Risk Factors for Symptomatic Radiation Pneumonitis after Stereotactic Body Radiotherapy (SBRT) for Early-Stage Lung Cancer

Abstract

To identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) in patients with early-stage lung cancer. We reviewed patients with clinical stage IA1-IIA non-small cell lung cancer treated by SBRT in our institution. The primary endpoint was grade ≥ 2 RP. To evaluate the relationship between clinical risk factors and grade ≥ 2 RP, the Gray test was used for univariate analysis and the Fine-Gray model for multivariate analysis. Dose parameters were univariate analyzed using the Fine-Gray model. Optimal thresholds for dose parameters were tested using receiver operating characteristic (ROC) curves. Among a total of 244 patients analyzed. The median age of patients was 77 years. The median follow-up period was 48 months. The 4-year cumulative incidence of grade ≥ 2 RP was 15.3% for all patients. In univariate analysis, tumor size (p = 0.01), central tumor (p < 0.001), interstitial pneumonia (p = 0.002), biological effective dose (BED, α/β ratio of 10 Gy) (p = 0.017), lung volume (%) receiving at least 8 Gy (V8) (p = 0.012), V10 (p = 0.011), V20 (p = 0.022) and mean lung dose (MLD) (p = 0.014) were significantly associated with the risk of grade ≥ 2 RP. In multivariate analysis, central tumor (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.88-7.55; p < 0.001) and interstitial pneumonia (HR, 4.88; 95% CI, 1.77-13.43; p = 0.002) were significantly associated with the risk of grade ≥ 2 RP. ROC curve analysis showed that the optimal diagnostic thresholds for lung V8, V10, V20, and MLD were 19.5% (the area under the curve [AUC]-0.629), 16.7% (AUC-0.629), 7.9% (AUC-0.621), and 5.2 Gy (AUC-0.623). The incidence of RP2 was found to be significantly high for values higher than the ROC threshold. The 4-year cumulative incidence of grade ≥ 2 RP in the V10 ≤ 16.7% vs V10 > 16.7% groups were 10% vs. 27% (p = 0.0013). Central tumor and interstitial pneumonia were significant risk factors for RP2 after SBRT. We recommend that lung V10 be kept below 16.7%.