Over 12 Years Single Institutional Experience Performing Percutaneous Hepatic Perfusion for Unresectable Liver Metastases.
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ABSTRACT:
SUBMITTER: Carr MJ
PROVIDER: S-EPMC8480350 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposePercutaneous hepatic perfusion with melphalan (M-PHP) is increasingly used in patients with liver metastases from various primary tumors, yet data on colorectal liver metastases (CRLM) are limited. The aim of this study was to prospectively evaluate the efficacy and safety of M-PHP in patients with CRLM.Materials and methodsProspective, single-center, single-arm phase II study of M-PHP with hemofiltration in patients with unresectable CRLM. Proven, extrahepatic metastatic disease was one of the exclusion criteria. Primary outcomes were overall response rate (ORR) and best overall response (BOR). Secondary outcomes were overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety.ResultsA total of 14 M-PHP procedures were performed in eight patients between March 2014 and December 2015. All patients (median age 56 years, ranging from 46 to 68) had received (extensive) systemic chemotherapy before entering the study. The ORR was 25.0%, with two out of eight patients showing partial response as BOR. Median OS was 17.3 months (ranging from 2.6 to 30.9) with a one-year OS of 50.0%. Median PFS and hPFS were 4.4 and 4.5 months, respectively. No serious adverse events occurred. Grade 3/4 hematologic adverse events were observed in the majority of patients, though all were transient and well-manageable.ConclusionM-PHP is a safe procedure with only limited efficacy in patients with unresectable CRLM who already showed progression of disease after receiving one or more systemic treatment regimens.
| S-EPMC8758076 | biostudies-literature
Project description:BackgroundOcular melanoma is the most common primary intraocular malignancy and has a very poor prognosis once liver metastases occur. The aim of this study was to prospectively assess the efficacy and safety of percutaneous hepatic perfusion with melphalan (M-PHP) using the new second-generation (GEN 2) hemofiltration system in patients with ocular melanoma metastases confined to the liver.MethodsProspective, single-center, single-arm, phase II study including patients with unresectable ocular melanoma metastases confined to the liver. Treatment consisted of two M-PHP procedures at 6-8 weeks interval. Procedures were performed using the CHEMOSAT (GEN 2) system with 3 mg/kg melphalan. Primary endpoints were overall response rate (ORR) and best overall response (BOR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety.ResultsSixty-four M-PHP procedures were performed in 35 patients between February 2014 and June 2017. The ORR was 72%. BOR was as follows: complete response in 3%, partial response in 69%, stable disease in 13%, and progressive disease in 16%. There was no treatment-related mortality. Fourteen serious adverse events occurred. At a median follow-up of 19.1 months (range 5.6-69.5), median OS was 19.1 months and was significantly longer in responders than in nonresponders (27.5 vs. 11.9 months, p < 0.001). The 1- and 2-year OS was 77% and 43%, respectively. PFS and hPFS were 7.6 and 11.2 months, respectively.ConclusionsM-PHP using the GEN 2 filter can achieve a high ORR and prolonged survival in patients with liver-only ocular melanoma metastases.
| S-EPMC7801354 | biostudies-literature
Project description:PurposeThe aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers.Materials and methodsRetrospective analysis including patients ([Formula: see text] 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0.ResultsIn total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases).ConclusionM-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.
| S-EPMC9458688 | biostudies-literature
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
Project description:Cholangiocarcinoma (CCA) are the second most common primary liver tumors and carry a dismal prognosis. Chemosaturation with percutaneous hepatic perfusion (PHP) is a palliative, intra-arterial therapeutic approach that provides a high dose chemotherapy of the liver with reduced systemic exposure. Aim of this retrospective, monocentric study was to analyze PHP as a palliative treatment for unresectable CCA. Toxicity, adverse events and complications were classified using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic mPFS (mhPFS) were computed using Kaplan-Meier estimation. In total 17 patients were treated with 42 PHP between 10/2014 and 09/2020. No significant complications occurred during the interventions. mOS was 27.6 (interquartile range (IQR) 16.5-37) months from first diagnosis and 9.9 (IQR 3.8-21) months from first PHP. mPFS was 4 (IQR 2-7) and mhPFS was 4 (IQR 3-10) months. ORR was 25% and DCR 75%. Significant, but transient hematotoxicity was frequent with grade 3/4 thrombopenia after 50%, leukopenia after 26% and anaemia after 21% of the interventions. An increase of transaminases (AST increase after 21% and ALT increase after 14% of the PHP) developed more often than a deterioration of the liver synthesis capacity. Salvage treatment with PHP has the potential to prolong life in selected patients with unresectable, refractory cholangiocarcinoma. The interventional procedure is safe. Post-interventional toxicity is frequent but manageable.
| S-EPMC9898387 | biostudies-literature
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
Project description:BackgroundPercutaneous hepatic melphalan perfusion (PHMP) for the selective treatment of hepatic metastases is known to be associated with procedural hypotension and coagulation disorders. Studies on anesthetic management, perioperative course, complications, and postoperative recovery in the intensive care unit (ICU) have not been published.MethodsIn a retrospective observational study, we analyzed consecutive patients who were admitted for PHMP over a 6-year period (2016-2021). Analyses included demographic, treatment, and outcome data with regard to short-term complications until ICU discharge.ResultsFifty-three PHMP procedures of 16 patients were analyzed. In all of the cases, procedure-related 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 (3-14) liters. Eighty-four PHMP-related complications were observed in 33 cases (62%), of which 9 cases (27%) involved grade III and IV complications. Complications included airway constriction (requiring difficult airway management), vascular catheterization issues (which resulted in the premature termination of PHMP, as well as to the postponement of PHMP and to the performance of endovascular bleeding control after PHMP), and renal failure that required hemodialysis. Discharge from the ICU was possible after one day in most cases (n = 45; 85%); however, in 12 cases (23%), prolonged mechanical ventilation was required. There were no procedure-related fatalities.ConclusionsPHMP is frequently associated with challenging cardiovascular conditions and complications that require profound anesthetic skills. For safety reasons, PHMP should only be performed in specialized centers that provide high-level hospital infrastructures and interdisciplinary expertise.
