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Esmail A, Badheeb M, Alnahar BW, Almiqlash B, Sakr Y, Al-Najjar E, Awas A, Alsayed M, Khasawneh B, Alkhulaifawi M, Alsaleh A, Abudayyeh A, Rayyan Y, Abdelrahim M. The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma. Pharmaceuticals (Basel) 2024; 17:910. [PMID: 39065760 PMCID: PMC11279608 DOI: 10.3390/ph17070910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06610, USA
| | | | - Bushray Almiqlash
- Zuckerman College of Public Health, Arizona State University, Tempe, AZ 85287, USA;
| | - Yara Sakr
- Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ali Awas
- Faculty of Medicine and Health Sciences, University of Science and Technology, Sanaa P.O. Box 15201-13064, Yemen
| | | | - Bayan Khasawneh
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | | | - Amneh Alsaleh
- Department of Medicine, Desert Regional Medical Center, Palm Springs, CA 92262, USA
| | - Ala Abudayyeh
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaser Rayyan
- Department of Gastroenterology & Hepatology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Maen Abdelrahim
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
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Li H, Chen L, Zhu GY, Yao X, Dong R, Guo JH. Interventional Treatment for Cholangiocarcinoma. Front Oncol 2021; 11:671327. [PMID: 34268114 PMCID: PMC8276166 DOI: 10.3389/fonc.2021.671327] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/09/2021] [Indexed: 12/11/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the second most common type of primary liver malignancy. The latest classification includes intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with the latter one further categorized into perihilar and distal cholangiocarcinoma. Although surgical resection is the preferred treatment for CCA, less than half of the patients are actually eligible for radical surgical resection. Interventional treatment, such as intra-arterial therapies, ablation, and brachytherapy (iodine-125 seed implantation), has become an acceptable palliative treatment for patients with unresectable CCA. For these patients, interventional treatment is helpful for locoregional control, symptom relief, and improving quality of life. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research in this article.
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Affiliation(s)
- Hang Li
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Li Chen
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Guang-Yu Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Xijuan Yao
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Rui Dong
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jin-He Guo
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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Filippi L, Cianni R, Schillaci O, Bagni O. Molecular and Metabolic Imaging of Hepatic Neuroendocrine Tumors Following Radioembolization with 90Y-microspheres. Curr Med Imaging 2020; 16:545-552. [PMID: 32484088 DOI: 10.2174/1573405615666190114150038] [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: 09/13/2018] [Revised: 12/15/2018] [Accepted: 12/20/2018] [Indexed: 11/22/2022]
Abstract
Liver is the predominant site of metastatization for neuroendocrine tumors (NETs). Up to 75% of patients affected by intestinal NETs present liver metastases at diagnosis. For hepatic NET, surgery represents the most effective approach but is often unfeasible due to the massive involvement of multifocal disease. In such cases, chemotherapy, peptide receptor radionuclide therapy and loco-regional treatments may represent alternative therapeutic options. In particular, radioembolization with 90Y-microspheres has been introduced as a novel technique for treating hepatic malignant lesions, combining the principles of embolization and radiation therapy. In order to evaluate the response to 90Y-radioembolization, standard radiologic criteria have been demonstrated to present several limitations. 18Fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) is routinely used for monitoring the response to therapy in oncology. Nevertheless, NETs often present low glycolytic activity thus the conventional 18FDG PET may not be adequate for these tumors. For many years, somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide has been used for diagnosis and staging of NETs. More recently, three 68Ga-DOTA-compounds have been developed and introduced for the imaging of NETs with PET technology. The aim of the present paper was to review the existing literature concerning the application of different metabolic and molecular probes for the imaging evaluation of hepatic NETs following 90Y-RE.
