci Rep 2021; 11:4472. [PMID: 33627727 PMCID: PMC7904911 DOI: 10.1038/s41598-021-84000-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 02/10/2021] [Indexed: 11/30/2022] Open
Abstract
We propose a new in vitro model to assess the impact of 90Y-microspheres derived low-dose beta radiation on colorectal cancer cell line under various oxygenation conditions that mimic the tumor environment. Cancer cells (HCT116) proliferation was assessed using Alamar Blue (AB) assay after 48, 72, and 96 h. FLUKA code assessed changes in cancer cell populations relative to the absorbed dose. In normoxia, mitochondrial activity measured by Alamar Blue after 48–72 h was significantly correlated with the number of microspheres (48 h: r = 0.87 and 72 h: r = 0.89, p < 0.05) and absorbed dose (48 h: r = 0.87 and 72 h: r = 0.7, p < 0.05). In hypoxia, the coefficients were r = 0.43 for both the number of spheres and absorbed dose and r = 0.45, r = 0.47, respectively. Impediment of cancer cell proliferation depended on the absorbed dose. Doses below 70 Gy could reduce colorectal cancer cell proliferation in vitro. Hypoxia induced a higher resistance to radiation than that observed under normoxic conditions. Hypoxia and radiation induced senescence in cultured cells. The new in vitro model is useful for the assessment of 90Y radioembolization effects at the micro-scale.
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Affiliation(s)
- Piotr Piasecki
- Department of Interventional Radiology, Military Institute of Medicine, Szaserow 128, 01-141, Warsaw, Poland
| | - Aleksandra Majewska
- Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, Warsaw, Poland.,Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Jerzy Narloch
- Department of Interventional Radiology, Military Institute of Medicine, Szaserow 128, 01-141, Warsaw, Poland.
| | - Maciej Maciak
- Radiological Metrology and Biomedical Physics Division, National Centre for Nuclear Research, Otwock, Poland
| | - Klaudia Brodaczewska
- Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, Warsaw, Poland
| | - Michal Kuc
- Radiological Metrology and Biomedical Physics Division, National Centre for Nuclear Research, Otwock, Poland
| | - Halina Was
- Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, Warsaw, Poland
| | - Marek Wierzbicki
- Department of Interventional Radiology, Military Institute of Medicine, Szaserow 128, 01-141, Warsaw, Poland
| | - Krzysztof Brzozowski
- Department of Interventional Radiology, Military Institute of Medicine, Szaserow 128, 01-141, Warsaw, Poland
| | - Piotr Ziecina
- Department of Interventional Radiology, Military Institute of Medicine, Szaserow 128, 01-141, Warsaw, Poland
| | - Andrzej Mazurek
- Department of Nuclear Medicine, Military Institute of Medicine, Warsaw, Poland
| | - Miroslaw Dziuk
- Department of Nuclear Medicine, Military Institute of Medicine, Warsaw, Poland
| | - Edward Iller
- POLATOM Radioisotope Centre, National Centre for Nuclear Research, Otwock, Poland
| | - Claudine Kieda
- Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, Warsaw, Poland
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Pellegrinelli J, Chevallier O, Manfredi S, Dygai-Cochet I, Tabouret-Viaud C, Nodari G, Ghiringhelli F, Riedinger JM, Popoff R, Vrigneaud JM, Cochet A, Aho S, Latournerie M, Loffroy R. Transarterial Radioembolization of Hepatocellular Carcinoma, Liver-Dominant Hepatic Colorectal Cancer Metastases, and Cholangiocarcinoma Using Yttrium90 Microspheres: Eight-Year Single-Center Real-Life Experience. Diagnostics (Basel) 2021; 11:122. [PMID: 33466706 PMCID: PMC7828820 DOI: 10.3390/diagnostics11010122] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/11/2021] [Accepted: 01/11/2021] [Indexed: 01/15/2023] Open
Abstract
Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26-0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.
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Affiliation(s)
- Julie Pellegrinelli
- Department of Vascular and Interventional Radiology, Image-Guided Therapy Center, François-Mitterrand University Hospital, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon, France; (J.P.); (O.C.)
| | - Olivier Chevallier
- Department of Vascular and Interventional Radiology, Image-Guided Therapy Center, François-Mitterrand University Hospital, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon, France; (J.P.); (O.C.)
| | - Sylvain Manfredi
- Department of Gastroenterology and Hepatology, François-Mitterrand University Hospital, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon, France; (S.M.); (M.L.)
| | - Inna Dygai-Cochet
- Department of Nuclear Medicine, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France; (I.D.-C.); (C.T.-V.); (G.N.); (J.-M.R.); (R.P.); (J.-M.V.); (A.C.)
| | - Claire Tabouret-Viaud
- Department of Nuclear Medicine, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France; (I.D.-C.); (C.T.-V.); (G.N.); (J.-M.R.); (R.P.); (J.-M.V.); (A.C.)
| | - Guillaume Nodari
- Department of Nuclear Medicine, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France; (I.D.-C.); (C.T.-V.); (G.N.); (J.-M.R.); (R.P.); (J.-M.V.); (A.C.)
