NTTS 2017

Melanoma patient blood-based biopsies have limited sensitivity in detecting early-stage regional lymph node metastasis and specific distant organ sites (i.e. melanoma brain metastasis; MBM). We investigated the clinical utility of a sensitive single-molecule next generation sequencing (smNGS) approach in patients’ plasma of early-stage regional lymph node melanoma metastasis and MBMs. We have evaluated bloods and matched tumor(s) when available from melanoma patients using smNGS. This study included a dozen patients with serial bleed analysis of follow-up from regional metastatic disease to distant organ metastasis recurrence including MBM patients. cfDNA genomic aberrations including therapeutic targets were detected in pre-operation of stage III/IV patients, including MBM patients. cfDNA mutation detection significantly correlated with tumor burden. Analysis demonstrated more efficiency of cfDNA compare to serum lactate dehydrogenase (LDH) a known blood prognostic marker for stage III/IV melanoma patients. cfDNA mutation analysis captured tumor heterogeneity and arising subclonal mutations upon recurrence. Patients with EGFR and/or MET cfDNA amplification were detect in plasma and were significantly associated with a shorter disease-free survival and overall survival compared. This study demonstrates the clinical utility of diagnosis and monitoring cutaneous melanoma from regional disease to brain metastasis. The studies demonstrate blood biopsy can detect subclinical disease well before onset of clinical disease progression. The approach also allows monitoring of tumor evolution/heterogeneity during distant metastasis progression during follow up.