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Criss CR, Makary MS. Liver-Directed Locoregional Therapies for Neuroendocrine Liver Metastases: Recent Advances and Management. Curr Oncol 2024; 31:2076-2091. [PMID: 38668057 PMCID: PMC11049250 DOI: 10.3390/curroncol31040154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 03/27/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such as carcinoid syndrome, which can manifest as a constellation of symptoms significantly impacting patients' quality of life. The prognosis of NETs is influenced by their tendency for metastasis, especially in cases involving the liver, where the estimated 5-year survival is between 20 and 40%. Although surgical resection remains the preferred curative option, challenges emerge in cases of neuroendocrine tumors with liver metastasis (NELM) with multifocal lobar involvement, and many patients may not meet the criteria for surgery. Thus, minimally invasive and non-surgical treatments, such as locoregional therapies, have surfaced. Overall, these approaches aim to prioritize symptom relief and aid in overall tumor control. This review examines locoregional therapies, encompassing catheter-driven procedures, ablative techniques, and radioembolization therapies. These interventions play a pivotal role in enhancing progression-free survival and managing hormonal symptoms, contributing to the dynamic landscape of evolving NELM treatment. This review meticulously explores each modality, presenting the current state of the literature on their utilization and efficacy in addressing NELM.
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Affiliation(s)
- Cody R. Criss
- Department of Internal Medicine, OhioHealth Riverside Methodist Hospital, Columbus, OH 43214, USA;
| | - Mina S. Makary
- Division of Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43240, USA
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DePietro DM, Li X, Shamimi-Noori SM. Chemoembolization Beyond Hepatocellular Carcinoma: What Tumors Can We Treat and When? Semin Intervent Radiol 2024; 41:27-47. [PMID: 38495263 PMCID: PMC10940046 DOI: 10.1055/s-0043-1777716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Liver metastases are the most common malignancy found in the liver and are 20 to 40 times more common than primary hepatic tumors, including hepatocellular carcinoma. Patients with liver metastases often present with advanced disease and are not eligible for curative-intent surgery or ablative techniques. The unique hepatic arterial blood supply of liver metastases allows interventional radiologists to target these tumors with transarterial therapies. Transarterial chemoembolization (TACE) has been studied in the treatment of liver metastases originating from a variety of primary malignancies and has demonstrated benefits in terms of hepatic progression-free survival, overall survival, and symptomatic relief, among other benefits. Depending on the primary tumor from which they originate, liver metastases may have different indications for TACE, may utilize different TACE regimens and techniques, and may result in different post-procedural outcomes. This review offers an overview of TACE techniques and specific considerations in the treatment of liver metastases, provides an in-depth review of TACE in the treatment of liver metastases originating from colorectal cancer, neuroendocrine tumor, and uveal melanoma, which represent some of the many tumors beyond hepatocellular carcinoma that can be treated by TACE, and summarizes data regarding when one should consider TACE in their treatment algorithms.
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Affiliation(s)
- Daniel M. DePietro
- Division of Interventional Radiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Xin Li
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Susan M. Shamimi-Noori
- Division of Interventional Radiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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Jain S, Blume H, Rodriguez L, Petre E, Moussa A, Zhao K, Sotirchos V, Raj N, Reidy D, Ziv E, Alexander E. Hepatic Hilar Block as an Adjunct to Transarterial Embolization of Neuroendocrine Tumors: A Retrospective Review of Safety and Efficacy. Cancers (Basel) 2023; 15:5202. [PMID: 37958376 PMCID: PMC10647661 DOI: 10.3390/cancers15215202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/09/2023] [Accepted: 10/27/2023] [Indexed: 11/15/2023] Open
Abstract
PURPOSE This study investigates whether hepatic hilar nerve blocks (HHNB) provide safe, effective analgesia in patients with neuroendocrine tumors (NET) treated with transarterial embolization (TAE). METHODS The retrospective study included all NETs treated with TAE or TAE + HHNB from 1/2020 to 8/2022. Eighty-five patients (45 men), mean age 62 years, were treated in 165 sessions (TAE, n = 153; TAE + HHNB, n = 12). For HHNBs, ≤10 mL bupivacaine HCl 0.25% ± 2 mg methylprednisolone were injected under ultrasound guidance. The aims were to assess safety of HHNB and reduction in pain. Groups were compared with Pearson's chi-squared and Wilcoxon rank sum tests. Logistic regression assessed independent risk factors for pain. RESULTS No immediate complications from HHNBs were reported. No difference in incidence of major complications between TAE and TAE + HHNB one month post-embolization was observed (7.19% vs. 8.33%, p = 0.895). No differences in mean length of hospital stay after treatment were observed (TAE 2.2 days [95%CI: 1.74-2.56] vs. TAE + HHNB 2.8 days [95%CI: 1.43-4.26]; p = 0.174). Post-procedure pain was reported in 88.2% of TAE and 75.0% of TAE + HHNB patients (p = 0.185). HHNB recipients were more likely to use analgesic patches (25.0% vs. 5.88%; p = 0.014). No other differences in analgesic use were observed. CONCLUSIONS HHNBs can safely be performed in patients with NETs. No difference in hospital stays or analgesic drug use was observed. Managing pain after TAE is an important goal; further study is warranted.
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Affiliation(s)
- Samagra Jain
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
- Baylor College of Medicine, School of Medicine, One Baylor Plaza, Houston, TX 77004, USA
| | - Harrison Blume
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
- Albert Einstein College of Medicine, School of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA
| | - Lee Rodriguez
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
| | - Elena Petre
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
| | - Amgad Moussa
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
| | - Ken Zhao
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
| | - Vlasios Sotirchos
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
| | - Nitya Raj
- Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (N.R.); (D.R.)
| | - Diane Reidy
- Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (N.R.); (D.R.)
| | - Etay Ziv
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
| | - Erica Alexander
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; (S.J.); (H.B.); (L.R.); (E.P.); (A.M.); (K.Z.); (V.S.); (E.Z.)
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Victory Srinivasan N, Venugopal S. A Comparison of the Outcomes of Transarterial Chemoembolization and Transarterial Radioembolization in the Management of Neuroendocrine Liver Metastases in Adults: A Systematic Review. Cureus 2023; 15:e40592. [PMID: 37469827 PMCID: PMC10353751 DOI: 10.7759/cureus.40592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 06/17/2023] [Indexed: 07/21/2023] Open
Abstract
The purpose of this article is to review the existing English scientific literature and determine the superior modality between transarterial chemoembolization (TACE) and radioembolization (TARE) in the treatment of neuroendocrine liver metastases (NELMs). To that end, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search PubMed, the Cochrane Library, and Google Scholar. We identified 14 observational studies and no randomized controlled trials (RCTs) investigating the use of TACE or TARE to treat NELM. We used the Newcastle-Ottawa Scale to assess the risk of bias in these studies. We concluded that TACE and TARE appeared to have similar outcomes when comparing overall survival, progression-free survival, radiological response, symptomatic response, and the incidence of severe adverse events. Further large-scale RCTs are needed to identify the superior modality conclusively. We also identified several unique prognostic factors for overall survival, such as the neutrophil-lymphocyte ratio, volumetric multiparametric magnetic resonance imaging, serum albumin, alkaline phosphatase, and pancreastatin.
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Affiliation(s)
| | - Sathish Venugopal
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Evaluation of the effectiveness of transarterial chemoembolization with drug-saturable microspheres with irinotecan for the treatment of patients with neuroendocrine tumors with liver metastases. КЛИНИЧЕСКАЯ ПРАКТИКА 2023. [DOI: 10.17816/clinpract115017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Since 2021, transarterial chemoembolization of the hepatic arteries (TACHE) has been included in the recommendations of professional communities for the treatment of liver metastases from neuroendocrine tumors. However, the heterogeneity of this group of patients and the methods of chemoembolization with a limited range of cytostatics used in the treatment makes it difficult to analyze the data and introduce the method into combination therapy regimens.The aim of the study was to study the effectiveness of transarterial chemoembolization with drug-saturable microspheres with irinotecan for the treatment of patients with neuroendocrine tumors with liver metastases.Materials and methods. A retrospective, observational, uncontrolled study of 34 patients with liver metastases from neuroendocrine cancer who underwent 52 TACs with irinotecan. Group 1 consisted of 15 patients who already had liver metastases at the time of detection of the primary focus, group 2 - 19 people in whom liver metastases appeared after a lapse of time since the detection of the primary focus. To plan and evaluate the effectiveness of chemoembolization, computed tomography and magnetic resonance imaging were used every 10-15 weeks during systemic treatment. All patients received systemic NEO therapy before and after embolization.Results. An increase in time without progression from 101 [57; 120] and 145 [89; 263] after chemotherapy up to 300 [134; 344] and 304 [240;342] after TACE in groups 1 and 2, respectively, with no difference between groups (p0.05). We did not find a linear relationship between the doubling time of the tumor and the difference in the volume of the tumor lesion (R2 0.1085 and 0.0265 in groups 1 and 2). When comparing intragroup scores, there was a statistically significant difference (p0.05) in tumor volume reduction and progression-free time between patients who underwent TACE immediately and those who underwent TACE after chemotherapy. Radiation and angiographic semiotics of liver metastases varied within the same organ and depended on the size of metastases.Conclusions. TACE with irinotecan drug-saturable microspheres is an effective method for the treatment of liver metastases of neuroendocrine cancer, allowing to increase the time without progression.