| | - François Ghiringhelli
- Department of Medical Oncology, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France;
| | - Jean-Marc Riedinger
- Department of Nuclear Medicine, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France; (I.D.-C.); (C.T.-V.); (G.N.); (J.-M.R.); (R.P.); (J.-M.V.); (A.C.)
| | - Romain Popoff
- Department of Nuclear Medicine, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France; (I.D.-C.); (C.T.-V.); (G.N.); (J.-M.R.); (R.P.); (J.-M.V.); (A.C.)
| | - Jean-Marc Vrigneaud
- Department of Nuclear Medicine, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France; (I.D.-C.); (C.T.-V.); (G.N.); (J.-M.R.); (R.P.); (J.-M.V.); (A.C.)
| | - Alexandre Cochet
- Department of Nuclear Medicine, Georges François Leclerc Center, 1 Rue Professeur Marion, 21000 Dijon, France; (I.D.-C.); (C.T.-V.); (G.N.); (J.-M.R.); (R.P.); (J.-M.V.); (A.C.)
| | - Serge Aho
- Department of Epidemiology and Biostatistics, François-Mitterrand University Hospital, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon, France;
| | - Marianne Latournerie
- Department of Gastroenterology and Hepatology, François-Mitterrand University Hospital, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon, France; (S.M.); (M.L.)
| | - Romaric Loffroy
- Department of Vascular and Interventional Radiology, Image-Guided Therapy Center, François-Mitterrand University Hospital, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon, France; (J.P.); (O.C.)
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Das S, Berlin J. Systemic Therapy Improvements Will Render Locoregional Treatments Obsolete for Patients with Cancer with Liver Metastases. Surg Oncol Clin N Am 2021; 30:189-204. [PMID: 33220805 PMCID: PMC7684942 DOI: 10.1016/j.soc.2020.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Hepatic metastases are a major cause of morbidity and mortality for patients with cancer. Apart from curative resection, which offers patients the potential for long-term survival, an array of locoregional therapies, with limited evidence of improving survival, are used to treat them. The authors use examples from the realm of gastrointestinal cancer, largely focusing on the experience of patients with neuroendocrine cancer, hepatobiliary cancer, and colorectal cancer, to suggest that current systemic therapies offer, at minimum, similar survival outcomes for patients compared with these locoregional approaches.
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Affiliation(s)
- Satya Das
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232, USA.
| | - Jordan Berlin
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232, USA. https://twitter.com/jordanberlin5
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Outcomes With Liver-Directed Therapy for Genitourinary Malignancies: Single-Institution Experience. Clin Genitourin Cancer 2020; 19:87-91. [PMID: 32778506 DOI: 10.1016/j.clgc.2020.07.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 05/31/2020] [Accepted: 07/12/2020] [Indexed: 11/20/2022]
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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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Wong YH, Tan HY, Kasbollah A, Abdullah BJJ, Acharya RU, Yeong CH. Neutron-activated biodegradable samarium-153 acetylacetonate-poly-L-lactic acid microspheres for intraarterial radioembolization of hepatic tumors. World J Exp Med 2020; 10:10-25. [PMID: 32266125 PMCID: PMC7117964 DOI: 10.5493/wjem.v10.i2.10] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 02/14/2020] [Accepted: 03/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver cancer is the 6th most common cancer in the world and the 4th most common death from cancer worldwide. Hepatic radioembolization is a minimally invasive treatment involving intraarterial administration of radioembolic microspheres.
AIM To develop a neutron-activated, biodegradable and theranostics samarium-153 acetylacetonate (153SmAcAc)-poly-L-lactic acid (PLLA) microsphere for intraarterial radioembolization of hepatic tumors.
METHODS Microspheres with different concentrations of 152SmAcAc (i.e., 100%, 150%, 175% and 200% w/w) were prepared by solvent evaporation method. The microspheres were then activated using a nuclear reactor in a neutron flux of 2 × 1012 n/cm2/s1, converting 152Sm to Samarium-153 (153Sm) via 152Sm (n, γ) 153Sm reaction. The SmAcAc-PLLA microspheres before and after neutron activation were characterized using scanning electron microscope, energy dispersive X-ray spectroscopy, particle size analysis, Fourier transform infrared spectroscopy, thermo-gravimetric analysis and gamma spectroscopy. The in-vitro radiolabeling efficiency was also tested in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.
RESULTS The SmAcAc-PLLA microspheres with different SmAcAc contents remained spherical before and after neutron activation. The mean diameter of the microspheres was about 35 µm. Specific activity achieved for 153SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc after 3 h neutron activation were 1.7 ± 0.05, 2.5 ± 0.05, 2.7 ± 0.07, and 2.8 ± 0.09 GBq/g, respectively. The activity of per microspheres were determined as 48.36 ± 1.33, 74.10 ± 1.65, 97.87 ± 2.48, and 109.83 ± 3.71 Bq for 153SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc. The energy dispersive X-ray and gamma spectrometry showed that no elemental and radioactive impurities present in the microspheres after neutron activation. Retention efficiency of 153Sm in the SmAcAc-PLLA microspheres was excellent (approximately 99%) in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.
