Top

CardioVascular and Interventional Radiology

Published in:

01-06-2017 | Clinical Investigation

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

Authors: Thomas J. Vogl, Silvia A. Koch, Gösta Lotz, Bernhard Gebauer, Winfried Willinek, Christoph Engelke, Roland Brüning, Martin Zeile, Frank Wacker, Arndt Vogel, Boris Radeleff, Jan-Erik Scholtz

Published in: CardioVascular and Interventional Radiology | Issue 6/2017

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.

Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9):1881–5. doi:10.1016/j.ophtha.2011.01.040.CrossRefPubMed

Abdel-Rahman MH, Cebulla CM, Verma V, Christopher BN, Carson WE 3rd, Olencki T, et al. Monosomy 3 status of uveal melanoma metastases is associated with rapidly progressive tumors and short survival. Exp Eye Res. 2012;100:26–31. doi:10.1016/j.exer.2012.04.010.CrossRefPubMedPubMedCentral

Damato B. Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye. 2012;26(9):1157–72. doi:10.1038/eye.2012.126.CrossRefPubMedPubMedCentral

Feldman ED, Pingpank JF, Alexander HR Jr. Regional treatment options for patients with ocular melanoma metastatic to the liver. Ann Surg Oncol. 2004;11(3):290–7.CrossRefPubMed

Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V. Ocular melanoma: an overview of the current status. Int J Clin Exp Pathol. 2013;6(7):1230–44.PubMedPubMedCentral

Gragoudas ES, Egan KM, Seddon JM, Glynn RJ, Walsh SM, Finn SM, et al. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991;98(3):383–9 (discussion 90).CrossRefPubMed

Burr JM, Mitry E, Rachet B, Coleman MP. Survival from uveal melanoma in England and Wales 1986 to 2001. Ophthalmic Epidemiol. 2007;14(1):3–8. doi:10.1080/09286580600977281.CrossRefPubMed

Singh AD, Borden EC. Metastatic uveal melanoma. Ophthalmol Clin N Am. 2005;18(1):143–50. doi:10.1016/j.ohc.2004.07.003.CrossRef

Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954;30(5):969–77.PubMedPubMedCentral

10.

Schenk WG Jr, Mc DJ, Mc DK, Drapanas T. Direct measurement of hepatic blood flow in surgical patients: with related observations on hepatic flow dynamics in experimental animals. Ann Surg. 1962;156:463–71.CrossRefPubMedPubMedCentral

11.

Alexander HR Jr, Butler CC. Development of isolated hepatic perfusion via the operative and percutaneous techniques for patients with isolated and unresectable liver metastases. Cancer J. 2010;16(2):132–41. doi:10.1097/PPO.0b013e3181db9c0a.CrossRefPubMed

12.

Alexander HR Jr, Libutti SK, Pingpank JF, Steinberg SM, Bartlett DL, Helsabeck C, et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003;9(17):6343–9.PubMed

13.

Grover A, Alexander HR Jr. The past decade of experience with isolated hepatic perfusion. Oncologist. 2004;9(6):653–64. doi:10.1634/theoncologist.9-6-653.CrossRefPubMed

14.

Vogl TJ, Emam A, Naguib NN, Eichler K, Zangos S. How effective are percutaneous liver-directed therapies in patients with non-colorectal liver metastases? Visz Med. 2015;31(6):406–13. doi:10.1159/000440677.

15.

Vogl T, Eichler K, Zangos S, Herzog C, Hammerstingl R, Balzer J, et al. Preliminary experience with transarterial chemoembolization (TACE) in liver metastases of uveal malignant melanoma: local tumor control and survival. J Cancer Res Clin Oncol. 2007;133(3):177–84. doi:10.1007/s00432-006-0155-z.CrossRefPubMed

16.

Ravikumar TS, Dixon K. Isolated liver perfusion for liver metastases: pharmacokinetic advantage? Surg Oncol Clin N Am. 1996;5(2):443–9.PubMed

17.

