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Abstract
Selective internal radiation therapy represents an endovascular treatment option for patients with primary liver malignancies, in different clinical stages. Potential applications of this treatment are in early-stage hepatocellular carcinoma, as a curative option, or in combination with systemic treatments in intermediate and advanced-stages. This review, based on existing literature and ongoing trials, will focus on the future of this treatment in patients with hepatocellular carcinoma, in combination with systemic treatments, or with the use of new devices and technological developments; it will also describe new potential future indications and structural and organizational perspectives.
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Outpatient Yttrium-90 microsphere radioembolization: assessment of radiation safety and quantification of post-treatment adverse events causing hospitalization. Radiol Med 2020; 125:971-980. [PMID: 32270335 DOI: 10.1007/s11547-020-01180-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 03/23/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Quantification of post-interventional adverse events of outpatient SIRT leading to hospitalization and quantification of radiation exposure. MATERIALS AND METHODS In this single-center, retrospective cohort study, we reviewed 212 patients treated with SIRT (90Y-microspheres) for primary and secondary liver malignancies. We searched for adverse events (AEs) and serious adverse events (SAEs), defined as AE's causing hospitalization. Additionally, radiation exposure was measured in 36 patients. RESULTS Seven patients had an SAE (3.3%), four patients had AE without readmission/hospitalization (1.9%) and 201 patients had no complications (94.8%). The mean ambient dose rate at 1 m distance from the source after administration of 90Y-microspheres was 1.88 µSv/h ± 0.74 (± SD) with a range from 4.3 to 0.2 µSv/h. CONCLUSION Outpatient radioembolization with 90Y-microspheres is safe and requires hospitalization only in a very small number of patients. The mean dose rate was low and met the national conditions for outpatient treatment (< 5 µSv/h).
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ÇINAR İ, YAYLA M, BİNNETOĞLU D. Gossypinin insan hepatom (Hep-3B) hücreleri üzerinde anti-proliferatif etkisi. CUKUROVA MEDICAL JOURNAL 2020. [DOI: 10.17826/cumj.732912] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov 2020; 19:589-608. [PMID: 32728208 PMCID: PMC7390460 DOI: 10.1038/s41573-020-0073-9] [Citation(s) in RCA: 464] [Impact Index Per Article: 92.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2020] [Indexed: 12/25/2022]
Abstract
Radiopharmaceutical therapy (RPT) is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the biodistribution of the therapeutic agent. Compared with almost all other systemic cancer treatment options, RPT has shown efficacy with minimal toxicity. With the recent FDA approval of several RPT agents, the remarkable potential of this treatment is now being recognized. This Review covers the fundamental properties, clinical development and associated challenges of RPT.
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Affiliation(s)
- George Sgouros
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Lisa Bodei
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Jessie R Nedrow
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Yang B, Liang J, Qu Z, Yang F, Liao Z, Gou H. Transarterial strategies for the treatment of unresectable hepatocellular carcinoma: A systematic review. PLoS One 2020; 15:e0227475. [PMID: 32074102 PMCID: PMC7029952 DOI: 10.1371/journal.pone.0227475] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 12/19/2019] [Indexed: 02/05/2023] Open
Abstract
Conventional transarterial chemoembolization (cTACE), drug-eluting beads (DEB-TACE) and transarterial radioembolization (TARE) are alternative strategies for unresectable hepatocellular carcinoma (HCC). However, which of these strategies is the best is still controversial. This meta-analysis was performed to evaluate the effects of DEB-TACE, TARE and cTACE in terms of overall survival (OS), tumor response and complications. A literature search was conducted using the EMBASE, PubMed, Google Scholar, and Cochrane databases from inception until July 2019 with no language restrictions. The primary outcome was overall survival, and the secondary outcomes included complete response and local recurrence. The comparison of DEB-TACE with cTACE indicated that DEB-TACE has a better OS at 1 year (RR 0.79, 95% CI 0.67–0.93, p = 0.006), 2 years (RR 0.89; 95% CI 0.81–0.99, p = 0.046), and 3 years (RR 0.89; 95% CI 0.81–0.99, p = 0.035). The comparison of TARE with cTACE indicated that TARE has a better OS than cTACE at 2 years (RR 0.87; 95% CI 0.80–0.95, p = 0.003) and 3 years (RR 0.90; 95% CI 0.85–0.96, p = 0.001). The comparison of DEB-TACE with TARE indicated that DEB-TACE has a better OS than TARE at 2 years (RR 0.40; 95% CI 0.19–0.84, p = 0.016). The current meta-analysis suggests that DEB-TACE is superior to both TARE and cTACE in terms of OS. TARE has significantly lower complications than both DEB-TACE and cTACE for patients with HCC. Further multicenter, well-designed randomized controlled trials are needed, especially for evaluating DEB-TACE versus TARE.
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Affiliation(s)
- Biao Yang
- Department of Gastroenterology, West China Hospital, West China Medical School, Sichuan University, Chengdu, P.R. China
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, P.R. China
- * E-mail: (ZYL); (HFG); (BY)
| | - Jie Liang
- Department of Head and Neck Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, P.R. China
| | - ZiYu Qu
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, P.R. China
| | - FangYun Yang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, P.R. China
| | - ZhengYin Liao
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, P.R. China
- * E-mail: (ZYL); (HFG); (BY)
| | - HongFeng Gou
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, P.R. China
- * E-mail: (ZYL); (HFG); (BY)
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Golse N, Adam R. Liver Metastases From Breast Cancer: What Role for Surgery? Indications and Results. Clin Breast Cancer 2017; 17:256-265. [DOI: 10.1016/j.clbc.2016.12.012] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 12/26/2016] [Indexed: 12/30/2022]
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Jreige M, Mitsakis P, Van Der Gucht A, Pomoni A, Silva-Monteiro M, Gnesin S, Boubaker A, Nicod-Lalonde M, Duran R, Prior JO, Denys A, Schaefer N. 18F-FDG PET/CT predicts survival after 90Y transarterial radioembolization in unresectable hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2017; 44:1215-1222. [PMID: 28233086 DOI: 10.1007/s00259-017-3653-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 02/08/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 (90Y-TARE) for unresectable hepatocellular carcinoma (uHCC). METHODS We analysed data from 48 patients in our prospective database undergoing 90Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent 18F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and 90Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of 18F-FDG PET/CT metabolic parameters, including SUVmax, tumour-to-liver (T/L) uptake ratio and SUVmean of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses. RESULTS The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after 90Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUVmax (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUVmax and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUVmax and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean SUVmax; HR 2.6, 95% CI 1.1-5.9, P = 0.02, for median SUVmax:) and OS (HR 3.2, 95% CI 1-10.9, P = 0.04 for Q1 SUVmax; HR 3.7, 95% CI 1.1-12.2, P = 0.03, for Q1 T/L uptake ratio), respectively, when testing with either the BCLC staging system or serum AFP level. CONCLUSION Lesion SUVmax and T/L uptake ratio as assessed by 18F-FDG PET/CT, but not morphological imaging, were predictive markers of survival in patients undergoing 90Y-TARE for uHCC.