CONCLUSION The 153SmAcAc-PLLA microsphere is potentially useful for hepatic radioembolization due to their biodegradability, favorable physicochemical characteristics and excellent radiolabeling efficiency. The synthesis of the formulation does not involve ionizing radiation and hence reducing the complication and cost of production.
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Affiliation(s)
- Yin-How Wong
- School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
| | - Hun-Yee Tan
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
| | - Azahari Kasbollah
- Medical Technology Division, Malaysian Nuclear Agency, Bangi 43000, Selangor, Malaysia
| | - Basri Johan Jeet Abdullah
- School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
| | - Rajendra Udyavara Acharya
- School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
- Department of Electronics and Computer Engineering, Ngee Ann Polytechnic, Singapore 599489, Singapore
| | - Chai-Hong Yeong
- School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
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Siman W, Mawlawi OR, Mourtada F, Kappadath SC. Systematic and random errors of PET‐based
90
Y 3D dose quantification. Med Phys 2020; 47:2441-2449. [DOI: 10.1002/mp.14117] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 01/21/2020] [Accepted: 02/26/2020] [Indexed: 11/10/2022] Open
Affiliation(s)
- W. Siman
- Department of Radiology The University of Colorado School of Medicine Denver CO USA
| | - O. R. Mawlawi
- Department of Imaging Physics The University of Texas MD Anderson Cancer Center Houston TX USA
- The University of Texas Graduate School of Biomedical Sciences at Houston Houston TX USA
| | | | - S. C. Kappadath
- Department of Imaging Physics The University of Texas MD Anderson Cancer Center Houston TX USA
- The University of Texas Graduate School of Biomedical Sciences at Houston Houston TX USA
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Quality of life in patients with liver tumors treated with holmium-166 radioembolization. Clin Exp Metastasis 2020; 37:95-105. [PMID: 31732841 PMCID: PMC7007912 DOI: 10.1007/s10585-019-10006-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 11/09/2019] [Indexed: 02/05/2023]
Abstract
Holmium-166 radioembolization is a palliative treatment option for patients with unresectable hepatic malignancies. Its influence on quality of life has not been evaluated yet. Since quality of life is very important in the final stages of disease, the aim of this study was to evaluate the effect of holmium-166 radioembolization on quality of life. Patients with hepatic malignancies were treated with holmium-166 radioembolization in the HEPAR I and II studies. The European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 questionnaires were used to evaluate quality of life at baseline, 1 week, 6 weeks and at 6, 9 and 12 months after treatment. The course of the global health status and symptom and functioning scales were analyzed using a linear mixed model. Quality of life was studied in a total of 53 patients with a compliance of 94%. Role functioning was the most affected functioning scale. Fatigue and pain were the most affected symptom scales. Changes in almost all categories were most notable at 1 week after treatment. A higher WHO performance score at baseline decreased global health status, physical functioning, role functioning and social functioning and it increased symptoms of fatigue, dyspnea and diarrhea. Quality of life in salvage patients with liver metastases treated with holmium-166 radioembolization was not significantly affected over time, although a striking decline was seen during the first week post-treatment. A WHO performance score > 0 at baseline significantly influenced quality of life.
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Currie BM, Hoteit MA, Ben-Josef E, Nadolski GJ, Soulen MC. Radioembolization-Induced Chronic Hepatotoxicity: A Single-Center Cohort Analysis. J Vasc Interv Radiol 2019; 30:1915-1923. [DOI: 10.1016/j.jvir.2019.06.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 05/23/2019] [Accepted: 06/07/2019] [Indexed: 01/28/2023] Open
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Lee EJ, Chung HW, Jo JH, So Y. Radioembolization for the Treatment of Primary and Metastatic Liver Cancers. Nucl Med Mol Imaging 2019; 53:367-373. [PMID: 31867071 DOI: 10.1007/s13139-019-00615-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/23/2019] [Accepted: 09/20/2019] [Indexed: 02/08/2023] Open
Abstract
Radioembolization using 90Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope 90Y is a β-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of 90Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12 weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.
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Affiliation(s)
- Eun Jeong Lee
- 1Department of Nuclear Medicine, Seoul Medical Center, 156 Sinnae-ro, Jungnang-gu, Seoul, South Korea
| | - Hyun Woo Chung
- 2Departments of Nuclear Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, South Korea
| | - Joon-Hyung Jo
- 2Departments of Nuclear Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, South Korea
| | - Young So
- 2Departments of Nuclear Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, South Korea
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Garlipp B, Gibbs P, Van Hazel GA, Jeyarajah R, Martin RCG, Bruns CJ, Lang H, Manas DM, Ettorre GM, Pardo F, Donckier V, Benckert C, van Gulik TM, Goéré D, Schoen M, Pratschke J, Bechstein WO, de la Cuesta AM, Adeyemi S, Ricke J, Seidensticker M. Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial. Br J Surg 2019; 106:1837-1846. [PMID: 31424576 PMCID: PMC6899564 DOI: 10.1002/bjs.11283] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 05/22/2019] [Accepted: 05/23/2019] [Indexed: 12/12/2022]
Abstract
Background Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX‐based chemotherapy. Methods Baseline and follow‐up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium‐90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. Results Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow‐up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). Conclusion Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.
