Skip to main content
Top
Published in: Annals of Surgical Oncology 4/2016

01-04-2016 | Hepatobiliary Tumors

Long-Term Follow-Up Evaluation of 68 Patients with Uveal Melanoma Liver Metastases Treated with Isolated Hepatic Perfusion

Authors: Ilan Ben-Shabat, Valerio Belgrano, Lars Ny, MD, PhD, Jonas Nilsson, PhD, Per Lindnér, MD, PhD, Roger Olofsson Bagge, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2016

Login to get access

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.
Literature
1.
go back to reference Bergman L, Seregard S, Nilsson B, Ringborg U, Lundell G, Ragnarsson-Olding B. Incidence of uveal melanoma in Sweden from 1960 to 1998. Invest Ophthalmol Vis Sci. 2002;43:2579–83.PubMed Bergman L, Seregard S, Nilsson B, Ringborg U, Lundell G, Ragnarsson-Olding B. Incidence of uveal melanoma in Sweden from 1960 to 1998. Invest Ophthalmol Vis Sci. 2002;43:2579–83.PubMed
2.
go back to reference Diener-West M, Reynolds SM, Agugliaro DJ, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005;123:1639–43.CrossRefPubMed Diener-West M, Reynolds SM, Agugliaro DJ, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005;123:1639–43.CrossRefPubMed
3.
go back to reference Kujala E, Makitie T, Kivela T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003;44:4651–9.CrossRefPubMed Kujala E, Makitie T, Kivela T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003;44:4651–9.CrossRefPubMed
4.
go back to reference Rietschel P, Panageas KS, Hanlon C, Patel A, Abramson DH, Chapman PB. Variates of survival in metastatic uveal melanoma. J Clin Oncol. 2005;23:8076–80.CrossRefPubMed Rietschel P, Panageas KS, Hanlon C, Patel A, Abramson DH, Chapman PB. Variates of survival in metastatic uveal melanoma. J Clin Oncol. 2005;23:8076–80.CrossRefPubMed
5.
go back to reference Gragoudas ES, Egan KM, Seddon JM, et al. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991;98:383–9; discussion 390.CrossRefPubMed Gragoudas ES, Egan KM, Seddon JM, et al. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991;98:383–9; discussion 390.CrossRefPubMed
6.
go back to reference Kivela T, Suciu S, Hansson J, et al. Bleomycin, vincristine, lomustine, and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer. 2003;39:1115–20.CrossRefPubMed Kivela T, Suciu S, Hansson J, et al. Bleomycin, vincristine, lomustine, and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer. 2003;39:1115–20.CrossRefPubMed
7.
go back to reference Carvajal RD, Sosman JA, Quevedo JF, et al. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014;311:2397–405.CrossRefPubMedPubMedCentral Carvajal RD, Sosman JA, Quevedo JF, et al. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014;311:2397–405.CrossRefPubMedPubMedCentral
8.
go back to reference Luke JJ, Callahan MK, Postow MA, et al. Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience. Cancer. 2013;119:3687–95.CrossRefPubMedPubMedCentral Luke JJ, Callahan MK, Postow MA, et al. Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience. Cancer. 2013;119:3687–95.CrossRefPubMedPubMedCentral
9.
go back to reference Mariani P, Piperno-Neumann S, Servois V, et al. Surgical management of liver metastases from uveal melanoma: 16 years’ experience at the Institut Curie. Eur J Surg Oncol. 2009;35:1192–7.CrossRefPubMed Mariani P, Piperno-Neumann S, Servois V, et al. Surgical management of liver metastases from uveal melanoma: 16 years’ experience at the Institut Curie. Eur J Surg Oncol. 2009;35:1192–7.CrossRefPubMed
10.
go back to reference Leyvraz S, Piperno-Neumann S, Suciu S, et al. Hepatic intraarterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol. 2014;25:742–6.CrossRefPubMedPubMedCentral Leyvraz S, Piperno-Neumann S, Suciu S, et al. Hepatic intraarterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol. 2014;25:742–6.CrossRefPubMedPubMedCentral
11.
go back to reference Valpione S, Aliberti C, Parrozzani R, et al. A retrospective analysis of 141 patients with liver metastases from uveal melanoma: a two-cohort study comparing transarterial chemoembolization with CPT-11 charged microbeads and historical treatments. Melanoma Res. 2015;25:164–8.CrossRefPubMed Valpione S, Aliberti C, Parrozzani R, et al. A retrospective analysis of 141 patients with liver metastases from uveal melanoma: a two-cohort study comparing transarterial chemoembolization with CPT-11 charged microbeads and historical treatments. Melanoma Res. 2015;25:164–8.CrossRefPubMed
