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1
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Shannon AB, Zager JS. Regional Therapies for Melanoma and Merkel Cell Carcinoma. Surg Clin North Am 2025; 105:591-613. [PMID: 40412888 DOI: 10.1016/j.suc.2024.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
Melanoma and Merkel cell carcinoma (MCC) have the potential to develop into advanced, regionally metastatic disease that is not always amenable to resection and is associated with a worse survival. Intralesional therapies, including oncolytic vaccines, xanthene dyes, immune modulating cytokines, and regional perfusions such as isolated limb infusion and perfusion, including isolated limb and hepatic perfusion and percutaneous hepatic perfusion, have been used in the treatment of advanced cutaneous and uveal melanoma and MCC. These therapies are effective and have a role in the multimodality treatment of these patients and may be synergistically used with conventional immune and targeted therapies.
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Affiliation(s)
- Adrienne B Shannon
- Department of Cutaneous Oncology, Moffit Cancer Center, 10920 N. McKinley Drive, Room 4.4123, Tampa, FL 33612, USA. https://twitter.com/ABShannonMD
| | - Jonathan S Zager
- Department of Cutaneous Oncology, Moffit Cancer Center, 10920 N. McKinley Drive, Room 4.4123, Tampa, FL 33612, USA; Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, 10920 McKinley Drive, Room 4123, Tampa, FL 33612, USA.
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Balsay-Patel C, Dugan MM, Zager JS. Advances in the management of regionally metastatic melanoma. Surg Oncol 2024; 57:102143. [PMID: 39326128 DOI: 10.1016/j.suronc.2024.102143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/14/2024] [Accepted: 09/19/2024] [Indexed: 09/28/2024]
Abstract
Despite numerous developments in systemic therapy, the prognosis for patients with locoregionally advanced melanoma remains poor. By delivering therapy directly to the targeted area via intralesional injections or intra-arterial isolated infusions, systemic side effects are minimized and oncolytic agents are delivered more directly and effectively to the melanoma. There has been significant progress in recent years with intralesional agents such as Talimogene laherparepvec (T-VEC), PV-10 and TAVOkinase/electrocorporation as well as advances in infusional therapies such as percutaneous hepatic perfusion (PHP) for hepatic metastasis of ocular melanoma. This review evaluates advances in intralesional and infusional therapies for melanoma while limiting discussion to those therapies currently approved and on trial.
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Affiliation(s)
- Caitlyn Balsay-Patel
- Department of Surgery, University of South Florida Morsani College of Medicine, USA
| | - Michelle M Dugan
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Jonathan S Zager
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA; Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa FL, USA.
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3
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Olofsson Bagge R, Nelson A, Shafazand A, Cahlin C, Carneiro A, Helgadottir H, Levin M, Rizell M, Ullenhag G, Wirén S, Lindnér P, Nilsson JA, Ny L. A phase Ib randomized multicenter trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab for uveal melanoma metastases (SCANDIUM II trial). ESMO Open 2024; 9:103623. [PMID: 38959698 PMCID: PMC11269777 DOI: 10.1016/j.esmoop.2024.103623] [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: 03/21/2024] [Revised: 06/02/2024] [Accepted: 06/03/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND Uveal melanoma (UM) is a rare malignancy where 50% of patients develop metastatic disease primarily affecting the liver. Approximately 40% of patients with metastatic UM respond to one-time isolated hepatic perfusion (IHP) with high-dose melphalan. This phase I trial investigates the safety and clinical efficacy of IHP combined with ipilimumab (IPI) and nivolumab (NIVO). PATIENTS AND METHODS Immunotherapy-naïve patients were randomized in this phase I trial to receive either IHP followed by IPI 3 mg/kg and NIVO 1 mg/kg (IPI3/NIVO1) for four cycles (post-operative arm), or one cycle of preoperative IPI3/NIVO1, IHP and then three cycles of IPI3/NIVO1 (pre-post-operative arm), followed by maintenance therapy with NIVO 480 mg for 1 year. RESULTS Eighteen patients were enrolled and randomized. Three patients did not undergo IHP as planned. In total, 11/18 patients (6 in the post-operative arm and 5 in the pre-post-operative arm) did not complete the planned four cycles of IPI3/NIVO1. Toxicity to IHP was similar in both groups, but the number of immune-related adverse events (AEs) was higher in the pre-post-operative arm. Among assessable patients, overall response rate was 57% in the post-operative arm (4/7) and 22% in the pre-post-operative arm (2/9). CONCLUSIONS Combination therapy with IHP and IPI3/NIVO1 was associated with severe AEs. The efficacy of this combination is encouraging with high response rates. One cycle of preoperative IPI/NIVO before IHP did not show potential benefits in terms of safety or efficacy.
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Affiliation(s)
- R Olofsson Bagge
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg; Department of Surgery, Sahlgrenska University Hospital, Gothenburg; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg.
| | - A Nelson
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Department of Oncology, Sahlgrenska University Hospital, Gothenburg
| | - A Shafazand
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg
| | - C Cahlin
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg
| | - A Carneiro
- Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital Comprehensive Cancer Center, Lund
| | - H Helgadottir
- Department of Oncology, Karolinska University Hospital, Stockholm
| | - M Levin
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Department of Oncology, Sahlgrenska University Hospital, Gothenburg
| | - M Rizell
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg
| | - G Ullenhag
- Department of Radiology, Immunology, Genetics, and Pathology, Uppsala University, Uppsala
| | - S Wirén
- Department of Radiation Sciences, Umeå University Hospital, Umeå, Sweden
| | - P Lindnér
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg
| | - J A Nilsson
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg; Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia
| | - L Ny
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Department of Oncology, Sahlgrenska University Hospital, Gothenburg
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Dugan MM, Shannon AB, DePalo DK, Perez MC, Zager JS. Intralesional and Infusional Updates for Metastatic Melanoma. Cancers (Basel) 2024; 16:1957. [PMID: 38893078 PMCID: PMC11171204 DOI: 10.3390/cancers16111957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/13/2024] [Accepted: 05/19/2024] [Indexed: 06/21/2024] Open
Abstract
Locoregionally advanced and metastatic melanoma represent a challenging clinical problem, but in the era of immune checkpoint blockade and intralesional and infusional therapies, more options are available for use. Isolated limb infusion (ILI) was first introduced in the 1990s for the management of advanced melanoma, followed by the utilization of isolated extremity perfusion (ILP). Following this, intralesional oncolytic viruses, xanthene dyes, and cytokines were introduced for the management of in-transit metastases as well as unresectable, advanced melanoma. In 2015, the Food and Drug Administration (FDA) approved the first oncolytic intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of advanced melanoma. Additionally, immune checkpoint inhibition has demonstrated efficacy in the management of advanced melanomas, and this improvement in outcomes has been extrapolated to aid in the management of in-transit metastatic disease. Finally, percutaneous hepatic perfusion (PHP), also approved by the FDA, has been reported to have a significant impact on the treatment of hepatic disease in uveal melanoma. While some of these treatments have less utility due to inferior outcomes as well as higher toxicity profiles, there are selective patient profiles for which these therapies carry a role. This review highlights intralesional and infusional therapies for the management of metastatic melanoma.
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Affiliation(s)
- Michelle M. Dugan
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (M.M.D.); (A.B.S.); (D.K.D.); (M.C.P.)
| | - Adrienne B. Shannon
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (M.M.D.); (A.B.S.); (D.K.D.); (M.C.P.)
| | - Danielle K. DePalo
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (M.M.D.); (A.B.S.); (D.K.D.); (M.C.P.)
- Department of General Surgery, University of Massachusetts Chan Medical School, Boston, MA 01655, USA
| | - Matthew C. Perez
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (M.M.D.); (A.B.S.); (D.K.D.); (M.C.P.)
| | - Jonathan S. Zager
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (M.M.D.); (A.B.S.); (D.K.D.); (M.C.P.)
- Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL 33602, USA
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Croley CR, Pumarol J, Delgadillo BE, Cook AC, Day F, Kaceli T, Ward CC, Husain I, Husain A, Banerjee S, Bishayee A. Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals. Pharmacol Ther 2023:108479. [PMID: 37330112 DOI: 10.1016/j.pharmthera.2023.108479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 06/05/2023] [Accepted: 06/12/2023] [Indexed: 06/19/2023]
Abstract
Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed.
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Affiliation(s)
- Courtney R Croley
- Healthcare Corporation of America, Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Hudson, FL 34667, USA
| | - Joshua Pumarol
- Ross University School of Medicine, Miramar, FL 33027, USA
| | - Blake E Delgadillo
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Andrew C Cook
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Faith Day
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Tea Kaceli
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Caroline C Ward
- Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA
| | - Imran Husain
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USA
| | - Ali Husain
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USA
| | - Sabyasachi Banerjee
- Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol 713 301, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.
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Olofsson Bagge R, Nelson A, Shafazand A, All-Eriksson C, Cahlin C, Elander N, Helgadottir H, Kiilgaard JF, Kinhult S, Ljuslinder I, Mattsson J, Rizell M, Sternby Eilard M, Ullenhag GJ, Nilsson JA, Ny L, Lindnér P. Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial). J Clin Oncol 2023; 41:3042-3050. [PMID: 36940407 PMCID: PMC10414734 DOI: 10.1200/jco.22.01705] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 02/09/2023] [Indexed: 03/22/2023] Open
Abstract
PURPOSE About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking. METHODS In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group. CONCLUSION IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
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Affiliation(s)
- Roger Olofsson Bagge
- Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Axel Nelson
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Amir Shafazand
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
- Department of Radiology, Alingsås Hospital, Alingsås, Sweden
| | - Charlotta All-Eriksson
- Department of Ophthalmology, Mölndal Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Christian Cahlin
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Nils Elander
- Department of Oncology and Department of Clinical and Biomedical Sciences, Linköping University, Linköping, Sweden
| | - Hildur Helgadottir
- Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
| | - Jens Folke Kiilgaard
- Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital Copenhagen, Copenhagen, Denmark
| | - Sara Kinhult
- Department of Oncology, Skåne University Hospital, Lund, Sweden
| | - Ingrid Ljuslinder
- Department of Radiation Sciences, Oncology, Umeå University Hospital, Umeå, Sweden
| | - Jan Mattsson
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Magnus Rizell
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Malin Sternby Eilard
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Gustav J. Ullenhag
- Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden
- Department of Oncology, Uppsala University Hospital, Uppsala, Sweden
| | - Jonas A. Nilsson
- Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lars Ny
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Per Lindnér
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
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7
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Carvajal RD, Sacco JJ, Jager MJ, Eschelman DJ, Olofsson Bagge R, Harbour JW, Chieng ND, Patel SP, Joshua AM, Piperno-Neumann S. Advances in the clinical management of uveal melanoma. Nat Rev Clin Oncol 2023; 20:99-115. [PMID: 36600005 DOI: 10.1038/s41571-022-00714-1] [Citation(s) in RCA: 114] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2022] [Indexed: 01/05/2023]
Abstract
Melanomas arising in the uveal tract of the eye are a rare form of the disease with a biology and clinical phenotype distinct from their more common cutaneous counterparts. Treatment of primary uveal melanoma with radiotherapy, enucleation or other modalities achieves local control in more than 90% of patients, although 40% or more ultimately develop distant metastases, most commonly in the liver. Until January 2022, no systemic therapy had received regulatory approval for patients with metastatic uveal melanoma, and these patients have historically had a dismal prognosis owing to the limited efficacy of the available treatments. A series of seminal studies over the past two decades have identified highly prevalent early, tumour-initiating oncogenic genomic aberrations, later recurring prognostic alterations and immunological features that characterize uveal melanoma. These advances have driven the development of a number of novel emerging treatments, including tebentafusp, the first systemic therapy to achieve regulatory approval for this disease. In this Review, our multidisciplinary and international group of authors summarize the biology of uveal melanoma, management of primary disease and surveillance strategies to detect recurrent disease, and then focus on the current standard and emerging regional and systemic treatment approaches for metastatic uveal melanoma.
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Affiliation(s)
- Richard D Carvajal
- Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
| | - Joseph J Sacco
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Martine J Jager
- Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands
| | - David J Eschelman
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | | | - J William Harbour
- Department of Ophthalmology and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
| | - Nicholas D Chieng
- Medical Imaging Services, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Sapna P Patel
- Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Anthony M Joshua
- Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital Sydney and Garvan Institute of Medical Research, Sydney, New South Wales, Australia.,School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, UNSW, Sydney, New South Wales, Australia
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Reiter S, Schroeder C, Broche J, Sinnberg T, Bonzheim I, Süsskind D, Flatz L, Forschner A. Successful treatment of metastatic uveal melanoma with ipilimumab and nivolumab after severe progression under tebentafusp: a case report. Front Oncol 2023; 13:1167791. [PMID: 37207136 PMCID: PMC10189013 DOI: 10.3389/fonc.2023.1167791] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 04/19/2023] [Indexed: 05/21/2023] Open
Abstract
Metastatic uveal melanoma (UM) is a rare form of melanoma differing from cutaneous melanoma by etiology, prognosis, driver mutations, pattern of metastases and poor response rate to immune checkpoint inhibitors (ICI). Recently, a bispecific gp100 peptide-HLA-directed CD3 T cell engager, tebentafusp, has been approved for the treatment of HLA-A*02:01 metastatic or unresectable UM. While the treatment regime is complex with weekly administrations and close monitoring, the response rate is limited. Only a few data exist on combined ICI in UM after previous progression on tebentafusp. In this case report, we present a patient with metastatic UM who first suffered extensive progression under treatment with tebentafusp but in the following had an excellent response to combined ICI. We discuss possible interactions that could explain responsiveness to ICI after pretreatment with tebentafusp in advanced UM.
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Affiliation(s)
- Selina Reiter
- Department of Dermatology, University Hospital of Tübingen, Tübingen, Germany
| | - Christopher Schroeder
- Institute of Medical Genetics and Applied Genomics, University Hospital of Tübingen, Tübingen, Germany
| | - Julian Broche
- Institute of Medical Genetics and Applied Genomics, University Hospital of Tübingen, Tübingen, Germany
| | - Tobias Sinnberg
- Department of Dermatology, University Hospital of Tübingen, Tübingen, Germany
| | - Irina Bonzheim
- Institute of Pathology and Neuropathology, University Hospital of Tübingen, Tübingen, Germany
| | - Daniela Süsskind
- Department of Ophthalmology, University Hospital of Tübingen, Tübingen, Germany
| | - Lukas Flatz
- Department of Dermatology, University Hospital of Tübingen, Tübingen, Germany
| | - Andrea Forschner
- Department of Dermatology, University Hospital of Tübingen, Tübingen, Germany
- *Correspondence: Andrea Forschner,
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9
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Toro MD, Gozzo L, Tracia L, Cicciù M, Drago F, Bucolo C, Avitabile T, Rejdak R, Nowomiejska K, Zweifel S, Yousef YA, Nazzal R, Romano GL. New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review. Biomedicines 2021; 9:biomedicines9101311. [PMID: 34680428 PMCID: PMC8533164 DOI: 10.3390/biomedicines9101311] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/15/2021] [Accepted: 09/21/2021] [Indexed: 12/13/2022] Open
Abstract
Uveal melanoma (UM) is a rare disease, but the most common primary intraocular cancer, mostly localized in the choroid. Currently, the first-line treatment options for UM are radiation therapy, resection, and enucleation. However, although these treatments could potentially be curative, half of all patients will develop metastatic disease, whose prognosis is still poor. Indeed, effective therapeutic options for patients with advanced or metastatic disease are still lacking. Recently, the development of new treatment modalities with a lower incidence of adverse events, a better disease control rate, and new therapeutic approaches, have merged as new potential and promising therapeutic strategies. Additionally, several clinical trials are ongoing to find new therapeutic options, mainly for those with metastatic disease. Many interventions are still in the preliminary phases of clinical development, being investigated in phase I trial or phase I/II. The success of these trials could be crucial for changing the prognosis of patients with advanced/metastatic UM. In this systematic review, we analyzed all emerging and available literature on the new perspectives in the treatment of UM and patient outcomes; furthermore, their current limitations and more common adverse events are summarized.