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Knavel Koepsel EM, Smolock AR, Pinchot JW, Kim CY, Ahmed O, Chamarthy MRK, Hecht EM, Hwang GL, Kaplan DE, Luh JY, Marrero JA, Monroe EJ, Poultsides GA, Scheidt MJ, Hohenwalter EJ. ACR Appropriateness Criteria® Management of Liver Cancer: 2022 Update. J Am Coll Radiol 2022; 19:S390-S408. [PMID: 36436965 DOI: 10.1016/j.jacr.2022.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/27/2022]
Abstract
The treatment and management of hepatic malignancies can be complex because it encompasses a variety of primary and metastatic malignancies and an assortment of local and systemic treatment options. When to use each of these treatments is critical to ensure the most appropriate care for patients. Interventional radiologists have a key role to play in the delivery of a variety of liver directed treatments including percutaneous ablation, transarterial embolization with bland embolic particles alone, transarterial chemoembolization (TACE) with injection of a chemotherapeutic emulsion, and transarterial radioembolization (TARE). Based on 9 clinical variants, the appropriateness of each treatment is described in this document. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Affiliation(s)
| | - Amanda R Smolock
- Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | - Charles Y Kim
- Panel Vice-Chair, Duke University Medical Center, Durham, North Carolina
| | - Osmanuddin Ahmed
- Vice-Chair of Wellness, Director of Venous Interventions, University of Chicago, Chicago, Illinois
| | - Murthy R K Chamarthy
- Vascular Institute of North Texas, Dallas, Texas; Commission on Nuclear Medicine and Molecular Imaging
| | - Elizabeth M Hecht
- Vice-Chair of Academic Affairs, Professor of Radiology, Weill Cornell Medicine, New York, New York; RADS Committee; Member of Appropriateness Subcommittees on Hepatobiliary Topics; Member of LI-RADS
| | - Gloria L Hwang
- Associate Chair of Clinical Performance Improvement, Stanford Radiology, Stanford Medical Center, Stanford, California
| | - David E Kaplan
- Section Chief of Hepatology at the University of Pennsylvania Division of Gastroenterology and Hepatology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; American Association for the Study of Liver Diseases
| | - Join Y Luh
- Providence Health Radiation Oncology Focus Group Chair, Providence St. Joseph Health, Eureka, California; Commission on Radiation Oncology; ACR CARROS President; ACR Council Steering Committee; California Radiological Society Councilor to ACR
| | - Jorge A Marrero
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; American Gastroenterological Association
| | | | - George A Poultsides
- Chief of Surgical Oncology and Professor of Surgery, Stanford University School of Medicine, Stanford, California; Society of Surgical Oncology
| | - Matthew J Scheidt
- Program Director of Independent IR Residency, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Eric J Hohenwalter
- Specialty Chair; Chief, MCW VIR, Froedtert & The Medical College of Wisconsin, Milwaukee, Wisconsin
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Surgery, Liver Directed Therapy and Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumor Liver Metastases. Cancers (Basel) 2022; 14:cancers14205103. [PMID: 36291892 PMCID: PMC9599940 DOI: 10.3390/cancers14205103] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 09/19/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are described by the World Health Organization (WHO) classification by grade (1–3) and degree of differentiation. Grade 1 and 2; well differentiated PNETs are often characterized as relatively “indolent” tumors for which locoregional therapies have been shown to be effective for palliation of symptom control and prolongation of survival even in the setting of advanced disease. The treatment of liver metastases includes surgical and non-surgical modalities with varying degrees of invasiveness; efficacy; and risk. Most of these modalities have not been prospectively compared. This paper reviews literature that has been published on treatment of pancreatic neuroendocrine liver metastases using surgery; liver directed embolization and peptide receptor radionuclide therapy (PRRT). Surgery is associated with the longest survival in patients with resectable disease burden. Liver-directed (hepatic artery) therapies can sometimes convert patients with borderline disease into candidates for surgery. Among the three embolization modalities; the preponderance of data suggests chemoembolization offers superior radiographic response compared to bland embolization and radioembolization; but all have similar survival. PRRT was initially approved as salvage therapy in patients with advanced disease that was not amenable to resection or embolization; though the role of PRRT is evolving rapidly
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Lucatelli P, Burrel M, Guiu B, de Rubeis G, van Delden O, Helmberger T. CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation. Cardiovasc Intervent Radiol 2021; 44:1851-1867. [PMID: 34694454 DOI: 10.1007/s00270-021-02968-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022]
Abstract
This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing transarterial chemoembolisation. It has been developed by an expert writing group under the guidance of the CIRSE Standards of Practice Committee. It will encompass all technical details reflecting European practice of different TACE procedures (Lp-TACE, DEM-TACE, DSM-TACE, b-TACE) as well as revising the existing literature on the various clinical indications (HCC, mCRC, ICC, NET). Finally, new frontiers of development will also be discussed.
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Affiliation(s)
- Pierleone Lucatelli
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
| | - Marta Burrel
- Radiology Department, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Boris Guiu
- Department of Radiology, Montpellier School of Medicine, St-Eloi University Hospital, Montpellier, France
| | - Gianluca de Rubeis
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy
- Department of Diagnostic Radiology, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Otto van Delden
- Department of Interventional Radiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Thomas Helmberger
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, Bogenhausen Hospital, Munich, Germany
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Mineur L, Boustany R, Vazquez L. Paraneoplastic Cushing Syndrome in Gastrointestinal Neuroendocrine Tumour. Case Rep Oncol 2021; 14:1407-1413. [PMID: 34720949 PMCID: PMC8525292 DOI: 10.1159/000518316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 07/05/2021] [Indexed: 11/19/2022] Open
Abstract
Ectopic production of adrenocorticotropic hormone (ACTH) by gastrointestinal neuroendocrine tumours (NETs) is relatively uncommon. We report a rare case of a liver metastatic G1 low-grade NET of the intestine that induced hypercortisolism after surgical resection. A 50-year-old man was admitted for an intestinal obstruction caused by a tumour of the intestine. Paraneoplastic Cushing syndrome was diagnosed more than a year later following the appearance of cushingoid symptoms, despite stable disease according to RECIST criteria but chromogranin A increase. Ketoconazole and sandostatin medical treatment and liver chemoembolization never managed to control the hypercortisolism unlike the bilateral adrenalectomy. The identification and effective management of this uncommon statement of ectopic ACTH secretion is important to improve the patient's prognosis and quality of life.
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Affiliation(s)
| | | | - Léa Vazquez
- Institute Sainte Catherine, Gastrointestinal and Liver Cancer Unit, Avignon, France
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D'Amico G, Uso TD, Del Prete L, Hashimoto K, Aucejo FN, Fujiki M, Eghtesad B, Sasaki K, David Kwon CH, Miller CM, Quintini C. Neuroendocrine liver metastases: The role of liver transplantation. Transplant Rev (Orlando) 2021; 35:100595. [PMID: 33548685 DOI: 10.1016/j.trre.2021.100595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 01/07/2021] [Accepted: 01/08/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE OF REVIEW Neuroendocrine tumor (NET) metastasis localized to the liver is an accepted indication for liver transplantation as such tumors have a low biological aggressiveness in terms of malignancy and are slow growing. RECENT FINDINGS The long-term results are comparable with and in some cases even better than those of transplantations performed for primary liver cancer. However, compared with nonmalignant conditions, neuroendocrine liver metastasis (NELM) may result in an inferior outcome of transplantation. In the face of the scarcity of donated organs and recent improved results of non-surgical treatment for NELM, controversy over patient selection and timing for liver transplantation continues. SUMMARY In this review, we provide an overview of the diagnostic work-up and selection criteria of patients with NELM being considered for liver transplantation. Thereafter, we provide a critical analysis of the reported outcomes of OLT.