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Affiliation(s)
- Mario Jreige
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Periklis Mitsakis
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Axel Van Der Gucht
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Anastasia Pomoni
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Marina Silva-Monteiro
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Silvano Gnesin
- Institute of Radiation Physics, Lausanne University Hospital, Lausanne, Switzerland
| | - Ariane Boubaker
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Marie Nicod-Lalonde
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Rafael Duran
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - John O Prior
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Alban Denys
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Niklaus Schaefer
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
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Van Der Gucht A, Jreige M, Denys A, Blanc-Durand P, Boubaker A, Pomoni A, Mitsakis P, Silva-Monteiro M, Gnesin S, Lalonde MN, Duran R, Prior JO, Schaefer N. Resin Versus Glass Microspheres for 90Y Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma Using Pretreatment Partition Model Dosimetry. J Nucl Med 2017; 58:1334-1340. [PMID: 28082436 DOI: 10.2967/jnumed.116.184713] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 12/20/2016] [Indexed: 12/13/2022] Open
Abstract
The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with 90Y transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD). Methods: We performed a retrospective analysis of prospectively collected data on 77 patients consecutively treated (mean age ± SD, 66.4 ± 12.2 y) for uHCC (36 uninodular, 5 multinodular, 36 diffuse) with 90Y TARE (41 resin, 36 glass) using pretreatment PMD. Study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier estimates. Several variables including Barcelona Clinic Liver Cancer (BCLC) staging system, tumor size, and serum α-fetoprotein (AFP) level were investigated using Cox proportional hazards regression. Results: The characteristics of 2 groups were comparable with regard to demographic data, comorbidities, Child-Pugh score, BCLC, serum AFP level, and 90Y global administered activity. The median follow-up time was 7.7 mo (range, 0.4-50.1 mo). Relapse occurred in 44 patients (57%) at a median of 6 mo (range, 0.4-27.9 mo) after 90Y TARE, and 41 patients (53%) died from tumor progression. Comparison between resin and glass microspheres revealed higher but not statistically significantly PFS and OS rates in the 90Y resin group than the 90Y glass group (resin PFS 6.1 mo [95% confidence interval CI, 4.7-7.4] and glass PFS 5 mo [95% CI, 0.9-9.2], P = 0.53; resin OS 7.7 mo [95% CI, 7.2-8.2] and glass OS 7 mo [95% CI 1.6-12.4], P = 0.77). No significant survival difference between both types of 90Y microspheres was observed in any subgroups of patients with early/intermediate or advanced BCLC stages. Among the variables investigated, Cox analyses showed that only in the glass group, the BCLC staging system and the serum AFP level were associated with PFS (P = 0.04) and OS (P = 0.04). Tumor size was a prognostic factor without significant influence on PFS and OS after 90Y TARE. Conclusion: Comparison between resin and glass microspheres revealed no significant survival difference in patients treated for uHCC with 90Y TARE using pretreatment PMD. Further, larger prospective studies are warranted to confirm these findings.
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Affiliation(s)
- Axel Van Der Gucht
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Mario Jreige
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Alban Denys
- Department of Radiology and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland; and
| | - Paul Blanc-Durand
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Ariane Boubaker
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Anastasia Pomoni
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Periklis Mitsakis
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Marina Silva-Monteiro
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Silvano Gnesin
- Institute of Radiation Physics, Lausanne University Hospital, Lausanne, Switzerland
| | - Marie Nicod Lalonde
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Rafael Duran
- Department of Radiology and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland; and
| | - John O Prior
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Niklaus Schaefer
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
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Lobo L, Yakoub D, Picado O, Ripat C, Pendola F, Sharma R, ElTawil R, Kwon D, Venkat S, Portelance L, Yechieli R. Unresectable Hepatocellular Carcinoma: Radioembolization Versus Chemoembolization: A Systematic Review and Meta-analysis. Cardiovasc Intervent Radiol 2016; 39:1580-1588. [PMID: 27586657 DOI: 10.1007/s00270-016-1426-y] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Accepted: 07/13/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Transarterial radioembolization (TARE) has emerged as a newer regional therapy to transarterial chemoembolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). The aim of this study is to compare clinical outcomes of both the techniques. METHODS Online search for studies comparing TARE to TACE from 2005 to present was performed. Primary outcome was overall survival rate for up to 4 years. Secondary outcomes included post-treatment complications and treatment response. Quality of included studies was evaluated by STrengthening the Reporting of OBservational studies in Epidemiology criteria. Relative risk (RR) and 95 % confidence intervals (CI) were calculated from pooled data. RESULTS The search strategy yielded 172 studies, five met selection criteria and included 553 patients with unresectable HCC, 284 underwent TACE and 269 underwent TARE. Median ages were 63 and 64 years for TACE and TARE, respectively. Meta-analysis showed no statistically significant difference in survival for up to 4 years between the two groups (HR = 1.06; 95 % CI 0.81-1.46, p = 0.567). TACE required at least one day of hospital stay compared to TARE which was mostly an outpatient procedure. TACE had more post-treatment pain than TARE (RR = 0.51, 95 % CI 0.36-0.72, p < 0.01), but less subjective fatigue (RR = 1.68, 95 % CI 1.08-2.62, p < 0.01). There was no difference between the two groups in the incidence of post-treatment nausea, vomiting, fever, or other complications. In addition, there was no difference in partial or complete response rates between the two groups. CONCLUSION TARE appears to be a safe alternative treatment to TACE with comparable complication profile and survival rates. Larger prospective randomized trials, focusing on patient-reported outcomes and cost-benefit analysis are required to consolidate these results.
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Affiliation(s)
- Laila Lobo
- Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Danny Yakoub
- Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Omar Picado
- Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Caroline Ripat
- Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Fiorella Pendola
- Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Rishika Sharma
- Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Rana ElTawil
- Division of Surgical Oncology at Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Deukwoo Kwon
- Department of Biostatistics and Bioinformatics, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Shree Venkat
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Loraine Portelance
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Raphael Yechieli
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA. .,Department of Radiation Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, 1475 NW 12th Ave, Suite 1500, Miami, FL, 33136, USA.
