The relationship of radiation-induced damage development with lung ultrasonography findings and KL-6, TGF-Beta, IFN-Gamma in patients receiving thoracic radiotherapy for lung cancer

Introduction and Objective: Radiation pneumonitis (RP) is a pulmonary toxicity that develops in patients undergoing radiotherapy (RT) , presenting with symptoms of varying severity that can adversely affect the treatment process. The primary objective of our study is to evaluate the effectiveness of B-line monitoring with lung ultrasound in patients undergoing radiotherapy to the thoracic region for lung cancer in terms of early diagnosis of radiation pneumonitis. A secondary objective is to evaluate the relationship between TGF-beta, IFN-gamma, and KL-6 molecular levels and the development of RP. Materials and Methods: Fifty-four patients diagnosed with lung cancer and scheduled for curative radiotherapy were included in the study. Patients were prospectively evaluated at three different controls: before radiotherapy (Control 0), at the end of radiotherapy (Control 1), 1.5–2 months after the end of radiotherapy (Control 2), and 4–6 months after radiotherapy (Control 3). Clinical and radiographic findings, as well as lung ultrasound findings, were recorded in detail. The anterolateral portion of each lung was examined along the parasternal, midclavicular, anterior axillary, and middle axillary lines; the posterior portion was examined along the paravertebral, midscapular, and posterior axillary lines. Each lobe was divided into two regions, upper and lower, and the number of B lines and other pathological ultrasound findings in each region were recorded for both lungs. Serum samples were collected to measure TGF-Beta, IFN-Gamma, and KL-6 levels during patient follow-ups. The diagnosis of radiation pneumonitis (RP) was made based on clinical findings and the patients' chest computed tomography (CT) findings. RP scoring was performed according to RTOG criteria. The assumption of normal distribution for continuous variables was tested using the Kolmogorov-Smirnov test, and data not showing normal distribution were presented as median (interquatile range (IQR)). Findings: Fifty-four patients who had completed radiotherapy treatment were included in the study. Thirty-six of these patients completed the 4-6 month evaluation. Fifty-two of the patients were male and two were female. The average age was 65. Radiation pneumonitis was detected in 22 patients (40.7%). In half of the cases (n:11), the diagnosis of RP was made within the first 2 months after RT, while in the other half (n:11), the diagnosis was made between 4-6 months after RT. The difference in B-line counts between the first and second follow-up periods was calculated for each patient. The median change was 10.00 (IQR: -6.00 to 18.00) in patients who developed RP and 1.00 (IQR: -7.50 to 10.50) in those who did not. A statistically significant difference was observed between the two groups (p = 0.041). In the 36 patients who could be evaluated at the third follow-up, B-line counts were significantly higher in patients with RP (n: 18) compared to those without RP (median: 53 vs 10, p: 0.001). The increase in B-line counts between the second and third controls was significantly higher in patients with RP (median: 10.5 vs. -6.0, p:0.003). Receiver operating characteristic (ROC) analysis was performed to assess the ability of the total B-line count in the tumor-side hemithorax to predict the development of RP. The area under the curve (AUC) for the total B-line count in the tumor-side hemithorax was calculated as 0.819. When the cutoff value for the B-line count was set at 14, the sensitivity was 85.71% (95% confidence interval: 63.7–97.0), and the specificity was 80.00% (95% confidence interval: 51.9–95.7). Radiotherapy doses and molecular markers (TGF-Beta, IFN-Gamma, KL-6) were analyzed in terms of the development of radiation pneumonitis, and no significant differences were observed. Conclusion: In patients undergoing radiotherapy, a significant increase in the number of B lines in the ultrasound evaluation performed within the first 2 months after RT may be indicative of RP development.