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Affiliation(s)
- Giuseppe D'Amico
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Teresa Diago Uso
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Luca Del Prete
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Koji Hashimoto
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Federico N Aucejo
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Masato Fujiki
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Bijan Eghtesad
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Kazunari Sasaki
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Choon H David Kwon
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Charles M Miller
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Cristiano Quintini
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
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Ngo L, Elnahla A, Attia AS, Hussein M, Toraih EA, Kandil E, Killackey M. Chemoembolization Versus Radioembolization for Neuroendocrine Liver Metastases: A Meta-analysis Comparing Clinical Outcomes. Ann Surg Oncol 2021; 28:1950-1958. [PMID: 33393019 DOI: 10.1245/s10434-020-09469-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/20/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Studies have shown intra-arterial therapies to be effective in controlling neuroendocrine liver metastases (NELMs), but the evidence supporting the selection of specific methods is limited. This meta-analysis is the first to compare survival outcomes between transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) in the treatment of NELM. METHODS A systematic search according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in PubMed and Embase databases was conducted in February 2020 for published studies comparing survival outcomes between TACE and TARE in the treatment of NELM. RESULTS Six eligible cohort studies with a total of 643 patients were identified. The TACE and TARE groups were similar in terms of age, sex, hepatic tumor burden, tumor grade, and Eastern Cooperative Oncology Group (ECOG) score. The patients treated with TACE had significantly better overall survival (odds ratio [OR], 1.92; 95% confidence interval [CI] 1.14-3.22, p = 0.014) than those treated with TARE. Overall survival ranged from 16.8 to 81.9 months with TACE and from 14.5 to 66.8 months with TARE. No significant differences in hepatic progression-free survival (OR, 1.01; 95% CI 0.75-1.35; p = 0.96) or tumor response were observed within the first 3 months (OR, 2.87; 95% CI 0.81-10.21; p = 0.10) or thereafter (OR, 0.98; 95% CI 0.12-7.86; p = 0.99). The complication rates were similar between the two groups, with 6.9% of the TACE patients versus 8.5% of TARE patients reporting major complications (OR, 1.16; 95% CI 0.54-2.48; p = 0.71) and respectively 44.6% and 58.8% of the TACE and TARE patients reporting minor adverse events (OR, 1.08; 95% CI 0.39-2.99; p = 0.88). CONCLUSIONS Despite similar tumor responses, an overall survival benefit was associated with TACE treatment of NELM compared with TARE treatment. Randomized controlled trials are warranted to confirm this finding and clarify whether certain subpopulations benefit from different transarterial methods.
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Affiliation(s)
- Lisa Ngo
- Tulane University School of Medicine, New Orleans, LA, USA
| | - Ahmed Elnahla
- Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA
| | - Abdallah S Attia
- Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA
| | - Mohamed Hussein
- Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA
| | - Eman A Toraih
- Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.,Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Emad Kandil
- Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA
| | - Mary Killackey
- Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.
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Kanabar R, Barriuso J, McNamara MG, Mansoor W, Hubner RA, Valle JW, Lamarca A. Liver Embolisation for Patients with Neuroendocrine Neoplasms: Systematic Review. Neuroendocrinology 2021; 111:354-369. [PMID: 32172229 DOI: 10.1159/000507194] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 03/12/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND Liver embolisation is one of the treatment options available for patients diagnosed with neuro-endocrine neoplasms (NEN). It is still uncertain whether the benefits of the various types of embolisation treatments truly outweigh the complications in NENs. This systematic review assesses the available data relating to liver embolisation in patients with NENs. METHODS Eligible studies (identified using MEDLINE-PubMed) were those reporting data on NEN patients who had undergone any type of liver embolisation. The primary end points were best radiological response and symptomatic response; secondary end-points included progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS Of 598 studies screened, 101 were eligible: 16 were prospective (15.8%). The eligible studies included a total of 5,545 NEN patients, with a median of 39 patients per study (range 5-214). Pooled rate of partial response was 36.6% (38.9% achieved stable disease) and 55.2% of patients had a symptomatic response to therapy when pooled data were analysed. The median PFS and OS were 18.4 months (95% CI 15.5-21.2) and 40.7 months (95% CI 35.2-46.2) respectively. The most common toxicities were found to be abdominal pain (48.8%) and nausea (48.1%). Outcome did not significantly vary depending on the type of embolisation performed. CONCLUSION Liver embolisation provides adequate symptom relief for patients with carcinoid syndrome and is also able to reach partial response in a significant proportion of patients and a reasonable PFS. Quality of studies was limited, highlighting the need of further prospective studies to confirm the most suitable form of liver embolisation in NENs.
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Affiliation(s)
- Rahul Kanabar
- Manchester Medical School, The University of Manchester, Manchester, United Kingdom,
| | - Jorge Barriuso
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Mairéad G McNamara
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Was Mansoor
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Richard A Hubner
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Angela Lamarca
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
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Tai E, Kennedy S, Farrell A, Jaberi A, Kachura J, Beecroft R. Comparison of transarterial bland and chemoembolization for neuroendocrine tumours: a systematic review and meta-analysis. Curr Oncol 2020; 27:e537-e546. [PMID: 33380868 PMCID: PMC7755439 DOI: 10.3747/co.27.6205] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Treatment of hepatic metastases from neuroendocrine tumours improves survival and symptom relief. Hepatic arterial embolotherapy techniques include transarterial chemoembolization (tace) and bland embolization (tae). The relative efficacy of the techniques is controversial. The purpose of the present study was to use a meta-analysis and systematic review to compare tace with tae in the treatment of hepatic metastases. Methods A literature search identified studies comparing tace and tae for treatment of hepatic metastases. Outcomes of interest included overall survival (os), progression-free survival (pfs), radiographic response, complications, and symptom control. The hazard ratios (hrs) and odds ratios (ors) were estimated and pooled. Results Eight studies and 504 patients were included. No statistically significant differences between tace and tae were observed for os at 1, 2, and 5 years or for hrs [1-year or: 0.72; 95% confidence interval (ci): 0.27 to 1.94; p < 0.52; 2-year or: 0.69; 95% ci: 0.43 to 1.11; p < 0.12; 5-year or: 0.91; 95% ci: 0.37 to 2.24; p < 0.85; hr: 0.96; 95% ci: 0.73 to 1.24; p < 0.74]. No statistically significant differences between tace and tae were observed for pfs at 1, 2, and 5 years or for hrs (1-year or: 0.71; 95% ci: 0.38 to 1.55; p < 0.30; 2-year or: 0.83; 95% ci: 0.33 to 2.06; p < 0.69; 5-year or: 0. 91; 95% ci: 0.37 to 2.24; p < 0.85; hr: 0.99-1.74; 95% ci: 0.74 to 1.73; p < 0.97). Both techniques are safe and effective for symptom control. Conclusions No statistically significant differences between tace and tae were observed for os and pfs.
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Affiliation(s)
- E Tai
- Division of Interventional Radiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON
| | - S Kennedy
- Division of Interventional Radiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON
| | - A Farrell
- Library and Information Services, Toronto General Hospital, Toronto, ON
| | - A Jaberi
- Division of Interventional Radiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON
| | - J Kachura
- Division of Interventional Radiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON
| | - R Beecroft
- Division of Interventional Radiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON
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Abstract
BACKGROUND Neuroendocrine tumors are becoming increasingly prevalent, with many patients presenting with or developing metastatic disease to the liver. METHODS In this landmark series paper, we highlight the critical studies that have defined the surgical management of neuroendocrine tumor liver metastases, as well as several randomized control trials which have investigated strategies for systemic control of metastatic disease. RESULTS Liver-directed surgical approaches and locally ablative procedures are recommended for patients with limited, resectable, and in some cases, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, chemoembolization, and radioembolization, offer another approach for management in patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising therapy for patients with hepatic and/or extrahepatic metastases. Various systemic medical therapies are also available as adjunct or definitive therapy for patients with metastatic disease. CONCLUSIONS This article reviews current data regarding management of neuroendocrine liver metastases and highlights areas for future study.
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Affiliation(s)
- Alexandra Gangi
- Division of Surgical Oncology, Department of Surgery, Cedars Sinai Medical Center, 8700 Beverly Blvd; AC 1049, Los Angeles, CA 90048
| | - James R. Howe
- Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 4644 JCP, 200 Hawkins Drive, University of Hospitals and Clinics, Iowa City, IA, 52242
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The Role of Interventional Radiology for the Treatment of Hepatic Metastases from Neuroendocrine Tumor: An Updated Review. J Clin Med 2020; 9:jcm9072302. [PMID: 32698459 PMCID: PMC7408651 DOI: 10.3390/jcm9072302] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/08/2020] [Accepted: 07/10/2020] [Indexed: 02/07/2023] Open
Abstract
Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall survival. These treatment options are proposed in patients with NELM not responding to systemic therapies and without extrahepatic progression. Currently, available data suggest that TAE should be preferred to TACE in patients with NELM from extrapancreatic origin because of similar efficacy and better patient tolerance. TACE is more effective in patients with pancreatic NELM and SIRT has shown promising results along with good tolerance. However, large randomized controlled trials are still lacking in this setting. Available literature mainly consists in small sample size and retrospective studies with important technical heterogeneity. The purpose of this review is to provide an updated overview of the currently reported endovascular interventional radiology procedures that are used for the treatment of NELM.
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16
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Surgical treatment of non-functioning pancreatic neuroendocrine tumors: current controversies and challenges. JOURNAL OF PANCREATOLOGY 2020. [DOI: 10.1097/jp9.0000000000000047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
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17
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Interventional Liver-Directed Therapy for Neuroendocrine Metastases: Current Status and Future Directions. Curr Treat Options Oncol 2020; 21:52. [PMID: 32447461 DOI: 10.1007/s11864-020-00751-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OPINION STATEMENT Liver-directed therapy should be considered for patients with unresectable liver metastases from neuroendocrine tumor if symptomatic or progressing despite medical management. Our experience and current literature shows that the bland embolization, chemoembolization, and radioembolization are very effective in controlling symptoms and disease burden in the liver, and that these embolization modalities are similar in terms of efficacy and radiologic response. Their safety profiles differ, however, with recent studies suggesting an increase in biliary toxicity with drug-eluting bead chemoembolization over conventional chemoembolization, and a risk of long-term hepatotoxicity with radioembolization. For this reason, we tailor the type of embolotherapy to each patient according to their clinical status, symptoms, degree of tumor burden, histologic grade, and life expectancy. We do not recommend a "one-size-fits-all" approach. Our general strategy is to use bland embolization as first-line embolotherapy, and radioembolization for patients with high-grade tumors or who have failed other embolotherapy.
