Mixed ctDNA dynamics and decreased detection rates in early-stage lung cancer patients during radiation treatment

Quantification and detection of circulating tumor DNA (ctDNA) has been used to identify the presence of cancers. Ablative radiation therapy kills tumor cells to reduce tumor burden and it follows that these dying tumor cells could lead to increased ctDNA abundance. We carried out deep, error-corrected sequencing of cell-free DNA collected serially from 12 stage I, and 2 stage II/III non-small cell lung cancer (NSCLC) patients undergoing external-beam radiation treatment (EBRT) after initial diagnosis. We found that ctDNA detection rates decreased at the first blood draw as compared to baseline (43% to 7% of patients). Total ctDNA abundance decreased in 6 patients and increased in 5 patients between those same blood draws, with one patient showing evidence of tumoral heterogeneity. Both patients with stage II/III disease had the largest increases in ctDNA abundance from baseline. Multiple blood draws improved ctDNA detection rates from 43% to 50% with a second blood draw and to 71% with 4 blood draws. Additionally, EGFR mutations were detectable in 6 patients during EBRT that were not detected prior to treatment. Taken together, these results provide an early-stage NSCLC counterpoint to previous work that reported improved ctDNA detection after radiation therapy in more advanced disease.