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Dervenis C, Xynos E, Sotiropoulos G, Gouvas N, Boukovinas I, Agalianos C, Androulakis N, Athanasiadis A, Christodoulou C, Chrysou E, Emmanouilidis C, Georgiou P, Karachaliou N, Katopodi O, Kountourakis P, Kyriazanos I, Makatsoris T, Papakostas P, Papamichael D, Pechlivanides G, Pentheroudakis G, Pilpilidis I, Sgouros J, Tekkis P, Triantopoulou C, Tzardi M, Vassiliou V, Vini L, Xynogalos S, Ziras N, Souglakos J. Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO). Ann Gastroenterol 2016; 29:390-416. [PMID: 27708505 PMCID: PMC5049546 DOI: 10.20524/aog.2016.0050] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.
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Affiliation(s)
- Christos Dervenis
- General Surgery, "Konstantopouleio" Hospital of Athens, Greece (Christos Dervenis)
| | - Evaghelos Xynos
- General Surgery, "InterClinic" Hospital of Heraklion, Greece (Evangelos Xynos)
| | | | - Nikolaos Gouvas
- General Surgery, "METROPOLITAN" Hospital of Piraeus, Greece (Nikolaos Gouvas)
| | - Ioannis Boukovinas
- Medical Oncology, "Bioclinic" of Thessaloniki, Greece (Ioannis Boukovinas)
| | - Christos Agalianos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Nikolaos Androulakis
- Medical Oncology, "Venizeleion" Hospital of Heraklion, Greece (Nikolaos Androulakis)
| | | | | | - Evangelia Chrysou
- Radiology, University Hospital of Heraklion, Greece (Evangelia Chrysou)
| | - Christos Emmanouilidis
- Medical Oncology, "Interbalkan" Medical Center, Thessaloniki, Greece (Christos Emmanoulidis)
| | - Panagiotis Georgiou
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | - Niki Karachaliou
- Medical Oncology, Dexeus University Institut, Barcelona, Spain (Niki Carachaliou)
| | - Ourania Katopodi
- Medical Oncology, "Iaso" General Hospital, Athens, Greece (Ourania Katopoidi)
| | - Panteleimon Kountourakis
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - Ioannis Kyriazanos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Thomas Makatsoris
- Medical Oncology, University Hospital of Patras, Greece (Thomas Makatsoris)
| | - Pavlos Papakostas
- Medical Oncology, "Ippokrateion" Hospital of Athens, Greece (Pavlos Papakostas)
| | - Demetris Papamichael
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - George Pechlivanides
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | | | - Ioannis Pilpilidis
- Gastroenterology, "Theageneion" Cancer Hospital, Thessaloniki, Greece (Ioannis Pilpilidis)
| | - Joseph Sgouros
- Medical Oncology, "Agioi Anargyroi" Hospital of Athens, Greece (Joseph Sgouros)
| | - Paris Tekkis
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | | | - Maria Tzardi
- Pathology, University Hospital of Heraklion, Greece (Maria Tzardi)
| | - Vassilis Vassiliou
- Radiation Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Vassilis Vassiliou)
| | - Louiza Vini
- Radiation Oncology, "Iatriko" Center of Athens, Greece (Lousa Vini)
| | - Spyridon Xynogalos
- Medical Oncology, "George Gennimatas" General Hospital, Athens, Greece (Spyridon Xynogalos)
| | - Nikolaos Ziras
- Medical Oncology, "Metaxas" Cancer Hospital, Piraeus, Greece (Nikolaos Ziras)
| | - John Souglakos
- Medical Oncology, University Hospital of Heraklion, Greece (John Souglakos)
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Camacho JC, Kokabi N, Xing M, Schuster DM, Kim HS. PET response criteria for solid tumors predict survival at three months after intra-arterial resin-based 90Yttrium radioembolization therapy for unresectable intrahepatic cholangiocarcinoma. Clin Nucl Med 2015; 39:944-50. [PMID: 25140563 DOI: 10.1097/rlu.0000000000000557] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE PET Response Criteria for Solid Tumors (PERCIST) were assessed and correlated with survival analysis after resin-based 90Yttrium (90Y) radioembolization therapy for intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS Target and overall PERCIST and Response Criteria for Solid Tumors (RECIST) treatment responses were assessed in consecutive patients treated with Y radioembolization for ICC refractory to standard chemotherapy. Significant measurable tumor was defined as 1 cm or greater in diameter and SUVpeak of 2.5 or greater in targeted and nontargeted lesions. The PERCIST defines complete response as resolution of 18F-FDG uptake within measurable lesions, and partial response as 30% reduction in 18F-FDG peak standardized uptake value in measurable lesions. Objective response included partial response and complete response. Survival analysis by Kaplan-Meier and log-rank proportional models was performed using SPSS software version 20.0 (IBM, Armonk, NY), and significance was set at P < 0.05. RESULTS Median overall survival (OS) of 9 consecutive patients (56% women; mean age, 58 years) from 90Y therapy was 21.7 months. At 3 months, PERCIST objective response rate of target lesions was 77.7%, and target objective response on PERCIST correlated significantly to prolonged OS (P = 0.022). Overall objective PERCIST response at 3 months had significant correlation with OS (P = 0.011). Probability of death was significantly higher in overall nonresponders by PERCIST (hazard ratio, 12.3). No objective response was seen with RECIST. CONCLUSIONS In patients with unresectable ICC refractory to standard chemotherapy, PERCIST at 3 months for assessment of imaging response after 90Y radioembolization therapy predict OS.
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Affiliation(s)
- Juan C Camacho
- From the *Interventional Radiology and Image-guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA; †Division of Interventional Radiology, Department of Radiology, Universityof Pittsburgh School of Medicine, Pittsburgh, PA; and ‡Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA; §Cancer TherapeuticsProgram of University of Pittsburgh Cancer Institute, Pittsburgh, PA
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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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Abstract
Hepatobiliary surgery outcomes have significantly improved since the early 1970s. Surgical and anesthetic advances related to patient selection, alternative surgical management options, and reduction of operative blood loss have been important. Postoperative analgesic regimens are being modified to include intrathecal opiates and to embrace enhanced recovery regimens.