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18
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Egger ME, Armstrong E, Martin RC, Scoggins CR, Philips P, Shah M, Konda B, Dillhoff M, Pawlik TM, Cloyd JM. Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis. J Am Coll Surg 2020; 230:363-370. [PMID: 32032719 DOI: 10.1016/j.jamcollsurg.2019.12.026] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 12/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown. STUDY DESIGN A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers. Postoperative morbidity, radiographic response according to response evaluation criteria in solid tumors (RECIST) criteria, and long-term outcomes were compared between patients who underwent TACE vs TARE. RESULTS Among 248 patients with NELM, 197 (79%) received TACE and 51 (21%) received TARE. While patients who underwent TACE were more likely to have carcinoid syndrome, larger tumors, and higher chromogranin A levels, there was no difference in tumor differentiation, primary site, bilobar disease, or synchronous presentation. Nearly all TARE treatments (92%) were performed as outpatient procedures, while 99% of TACE patients spent at least 1 night in the hospital. There were no differences in overall morbidity (TARE 13.7% vs TACE 22.6%, p = 0.17), grade III/IV complication (5.9% vs 9.2%, p = 0.58), or 90-day mortality. The disease control rate (DCR) on first post-treatment imaging (RECIST partial/complete response or stable disease) was greater for TACE compared with TARE (96% vs 83%, p < 0.01). However, there was no difference in median overall survival (OS, 35.9 months vs 50.1 months, p = 0.3) or progression-free survival (PFS, 15.9 months vs 19.9 months, p = 0.37). CONCLUSIONS In this retrospective multi-institutional analysis, both TACE and TARE with Y-90 were safe and effective liver-directed therapies for unresectable NELM. Although TARE was associated with a shorter length of hospital stay, TACE demonstrated improved short-term DCR, and both resulted in comparable long term outcomes.
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Affiliation(s)
- Michael E Egger
- Hiram C Polk Jr, MD Department of Surgery, University of Louisville, Louisville, KY
| | - Emily Armstrong
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Robert Cg Martin
- Hiram C Polk Jr, MD Department of Surgery, University of Louisville, Louisville, KY
| | - Charles R Scoggins
- Hiram C Polk Jr, MD Department of Surgery, University of Louisville, Louisville, KY
| | - Prejesh Philips
- Hiram C Polk Jr, MD Department of Surgery, University of Louisville, Louisville, KY
| | - Manisha Shah
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Bhavana Konda
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Mary Dillhoff
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.
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Dermine S, Palmieri LJ, Lavolé J, Barré A, Dohan A, Abou Ali E, Cottereau AS, Gaujoux S, Brezault C, Chaussade S, Coriat R. Non-Pharmacological Therapeutic Options for Liver Metastases in Advanced Neuroendocrine Tumors. J Clin Med 2019; 8:jcm8111907. [PMID: 31703375 PMCID: PMC6912565 DOI: 10.3390/jcm8111907] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 10/29/2019] [Accepted: 11/05/2019] [Indexed: 12/18/2022] Open
Abstract
The incidence of liver metastasis in digestive neuroendocrine tumors is high. Their presence appears as an important prognostic factor in terms of quality of life and survival. These tumors may be symptomatic because of the tumor burden itself and/or the hormonal hyper-secretion induced by the tumor. Surgery is the treatment of choice for resectable tumors and metastasis. Nevertheless, surgery is only possible in a small number of cases. The management of non-resectable liver metastasis is a challenge. The literature is rich but consists predominantly in small retrospective series with a low level of proof. Thus, the choice of one technique over another could be difficult. Local ablative techniques (radiofrequency) or trans-catheter intra-arterial liver-directed treatments (hepatic artery embolization, chemo-embolization, and radio-embolization) are frequently considered for liver metastasis. In the present review, we focus on these different therapeutic approaches in advanced neuroendocrine tumors, results (clinical and radiological), and overall efficacy, and summarize recommendations to help physicians in their clinical practice.
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Affiliation(s)
- Solène Dermine
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Correspondence: (S.D.); (R.C.); Tel.: +33-(1)58411952 (R.C.); Fax: +33-(1)58411965 (R.C.)
| | - Lola-Jade Palmieri
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Julie Lavolé
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Amélie Barré
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Antony Dohan
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Department of Radiology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Einas Abou Ali
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Anne-Ségolène Cottereau
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Department of Nuclear Medicine, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Sébastien Gaujoux
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Digestive Surgery Unit, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Catherine Brezault
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Stanislas Chaussade
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Romain Coriat
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Correspondence: (S.D.); (R.C.); Tel.: +33-(1)58411952 (R.C.); Fax: +33-(1)58411965 (R.C.)
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Herren JL, Disomma N, Ray CE. Hepatocellular Carcinoma: Combined Transarterial Chemoembolization and Ablation. Semin Intervent Radiol 2019; 36:279-284. [PMID: 31435137 PMCID: PMC6699963 DOI: 10.1055/s-0039-1694066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Josi L. Herren
- Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois
| | - Nerina Disomma
- Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois
| | - Charles E. Ray
- Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois
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21
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Strosberg D, Schneider EB, Onesti J, Saunders N, Konda B, Shah M, Dillhoff M, Schmidt CR, Shirley LA. Prognostic Impact of Serum Pancreastatin Following Chemoembolization for Neuroendocrine Tumors. Ann Surg Oncol 2018; 25:3613-3620. [PMID: 30182331 DOI: 10.1245/s10434-018-6741-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Indexed: 12/31/2022]
Abstract
PURPOSE The objective of this study was to investigate the prognostic impact of the biomarker serum pancreastatin in patients with metastatic neuroendocrine tumors (NETs) treated with transarterial chemoembolization (TACE). METHODS Patients with metastatic NET treated with TACE at a single institution from 2000 to 2013 were analyzed. Patient demographics, response to therapy, and long-term survival were compared with baseline pancreastatin level and changes in pancreastatin levels after TACE. RESULTS A total of 188 patients underwent TACE during the study period. An initial pancreastatin level greater than 5000 pg/mL correlated with worse overall survival (OS) from time of first TACE (median OS, 58.5 vs. 22.1 months, p < 0.001). A decrease in pancreastatin level by 50% or more after TACE treatment correlated with improved OS (median OS 53.8 vs. 29.9 months, p = 0.032). Patients with carcinoid syndrome were more likely to have a subsequent increase in pancreastatin after initial drop post-TACE (78.1 vs. 55.2%, p = 0.002). Patients with an increase in pancreastatin levels after initial drop post-TACE were more likely to have liver progression on imaging (70.7 vs. 40.7%, p = 0.005) and more likely to need repeat TACE (21.1 vs. 6.7%, p = 0.009). CONCLUSIONS For patients with liver metastases from NET treated with TACE, pancreastatin measurement may be a useful prognostic indicator. Extreme high levels before TACE can predict poor outcomes, whereas significant drops in pancreastatin after TACE correlate with improved survival. An increase in levels after initial decrease may predict progressive liver disease requiring repeat TACE. As such, pancreastatin levels should be measured throughout the TACE treatment period.
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Affiliation(s)
- David Strosberg
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Eric B Schneider
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jill Onesti
- Mercy Health Grand Rapids, Grand Rapids, MI, USA
| | - Neil Saunders
- Emory University School of Medicine, Atlanta, GA, USA
| | - Bhavana Konda
- Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Manisha Shah
- Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Mary Dillhoff
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Carl R Schmidt
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Lawrence A Shirley
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial. Trials 2018; 19:390. [PMID: 30016989 PMCID: PMC6050671 DOI: 10.1186/s13063-018-2782-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 07/04/2018] [Indexed: 01/24/2023] Open
Abstract
Background Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial. Methods/design A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm. Discussion The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases. Trial registration ClinicalTrials.gov, NCT02724540. Registered on March 31, 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2782-5) contains supplementary material, which is available to authorized users.
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Grozinsky-Glasberg S, Kaltsas G, Kaltsatou M, Lev-Cohain N, Klimov A, Vergadis V, Uri I, Bloom AI, Gross DJ. Hepatic intra-arterial therapies in metastatic neuroendocrine tumors: lessons from clinical practice. Endocrine 2018; 60:499-509. [PMID: 29383678 DOI: 10.1007/s12020-018-1537-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 01/15/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver metastases are common in patients with neuroendocrine tumors (NETs), having a negative impact on disease prognosis. The options for selective therapy in patients with unresectable multiple liver metastases are limited to TACE (transarterial chemoembolization), TAE (transarterial embolization), or SIRT (selective internal radiation therapy). AIM To explore the clinical outcome, survival and safety of these therapies in NETs patients. METHODS Retrospective case series of consecutive patients (mean age 56.6 years, 59% male) treated at two tertiary university medical centers from 2005 to 2015. RESULTS Fifty-seven patients with G1, G2, and low G3 NETs with liver metastases were investigated (pancreatic NET (pNET), 24; small bowel, 16; unknown origin (UKO), 9; rectal, 3; lung, 3; and gastric, 2). Fifty-three patients underwent TACE, three patients underwent TAE, and one patient underwent SIRT. Clinical improvement and tumor response were observed in 54/57 patients (95%), together with marked decreased in tumor markers. The median time to tumor progression following the first treatment was 14 ± 16 months. The median overall survival was 22 ± 18 months, more pronounced in the pNET, followed by small bowel and UKO subgroups. There was a trend for a better survival in patients with disease limited to the liver and in whom the primary tumor was resected. CONCLUSION Hepatic intra-arterial therapies are well tolerated in the majority of patients with NETs and liver metastases and associated with both clinical improvement and tumor stabilization for prolonged periods. These therapies should be always considered, irrespective of the presence of extrahepatic metastasis.
