Saturday, December 9, 2017

Measuring cell-free DNA in melanoma patient's blood to determine tumor burden and prognosis


I have spent years yelling about finding a reasonable marker through a simple blood draw to determine disease burden, response to therapy, and prognosis for melanoma patients.  Here's a zillion reports - Markers for melanoma- looking at utilizing everything from progression on scans, t-cell exhaustion, lymphocytes, circulating CD8 and CD4 t cells, eosinophils, LDH, melanoma antigens, to circulating tumor cells to determine the status of a melanoma patient's disease burden.

On the topic of circulating tumor DNA alone there are these:  Circulating tumor DNA in melanoma
It can be used to determine level of disease, progression, BRAF status and response to treatment.
Now there's this:

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients. Valpione, Gremel, Mundra, et al.  Eur J Cancer. 2017 Nov 23.


Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients.

A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients.

Baseline cfDNA concentration correlated with pre-treatment tumour burden. Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups. Patients with cfDNA greater than/= to 89 pg/μl had shorter OS (10.0 versus 22.7 months) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden. In addition, the ratio between baseline cfDNA and tumour burden was prognostic.

We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.

These tests work!  It is time to make them a reality for those with melanoma! - c

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