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Affiliation(s)
- Luca Filippi
- Department of Nuclear Medicine, Santa Maria Goretti Hospital, Via Canova 3, Latina 04100, Italy
| | - Roberto Cianni
- Department of Interventional Radiology, San Camillo-Forlanini Hospital, Rome, Italy
| | - Orazio Schillaci
- Department of Biomedicine and Prevention, University Tor Vergata, Viale Oxford 81, Rome 00133, Italy.,IRCCS Neuromed, Pozzilli, Italy
| | - Oreste Bagni
- Department of Nuclear Medicine, Santa Maria Goretti Hospital, Via Canova 3, Latina 04100, Italy
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Scott NP, McGowan DR. Optimising quantitative 90Y PET imaging: an investigation into the effects of scan length and Bayesian penalised likelihood reconstruction. EJNMMI Res 2019; 9:40. [PMID: 31076913 PMCID: PMC6510762 DOI: 10.1186/s13550-019-0512-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 04/23/2019] [Indexed: 01/03/2023] Open
Abstract
Background Positron emission tomography (PET) imaging of 90Y following selective internal radiation therapy (SIRT) is possible, but image quality is poor, and therefore, accurate quantification and dosimetry are challenging. This study aimed to quantitatively optimise 90Y PET imaging using a new Bayesian penalised likelihood (BPL) reconstruction algorithm (Q.Clear, GE Healthcare). The length of time per bed was also investigated to study its impact on quantification accuracy. Methods A NEMA IQ phantom with an 8:1 sphere-to-background ratio was scanned overnight on a GE Discovery 710 PET/CT scanner. Datasets were rebinned into varying lengths of time (5–60 min); the 15-min rebins were reconstructed using BPL reconstruction with a range of noise penalisation weighting factors (beta values). The metrics of contrast recovery (CR), background variability (BV), and recovered activity percentage (RAP) were calculated in order to identify the optimum beta value. Reconstructions were then carried out on the rest of the timing datasets using the optimised beta value; the same metrics were used to assess the quantification accuracy of the reconstructed images. Results A beta value of 1000 produced the highest CR and RAP (76% and 73%, 37 mm sphere) without overly accentuating the noise (BV) in the image. There was no statistically significant increase (p < 0.05) in either the CR or RAP for scan times of > 15 min. For the 5-min acquisitions, there was a statistically significant decrease in RAP (28 mm sphere, p < 0.01) when compared to the 15-min acquisition. Conclusion Our results indicate that an acquisition length of 15 min and beta value of 1000 (when using Q.Clear reconstruction) are optimum for quantitative 90Y PET imaging. Increasing the acquisition time to more than 15 min reduces the image noise but has no significant impact on image quantification. Electronic supplementary material The online version of this article (10.1186/s13550-019-0512-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Nathaniel P Scott
- Radiation Physics and Protection, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Old Road, Oxford, OX37LE, UK. .,Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, UK.
| | - Daniel R McGowan
- Radiation Physics and Protection, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Old Road, Oxford, OX37LE, UK.,Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, UK
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Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis and systematic review. Radiother Oncol 2018; 129:112-122. [DOI: 10.1016/j.radonc.2017.11.013] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 10/26/2017] [Accepted: 11/13/2017] [Indexed: 02/01/2023]
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Filippi L, Schillaci O, Cianni R, Bagni O. Yttrium-90 resin microspheres and their use in the treatment of intrahepatic cholangiocarcinoma. Future Oncol 2018; 14:809-818. [DOI: 10.2217/fon-2017-0443] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a severe and rapidly progressive hepatic tumor. Surgery is often impracticable due to locally advanced presentation. On the other hand, chemotherapy has demonstrated only limited effectiveness. For these reasons, liver-directed therapies have been successfully applied for treating ICC. In particular, radioembolization with Yttrium-90 (90Y)-labeled spheres has been reported to be a promising therapeutic approach for this neoplasia. Two commercial forms of 90Y-labeled spheres are available: glass (TheraSphere®) and resin (SIR-Spheres®) microspheres. The aim of the present paper is to review the existing literature on the use of the resin microspheres for the treatment of unresectable and chemorefractory ICC, focusing on the methodology, clinical applications and side effects.