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Affiliation(s)
- S Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
| | - G Kaltsas
- Department of Pathophysiology, Division of Endocrinology, National University of Athens, Athens, Greece
| | - M Kaltsatou
- Department of Pathophysiology, Division of Endocrinology, National University of Athens, Athens, Greece
| | - N Lev-Cohain
- Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - A Klimov
- Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - V Vergadis
- Department of Radiology, Laiko General Hospital, Athens, Greece
| | - I Uri
- Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - A I Bloom
- Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - D J Gross
- Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
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de Mestier L, Zappa M, Hentic O, Vilgrain V, Ruszniewski P. Liver transarterial embolizations in metastatic neuroendocrine tumors. Rev Endocr Metab Disord 2017; 18:459-471. [PMID: 28975561 DOI: 10.1007/s11154-017-9431-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The management of patients with well-differentiated neuroendocrine tumors (NET) and non-resectable liver metastases is challenging. Liver-directed transarterial embolization (TAE), transarterial chemo-embolization (TACE) and selective internal radiation therapy (SIRT) have a place of choice among other treatment modalities. However, their utilization relies on a low level of proof, due to the lack of prospective data, the absence of comparative studies and considerable heterogeneity between local practices. TAE and TACE generally achieve average symptomatic, biological and radiological responses of 75%, 56% and 50%, with progression-free survival of 12-18 months, with acceptable tolerance. Although not clearly demonstrated, TACE may be more effective than TAE in pancreatic NET, but not in small-intestine NET. SIRT has been developed more recently and may achieve similar results, with improved tolerance, but decreased cost-effectiveness, although no prospective comparison has been published to date. There is currently no strong argument to choose between TAE, TACE and SIRT, and they have not been compared to other treatment modalities. The evaluation of their efficacy has mostly relied on criteria based on size variations, which do not take into account tumor viability and metabolism, and thus may not be relevant. These techniques may be especially effective when performed as first-line therapies, in patients with non-major liver involvement (<75%) and with hypervascular metastases. Finally, studies exploring their combination with systemic therapies are ongoing.
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Affiliation(s)
- Louis de Mestier
- Department of Gastroenterology and Pancreatology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, 100 boulevard du Général Leclerc, 92110, Clichy, France.
| | - Magaly Zappa
- Department of Radiology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, Clichy, France
| | - Olivia Hentic
- Department of Gastroenterology and Pancreatology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, 100 boulevard du Général Leclerc, 92110, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, Clichy, France
| | - Philippe Ruszniewski
- Department of Gastroenterology and Pancreatology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, 100 boulevard du Général Leclerc, 92110, Clichy, France
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Sposito C, Droz Dit Busset M, Citterio D, Bongini M, Mazzaferro V. The place of liver transplantation in the treatment of hepatic metastases from neuroendocrine tumors: Pros and cons. Rev Endocr Metab Disord 2017; 18:473-483. [PMID: 29359266 DOI: 10.1007/s11154-017-9439-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Liver metastases occur in nearly half of NET patients (MNETs) and heavily affect prognosis, with 5-yr. OS around 19-38%. Although it is difficult to show outcome differences for available treatments, due to the long course of disease, surgery for MNETs remains the most effective option in terms of survival and symptom control. Since MNETs frequently present as an oligo-metastatic, liver-limited disease, unresectable in 80% of cases, liver transplantation (LT) has emerged as a potential curative treatment. Nevertheless, experience with LT for MNETs is limited and burdened by highly heterogeneous outcomes and significant recurrence rate, mostly explained by the variability of selection criteria. Several prognostic factors have been identified: extended surgery on primary tumor associated to LT, elderly patients, pancreatic primary (pNET), extensive liver involvement, poorly differentiated tumors, high Ki67 levels and short wait time to LT. A proper patients' selection based on these data (Milan NET criteria) allows a significant survival advantage over non-transplant strategies, with excellent outcomes in recent series (69-97.2% 5-yr. OS) as opposed to patients undergoing non-surgical treatments (34-50.9%). Evidence indicates LT as the best option for selected patients with MNETs. The use of organs for MNETs is therefore justified.
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Affiliation(s)
- Carlo Sposito
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Michele Droz Dit Busset
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Davide Citterio
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Marco Bongini
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy.
- University of Milan, Milan, Italy.
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Jia Z, Paz-Fumagalli R, Frey G, Sella DM, McKinney JM, Wang W. Single-institution experience of radioembolization with yttrium-90 microspheres for unresectable metastatic neuroendocrine liver tumors. J Gastroenterol Hepatol 2017; 32:1617-1623. [PMID: 28132407 DOI: 10.1111/jgh.13752] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Revised: 01/25/2017] [Accepted: 01/25/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM The aim of this study was to assess the effectiveness of yttrium-90 (90 Y) microspheres for the treatment of unresectable metastatic liver neuroendocrine tumors (NET). METHODS From February 2006 to September 2015, 36 patients (19 male and 17 female, age 63.6 ± 9.4 years) who underwent 90 Y therapy for unresectable liver metastases of NET were included and analyzed retrospectively. All patients received a variety of treatments before 90 Y therapy. The radiological response, symptoms improvement of carcinoid syndrome, tumor marker changes, complications, side effects/toxicity, survival, and factors related to survival were evaluated and analyzed. RESULTS Of the 36 patients, the mean delivered dose of 90 Y was 1.8 ± 0.7 GBq with a total of 40 treatments. Overall disease control rate was 88.9% (32/36) at 3 months following therapy. In 16 patients with carcinoid syndrome, 15 (93.8%) patients had symptomatic improvement. Tumor marker response (5-hydroxyindoleacetic acid [n = 7] and chromogranin A [n = 13]) at 3 months after treatment were as follows: none (n = 0, 4), partial (n = 6, 7), and complete (n = 1, 2). Radiation-induced gastrointestinal ulcers (n = 2, 5.6%) were identified. Side effects included fatigue (n = 31, 86.1%), anorexia (n = 26, 72.2%), nausea (n = 15, 41.7%), vomiting (n = 14, 38.9%), abdominal pain (n = 10, 27.8%), and fever (n = 8, 22.2%). The mean follow-up was 27.0 ± 16.4 months, with a median survival of 41.0 months. Child-Pugh classification (P = 0.008) and lymph node metastases (P = 0.045) had statistically significant influence on overall survival. CONCLUSIONS Yttrium-90 radioembolization can be effective in the treatment of unresectable liver metastases of NET who failed to respond to other treatments.
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Affiliation(s)
- Zhongzhi Jia
- Department of Interventional Radiology, The Second People's Hospital of Changzhou, Nanjing Medical University, Changzhou, China
| | | | - Gregory Frey
- Department of Radiology, Mayo Clinic, Jacksonville, Florida, USA
| | - David M Sella
- Department of Radiology, Mayo Clinic, Jacksonville, Florida, USA
| | - J Mark McKinney
- Department of Radiology, Mayo Clinic, Jacksonville, Florida, USA
| | - Weiping Wang
- Department of Radiology, Mayo Clinic, Jacksonville, Florida, USA
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27
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Do Minh D, Chapiro J, Gorodetski B, Huang Q, Liu C, Smolka S, Savic LJ, Wainstejn D, Lin M, Schlachter T, Gebauer B, Geschwind JF. Intra-arterial therapy of neuroendocrine tumour liver metastases: comparing conventional TACE, drug-eluting beads TACE and yttrium-90 radioembolisation as treatment options using a propensity score analysis model. Eur Radiol 2017; 27:4995-5005. [PMID: 28677067 DOI: 10.1007/s00330-017-4856-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 04/05/2017] [Accepted: 04/18/2017] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To compare efficacy, survival outcome and prognostic factors of conventional transarterial chemoembolisation (cTACE), drug-eluting beads TACE (DEB-TACE) and yttrium-90 radioembolisation (Y90) for the treatment of liver metastases from gastroenteropancreatic (GEP) neuroendocrine tumours (NELM). METHODS This retrospective analysis included 192 patients (58.6 years mean age, 56% men) with NELM treated with cTACE (N = 122), DEB-TACE (N = 26) or Y90 (N = 44) between 2000 and 2014. Radiologic response to therapy was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) and World Health Organization (WHO) criteria using periprocedural MR imaging. Survival analysis included propensity score analysis (PSA), median overall survival (MOS), hepatic progression-free survival, Kaplan-Meier using log-rank test and the uni- and multivariate Cox proportional hazards model (MVA). RESULTS MOS of the entire study population was 28.8 months. As for cTACE, DEB-TACE and Y90, MOS was 33.8 months, 21.7 months and 23.6 months, respectively. According to the MVA, cTACE demonstrated a significantly longer MOS as compared to DEB-TACE (p <.01) or Y90 (p = .02). The 5-year survival rate after initial cTACE, DEB-TACE and Y90 was 28.2%, 10.3% and 18.5%, respectively. CONCLUSIONS Upon PSA, our study suggests significant survival benefits for patients treated with cTACE as compared to DEB-TACE and Y90. This data supports the therapeutic decision for cTACE as the primary intra-arterial therapy option in patients with unresectable NELM until proven otherwise. KEY POINTS • cTACE achieved a significantly longer overall survival in patients with unresectable NELM. • Patients treated with cTACE showed a prolonged hepatic progression-free survival. • cTACE, DEB-TACE and Y90 radioembolisation demonstrated comparable safety and toxicity profiles. • Age >70 years, extrahepatic metastases and tumour burden >50% were identified as negative predictors. • Propensity score analysis suggests the superiority of cTACE over DEB-TACE and Y90.