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Impact of Prior Hepatectomy on the Safety and Efficacy of Radioembolization With Yttrium-90 Microspheres for Patients With Unresectable Liver Tumors. Am J Clin Oncol 2014; 37:454-60. [PMID: 23388564 DOI: 10.1097/coc.0b013e31827deea1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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15
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Hsu WH, Liu SY, Chang YJ, Chang CH, Ting G, Lee TW. The PEGylated liposomal doxorubicin improves the delivery and therapeutic efficiency of 188Re-Liposome by modulating phagocytosis in C26 murine colon carcinoma tumor model. Nucl Med Biol 2014; 41:765-71. [DOI: 10.1016/j.nucmedbio.2014.05.142] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2013] [Revised: 05/16/2014] [Accepted: 05/27/2014] [Indexed: 11/30/2022]
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The role of 18F-FDG-PET and PET/CT in patients with colorectal liver metastases undergoing selective internal radiation therapy with yttrium-90: a first evidence-based review. ScientificWorldJournal 2014; 2014:879469. [PMID: 24672385 PMCID: PMC3929576 DOI: 10.1155/2014/879469] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Accepted: 10/19/2013] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To provide a first evidence-based review of the literature on the role of fluorine-18-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography (FDG-PET and PET/CT) in patients with colorectal liver metastases (CRLM) undergoing selective internal radiation therapy (SIRT) with yttrium-90 ((90)Y) microspheres. METHODS A comprehensive computer literature search was conducted to find relevant published articles on whole-body FDG-PET or PET/CT in patients with CRLM undergoing SIRT. RESULTS We identified 19 studies including 833 patients with CRLM undergoing SIRT. The role of FDG-PET or PET/CT was analysed in treatment planning, treatment response evaluation, and as prognostic tool. CONCLUSION FDG-PET and PET/CT provide additional information in treatment evaluation of CRLM patients treated with SIRT and may have a role in treatment planning and patient selection. FDG-PET/CT is emerging as good prognostic tool in these patients.
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18
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Complications after 90Y microsphere radioembolization for unresectable hepatic tumors: An evaluation of 112 patients. Brachytherapy 2013; 12:573-9. [DOI: 10.1016/j.brachy.2013.05.008] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Revised: 05/20/2013] [Accepted: 05/21/2013] [Indexed: 11/19/2022]
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Fendler WP, Philippe Tiega DB, Ilhan H, Paprottka PM, Heinemann V, Jakobs TF, Bartenstein P, Hacker M, Haug AR. Validation of Several SUV-Based Parameters Derived from 18F-FDG PET for Prediction of Survival After SIRT of Hepatic Metastases from Colorectal Cancer. J Nucl Med 2013; 54:1202-8. [DOI: 10.2967/jnumed.112.116426] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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Müller T, Mehrle S, Schieck A, Haberkorn U, Urban S, Mier W. Liver Imaging with a Novel Hepatitis B Surface Protein Derived SPECT-Tracer. Mol Pharm 2013; 10:2230-6. [DOI: 10.1021/mp400038r] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Thomas Müller
- Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg,
Germany
| | - Stefan Mehrle
- Department of Infectious
Diseases, Molecular Virology, University Hospital Heidelberg, INF 345, 69120 Heidelberg, Germany
| | - Alexa Schieck
- Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg,
Germany
| | - Uwe Haberkorn
- Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg,
Germany
| | - Stephan Urban
- Department of Infectious
Diseases, Molecular Virology, University Hospital Heidelberg, INF 345, 69120 Heidelberg, Germany
| | - Walter Mier
- Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg,
Germany
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Sharma B, Martin A, Zerizer I. Positron Emission Tomography-Computed Tomography in Liver Imaging. Semin Ultrasound CT MR 2013; 34:66-80. [DOI: 10.1053/j.sult.2012.11.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Wu SY, Kuo JW, Chang TK, Liu RS, Lee RC, Wang SJ, Lin WJ, Wang HE. Preclinical characterization of 18F-MAA, a novel PET surrogate of 99mTc-MAA. Nucl Med Biol 2012; 39:1026-33. [DOI: 10.1016/j.nucmedbio.2012.04.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2012] [Revised: 04/13/2012] [Accepted: 04/23/2012] [Indexed: 10/28/2022]
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Kritzinger J, Klass D, Ho S, Lim H, Buczkowski A, Yoshida E, Liu D. Hepatic embolotherapy in interventional oncology: technology, techniques, and applications. Clin Radiol 2012; 68:1-15. [PMID: 22917735 DOI: 10.1016/j.crad.2012.06.112] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 05/27/2012] [Accepted: 06/01/2012] [Indexed: 01/17/2023]
Abstract
Embolotherapy continues to play a growing role in the management of primary and secondary hepatic malignancies. In this review article, we examine the basis of therapy with a focus on neovascularization, which makes treatments via the hepatic artery possible. An overview of the three generations of embolic and therapeutic agents follows. The techniques, technologies, and complications of bland embolization, transarterial chemoembolization, drug-eluting beads, and selective internal radiotherapy are covered to give the reader an overview of this exciting field in interventional radiology.
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Affiliation(s)
- J Kritzinger
- Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada.
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Zerizer I, Al-Nahhas A, Towey D, Tait P, Ariff B, Wasan H, Hatice G, Habib N, Barwick T. The role of early ¹⁸F-FDG PET/CT in prediction of progression-free survival after ⁹⁰Y radioembolization: comparison with RECIST and tumour density criteria. Eur J Nucl Med Mol Imaging 2012; 39:1391-9. [PMID: 22644713 DOI: 10.1007/s00259-012-2149-1] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2012] [Accepted: 04/30/2012] [Indexed: 01/09/2023]
Abstract
PURPOSE This study evaluated the ability of (18)F-FDG PET/CT imaging to predict early response to (90)Y-radioembolization in comparison with contrast-enhanced CT (CECT) using RECIST and lesion density (Choi) criteria. Progression-free survival (PFS) in patients with liver metastases at 2 years and decline in tumour markers were the primary end-points of the study. METHODS A total of 121 liver lesions were evaluated in 25 patients (14 men, 11 women) with liver-dominant metastatic colorectal cancer who underwent (18)F-FDG PET/CT and CECT before and 6-8 weeks after treatment. Changes in SUV(max), tumour density measured in terms of Hounsfield units and the sum of the longest diameters (LD) were calculated for the target liver lesions in each patient. The patient responses to treatment were categorized using EORTC PET criteria, tumour density criteria (Hounsfield units) and RECIST, and were correlated with the responses of tumour markers and 2-year PFS using Kaplan-Meier plots and the log-rank test for comparison. Multivariate proportional hazards (Cox) regression analysis was performed to assess the effect of relevant prognostic factors on PFS. RESULTS Using (18)F-FDG PET/CT response criteria, 15 patients had a partial response (PR) and 10 patients had stable disease (SD), while using RECIST only 2 patients had a PR and 23 had SD. Two patients had a PR, 21 SD and 2 progressive disease using tumour density criteria. The mean changes in SUV(max), sum of the LDs and tumour density after treatment were 2.9 ± 2.6, 7.3 ± 14.4 mm and 1.9 ± 13.18 HU, respectively. Patients who had a PR on (18)F-FDG PET/CT had a mean decrease of 44.5 % in SUV(max) compared to those with SD who had a decrease of only 10.3 %. The decreases in SUV(max) and sum of the LDs were significant (p < 0.0001, p < 0.05, respectively) while the decrease in tumour density was not (p > 0.1065). The responses on the (18)F-FDG PET/CT studies were highly correlated with the responses of tumour markers (p < 0.0001 for LDH, p = 0.01 for CEA and p = 0.02 for Ca19-9), while the responses on the CECT studies using both RECIST and tumour density criteria were not significantly correlated with the responses of tumour markers. The responses on (18)F-FDG PET/CT studies also significantly predicted PFS (the median PFS in those with a PR was 12.0 months and in those with SD was 5 months, p < 0.0001), while RECIST and tumour density did not significantly predict PFS. Multivariate analysis demonstrated that responses on (18)F-FDG PET/CT studies and decreases in SUV(max) of ≤ 2.0 were the strongest predictors of PFS. CONCLUSION Early response assessment to (90)Y-radioembolization using (18)F-FDG PET/CT is superior to RECIST and tumour density, demonstrating a correlation with tumour markers and significantly predicting PFS in patients with liver metastases. This could enable early response-adapted treatment strategies to be employed.