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Affiliation(s)
- B Garlipp
- Otto-von-Guericke-University Hospital, Magdeburg, Germany
| | - P Gibbs
- Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
| | - G A Van Hazel
- Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - R Jeyarajah
- Methodist Richardson Medical Center, Dallas, Texas, USA
| | - R C G Martin
- Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - C J Bruns
- University Hospital Cologne, Cologne, Germany
| | - H Lang
- General, Visceral and Transplant Surgery, University Medical Centre of Johannes Gutenberg University, Mainz, Germany
| | - D M Manas
- Department of Hepato-Pancreato-Biliary Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | | | - F Pardo
- Hepato-Pancreatico-Biliary Surgery and Oncology, Clinica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - V Donckier
- Jules Bordet Institute, Brussels, Belgium
| | - C Benckert
- Vivantes Klinikum Am Friedrichshain, Berlin, Germany
| | | | - D Goéré
- Institut Gustave Roussy, Villejuif, France
| | - M Schoen
- Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
| | - J Pratschke
- Charité Universitätsmedizin Berlin, Berlin, Germany
| | - W O Bechstein
- Department of General and Visceral Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | | | - S Adeyemi
- Statsxperts Consulting Limited, Hemel Hempstead, UK
| | - J Ricke
- Deutsche Akademie für Mikrotherapie, Magdeburg, Germany.,Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
| | - M Seidensticker
- Otto-von-Guericke-University Hospital, Magdeburg, Germany.,Deutsche Akademie für Mikrotherapie, Magdeburg, Germany.,Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
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Kemeny N, Kurilova I, Li J, Camacho JC, Sofocleous CT. Liver-Directed and Systemic Therapies for Colorectal Cancer Liver Metastases. Cardiovasc Intervent Radiol 2019; 42:1240-1254. [PMID: 31312902 DOI: 10.1007/s00270-019-02284-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 07/03/2019] [Indexed: 02/07/2023]
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Bala MM, Riemsma RP, Wolff R, Pedziwiatr M, Mitus JW, Storman D, Swierz MJ, Kleijnen J, Cochrane Hepato‐Biliary Group. Cryotherapy for liver metastases. Cochrane Database Syst Rev 2019; 7:CD009058. [PMID: 31291464 PMCID: PMC6620095 DOI: 10.1002/14651858.cd009058.pub3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma. Liver metastases are significantly more common than primary liver cancer and long-term survival rates reported for patients after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients. Cryotherapy is performed with the use of an image-guided cryoprobe which delivers liquid nitrogen or argon gas to the tumour tissue. The subsequent process of freezing is associated with formation of ice crystals, which directly damage exposed tissue, including cancer cells. OBJECTIVES To assess the beneficial and harmful effects of cryotherapy compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and six other databases up to June 2018. SELECTION CRITERIA Randomised clinical trials assessing beneficial and harmful effects of cryotherapy and its comparators for liver metastases, irrespective of the location of the primary tumour. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, and data on the outcomes important for our review, as well as information on the design and methodology of the trials. Two review authors independently assessed risk of bias in each study. One review author performed data extraction and a second review author checked entries. MAIN RESULTS We found no randomised clinical trials comparing cryotherapy versus no intervention or versus systemic treatments; however, we identified one randomised clinical trial comparing cryotherapy with conventional surgery. The trial was conducted in Ukraine. The trial included 123 participants with solitary, or multiple unilobar or bilobar liver metastases; 63 participants received cryotherapy and 60 received conventional surgery. There were 36 women and 87 men. The primary sites for the metastases were colon and rectum (66.6%), stomach (7.3%), breast (6.5%), skin (4.9%), ovaries (4.1%), uterus (3.3%), kidney (3.3%), intestines (1.6%), pancreas (1.6%), and unknown (0.8%). The trial was not reported sufficiently enough to assess the risk of bias of the randomisation process, allocation concealment, or presence of blinding. It was also not possible to assess incomplete outcome data and selective outcome reporting bias. The certainty of evidence was low because of risk of bias and imprecision.The participants were followed for up to 10 years (minimum five months). The trial reported that the mortality at 10 years was 81% (51/63) in the cryotherapy group and 92% (55/60) in the conventional surgery group. The calculated by us relative risk (RR) with 95% Confidence Interval (CI) was: RR 0.88, 95% CI 0.77 to 1.02. We judged the evidence as low-certainty evidence. Regarding adverse events and complications, separately and in total, our calculation showed no evidence of a difference in recurrence of the malignancy in the liver: 86% (54/63) of the participants in the cryotherapy group and 95% (57/60) of the participants in the conventional surgery group developed a new malignancy (RR 0.90, 95% CI 0.80 to 1.01; low-certainty evidence). The frequency of reported complications was similar between the cryotherapy group and the conventional surgery group, except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the conventional surgery group. However, the authors did not report whether there was any evidence of a difference. There were no intervention-related mortality or bile leakages.We identified no evidence for health-related quality of life, cancer mortality, or time to progression of liver metastases. The study reported tumour response in terms of the carcinoembryonic antigen level in 69% of participants, and reported results in the form of a graph for 30% of participants. The carcinoembryonic antigen level was lower in the cryotherapy group, and decreased to normal values faster in comparison with the control group (P < 0.05). FUNDING the trial did not provide information on funding. AUTHORS' CONCLUSIONS The evidence for the effectiveness of cryotherapy versus conventional surgery in people with liver metastases is of low certainty. We are uncertain about our estimate and cannot determine whether cryotherapy compared with conventional surgery is beneficial or harmful. We found no evidence for the benefits or harms of cryotherapy compared with no intervention, or versus systemic treatments.