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Affiliation(s)
- Duc Do Minh
- Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Campus Virchow Klinikum, Berlin, Germany.,Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
| | - Boris Gorodetski
- Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Campus Virchow Klinikum, Berlin, Germany.,Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
| | - Qiang Huang
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.,Department of Interventional Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Cuihong Liu
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.,The Ultrasound Department, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Susanne Smolka
- Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Campus Virchow Klinikum, Berlin, Germany.,Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
| | - Lynn Jeanette Savic
- Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Campus Virchow Klinikum, Berlin, Germany.,Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
| | - David Wainstejn
- Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Campus Virchow Klinikum, Berlin, Germany.,Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
| | - MingDe Lin
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.,U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, MA, USA
| | - Todd Schlachter
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA
| | - Bernhard Gebauer
- Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Campus Virchow Klinikum, Berlin, Germany
| | - Jean-François Geschwind
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA. .,Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 330 Cedar Street, TE 2-230, New Haven, CT, 06520, USA.
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28
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Gaba RC, Lokken RP, Hickey RM, Lipnik AJ, Lewandowski RJ, Salem R, Brown DB, Walker TG, Silberzweig JE, Baerlocher MO, Echenique AM, Midia M, Mitchell JW, Padia SA, Ganguli S, Ward TJ, Weinstein JL, Nikolic B, Dariushnia SR. Quality Improvement Guidelines for Transarterial Chemoembolization and Embolization of Hepatic Malignancy. J Vasc Interv Radiol 2017; 28:1210-1223.e3. [PMID: 28669744 DOI: 10.1016/j.jvir.2017.04.025] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Accepted: 04/29/2017] [Indexed: 02/07/2023] Open
Affiliation(s)
- Ron C Gaba
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612.
| | - R Peter Lokken
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Ryan M Hickey
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Andrew J Lipnik
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Robert J Lewandowski
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Riad Salem
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Daniel B Brown
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - T Gregory Walker
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | | | | | - Ana Maria Echenique
- Department of Interventional Radiology, University of Miami School of Medicine, Coral Gables, Florida
| | - Mehran Midia
- Interventional Radiology, McMaster University, Hamilton, Ontario, Canada
| | - Jason W Mitchell
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Siddharth A Padia
- Division of Interventional Radiology, Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Suvranu Ganguli
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Thomas J Ward
- Vascular and Interventional Radiology, Florida Hospital, Orlando, Florida
| | - Jeffrey L Weinstein
- Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Boris Nikolic
- Department of Radiology, Stratton Medical Center, Albany, New York
| | - Sean R Dariushnia
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
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Gaba RC, Mendoza-Elias N, Morrison JD, Valeshabad AK, Lipnik AJ. Decision Making for Selection of Transarterial Locoregional Therapy of Metastatic Neuroendocrine Tumors. Semin Intervent Radiol 2017; 34:101-108. [PMID: 28579677 DOI: 10.1055/s-0037-1602590] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Transarterial locoregional therapies (LRTs) are indispensable components of the modern interventional oncologic therapy of liver-dominant metastatic neuroendocrine tumors (NETs). The scope of available LRTs and their nuanced differences mandates a thorough understanding of their relative applicability and effectiveness in certain clinical circumstances to prescribe appropriate, patient-specific, image-guided therapy. This article aims to provide an overview of transarterial LRT options for liver-dominant metastatic NETs and therapy selection by reviewing procedure types, their advantages and disadvantages, and comparative efficacy in common case scenarios.
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Affiliation(s)
- Ron C Gaba
- Department of Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.,Division of Interventional Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois
| | - Nasya Mendoza-Elias
- College of Medicine, University of Illinois Hospital and Health Sciences System, Chicago, Illinois
| | - Joseph D Morrison
- College of Medicine, University of Illinois Hospital and Health Sciences System, Chicago, Illinois
| | - Ali Kord Valeshabad
- Department of Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois
| | - Andrew J Lipnik
- Department of Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.,Division of Interventional Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois
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30
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Schippers AC, Collettini F, Steffen IG, Wieners G, Denecke T, Pavel M, Wust P, Gebauer B. Initial Experience with CT–Guided High-Dose-Rate Brachytherapy in the Multimodality Treatment of Neuroendocrine Tumor Liver Metastases. J Vasc Interv Radiol 2017; 28:672-682. [DOI: 10.1016/j.jvir.2016.07.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 07/09/2016] [Accepted: 07/09/2016] [Indexed: 02/07/2023] Open
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Fairweather M, Swanson R, Wang J, Brais LK, Dutton T, Kulke MH, Clancy TE. Management of Neuroendocrine Tumor Liver Metastases: Long-Term Outcomes and Prognostic Factors from a Large Prospective Database. Ann Surg Oncol 2017; 24:2319-2325. [PMID: 28303430 DOI: 10.1245/s10434-017-5839-x] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Liver-directed therapies have been used to treat neuroendocrine liver metastases (NELM) for both symptomatic improvement and tumor growth control. We reviewed our experience with NELM to investigate the outcomes of available treatment modalities and to identify prognostic factors for survival. METHODS We identified all patients with NELM, who were managed at our institution, from a prospectively collected institutional database. Overall survival (OS) was determined for each treatment modality. RESULTS Between 2003 and 2010, we identified 939 patients with neuroendocrine tumors, of whom 649 patients had NELM. The primary tumor site was the small intestine in 245 patients (38%) and pancreas in 194 patients (30%). With a median follow-up of 44 months, the median, 5 and 10 year OS for each treatment group was as follows: hepatic resection (n = 58, 9%), 160 months, 90%, 70%; radiofrequency ablation (n = 28, 4%), 123 months, 84%, 55%; chemoembolization (n = 130, 20%), 66 months, 55%, 28%; systemic therapy (n = 316, 49%), 70 months, 58%, 31%; and observation (n = 117, 18%), 38 months, 38%, 20%. Age [hazard ratio (HR) 1.0, p < 0.001), small bowel primary site (HR 0.5, p < 0.001), hepatic resection (HR 0.3, p = 0.001), well-differentiated tumors (HR 0.3, p < 0.001), alkaline phosphatase within normal limit (WNL) (HR 0.4, p < 0.001), and chromogranin A WNL (HR 0.5, p < 0.001) were significant independent prognosticators for OS. CONCLUSIONS This series represents one of the largest single-institution studies of NELM reported. We found that hepatic resection was associated with highly favorable OS. Our observations support hepatic resection in appropriately selected patients.
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Affiliation(s)
- Mark Fairweather
- Department of Surgery, Division of Surgical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Richard Swanson
- Department of Surgery, Division of Surgical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Jiping Wang
- Department of Surgery, Division of Surgical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Lauren K Brais
- Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Trevor Dutton
- Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Matthew H Kulke
- Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
| | - Thomas E Clancy
- Department of Surgery, Division of Surgical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA.
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Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival. Cardiovasc Intervent Radiol 2016; 40:69-80. [PMID: 27738818 DOI: 10.1007/s00270-016-1478-z] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 09/27/2016] [Indexed: 12/27/2022]
Abstract
PURPOSE The purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases. MATERIALS AND METHODS This was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models. RESULTS Median HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE. CONCLUSION Higher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.
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Onesti JK, Shirley LA, Saunders ND, Davidson GW, Dillhoff ME, Khabiri H, Guy GE, Dowell JD, Schmidt CR, Shah MH, Bloomston M. Elevated Alkaline Phosphatase Prior to Transarterial Chemoembolization for Neuroendocrine Tumors Predicts Worse Outcomes. J Gastrointest Surg 2016; 20:580-6. [PMID: 26489743 DOI: 10.1007/s11605-015-2998-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Accepted: 10/14/2015] [Indexed: 01/31/2023]
Abstract
INTRODUCTION We hypothesized that an elevated preoperative alkaline phosphatase (AP) predicted worse outcomes for patients undergoing transarterial chemoembolization (TACE) for neuroendocrine tumor (NET) liver metastases. METHODS We reviewed all patients who underwent TACE for metastatic NET between 2009 and 2013. Survival was evaluated using preprocedure variables. RESULTS One hundred and nine patients underwent 210 TACE procedures. The average age was 57.7 years (range 20-78). Primary sites included pancreas (N = 20), other gastrointestinal (N = 52), lung (N = 9), and unknown (N = 28). The tumor was grade 1 in 68 (62 %), grade 2 in 21 (19 %), and grade 3 in 3 (3 %). Extrahepatic disease was present in 54 (50 %) and greater than 50 % hepatic tumor burden by imaging in 63 (58 %). Elevated bilirubin occurred in 8 (7 %), elevated AP in 22 (20 %), elevated ALT in 21 (19 %), and elevated AST in 41 (38 %). Univariate predictors included tumor grade (43 vs 27 vs 21 months, p = 0.015), hepatic tumor burden (59 vs 37 months, p = 0.009), and elevated AP (59 vs 23 months, p < 0.001). On multivariate analysis, only elevated AP (p = 0.001) predicted worse survival. CONCLUSIONS Elevated AP prior to TACE for metastatic NET portends a worse survival outcome, even more so than tumor grade or extent of hepatic disease.
