ctDNA After Hypofractionated Radiation Therapy in Patients With Lung Cancer

By Mary Grecco - Last Updated: January 31, 2024

Results of a study that sought to determine a dynamic pattern of ctDNA during hypofractionated radiation therapy (RT) and its clinical relevance among patients with pathologically or clinically diagnosed early-stage lung cancer were presented at the ESMO Congress 2023.

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Patients who underwent definitive RT alone were enrolled prospectively. RT was curatively prescribed with 60 to 64 Gy in 4 to 20 fractions. Blood samples were obtained before and after the start of RT, including the first, second, and third day (T0-3), and ctDNA was longitudinally analyzed. A total of 13 patients were ultimately evaluated, excluding undetected cases or patients without samples within 3 days after starting RT. The researchers used comprehensive variables quantifying various types of ctDNA, including sum of variant allele frequency (total VAF, %), maximum of VAF (%), sum of genomic equivalent (total GE, hGE/mL), and maximum of GE (max GE, hGE/mL) to find a feasible index associated with progression.

Results showed that during a median 22.2-month follow-up, four patients experienced progressive disease (PD) between 7.9 and 16.6 months after RT (PD group); two experienced local or locoregional recurrence and two had lung-to-lung metastasis. The remaining nine patients exhibited no evidence of disease (NED group) but showed the highest ctDNA ratio [NJ1; 1.76-2.34) compared with the baseline level. With regard to the timing of ctDNA elevation, the researchers found that the Tmax, the day with the highest ctDNA level among T0-3, was significantly different between the NED and PD groups with total GE and max GE (P=.035 and P=.021, respectively). At ROC curves, the max GE showed the best AUC (86.1%), and the cutoff value of the Tmax was 1.5 (sensitivity, 55.6%; specificity, 100%; positive-predictive value, 100%; negative-predictive value, 50.0%). Tumor size greater than 0.3 cm, 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=.081).

The researchers concluded that the timing of early ctDNA elevation after RT may be a potential predictive marker of good clinical response. They also suggested that “max GE was a feasible index to check ctDNA level after RT.”

Source: Yang K, Noh JM, Kim YJ, Pyo H. Early dynamics of circulating tumor DNA following curative hypofractionated radiotherapy related to disease control in lung cancer. Abstract of a poster presented at the ESMO Congress 2023; October 20-24, 2023; Madrid, Spain.

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