1274P - Early dynamics of circulating tumor DNA following curative hypofractionated radiotherapy related to disease control in lung cancer

Background

We aimed to find out a dynamic pattern of ctDNA during hypofractionated RT in patients with lung cancer and its clinical relevance.

Methods

Prospectively, 24 patients with pathologically or clinically diagnosed early stage lung cancer who underwent definitive RT alone were enrolled. RT was curatively prescribed with 60 – 64 Gy in 4–20 fractions. Using the blood samples obtained before and after the start of RT including the first, second, and third day (T0–3), ctDNA was longitudinally analyzed with targeted deep sequencing by LiquidSCAN. To find a feasible index associated with progression, comprehensive variables quantifying various types of ctDNA including sum of variant allele frequency (total VAF, %), maximum of VAF (max VAF, %), sum of genomic equivalent (total GE, hGE/ml), and maximum of GE (max GE, hGE/ml) were used for the statistics.

Results

A total of 13 patients were analyzed excluding undetected cases or patients without samples within 3 days after starting RT. During median 22.2-month follow-up (range 5.2– 34.3 months), 4 patients experienced progressive disease (PD) between 7.9 and 16.6 months after RT (PD group); two local or locoregional recurrence and two lung-to-lung metastasis. The remaining 9 patients were in the state of no evidence of disease (NED group). Despite of no significance, NED group showed the highest ctDNA ratio [NJ1] (1.76–2.34) compared to the baseline level. Regarding the timing of ctDNA elevation, the Tmax, the day with the highest ctDNA level among T0–3, was significantly different between NED and PD group with total GE and max GE (p=0.035 and 0.021, respectively). At ROC curves, the max GE showed the best AUC (86.1%) and the cut-off value of the Tmax was 1.5 (sensitivity 55.6%, specificity 100%, positive-predictive value 100%, and negative-predictive value 50%). Tumor size >=3cm, squamous histology, and daily dose of 3–4 Gy were correlated to the Tmax T2 or T3. At survival analysis, only Tmax showed better disease control rate, which was marginally significant (p=0.081).

Conclusions

The timing of early ctDNA elevation after RT might be a potential predictive marker of good clinical response. Also, we suggested that max GE was a feasible index to check ctDNA level after RT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National research Foundation by Ministry of Science and ICT.

Disclosure

All authors have declared no conflicts of interest.