3416 - Escalating Cumulative Dose Improves Survival in Thoracic Re-Irradiation without Increased Severe Pneumonitis: Results from Twelve Years of Experience

Purpose/Objective(s): Re-irradiation is increasingly utilized for locally advanced lung cancer, yet optimal dosing and toxicity remain critical considerations. This study evaluated treatment outcomes and toxicity in patients undergoing thoracic re-irradiation with SBRT, hypofractionated, or conventional RT.

Materials/Methods: We retrospectively analyzed 46 locally advanced lung cancer patients who received re-irradiation between 2013-2025. All re-RT utilized 4D image-guided techniques with =50% isodose overlap between initial and subsequent PTVs. Toxicities were graded by CTCAE v5.0. Survival was estimated using Kaplan–Meier, and prognostic factors assessed via Cox regression and appropriate statistical methods. Statistical significance was p < 0.05.

Results: Among the 46 patients included, 37 were male (80.4%) and 9 were female (19.6%) with a median age of 66.5 years (38–79). Stage III disease accounted for 93.5% of cases. Primary tumor histology was dominantly NSCLC (n=39, 84.8%). The median follow-up was 29 months (8–112). Median EQD2 (a/ß = 8) of initial RT was 60 Gy (range:48.9–72) in 30 fractions (15-35). The median interval between initial RT and locoregional recurrence was 15 months (3–69). Re-RT was administered for in-field recurrence in 26 patients (56.5%). Re-RT modalities included SBRT (n=16, 34.8%), hypofractionated RT (n=25, 54.3%), and conventional RT (n=5, 10.9%). During re-RT, 87% of patients had PTV overlap. The median re-RT EQD2 (a/ß = 8) was 42 Gy (30–138) and 2 (n=2, 4.4%) patients received chemotherapy concurrently. After re-RT in-field recurrence occurred in 18 patients (39.1%), with an estimated median locoregional recurrence-free interval of 4 months (SE ±0.71). There was no significant association between in-field recurrence after re-RT and cumulative EQD2 dose (p = 0.13), re-RT fraction dose (p = 0.5), histology (p = 0.9), or stage (p=0.9). The 1-, 2-, and 3-year overall survival rates were 96%, 69%, and 49%, respectively, corresponding cancer-specific survival (CSS) rates were 95.5%, 76%, and 57%. In univariable and multivariable Cox regression analysis, cumulative EQD2 remained an independent predictor of CSS (HR 0.946, 95% CI 0.916–0.977, p=0.001), corresponding to a 5.4% reduction in mortality risk per 1 Gy increase. Exploratory ROC analysis identified a potential cumulative EQD2 threshold of approximately 127 Gy (sensitivity:84%, specificity:60%) for cancer-specific survival (AUC 0.65). No grade=3 acute adverse events occurred during re-RT. Late RT pneumonitis occurred as grade 1 in 3 (6.5%), grade 2 in 4 (8.7%), and grade 3 in 3 patients (6.5%), with no grade =4 events and pneumonitis was not significantly associated with cumulative BED10 (p = 0.739).

Conclusion: Thoracic re-irradiation provides encouraging survival with acceptable toxicity. Higher cumulative EQD2 independently predicted improved CSS without increasing severe pneumonitis, suggesting dose optimization can enhance outcomes in selected patients.