12.
go back to reference Gonsalves CF, Eschelman DJ, Thornburg B, Frangos A, Sato T. Uveal melanoma metastatic to the liver: chemoembolization with 1,3-bis-(2-chloroethyl)-1-nitrosourea. AJR Am J Roentgenol. 2015;205:1–5.CrossRef Gonsalves CF, Eschelman DJ, Thornburg B, Frangos A, Sato T. Uveal melanoma metastatic to the liver: chemoembolization with 1,3-bis-(2-chloroethyl)-1-nitrosourea. AJR Am J Roentgenol. 2015;205:1–5.CrossRef
13.
go back to reference Eldredge-Hindy H, Ohri N, Anne PR, et al. Yttrium-90 microsphere brachytherapy for liver metastases from uveal melanoma: clinical outcomes and the predictive value of fluorodeoxyglucose positron emission tomography. Am J Clin Oncol. 2014. Eldredge-Hindy H, Ohri N, Anne PR, et al. Yttrium-90 microsphere brachytherapy for liver metastases from uveal melanoma: clinical outcomes and the predictive value of fluorodeoxyglucose positron emission tomography. Am J Clin Oncol. 2014.
14.
go back to reference 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;6:3062–70.PubMed 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;6:3062–70.PubMed
15.
go back to reference Alexander HR Jr, Libutti SK, Pingpank JF, et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003;9:6343–9.PubMed Alexander HR Jr, Libutti SK, Pingpank JF, et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003;9:6343–9.PubMed
16.
go back to reference Noter SL, Rothbarth J, Pijl ME, et al. Isolated hepatic perfusion with high-dose melphalan for the treatment of uveal melanoma metastases confined to the liver. Melanoma Res. 2004;14:67–72.CrossRefPubMed Noter SL, Rothbarth J, Pijl ME, et al. Isolated hepatic perfusion with high-dose melphalan for the treatment of uveal melanoma metastases confined to the liver. Melanoma Res. 2004;14:67–72.CrossRefPubMed
17.
go back to reference Pingpank JF, Libutti SK, Chang R, et al. Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies. J Clin Oncol. 2005;23:3465–74.CrossRefPubMedPubMedCentral Pingpank JF, Libutti SK, Chang R, et al. Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies. J Clin Oncol. 2005;23:3465–74.CrossRefPubMedPubMedCentral
18.
go back to reference Rizell M, Mattson J, Cahlin C, Hafstrom L, Lindner P, Olausson M. Isolated hepatic perfusion for liver metastases of malignant melanoma. Melanoma Res. 2008;18:120–6.CrossRefPubMed Rizell M, Mattson J, Cahlin C, Hafstrom L, Lindner P, Olausson M. Isolated hepatic perfusion for liver metastases of malignant melanoma. Melanoma Res. 2008;18:120–6.CrossRefPubMed
19.
go back to reference Verhoef C, de Wilt JH, Brunstein F, et al. Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion. Ann Surg Oncol. 2008;15:1367–74.CrossRefPubMedPubMedCentral Verhoef C, de Wilt JH, Brunstein F, et al. Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion. Ann Surg Oncol. 2008;15:1367–74.CrossRefPubMedPubMedCentral
20.
go back to reference van Iersel LB, Hoekman EJ, Gelderblom H, et al. Isolated hepatic perfusion with 200-mg melphalan for advanced noncolorectal liver metastases. Ann Surg Oncol. 2008;15:1891–8.CrossRefPubMedPubMedCentral van Iersel LB, Hoekman EJ, Gelderblom H, et al. Isolated hepatic perfusion with 200-mg melphalan for advanced noncolorectal liver metastases. Ann Surg Oncol. 2008;15:1891–8.CrossRefPubMedPubMedCentral
21.
go back to reference van Etten B, de Wilt JH, Brunstein F, Eggermont AM, Verhoef C. Isolated hypoxic hepatic perfusion with melphalan in patients with irresectable ocular melanoma metastases. Eur J Surg Oncol. 2009;35:539–45.CrossRefPubMed van Etten B, de Wilt JH, Brunstein F, Eggermont AM, Verhoef C. Isolated hypoxic hepatic perfusion with melphalan in patients with irresectable ocular melanoma metastases. Eur J Surg Oncol. 2009;35:539–45.CrossRefPubMed
22.
go back to reference Ben-Shabat I, Hansson C, Sternby Eilard M, et al. Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma. J Vis Exp. 2015;95:52490.PubMed Ben-Shabat I, Hansson C, Sternby Eilard M, et al. Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma. J Vis Exp. 2015;95:52490.PubMed
23.
