skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

Abstract

PurposePercutaneous 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 MethodsBetween 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.ResultsOf 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 overallmore » health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.« less

Authors:
;  [1];  [2];  [3];  [4];  [5]; ;  [6];  [7];  [8];  [9];  [1]
  1. University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)
  2. University Hospital Frankfurt, Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy (Germany)
  3. Universitätsmedizin Berlin, Department of Diagnostic and Interventional Radiology, Campus Charité Mitte (Germany)
  4. Brüderkrankenhaus Trier, Department of Diagnostic and Interventional Radiology (Germany)
  5. Evangelisches Krankenhaus Göttingen-Weende gGmbH, Department of Diagnostic and Interventional Radiology (Germany)
  6. Asklepios Klinik Barmbek, Department of Diagnostic and Interventional Radiology (Germany)
  7. Medizinische Hochschule Hannover, Department of Diagnostic and Interventional Radiology (Germany)
  8. Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology (Germany)
  9. Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology (Germany)
Publication Date:
OSTI Identifier:
22645171
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cardiovascular and Interventional Radiology; Journal Volume: 40; Journal Issue: 6; Other Information: Copyright (c) 2017 Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE); http://www.springer-ny.com; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; AUGER ELECTRON SPECTROSCOPY; LEUKOPENIA; LIVER; MELANOMAS; METASTASES; PATIENTS; SAFETY; SURVIVAL TIME

