Melanoma is an aggressive form of skin cancer that is increasing in prevalence worldwide . In patients with advanced stage melanoma, treatment decisions are based upon clinical and imaging findings. In recent years, positron emission tomography with 2=deoxy-2[fluorine-18] fluoro= D-glucose integrated with computed tomography (FDG PET/CT) has emerged as a powerful imaging tool for initial staging and evaluating treatment response in metastatic melanoma [2, 3]. 18F–FDG is a radio labelled glucose analogue which reflects tumour metabolic activity. Commonly, FDG PET/CT is used to determine tumour burden as it provides a high tumour-to-background intensity ratio which facilitates computer generated measurements of total body metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from which metabolic tumour burden (MTB) can be quantitatively calculated [4, 5].
As a blood-based biomarker, circulating tumour DNA (ctDNA) offers a non-invasive and easily accessible method of providing a real-time “snap shot” of tumour burden. The level of ctDNA sensitivity however differs between tumour types, AJCC stages, mutant forms and between patients . The lower limit in tumour size that shed detectable amounts of ctDNA into the blood is however unclear, and it may vary between cancer types. Furthermore, ctDNA is not always detectable in patients at time of diagnosis of metastatic disease. Therefore, there is a need to understand the correlation between ctDNA levels and the patients’ overall metabolic tumour burden (MTB).
Patients and methods
Thirty-two treatment naïve metastatic melanoma patients were included in the study. MTB and metabolic tumour volume (MTV) was measured by 18F-fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT). Plasma ctDNA was quantified using droplet digital PCR (ddPCR).
Mutant specific ctDNA was detected in 23 of 32 patients. Overall, a significant correlation was observed between ctDNA levels and MTB (p<0.001). CtDNA was not detectable in patients with an MTB of ≤10, defining this value as the lower limit of tumour burden that can be detected through ctDNA analysis by ddPCR.
We showed that ctDNA levels measured by ddPCR correlate with MTB in treatment naïve metastatic melanoma patients and define a limit in tumour size for which ctDNA cannot be detected in blood. Nevertheless, our findings support the use of ctDNA as a non-invasive complementary modality to functional imaging for monitoring tumour burden.