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Affiliation(s)
- Mario Damiano Toro
- Department of Ophthalmology, University of Zurich, 8091 Zurich, Switzerland; (M.D.T.); (S.Z.)
- Department of General and Pediatric Ophthalmology, Medical University of Lublin, 20079 Lublin, Poland; (R.R.); (K.N.)
| | - Lucia Gozzo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (F.D.); (C.B.); (G.L.R.)
- Clinical Pharmacology Unit, Regional Pharmacovigilance Centre, University Hospital of Catania, 95123 Catania, Italy
- Correspondence: ; Tel.: +39-095-3781757
| | - Luciano Tracia
- Plastic and Reconstructive Surgery Department, American Hospital Dubai, Dubai, United Arab Emirates;
| | - Marco Cicciù
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, AOU ‘G. Martino’, 98124 Messina, Italy;
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (F.D.); (C.B.); (G.L.R.)
- Clinical Pharmacology Unit, Regional Pharmacovigilance Centre, University Hospital of Catania, 95123 Catania, Italy
- Centre for Research and Consultancy in HTA and Drug Regulatory Affairs (CERD), University of Catania, 95123 Catania, Italy
| | - Claudio Bucolo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (F.D.); (C.B.); (G.L.R.)
- Center of Research in Ocular Pharmacology—CERFO, University of Catania, 95123 Catania, Italy
| | - Teresio Avitabile
- Department of Ophthalmology, University of Catania, 95123 Catania, Italy;
| | - Robert Rejdak
- Department of General and Pediatric Ophthalmology, Medical University of Lublin, 20079 Lublin, Poland; (R.R.); (K.N.)
| | - Katarzyna Nowomiejska
- Department of General and Pediatric Ophthalmology, Medical University of Lublin, 20079 Lublin, Poland; (R.R.); (K.N.)
| | - Sandrine Zweifel
- Department of Ophthalmology, University of Zurich, 8091 Zurich, Switzerland; (M.D.T.); (S.Z.)
| | - Yacoub A. Yousef
- Department of Surgery/Ophthalmology, King Hussein Cancer Center, Amman 11941, Jordan;
| | | | - Giovanni Luca Romano
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (F.D.); (C.B.); (G.L.R.)
- Center of Research in Ocular Pharmacology—CERFO, University of Catania, 95123 Catania, Italy
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Bethlehem MS, Katsarelias D, Olofsson Bagge R. Meta-Analysis of Isolated Hepatic Perfusion and Percutaneous Hepatic Perfusion as a Treatment for Uveal Melanoma Liver Metastases. Cancers (Basel) 2021; 13:cancers13184726. [PMID: 34572953 PMCID: PMC8469397 DOI: 10.3390/cancers13184726] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/17/2021] [Accepted: 09/19/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary Isolated hepatic perfusion is one of the available treatment options for patients with liver metastases from uveal melanoma. This is an open surgical procedure where the liver is isolated from the circulation and perfused with a chemotherapeutic agent. A modern development is the minimally invasive percutaneous hepatic perfusion, where the liver is endovascularly isolated and then perfused with a chemotherapeutic agent through a catheter in the arterial system. Within this systematic review and meta-analysis, we aim to compare these modalities in terms of overall survival, progression-free survival, complications and response. Abstract Background: Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous hepatic perfusion (PHP), a minimally invasive technique, is available as well. PHP benefits from the fact that the procedure can be repeated and therefore possibly offers better survival. We conducted a systematic review and meta-analysis comparing both techniques. Methods: A systematic literature search was performed using the electronic databases of Scopus, MEDLINE, Web of Science, PubMed and Cochrane CENTRAL. A total of nine articles reporting on eight studies were included in the analysis. Individual survival data were extracted from each study. Results: The median overall survival (OS) was 17.1 months for IHP and 17.3 months for PHP. The median progression-free survival (PFS) was 7.2 months for IHP and 9.6 months for PHP. The median hepatic progression-free survival was 10 months for IHP and 9.5 months for PHP. The complication rate and 30-day mortality rate were 39.1% and 5.5% for IHP and 23.8% and 1.8% for PHP. Conclusion: There was no difference in OS or PFS between IHP and PHP for patients with uveal melanoma liver metastases, but patients have significantly less of a risk for complications and mortality following PHP.
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Affiliation(s)
- Martijn S. Bethlehem
- Department of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden; (D.K.); (R.O.B.)
- Institute of Clinical Sciences/Sahlgrenska Academy, University of Gothenburg, 413 90 Gothenburg, Sweden
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 413 45 Gothenburg, Sweden
- Correspondence:
| | - Dimitrios Katsarelias
- Department of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden; (D.K.); (R.O.B.)
- Institute of Clinical Sciences/Sahlgrenska Academy, University of Gothenburg, 413 90 Gothenburg, Sweden
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 413 45 Gothenburg, Sweden
| | - Roger Olofsson Bagge
- Department of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden; (D.K.); (R.O.B.)
- Institute of Clinical Sciences/Sahlgrenska Academy, University of Gothenburg, 413 90 Gothenburg, Sweden
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 413 45 Gothenburg, Sweden
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Szeligo BM, Ivey AD, Boone BA. Poor Response to Checkpoint Immunotherapy in Uveal Melanoma Highlights the Persistent Need for Innovative Regional Therapy Approaches to Manage Liver Metastases. Cancers (Basel) 2021; 13:3426. [PMID: 34298647 PMCID: PMC8307800 DOI: 10.3390/cancers13143426] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/24/2021] [Accepted: 07/02/2021] [Indexed: 12/12/2022] Open
Abstract
Uveal melanoma is a cancer that develops from melanocytes in the posterior uveal tract. Metastatic uveal melanoma is an extremely rare disease that has a poor long-term prognosis, limited treatment options and a strong predilection for liver metastasis. Median overall survival has been reported to be 6 months and 1 year mortality of 80%. Traditional chemotherapy used in cutaneous melanoma is ineffective in uveal cases. Surgical resection and ablation is the preferred therapy for liver metastasis but is often not feasible due to extent of disease. In this review, we will explore treatment options for liver metastases from uveal melanoma, with a focus on isolated hepatic perfusion (IHP). IHP offers an aggressive regional therapy approach that can be used in bulky unresectable disease and allows high-dose chemotherapy with melphalan to be delivered directly to the liver without systemic effects. Long-term median overall survival has been reported to be as high as 27 months. We will also highlight the poor responses associated with checkpoint inhibitors, including an overview of the biological rationale driving this lack of immunotherapy effect for this disease. The persistent failure of traditional treatments and immunotherapy suggest an ongoing need for regional surgical approaches such as IHP in this disease.