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Affiliation(s)
- Luca Filippi
- Nuclear Medicine Unit, “Santa Maria Goretti” Hospital, Latina, Italy
| | - Orazio Schillaci
- Department of Biomedicine & Prevention, University Tor Vergata, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy
| | - Roberto Cianni
- Interventional Radiology Unit, “San Camillo Hospital”, Rome, Italy
| | - Oreste Bagni
- Nuclear Medicine Unit, “Santa Maria Goretti” Hospital, Latina, Italy
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Wright GP, Marsh JW, Varma MK, Doherty MG, Bartlett DL, Chung MH. Liver Resection After Selective Internal Radiation Therapy with Yttrium-90 is Safe and Feasible: A Bi-institutional Analysis. Ann Surg Oncol 2016; 24:906-913. [PMID: 27878478 DOI: 10.1245/s10434-016-5697-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Treatment with yttrium-90 (Y90) microspheres has emerged as a viable liver-directed therapy for patients with unresectable tumors and those outside transplantation criteria. A select number of patients demonstrate a favorable response and become candidates for surgical resection. METHODS Patients who underwent selective internal radiation therapy (SIRT) with Y90 microspheres at two institutions were reviewed. Patients who underwent liver resection were included in the study. The data gathered included demographics, tumor characteristics, response to Y90, surgical details, perioperative outcomes, and survival. RESULTS The inclusion criteria were met by 12 patients. The diagnoses included metastatic disease from colorectal adenocarcinoma (n = 6), neuroendocrine tumor (n = 1), and ocular melanoma (n = 1) in addition to hepatocellular carcinoma (n = 4). The median time from liver disease diagnosis to Y90 treatment was 5.5 months (range 2-92 months). The median time from Y90 treatment to surgery was 9.5 months (range 3-20 months). The surgical approach included right hepatectomy (n = 3), extended right hepatectomy (n = 5), extended left hepatectomy (n = 1), segmentectomy with ablation (n = 2), and segmentectomy with isolated liver perfusion (n = 1). The hospital stay was 7 days (range 4-31 days), and 67% of the patients were discharged home. The readmission rate was 42%. The 90-day morbidity and mortality rates were respectively 42 and 8%. At this writing, the median overall survival has not been reached at 25 months. CONCLUSION Liver resection after Y90 SIRT is a challenging surgical procedure with high rates of perioperative morbidity and hospital readmission. However, for properly selected patients, potential exists for extending disease-free and overall survival in the current era of multimodal therapy for malignant liver disease.
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Affiliation(s)
- G Paul Wright
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| | - J Wallis Marsh
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | | | | | - David L Bartlett
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mathew H Chung
- Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, MI, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, MI, USA
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Kuei A, Saab S, Cho SK, Kee ST, Lee EW. Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors. World J Gastroenterol 2015; 21:8271-8283. [PMID: 26217079 PMCID: PMC4507097 DOI: 10.3748/wjg.v21.i27.8271] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 04/29/2015] [Accepted: 06/16/2015] [Indexed: 02/06/2023] Open
Abstract
The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. The severe prognostic implications of hepatic metastases have made surgical resection an important first line treatment in management. However, limitations such as the presence of extrahepatic spread or poor functional hepatic reserve exclude the majority of patients as surgical candidates, leaving chemotherapy and locoregional therapies as next best options. Selective internal radiation therapy (SIRT) is a form of catheter-based locoregional cancer treatment modality for unresectable tumors, involving trans-arterial injection of microspheres embedded with a radio-isotope Yttrium-90. The therapeutic radiation dose is selectively delivered as the microspheres permanently embed themselves within the tumor vascular bed. Use of SIRT has been conventionally aimed at treating primary hepatic tumors (hepatocellular carcinoma) or colorectal and neuroendocrine metastases. Numerous reviews are available for these tumor types. However, little is known or reviewed on non-colorectal or non-neuroendocrine primaries. Therefore, the aim of this paper is to systematically review the current literature to evaluate the effects of Yttrium-90 radioembolization on non-conventional liver tumors including those secondary to breast cancer, cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.
