Fotemustine Chemoembolization of Hepatic Metastases From Uveal Melanoma: A Retrospective Single-Center Analysis

Background Overall survival (OS) of patients with hepatic metastases of uveal melanoma is strongly linked with hepatic tumor control. Due to the lack of an effective systemic chemotherapy, locoregional therapies like radioembolization should play an increasingly important role. Purpose To report complications and response rates of radioembolization as salvage therapy for hepatic uveal melanoma metastases. Material and Methods Between October 2006 and January 2014, eight patients (age, 59.1 ± 15.3 years; 5 men) with histologically proven uveal melanoma and hepatic metastases received radioembolization with glass microspheres at a single center. All patients had been heavily pretreated with multiple systemic/locoregional therapies resulting in a long median interval between diagnosis of hepatic metastases and radioembolization (17.1 months; range, 6.4–23.2 months). Follow-up consisted of clinical assessment, laboratory tests and tri-phasic computed tomography (CT) before and 1, 3, 6, 9, and 12 months after radioembolization. Response to therapy was evaluated by CT using RECIST version 1.1 and by survival time. Safety (laboratory and clinical toxicity) was rated according to Common Terminology Criteria for Adverse Events 4.03. Using Kaplan-Meier analysis time to progression of hepatic metastases (hTTP) and OS were calculated. Results One month after radioembolization 50% of patients presented with stable and 50% with progressive disease. Median hTTP and OS after radioembolization were 4.3 weeks (range, 3.4–28.6 weeks) and 12.3 weeks (range, 3.7–62.6 weeks), respectively. Median OS after diagnosis of hepatic metastases was 19.9 months (range, 7.3–31.4 months). Radioembolization was tolerated well in all patients without toxicity higher than grade 2. Conclusion Radioembolization is a safe salvage therapy even in heavily pretreated hepatic metastases of uveal melanoma.

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Treatment of bulky uveal melanoma (UN) hepatic metastases with doxorubicin eluting beads (DEBDOX) followed by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) TACE: an initial experience

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2013.12.107 ◽

2014 ◽

Vol 25 (3) ◽

pp. S45

Author(s):

A.L. Tan ◽

D.J. Eschelman ◽

C.F. Gonsalves ◽

A. Frangos ◽

T. Sato

Keyword(s):

Uveal Melanoma ◽

Hepatic Metastases ◽

Initial Experience

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MRI in the detection of hepatic metastases from high-risk uveal melanoma: a prospective study in 188 patients

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2012-302323 ◽

2012 ◽

Vol 97 (2) ◽

pp. 159-163 ◽

Cited By ~ 56

Author(s):

Ernie Marshall ◽

Christopher Romaniuk ◽

Paula Ghaneh ◽

Helen Wong ◽

Marie McKay ◽

...

Keyword(s):

High Risk ◽

Prospective Study ◽

Uveal Melanoma ◽

Hepatic Metastases ◽

A Prospective Study

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Systematic review of liver directed therapy for uveal melanoma hepatic metastases

HPB ◽

10.1016/j.hpb.2019.11.002 ◽

2020 ◽

Vol 22 (4) ◽

pp. 497-505 ◽

Cited By ~ 6

Author(s):

Alistair Rowcroft ◽

Benjamin P.T. Loveday ◽

Benjamin N.J. Thomson ◽

Simon Banting ◽

Brett Knowles

Keyword(s):

Systematic Review ◽

Uveal Melanoma ◽

Hepatic Metastases

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Initial report of treatment of uveal melanoma with hepatic metastases with yttrium90 internal radiation followed by ipilimumab and nivolumab.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.10025 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 10025-10025 ◽

Cited By ~ 1

Author(s):

David R. Minor ◽

Takami Sato ◽

Marlana M. Orloff ◽

Jason J. Luke ◽

David J. Eschelman ◽

...

Keyword(s):

Uveal Melanoma ◽

Checkpoint Inhibitors ◽

Package Insert ◽

Hepatic Metastases ◽

Normal Liver ◽

Hepatic Artery Infusion ◽

Hepatic Toxicity ◽

Internal Radiation ◽

Initial Report ◽

Grade 3

10025 Background: Hepatic metastases from uveal melanoma have no established therapy, with a median survival of only 6-12 months. To date therapy with checkpoint inhibitors has yielded minimal results. To take advantage of possible synergy between radiation and immunotherapy we treated patients with yttrium90 internal radiation followed by immunotherapy. Methods: Patients received yttrium90 (Sir-Spheres) via hepatic artery infusion in two treatments, one to each lobe 3-4 weeks apart, followed in 3-6 weeks by ipilimumab and nivolumab for 4 doses, then nivolumab maintenance. Results: We are presenting interim results because of the excessive toxicity seen when these FDA-approved modalities were used in sequence with the FDA-approved dosages. Initially dosing of yttrium90 (Y90) followed the package insert “BSA method” but after 8 patients we had 5 cases of grade 3-4 hepatic toxicity; in 4 cases the toxicity was observed after just the Y90. One case of cirrhosis occurred in a patient whose liver received 40-45Gy; her cirrhosis was felt most likely due to the Y90. Y90 dosing was then reduced to limit dosage to normal liver to 35Gy, and none of the next 5 patients have had more than grade 2 hepatic toxicity. Dosage to the normal liver is approximated by the MIRD formula: Actual delivered liver dose [Gy] = 50 * Administered activity [GBq] * (1 – Lung shunt fraction) / kg of treated liver. If calculated dose was > 35GY, dosage in GBq is reduced proportionally. Toxicity in the first 5 patients to receive immunotherapy included one grade 4, two grade 3 and two grade 2 hepatic toxicities, and only 3 of the 5 patients received more than one dose of ipilimumab. We then reduced dosing of ipilimumab from 3mg/kg x 4 to 1mg/kg x 4 because of this excessive autoimmune toxicity. Of 13 patients, 10 received both Y90 and immunotherapy, and 3 had responses (1 CR, 2 PR) with 3 patients stable > 5months. Median progression-free survival for all patients is 27 weeks and median overall survival is greater than 48 weeks. Treatment with Y90 produced an over 50% fall in peripheral blood lymphocytes which was reversed in most patients by the immunotherapy. Conclusions: With dose modifications this therapy appears feasible and objective tumor responses were seen. Sequential therapy with Y90 and immunotherapy appears tolerable if radiation to normal liver is limited to 35Gy and ipilimumab dose is 1mg/kg. Clinical trial information: NCT02913417.

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