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Affiliation(s)
- Brett M. Szeligo
- Division of Surgical Oncology, Department of Surgery, West Virginia University, Morgantown, WV 26508, USA;
| | - Abby D. Ivey
- Cancer Cell Biology, West Virginia University, Morgantown, WV 26508, USA;
| | - Brian A. Boone
- Division of Surgical Oncology, Department of Surgery, West Virginia University, Morgantown, WV 26508, USA;
- Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26508, USA
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Foti PV, Travali M, Farina R, Palmucci S, Spatola C, Liardo RLE, Milazzotto R, Raffaele L, Salamone V, Caltabiano R, Broggi G, Puzzo L, Russo A, Reibaldi M, Longo A, Vigneri P, Avitabile T, Ettorre GC, Basile A. Diagnostic methods and therapeutic options of uveal melanoma with emphasis on MR imaging-Part II: treatment indications and complications. Insights Imaging 2021; 12:67. [PMID: 34085131 PMCID: PMC8175681 DOI: 10.1186/s13244-021-01001-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 04/21/2021] [Indexed: 12/31/2022] Open
Abstract
Therapy of uveal melanoma aims to preserve the eye and its function and to avoid metastatic dissemination. The treatment choice is difficult and must keep into account several factors; the therapeutic strategy of uveal melanoma should therefore be personalized, sometimes requiring to combine different treatment techniques. Nowadays globe-sparing radiotherapy techniques are often preferred to enucleation. Plaque brachytherapy, the most commonly used eye-preserving therapy, is suitable for small- and medium-sized uveal melanomas. Proton beam radiotherapy is indicated for tumours with noticeable size, challenging shape and location, but is more expensive and less available than brachytherapy. Enucleation is currently restricted to advanced tumours, uveal melanomas with orbital or optic nerve involvement, blind and painful eyes because of treatment-related complications (neovascular glaucoma, chronic inflammatory processes). The effect of proton beam therapy on neoplastic tissue is related to direct cytotoxic action of the radiations, impairment of neoplastic vascular supply and immunologic response. Complications after radiotherapy are frequent and numerous and mainly related to tumour thickness, radiation dose and distance between the tumour and optic nerve. The purpose of this pictorial review is to provide the radiologists with awareness about diagnostic methods and therapeutic options of uveal melanoma. In the present second section, we discuss the therapeutic management of uveal melanoma, describing the main ocular-conserving radiotherapic techniques. We subsequently present an overview of the effects of radiations on neoplastic tissue. Lastly, we review ocular complications following radiotherapy that should be evaluated by radiologists during follow-up MRI examinations.
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Affiliation(s)
- Pietro Valerio Foti
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy.
| | - Mario Travali
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Renato Farina
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Stefano Palmucci
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Corrado Spatola
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Rocco Luca Emanuele Liardo
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Roberto Milazzotto
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Luigi Raffaele
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Vincenzo Salamone
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Rosario Caltabiano
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Section of Anatomic Pathology, University of Catania, Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Giuseppe Broggi
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Section of Anatomic Pathology, University of Catania, Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Lidia Puzzo
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Section of Anatomic Pathology, University of Catania, Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Andrea Russo
- Department of Ophthalmology, University of Catania, Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Michele Reibaldi
- Department of Ophthalmology, University of Catania, Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Antonio Longo
- Department of Ophthalmology, University of Catania, Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Paolo Vigneri
- Department of Clinical and Experimental Medicine, Center of Experimental Oncology and Hematology, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Teresio Avitabile
- Department of Ophthalmology, University of Catania, Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Giovani Carlo Ettorre
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
| | - Antonio Basile
- Department of Medical Surgical Sciences and Advanced Technologies "G.F. Ingrassia" - Radiology I Unit, University Hospital Policlinico "G. Rodolico-San Marco", Via Santa Sofia, 78 - 95123, Catania, Italy
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Carle X, Gastaud L, Salleron J, Tardy MP, Caujolle JP, Thyss A, Thariat J, Chevallier P. Optimizing the treatment of liver metastases from uveal melanomas with transarterial chemoembolization using melphalan and calibrated microspheres. Bull Cancer 2020; 107:1274-1283. [PMID: 33183739 DOI: 10.1016/j.bulcan.2020.09.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 09/14/2020] [Accepted: 09/27/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Patients with liver metastasis from uveal melanoma have a poor prognosis. Efficacy and safety of hepatic transarterial chemoembolization (TACE) using melphalan and microspheres was evaluated. MATERIALS AND METHODS Monocentric retrospective study of all consecutive patients treated by TACE using melphalan and 250μm calibrated microspheres between 2004 and 2016. Radiological response was assessed according to RECIST 1.1, modified (m)-RECIST and EASL on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The primary endpoint was overall survival (OS). Liver metastasis response, hepatic, extrahepatic and global progression free survival (PFS) complications were evaluated with the common terminology criteria for adverse events version 4.0 (CTCAE 4.0) and survival factors were secondary endpoints. RESULTS Thirty-four patients underwent 138 TACE (4; 4.1 sessions; range 1-9). Median OS was 16.5 months (mean 21.6 months). Liver metastasis response combining partial and complete response was 42.4%, 97%, 97% with RECIST 1.1, mRECIST, EASL, respectively. There were 58 severe (CTCAE≥3) but manageable complications in 28 patients, except for 1 toxic death. CONCLUSION For patients with liver metastases from uveal melanoma ineligible for local treatments, TACE using melphalan may be performed as first line therapy in metastatic miliary disease from uveal melanomas with careful supportive care.
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Affiliation(s)
- Xavier Carle
- University Hospital Archet 2, Department of Diagnostic and Interventional Radiology, 151 Route de Saint-Antoine, 06200 Nice, France
| | - Lauris Gastaud
- Antoine-Lacassagne Centre, Cancer Research Center, Department of Oncology, 133, avenue de Valombrose, 06189 Nice, France
| | - Julia Salleron
- Lorraine Institute of Oncology, Department of Biostatistics, 6 avenue de Bourgogne, 54519 Vandoeuvre-lès-Nancy, France
| | - Magali Pascale Tardy
- Antoine-Lacassagne Centre, Cancer Research Center, Department of Oncology, 133, avenue de Valombrose, 06189 Nice, France
| | - Jean-Pierre Caujolle
- University Hospital Pasteur 2, Department of Ophtalmology, 30, voie Romaine, 06001 Nice, France
| | - Antoine Thyss
- Antoine-Lacassagne Centre, Cancer Research Center, Department of Oncology, 133, avenue de Valombrose, 06189 Nice, France
| | - Juliette Thariat
- Francois-Baclesse Centre, Cancer Research Center, Department of Oncology, 3, avenue du Général Harris, 14000 Caen, France
| | - Patrick Chevallier
- University Hospital Archet 2, Department of Diagnostic and Interventional Radiology, 151 Route de Saint-Antoine, 06200 Nice, France.
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14
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Mallone F, Sacchetti M, Lambiase A, Moramarco A. Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma. Cancers (Basel) 2020; 12:E2761. [PMID: 32992823 PMCID: PMC7600598 DOI: 10.3390/cancers12102761] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/14/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022] Open
Abstract
Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.
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Affiliation(s)
| | | | - Alessandro Lambiase
- Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy; (F.M.); (M.S.); (A.M.)
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Rowcroft A, Loveday BPT, Thomson BNJ, Banting S, Knowles B. Systematic review of liver directed therapy for uveal melanoma hepatic metastases. HPB (Oxford) 2020; 22:497-505. [PMID: 31791894 DOI: 10.1016/j.hpb.2019.11.002] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 10/29/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Uveal melanoma (UM) is a rare malignancy with a propensity for metastasis to the liver. Systemic chemotherapy is typically ineffective in these patients with liver metastases and overall survival is poor. There are no evidence-based guidelines for management of UM liver metastases. The aim of this study was to review the evidence for management of UM liver metastases. METHODS A systematic review of English literature publications was conducted across Ovid Medline, Ovid MEDLINE and Cochrane CENTRAL databases until April 2019. The primary outcome was overall survival, with disease free survival as a secondary outcome. RESULTS 55 studies were included in the study, with 2446 patients treated overall. The majority of these studies were retrospective, with 17 of 55 including comparative data. Treatment modalities included surgery, isolated hepatic perfusion (IHP), hepatic artery infusion (HAI), transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) and Immunoembolization (IE). Survival varied greatly between treatments and between studies using the same treatments. Both surgery and liver-directed treatments were shown to have benefit in selected patients. CONCLUSION Predominantly retrospective and uncontrolled studies suggest that surgery and locoregional techniques may prolong survival. Substantial variability in patient selection and study design makes comparison of data and formulation of recommendations challenging.