Vogel A, Gupta S, Zeile M, von Haken R, Bruning R, Lotz G, et al. Chemosaturation percutaneous hepatic perfusion: a systematic review. Adv Ther. 2016;. doi:10.1007/s12325-016-0424-4.PubMedPubMedCentral

18.

Alexander HR, Libutti SK, Bartlett DL, Puhlmann M, Fraker DL, Bachenheimer LC. A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2000;6(8):3062–70.PubMed

19.

Olofsson R, Cahlin C, All-Ericsson C, Hashimi F, Mattsson J, Rizell M, et al. Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests a survival benefit. Ann Surg Oncol. 2014;21(2):466–72. doi:10.1245/s10434-013-3304-z.CrossRefPubMed

20.

Burgmans MC, de Leede EM, Martini CH, Kapiteijn E, Vahrmeijer AL, van Erkel AR. Percutaneous isolated hepatic perfusion for the treatment of unresectable liver malignancies. Cardiovasc Intervent Radiol. 2016;39(6):801–14. doi:10.1007/s00270-015-1276-z.CrossRefPubMed

21.

Forster MR, Rashid OM, Perez MC, Choi J, Chaudhry T, Zager JS. Chemosaturation with percutaneous hepatic perfusion for unresectable metastatic melanoma or sarcoma to the liver: a single institution experience. J Surg Oncol. 2014;109(5):434–9. doi:10.1002/jso.23501.CrossRefPubMed

22.

Agarwala SS, Eggermont AM, O’Day S, Zager JS. Metastatic melanoma to the liver: a contemporary and comprehensive review of surgical, systemic, and regional therapeutic options. Cancer. 2014;120(6):781–9. doi:10.1002/cncr.28480.CrossRefPubMed

23.

Fournier L, Ammari S, Thiam R, Cuénod CA. Imaging criteria for assessing tumour response: RECIST, Mrecist, Cheson. Diagn Interv Imaging. 2014;95(7–8):689–703. doi:10.1016/j.diii.2014.05.002.CrossRefPubMed

24.

Hughes MS, Zager J, Faries M, Alexander HR, Royal RE, Wood B, et al. 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. 2016;23(4):1309–19. doi:10.1245/s10434-015-4968-3.CrossRefPubMed

25.

Rashid OM, Sloot S, Zager JS. Regional therapy in metastatic melanoma: an update on minimally invasive intraarterial isolated limb infusion and percutaneous hepatic perfusion. Expert Opin Drug Metab Toxicol. 2014;10(10):1355–64. doi:10.1517/17425255.2014.951330.CrossRefPubMed

26.

Vogl TJ, Zangos S, Scholtz JE, Schmitt F, Paetzold S, Trojan J, et al. Chemosaturation with percutaneous hepatic perfusions of melphalan for hepatic metastases: experience from two European centers. RoFo: Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin. 2014;186(10):937–44. doi:10.1055/s-0034-1366081.CrossRefPubMed

27.

Ben-Shabat I, Belgrano V, Ny L, Nilsson J, Lindner 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. 2016;23(4):1327–34. doi:10.1245/s10434-015-4982-5.CrossRefPubMed

28.

Noter SL, Rothbarth J, Pijl ME, Keunen JE, Hartgrink HH, Tijl FG, et al. Isolated hepatic perfusion with high-dose melphalan for the treatment of uveal melanoma metastases confined to the liver. Melanoma Res. 2004;14(1):67–72.CrossRefPubMed

29.

Rietschel P, Panageas KS, Hanlon C, Patel A, Abramson DH, Chapman PB. Variates of survival in metastatic uveal melanoma. J Clin Oncol. 2005;23(31):8076–80. doi:10.1200/jco.2005.02.6534.CrossRefPubMed

30.

Mariani P, Servois V, Piperno-Neumann S. Therapeutic options in metastatic uveal melanoma. Dev Ophthalmol. 2012;49:166–81. doi:10.1159/000328333.CrossRefPubMed

31.