go back to reference Ku Y, Saitoh M, Nishiyama H, et al. Extracorporeal adriamycin-removal following hepatic artery infusion: use of direct hemoperfusion combined with veno-venous bypass (in Japanese). Nihon Geka Gakkai Zasshi. 1989;90:1758–64.PubMed Ku Y, Saitoh M, Nishiyama H, et al. Extracorporeal adriamycin-removal following hepatic artery infusion: use of direct hemoperfusion combined with veno-venous bypass (in Japanese). Nihon Geka Gakkai Zasshi. 1989;90:1758–64.PubMed
24.
go back to reference Curley SA, Byrd DR, Newman RA, et al. Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system. Anticancer Drugs. 1991;2:175–83.CrossRefPubMed Curley SA, Byrd DR, Newman RA, et al. Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system. Anticancer Drugs. 1991;2:175–83.CrossRefPubMed
25.
go back to reference Beheshti MV, Denny DF Jr, Glickman MG, et al. Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report. J Vasc Interv Radiol. 1992;3:453–8.CrossRefPubMed Beheshti MV, Denny DF Jr, Glickman MG, et al. Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report. J Vasc Interv Radiol. 1992;3:453–8.CrossRefPubMed
26.
go back to reference Ravikumar TS, Pizzorno G, Bodden W, et al. Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors. J Clin Oncol. 1994;12:2723–36.PubMed Ravikumar TS, Pizzorno G, Bodden W, et al. Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors. J Clin Oncol. 1994;12:2723–36.PubMed
27.
go back to reference Curley SA, Newman RA, Dougherty TB, et al. Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study. Ann Surg Oncol. 1994;1:389–99.CrossRefPubMed Curley SA, Newman RA, Dougherty TB, et al. Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study. Ann Surg Oncol. 1994;1:389–99.CrossRefPubMed
28.
go back to reference Pingpank JF, Hughes MS, Alexander HR, Faries MB, Zager JS, Royal R, Whitman ED, Nutting CW, Siskin GP, Agarwala SS. A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma. J Clin Oncol. 2010;28(18 Suppl):LBA8512. Pingpank JF, Hughes MS, Alexander HR, Faries MB, Zager JS, Royal R, Whitman ED, Nutting CW, Siskin GP, Agarwala SS. A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma. J Clin Oncol. 2010;28(18 Suppl):LBA8512.
29.
go back to reference Carvajal RD, Schwartz GK, Mann H, Smith I, Nathan PD. Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT). BMC Cancer. 2015;15:467.CrossRefPubMedPubMedCentral Carvajal RD, Schwartz GK, Mann H, Smith I, Nathan PD. Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT). BMC Cancer. 2015;15:467.CrossRefPubMedPubMedCentral
30.
go back to reference Olofsson R, Lindberg E, Karlsson-Parra A, Lindner P, Mattsson J, Andersson B. Melan-A-specific CD8 + T lymphocytes after hyperthermic isolated limb perfusion: a pilot study in patients with in-transit metastases of malignant melanoma. Int J Hyperthermia. 2013;29:234–8.CrossRefPubMed Olofsson R, Lindberg E, Karlsson-Parra A, Lindner P, Mattsson J, Andersson B. Melan-A-specific CD8 + T lymphocytes after hyperthermic isolated limb perfusion: a pilot study in patients with in-transit metastases of malignant melanoma. Int J Hyperthermia. 2013;29:234–8.CrossRefPubMed
31.
go back to reference Dudek-Peric AM, Ferreira GB, Muchowicz A, et al. Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin. Cancer Res. 2015;75:1603–14.CrossRefPubMed Dudek-Peric AM, Ferreira GB, Muchowicz A, et al. Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin. Cancer Res. 2015;75:1603–14.CrossRefPubMed
32.
go back to reference Olofsson R, Cahlin C, All-Ericsson C, et al. Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests a survival benefit. Ann Surg Oncol. 2014;21:466–72.CrossRefPubMed Olofsson R, Cahlin C, All-Ericsson C, et al. Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests a survival benefit. Ann Surg Oncol. 2014;21:466–72.CrossRefPubMed
33.
go back to reference Olofsson R, Ny L, Eilard MS, et al. 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.CrossRefPubMedPubMedCentral Olofsson R, Ny L, Eilard MS, et al. 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.CrossRefPubMedPubMedCentral
Metadata
Title
Long-Term Follow-Up Evaluation of 68 Patients with Uveal Melanoma Liver Metastases Treated with Isolated Hepatic Perfusion
Authors
Ilan Ben-Shabat
Valerio Belgrano
Lars Ny, MD, PhD
Jonas Nilsson, PhD
Per Lindnér, MD, PhD
Roger Olofsson Bagge, MD, PhD
Publication date
01-04-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4982-5

Other articles of this Issue 4/2016

Annals of Surgical Oncology 4/2016 Go to the issue