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Fischman AM, Ward TJ, Patel RS, Arepally A, Kim E, Nowakowski FS, Lookstein RA. Prospective, Randomized Study of Coil Embolization versus Surefire Infusion System during Yttrium-90 Radioembolization with Resin Microspheres. J Vasc Interv Radiol 2014; 25:1709-16. [DOI: 10.1016/j.jvir.2014.08.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 07/21/2014] [Accepted: 08/04/2014] [Indexed: 12/20/2022] Open
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Powerski MJ, Scheurig-Münkler C, Hamm B, Gebauer B. Impaired hepatic Gd-EOB-DTPA enhancement after radioembolisation of liver malignancies. J Med Imaging Radiat Oncol 2014; 58:472-80. [PMID: 24964737 DOI: 10.1111/1754-9485.12187] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Accepted: 03/28/2014] [Indexed: 11/30/2022]
Abstract
INTRODUCTION To evaluate the uptake of the liver-specific magnetic resonance imaging (MRI) contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by functional liver parenchyma after radioembolisation (RE) of hepatic malignancies. METHODS Uptake of Gd-EOB-DTPA prior to RE versus 60+/-24d and 126+/-32d after RE was compared in a group of 33 patients with primary or secondary hepatic malignancies. In patients who underwent single-lobe treatment, left and right lobes were compared 59+/-24 days after RE. Gd-EOB-DTPA uptake was determined as follows: ratio of mean signal intensity in liver parenchyma to muscle in Gd-EOB-DTPA-enhanced T1-weighted MRI was subtracted from ratio of mean intensity in liver parenchyma to muscle in unenhanced T1-weighted MRI. RESULTS Gd-EOB-DTPA uptake in liver parenchyma was 0.845+/-0.29 before RE, 0.615+/-0.38 (P = 0.0022) at day 60+/-24, and 0.739+/-0.30 at day 126+/-32 after RE. In cases of single-lobe treatment, Gd-EOB-DTPA uptake was 0.581+/-0.256 for treated and 0.828+/-0.32 (P = 0.0164) for untreated hepatic lobes. CONCLUSIONS Uptake of Gd-EOB-DTPA by liver parenchyma is impaired after RE, indicating dysfunction of the local hepatic system. These findings suggest that Gd-EOB-DTPA-enhanced MRI has the potential to be used for monitoring liver damage after RE.
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Affiliation(s)
- Maciej Janusz Powerski
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany
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Quick AM, Lo SS, Mayr NA, Kim EY. Radiation therapy for intrahepatic malignancies. Expert Rev Anticancer Ther 2014; 9:1511-21. [DOI: 10.1586/era.09.114] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Chakravarty R, Dash A, Pillai MRA. Availability of yttrium-90 from strontium-90: a nuclear medicine perspective. Cancer Biother Radiopharm 2012; 27:621-41. [PMID: 23009585 DOI: 10.1089/cbr.2012.1285] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Yttrium-90 (T(½) 64.1 hours, E(βmax)=2.28 MeV) is a pure β⁻ particle emitting radionuclide with well-established applications in targeted therapy. There are several advantages of ⁹⁰Y as a therapeutic radionuclide. It has a suitable physical half-life (∼64 hours) and decays to a stable daughter product ⁹⁰Zr by emission of high-energy β⁻ particles. Yttrium has a relatively simple chemistry and its suitability for forming complexes with a variety of chelating agents is well established. The ⁹⁰Sr/⁹⁰Y generator is an ideal source for the long-term continuous availability of no-carrier-added ⁹⁰Y suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The parent radionuclide ⁹⁰Sr, which is a long-lived fission product, is available in large quantities from spent fuel. Several useful technologies have been developed for the preparation of ⁹⁰Sr/⁹⁰Y generators. There are several well-established radiopharmaceuticals based on monoclonal antibodies, peptides, and particulates labeled with ⁹⁰Y, that are in regular use for the treatment of some forms of primary cancers and arthritis. At present, there are no generators for the elution of ⁹⁰Y that can be set up in a hospital radiopharmacy. The radionuclide is procured from manufacturers and the radiopharmaceuticals are formulated on site. This article reviews the development of ⁹⁰Sr/⁹⁰Y generator and the development of ⁹⁰Y radiopharmaceuticals.
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Affiliation(s)
- Rubel Chakravarty
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India
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Muylle K, Nguyen J, de Wind A, Meuleman N, Delatte P, Vanderlinden B, Roelandts M, Van der Stappen A, Bron D, Flamen P. Radioembolization of the Spleen: A Revisited Approach for the Treatment of Malignant Lymphomatous Splenomegaly. Cardiovasc Intervent Radiol 2012; 36:1155-60. [DOI: 10.1007/s00270-012-0484-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Accepted: 08/27/2012] [Indexed: 12/11/2022]
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Abstract
Surgical hepatectomy or liver transplantation are considered as curative treatment modalities for hepatocellular carcinoma (HCC). However, many patients are not surgical candidates at the time of diagnosis. Great improvements in locoregional therapies including local ablative therapy [radiofrequency (RF) ablation or ethanol ablation] and transarterial techniques (transarterial embolization or transarterial radioembolization) have made possible local control of HCC. For unresectable HCC, a targeted therapy with sorafenib may improve survival. Unlike treatment of other oncologic tumor, the locoregional therapies are mainstay in the treatment of HCC. Therefore, the application of classical criteria such as the World Health Organization (WHO) guideline may not be suitable for accurate treatment response assessment of locoregional therapies or targeted therapy of HCC. An understanding of the imaging features of post-treatment imaging after various treatment modalities for HCC is crucial for treatment response assessment and for determining further therapy. In this article, we review the role of various imaging modalities in assessing treatment response of locoregional therapies and the targeted molecular therapy.
