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S.A. Callejo, E. Antecka, P. Blanco, C. Edelstein, M.N. Burnier, Jr; Detection of Circulating Malignant Cells in Uveal Melanoma Patients . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3382.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Metastasis is the major cause of treatment failure and death in uveal melanoma patients (UMP). The majority of UMP do not show clinical, radiological or biochemical evidence of metastases upon diagnosis. Despite this negative initial work–up and an excellent local tumor control, approximately 40% of UMP will progress to develop metastases after a latent period of 6 to 10 years. These findings suggest that tumor cells have already disseminated by the time of initial diagnosis and UMP may have undetectable subclinical systemic disease in the form of circulating malignant cells (CMCs) or micrometastasis. Therefore, the purpose of the study was to detect CMCs in peripheral blood of UMP at various stages of disease progression (diagnosis, treatment, and latent period). The presence of CMCs was correlated with clinical prognostic factors and type of therapy. Methods: We conducted a prospective clinical study. At enrollment, the date of diagnosis, the largest tumor dimension, the tumor size at enrollment, and the type and date of treatment were obtained. The time period between treatment and enrollment (T T/E) was calculated. To detect CMCs nested RT–PCR with Melan A as a marker was used (lower detection level: 10 cells in 2ml of blood). Blood samples were collected every 3 months. In each visit, 20ml of peripheral blood was obtained and subdivided in 10 aliquots of 2 ml each, for a total of 10 RT–PCR per visit. If ≥ 1 of 10 aliquots tested positive, the patient was considered positive for that visit. The presence of CMCs was correlated with tumor location, tumor size at diagnosis, tumor size at enrollment, treatment, and T T/E. Results: 30 UMP, 22 radiated, 4 enucleated, and 4 observed, were enrolled in the study. During 18 months, a total of 136 visits were recorded with 1360 blood samples collected. 23 of 30 UMP were followed ≥ 4 times (range 4 to 7). All UMP tested positive for the presence of CMCs in at least one visit with an average of 2/10 samples positive per visit. 106 of 136 visits were positive (282 of 1360 samples). No correlation was found between CMC's and tumor location, tumor size at diagnosis or enrollment, type of treatment, and T T/E. Conclusions: This study confirms the presence of subclinical extraocular disease in UMP. All UMP tested positive for CMCs irrespective of the size and location of the primary tumor and modality of treatment. Although the relationship between CMCs and final outcome still need to be established based on a longer follow–up period, this study lays the foundation to recommend adjuvant therapies to target subclinical stages of tumor cell dissemination.
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