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Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers

ABSTRACT: Chemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2–6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0–354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153–701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00270-021-02983-2.

SUBMITTER: Veelken R

PROVIDER: S-EPMC8555734 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Percutaneous Hepatic Perfusion (PHP) with Melphalan in Liver-Dominant Metastatic Uveal Melanoma: The German Experience.

Project description: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.

| S-EPMC8749811 | biostudies-literature

Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma.

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| S-EPMC8893121 | biostudies-literature

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| S-EPMC8758076 | biostudies-literature

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| S-EPMC7801354 | biostudies-literature

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| S-EPMC9458688 | biostudies-literature

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

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Meta-Analysis of Isolated Hepatic Perfusion and Percutaneous Hepatic Perfusion as a Treatment for Uveal Melanoma Liver Metastases.

Project description:Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous hepatic perfusion (PHP), a minimally invasive technique, is available as well. PHP benefits from the fact that the procedure can be repeated and therefore possibly offers better survival. We conducted a systematic review and meta-analysis comparing both techniques. A systematic literature search was performed using the electronic databases of Scopus, MEDLINE, Web of Science, PubMed and Cochrane CENTRAL. A total of nine articles reporting on eight studies were included in the analysis. Individual survival data were extracted from each study. The median overall survival (OS) was 17.1 months for IHP and 17.3 months for PHP. The median progression-free survival (PFS) was 7.2 months for IHP and 9.6 months for PHP. The median hepatic progression-free survival was 10 months for IHP and 9.5 months for PHP. The complication rate and 30-day mortality rate were 39.1% and 5.5% for IHP and 23.8% and 1.8% for PHP. There was no difference in OS or PFS between IHP and PHP for patients with uveal melanoma liver metastases, but patients have significantly less of a risk for complications and mortality following PHP.

| S-EPMC8469397 | biostudies-literature

Isolated hepatic perfusion with 200 mg melphalan for advanced noncolorectal liver metastases.

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| S-EPMC2467497 | biostudies-other

Evaluation of Delcath Systems' Generation 2 (GEN 2) melphalan hemofiltration system in a porcine model of percutaneous hepatic perfusion.

Project description:PURPOSE: A new melphalan hemoperfusion filter (GEN 2) was evaluated in a simulated-use porcine model of percutaneous hepatic perfusion (PHP). The current study evaluated melphalan filtration efficiency, the transfilter pressure gradient, and the removal of specific blood products. MATERIALS AND METHODS: A porcine PHP procedure using the GEN 2 filter was performed under Good Laboratory Practice conditions to model the 60-min clinical PHP procedure. RESULTS: The mean filter efficiency for removing melphalan in six filters was 99.0 ± 0.4 %. The transfilter pressure gradient across the filter averaged 20.9 mmHg for the 60-min procedure. Many blood components, including albumin and platelets, decreased on average from 3.55 to 2.02 g/dL and from 342 to 177 × 10.e3/μL, respectively, during the procedure. CONCLUSION: The increased melphalan extraction efficiency of the new filter is expected to decrease systemic melphalan exposure. In addition, the low transfilter pressure gradient resulted in low resistance to blood flow in the GEN 2 filter, and the changes to blood components are expected to be clinically manageable.

| S-EPMC4024156 | biostudies-literature

Over 12 Years Single Institutional Experience Performing Percutaneous Hepatic Perfusion for Unresectable Liver Metastases.

Project description:Patients with unresectable hepatic metastases, from uveal or ocular melanoma, are challenging to treat with an overall poor prognosis. Although over the past decade significant advances in systemic therapies have been made, metastatic disease to the liver, especially from uveal melanoma, continues to be a poor prognosis. Percutaneous hepatic perfusion (PHP) is a safe, viable treatment option for these patients. PHP utilizes high dose chemotherapy delivered directly to the liver while minimizing systemic exposure and can be repeated up to 6 times. Isolation of the hepatic vasculature with a double-balloon catheter allows for high concentration cytotoxic therapy to be administered with minimal systemic adverse effects. A detailed description of the multidisciplinary treatment protocol used at an institution with over 12 years of experience is discussed and recommendations are given. A dedicated team of a surgical or medical oncology, interventional radiology, anesthesiology and a perfusionist allows PHP to be repeatedly performed as a safe treatment strategy for unresectable hepatic metastases.

| S-EPMC8480350 | biostudies-literature

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