Thoracic radiotherapy increased the risk of secondary lung cancers compared to no radiotherapy (aHR 1.18; 95% CI 1.09-1.28; P<0.001), with a 5-year cumulative incidence of 1.2% vs 0.8%.
Cohort (n=45,678)
Yes
Does thoracic radiotherapy increase the risk of secondary lung cancers in patients with primary thoracic cancers?
Thoracic radiotherapy for primary malignancies increases the risk of secondary lung cancers by 18% within 5 years, highlighting the need for early surveillance.
Effect estimate: aHR 1.18 (95% CI 1.09-1.28)
Absolute Event Rate: 1.2% vs 0.8%
p-value: p=<0.001
Abstract Rationale Thoracic radiotherapy (RT) for primary malignancies, such as breast and lung cancers, elevates the risk of secondary lung cancers (SLCs). With recent data emphasizing shorter follow-up periods, we examined 5-year trends in risk factors, early latency, and outcomes to inform timely surveillance. Methods Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database (2016-2020), identifying 45,678 patients with thoracic cancers (breast, lung, esophageal) treated with or without RT. SLCs were defined as incident lung primaries ≥1 year post-diagnosis to capture early latency. Multivariable Cox regression assessed risk factors (adjusted hazard ratios aHRs). Latency evaluated via dynamic cumulative incidence and standardized incidence ratios (SIRs) up to 5 years. Overall survival (OS) compared using Kaplan-Meier and propensity score-matched analyses. Measurements and Main Results RT exposure increased SLC risk (aHR 1.18, 95% CI 1.09-1.28; P 0.001), with elevated risks for breast (aHR 1.20) and lung (aHR 1.25) primaries. Risk factors included older age at primary diagnosis (aHR 1.85-2.05 for ≥50 years), Black race (aHR 1.15), and smoking history (aHR 1.32). Cumulative SLC incidence at 5 years was 1.2% with RT versus 0.8% without (P 0.001). Latency analysis showed rising risk after 2 years (SIR 1.12 overall; 2.45 for lung primaries), peaking by year 5. No significant OS differences between RT and non-RT SLC groups (5-year OS ∼45%), but RT-associated SLCs trended worse than primary lung cancers (42.1% vs. 51.3%; P = 0.02). Younger age and smoking amplified early RT-attributable risk (relative risk up to 1.45 at 3 years). Conclusions In recent 5-year data, thoracic RT raises SLC risk by 18%, driven by age, race, and smoking, with latency emerging within 2-5 years. Outcomes remain guarded, highlighting the value of early, risk-stratified screening in RT survivors to address rising late effects. This abstract is funded by: None
Gulraiz et al. (Fri,) conducted a cohort in Thoracic cancers (breast, lung, esophageal) (n=45,678). Thoracic radiotherapy (RT) vs. No radiotherapy was evaluated on Secondary lung cancers (SLCs) risk (aHR 1.18, 95% CI 1.09-1.28, p=<0.001). Thoracic radiotherapy increased the risk of secondary lung cancers compared to no radiotherapy (aHR 1.18; 95% CI 1.09-1.28; P<0.001), with a 5-year cumulative incidence of 1.2% vs 0.8%.