Mariani P, Almubarak MM, Kollen M, Wagner M, Plancher C, Audollent R, et al. Radiofrequency ablation and surgical resection of liver metastases from uveal melanoma. Eur J Surg Oncol: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2016;42(5):706–12. doi:10.1016/j.ejso.2016.02.019.CrossRef

32.

Huppert PE, Fierlbeck G, Pereira P, Schanz S, Duda SH, Wietholtz H, et al. Transarterial chemoembolization of liver metastases in patients with uveal melanoma. Eur J Radiol. 2010;74(3):e38–44. doi:10.1016/j.ejrad.2009.03.064.CrossRefPubMed

33.

Gonsalves CF, Eschelman DJ, Sullivan KL, Anne PR, Doyle L, Sato T. Radioembolization as salvage therapy for hepatic metastasis of uveal melanoma: a single-institution experience. AJR Am J Roentgenol. 2011;196(2):468–73. doi:10.2214/AJR.10.4881.CrossRefPubMed

34.

Klingenstein A, Haug AR, Zech CJ, Schaller UC. Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients. Cardiovasc Intervent Radiol. 2013;36(1):158–65. doi:10.1007/s00270-012-0373-5.CrossRefPubMed

35.

Schelhorn J, Richly H, Ruhlmann M, Lauenstein TC, Theysohn JM. A single-center experience in radioembolization as salvage therapy of hepatic metastases of uveal melanoma. Acta Radiol Open. 2015;4(4):2047981615570417. doi:10.1177/2047981615570417.PubMedPubMedCentral

36.

Schelhorn J, Theysohn J, Ertle J, Schlaak JF, Mueller S, Bockisch A, et al. Selective internal radiation therapy of hepatic tumours: is coiling of the gastroduodenal artery always beneficial? Clin Radiol. 2014;69(5):e216–22. doi:10.1016/j.crad.2013.12.015.CrossRefPubMed

37.

Fiore F, Del Prete M, Franco R, Marotta V, Ramundo V, Marciello F, et al. Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. Endocrine. 2014;47(1):177–82. doi:10.1007/s12020-013-0130-9.CrossRefPubMed

38.

Barbier CE, Garske-Román U, Sandström M, Nyman R, Granberg D. Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. Eur J Nucl Med Mol Imaging. 2016;43(8):1425–31. doi:10.1007/s00259-015-3264-6.CrossRefPubMed

39.

Khajornjiraphan N, Thu NA, Chow PK. Yttrium-90 microspheres: a review of its emerging clinical indications. Liver Cancer. 2015;4(1):6–15. doi:10.1159/000343876.CrossRefPubMed

Title: Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study
Authors: Thomas J. Vogl
Silvia A. Koch
Gösta Lotz
Bernhard Gebauer
Winfried Willinek
Christoph Engelke
Roland Brüning
Martin Zeile
Frank Wacker
Arndt Vogel
Boris Radeleff
Jan-Erik Scholtz
Publication date: 01-06-2017
Publisher: Springer US
Published in: CardioVascular and Interventional Radiology / Issue 6/2017
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI: https://doi.org/10.1007/s00270-017-1588-2

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purpose

Materials and Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Materials and Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2017

Hybrid Approach for Biliary Interventions Employing MRI-Guided Bile Duct Puncture with Near-Real-Time Imaging

The Usefulness of Virtual Fluoroscopic Preprocedural Planning During Percutaneous Transhepatic Biliary Drainage

Stabilization Improves Theranostic Properties of Lipiodol®-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model

The Steerable Microcatheter: A New Device for Selective Catheterisation

Efficacy of Preoperative Transcatheter Arterial Embolization for Nasopharyngeal Angiofibroma: A Comparative Study

Helical-Tip Needle for Transthoracic Percutaneous Image-Guided Biopsy of Lung Tumors: Results of a Pilot Prospective Comparative Study with a Standard Tru-Cut Needle