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Affiliation(s)
- Malgorzata M Bala
- Jagiellonian University Medical CollegeChair of Epidemiology and Preventive Medicine; Department of Hygiene and Dietetics; Systematic Reviews UnitKopernika 7KrakowPoland31‐034
| | - Robert P Riemsma
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Robert Wolff
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Michal Pedziwiatr
- Jagiellonian University Medical College2nd Department of General SurgeryKopernika Street 21KrakówMalopolskaPoland31‐501
| | - Jerzy W Mitus
- Centre of Oncology, Maria Skłodowska – Curie Memorial Institute, Krakow Branch. Department of Anatomy, Jagiellonian University Medical College Krakow, PolandDepartment of Surgical Oncologyul. Garncarska 11KrakowPoland31‐115
| | - Dawid Storman
- University HospitalDepartment of Hygiene and Dietetics, Systematic Reviews Unit, Jagiellonian University Medical College, Department of Adult PsychiatryKrakowPoland
| | - Mateusz J Swierz
- Jagiellonian University Medical CollegeDepartment of Hygiene and Dietetics, Systematic Reviews UnitKrakowPoland
| | - Jos Kleijnen
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
- School for Public Health and Primary Care (CAPHRI), Maastricht UniversityMaastrichtNetherlands6200 MD
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Wang DS, Louie JD, Sze DY. Evidence-Based Integration of Yttrium-90 Radioembolization in the Contemporary Management of Hepatic Metastases from Colorectal Cancer. Tech Vasc Interv Radiol 2019; 22:74-80. [DOI: 10.1053/j.tvir.2019.02.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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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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Tchelebi L, Sharma NK. Selective Internal Radiation Therapy in the Multidisciplinary Management of Liver Metastases From Colorectal Carcinoma. Semin Nucl Med 2019; 49:182-188. [DOI: 10.1053/j.semnuclmed.2019.01.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Multi-Objective Design Optimization of a Shape Memory Alloy Flexural Actuator. ACTUATORS 2019. [DOI: 10.3390/act8010013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
This paper presents a computational model and design optimization strategy for shape memory alloy (SMA) flexural actuators. These actuators consist of curved SMA wires embedded within elastic structures; one potential application is positioning microcatheters inside blood vessels during clinical treatments. Each SMA wire is shape-set to an initial curvature and inserted along the neutral axis of a straight elastic member (cast polydimethylsiloxane, PDMS). The elastic structure preloads the SMA, reducing the equilibrium curvature of the composite actuator. Temperature-induced phase transformations in the SMA are achieved via Joule heating, enabling strain recovery and increased bending (increased curvature) in the actuator. Actuator behavior is modeled using the homogenized energy framework, and the effects of two critical design parameters (initial SMA curvature and flexural rigidity of the elastic sleeve) on activation curvature are investigated. Finally, a multi-objective genetic algorithm is utilized to optimize actuator performance and generate a Pareto frontier, which is subsequently experimentally validated.
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Coretti S, Rumi F, Sacchini D, Cicchetti A. SIR-Spheres ® Y-90 resin microspheres in chemotherapy refractory or intolerant patients with metastatic colorectal cancer. GLOBAL & REGIONAL HEALTH TECHNOLOGY ASSESSMENT 2019. [DOI: 10.1177/2284240319847446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Selective internal radiation therapy is a form of intra-arterial brachytherapy used to treat primary liver cancer and liver metastases. This article aims to provide an overview of the clinical, economic, organizational legal, social and ethical impact of selective internal radiation therapy using SIR-Spheres Y-90 resin microspheres in the treatment of patients with unresectable, liver-dominant metastatic colorectal cancer who are refractory to or intolerant of chemotherapy. A systematic literature review was performed by querying PubMed, Scopus, EBSCO, CRD and GIN. Two reviewers blindly screened the records retrieved against predefined inclusion/exclusion criteria. The selected studies where summarized following a simplified version of the EuNetHTA Core Model® 2.1. The studies included evaluated selective internal radiation therapy in first-line or further-line treatment and showed a good safety and tolerability profile and significant improvement in efficacy expressed as time to liver progression, progression-free survival and overall survival. Selective internal radiation therapy should be provided in specialized centres and administered by a multidisciplinary team. A hub-and-spoke network could be a viable option to guarantee access to this technology across jurisdictions. The lack of a specific diagnosis-related group tariff accounting for the cost of the device could be seen as the major obstacle to a fair diffusion of this technology. The economic evaluations currently available show the cost-effectiveness of this technology in the population under study. Selective internal radiation therapy using SIR-Spheres Y-90 resin microspheres appears to be a clinically effective and cost-effective option in the treatment of metastatic colorectal cancer patients who are chemotherapy refractory or chemotherapy intolerant.