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Affiliation(s)
- I Zerizer
- Department of Radiology/Nuclear Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, Du Cane Road, London W12 0HS, UK.
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Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients. Cardiovasc Intervent Radiol 2012; 36:158-65. [PMID: 22526099 DOI: 10.1007/s00270-012-0373-5] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Accepted: 03/07/2012] [Indexed: 10/28/2022]
Abstract
PURPOSE To retrospectively evaluate the overall survival, safety, and efficacy of metastatic uveal melanoma patients after radioembolization as salvage therapy. MATERIALS AND METHODS Thirteen patients were treated with radioembolization of branches of the hepatic artery with resin-based yttrium-90 ((90)Y)-labelled microspheres. Twelve patients underwent a single application, and 1 patient underwent 4 interventions. Dosages from 644 to 2,450 MBq (mean activity 1,780) were applied. Treatment response was evaluated by way of liver magnetic resonance imaging and computed tomography (CT) as well as whole-body fluorodeoxyglucose positron emission tomography (PET)/CT with evaluation of percentage changes in SUV(max) before and at 2-3 months after therapy. Kaplan-Meier analysis was calculated to determine overall survival. RESULTS Partial remission (PR) was observed in 8 (62 %), stable disease (SD) in 2 (15 %), and progressive disease (PD) in 3 (23 %) patients under terms of standard criteria and PR in 3 (23 %), SD in 3 (23 %), and PD in 7 (54 %) patients according to PET criteria. Neither RECIST nor PET criteria showed a significant difference in predicting overall survival (P = 0.12 and 0.11, respectively). Median survival time after radioembolization was 7 months. No acute toxicity with in-hospital morbidity was observed. One patient developed hepatomegaly, and 1 patient developed gastric ulceration. Throughout follow-up, progression of extrahepatic metastases was observed. CONCLUSION Radioembolization may be a promising therapy in uveal melanoma patients with predominant hepatic metastases. At first follow-up, we observed PR or SD in 77 % patients under terms of standard criteria with an acceptable toxicity profile.
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Treatment of hepatocellular carcinoma (HCC) by intra-arterial infusion of radio-emitter compounds: trans-arterial radio-embolisation of HCC. Cancer Treat Rev 2011; 38:641-9. [PMID: 22169503 DOI: 10.1016/j.ctrv.2011.11.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Revised: 11/17/2011] [Accepted: 11/21/2011] [Indexed: 12/17/2022]
Abstract
Traditional radiotherapy is only effective in treating hepatocellular cancer (HCC) in doses above 50 Gy, but this is above the recommended liver radiation exposure of about 35 Gy, which is an important limitation making this treatment unsuitable for routine clinical practice. Trans-arterial radio-embolisation (TARE), consists of delivery of compounds linked to radio-emitter particles which end up in hepatic end-arterioles or show affinity for the neoplasm itself, allowing localised delivery of doses beyond 120 Gy. These are well tolerated in patients treated with this type of internal radiation therapy. TARE for HCC is used for palliative treatment of advanced disease which cannot be treated in other ways, or for tumour down-staging before liver transplantation, or as adjuvant therapy for surgically resected HCC. Tumour response after TARE is between 25% and 60% if assessed by using RECIST criteria, and 80% by EASL criteria. In this review we outline the advantages and limitations of radio-emitter therapy including 131-I, 90-Y and 188-Re. We include several observational, and all comparative studies using these compounds. In particular we compare TARE to trans-arterial chemo-embolisation and other intra-arterial techniques.
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Rajekar H, Bogammana K, Stubbs RS. Selective internal radiation therapy for gastrointestinal neuroendocrine tumour liver metastases: a new and effective modality for treatment. Int J Hepatol 2011; 2011:404916. [PMID: 22164335 PMCID: PMC3227504 DOI: 10.4061/2011/404916] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2011] [Revised: 09/03/2011] [Accepted: 09/03/2011] [Indexed: 01/28/2023] Open
Abstract
Background. Nonresectable neuroendocrine tumour (NET) liver metastases respond poorly to most widely available and used therapies. Selective Internal Radiation Therapy (SIRT) is becoming recognized as a new modality for selectively treating non-resectable liver tumours. This paper presents an experience of 14 patients with non-resectable NET liver metastases treated with SIRT. Methods. Between September 1997 and October 2009 14 patients with extensive NET liver metastases were treated with 2.0 to 3.0 GBq of (90)Yttrium microspheres. Repeat SIRT was undertaken in three patients after 16, 27, and 48 months, respectively. Responses were assessed clinically, biochemically, and with serial CT scans. Survival was measured from initial SIRT. Results. Some response was seen in all 14 patients. Carcinoid syndrome improved or resolved in 10/10 instances. 24-hour urinary 5-HIAA or serum chromogranin A levels fell dramatically in 5/7 patients following SIRT. Serial CT scans revealed partial response or stable disease in all 14 patients. Repeat treatment in three patients experiencing progression was associated with a further response. Median survival after SIRT is 25 months with 6 patients being alive (and 3 patients still asymptomatic), at 19, 22, 23, 23, 58, and 60 months. Conclusions. SIRT is an effective and well-tolerated treatment for non-resectable NET liver metastases capable of both alleviating the carcinoid syndrome and achieving significant tumour regression. Repeat treatment is an option and liver resection after downstaging may also become possible.
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Affiliation(s)
| | | | - Richard S. Stubbs
- Wakefield Gastroenterology Centre and University of Otago, Private Bag 7909, Wellington 6242, New Zealand
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Lewandowski RJ, Salem R. Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease to the liver. Semin Intervent Radiol 2011; 23:64-72. [PMID: 21326721 DOI: 10.1055/s-2006-939842] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Yttrium-90 ((90)Y) radioembolization is a catheter-based therapy that delivers internal radiation to hepatic tumors in the form of microspheres. (90)Y can be delivered to the hepatic tumor as either a constituent of a glass microsphere, TheraSphere(®), or as a biocompatible resin-based microsphere, SIR-Spheres(®). Once embedded within the tumor microcirculation, these microspheres emit β-radiation at therapeutic levels. While the technical aspects of radioembolization are quite complex, the collective clinical experience presented in the literature supports the use of (90)Y radioembolization for unresectable hepatic malignancies.