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Affiliation(s)
- Alistair Rowcroft
- Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Benjamin P T Loveday
- Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Benjamin N J Thomson
- Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Surgery, University of Melbourne, Melbourne, Australia
| | - Simon Banting
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Brett Knowles
- Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
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Iterative treatment with surgery and radiofrequency ablation of uveal melanoma liver metastasis: Retrospective analysis of a series of very long-term survivors. Eur J Surg Oncol 2019; 45:1717-1722. [DOI: 10.1016/j.ejso.2019.06.036] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 03/20/2019] [Accepted: 06/24/2019] [Indexed: 12/12/2022] Open
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Development of a Prognostic Nomogram for Liver Metastasis of Uveal Melanoma Patients Selected by Liver MRI. Cancers (Basel) 2019; 11:cancers11060863. [PMID: 31234340 PMCID: PMC6627813 DOI: 10.3390/cancers11060863] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 06/17/2019] [Accepted: 06/19/2019] [Indexed: 12/17/2022] Open
Abstract
Patients with liver metastases of uveal melanoma (LMUM) die from their metastatic evolution within 2 years. We established a nomogram to choose a treatment adapted to life expectancy. From 2002 to 2013, we reviewed 224 patients with LMUM selected by liver MRI. A nomogram was developed based on a Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan–Meier curve, and calibration plots. The median follow-up was 49.2 months (range, 0.6–70.9). The survival rates at 6, 12, and 24 months were 0.88 (0.95 CI [0.84–0.93]), 0.68 (0.95 CI [0.62–0.75]), and 0.26 (0.95 CI [0.21–0.33]), respectively. The four factors selected for the nomogram with a worse prognosis were: A disease-free interval between the UM and LMUM groups of less than 6 months (HR = 3.39; 0.95 CI [1.90–6.05]), more than 10 LMUM (HR = 3.95; 0.95 CI [1.97–4.43]), a maximum LMUM of more than 1200 mm2 (HR = 2.47; 0.95 CI [1.53–3.98]), and a lactate dehydrogenase (LDH) value greater than 1.5 (HR = 3.72; 0.95 CI [2.30–6.00]). The model achieved relatively good discrimination and calibration (C-statistic 0.71). This nomogram could be useful for decision-making and risk stratification for therapeutic options.
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Local treatment of liver metastases by administration of 177Lu-octreotate via isolated hepatic perfusion - A preclinical simulation of a novel treatment strategy. Surg Oncol 2019; 29:148-156. [PMID: 31196481 DOI: 10.1016/j.suronc.2019.05.002] [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: 11/09/2018] [Revised: 04/17/2019] [Accepted: 05/10/2019] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Systemic 177Lu-octreotate treatment for metastatic neuroendocrine tumours is restricted by organs at risk. By administering 177Lu-octreotate during isolated hepatic perfusion (IHP), the uptake in organs at risk might be strongly reduced. The aim of this study was to investigate the feasibility to use the combination of IHP and radionuclide therapy. METHODS To simulate IHP, the liver of a pig was prepared for ex vivo perfusion. Blood containing 490 MBq 177Lu-octreotate was circulated through the liver for 60 min, after which the liver was rinsed. After IHP, the liver was examined by SPECT/CT. Lastly, an intraoperative gamma detector (IGD) was used to determine 177Lu activity concentration in the liver and results were compared with the activity concentration in corresponding liver biopsies. RESULTS Detector measurements over the liver during the IHP showed a fast increase with a maximum after approximately 10-15 min. After IHP, about 75% of the 177Lu in the liver could be washed out. The SPECT/CT images revealed a relatively inhomogeneous distribution. Nevertheless, the IGD values of 177Lu activity concentration showed acceptable agreement with the biopsy values. CONCLUSIONS Our results in pig show that it could be feasible to treat patients with liver metastases from NETs with 177Lu-octreotate via IHP 177. However, an inhomogeneous distribution of 177Lu-octreotate in normal liver tissue is expected, and in order to determine the activity concentration with satisfactory accuracy using an IGD, measurements need to be performed at several positions over the liver.
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Violanti SS, Bononi I, Gallenga CE, Martini F, Tognon M, Perri P. New Insights into Molecular Oncogenesis and Therapy of Uveal Melanoma. Cancers (Basel) 2019; 11:E694. [PMID: 31109147 PMCID: PMC6562554 DOI: 10.3390/cancers11050694] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/14/2019] [Accepted: 05/15/2019] [Indexed: 12/15/2022] Open
Abstract
Uveal melanoma (UM), which is the most common cancer of the eye, was investigated in recent years by many teams in the field of biomedical sciences and eye clinicians. New knowledge was acquired on molecular pathways found to be dysregulated during the multistep process of oncogenesis, whereas novel therapeutic approaches gave significant results in the clinical applications. Uveal melanoma-affected patients greatly benefited from recent advances of the research in this eye cancer. Tumour biology, genetics, epigenetics and immunology contributed significantly in elucidating the role of different genes and related pathways during uveal melanoma onset/progression and UM treatments. Indeed, these investigations allowed identification of new target genes and to develop new therapeutic strategies/compounds to cure this aggressive melanoma of the eye. Unfortunately, the advances reported in the treatment of cutaneous melanoma have not produced analogous benefits in metastatic uveal melanoma. Nowadays, no systemic adjuvant therapy has been shown to improve overall survival or reduce the risk of metastasis. However, the increasing knowledge of this disease, and the encouraging results seen in clinical trials, offer promise for future effective therapies. Herein, different pathways/genes involved in uveal melanoma onset/progression were taken into consideration, together with novel therapeutic approaches.
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Affiliation(s)
- Sara Silvia Violanti
- Department of Biomedical Sciences and Specialized Surgeries, School of Medicine, University of Ferrara and Eye Unit of University Hospital of Ferrara, 44124 Ferrara, Italy.
| | - Ilaria Bononi
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, 44121 Ferrara, Italy.
| | - Carla Enrica Gallenga
- Department of Biomedical Sciences and Specialized Surgeries, School of Medicine, University of Ferrara and Eye Unit of University Hospital of Ferrara, 44124 Ferrara, Italy.
| | - Fernanda Martini
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, 44121 Ferrara, Italy.
| | - Mauro Tognon
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, 44121 Ferrara, Italy.
| | - Paolo Perri
- Department of Biomedical Sciences and Specialized Surgeries, School of Medicine, University of Ferrara and Eye Unit of University Hospital of Ferrara, 44124 Ferrara, Italy.
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Abbott AM, Doepker MP, Kim Y, Perez MC, Gandle C, Thomas KL, Choi J, Shridhar R, Zager JS. Hepatic Progression-free and Overall Survival After Regional Therapy to the Liver for Metastatic Melanoma. Am J Clin Oncol 2018; 41:747-753. [PMID: 28059929 PMCID: PMC7771287 DOI: 10.1097/coc.0000000000000356] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
OBJECTIVES Regional therapy for metastatic melanoma to the liver represents an alternative to systemic therapy. Hepatic progression-free survival (HPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. MATERIALS AND METHODS A retrospective review of patients with liver metastases from cutaneous or uveal melanoma treated with yttrium-90 (Y90), chemoembolization (CE), or percutaneous hepatic perfusion (PHP) was conducted. RESULTS Thirty patients (6 Y90, 10 PHP, 12 CE, 1 PHP then Y90, 1 CE then PHP) were included. Multivariate analysis showed improved HPFS for PHP versus Y90 (P=0.004), PHP versus CE (P=0.02) but not for CE versus Y90. PFS was also significantly different: Y90 (54 d), CE (52 d), PHP (245 d), P=0.03. PHP treatment and lower tumor burden were significant predictors of prolonged PFS on multivariate analysis. Median OS from time of treatment was longest, but not significant, for PHP at 608 days versus Y90 (295 d) and CE (265 d), P=0.24. Only PHP treatment versus Y90 and lower tumor burden had improved OS on multivariate analysis (P=0.03, 0.03, respectively). CONCLUSIONS HPFS and PFS were significantly prolonged in patients treated with PHP versus CE or Y90. Median OS in PHP patients was over double that seen in Y90 or CE patients but was significant only between PHP and Y90.