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Wadas TJ, Wong EH, Weisman GR, Anderson CJ. Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease. Chem Rev 2010; 110:2858-902. [PMID: 20415480 PMCID: PMC2874951 DOI: 10.1021/cr900325h] [Citation(s) in RCA: 700] [Impact Index Per Article: 46.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Thaddeus J Wadas
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., Campus Box 8225 St. Louis, Missouri 63110, USA.
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Radioembolisation using yttrium 90 (Y-90) in patients affected by unresectable hepatic metastases. Radiol Med 2010; 115:619-33. [PMID: 20091135 DOI: 10.1007/s11547-010-0496-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 06/23/2009] [Indexed: 12/19/2022]
Abstract
PURPOSE This study was done to evaluate the effectiveness of radioembolisation of liver metastases with yttrium 90 (Y-90) in patients with no response to chemotherapy. MATERIALS AND METHODS From February 2005 to January 2008, we treated 110 patients affected by liver metastatic disease from colorectal, breast, gastric, pancreatic, pulmonary, oesophageal and pharyngeal cancers and from cholangiocarcinoma and melanoma. We excluded patients with bilirubin level >1.8 mg/dl and pulmonary shunt >20% but not patients with minor extrahepatic metastases. RESULTS We obtained a complete /partial response in 45 patients, stable disease in 42 patients and progressive disease in 23 patients. In 90 cases, we obtained a decrease in specific tumour marker level. The technical success rate was 96%, and technical effectiveness estimated at 3 months after treatment was 83.6%. Side effects were grade 4 hepatic failure in one case, grade 2 gastritis in six cases and grade 2 cholecystitis in two cases. The median survival and progression-free survival calculated by Kaplan-Meier analysis were 323 days and 245 days, respectively. CONCLUSIONS According to our 3-year experience, Y-90 radioembolisation (SIR-spheres) is a feasible and safe method to treat liver metastases with an acceptable level of complications and a good response rate.
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Abstract
Vascular embolizations are complex and sophisticated procedures and can be a powerful alternative or useful adjunct to surgery in many clinical situations. Hemorrhage, vascular malformations, and tumors are the main indications for embolization procedures. Establishing the correct indication for intervention as well as the proper embolic agent and the most suitable catheterization technique requires advanced knowledge in interventional radiology, and an interdisciplinary approach is a prerequisite. A broad spectrum of microcatheters and embolization materials is available for these therapies. The desired level of occlusion and the individual vascular territory determine the choice of mechanical devices, particles, or liquid substances. Sclerosing agents and thrombin are used in special situations such as varicoceles and pseudoaneurysms.
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Gaba RC, Lewandowski RJ, Kulik LM, Riaz A, Ibrahim SM, Mulcahy MF, Ryu RK, Sato KT, Gates V, Abecassis MM, Omary RA, Baker TB, Salem R. Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization. Ann Surg Oncol 2009; 16:1587-96. [PMID: 19357924 DOI: 10.1245/s10434-009-0454-0] [Citation(s) in RCA: 174] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2008] [Revised: 03/13/2009] [Accepted: 03/14/2009] [Indexed: 12/11/2022]
Abstract
PURPOSE To describe volumetric changes of "radiation lobectomy," a manifestation of hepatic parenchymal response to lobar (90)Y microsphere radioembolization. METHODS Twenty patients exhibiting this phenomenon were identified. Pre- and posttreatment absolute right and left hepatic lobar volume (HLV), relative HLV (rHLV = HLV/total liver volume), and degree of lobar atrophy (DA) or hypertrophy (DH) (DA or DH = |posttreatment rHLV - pretreatment rHLV|) were determined. Laboratory toxicities, tumor response, and patient survival were also assessed. RESULTS Twenty patients with primary (HCC, n = 17; peripheral cholangiocarcinoma, n = 3) liver malignancies demonstrated findings of radiation lobectomy. Initial absolute right and left HLV was 955 cm(3) (range 644-1,842 cm(3), rHLV = 57%) and 719 cm(3) (range 328-1,387 cm(3), rHLV = 43%), respectively. Following (90)Y, absolute right HLV decreased to 460 cm(3) (range 185-948 cm(3), 52% reduction, rHLV = 31%, DA = 26%, P < 0.0001), while absolute left HLV increased to 1,004 cm(3) (range 560-1,558 cm(3), 40% increase, rHLV = 69%, DH = 26%, P < 0.0001). No grade 3 or 4 bilirubin toxicities were encountered. Tumor response ranged from 55% to 70% by size criteria. Forty-six percent 5-year survival was achieved in HCC patients. CONCLUSIONS Radiation lobectomy following (90)Y radioembolization of right lobe tumors manifests extensive contralateral lobar hypertrophy, high response rates, and prolonged survival. This phenomenon was noted in 6.4% (20/315) of the entire cohort and 19.8% (20/101) of patients with unilobar right lobe tumors. Further investigation is necessary to determine contributing factors that may predict this effect.
