Abstract 1785P
Background
The mutation-based analysis of circulating tumor DNA (ctDNA) in plasma or other body fluids is a promising diagnostic tool for clinical oncology. However, the ctDNA-based liquid biopsy procedure is compromised by low sensitivity; indeed, many cancer patients do not have detectable ctDNA in the bloodstream. We aimed to evaluate whether preoperative tumor irradiation, which is routinely applied to patients with locally advanced RAS/RAF-mutated rectal cancer, may result in a transient increase of ctDNA content due to the induction of tumor cell death.
Methods
The study included 9 treatment-naïve patients with locally advanced RAS/RAF-mutated rectal cancer. Radiotherapy was performed according to routine procedures either with 45–50 Gy in 25–28 fractions or short-course radiation therapy (25 Gy in 5 fractions). Patients provided blood at 11 different time points: 1 hour before the first fraction of irradiation (at baseline), immediately after the first fraction (time 0), and at 1, 3, 6, 12, 24, 36, 48, 72 and 96 hours after the first fraction. The concentration of KRAS/NRAS/BRAF mutations in plasma ctDNA was measured by droplet digital PCR (ddPCR).
Results
Five out of nine patients had no detectable RAS/RAF mutations in plasma DNA at baseline; two of these subjects demonstrated an emergence of the mutated DNA copies in the bloodstream within the next 96 hours after the first fraction. Four patients were recognized as “plasma-positive” at baseline; three of them showed an evident treatment-induced increase of the content of mutated RAS/RAF copies in the plasma with the maximum percent changes equal to 509%, 174% and 71%, respectively. No correlation was detected between the concentration of mutated ctDNA and the total RT dose accumulated during the blood collection time..
Conclusions
We conclude that the local tumor irradiation may facilitate the detection of tumor-specific DNA in the bloodstream. This study calls for a comprehensive evaluation of the clinical feasibility of irradiation-assisted liquid biopsy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Russian Science Foundation (grant 20-75-10163).
Disclosure
All authors have declared no conflicts of interest.