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Affiliation(s)
- Andrea M. Abbott
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL
| | | | - Youngchul Kim
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL
| | - Matthew C. Perez
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL
| | - Cassandra Gandle
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL
| | | | - Junsung Choi
- Department of Interventional Radiology, Moffitt Cancer Center, Tampa, FL
| | - Ravi Shridhar
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL
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Isolated (hypoxic) hepatic perfusion with high-dose chemotherapy in patients with unresectable liver metastases of uveal melanoma: results from two experienced centres. Melanoma Res 2018; 26:588-594. [PMID: 27513071 DOI: 10.1097/cmr.0000000000000286] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Uveal melanoma patients have a poor survival after the diagnosis of metastatic disease. Isolated hepatic perfusion (IHP) was developed to treat patients with unresectable metastases confined to the liver. This retrospective analysis focuses on treatment characteristics, complications, toxicity and survival after IHP. Patients with uveal melanoma metastases confined to the liver treated with IHP in two experienced hepato-pancreatic-biliary surgery centres (Erasmus MC Cancer Institute and Leiden University Medical Center) were included. Between March 1999 and April 2009, 30 patients were treated with IHP. The duration of surgery was 3.7 h (Erasmus MC Cancer Institute) versus 8.7 h (Leiden University Medical Center) and also the dosage of melphalan differed: 1 mg/kg body weight (n=12) versus a dose of 170-200 mg (n=18) or melphalan (100 mg) combined with oxaliplatin (50 or 100 mg) (n=3). The length of hospital stay was 10 days. Two patients developed occlusion of the hepatic artery and died, respectively, 3 days and 1.5 months after surgery. Progression-free survival was 6 (1-16) months and recurrences occurred mainly in the liver. The median overall survival was 10 (3-50) months. IHP is a potentially beneficial treatment modality resulting in a reasonable overall survival for uveal melanoma patients. Because of considerable morbidity related to the open procedure, a percutaneous system has been developed and is currently being investigated.
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Abstract
Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11. Cytogenetic alterations, in particular monosomy of chromosome 3 and amplification of the long arm of chromosome 8, and mutation of the BRCA1-associated protein 1, BAP1, a tumor suppressor gene, or the splicing factor SF3B1 determine UM metastasis. Cytogenetic and molecular profiling allow for a very precise prognostication that is still not matched by efficacious adjuvant therapies. G protein signaling has been shown to activate the YAP/TAZ pathway independent of HIPPO, and conventional signaling via the mitogen-activated kinase pathway probably also contributes to UM development and progression. Several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases. UM cells benefit from the immune privilege in the eye and may adopt several mechanisms involved in this privilege for tumor escape that act even after leaving the niche. Here, we review the current knowledge of the biology of UM and discuss recent approaches to UM treatment.
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Affiliation(s)
- Adriana Amaro
- Laboratory of Molecular Pathology, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, L.go Rosanna Benzi 10, 16132, Genoa, Italy
| | - Rosaria Gangemi
- Laboratory of Biotherapies, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
| | - Francesca Piaggio
- Laboratory of Molecular Pathology, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, L.go Rosanna Benzi 10, 16132, Genoa, Italy
| | - Giovanna Angelini
- Laboratory of Molecular Pathology, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, L.go Rosanna Benzi 10, 16132, Genoa, Italy
| | - Gaia Barisione
- Laboratory of Biotherapies, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
| | - Silvano Ferrini
- Laboratory of Biotherapies, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
| | - Ulrich Pfeffer
- Laboratory of Molecular Pathology, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, L.go Rosanna Benzi 10, 16132, Genoa, Italy.
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Vogl TJ, Koch SA, Lotz G, Gebauer B, Willinek W, Engelke C, Brüning R, Zeile M, Wacker F, Vogel A, Radeleff B, Scholtz JE. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study. Cardiovasc Intervent Radiol 2017; 40:864-872. [PMID: 28144756 DOI: 10.1007/s00270-017-1588-2] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 01/25/2017] [Indexed: 12/22/2022]
Abstract
PURPOSE Percutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study. MATERIALS AND METHODS Between 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients' life quality was assessed using four-point scale questionnaires. RESULTS Of 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6-41.0 months). Median progression-free survival time was 12.4 months (range 0.9-41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients' self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment. CONCLUSION PIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.
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Affiliation(s)
- Thomas J Vogl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
| | - Silvia A Koch
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
| | - Gösta Lotz
- Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
| | - Bernhard Gebauer
- Department of Diagnostic and Interventional Radiology, Campus Charité Mitte, Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Winfried Willinek
- Department of Diagnostic and Interventional Radiology, Brüderkrankenhaus Trier, Nordallee 1, 54292, Trier, Germany
| | - Christoph Engelke
- Department of Diagnostic and Interventional Radiology, Evangelisches Krankenhaus Göttingen-Weende gGmbH, An der Lutter 24, 37075, Göttingen, Germany
| | - Roland Brüning
- Department of Diagnostic and Interventional Radiology, Asklepios Klinik Barmbek, Rübenkamp 220, 22291, Hamburg, Germany
| | - Martin Zeile
- Department of Diagnostic and Interventional Radiology, Asklepios Klinik Barmbek, Rübenkamp 220, 22291, Hamburg, Germany
| | - Frank Wacker
- Department of Diagnostic and Interventional Radiology, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
| | - Boris Radeleff
- Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Voßstraße 2, 69115, Heidelberg, Germany
| | - Jan-Erik Scholtz
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany. .,Cardiac MR PET CT Program, Massachusetts General Hospital, Harvard Medical School, 165 Cambridge StreetSuite 400, Boston, MA, 02141, USA.
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Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD. Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol 2017; 101:38-44. [PMID: 27574175 PMCID: PMC5256122 DOI: 10.1136/bjophthalmol-2016-309034] [Citation(s) in RCA: 284] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Revised: 08/01/2016] [Accepted: 08/08/2016] [Indexed: 12/12/2022]
Abstract
Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care.
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Affiliation(s)
- Richard D Carvajal
- Division of Hematology/Oncology, Columbia University Medical Center, New York, USA
| | - Gary K Schwartz
- Division of Hematology/Oncology, Columbia University Medical Center, New York, USA
| | - Tongalp Tezel
- Department of Ophthalmology, Columbia University Medical Center, New York, USA
| | - Brian Marr
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Jasmine H Francis
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Paul D Nathan
- Division of Cancer Services, Mt Vernon Cancer Centre, Northwood, UK
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Meng T, Li GQ, Dai MH. Isolated hepatic perfusion for unresectable hepatic malignancies: A systematic review and meta-analysis. World J Meta-Anal 2016; 4:105-117. [DOI: 10.13105/wjma.v4.i5.105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 06/24/2016] [Accepted: 08/16/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the efficacy and safety of isolated hepatic perfusion (IHP) in the management of unresectable liver malignancies.
METHODS Studies were identified manually and on-line by using PubMed and EMBASE database. We formulate the eligibility criteria according to the PICOS elements, and accessed the quality of studies using the MINORS instrument. Data from all included studies were carefully investigated. We calculated the pooled response rate and incidences of mortality reported from all eligible studies by using the Meta-Analyst software, and we computed a pooled relative risk (RR) and 95%CI by using the Comprehensive Meta-Analysis software. Heterogeneity was quantified evaluated using I2 statistic.
RESULTS Eight studies, including 502 patients, were selected. Of these, six studies performed IHP, while the other two studies performed percutaneous IHP. The results showed that the pooled response rate was 60.8% (95%CI: 53.1%-68%), I2 = 37.1%. The median overall survival was 20 mo (range: 12.1 to 25 mo) following IHP or PIHP. The pooled mortality rate was 5.4% (95%CI: 2.5%-11.2%), I2 = 37.5%. Prognostic factors predict the response to IHP or survival, and were reported in six studies. Meta-analysis demonstrated that Gender was not associated with overall survival (RR = 0.877, 95%CI: 0.564-1.365); however, carcino-embryonic antigen ≤ 30 ng/mL was associated with a significant improvement in survival outcomes with colorectal cancer patients (RR = 2.082, 95%CI: 1.371-3.163), and there was no significant heterogeneity.
CONCLUSION The present systemic review and meta-analysis suggest that IHP and PIHP are potentially efficient and safe techniques for unresectable liver primary and secondary malignancies.