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Affiliation(s)
- Silvia Coretti
- Graduate School of Health Economics and Management, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Filippo Rumi
- Graduate School of Health Economics and Management, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Dario Sacchini
- Institute of Bioethics, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Americo Cicchetti
- Graduate School of Health Economics and Management, Università Cattolica del Sacro Cuore, Rome, Italy
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Siman W, Mikell JK, Mawlawi OR, Mourtada F, Kappadath SC. Dose volume histogram-based optimization of image reconstruction parameters for quantitative 90 Y-PET imaging. Med Phys 2018; 46:229-237. [PMID: 30375655 DOI: 10.1002/mp.13269] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 10/21/2018] [Accepted: 10/22/2018] [Indexed: 12/20/2022] Open
Abstract
PURPOSE 90 Y-microsphere radioembolization or selective internal radiation therapy is increasingly being used as a treatment option for tumors that are not candidates for surgery and external beam radiation therapy. Recently, volumetric 90 Y-dosimetry techniques have been implemented to explore tumor dose-response on the basis of 3D 90 Y-activity distribution from PET imaging. Despite being a theranostic study, the optimization of quantitative 90 Y-PET image reconstruction still uses the mean activity concentration recovery coefficient (RC) as the objective function, which is more relevant to diagnostic and detection tasks than is to dosimetry. The aim of this study was to optimize 90 Y-PET image reconstruction by minimizing errors in volumetric dosimetry via the dose volume histogram (DVH). We propose a joint optimization of the number of equivalent iterations (the product of the iterations and subsets) and the postreconstruction filtration (FWHM) to improve the accuracy of voxel-level 90 Y dosimetry. METHODS A modified NEMA IEC phantom was used to emulate clinically relevant 90 Y-PET imaging conditions through various combinations of acquisition durations, activity concentrations, sphere-to-background ratios, and sphere diameters. PET data were acquired in list mode for 300 min in a single-bed position; we then rebinned the list mode PET data to 60, 45, 30, 15, and 5 min per bed, with 10 different realizations. Errors in the DVH were calculated as root mean square errors (RMSE) of the differences in the image-based DVH and the expected DVH. The new optimization approach was tested in a phantom study, and the results were compared with the more commonly used objective function of the mean activity concentration RC. RESULTS In a wide range of clinically relevant imaging conditions, using 36 equivalent iterations with a 5.2-mm filtration resulted in decreased systematic errors in volumetric 90 Y dosimetry, quantified as image-based DVH, in 90 Y-PET images reconstructed using the ordered subset expectation maximization (OSEM) iterative reconstruction algorithm with time of flight (TOF) and point spread function (PSF) modeling. Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of 90 Y-PET iterations and filtration for volumetric quantification of the 90 Y dose, was shown to be superior to conventional RC-based optimization approaches for image-based absorbed dose quantification. CONCLUSION Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of iterations and filtration to reduce errors in the PET-based volumetric quantification 90 Y dose, is relevant to dosimetry in therapy procedures. The proposed optimization method using DVH as the objective function could be applied to any imaging modality used to assess voxel-level quantitative information.
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Affiliation(s)
- Wendy Siman
- Department of Radiology, The University of Tennessee Medical Center, Knoxville, TN, USA.,The University of Tennessee Graduate School of Medicine, Knoxville, TN, USA
| | - Justin K Mikell
- Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, MI, USA
| | - Osama R Mawlawi
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA
| | | | - S Cheenu Kappadath
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA
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Kleynhans J, Grobler AF, Ebenhan T, Sathekge MM, Zeevaart JR. Radiopharmaceutical enhancement by drug delivery systems: A review. J Control Release 2018; 287:177-193. [DOI: 10.1016/j.jconrel.2018.08.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 08/02/2018] [Accepted: 08/03/2018] [Indexed: 12/17/2022]
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Kurilova I, Beets-Tan RGH, Flynn J, Gönen M, Ulaner G, Petre EN, Edward Boas F, Ziv E, Yarmohammadi H, Klompenhouwer EG, Cercek A, Kemeny NA, Sofocleous CT. Factors Affecting Oncologic Outcomes of 90Y Radioembolization of Heavily Pre-Treated Patients With Colon Cancer Liver Metastases. Clin Colorectal Cancer 2018; 18:8-18. [PMID: 30297264 DOI: 10.1016/j.clcc.2018.08.