Treatment of Metastatic Uveal Melanoma: Systematic Review

Abstract

Introduction: More than 50% of patients with uveal melanoma end up developing metastases. Currently, there is no standard first-line treatment that facilitates proper management of the metastatic disease. Methods: A systematic review of the last 40 years in PubMed with an exhaustive and strict selection of studies was conducted, in which the unit of measurement was overall survival (OS) expressed in Kaplan–Meier curves or numerically. Results: After the selection process, 110 articles were included. Regional therapies, such as intra-arterial liver chemotherapy (OS: 2, 9–22 months), isolated liver perfusion (OS: 9, 6–27, 4 months), or selective internal radiation therapy (OS: 18 months in monotherapy and 26 months in combination with other therapies) showed some superiority when compared to systemic therapies, such as chemotherapy (OS: 4, 6–17 months), immunotherapy (OS: 5–19, 1 month), immunosuppression (OS: 11 months), or targeted therapy (OS: 6–12 months), without being significant. Conclusions: The results of this review suggest that there are no important differences in OS when comparing the different current treatment modalities. Most of the differences found seem to be explained by the heterogenicity of the different studies and the presence of biases in their design, rather than actual extensions of patient survival.

Monosomy 3 Is Linked to Resistance to MEK Inhibitors in Uveal Melanoma

“…Metastatic UM is a rare but fatal disease that is elusive from current therapies, including chemotherapy and immune checkpoint inhibitors [7]. In order to find potential new therapeutic approaches for the treatment of UM, we evaluated the response of six UM cell lines to a variety of chemotherapeutic and targeted compounds.…”

“…Once metastasized, median survival is very low, ranging between 3.7 to 7 months, and has not changed during the past decades due to a persisting lack of effective treatment options [3][4][5][6]. Since UM is highly resistant to chemotherapy and immunotherapy-based approaches (reviewed in [7]), targeted therapeutic compounds specifically affecting dysregulated cancer-promoting molecular pathways could serve as promising alternatives. Targeted therapy has been proven beneficial in cancers with certain molecular changes resulting in a dependency on specific signaling pathways.…”

Diagnostic methods and therapeutic options of uveal melanoma with emphasis on MR imaging—Part II: treatment indications and complications

“…Hepatic intra-arterial (HIA) chemotherapy involves the administration of different chemotherapeutic agents (fotemustine, melphalan, cisplatin) by the intra-arterial route through temporary or implantable catheters placed into the hepatic artery surgically or radiologically (via transfemoral approach); the catheters may be connected with a subcutaneous infusion pump. Median overall survival ranges between 9 and 21 months [ 59 , 65 ]. Procedure-related complications range between 0 and 17% and encompass: thrombosis, infection, leakage and catheter displacement [ 59 ].…”

“…The procedure involves the transarterial administration of chemotherapeutic agents followed by an embolic agent. Median overall survival is about 10 months [ 59 , 65 ]; nevertheless, when interpreting the data, it should be considered that this interventional technique is often employed as a second-line treatment [ 65 ].…”

“…Localized radioembolization of branches of the hepatic artery employing yttrium-90 ( 90 Y) microspheres can be used as a first-line treatment or a second-line treatment in patients no longer responding to previous local or systemic therapies. This procedure allows to deliver high radiation dose within tumor tissue with relative protection of the surrounding parenchyma, since radioactive microspheres, due to their small size, mainly localize within neoplastic microcirculation [ 60 , 65 , 68 ]. Activity delivered to hepatic parenchyma is limited to ≤ 35 Gy in order to reduce the risk of radiation-induced disease and treatment-related toxicity.…”