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Affiliation(s)
- Robert J Lewandowski
- Department of Radiology, Division of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, Chicago, Illinois
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Hellman RS, Krasnow AZ, Sudakoff GS. Positron emission tomography for staging and assessment of tumor response of hepatic malignancies. Semin Intervent Radiol 2011; 23:21-32. [PMID: 21326717 DOI: 10.1055/s-2006-939838] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a useful functional imaging method that complements conventional anatomic imaging modalities for screening patients with colorectal hepatic metastases and hepatocellular cancer to determine their suitability for interventional procedures. FDG PET is more sensitive in detecting colorectal cancer than hepatocellular cancer (~90% versus ~50%). The likelihood of detecting hepatic malignancy with FDG PET rapidly diminishes for lesions smaller than 1 cm. The greatest value of FDG PET in these patients is in excluding extrahepatic disease that might lead to early recurrence after interventional therapy. Promising results have been reported with FDG PET that may show residual (local) or recurrent disease before conventional imaging methods in patients receiving interventional therapy. For patients with colorectal hepatic metastases, many investigators believe that patients with PET evidence of recurrent hepatic disease should receive additional treatment even when there is no confirmatory evidence present on other methodologies. For patients with hepatocellular cancer no conclusions regarding the value of FDG PET for assessment of response to interventional therapy can be reached as there is almost no published data.
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Affiliation(s)
- Robert S Hellman
- Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin
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Side-Branch Embolization Before 90Y Radioembolization: Rate of Recanalization and New Collateral Development. AJR Am J Roentgenol 2011; 197:W169-74. [DOI: 10.2214/ajr.10.5600] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Kosmider S, Tan TH, Yip D, Dowling R, Lichtenstein M, Gibbs P. Radioembolization in combination with systemic chemotherapy as first-line therapy for liver metastases from colorectal cancer. J Vasc Interv Radiol 2011; 22:780-786. [PMID: 21515072 DOI: 10.1016/j.jvir.2011.02.023] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2009] [Revised: 01/31/2011] [Accepted: 02/16/2011] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To report clinical experience with radioembolization (RE) plus systemic chemotherapy as a first-line treatment for liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS Clinical outcomes were evaluated retrospectively among 19 patients with unresectable liver metastases from CRC who had a good performance status and a low burden of extrahepatic disease (EHD) and were eligible for RE. Most (74%) had disease confined to the liver. Concurrent treatment with 5-fluorourail/leucovorin (n = 7) or 5-fluorourail/leucovorin/oxaliplatin (FOLFOX; n = 12) was started 3-4 days before single treatment with RE. RESULTS Overall response rate according to the Response Evaluation Criteria in Solid Tumors was 84% (two complete responses and 14 partial responses). Median progression-free survival (PFS) time was 10.4 months and median overall survival (OS) time was 29.4 months. For patients with disease confined to the liver, PFS improved (10.7 mo vs 3.6 mo; P = .09), with significant prolongation of OS (median, 37.8 mo vs 13.4 mo; P = .03) compared with those who had EHD. Nine patients, including three long-term (> 3 y) survivors, remained alive after a median follow-up of 18.6 months. Serious treatment-related toxicities included febrile neutropenia with concurrent FOLFOX treatment, a perforated duodenal ulcer, and one death from hepatic toxicity. CONCLUSIONS The present findings confirm the effectiveness of RE plus systemic chemotherapy for metastatic CRC. Patients with liver-confined disease derived the greatest benefit, with median survival times beyond 36 months. Larger datasets from ongoing phase III trials are needed to further define the safety and efficacy of RE in the first-line setting.
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Affiliation(s)
- Suzanne Kosmider
- BioGrid Australia, Level 6 North, Royal Melbourne Hospital, Grattan St., Parkville, Victoria 3050, Australia.
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Lin M, Wong K, Ng WL, Shon IH, Morgan M. Positron emission tomography and colorectal cancer. Crit Rev Oncol Hematol 2011; 77:30-47. [PMID: 20619671 DOI: 10.1016/j.critrevonc.2010.04.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2009] [Revised: 04/30/2010] [Accepted: 04/30/2010] [Indexed: 12/16/2022] Open
Abstract
Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality. Molecular imaging using positron emission tomography (PET) is now an integral part of multidisciplinary cancer care. In this review, we discuss the role of PET in CRC including well established indications in the assessment of recurrent disease and emerging applications such as initial staging, monitoring therapy efficacy and using PET for radiotherapy planning. With rapid advancement in imaging technology, we also discuss the future potential of combining PET and magnetic resonance imaging and the use of novel radiotracers.
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Affiliation(s)
- Michael Lin
- Department of Nuclear Medicine and PET, Liverpool Hospital, Sydney, Australia; University of New South Wales, Sydney, Australia.
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Bester L, Hobbins PG, Wang SC, Salem R. Imaging characteristics following 90yttrium microsphere treatment for unresectable liver cancer. J Med Imaging Radiat Oncol 2011; 55:111-8. [DOI: 10.1111/j.1754-9485.2011.02241.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Šrank J, Melichar F, Filyanin A, Tomeš M, Beran M. Preparation of 90YCl3 radiopharmaceutical precursor for nuclear medicine using technology of centrifugal extractors. Appl Radiat Isot 2010; 68:2163-8. [DOI: 10.1016/j.apradiso.2010.07.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2009] [Revised: 06/29/2010] [Accepted: 07/21/2010] [Indexed: 10/19/2022]
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[Multimodality treatment concepts for metastatic breast cancer]. Internist (Berl) 2010; 51:1358-65. [PMID: 21107788 DOI: 10.1007/s00108-010-2676-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
While metastatic breast cancer is a systemic disease in most patients, there is a smaller subset of patients who suffer from oligometastatic disease defined by single or few resectable metastases. After verification of disease stabilization by systemic therapy, locoregional treatment such as surgery or radiation can be applied. While large prospective trials are missing to support the beneficial effect of this strategy, retrospective analyses are highly suggestive offering rapid disease control and even long-term survival in selected patients.