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 08/22/2018] [Accepted: 08/23/2018] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The purpose of this study was to identify predictors of overall (OS) and liver progression-free survival (LPFS) following Yttrium-90 radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM), as well as to create and validate a predictive nomogram for OS. MATERIALS AND METHODS Metabolic, anatomic, laboratory, pathologic, genetic, primary disease, and procedure-related factors, as well as pre- and post-RAE therapies in 103 patients with CLM treated with RAE from September 15, 2009 to March 21, 2017 were analyzed. LPFS was defined by Response Evaluation Criteria In Solid Tumors 1.1 and European Organization for Research and Treatment of Cancer criteria. Prognosticators of OS and LPFS were selected using univariate Cox regression, adjusted for clustering and competing risk analysis (for LPFS), and subsequently tested in multivariate analysis (MVA). The nomogram was built using R statistical software and internally validated using bootstrap resampling. RESULTS Patients received RAE at a median of 30.9 months (range, 3.4-161.7 months) after detection of CLM. The median OS and LPFS were 11.3 months (95% confidence interval, 7.9-15.1 months) and 4 months (95% confidence interval, 3.3-4.8 months), respectively. Of the 40 parameters tested, 6 were independently associated with OS in MVA. These baseline parameters included number of extrahepatic disease sites (P < .001), carcinoembryonic antigen (P < .001), albumin (P = .005), alanine aminotransferase level (P < .001), tumor differentiation level (P < .001), and the sum of the 2 largest tumor diameters (P < .001). The 1-year OS of patients with total points of < 25 versus > 80 was 90% and 10%, respectively. Bootstrap resampling showed good discrimination (optimism corrected c-index = 0.745) and calibration (mean absolute prediction error = 0.299) of the nomogram. Only baseline maximum standardized uptake value was significant in MVA for LPFS prediction (P < .001; SHR = 1.06). CONCLUSION The developed nomogram included 6 pre-RAE parameters and provided good prediction of survival post-RAE in heavily pretreated patients. Baseline maximum standardized uptake value was the single significant predictor of LPFS.
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Affiliation(s)
- Ieva Kurilova
- Department of Interventional Oncology/Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Regina G H Beets-Tan
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Jessica Flynn
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mithat Gönen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Gary Ulaner
- Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Elena N Petre
- Department of Interventional Oncology/Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - F Edward Boas
- Department of Interventional Oncology/Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Etay Ziv
- Department of Interventional Oncology/Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Hooman Yarmohammadi
- Department of Interventional Oncology/Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Andrea Cercek
- Department of Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Nancy A Kemeny
- Department of Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Constantinos T Sofocleous
- Department of Interventional Oncology/Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
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Genomic mutations and histopathologic biomarkers in Y 90 radioembolization for chemorefractory colorectal liver metastases. Oncotarget 2018; 9:32523-32533. [PMID: 30197760 PMCID: PMC6126695 DOI: 10.18632/oncotarget.25992] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 08/02/2018] [Indexed: 12/20/2022] Open
Abstract
Background To investigate mutational load and histologic biomarkers as prognostic factors in patients with chemorefractory colorectal liver metastases (CRLM) treated with Y-90 radioembolization therapy. Materials and Methods Single institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed. Patient demographics, systemic therapy regimens, tumor characteristics and overall survival were analyzed between patients with differing histopathologic and genomic status. PIK3CA, KRAS, NRAS, AKT1, MEK1, MLH1, MSH2, MSH6 and PMS2 were analyzed. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results 23 patients underwent genomic analysis prior to Y-90. Eleven (47.8%) had mutations identified (MUT), and 12 were sequenced as wild type (WT) (52.2%). Median OS of 23 patients after Y-90 was 9.6 months (95% CI 6.67-16.23). Median OS from first Y-90 was significantly greater in WT patients (16.2 mo vs 6.5 mo; p =.0054). The survival difference between poorly differentiated tumors compared to all other histologic grades was significant (poor vs. well p=0.025, HR=26.8; poor vs. moderate p=.014, HR=23.07; poor vs. moderate/poor p=0.014, HR=23.68). When separated into 3 different groups (WT vs. MUT/moderate differentiation vs. MUT/poor differentiation) there was a difference in median OS observed (16.2 vs. 8.0 vs. 3.8 mos; p<.0001). Imaging response via RECIST criteria was significantly different between MUT and WT groups (p=0.02). Conclusions Mutational status and histopathologic grade may predict survival after Y-90 radioembolization therapy for CRLM.
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Voutsinas N, Lekperic S, Barazani S, Titano JJ, Heiba SI, Kim E. Treatment of Primary Liver Tumors and Liver Metastases, Part 1: Nuclear Medicine Techniques. J Nucl Med 2018; 59:1649-1654. [PMID: 30072501 DOI: 10.2967/jnumed.116.186346] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 07/18/2018] [Indexed: 12/14/2022] Open
Abstract
90Y radioembolization is an increasingly used treatment for both primary and metastatic malignancy in the liver. Understanding the biophysical properties, dosing concerns, and imaging appearance of this treatment is important for interventional radiologists and nuclear medicine physicians to provide important therapy. 90Y radioembolization is efficacious and safe, although the possibility of complications does exist. This article provides a comprehensive in-depth discussion about the indications for 90Y radioembolization, reviews the role of preprocedural angiography and 99mTc-macroaggregated albumin scans, illustrates different dosing techniques, compares and contrasts resin and glass microspheres, and describes potential complications.
