Locoregional Therapies for the Treatment of Uveal Melanoma Hepatic Metastases

AbstractUveal melanoma is the most common primary intraocular malignant tumor in adults. Approximately 50% of patients develop metastatic disease of which greater than 90% of patients develop hepatic metastases. Following the development of liver tumors, overall survival is dismal with hepatic failure being the cause of death in nearly all cases. To prolong survival for patients with metastatic uveal melanoma, controlling the growth of hepatic tumors is essential. This article will discuss imaging surveillance following the diagnosis of primary uveal melanoma; locoregional therapies used to control the growth of hepatic metastases including chemoembolization, immunoembolization, radioembolization, percutaneous hepatic perfusion, and thermal ablation; as well as currently available systemic treatment options for metastatic uveal melanoma.

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

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-020-03289-5 ◽

2020 ◽

Vol 146 (11) ◽

pp. 3003-3012 ◽

Cited By ~ 1

Author(s):

Leon Schönfeld ◽

Jan B. Hinrichs ◽

Steffen Marquardt ◽

Torsten Voigtländer ◽

Cornelia Dewald ◽

...

Keyword(s):

Medical School ◽

Liver Tumors ◽

Interventional Procedure ◽

Venous Blood ◽

Hepatic Metastases ◽

Ocular Melanoma ◽

Liver Malignancies ◽

Hannover Medical School ◽

Hepatic Perfusion ◽

Percutaneous Hepatic Perfusion

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.

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Complications of thermal ablation of hepatic tumors: Comparison of radiofrequency and microwave techniques.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15040 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15040-e15040 ◽

Cited By ~ 1

Author(s):

Xiang Jing ◽

Jianmin Ding ◽

Jibin Liu ◽

Yandong Wang ◽

Fengmei Wang ◽

...

Keyword(s):

Liver Cancer ◽

Thermal Ablation ◽

Liver Tumors ◽

Major Complication ◽

Mortality Rates ◽

Complication Rates ◽

Hepatic Tumors ◽

Ablation Therapy ◽

Liver Cancers ◽

Significant Difference

e15040 Background: The efficacy and safety of radiofrequency ablation (RFA) have been reported in the literatures, which are considered as frontline choice for treatment of liver cancer. Recently, microwave ablation (MWA) has emerged and gained great attention over RFA. However, in comparison to RFA, the safety of MWA for treatment of liver cancer has not been fully reported in the literatures. Studies with large clinical data sets are still needed to understand the technique and avoid the complications. The objective of this study was to retrospectively investigate the common complications of thermal ablations of liver tumors using both RFA and MWA techniques, and compare the safety between these two procedures. Methods: This retrospective study protocol was approved by our institutional ethics committee to allow investigators to review the existing patient’s medical records. A total of 879 patients with hepatic tumors underwent thermal ablation. There were 323 cases having the RFA procedures and 556 cases having MWA procedures. The complications of thermal ablations of liver tumors were compared using both RFA and MWA techniques. Results: A total of 1,030 thermal ablation sessions was performed in 879 patients with a total of 1,652 tumors. There were 323 patients with 562 tumors received a total of 376 RFA with averaged 1.16±0.48 sessions per patient. The other 556 patients with 1,090 tumors received a total of 654 MWA with averaged1.18±0.51 sessions per patient. The mortality rates were 0.31% (1/323) and 0.36% (2/556) in RFA and MWA group. In RFA and MWA group, the major complication rates were 3.5% (13/376) and 3.1% (20/654) (Table 1), meanwhile the minor complication rates were 5.9% (22/376) and 5.7% (37/654). There was no statistical significant difference for the mortality rates, the major complications, the minor complications between the RFA and MWA groups (P>0.05). Conclusions: Thermal ablation therapy in the treatment of liver cancers is relatively safe with low mortality and low incidence of serious complications. The types and incidences of complications caused by RFA and MWA are similar and comparable for safety consideration in clinical settings.

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

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren ◽

10.1055/a-1348-1932 ◽

2021 ◽

Author(s):

Cornelia Lieselotte Angelika Dewald ◽

Jan B. Hinrichs ◽

Lena Sophie Becker ◽

Sabine Maschke ◽

Timo C. Meine ◽

...