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Naymagon S, Warner RRP, Patel K, Harpaz N, Machac J, Weintraub JL, Kim MK. Gastroduodenal ulceration associated with radioembolization for the treatment of hepatic tumors: an institutional experience and review of the literature. Dig Dis Sci 2010; 55:2450-8. [PMID: 20198431 DOI: 10.1007/s10620-010-1156-y] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2009] [Accepted: 02/04/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND Microsphere radioembolization is a method of delivering radiation therapy directly to tumors, thereby minimizing toxicity to adjacent structures. Despite the relatively high precision of this modality, numerous adverse effects have been recognized. One particularly untoward complication is the development of severe gastroduodenal ulceration. METHODS In order to further characterize gastroduodenal ulceration associated with radioembolization, our institutional experience as well as the reported literature were reviewed. RESULTS The current evidence suggests that radioembolization-associated gastroduodenal ulceration results from inadvertent delivery of microspheres to the microvasculature of the gastrointestinal tract, leading to direct radiation toxicity. The reported incidence of this entity ranges between 2.9% and 4.8%. Most patients with this complication present with abdominal pain, often associated with nausea, vomiting, and anorexia. Symptoms can arise from hours to months after radioembolization treatment; diagnosis is made by endoscopic biopsy and histopathologic evaluation of the ulcer specimen. Radiation-induced ulcers have proven to be extremely difficult to treat. Current therapy based on acid suppression has had limited success, and the evidence for the addition of antioxidants and anti-inflammatory agents is still sparse. CONCLUSIONS The increasing utilization of radioembolization will lead to adverse events including gastroduodenal ulceration. This entity must be considered in any patient treated with radioactive microspheres presenting with symptoms of dyspepsia. Accurate diagnosis and aggressive treatment are necessary to improve patient outcomes.
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Affiliation(s)
- Steven Naymagon
- Department of Medicine, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA.
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Smits MLJ, Nijsen JFW, van den Bosch MAAJ, Lam MGEH, Vente MAD, Huijbregts JE, van het Schip AD, Elschot M, Bult W, de Jong HWAM, Meulenhoff PCW, Zonnenberg BA. Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2010; 29:70. [PMID: 20550679 PMCID: PMC2903532 DOI: 10.1186/1756-9966-29-70] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2010] [Accepted: 06/15/2010] [Indexed: 12/14/2022]
Abstract
BACKGROUND Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases. METHODS The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution. DISCUSSION This will be the first clinical study on 166Ho-RE. Based on preclinical studies, it is expected that 166Ho-RE has a safety and toxicity profile comparable to that of 90Y-RE. The biochemical and radionuclide characteristics of 166Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.
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Affiliation(s)
- Maarten L J Smits
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, E01,132, 3584 CX Utrecht, The Netherlands
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Wang XD, Yang RJ, Cao XC, Tan J, Li B. Dose delivery estimated by bremsstrahlung imaging and partition model correlated with response following intra-arterial radioembolization with 32P-glass microspheres for the treatment of hepatocellular carcinoma. J Gastrointest Surg 2010; 14:858-66. [PMID: 20224983 DOI: 10.1007/s11605-010-1180-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2009] [Accepted: 02/18/2010] [Indexed: 01/31/2023]
Abstract
RATIONALE The objective of this study was to retrospectively evaluate the efficacy of a combination of (32)P-glass microsphere-mediated intra-arterial internal radiation and chemoembolization for the treatment of hepatocellular carcinoma. METHODS Twenty-five consecutive patients with primary hepatocellular carcinoma referred for radiation therapy were treated with intra-arterial infusion of (32)P-glass microspheres followed by chemoembolization. beta-bremsstrahlung imaging was performed to monitor microsphere distribution. A partition model and a radiation dose equation were used for determination of radiation exposure in various tissues. Clinical response was evaluated using computed axial tomography scans. RESULTS The mean estimated absorption dose in tumor tissue was 137.42 +/- 56.69 Gy. A receiver operating characteristic curve was used to establish 90.65 Gy as the cutoff absorption dose with the best sensitivity and specificity for predicting response. The overall tumor response rate was 92%, while response in patients with radiation doses >90.65 Gy was 100%. Overall median patient survival was 15 months. CONCLUSION beta-bremsstrahlung imaging following intra-arterial infusion of (32)P-glass microspheres and chemoembolization incorporates effective treatment with convenient dosimetry monitoring and manageable adverse events using a single surgical procedure. This approach is a safe and effective method for ameliorating hepatocellular carcinoma.
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Affiliation(s)
- Xiao-Dong Wang
- Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of interventional therapy, Beijing Cancer Hospital and Institute, Peking University Oncology School, Beijing 100142, China
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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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Kooby DA, Egnatashvili V, Srinivasan S, Chamsuddin A, Delman KA, Kauh J, Staley CA, Kim HS. Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol 2009; 21:224-30. [PMID: 20022765 DOI: 10.1016/j.jvir.2009.10.013] [Citation(s) in RCA: 146] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2008] [Revised: 10/01/2009] [Accepted: 10/01/2009] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To compare the effectiveness and toxicity of transcatheter arterial chemoembolization (chemoembolization) and yttrium-90-labeled microspheres (radioembolization) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Outcomes from patients who underwent radioembolization or chemoembolization as the only treatment for unresectable HCC from 1996 to 2006 were compared. Response was assessed with Response Evaluation Criteria in Solid Tumors, survival was assessed with the Kaplan-Meier method, and toxicity was graded with National Cancer Institute criteria. Multivariate analysis for factors affecting survival was performed. RESULTS Seventy-one patients were treated with either chemoembolization (n = 44, 62%) or radioembolization (n = 27, 38%). Treatment groups were similar in age, sex, Child class, Model for End-Stage Liver Disease score, tumor size, and vascular invasion. Progressive disease at 3 months was observed in 16 (36%) of the 44 patients treated with chemoembolization and nine (33%) of the 27 patients treated with radioembolization (P = not statistically significant). The median overall survival was similar for both groups (6 months with chemoembolization vs 6 months with radioembolization, P= .7). Grade 3 or higher toxicity was observed in 24 of the 71 patients (34%). Tumor multifocality, vascular invasion, and hepatitis C seropositivity were independently associated with worse survival, whereas method of treatment was not. CONCLUSIONS In this single-center study, preliminary evidence suggests that chemoembolization and radioembolization provided similar effectiveness and toxicity in patients with unresectable HCC.
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Affiliation(s)
- David A Kooby
- Department of Surgery, Emory University, 1365C Clifton Rd, NE, 2nd Fl, Atlanta, GA 30322, USA.
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Liu DM, Kennedy A, Turner D, Rose SC, Kee ST, Whiting S, Murthy R, Nutting C, Heran M, Lewandowski R, Knight J, Gulec S, Salem R. Minimally invasive techniques in management of hepatic neuroendocrine metastatic disease. Am J Clin Oncol 2009; 32:200-15. [PMID: 19346815 DOI: 10.1097/coc.0b013e318172b3b6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- David M Liu
- Department of Radiology, Interventional Radiology Section, University of British Columbia, Vancouver, BC, Canada.