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Affiliation(s)
- Jill K Onesti
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA.
| | - Lawrence A Shirley
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Neil D Saunders
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Gail W Davidson
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Mary E Dillhoff
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Hooman Khabiri
- Division of Interventional Radiology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Gregory E Guy
- Division of Interventional Radiology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Joshua D Dowell
- Division of Interventional Radiology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Carl R Schmidt
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Manisha H Shah
- Division of Medical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
| | - Mark Bloomston
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 250 Cherry St, Grand Rapids, MI, 49503, USA
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Barbier CE, Garske-Román U, Sandström M, Nyman R, Granberg D. Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. Eur J Nucl Med Mol Imaging 2015; 43:1425-31. [DOI: 10.1007/s00259-015-3264-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 11/10/2015] [Indexed: 12/31/2022]
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Abstract
Neuroendocrine tumors (NETs) of the gastrointestinal (GI) tract have a propensity for producing hepatic metastases. Most GI NETs arise from the foregut or midgut, are malignant, and can cause severe debilitating symptoms adversely affecting quality of life. Aggressive treatments to reduce symptoms have an important role in therapy. Patients with GI NETs usually present with inoperable metastatic disease and severe symptoms from a variety of hormones and biogenic amines. This article describes intra-arterial hepatic-directed therapies for metastases from NETs, a group of treatments in which the therapeutic and/or embolic agents are released intra-arterially in specific hepatic vessels to target tumors.
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Affiliation(s)
- Andrew S Kennedy
- Radiation Oncology Research, Sarah Cannon Research Institute, Nashville, TN, USA; Department of Biomedical Engineering, Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC, USA.
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de Baere T, Deschamps F, Tselikas L, Ducreux M, Planchard D, Pearson E, Berdelou A, Leboulleux S, Elias D, Baudin E. GEP-NETS update: Interventional radiology: role in the treatment of liver metastases from GEP-NETs. Eur J Endocrinol 2015; 172:R151-66. [PMID: 25385817 DOI: 10.1530/eje-14-0630] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible for liver metastases. Such metastases can be the dominant part of the disease as well due to the tumor burden itself or the symptoms related to such liver metastases. Intra-arterial therapies are commonly used in liver only or liver-dominant disease and encompass trans-arterial chemoembolization (TACE), trans-arterial embolization (TAE), and radioembolization (RE). TACE performed with drug emulsified in Lipiodol has been used for the past 20 years with reported overall survival in the range of 3-4 years, with objective response up to 75%. Response to TACE is higher when treatment is used as a first-line therapy and degree of liver involvement is lower. Benefit of TACE over TAE is unproven in randomized study, but reported in retrospective studies namely in pancreatic NETs. RE provides early interesting results that need to be further evaluated in terms of benefit and toxicity. Radiofrequency ablation allows control of small size and numbered liver metastases, with low invasiveness. Ideal metastases to target are one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all metastases below 8 cm. Ablation therapies can be applied in the lung or in the bones when needed, and more invasive surgery should be probably saved for large-size metastases. Even if the indication of image-guided therapy in the treatment of GEP-NET liver metastases needs to be refined, such therapies allow for manageable invasive set of treatments able to address oligometastatic patients in liver, lung, and bones. These treatments applied locally will save the benefit and the toxicity of systemic therapy for more advanced stage of the disease.
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Affiliation(s)
- Thierry de Baere
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Frederic Deschamps
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Lambros Tselikas
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Michel Ducreux
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - David Planchard
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Ernesto Pearson
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Amandine Berdelou
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Sophie Leboulleux
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Dominique Elias
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Eric Baudin
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
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Clancy TE. Liver-directed therapy for neuroendocrine liver metastases. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015. [DOI: 10.2217/ije.14.36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract: Neuroendocrine tumors are relatively uncommon neoplasms presenting with a wide spectrum of clinical behavior. Many patients may present with or develop liver metastases from neuroendocrine tumors, which significantly influences prognosis and the potential for symptoms. Data suggest that some patients may have symptomatic relief and oncologic benefit from liver-directed therapy for neuroendocrine tumor metastases. Surgical resection, tumor ablation, transarterial therapy such as bland embolization, chemoembolization and radioembolization, as well as liver transplantation have been studied as liver-directed therapies. Data continue to emerge to help guide selection of treatment modality for an individual patient. The spectrum of behavior of neuroendocrine metastases and heterogeneity in the literature are a challenge to arriving at cohesive recommendations for all patients.
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Kennedy A, Bester L, Salem R, Sharma RA, Parks RW, Ruszniewski P. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB (Oxford) 2015; 17:29-37. [PMID: 25186181 PMCID: PMC4266438 DOI: 10.1111/hpb.12326] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 07/09/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Liver metastasis from a neuroendocrine tumour (NET) represents a significant clinical entity. A multidisciplinary group of experts was convened to develop state-of-the-art recommendations for its management. METHODS Peer-reviewed published reports on intra-arterial therapies for NET hepatic metastases were reviewed and the findings presented to a jury of peers. The therapies reviewed included transarterial embolization (TAE), transarterial chemoembolization (TACE) and radioembolization (RE). Two systems were used to evaluate the level of evidence in each publication: (i) the US National Cancer Institute (NCI) system, and (ii) the GRADE system. RESULTS Eighteen publications were reviewed. These comprised 11 reports on TAE or TACE and seven on RE. Four questions posed to the panel were answered and recommendations offered. CONCLUSIONS Studies of moderate quality support the use of TAE, TACE and RE in hepatic metastases of NETs. The quality and strength of the reports available do not allow any modality to be determined as superior in terms of imaging response, symptomatic response or impact on survival. Radioembolization may have advantages over TAE and TACE because it causes fewer side-effects and requires fewer treatments. Based on current European Neuroendocrine Tumor Society (ENETS) Consensus Guidelines, RE can be substituted for TAE or TACE in patients with either liver-only disease or those with limited extrahepatic metastases.
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Affiliation(s)
- Andrew Kennedy
- Radiation Oncology Research, Sarah Cannon Research InstituteNashville, TN, USA,Correspondence, Andrew S. Kennedy, Radiation Oncology Research, Sarah Cannon Research Institute, 3322 West End Avenue, Suite 800, Nashville, TN 37203, USA. Tel: + 1 615 524 4200. Fax: + 1 615 524 4700. E-mail:
| | - Lourens Bester
- Department of Radiology, St Vincent's Public HospitalSydney, NSW, Australia
| | - Riad Salem
- Department of Radiology, Northwestern UniversityChicago, IL, USA
| | - Ricky A Sharma
- Oncology Department, Gray Institute, University of Oxford, Churchill HospitalOxford, UK
| | - Rowan W Parks
- Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of EdinburghEdinburgh, UK
| | - Philippe Ruszniewski
- Centre for Gastroenterological and Pancreatic Disease, Beaujon Hospital, University of Paris Denis-DiderotParis, France
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Alagusundaramoorthy SS, Gedaly R. Role of surgery and transplantation in the treatment of hepatic metastases from neuroendocrine tumor. World J Gastroenterol 2014; 20:14348-14358. [PMID: 25339822 PMCID: PMC4202364 DOI: 10.3748/wjg.v20.i39.14348] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2014] [Revised: 04/24/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NET) are a heterogeneous group of cancers, with indolent behavior. The most common primary origin is the gastro-intestinal tract but can also appear in the lungs, kidneys, adrenals, ovaries and other organs. In general, NET is usually discovered in the metastatic phase (40%-80%). The liver is the most common organ involved when metastases occur (40%-93%), followed by bone (12%-20%) and lung (8%-10%).A number of different therapeutic options are available for the treatment of hepatic metastases including surgical resection, transplantation, ablation, trans-arterial chemoembolization, chemotherapy and somatostatin analogues. Recently, molecular targeted therapies have been used, usually in combination with other treatment options, to improve outcomes in patients with metastases. This article emphasizes on the role of surgery in the treatment of liver metastases from NET.