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Affiliation(s)
- Ron C Gaba
- Department of Radiology, University of Illinois at Chicago, USA
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Flamen P, Vanderlinden B, Delatte P, Ghanem G, Ameye L, Van Den Eynde M, Hendlisz A. Multimodality imaging can predict the metabolic response of unresectable colorectal liver metastases to radioembolization therapy with Yttrium-90 labeled resin microspheres. Phys Med Biol 2008; 53:6591-603. [PMID: 18978442 DOI: 10.1088/0031-9155/53/22/019] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Selective internal radiotherapy (SIRT) using Yttrium-90 labeled resin microspheres is increasingly used for the radioembolization of unresectable liver metastases of colorectal cancer (CRC). The treatment can be simulated by scintigraphy with Tc(99m)-labeled macroaggregates of albumin (MAA). The aim of the study was to develop a predictive dosimetric model for SIRT and to validate it by correlating results with the metabolic treatment response. The simulation of the dosimetry was performed by mathematically converting all liver voxel MAA-SPECT uptake values to the absolute Y(90) activity. The voxel values were then converted to a simulated absorbed dose (Gy) using simple MIRD formalism. The metabolic response was defined as the change in total lesion glycolysis (TLG) on FDG-PET. A total of 39 metastatic liver lesions were studied in eight evaluable patients. The mean administered Y(90) activity was 1.69 GBq (range: 1.33-2.04 GBq). The median (95% CI) simulated absorbed dose (Gy) was 29 Gy (1–98 Gy) and 66 Gy(32–159 Gy) in the poor (<50% TLG change) and the good responders (TLG change > 50%),respectively [DOSAGE ERROR CORRECTED].Using a simple cut-off value of 1 for the MAA-tumor-to-normal uptake ratio, a significant metabolic response was predicted with a sensitivity of 89% (17/19), a specificity of 65% (13/20), a positive predictive value of 71% (17/24) and a negative predictive value of 87% (13/15). Integrated multimodality imaging allows prediction of metabolic response post radioembolization using Y(90)-resin microspheres, and should be used for patient selection.
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Affiliation(s)
- Patrick Flamen
- Departmentof Nuclear Medicine, Bordet Institute, Bordet Institute, Université Libre de Bruxelles, Rue Héger-Bordet 1, B-1000 Brussels, Belgium.
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Kidner T, Dai M, Adusumilli PS, Fong Y. Advances in experimental and translational research in the treatment of hepatocellular carcinoma. Surg Oncol Clin N Am 2008; 17:377-89, ix. [PMID: 18375358 DOI: 10.1016/j.soc.2008.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Hepatocellular cancer (HCC) is the fifth-leading cause of cancer and the third-leading cause of cancer related deaths world-wide. Current treatment options are limited, as HCC has been shown to be a highly resistant type of cancer to most current treatment modalities. Novel approaches are being explored in the fields of gene therapy, viral oncolytics, radioembolization, and several new biologic therapies. This article summarizes these recent clinical findings and discusses what role they will have in the future treatment of HCC.
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Affiliation(s)
- Travis Kidner
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
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Quality control of no-carrier-added 90YCl3 by estimating the labeling efficiency using its reaction with DOTATOC. J Radioanal Nucl Chem 2008. [DOI: 10.1007/s10967-007-7186-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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