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de Leede EM, Burgmans MC, Martini CH, Tijl FGJ, van Erkel AR, Vuyk J, Kapiteijn E, Verhoef C, van de Velde CJH, Vahrmeijer AL. Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver. J Vis Exp 2016. [PMID: 27501370 DOI: 10.3791/53795] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.
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Affiliation(s)
| | | | | | - Fred G J Tijl
- Department of Extracorporeal Circulation, Leiden University Medical Centre
| | | | - Jaap Vuyk
- Department of Anesthesiology, Leiden University Medical Centre
| | - Ellen Kapiteijn
- Department of Medical Oncology, Leiden University Medical Centre
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Abstract
Isolated hepatic perfusion uses the unique vascular supply of hepatic malignancies to deliver cytotoxic chemotherapy. The procedure involves vascular isolation of the liver and delivery of chemotherapy via the hepatic artery and extraction from retrohepatic vena cava. Benefits of hepatic perfusion have been observed in hepatic metastases of ocular melanoma and colorectal cancer and primary hepatocellular carcinoma. Percutaneous and prophylactic perfusions are avenues of ongoing research.
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Affiliation(s)
- Rahul Rajeev
- Division of Surgical Oncology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - T Clark Gamblin
- Division of Surgical Oncology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - Kiran K Turaga
- Division of Surgical Oncology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.
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28
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Helmick RA, McMenomy BP, Huebert RC. Black and White Liver. Clin Gastroenterol Hepatol 2016; 14:A39-40. [PMID: 26385443 DOI: 10.1016/j.cgh.2015.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 09/08/2015] [Accepted: 09/09/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Ryan A Helmick
- Division of Transplant Surgery, Mayo Clinic and Foundation, Rochester, Minnesota
| | - Brendan P McMenomy
- Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota
| | - Robert C Huebert
- Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota
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Ben-Shabat I, Belgrano V, Ny L, Nilsson J, Lindnér P, Olofsson Bagge R. Long-Term Follow-Up Evaluation of 68 Patients with Uveal Melanoma Liver Metastases Treated with Isolated Hepatic Perfusion. Ann Surg Oncol 2015; 23:1327-34. [PMID: 26628434 DOI: 10.1245/s10434-015-4982-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Indexed: 11/18/2022]
Abstract
BACKGROUND This report describes the outcomes and long-term follow-up data from all isolated hepatic perfusions (IHPs) performed at a single institution in Sweden between the years 1989 and 2013 for patients with isolated uveal melanoma metastases. METHODS A total of 68 patients (median age, 61 years) were treated consecutively at Sahlgrenska University Hospital. Of the 68 patients, 67 % had fewer than 10 tumors. The median diameter of the largest lesion was 2.5 cm. The patients underwent IHP with either melphalan alone or the addition of either tumor necrosis factor-alpha or cisplatin. The response was assessed after 8-12 weeks by computed tomography or magnetic resonance imaging. RESULTS The overall response rate was 67 and 20 % of the patients had a complete response. The median times to local and systemic progression were respectively 10 and 14 months. The prognostic factors for time to local recurrence were response and number of tumors. The median survival time was 22 months. The prognostic factors for survival were response, largest tumor diameter, and number of tumors. Five patients (7 %) died within 30 days, and six patients (9 %) experienced major complications (Clavien-Dindo 3/4). CONCLUSIONS Isolated hepatic perfusion is a treatment option with high response rates and tolerable mortality and morbidity. Whether IHP has a survival benefit compared with other treatment options currently is being investigated in a randomized trial.
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Affiliation(s)
- Ilan Ben-Shabat
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Valerio Belgrano
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Lars Ny
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Jonas Nilsson
- Sahlgrenska Cancer Center, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Per Lindnér
- Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Roger Olofsson Bagge
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Hughes MS, Zager J, Faries M, Alexander HR, Royal RE, Wood B, Choi J, McCluskey K, Whitman E, Agarwala S, Siskin G, Nutting C, Toomey MA, Webb C, Beresnev T, Pingpank JF. Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases. Ann Surg Oncol 2015; 23:1309-19. [PMID: 26597368 DOI: 10.1245/s10434-015-4968-3] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Indexed: 11/18/2022]
Abstract
PURPOSE There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver. PATIENTS AND METHODS A total of 93 patients were randomized to PHP-Mel (n = 44) or BAC (n = 49). On the PHP-Mel arm, melphalan was delivered via the hepatic artery, and the hepatic effluent captured and filtered extracorporeally prior to return to the systemic circulation via a venovenous bypass circuit. PHP-Mel was repeatable every 4-8 weeks. The primary endpoint was hepatic progression-free survival (hPFS), and secondary endpoints included overall PFS (oPFS), overall survival (OS), hepatic objective response (hOR), and safety. RESULTS hPFS was 7.0 months for PHP-Mel and 1.6 months for BAC (p < 0.0001), while oPFS was 5.4 months for PHP-Mel and 1.6 months for BAC (p < 0.0001). Median OS was not significantly different (PHP-Mel 10.6 months vs. BAC 10.0 months), likely due to crossover to PHP-Mel treatment (57.1 %) from the BAC arm, and the hOR was 36.4 % for PHP-Mel and 2.0 % for BAC (p < 0.001). The majority of adverse events were related to bone marrow suppression. Four deaths were attributed to PHP-Mel, three in the primary PHP-Mel group, and one post-crossover to PHP-Mel from BAC. CONCLUSION This randomized, phase III study demonstrated the efficacy of the PHP-Mel procedure. hPFS, oPFS, and hOR were significantly improved with PHP-Mel. PHP with melphalan should provide a new treatment option for unresectable metastatic melanoma in the liver.
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Affiliation(s)
- Marybeth S Hughes
- Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Jonathan Zager
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Mark Faries
- John Wayne Cancer Institute, Providence St. John's Health Center, Santa Monica, CA, USA
| | - H Richard Alexander
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA
| | - Richard E Royal
- M.D. Anderson Cancer Center, University of Texas, Houston, TX, USA
| | - Bradford Wood
- Center for Interventional Oncology, National Institutes of Health, Bethesda, MD, USA
| | - Junsung Choi
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Kevin McCluskey
- University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Eric Whitman
- Carol G. Simon Cancer Center, Atlantic Health System, Morristown, NJ, USA
| | | | - Gary Siskin
- Albany Medical Neurosciences Institute, Albany, NY, USA
| | | | - Mary Ann Toomey
- Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Carole Webb
- Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Tatiana Beresnev
- Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - James F Pingpank
- University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. .,Division of Hepatobiliary Surgery, Surgical Oncology Services, Hillman Cancer Center, UPMC, Pittsburgh, PA, USA.
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Transarterial Chemoembolization of Liver Metastases from Uveal Melanoma Using Irinotecan-Loaded Beads: Treatment Response and Complications. Cardiovasc Intervent Radiol 2015; 38:1532-41. [PMID: 25832764 DOI: 10.1007/s00270-015-1093-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 03/15/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE The purpose of this study was to evaluate treatment response and complications of transarterial chemoembolization using drug-eluting beads loaded with irinotecan (DEBIRI) in patients with liver metastases from uveal melanoma (UM). MATERIALS AND METHODS Patients treated with DEBIRI (n = 14) were retrospectively analyzed regarding overall survival, compared to patients (n = 14) treated with intravenous dacarbazine (DTIC). Median overall survival was calculated from time of diagnosis of metastatic disease (OS1) and start of treatment (OS2). Radiological response for DEBIRI was assessed according to RECIST 1.1 on contrast-enhanced computed tomography (CT), obtained 1.5 months (range 1.2-3.7) post treatment. Major complications of DEBIRI were defined according to the Society of Interventional Radiology classification for complications by outcome. RESULTS In the DEBIRI group, OS1 was 14.8 months (range 3.9-47.5), and OS2 was 9.4 months (range 1.7-39). Further, 11/13 (84.6%) of these patients had progressive disease on first follow-up CT and new lesions were seen in nine. There were 12 major complications in nine patients, possibly including one case of mortality due to disseminated intravascular coagulation (DIC). CONCLUSION For patients with liver metastases from UM, the effect on overall survival of DEBIRI alone is questionable. Compared to previous reports, the response rate of DEBIRI was poor, with new liver lesions observed in the majority of patients. Major complications possibly included one case of DIC.