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40
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Frilling A, Clift AK. Therapeutic strategies for neuroendocrine liver metastases. Cancer 2014; 121:1172-86. [PMID: 25274401 DOI: 10.1002/cncr.28760] [Citation(s) in RCA: 123] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 04/09/2014] [Accepted: 04/10/2014] [Indexed: 12/16/2022]
Abstract
Patients who have neuroendocrine tumors frequently present with liver metastases. A wide panel of treatment options exists for these patients. Liver resection with curative intent achieves the best long-term results. Highly selected patients may be considered for liver transplantation. Substantial recurrence rates reported after surgical approaches call for neoadjuvant and adjuvant concepts. Liver-directed, locally ablative procedures are recommended for patients with limited, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, transarterial chemoembolization, and selective internal radiotherapy, offer excellent palliation for patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising palliative procedure for patients with hepatic and/or extrahepatic metastases. The efficacy of these treatment options needs to be evaluated in randomized trials. Somatostatin analogues have demonstrated effectiveness not only for symptomatic relief in patients with secreting tumors but also for the control of proliferation in small intestinal neuroendocrine tumors and most recently also in those originating from the pancreas. Chemotherapy is an option mainly for those with pancreatic neuroendocrine tumors and high-grade tumors irrespective of the origin. Novel drugs targeting specific pathways within the tumor cell have produced improved progression-free survival compared with placebo in patients with pancreatic neuroendocrine tumors. Despite such a diverse armamentarium, there is uncertainty with regard to the optimal treatment regimens. Newly introduced molecular-based markers, along with the conduction of clinical trials comparing the efficacy of treatment modalities, offer a chance to move the treatment of neuroendocrine tumor disease toward personalized patient care. In this report, the authors review the approaches for treatment of neuroendocrine liver metastases, identify shortcomings, and anticipate future perspectives. Furthermore, clinical practice recommendations are provided for currently available treatment options. Although multiple modalities are available for the treatment of neuroendocrine liver metastases, optimal management is unclear. The current knowledge pertaining to these treatment options is analyzed.
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Affiliation(s)
- Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
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Hickey RM, Lewandowski RJ, Salem R. Rationale of transcatheter intra-arterial therapies of hepatic cancers. Hepat Oncol 2014; 1:285-291. [PMID: 30190963 DOI: 10.2217/hep.14.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Transcatheter, intra-arterial therapies for primary and metastatic hepatic malignancies comprise angiographically guided procedures that provide for the administration of tumoricidal agents directly to liver tumors. These locoregional therapies have demonstrated encouraging clinical outcomes for liver tumors that are otherwise not amenable or not responsive to standard surgical or systemic treatments. This article provides a review of transcatheter therapies for hepatic cancers and reported clinical outcomes.
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Affiliation(s)
- Ryan M Hickey
- Northwestern University, Department of Radiology, Division of Vascular & Interventional Radiology, Chicago, IL 60611, USA
| | - Robert J Lewandowski
- Northwestern University, Department of Radiology, Division of Vascular & Interventional Radiology, Chicago, IL 60611, USA
| | - Riad Salem
- Northwestern University, Department of Radiology, Division of Vascular & Interventional Radiology, Chicago, IL 60611, USA
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Abstract
Neuroendocrine tumors have a disposition toward metastasis to the liver. A range of treatment modalities for neuroendocrine liver metastases is available in the clinical arena, the indications for which depend on tumor characteristics such as patterns of metastasis, tumor grade, and anatomical origin. The complete surgical resection of liver deposits represents the only option with the intent to cure and is the gold standard approach, whereas cytoreductive resection (debulking) presents another surgical option aiming to ameliorate the symptoms and prolong survival. Liver transplantation is generally an accepted option for highly selected patients. For patients ineligible for radical surgery, liver-directed therapies-transarterial embolization/chemoembolization, selective internal radiotherapy, and local tumor ablation-present alternative strategies. Systemic therapies include peptide receptor radiotherapy, somatostatin analogues, cytotoxic chemotherapeutics, and novel molecularly targeted drugs. However, despite the variety of treatments available, there exists little evidence to guide optimal clinical practice with currently available data predominantly retrospective in nature. In this review, we discuss the diagnostic procedures that influence the trajectory of treatment of patients with neuroendocrine liver metastases before critically appraising the evidence pertaining to these therapeutic strategies.
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Affiliation(s)
| | - Andrea Frilling
- Prof. Andrea Frilling, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, DuCane Road, London W12 0NN, United Kingdom, T: 00442083833210, F: 00442083833963,
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Gupta S. Intra-arterial liver-directed therapies for neuroendocrine hepatic metastases. Semin Intervent Radiol 2014; 30:28-38. [PMID: 24436515 DOI: 10.1055/s-0033-1333651] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatic metastases, which are frequently seen in patients with neuroendocrine tumors (NETs), have a major adverse impact on the patient's quality of life and survival. Surgery is the treatment of choice for hepatic metastases but is possible in only a small percentage of patients. Systemic chemotherapy yields disappointing results. Somatostatin analogs are effective in controlling symptoms in many of these patients; however, the disease can become refractory to treatment. Transcatheter intra-arterial liver-directed therapies, such as hepatic artery embolization, chemoembolization, and radioembolization are frequently used in patients with NETs metastatic to the liver, especially in patients with refractory, unresectable, or recurrent disease. These treatments are effective in palliating the hormonal symptoms as well as achieving objective tumor responses. This review focuses on the technique, safety, and clinical efficacy of hepatic artery embolization, chemoembolization, and radioembolization in patients with metastatic NETs.
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Affiliation(s)
- Sanjay Gupta
- Department of Diagnostic Radiology, the University of Texas MD Anderson Cancer Center, Houston, Texas
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Benson AB, Geschwind JF, Mulcahy MF, Rilling W, Siskin G, Wiseman G, Cunningham J, Houghton B, Ross M, Memon K, Andrews J, Fleming CJ, Herman J, Nimeiri H, Lewandowski RJ, Salem R. Radioembolisation for liver metastases: Results from a prospective 151 patient multi-institutional phase II study. Eur J Cancer 2013; 49:3122-30. [DOI: 10.1016/j.ejca.2013.05.012] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Revised: 05/10/2013] [Accepted: 05/14/2013] [Indexed: 12/14/2022]
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Overview of neuroendocrine liver metastases treatment. EJC Suppl 2012. [DOI: 10.1016/s1359-6349(12)70048-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Memon K, Lewandowski RJ, Riaz A, Salem R. Chemoembolization and Radioembolization for Metastatic Disease to the Liver: Available Data and Future Studies. Curr Treat Options Oncol 2012; 13:403-15. [DOI: 10.1007/s11864-012-0200-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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A multimodal approach to the management of neuroendocrine tumour liver metastases. Int J Hepatol 2012; 2012:819193. [PMID: 22518323 PMCID: PMC3296190 DOI: 10.1155/2012/819193] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Accepted: 12/02/2011] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine tumours (NETs) are often indolent malignancies that commonly present with metastatic disease in the liver. Surgical, locoregional, and systemic treatment modalities are reviewed. A multidisciplinary approach to patient care is suggested to ensure all therapeutic options explored.
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Abstract
In the care of patients with hepatic neuroendocrine metastases, medical oncologists should work in multidisciplinary fashion with surgeons, interventional radiologists, and radiation oncologists to assess the potential utility of liver-directed and systemic therapies. This paper addresses the various roles and evidence basis for cytoreductive surgery, thermal ablation (radiofrequency, microwave, and cryoablation), and embolization (bland embolization (HAE), chemoembolization (HACE), and radioembolization) as liver-directed therapies. Somatostatin analogues, cytotoxic chemotherapy, and the newer agents everolimus and suntinib are discussed as a means for controlling intra- and extrahepatic disease, along with peptide receptor radiotherapy (PRRT). Finally, the experience with orthotopic liver transplant for neuroendocrine tumors is described.
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Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes. Int J Radiat Oncol Biol Phys 2011; 83:887-94. [PMID: 22137020 DOI: 10.1016/j.ijrobp.2011.07.041] [Citation(s) in RCA: 121] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Revised: 07/14/2011] [Accepted: 07/28/2011] [Indexed: 12/17/2022]
Abstract
PURPOSE To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. METHODS AND MATERIALS This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with (90)Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. RESULTS The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden ≤25% (p = 0.0019), albumin ≥3.5 g/dL (p = 0.017), and bilirubin ≤1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin ≤1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). CONCLUSION Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival with low toxicity, in line with published national guidelines recommending radioembolization as a potential option for unresectable hepatic neuroendocrine metastases.
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Lewis MA, Hubbard J. Multimodal liver-directed management of neuroendocrine hepatic metastases. Int J Hepatol 2011; 2011:452343. [PMID: 22121491 PMCID: PMC3205732 DOI: 10.4061/2011/452343] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Revised: 08/22/2011] [Accepted: 09/18/2011] [Indexed: 12/23/2022] Open
Abstract
A preponderance of patients with neuroendocrine tumors (NETs) will experience hepatic metastases during the course of their disease. Many diagnoses of NETs are made only after the neoplasms have spread from their primary gastroenteropancreatic sites to the liver. This paper reviews current evidence-based treatments for neuroendocrine hepatic metastases, encompassing surgery, hepatic artery embolization (HAE) and chemoembolization (HACE), radioembolization, hepatic artery infusion (HAI), thermal ablation (radiofrequency, microwave, and cryoablation), alcohol ablation, and liver transplantation as therapeutic modalities. Consideration of a multidisciplinary approach to liver-directed therapy is strongly encouraged to limit morbidity and mortality in this patient population.
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