3550 - Early Mortality after Thoracic Radiotherapy for Lung Cancer: Identifying a High-Risk Subgroup through Initial Radiation Pneumonitis Severity

Purpose/Objective(s):

While radiation pneumonitis (RP) is a common and potentially severe complication of thoracic radiotherapy for lung cancer, prior research has predominantly focused on predicting its occurrence. The prognostic significance of RP severity at the time of initial diagnosis, particularly for short-term outcomes, remained unclear. This study aimed to determine if the initial RP grade is an independent predictor of all-cause mortality within 90 days of diagnosis.

Materials/Methods:

312 lung cancer patients diagnosed with RP included after thoracic radiotherapy at a single tertiary center between June 2020 and February 2024. RP was diagnosed based on compatible respiratory symptoms and characteristic imaging findings on chest CT. Its severity at first clinical recognition was graded according to CTCAE v5.0 and categorized as Grade 1 (asymptomatic or mild) versus Grade =2 (symptomatic and clinically significant). The primary endpoint was all-cause mortality within 90 days of RP diagnosis. Multivariable logistic regression models were constructed to assess the association between initial RP severity and 90-day mortality, adjusting for age, sex, TNM stage (I-III vs. IV), baseline DLCO (% predicted), mean lung dose (MLD), and the interval from radiotherapy completion to RP diagnosis (RT-to-RP interval). A sensitivity analysis excluded patients presenting with Grade =3 RP. Post-diagnosis therapeutic interventions (e.g., corticosteroids) were intentionally excluded from the models to isolate the prognostic value of RP severity at presentation.

Results:

Among the 312 patients with RP, 59 (18.9%) died within 90 days of diagnosis. Patients who died early were older, had higher lung radiation doses (MLD, V5, V20), and developed RP sooner after radiotherapy (shorter RT-to-RP interval) compared to survivors (all P<0.001). Initial Grade =2 RP was a strong, independent predictor of 90-day mortality. In the fully adjusted multivariable model, Grade =2 RP was associated with an 8-fold higher odds of early death (Adjusted Odds Ratio [aOR] 8.02, 95% Confidence Interval 1.85–34.85; P=0.005) compared to Grade 1 RP. Other factors independently associated with higher 90-day mortality were: higher Mean Lung Dose (MLD) (per 1 Gy increase: aOR 1.21, 95% CI 1.09–1.34; P<0.001), and shorter RT-to-RP interval (per 10-day increase: aOR 0.87, 95% CI 0.79–0.96; P=0.007).The significant association between initial RP Grade =2 and early mortality persisted in the sensitivity analysis that excluded patients with Grade =3 RP, indicating the finding is robust and not solely driven by the most severe cases.

Conclusion:

The initial severity of radiation pneumonitis at diagnosis is an independent predictor of early mortality after thoracic radiotherapy for lung cancer. An initial presentation of RP Grade =2 identifies a high-risk subgroup of patients with a significantly elevated risk of death within 90 days.