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Valpione S, Moser JC, Parrozzani R, Bazzi M, Mansfield AS, Mocellin S, Pigozzo J, Midena E, Markovic SN, Aliberti C, Campana LG, Chiarion-Sileni V. Development and external validation of a prognostic nomogram for metastatic uveal melanoma. PLoS One 2015; 10:e0120181. [PMID: 25780931 PMCID: PMC4363319 DOI: 10.1371/journal.pone.0120181] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Accepted: 02/03/2015] [Indexed: 12/21/2022] Open
Abstract
Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials.
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Affiliation(s)
- Sara Valpione
- Melanoma Oncology Unit, Veneto Region Oncology Research Institute (IOV-IRCCS), Padova, Italy; Department of Surgery, Oncology and Gastroenterology, Padova, Italy
| | - Justin C Moser
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, US
| | | | - Marco Bazzi
- Department of Statistical Sciences, University of Padova, Padova, Italy
| | - Aaron S Mansfield
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Simone Mocellin
- Department of Surgery, Oncology and Gastroenterology, Padova, Italy
| | - Jacopo Pigozzo
- Melanoma Oncology Unit, Veneto Region Oncology Research Institute (IOV-IRCCS), Padova, Italy
| | - Edoardo Midena
- Department of Statistical Sciences, University of Padova, Padova, Italy; Department of Ophthalmology, University of Padova, Padova, Italy
| | - Svetomir N Markovic
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Camillo Aliberti
- Interventional Radiology, Veneto Region Oncology Research Institute (IOV-IRCCS) Padova, Italy
| | - Luca G Campana
- Sarcoma and Melanoma Unit, Veneto Region Oncology Research Institute (IOV-IRCCS) Padova, Italy
| | - Vanna Chiarion-Sileni
- Melanoma Oncology Unit, Veneto Region Oncology Research Institute (IOV-IRCCS), Padova, Italy
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Ben-Shabat I, Hansson C, Sternby Eilard M, Cahlin C, Rizell M, Lindnér P, Mattsson J, Olofsson Bagge R. Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma. J Vis Exp 2015:52490. [PMID: 25650893 DOI: 10.3791/52490] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation. In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.
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Affiliation(s)
- Ilan Ben-Shabat
- Department of Surgery, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg
| | - Christoffer Hansson
- Department of Thoracic Surgery, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg
| | - Malin Sternby Eilard
- Transplant Institute, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg
| | - Christian Cahlin
- Transplant Institute, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg
| | - Magnus Rizell
- Transplant Institute, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg
| | - Per Lindnér
- Transplant Institute, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg
| | - Jan Mattsson
- Department of Surgery, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg
| | - Roger Olofsson Bagge
- Department of Surgery, Institute of Clinical Sciences; Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg;
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Olofsson R, Ny L, Eilard MS, Rizell M, Cahlin C, Stierner U, Lönn U, Hansson J, Ljuslinder I, Lundgren L, Ullenhag G, Kiilgaard JF, Nilsson J, Lindnér P. Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial. Trials 2014; 15:317. [PMID: 25106493 PMCID: PMC4138407 DOI: 10.1186/1745-6215-15-317] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 07/25/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). METHODS/DESIGN This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. DISCUSSION Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint. TRIAL REGISTRATION ClinicalTrials.gov registration number: NCT01785316 (registered 1 February 2013). EudraCT registration number: 2013-000564-29.
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Affiliation(s)
- Roger Olofsson
- />Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Blå stråket 5, 413 45 Gothenburg, Sweden
| | - Lars Ny
- />Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Blå stråket 5, 413 45 Gothenburg, Sweden
| | - Malin Sternby Eilard
- />Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
| | - Magnus Rizell
- />Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
| | - Christian Cahlin
- />Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
| | - Ulrika Stierner
- />Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Blå stråket 5, 413 45 Gothenburg, Sweden
| | - Ulf Lönn
- />Department of Oncology, Linköping University Hospital, Garnisonsvägen 10, 581 85 Linköping, Sweden
| | - Johan Hansson
- />Department of Oncology, Karolinska University Hospital, Karolinska vägen, 171 76 Stockholm, Sweden
| | - Ingrid Ljuslinder
- />Department of Oncology, Norrlands University Hospital, 901 85 Umeå, Sweden
| | - Lotta Lundgren
- />Department of Oncology, Skåne University Hospital, Getingevägen 4, 221 85 Lund, Sweden
| | - Gustav Ullenhag
- />Department of Radiology, Oncology and Radiation Science, Section of Oncology, Uppsala University, 751 05 Uppsala, Sweden
| | - Jens Folke Kiilgaard
- />Department of Ophthalmology, Glostrup Hospital, Copenhagen University Hospital Glostrup, Nordre Ringvej 57, 2600 Glostrup, Denmark
| | - Jonas Nilsson
- />Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Medicinaregatan 1F, 405 30 Gothenburg, Sweden
| | - Per Lindnér
- />Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
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Francis JH, Abramson DH. Update on Ophthalmic Oncology 2013: Retinoblastoma and Uveal Melanoma. Asia Pac J Ophthalmol (Phila) 2014; 3:241-56. [PMID: 26107765 DOI: 10.1097/apo.0000000000000079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
PURPOSE The aim of this study was to discuss the clinical and translational content of the literature as well as advancement in our knowledge pertaining to retinoblastoma and uveal melanoma that were published from January to December 2013. DESIGN This study is a literature review. METHODS The search terms retinoblastoma and uveal melanoma were used in a MEDLINE literature search. Abstracts were studied, and the most relevant articles were selected for inclusion and further in-depth review. RESULTS In retinoblastoma, fewer eyes are lost because of the expanded use of ophthalmic artery chemosurgery and intravitreal melphalan, and the past year marks a deepening in our understanding of these modalities. Knowledge on the genetic underpinnings of uveal melanoma has broadened to include genes associated with a favorable prognosis. This is accompanied by promising results in the treatment of metastatic uveal melanoma. CONCLUSIONS This past year, there were important advancements in our knowledge of retinoblastoma and uveal melanoma.
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Affiliation(s)
- Jasmine H Francis
- From the Ophthalmic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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Eichler K, Zangos S, Gruber-Rouh T, Vogl TJ, Mack MG. MR-guided laser-induced thermotherapy (LITT) in patients with liver metastases of uveal melanoma. J Eur Acad Dermatol Venereol 2014; 28:1756-60. [PMID: 24593299 DOI: 10.1111/jdv.12405] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 01/19/2014] [Indexed: 01/13/2023]
Abstract
PURPOSE Evaluation of the local tumour control rate and survival data for magnetic resonance (MR) imaging-guided laser ablation of uveal malignant melanoma liver metastases by using laser-induced interstitial thermotherapy (LITT). MATERIALS AND METHODS The LITT was performed in 18 patients with liver metastases (n = 44) from uveal malignant melanoma. All patients tolerated this intervention well. With the Kaplan-Meier method, the survival rates were calculated. Indications for the procedure were defined for patients with no more than five metastases, none of which were larger than 5 cm in diameter: The Indication for LITT treatment were recurrent liver metastases after partial liver resection (22%), locally non-resectable tumours (17%) or metastases in both liver lobes (61%). RESULTS The mean survival rate for all treated patients was 3.6 years (95% CI: 2.19, 5.06). We started the calculation on the date of diagnosis of the metastases treated with LITT. The median survival was 1.83 years; 1-year survival, 88%; 3-year survival 47%, 5-year survival 17%. Calculated after the first LITT treatment the median survival was 2.8 years (95% CI: 1.0, 5.0). 10 patients were treated by transarterial chemoembolization before LITT. CONCLUSION MR-guided LITT treatment shows a high local tumour control and survival rates in patients with liver metastases of uveal malignant melanoma.
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Affiliation(s)
- K Eichler
- Department of Diagnostic and Interventional Radiology, University of Frankfurt, Frankfurt, Germany
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