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

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.

Percutaneous hepatic melphalan perfusion: Single center experience of procedural characteristics, hemodynamic response, complications, and postoperative recovery

“…Our results suggested that the perioperative management of PHMP is frequently associated with procedure-related issues. These findings are in similarity with previous studies from other centers [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. The main issues related to PHMP were hemodynamic depression, vascular access complications, and coagulopathy.…”

“…Hemodynamic instability, particularly during balloon occlusion and melphalan wash-in, required advanced anesthetic expertise. We frequently observed large intraindividual ranges of SBP and heart rate, which were similar to previous studies that have reported significant transient hypotension during hemofiltration [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Hence, patients scheduled for PHMP should present with appropriate cardiovascular fitness and without pathologies of the brain-supplying vessels to avoid cerebral ischemia.…”

“…Fifty-three PHMP procedures of 16 patients were analyzed. In all of the cases, procedurerelated hypotension required the median (range) highest noradrenaline infusion rate of 0.5 (0.17-2.1) μg kg min -1 and fluid resuscitation volume of 5 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) liters. Eighty-four PHMPrelated complications were observed in 33 cases (62%), of which 9 cases (27%) involved grade III and IV complications.…”

“…Percutaneous hepatic melphalan perfusion (PHMP) is a third-line treatment option in patients with unresectable, isolated liver metastases or primary liver tumors [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Liver metastases and liver cancer tissues are primarily supplied by branches of the hepatic artery, whereas normal hepatocytes are supplied by the portal vein.…”

“…Although recent studies have shown promising long-term results, PHMP itself is reported to be associated with severe cardiovascular issues and potentially life-threatening adverse events, including myocardial infarction, cerebral stroke, and bleeding complications [1,[3][4][5][6][7][8][9][10][11][12][13][14][15]. Considerable hemodynamic instability can frequently occur after engagement of the filters and the clamping of the bypass circuit [3,13].…”