Tumor irradiation may facilitate the detection of tumor-specific mutations in plasma.

Abstract

BACKGROUNDThe mutation-based analysis of circulating tumor DNA (ctDNA) is a promising diagnostic tool for clinical oncology. However, it has low success rate because many cancer patients do not have detectable ctDNA in the bloodstream. AIMTo evaluate whether preoperative tumor irradiation results in a transient increase of plasma ctDNA concentration due to the induction of apoptosis in radiation-exposed cells.METHODSThis study focused on patients with locally advanced rectal cancer, because preoperative tumor irradiation is a part of their standard treatment plan. Nine subjects, whose tumors contained KRAS, NRAS or BRAF mutations, donated serial blood samples 1 h prior to the first fraction of irradiation (at baseline), immediately after the first fraction (time 0), and 1, 3, 6, 12, 24, 36, 48, 72 and 96 h after the first fraction. The amount of mutated gene copies was measured by droplet digital PCR.RESULTSFive out of nine patients were mutation-negative by ctDNA test at baseline; two of these subjects demonstrated an emergence of the mutated DNA copies in the bloodstream within the follow-up period. There were 4 patients, who had detectable ctDNA in the plasma at the start of the experiment; three of them showed an evident treatment-induced increase of the content of mutated RAS/RAF alleles. CONCLUSIONLocal tumor irradiation may facilitate the detection of tumor-specific DNA in the bloodstream. These data justify further assessment of the clinical feasibility of irradiation-assisted liquid biopsy.