Lung V5 and Planning Target Volume/Lung Volume Ratio as Independent Risk Factors for ≥Grade 2 Radiation Pneumonitis after Moderately Hypofractionated Radiotherapy: A Retrospective Study

ABSTRACT Purpose This study aimed to identify dosimetric and clinical risk factors for ≥Grade 2 radiation pneumonitis (RP) in patients with primary lung cancer undergoing moderately hypofractionated radiotherapy (MHRT). Methods We retrospectively analyzed 126 patients with primary lung cancer who received MHRT (total dose 35–56 Gy in 10–15 fractions) between December 2023 and December 2024. The primary endpoint was the occurrence of ≥Grade 2 RP, graded according to CTCAE v5.0. Logistic regression analysis was used to identify risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate predictive performance. To account for the differential biological effects of various fractionation regimens, a biologically effective dose (BED) correction (using an α/β ratio of 3 Gy for lung tissue) was applied to key dosimetric parameters, including the lung volume receiving ≥5 Gy (V5). Results With a median follow‐up of 7.5 months, 45 patients (35.7%) developed ≥Grade 2 RP. Univariate analysis identified planning target volume/lung volume (PTV/LV) ratio, lung V5, lung V20, fraction dose, and chemotherapy history as significant factors (all p < 0.05). Multivariate analysis confirmed both lung V5 (odds ratio OR = 3.335, 95% confidence interval CI: 1.208–9.212; p = 0.020) and PTV/LV ratio (OR = 2.097, 95% CI: 1.027–8.607; p = 0.045) as independent risk factors. BED‐corrected analysis confirmed BED‐V5 as an independent risk factor (OR = 1.10, 95% CI: 1.03‐1.18, p = 0.007). ROC analysis showed that lung V5 had significant predictive value (area under the curve AUC = 0.667, p = 0.002), while BED‐V5 had an AUC of 0.698 ( p < 0.001) with an optimal cutoff of 40.1%. PTV/LV ratio did not reach statistical significance (AUC = 0.584, p = 0.117). Model diagnostics indicated good calibration (Hosmer‐Lemeshow p = 0.620) and no significant multicollinearity (variance inflation factors = 1.021). Conclusion Lung V5 and PTV/LV ratio are independent risk factors for ≥Grade 2 RP in patients receiving MHRT for primary lung cancer. The significance of V5 persisted after BED correction. Lung V5 demonstrates significant predictive value. Optimizing treatment plans to maintain lung V5 < 34.75% and PTV/LV ratio < 4.25% may help reduce the risk of RP in this setting.