Oncotarget

Research Papers:

Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies

Ashleigh C. McEvoy, Michelle R. Pereira, Anna Reid, Robert Pearce, Lester Cowell, Zeyad Al-Ogaili, Muhammad A. Khattak, Michael Millward, Tarek M. Meniawy, Elin S. Gray _ and Melanie Ziman

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Abstract

Ashleigh C. McEvoy1, Michelle R. Pereira1, Anna Reid1, Robert Pearce1, Lester Cowell2, Zeyad Al-Ogaili3, Muhammad A. Khattak1,4,5, Michael Millward5,6, Tarek M. Meniawy5,6, Elin S. Gray1,7 and Melanie Ziman1,8

1School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia

2Level1 Melanoma Clinic, Hamilton Hill, Western Australia 6163, Australia

3Department of Molecular Imaging and Therapy Service, Fiona Stanley Hospital, Murdoch, Western Australia 6150, Australia

4Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia 6150, Australia

5School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia 6009, Australia

6Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia

7Centre for Ophthalmology and Visual Science, University of Western Australia, Crawley, Western Australia 6009, Australia

8School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia

Correspondence to:

Elin S. Gray, email: e.gray@ecu.edu.au

Keywords: circulating tumor DNA; ctDNA; melanoma; recurrence; droplet digital PCR

Received: June 24, 2018     Accepted: November 26, 2018     Published: January 04, 2019

ABSTRACT

Background: A significant number of melanoma patients experience recurrence to distant sites, despite having had surgical treatment of the primary lesion, with curative intent. Monitoring of patients for early evidence of disease recurrence would significantly improve management of the disease, allowing timely therapeutic intervention. Circulating tumor DNA (ctDNA) is becoming a well-recognized biomarker for monitoring malignancies and has, in a few studies, been shown to signify disease recurrence earlier than conventional methods.

Methods: We performed a retrospective analysis of plasma ctDNA using droplet digital PCR (ddPCR) in 30 primary melanoma patients with tumors harboring BRAF, NRAS or TERT promoter mutations. Mutant specific ctDNA, measured during clinical disease course, was compared with disease status in patients with confirmed disease recurrence (n = 3) and in those with no evidence of disease recurrence (n = 27).

Results: Mutant specific ctDNA was detected in all three patients with disease recurrence at the time of clinically confirmed progression. In one case, plasma ctDNA detection preceded clinical identification of recurrence by an interval of 4 months. CtDNA was not detected in patients who were asymptomatic and had no radiological evidence of recurrence.

Conclusions: This study demonstrates promising results for the use of ctDNA as an informative monitoring tool for melanoma patients having undergone tumor resection of an early stage primary tumor. The clinical utility of ctDNA for monitoring disease recurrence warrants investigation in prospective studies as it may improve patient outcome.


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