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Affiliation(s)
- Nicholas Voutsinas
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | - Safet Lekperic
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | - Sharon Barazani
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | - Joseph J Titano
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | - Sherif I Heiba
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | - Edward Kim
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
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Weiner AA, Gui B, Newman NB, Nosher JL, Yousseff F, Lu SE, Foltz GM, Carpizo D, Lowenthal J, Zuckerman DA, Benson B, Olsen JR, Jabbour SK, Parikh PJ. Predictors of Survival after Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases. J Vasc Interv Radiol 2018; 29:1094-1100. [PMID: 29754852 PMCID: PMC10905616 DOI: 10.1016/j.jvir.2018.02.020] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 02/14/2018] [Accepted: 02/17/2018] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS A total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses. RESULTS The median OS from first RE procedure was 10.7 months (95% confidence interval [CI], 9.4-12.7 months). Several pretreatment factors, including lower carcinoembryonic antigen (CEA; ≤20 ng/mL), lower aspartate transaminase (AST; ≤40 IU/L), neutrophil-lymphocyte ratio (NLR) <5, and absence of extrahepatic disease at baseline were associated with significantly improved OS after RE, compared with high CEA (>20 ng/mL), high AST (>40 IU/L), NLR ≥5, and extrahepatic metastases (P values of <.001, <.001, .0001, and .04, respectively). On multivariate analysis, higher CEA, higher AST, NLR ≥5, extrahepatic disease, and larger volume of liver metastases remained independently associated with risk of death (hazard ratios of 1.63, 2.06, 2.22, 1.48, and 1.02, respectively). CONCLUSIONS The prognosis of patients with metastases from CRC is impacted by a complex set of clinical parameters. This analysis of pretreatment factors identified lower AST, lower CEA, lower NLR, and lower tumor burden (intra- or extrahepatic) to be independently associated with higher survival after hepatic RE. Optimal selection of patients with CRC liver metastases may improve survival rates after administration of yttrium-90.
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Affiliation(s)
- Ashley A Weiner
- Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Bin Gui
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Neil B Newman
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - John L Nosher
- Department of Radiology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Fady Yousseff
- Department of Radiation Oncology, Washington University School of Medicine, 660 South Euclid Ave, St Louis, Missouri 63110
| | - Shou-En Lu
- Rutgers School of Public Health, New Brunswick, New Jersey
| | - Gretchen M Foltz
- Department of Radiology, Washington University School of Medicine, 660 South Euclid Ave, St Louis, Missouri 63110
| | - Darren Carpizo
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Jonathan Lowenthal
- Department of Radiology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Darryl A Zuckerman
- Department of Radiology, Washington University School of Medicine, 660 South Euclid Ave, St Louis, Missouri 63110
| | - Ben Benson
- Department of Radiology, Jacobi Medical Center, Bronx, New York
| | - Jeffrey R Olsen
- Department of Radiation Oncology, University of Colorado, Denver, Colorado
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Parag J Parikh
- Department of Radiation Oncology, Washington University School of Medicine, 660 South Euclid Ave, St Louis, Missouri 63110.
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50
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Gibbs P, Heinemann V, Sharma NK, Taieb J, Ricke J, Peeters M, Findlay M, Robinson B, Jackson C, Strickland A, Gebski V, Van Buskirk M, Zhao H, van Hazel G. Effect of Primary Tumor Side on Survival Outcomes in Untreated Patients With Metastatic Colorectal Cancer When Selective Internal Radiation Therapy Is Added to Chemotherapy: Combined Analysis of Two Randomized Controlled Studies. Clin Colorectal Cancer 2018; 17:e617-e629. [PMID: 30033117 DOI: 10.1016/j.clcc.2018.06.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 05/27/2018] [Accepted: 06/04/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone. PATIENTS AND METHODS Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side. RESULTS In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002). CONCLUSION The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain.
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Affiliation(s)
- Peter Gibbs
- Department of Oncology, Western Hospital, Footscray, VIC, Australia.
| | - Volker Heinemann
- Comprehensive Cancer Center, Ludwig Maximilian University of Munich, Munich, Germany
| | | | - Julien Taieb
- Department of Gastroenterology and Gastrointestinal Oncology, Paris Descartes University, Georges Pompidou European Hospital, Paris, France
| | - Jens Ricke
- Department of Radiology, Ludwig Maximilian University of Munich, Munich, Germany
| | - Marc Peeters
- Department of Oncology, Antwerp University Hospital, Antwerp, Belgium
| | - Michael Findlay
- Auckland City Hospital and Cancer Trials, Auckland, New Zealand
| | - Bridget Robinson
- Oncology Service, Christchurch Hospital, Christchurch, New Zealand
| | | | - Andrew Strickland
- Medical Oncology Hospital, Monash Medical Centre, Clayton, VIC, Australia
| | - Val Gebski
- National Health and Medical Research Council Clinical Trials Centre, Camperdown, NSW, Australia
| | | | | | - Guy van Hazel
- School of Medicine and Pharmacology, University of Western Australia, West Perth, WA, Australia
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