Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan-Long-Term Overall Survival Negatively Correlates with Tumor Burden.

R Brüning,P Wohlmuth,H Weilert,M Schneider,K Oldhafer,A Stang,M Tiede

doi:10.1155/2020/5672048

R Brüning, P Wohlmuth + Show 5 more

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https://doi.org/10.1155/2020/5672048

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Abstract

Introduction Percutaneous hepatic perfusion with melphalan (PHP-M) for hepatic metastasis of uveal melanoma (LMUM) achieves high local response rates, but the individual clinical benefit is poorly defined. We aimed to determine cofactors of response and clinical outcomes including the probability of long-term (5-years) overall survival (OS) in PHP-M-treated patients with LMUM. Patients and Methods. We retrospectively reviewed clinicopathological, radiological, and outcome data of 19 patients with unresectable LMUM treated with 43 PHP-M (median 2 PHP-M) between 2014 and 2019. Tumor response and adverse events were evaluated using RECIST 1.1 and the Clavien–Dindo classification. Kaplan–Meier methods and Cox regression hazard proportional models were used. Results Of 19 patients, 10 (53%) achieved a partial response (PR) and 9 (47%) had stable disease (SD). There was no progressive disease (PD) and no adverse events exceeding Clavien–Dindo grade IV. Median OS was 16.7 months after the first PHP-M treatment and 26.4 months after initial diagnosis. Low hepatic tumor volume (median of 10 mL vs. 150 mL) was an independent predictor of favorable OS (hazard ratio (95% confidence interval): 0.190 (0.041, 0.893); p < 0.05), and female patients were at a lower risk compared with males (0.146 (0.017, 1.240)). Estimates of the overall survival were 0.213 (0.0449, 1) from first imaging (95% confidence interval) to 5 years and 0.793 (0.609, 1) and 0.604 (0.380, 0.960) for 1 and 2 years after chemosaturation, respectively. Discussion. PHP-M for nonresectable LMUV provides a safe and locally efficient liver-directed procedure that offers patients a chance for long-term OS, especially for patients with a low hepatic tumor burden.

Highlights

Percutaneous hepatic perfusion with melphalan (PHP-M) for hepatic metastasis of uveal melanoma (LMUM) achieves high local response rates, but the individual clinical benefit is poorly defined
We aimed to determine cofactors of response and clinical outcomes including the probability of long-term (5-years) overall survival (OS) in PHP-M-treated patients with LMUM
Radiological, and outcome data of 19 patients with unresectable LMUM treated with 43 PHP-M between 2014 and 2019

Summary

Introduction

Percutaneous hepatic perfusion with melphalan (PHP-M) for hepatic metastasis of uveal melanoma (LMUM) achieves high local response rates, but the individual clinical benefit is poorly defined. Up to 50% of uveal melanomas develop hepatic metastasis [3] with reported median survival ranging from 4 to 15 months [4], suggesting a role for liver-directed local therapy in patients without extrahepatic disease. A meta-analysis of 29 phase II trials in metastatic uveal melanoma until 2015 aimed to define progression-free survival (PFS) and OS Poor outcomes such as a median PFS of 3.3 months (6-month PFS 27%) and median OS of 10.2 months (1-year OS 43%) were described across all treatment groups based on more than 900 patients [6]. Immune checkpoint inhibitors, such as ipilimumab, nivolumab, and pembrolizumab, achieve long-term OS with 5-year OS rates of 34–52% in metastatic cutaneous melanoma [7,8,9] but yield poor outcome results in metastatic uveal melanoma (UM) with a median OS of 10–14 months

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