Keyword(s):

Adverse Events ◽

Uveal Melanoma ◽

Cardiovascular Events ◽

Liver Tumors ◽

Progression Free Survival ◽

Response To Therapy ◽

High Dose ◽

Free Survival ◽

Hepatic Perfusion ◽

Percutaneous Hepatic Perfusion

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

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A single-center experience in radioembolization as salvage therapy of hepatic metastases of uveal melanoma

Acta Radiologica Open ◽

10.1177/2047981615570417 ◽

2015 ◽

Vol 4 (4) ◽

pp. 204798161557041 ◽

Cited By ~ 7

Author(s):

Juliane Schelhorn ◽

Heike Richly ◽

Marcus Ruhlmann ◽

Thomas C Lauenstein ◽

Jens M Theysohn

Keyword(s):

Uveal Melanoma ◽

Salvage Therapy ◽

Hepatic Metastases ◽

Response To Therapy ◽

Tumor Control ◽

Single Center ◽

Single Center Experience ◽

Kaplan Meier ◽

Heavily Pretreated ◽

Locoregional Therapies

Background Overall survival (OS) of patients with hepatic metastases of uveal melanoma is strongly linked with hepatic tumor control. Due to the lack of an effective systemic chemotherapy, locoregional therapies like radioembolization should play an increasingly important role. Purpose To report complications and response rates of radioembolization as salvage therapy for hepatic uveal melanoma metastases. Material and Methods Between October 2006 and January 2014, eight patients (age, 59.1 ± 15.3 years; 5 men) with histologically proven uveal melanoma and hepatic metastases received radioembolization with glass microspheres at a single center. All patients had been heavily pretreated with multiple systemic/locoregional therapies resulting in a long median interval between diagnosis of hepatic metastases and radioembolization (17.1 months; range, 6.4–23.2 months). Follow-up consisted of clinical assessment, laboratory tests and tri-phasic computed tomography (CT) before and 1, 3, 6, 9, and 12 months after radioembolization. Response to therapy was evaluated by CT using RECIST version 1.1 and by survival time. Safety (laboratory and clinical toxicity) was rated according to Common Terminology Criteria for Adverse Events 4.03. Using Kaplan-Meier analysis time to progression of hepatic metastases (hTTP) and OS were calculated. Results One month after radioembolization 50% of patients presented with stable and 50% with progressive disease. Median hTTP and OS after radioembolization were 4.3 weeks (range, 3.4–28.6 weeks) and 12.3 weeks (range, 3.7–62.6 weeks), respectively. Median OS after diagnosis of hepatic metastases was 19.9 months (range, 7.3–31.4 months). Radioembolization was tolerated well in all patients without toxicity higher than grade 2. Conclusion Radioembolization is a safe salvage therapy even in heavily pretreated hepatic metastases of uveal melanoma.

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Development of Alpha-emitting radioembolization for Hepatocellular Carcinoma: Longitudinal Monitoring of Actinium-225’s Daughters Through SPECT Imaging

10.21203/rs.3.rs-134829/v1 ◽

2020 ◽

Author(s):

Yong Du ◽

Angel Cortez ◽

Mohammadreza Zarisfi ◽

Anders Josefsson ◽

Rebecca Krimins ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Mouse Model ◽

Normal Tissue ◽

Liver Tumors ◽

Primary Liver Cancer ◽

Treatment Options ◽

Spect Imaging ◽

Hepatic Tumors

Abstract Hepatocellular carcinoma is the most common primary liver cancer and the fifth most frequently diagnosed cancer worldwide. Most patients with advanced disease are offered non-surgical palliative treatment options. This work explores the first α-emitting radioembolization for the treatment and monitoring of hepatic tumors. Furthermore, this works demonstrates the first in vivo simultaneous multiple-radionuclide SPECT images of the complex decay chain of an [225Ac]Ac-labeled agent using a clinical SPECT system to monitor the temporal distribution. Methods: A DOTA chelator was modified with a lipophilic moiety and radiolabeled with Actinium-225. The resulting agent, [225Ac]Ac-DOTA-TDA, was emulsified in Lipiodol® and evaluated in vivo in mouse model and the VX2 rabbit technical model of liver cancer. SPECT imaging was performed to monitor distribution of the TAT agent and the free daughters.Results: [225Ac]Ac-DOTA-TDA was shown to retain within the HEP2G tumors and VX2 tumor, with minimal uptake within normal tissue. In the mouse model, significant improvements in overall survival were observed. SPECT imaging was able to distinguish between the Actinium-225 agent (Francium-221) and the loss of the longer lived daughter, Bismuth-213. Conclusion: A TAT agent emulsified in Lipiodol® is capable of targeting liver tumors with minimal accumulation in normal tissue, providing a potential therapeutic agent for the treatment of HCC as well as a variety of hepatic tumors. In addition, SPECT imaging presented here provides a foundation for imaging methodology and protocols that can be rapidly translated into the clinic to monitor Actinium-225-labeled agents.

