219P - Assessment of circulating free DNA (CFDNA) and circulating melanoma cells (CMCs) as prognostic biomarkers in metastatic cutaneous melanoma

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Melanoma and other Skin Tumours
Translational Research
Presenter Kyaw Aung
Authors K. Aung1, L.T. Khoja2, C. Zhou3, M. Lancashire3, R. Sloane3, G. Brady3, G. Clack4, A. Hughes4, P. Lorigan5, C. Dive3
  • 1Clinical And Experimental Pharmacology, The Paterson Institute for Cancer Research, Manchester/UK
  • 2The Paterson Institute for Cancer Research, Manchester/UK
  • 3Clinical And Experimental Pharmacology, The Paterson Institute for Cancer Research, M20 - 4BX/UK
  • 4Early Phase Oncology, AstraZeneca Pharmaceuticals, SK10 - 4TG/UK
  • 5Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/UK

Abstract

Background

cfDNA is detectable in patients with metastatic cutaneous melanoma and its plasma concentration could potentially predict their clinical outcomes. We assessed the correlation between cfDNA concentration and patients' overall survival and clinical characteristics including known poor prognostic factors in melanoma. Prognostic value of CMCs number and its association with cfDNA level was also explored.

Methods

Pre-treatment blood samples from 50 patients with metastatic cutaneous melanoma were collected prospectively. cfDNA was extracted from 1 ml of plasma using QIAamp Circulating Nucleic Acids Kit (Qiagen, Hilden, Germany) and quantified by RNase P qPCR (ABI Life Technologies, Foster City, NJ, USA). CMC enumeration per 7.5 ml whole blood was performed within 96 hours of sample collection using the CellSearch Melanoma Kit (Veridex, NJ, USA). Correlation between cfDNA concentration and clinical characteristics and CMC number was performed using ?2-test and Fisher's exact test where appropriate. Survival curves were produced and compared by the Kaplan-Meier method and log-rank test respectively.

Results

The median concentration of cfDNA was 6.8 ng/ml (range 0-205.8) and median CMC number was 0/7.5ml (range 0-16). Patients with cfDNA concentration of >75% percentile had significantly shorter overall survival compared to those with cfDNA level <75% percentile (median survival 100 vs. 242 days, p = 0.01). Similarly, patients with ≥ 1 CMC/7.5ml had poorer overall survival compared to those with non-detectable CMC (median survival 111 vs. 283 days, p = 0.001). No correlation was found between cfDNA concentration and CMC number. Median cfDNA concentration was significantly correlated with LDH level (p = 0.001) but not with age, performance status, AJCC stage, period with metastatic disease, number of metastatic sites and tumour BRAF mutation status.

Conclusions

Plasma cfDNA concentration and presence of CMC in 7.5 ml whole blood can predict patient's survival outcomes in metastatic cutaneous melanoma. No association was found between these two biomarkers and this highlights the possibility that they may represent different tumour biological process.

Disclosure

G. Brady: has an advisory role in Epistem and owns shares in Epistem.

G. Clack: employee of Astra-Zeneca pharamceuticals and ownes stock in Astra-zeneca.

A. Hughes: Employee of Astra-Zeneca and ownes stock in Astra-Zeneca.

All other authors have declared no conflicts of interest.