Purpose Chemosaturation percutaneous hepatic perfusion (CS-PHP) allows selective intrahepatic delivery of high dose cytotoxic melphalan in patients with curatively untreatable liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. Aim of this study was to investigate the response to therapy, survival and safety of the CS-PHP procedure in patients with liver-dominant metastatic uveal melanoma (UM).
Materials and Methods Overall response rate (ORR) and disease control rate (DCR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic progression-free survival (mhPFS) were analyzed using Kaplan-Meier estimation. Adverse events were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v5.
Results Overall, 30 patients were treated with 70 CS-PHP in a salvage setting from October 2014 to January 2019. In total, ORR and DCR were 42.3 % and 80.8 %, respectively. Overall, mOS was 12 (95 % confidence interval (CI) 7–15) months, and both, mPFS and mhPFS were 6 months, respectively (95 % CI 4–10; 95 % CI 4–13). Adverse events (AE) most frequently included significant but transient hematologic toxicities (87 % of grade 3/4 thrombocytopenia), less frequent AEs were hepatic injury extending to liver failure (3 %), cardiovascular events including one case of ischemic stroke (3 %).
Conclusion Salvage treatment with CS-PHP is effective in selected patients with UM. The interventional procedure is safe. Serious hepatic and cardiovascular events, although rare, require careful patient selection and should be closely monitored.
Key Points:
Citation Format
To evaluate feasibility, frequency and severity of peri-procedural complications and post-procedural adverse events (AEs) in patients with advanced cholangiocarcinoma or liver metastasis of uveal melanoma and prior hemihepatectomy undergoing chemosaturation percutaneous hepatic perfusion (CS-PHP) and to analyze therapy response and overall survival compared to a matched group without prior surgery. CS-PHP performed between 10/2014 and 02/2018 were retrospectively assessed. To determine peri-procedural safety and post-procedural adverse events, hospital records and hematological, hepatic and biliary function were categorized using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (1–5; mild-death). Significance was tested using Wilcoxon signed-rank and Mann–Whitney U test. Kaplan–Meier estimation and log-rank test assessed survival. Overall 21 CS-PHP in seven patients (4/7 males; 52 ± 10 years) with hemihepatectomy (grouphemihep) and 22 CS-PHP in seven patients (3/7 males; 63 ± 12 years) without prior surgery (groupnoresection) were included. No complications occurred during the CS-PHP procedures. Transient changes (CTCAE grade 1–2) of liver enzymes and blood cells followed all procedures. In comparison, grouphemihep presented slightly more AEs grade 3–4 (e.g. thrombocytopenia in 57% (12/21) vs. 41% (9/22; p = 0.37)) 5–7 days after CS-PHP. These AEs were self-limiting or responsive to treatment (insignificant difference of pre-interventional to 21–45 days post-interventional values (p > 0.05)). One patient in grouphemihep with high tumor burden died eight days following CS-PHP. No deaths occurred in groupnoresection. In comparison, overall survival after first diagnosis was insignificantly shorter in groupnoresection (44.7(32–56.1) months) than in grouphemihep (48.3(34.6–72.8) months; p = 0.48). The severity of adverse events following CS-PHP in patients after hemihepatectomy was comparable to a matched group without prior liver surgery. Thus, the performance of CS-PHP is not substantially compromised by a prior hemihepatectomy.
Conventional detector-dose driven exposure controls (DEC) do not consider the contrasting material of interest in angiography. Considering the latter when choosing the acquisition parameters should allow for optimization of x-ray quality and consecutively lead to a substantial reduction of radiation exposure. Therefore, the impact of a material-specific, contrast-to-noise ratio (CNR) driven exposure control (CEC) compared to DEC on radiation exposure was investigated. A 3D-printed phantom containing iron, tantalum, and platinum foils and cavities, filled with iodine, barium, and gas (carbon dioxide), was developed to measure the CNR. This phantom was placed within a stack of polymethylmethacrylate and aluminum plates simulating a patient equivalent thickness (PET) of 2.5–40 cm. Fluoroscopy and digital radiography (DR) were conducted applying either CEC or three, regular DEC protocols with parameter settings used in abdominal interventions. CEC protocols where chosen to achieve material-specific CNR values similar to those of DEC. Incident air kerma at the reference point(Ka,r), using either CEC or DEC, was assessed and possible Ka,r reduction for similar CNR was estimated. We show that CEC provided similar CNR as DEC at the same or lower Ka,r. When imaging barium, iron, and iodine Ka,r was substantially reduced below a PET of 20 cm and between 25 cm and 30 cm for fluoroscopy and Dr When imaging platinum and tantalum using fluoroscopy and DR and gas using DR, the Ka,r reduction was substantially higher. We estimate the Ka,r reduction for these materials between 15% and 84% for fluoroscopy and DR between 15% and 93% depending on the PET. The results of this study demonstrate a high potential for skin dose reduction in abdominal radiology when using a material-specific CEC compared to DEC. This effect is substantial in imaging materials with higher energy K-edges, which is beneficial, for example, in long-lasting embolization procedures with tantalum-based embolization material in young patients with arterio-venous malformations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.