Abstract A12: Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma

Abstract

Abstract Introduction: Uveal melanoma (UM) is a rare melanoma; only 5% of cases at initial presentation have distant metastasis. As approximately 50% of patients will develop metastatic disease, there is a need to detect minimal residual disease (MRD). Liquid biopsy using circulating tumor cells (CTCs) has been evaluated in multiple tumors; high CTC count predicts for increased risk of metastasis. We conducted a pilot study to check feasibility of CTCs in UM and evaluate if CTCs vary with risk status in early-stage UM. Methods: We enrolled 40 UM patients ≥18 years, after obtaining informed consent in an IRB-approved protocol from 12/1/2014 to 2/1/2018. Peripheral blood was obtained to detect CTCs using CellSearch Circulating Melanoma Cell Assay. Demographic information, mutational analysis, date of diagnosis of primary UM or metastasis, and dates of CTC collection were collected. Risk stratification was done by gene expression profiling (GEP) by DecisionDX-UM assay. Landmark overall survival (OS) was calculated using “Landest” R package comparing CTC detected vs. not detected in early-stage UM. Results: 39 patients were available for analysis. Median age of whole cohort was 52 years (20-83 years), 100% were non-Hispanic Caucasians, and 44% were male and 56% female. 20 patients had early-stage vs. 19 patients had metastatic disease at enrollment. 87% (13/15) of early-stage disease had class II disease. GNAQ & GNA11 mutations were present in 36% (12/39) and 13% (5/29), respectively. At initial blood draw, 36% of the patients had detectable CTCs [30% (6/20) in early stage vs. 42% (8/19) in metastatic], which increased to 54% at median study follow-up of 16.4 months [40% (8/20) in early stage vs. 68% (13/19) in metastatic]. Mean CTCs were higher in metastatic (9) vs. early stage (1.83) (p>0.05). 5 patients in early-stage disease developed distant metastasis; 60% (3/5) had detectable CTCs before radiographic detection of metastasis. Out 5, 80% had class II disease and 20% had unknown GEP. Landmark overall survival (from study enrollment) at 24 months was statistically worse in CTC detected vs. not detected in early-stage UM (P<0.05). Conclusion: CTCs are more frequently detected in metastatic compared to early-stage UM. In early-stage UM, presence of CTCs predicts for increased risk of metastatic disease and is associated with worse outcome. Citation Format: Jason Roszik, Dan Gombos, Joshua Upshaw, Vanessa Sarli, Salyna Meas, Anthony Lucci, Carolyn Hall, Sapna Patel, Kartik Anand. Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A12.