Abstract:

Objective

To analyze the predictive value of brain-derived cell-free DNA （bd-cfDNA） for radiation brain injury （RBI） in patients with lung cancer brain metastases.

Methods

A total of 83 patients with advanced lung cancer complicated with brain metastasis admitted to our hospital from March 2020 to March 2022 were selected as the subjects，33 patients with RBI after brain radiotherapy were selected as the observation group，and 50 patients without RBI were selected as the control group.The total cfDNA levels in plasma were measured before and after radiotherapy，and the origin of cfDNA was traced using tissue-specific methylation patterns.Multivariate binary Logistic and receiver operating characteristic （ROC） curve were used to analyze the prediction of RBI by bd-cfDNA.

Results

After radiotherapy，PLR 256.00 （226.50，289.00）and GTV Dmax 5 032.10 （4 936.25，5 125.35） in observation group were higher than those in control group 252.25 （221.50，184.25） and GTV Dmax 4 938.50 （4 833.40，5 032.93） （P ＜0.05）.There was no significant difference in cfDNA between the two groups before radiotherapy （P＞0.05）.After radiotherapy，cfDNA from oligodendrocytes，cfDNA from neurons，cfDNA from astrocytes and total bd-cfDNA were increased between the two groups （P＜0.05）.In the observation group，after radiotherapy，the source of oligodendrocytes was 12.07 （0.28，2 706.43） copies/ml，the source of neurons was 11.88 （1.44，4 394.05） copies/ml，and the source of astrocytes was cfDNA295.84 （5.63，5.28，4 394.05） copies/ml and total bd-cfDNA 8 433.13（348.75，29 514.12） copies/ml were higher than those in the control group 2.95（0.01，16.90）copies/ml，3.48（0.52，22.54）copies/ml，13.69（2.07，89.33）copies/ml，72.38（25.44，1343.92）copies/ml （P＜0.001）.In the observation group before and after radiotherapy，oligodendrocyte sources were cfDNA19.80 （0.25，3 159.96） copies/ml，neuronal sources ΔcfDNA19.61 （0.48，4 646.08） copies/ml，astrocyte sources ΔcfDNA 262.05 （1.62，8 298.91） copies/ml and Δ total bd-cfDNA 4 936.47 （229.22，24 740.52） copies/ml were higher than that of the control group 0.65 （-0.11，14.54） copies/ml，1.63 （0.07，0.07） copies/ml.15.45）copies/ml，3.93 （-2.25，77.83） copies/ml，34.71 （0.57，433.65） copies/ml （P＜0.05）.Multivariate binary Logistic analysis showed that total bd-cfDNA≥568.68 copies/ml after radiotherapy increased the risk of RBI［HR： 5.194 （95%CI： 1.760-15.326）， P＝0.003］.ROC curve analysis showed that the area under the curve of total bd-cfDNA predicting RBI after radiotherapy was 0.782 （95%CI： 0.674-0.891）（P＜0.05）.

Conclusion

bd-cfDNA can predict RBI of lung cancer brain metastases after radiotherapy，which has clinical significance.

Key words: Bronchogenic carcinoma, Brain-derived circulating free DNA, Radiation brain injury, Brain metastasis