| S-EPMC8284610 | biostudies-literature
Project description:PURPOSE:A mandibular metastasis is uncommon in patients with hepatocellular carcinoma (HCC). We report the clinical features of this rare lesion and evaluate the effectiveness of radiotherapy in affected patients. MATERIALS AND METHODS:We retrospectively reviewed our institutional medical records for HCC patients who received radiotherapy for bone metastasis, and included cases of mandible metastasis. The clinical features of these cases, and the characteristics and outcomes of the treatments were assessed. RESULTS:A total of 1,498 patients with a bone metastasis from HCC were treated with radiotherapy between July 1998 and April 2012 at our institution. We identified 9 patients (0.6%) in this cohort that received radiotherapy for a mandibular metastasis. The condyle was the most common location of mandibular metastasis. The median radiation dose was 40 Gy (range, 27.5 to 60 Gy), with a daily dose of 2-3 Gy. All of these 9 patients died during a median follow-up of 9 months (range, 1 to 19 months). Symptom relief was achieved in 7 of 8 patients who completed radiotherapy. Tumor size reduction was observed in 2 of 4 patients who underwent radiologic evaluation after radiotherapy. CONCLUSION:Metastasis to the mandible from HCC has a poor prognosis. Radiotherapy can be an effective local treatment option for symptomatic relief in these cases.
| S-EPMC6952715 | biostudies-literature
Project description:Isolated hepatic perfusion (IHP) with melphalan is an established approach for patients with unresectable metastatic liver lesions. This study determined the safety and maximum tolerated dose (MTD) of 5-FU with oxaliplatin via IHP.Standard 3 × 3 Phase I design. Subjects with unresectable isolated CRC liver metastases scheduled for HAI pump were eligible. IHP used fixed-dose oxaliplatin with escalating 5-FU doses. Toxicity (CTCAE v 4.0) and response (RECIST), progression-free survival, and overall survival (OS) were assessed. Systemic and IHP plasma PK of 5-FU, anabolites, and platinum were determined.All 12 patients had received ? 1 line of pre-IHP chemotherapy. There were 4 grade 3 serious adverse events (33.3 %) and 1 grade 4 event (8.3 %). Also, 2 dose-limiting toxicities occurred at DL2 at 300 mg/m(2), resulting in expansion of DL1 at 200 mg/m(2) 5-FU, the eventual MTD. At 6-month follow-up, 9 patients (82 %) demonstrated partial response, while 2 (18 %) exhibited stable disease. Also, 64 % of patients demonstrated a >50 % decrease in CEA. The 1- and 2-year OS probabilities were 90.9 and 71.6 %, respectively, with median follow-up of 24 months. IHP exposures (AUC0-60 min) were 10.9 ± 4.5 ?gPt h/mL, 49.3 ± 30.7 ?g h/mL 5-FU (DL1), and 70.5 ± 35.5 ?g h/mL 5-FU (DL2). Systemic exposure (AUC0-inf) relative to IHP exposure was negligible for both platinum (1.1 ± 1.5 %) and 5-FU (0.09 ± 0.10 %).The MTD for IHP was 200 mg/m(2) 5-FU with 40 mg/m(2) oxaliplatin. Systemic exposure to the agents was minimal during IHP. The response and survival observed warrants assessment in a larger phase II trial.
| S-EPMC3808182 | biostudies-literature
Project description:Uveal melanoma, the most common primary ocular malignancy in adults, carries a poor prognosis: 50% of patients develop the metastatic disease with a 10-25% 1-year survival and no established standard of care treatment. Prior studies of melphalan percutaneous hepatic perfusion (M-PHP) have shown promise in metastatic uveal melanoma (mUM) patients with liver predominant disease but are limited by small sample sizes. We contribute our findings on the safety and efficacy of the procedure in the largest sample population to date. A retrospective analysis of outcome and safety data for all mUM patients receiving M-PHP was performed. Tumour response and treatment toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events v5.03, respectively. 250 M-PHP procedures were performed in 81 patients (median of three per patient). The analysis demonstrated a hepatic disease control rate of 88.9% (72/81), a hepatic response rate of 66.7% (54/81), and an overall response rate of 60.5% (49/81). After a median follow-up of 12.9 months, median overall progression-free (PFS) and median overall survival (OS) were 8.4 and 14.9 months, respectively. There were no fatal treatment-related adverse events (TRAE). Forty-three grade 3 (29) or 4 (14) TRAE occurred in 23 (27.7%) patients with a significant reduction in such events between procedures performed in 2016-2020 vs. 2012-2016 (0.17 vs. 0.90 per patient, P < 0.001). M-PHP provides excellent response rates and PFS compared with other available treatments, with decreasing side effect profile with experience. Combination therapy with systemic agents may be viable to further advance OS.
| S-EPMC8893121 | biostudies-literature