Correlation between circulating tumour DNA and metabolic tumour burden in metastatic melanoma patients

Abstract

BackgroundCirculating tumour DNA (ctDNA) may serve as a measure of tumour burden and a useful tool for non-invasive monitoring of cancer. However, 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).MethodsThirty-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).ResultsCtDNA 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.ConclusionsWe showed that ctDNA levels measured by ddPCR correlate with MTB in treatment naïve metastatic melanoma patients and observed 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.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4637-6) contains supplementary material, which is available to authorized users.

Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients

“…We detected plasma ctDNA in seven of seventeen patients who had at least one somatic mutation in tumor tissue. This is in agreement with three other similar studies using ddPCR, which indicated that ctDNA detection rates are associated with tumor burden 18 , 23 , 43 . McEvoy et al 18 demonstrated a detection rate of 71.8% in a cohort of 32 stage IV patients.…”

“…This is in agreement with three other similar studies using ddPCR, which indicated that ctDNA detection rates are associated with tumor burden 18 , 23 , 43 . McEvoy et al 18 demonstrated a detection rate of 71.8% in a cohort of 32 stage IV patients. In keeping with the relationship to burden, detection rates fell to 12% in lower stage patients (EC II and III) 23 .…”

“…Recently, the detection of ctDNA alterations in melanoma patients has gain attention, due to its practical advantages: it is minimally invasive, allows serial collection, and is less prone to limitations such as quality of the material and tumor heterogeneity than traditional tissue biopsies 14 – 16 . Some relevant findings of this method include the association of ctDNA levels to tumor burden in metastatic melanoma patients and the ability of baseline values to predict outcomes 11 , 17 , 18 . The ctDNA variability during melanoma treatment is another possible tool for early assessment of therapy response or resistance 18 – 23 .…”

“…Some relevant findings of this method include the association of ctDNA levels to tumor burden in metastatic melanoma patients and the ability of baseline values to predict outcomes 11 , 17 , 18 . The ctDNA variability during melanoma treatment is another possible tool for early assessment of therapy response or resistance 18 – 23 .…”

Life and death of circulating cell-free DNA

“…47,48 For example, in patients with melanoma, ctDNA levels were correlated with metabolic disease volume, estimated with 18 F-labelled fluorodeoxyglucose positron emission tomography. 49,50 Therefore, the ctDNA level was a complex reflection of tumor biology, rather than simply associated with tumor burden or the number of dying cells. This finding suggested that ctDNA measurements might be more relevant to advanced stages of the disease and less relevant to precancerous lesions.…”