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Purpose CtDNA can be detected in the plasma of MUM pts using a real-time PCR based on the pyrophosphorolysis-activated polymerization (bi-PAP) targeting the most frequent GNAQ and GNA11 mutations present in 85% of UM (Madic et al, 2012). Methods May 2011-March 2013:87 MUM pts were included in 3 prospective studies to assess the bi-PAP assay and analyse clinical and outcome correlations. Results Median (med) age 57, primary tumor med diameter 15 mm; enucleation 32, proton beam 52, iodine disk 3. Enucleated eyes showed mostly mixed histotype and genomic high risk by array-CGH: 8q gain and/or 3p loss. With a med disease free interval of 39 months (mo), 83 pts developed liver metastases first, with radiological miliary disease in 55; 4 had extra hepatic lesions without liver involvement. 35 pts were enrolled at the time of metastasis diagnostic. With a med follow-up of 8 mo, 28 patients had disease progression and 34 died of metastasis. The med survival was 13 mo. Tumor samples were available in 82 pts, genotyping is ongoing for 8. GNAQ 626A>T or A>C, GNA11 626A>T and rare mutations were found in 9, 19, 26 is and 6 cases respectively; 14 were wild-type tumors. CtDNA was detected in 51/54 samples (med 30 copies/ml, range 1-11421) and correlated with the metastatic tumor burden as assessed by liver MRI (med 64 cm3, range 0.2-7384). Correlation with progression-free and overall survival will be presented. Conclusion ctDNA is a promising tool to assess the tumor burden and the micrometastatic dissemination of uveal melanoma, and a potential biomarker to evaluate the efficacy of targeted therapies in pts carrying GNA Q/11 mutated tumors. |
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