Chemosaturation with percutaneous hepatic perfusion is effective in patients with ocular melanoma and cholangiocarcinoma

Abstract

Background Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System; Delcath Systems Inc, USA) is a novel interventional procedure, which delivers high doses of melphalan directly to the liver in patients with liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. We have previously shown promising efficacy for patients with ocular melanoma (OM) and cholangiocarcinoma (CCA) within our single-center and multi-center experiences. The aim of this study was to analyze the safety and efficacy of CS-PHP after 141 treatments at Hannover Medical School, Germany. Methods Overall response rates (ORR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median Overall survival (mOS), median progression-free survival (mPFS), and median hepatic PFS (mhPFS) were analyzed using the Kaplan–Meier estimation. Results Overall, 60 patients were treated with CS-PHP in the salvage setting from October 2014 until January 2019 at Hannover Medical School with a total of 141 procedures. Half of the patients were patients with hepatic metastases of ocular melanoma (OM) (n = 30), 14 patients had CCA (23.3%), 6 patients had hepatocellular carcinoma (10%), and 10 patients were treated for other secondary liver malignancies (16.7%). In total, ORR and disease stabilization rate were 33.3% and 70.3% (n = 25), respectively. ORR was highest for patients with OM (42.3%), followed by patients with CCA (30.8%). Independent response-associated factors were normal levels of lactate dehydrogenase (odds ratio (OR) 13.7; p = 0.015) and diagnosis with OM (OR 9.3; p = 0.028). Overall, mOS was 9 months, mPFS was 4 months, and mhPFS was 5 months. Patients with OM had the longest mOS, mPFS, and mhPFS with 12, 6, and 6 months, respectively. Adverse events included most frequently significant, but transient, hematologic toxicities (80% of grade 3/4 thrombopenia), less frequently hepatic injury up to liver failure (3.3%) and cardiovascular events including two cases of ischemic insults (5%). Conclusion Salvage treatment with CS-PHP is safe and effective particularly in patients OM and CCA. Careful attention should be paid to possible, serious hepatic, and cardiovascular complications.

Chemosaturation with Percutaneous Hepatic Perfusion: Outcome and Safety in Patients with Metastasized Uveal Melanoma

“…Concurring with several studies that investigated 2 nd generation CS-PHP in different patient cohorts (patients with exclusively metastatic UM [3,10,11] or patients with various liver tumors [7,8,12,16]), hemotoxicity after CS-PHP in our study was significant, but treatable and transient. The literature reports the rate of transaminitis in patients with UM after CS-PHP to be between 6 and 20 % [10].…”

“…The study population is part of a current study analyzing the totality of chemosaturations performed at our institution for different primary tumor entities [16]. Part of the study population (n = 19) was already included in a single-center observational study [7].…”

“…Die Studienpopulation ist Bestandteil einer aktuellen Studie, welche die Gesamtheit der in unserer Institution durchgeführten Chemosaturationen bei unterschiedlichen Primärtumorentitäten analysiert [16]. Ein Teil der Studienpopulation (n = 19) wurde bereits in einer monozentrischen Beobachtungsstudie inkludiert [7].…”

Percutaneous isolated hepatic perfusion (chemosaturation) with melphalan following right hemihepatectomy in patients with cholangiocarcinoma and metastatic uveal melanoma: peri- and post-interventional adverse events and therapy response compared to a matched group without prior liver surgery

“…In the setting of unresectable iCCA, guidelines suggest locoregional therapy approaches in patients with tumor progression under first-line systemic chemotherapy [ 6 ]. CS-PHP in iCCA has so far only been evaluated in small cohorts, but presented long-lasting tumor stabilization in selected patients [ 1 , 13 , 20 ]. In order to provide optimal patient tailored treatment options, possible benefits over other locoregional therapy approaches (e.g.…”

“…All patients gave written consent before CS-PHP. Part of this study population has previously been reported [11,13]. These articles dealt with safety and efficacy of the second-generation CS-PHP, whereas this study focuses on peri-and post-interventional adverse events and therapy response of patients with previous right hemihepatectomy compared to a matched group without prior liver surgery.…”