Citation Formats

Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de, Koch, Silvia A., E-mail: silvia.koch@web.de, Lotz, Gösta, E-mail: goesta.lotz@kgu.de, Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de, Willinek, Winfried, E-mail: w.willinek@bk-trier.de, Engelke, Christoph, E-mail: engelke@ekweende.de, Brüning, Roland, E-mail: r.bruening@asklepios.com, Zeile, Martin, E-mail: m.zeile@asklepios.com, Wacker, Frank, E-mail: wacker.frank@mh-hannover.de, Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de, Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de, and Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study. United States: N. p., 2017. Web. doi:10.1007/S00270-017-1588-2.
Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de, Koch, Silvia A., E-mail: silvia.koch@web.de, Lotz, Gösta, E-mail: goesta.lotz@kgu.de, Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de, Willinek, Winfried, E-mail: w.willinek@bk-trier.de, Engelke, Christoph, E-mail: engelke@ekweende.de, Brüning, Roland, E-mail: r.bruening@asklepios.com, Zeile, Martin, E-mail: m.zeile@asklepios.com, Wacker, Frank, E-mail: wacker.frank@mh-hannover.de, Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de, Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de, & Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study. United States. doi:10.1007/S00270-017-1588-2.
Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de, Koch, Silvia A., E-mail: silvia.koch@web.de, Lotz, Gösta, E-mail: goesta.lotz@kgu.de, Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de, Willinek, Winfried, E-mail: w.willinek@bk-trier.de, Engelke, Christoph, E-mail: engelke@ekweende.de, Brüning, Roland, E-mail: r.bruening@asklepios.com, Zeile, Martin, E-mail: m.zeile@asklepios.com, Wacker, Frank, E-mail: wacker.frank@mh-hannover.de, Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de, Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de, and Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com. Thu . "Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study". United States. doi:10.1007/S00270-017-1588-2.
@article{osti_22645171,
title = {Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study},
author = {Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de and Koch, Silvia A., E-mail: silvia.koch@web.de and Lotz, Gösta, E-mail: goesta.lotz@kgu.de and Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de and Willinek, Winfried, E-mail: w.willinek@bk-trier.de and Engelke, Christoph, E-mail: engelke@ekweende.de and Brüning, Roland, E-mail: r.bruening@asklepios.com and Zeile, Martin, E-mail: m.zeile@asklepios.com and Wacker, Frank, E-mail: wacker.frank@mh-hannover.de and Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de and Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de and Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com},
abstractNote = {PurposePercutaneous 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 MethodsBetween 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.ResultsOf 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.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.},
doi = {10.1007/S00270-017-1588-2},
journal = {Cardiovascular and Interventional Radiology},
number = 6,
volume = 40,
place = {United States},
year = {Thu Jun 15 00:00:00 EDT 2017},
month = {Thu Jun 15 00:00:00 EDT 2017}
}
  • Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significantmore » improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.« less
  • Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest andmore » the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.« less
  • To retrospectively evaluate the overall survival, safety, and efficacy of metastatic uveal melanoma patients after radioembolization as salvage therapy. Thirteen patients were treated with radioembolization of branches of the hepatic artery with resin-based yttrium-90 ({sup 90}Y)-labelled microspheres. Twelve patients underwent a single application, and 1 patient underwent 4 interventions. Dosages from 644 to 2,450 MBq (mean activity 1,780) were applied. Treatment response was evaluated by way of liver magnetic resonance imaging and computed tomography (CT) as well as whole-body fluorodeoxyglucose positron emission tomography (PET)/CT with evaluation of percentage changes in SUV{sub max} before and at 2-3 months after therapy. Kaplan-Meiermore » analysis was calculated to determine overall survival. Partial remission (PR) was observed in 8 (62 %), stable disease (SD) in 2 (15 %), and progressive disease (PD) in 3 (23 %) patients under terms of standard criteria and PR in 3 (23 %), SD in 3 (23 %), and PD in 7 (54 %) patients according to PET criteria. Neither RECIST nor PET criteria showed a significant difference in predicting overall survival (P = 0.12 and 0.11, respectively). Median survival time after radioembolization was 7 months. No acute toxicity with in-hospital morbidity was observed. One patient developed hepatomegaly, and 1 patient developed gastric ulceration. Throughout follow-up, progression of extrahepatic metastases was observed. Radioembolization may be a promising therapy in uveal melanoma patients with predominant hepatic metastases. At first follow-up, we observed PR or SD in 77 % patients under terms of standard criteria with an acceptable toxicity profile.« less
  • Prognostic factors for visual loss following proton irradiation of uveal melanoma were evaluated for 440 eyes treated from 1975 to 1984, with visual acuity 20/200 or better before treatment. Analysis involved Kaplan-Meier survival curves and Cox proportional hazards analysis with visual outcome defined as worse than 20/200. Prognostic factors were tumor height: rate ratio (ratio of rate of visual loss for one category of the variable relative to the rate of visual loss for a reference category of that variable) of 5.26 (95% confidence interval, 2.66-10.39) for tumors greater than 5 mm compared to tumors 3.0 mm or less inmore » height; distance of tumor from the optic disc and fovea: rate ratio 2.59 (1.63-4.11) for tumors 2DD or less from both the optic disc and fovea compared to those greater than 2 DD from these structures. Also predictive of visual loss were tumor location close to disc only, or close to fovea only, macular detachment, worse pretreatment vision, and higher radiation doses delivered to both the disc and fovea, and lens. Regression analysis using a visual acuity scale gave similar results.« less
  • Purpose: To develop a method for isolated perfusion of the liver using radiological methods. Methods: Twenty-one pigs, weighing about 20 kg, were divided into three groups. By transjugular and transfemoral approaches two occlusion balloons were placed in the inferior vena cava cranial and caudal, respectively, to the origin of the hepatic veins. One occlusion balloon was placed transfemorally in the common hepatic artery. Another occlusion balloon was inserted in the main branch of the portal vein via the transjugular-transhepatic approach in 11 pigs (groups 1 and 2), and in 10 pigs (group 3) by a percutaneous transhepatic route. After inflationmore » of the balloons, patency of the isolated liver circulation was evaluated by recirculation of {sup 99}Tc{sup m}-labelled human albumin during 30 min. Blood tests were obtained after 1, 3, 5, 10, 15, and 30 min to evaluate leakage from the liver to the systemic circulation. Results: Increasing leakage to the systemic circulation from the isolated liver circulation was observed in groups 1 and 2. In the third group the leakage was less than 10%. Conclusion: In an experimental animal model, isolated perfusion of the liver with minor leakage to the systemic circulation may be achieved using radiological methods.« less