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▪ Cryosurgery and Thermal Ablation of Primary Liver Tumors and Hepatic Metastases

Surgical Ultrasound ◽

10.1055/b-0034-76198 ◽

2007 ◽

Keyword(s):

Thermal Ablation ◽

Liver Tumors ◽

Hepatic Metastases ◽

Primary Liver Tumors

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Immunoembolization of Malignant Liver Tumors, Including Uveal Melanoma, Using Granulocyte-Macrophage Colony-Stimulating Factor

Journal of Clinical Oncology ◽

10.1200/jco.2008.16.0705 ◽

2008 ◽

Vol 26 (33) ◽

pp. 5436-5442 ◽

Cited By ~ 50

Author(s):

Takami Sato ◽

David J. Eschelman ◽

Carin F. Gonsalves ◽

Mizue Terai ◽

Inna Chervoneva ◽

...

Keyword(s):

Uveal Melanoma ◽

Liver Tumors ◽

Hepatic Metastases ◽

Gm Csf ◽

Malignant Liver Tumors ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

High Doses ◽

Malignant Liver ◽

Stimulating Factor

Purpose We conducted a phase I study to investigate the feasibility and safety of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for malignant liver tumors, predominantly hepatic metastases from patients with primary uveal melanoma. Patients and Methods Thirty-nine patients with surgically unresectable malignant liver tumors, including 34 patients with primary uveal melanoma, were enrolled. Hepatic artery embolization accompanied an infusion of dose-escalated GM-CSF (25 to 2,000 μg) given every 4 weeks. Primary end points included dose-limiting toxicity and maximum tolerated dose (MTD). Patients who completed two cycles of treatments were monitored for hepatic antitumor response. Survival rates of patients were also monitored. Results MTD was not reached up to the dose level of 2,000 μg, and there were no treatment-related deaths. Thirty-one assessable patients with uveal melanoma demonstrated two complete responses, eight partial responses, and 10 occurrences of stable disease in their hepatic metastases. The median overall survival of intent-to-treat patients who had metastatic uveal melanoma was 14.4 months. Multivariate analyses indicated that female sex, high doses of GM-CSF (≥ 1,500 μg), and regression of hepatic metastases (complete and partial responses) were correlated to longer overall survival. Moreover, high doses of GM-CSF were associated with prolonged progression-free survival in extrahepatic sites. Conclusion Immunoembolization with GM-CSF is safe and feasible in patients with hepatic metastasis from primary uveal melanoma. Encouraging preliminary efficacy and safety results warrant additional clinical study in metastatic uveal melanoma.

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Radiofrequency Thermal Ablation of Metastatic Liver Tumors: Usefulness of Combined Chemotherapy

Journal of the Korean Radiological Society ◽

10.3348/jkrs.2001.45.2.147 ◽

2001 ◽

Vol 45 (2) ◽

pp. 147

Author(s):

Jeong Nam Heo ◽

Hyun Chul Rhim ◽

Yong Soo Kim ◽

Byung Hee Koh ◽

On Koo Cho ◽

...

Keyword(s):

Thermal Ablation ◽

Liver Tumors ◽

Combined Chemotherapy ◽

Radiofrequency Thermal Ablation ◽

Metastatic Liver Tumors ◽

Metastatic Liver

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Interventional Oncology Approach to Hepatic Metastases

Seminars in Interventional Radiology ◽

10.1055/s-0040-1719189 ◽

2020 ◽

Vol 37 (05) ◽

pp. 484-491

Author(s):

Cathal O'Leary ◽

Michael C. Soulen ◽

Susan Shamimi-Noori

Keyword(s):

Liver Disease ◽

Liver Function ◽

Interventional Oncology ◽

Hepatic Metastases ◽

Locoregional Therapy ◽

Treatment Modalities ◽

Patient Specific ◽

Curative Intent ◽

Locoregional Therapies ◽

Metastatic Liver

AbstractMetastatic liver disease is one of the major causes of cancer-related morbidity and mortality. Locoregional therapies offered by interventional oncologists alleviate cancer-related morbidity and in some cases improve survival. Locoregional therapies are often palliative in nature but occasionally can be used with curative intent. This review will discuss important factors to consider prior to palliative and curative intent treatment of metastatic liver disease with locoregional therapy. These factors include those specific to the tumor, liver function, liver reserve, differences between treatment modalities, and patient-specific considerations.

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