2411 - Lung V5 and Post-Radiation Lymphopenia as Predictors of Symptomatic Radiation Pneumonitis in Real-World Lung Cancer Patients in China: A Retrospective Analysis

Purpose/Objective(s): Lung cancer is the leading cause of cancer-related mortality globally, with radiotherapy (RT) being a cornerstone of its multidisciplinary management. Approximately 70% of lung cancer patients require thoracic RT, yet radiation pneumonitis (RP) remains a major complication, occurring in 5% - 31% of cases (Grade 3 - 4: 2.5% -18.1%). RP may progress to pulmonary fibrosis, significantly impairing quality of life. Real-world data on RP epidemiology and risk factors are limited. The aim of this study was to understand the characteristics of RP patients with lung cancer in the real-world in China.

Materials/Methods: This retrospective study analyzed 314 lung cancer patients diagnosed with RP after thoracic RT (= 40 Gy) at a single institution from June 2020 to February 2024. RP severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0). Data collected included clinical characteristics, dosimetric parameters (lung volumes and Lung V5, V10, V20, V30, V40, Dmean), lymphocyte dynamics, and concurrent therapies. Statistical analyses were conducted using SPSS 25.0, with continuous variables presented as median (IQR) and categorical variables compared using ?² or Fisher’s exact tests.

Results: The median age of the 314 patients was 60 years (range: 36-86), with 81% being male. Squamous cell carcinoma (42%) and adenocarcinoma (38%) were the most common histologies. Asymptomatic RP (Grade 1) was present in 25% (77/314) of patients, while symptomatic RP (Grade = 2) occurred in 75% (237/314). Comparative analysis revealed no significant differences in gender, age, performance status (PS) score, smoking/diabetes history, histology or stage between Grade 1 and Grade = 2 RP groups (all p > 0.05). Lung V5 (the percentage of lung volume receiving = 5 Gy) was significantly associated with RP severity (Grade = 2 vs. Grade 1: 46% vs. 43%, p = 0.045). No significant correlation was found for Lung V10, V20, V30, V40, Dmean, or total lung volume. Patients with Grade = 2 RP had greater post-RT lymphocyte reduction (-64% vs. -57%, p = 0.012) and lower absolute lymphocyte counts (0.45 vs. 0.51 ×10?/L, p = 0.003). A trend towards milder RP was observed in younger patients (= 65 years: 77% in Grade 1 vs. 66% in Grade = 2, p = 0.088) and those with higher baseline FEV1 (83% vs. 74%, p = 0.068). Concurrent chemotherapy (26%) or EGFR-TKIs (9.2%) did not significantly affect RP severity (p > 0.05).

Conclusion: This real-world study identifies Lung V5 as a key predictor of RP severity, emphasizing the importance of minimizing low-dose radiation exposure in precision RT. Post-RT lymphopenia, particularly impaired lymphocyte-mediated repair, correlates with symptomatic RP, implicating immune dysregulation as a critical mechanism. Although further validation is needed, our findings suggest: 1) stricter Lung V5 constraints, especially for elderly or pulmonary-compromised patients (e.g., low FEV1), and 2) routine lymphocyte monitoring to guide early intervention in high-risk patients.