Percutaneous hepatic perfusion (PHP) delivers high-dose melphalan to the liver while minimizing systemic toxicity via filtration of the venous hepatic blood. This two-center study aimed to examine the safety, response to therapy, and survival of patients with hepatic-dominant metastatic uveal melanoma (UM) treated with PHP. A total of 66 patients with liver-dominant metastasized uveal melanoma, treated with 145 PHP between April 2014 and May 2020, were retrospectively analyzed with regard to adverse events (AEs; CTCAE v5.0), response (overall response rate (ORR)), and disease control rate (DCR) according to RECIST1.1, as well as progression-free and overall survival (PFS and OS). With an ORR of 59% and a DCR of 93.4%, the response was encouraging. After initial PHP, median hepatic PFS was 12.4 (confidence interval (CI) 4–18.4) months and median OS was 18.4 (CI 7–24.6) months. Hematologic toxicity was the most frequent AE (grade 3 or 4 thrombocytopenia after 24.8% of the procedures); less frequent was grade 3 or 4 hepatic toxicity (increased aspartate transaminase (AST) and alanine transaminase (ALT) after 7.6% and 6.9% of the interventions, respectively). Cardiovascular events included four cases of ischemic stroke (2.8%) and one patient with central pulmonary embolism (0.7%). In conclusion, PHP is a safe and effective salvage treatment for liver-dominant metastatic uveal melanoma. Serious AEs—though rare—demand careful patient selection.

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); ), 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.

Purpose: Percutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the hepatic artery to saturate tumor in the liver with the chemotherapeutic substance. The venous hepatic blood is filtered by an extracorporeal melphalan specific filtration system. Blood clotting in the extracorporeal filter system is prevented by administering unfractionated heparin (UFH) in high doses, which might be reversed with protamine sulfate after the procedure. Aim of this retrospective two-center-study was to analyze the potential effect of UFH reversal with protamine sulfate on complication rates following PHP. Materials and methods: All patients receiving PHP treatment between 10/2014 and 04/2021 were classified according to their intraprocedural coagulation management: 92 patients/192 PHP received full UFH reversal with protamine (group_PROTAMINE); 13 patients/21 PHP in group_{REDUCED_PROTAMINE} received a reduced amount of protamine, and 28 patients/43 PHP did not receive UFH reversal with protamine (group_{NO_PROTAMINE}). Periinterventional clinical reports, findings and laboratory values were retrospectively evaluated. Complications and adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAEv5.0). Results: Thromboembolic events were recorded after 10 PHP procedures (5%) in group_PROTAMINE, six of which (3%) were major events (CTCAE grade 3-5). No (0%) thromboembolic events were recorded in group_{REDUCED_PROTAMINE} and group_{NO_PROTAMINE}. Hemorrhagic events were registered after 24 PHP (13%) in group_PROTAMINE, two of which (1%) were major (CTCAE grade 3-4). In group_{REDUCED_PROTAMINE}, only minor bleeding events were recorded, and one major hemorrhagic event was documented in group_{NO_PROTAMINE} (2%). There was a significant difference between the percentage of post-interventional thrombopenia in group_PROTAMINE (39%) and group_{REDUCED_PROTAMINE} (14%) versus group_{NO_PROTAMINE} (23%) (p=.00024). In group_PROTAMINE one patient suffered from a severe anaphylactic shock after the administration of protamine. Conclusion: Our retrospective study implies that there might be a link between the practice of protamine sulfate administration to reverse the full hemodilutive effect of UFH after PHP and the post-interventional risk of thromboembolic events as well as clinically significant thrombopenia. Our data suggest that the standard use of protamine sulfate after PHP in low-risk patients without clinical signs of active bleeding should be critically re-evaluated.

Background/Objectives: Melphalan-based percutaneous hepatic perfusion (M-PHP) became approved in 2023 for treatment of liver-dominant metastatic uveal melanoma (mUM). Patients with liver-dominant mUM have a poor overall survival (OS) ≤ 12 months; however, the reported OS benefit from M-PHP varies in clinical trials from 9.6 to 27.4 months and remains uncertain. Here, we report the OS outcome after 10 years’ experience with M-PHP treatment of patients with liver-dominant mUM. Methods: A total of 38 consecutive patients (19 women, median age 57.7 years) with liver-dominant mUM underwent 99 M-PHP procedures (median: 2.6 M-PHP/patient) between April 2014 and March 2024 at our institution. OS outcomes were retrospectively analyzed using Kaplan–Meier methods and Cox proportional hazard models. Results: Median OS was 29.1 months after first M-PHP treatment (median follow-up: 25.8 months). The estimated percentage of patients surviving at 1, 2, and 3 years was 79.5%, 53.2%, and 28.5%, respectively. Each additional M-PHP cycle was associated with about 40% reduction in the risk of death (hazard ratio = 0.414). Median OS was numerically improved by 8.4 months with ≥3 versus ≤2 cycles of M-PHP administered (29.8 versus 21.4 months, p = 0.058). No treatment-related deaths occurred. Conclusions: This study found a clinically meaningful OS benefit in M-PHP-treated patients with liver-dominant mUM, reaching nearly 2.5-year median OS with ≥3 M-PHP cycles administered. This finding supports the need to account for the institutional volume and experience with the M-PHP procedure in both clinical practice and research, and may provide an OS reference for estimating OS gains in the evolving therapeutic landscape for mUM patients.