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Granberg D, Garske U, Welin S, Kindmark H, Öberg K, Eriksson B, Nyman R. Selective internal radiation therapy in patients with carcinoid liver metastases. Acta Oncol 2009; 47:1169-71. [PMID: 18607860 DOI: 10.1080/02841860701843738] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Bilbao JI, de Martino A, de Luis E, Díaz-Dorronsoro L, Alonso-Burgos A, Martínez de la Cuesta A, Sangro B, García de Jalón JA. Biocompatibility, inflammatory response, and recannalization characteristics of nonradioactive resin microspheres: histological findings. Cardiovasc Intervent Radiol 2009; 32:727-36. [PMID: 19449060 PMCID: PMC2711916 DOI: 10.1007/s00270-009-9592-9] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2009] [Revised: 04/03/2009] [Accepted: 04/07/2009] [Indexed: 12/11/2022]
Abstract
Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10–30 microspheres (15–30 μm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15–30 μm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.
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Affiliation(s)
- José I Bilbao
- Department of Radiology, Clínica Universitaria de Navarra, Universidad de Navarra, Avenida de Pio XII, 36, Pamplona, 31008, Spain.
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Abstract
Hepatocellular carcinoma (HCC) annually causes about one million deaths. Because of advanced stage at diagnosis, HCC carries a five-year survival rate of less than 5% in patients diagnosed with unresectable disease. Incidence for HCC is higher in men and individuals of Asian descent, where viral hepatitis, a leading cause of HCC, is endemic. This article will provide an overview of the complex symptom management of patients with HCC. The occurrence of multiple symptoms, including pain, fatigue, weight loss, and obstructive syndromes (e.g., ascites, jaundice) in patients with HCC is common. Because of limitations in the efficacy of current treatment options, aggressive symptom management is key to preserving physical functioning and quality of life in patients with HCC. A multidisciplinary team approach to symptom management of patients with HCC is critical, with oncology nurses playing an integral role.
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Affiliation(s)
- Virginia Chih-Yi Sun
- Department of Nursing Research and Education in Division of Population Sciences, City of Hope National Medical Center, Duarte, CA, USA.
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Ogawa F, Mino-Kenudson M, Shimizu M, Ligato S, Lauwers GY. Gastroduodenitis associated with yttrium 90-microsphere selective internal radiation: an iatrogenic complication in need of recognition. Arch Pathol Lab Med 2008; 132:1734-8. [PMID: 18976008 DOI: 10.5858/132.11.1734] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2008] [Indexed: 11/06/2022]
Abstract
CONTEXT Selective internal radiation (SIR) therapy (SIRT) with yttrium 90 microspheres is increasingly used as an alternative therapeutic modality for patients with inoperable liver tumors. During administration of microspheres via the hepatic artery branches, some may on occasion be misdirected and be caught in the capillary bed of the duodenal and/or stomach. OBJECTIVE To better characterize the histopathologic features of these complications. DESIGN We report herein our experience with 3 patients who received SIR and developed gastroduodenal complications. RESULTS SIR-microsphere-induced gastroduodenitis was diagnosed from 10 days to 5 months after treatment. In all 3 cases, purple particles measuring about 40 microm in diameter were observed. An array of changes ranging from mucosal ulceration to epithelial changes were seen. Fibrinopurulent exudate was admixed with granulation tissue and reactive stromal cells. Epithelial changes included apoptosis and mucin depletion. Glandular cystic dilatation and epithelial flattening were also common as well as foveolar hyperplasia, suggestive of reparative changes in one case. Capillary ectasia and prominent plump endothelial cells were also present. CONCLUSION The spectrum of the alterations is consistent with radiotherapy-induced changes. Given the recent approval by the US Food and Drug Administration for the use of SIRT, it is anticipated that more patients will be treated with this modality. Pathologists should become aware of the adverse effects associated with its use.
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Affiliation(s)
- Fumihiro Ogawa
- Gastrointestinal Pathology Service, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, MA 02114-2696, USA
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Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis. Eur Radiol 2008; 19:951-9. [PMID: 18989675 DOI: 10.1007/s00330-008-1211-7] [Citation(s) in RCA: 169] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2008] [Revised: 07/28/2008] [Accepted: 09/08/2008] [Indexed: 02/06/2023]
Abstract
Radioembolization with yttrium-90 microspheres ((90)Y-RE), either glass- or resin-based, is increasingly applied in patients with unresectable liver malignancies. Clinical results are promising but overall response and survival are not yet known. Therefore a meta-analysis on tumor response and survival in patients who underwent (90)Y-RE was conducted. Based on an extensive literature search, six groups were formed. Determinants were cancer type, microsphere type, chemotherapy protocol used, and stage (deployment in first-line or as salvage therapy). For colorectal liver metastases (mCRC), in a salvage setting, response was 79% for (90)Y-RE combined with 5-fluorouracil/leucovorin (5-FU/LV), and 79% when combined with 5-FU/LV/oxaliplatin or 5-FU/LV/irinotecan, and in a first-line setting 91% and 91%, respectively. For hepatocellular carcinoma (HCC), response was 89% for resin microspheres and 78% for glass microspheres. No statistical method is available to assess median survival based on data presented in the literature. In mCRC, (90)Y-RE delivers high response rates, especially if used neoadjuvant to chemotherapy. In HCC, (90)Y-RE with resin microspheres is significantly more effective than (90)Y-RE with glass microspheres. The impact on survival will become known only when the results of phase III studies are published.
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Abstract
Selective internal radiation therapy involves the intra-arterial delivery of radioactive beads to the tumor while minimizing dosing to the adjacent organ. Because this technique invariably results in some degree of embolization, it has also been termed radioembolization. More than 8000 patients have been treated worldwide, with a large body of experience with primary hepatocellular carcinoma (HCC) and metastatic colorectal carcinoma (MCRC) and growing experience with other tumors (metastatic neuroendocrine, breast carcinoma, cholangiocarcinoma). Response rates by FDG-PET are 80% to 90%. Complications are uncommon and most often consist of self-limited malaise. More significant complications, including radiation-induced liver disease, ischemic cholecystitis, and gastrointestinal ulceration may be seen in up to 10% of patients. This underscores the critical importance of patient selection and meticulous technique. Median survival times in patients who have HCC and MCRC are significantly improved compared with historic controls. Further study is required to determine the appropriate role of radioembolization in the context of state-of-the-art chemotherapy and other liver-directed therapies.
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Affiliation(s)
- Gregory J Dubel
- Department of Diagnostic Imaging, Warren Alpert School of Medicine Brown University, Division of Interventional Radiology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.
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Radiographic Response to Yttrium-90 Radioembolization in Anterior Versus Posterior Liver Segments. Cardiovasc Intervent Radiol 2008; 31:1124-32. [DOI: 10.1007/s00270-008-9348-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2008] [Revised: 03/26/2008] [Accepted: 04/02/2008] [Indexed: 10/22/2022]
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