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

BACKGROUND The 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.AIM To evaluate whether preoperative tumor irradiation results in a transient increase of plasma ctDNA concentration due to the induction of apoptosis in radiationexposed cells.METHODS This 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.RESULTS Five 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.CONCLUSION Local 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.