KEY POINTS
- This retrospective single-institution study included 86 Appalachian patients with biopsy-confirmed lung cancer treated with definitive chemoradiotherapy from 2013–2025. Median follow-up was 30.5 months; the cohort was cardiovascularly high risk, with 74% having pre-existing cardiovascular disease and 95% being current or former smokers.
- Most patients had locally advanced disease and received contemporary thoracic radiotherapy. Median prescription was 60 Gy in 30 fractions, while 77% subsequently or concurrently received immunotherapy; carboplatin/paclitaxel was the most common chemotherapy regimen.
- A new cardiovascular adverse event occurred in 51/86 patients (59%) during or after treatment. The most frequent events were non-ST-elevation myocardial infarction in 15/51 (29.4%) and pericarditis or pericardial effusion in 15/51 (29.4%), followed by arrhythmia in 8/51 (15.7%).
- Cardiovascular morbidity accumulated over time: estimated cumulative event incidence was 16.5% at 6 months, 28.3% at 1 year, 50.0% at 2 years and 75.3% at 5 years. Ischemic events clustered early, with 60% occurring within the first year, while most pericardial events occurred within two years.
- Whole-heart dose-volume exposure showed the clearest treatment-related association. After adjustment for age, baseline cardiovascular comorbidity and metastatic status, each 1-percentage-point increase in heart V20 increased cardiovascular-event hazard by 2.4% (HR 1.024, 95% CI 1.005–1.044; p=.015), while heart V30 increased hazard by 3.1% per percentage point (HR 1.031, 95% CI 1.004–1.058; p=.025). Mean heart dose and V40 showed nonsignificant trends, while V50 was not associated with risk.
- Median overall survival was 29 months, with estimated survival of 73.1% at 1 year, 60.1% at 2 years and 34.5% at 5 years. Pre-existing cardiovascular comorbidity was consistently associated with approximately 2.2–2.5-fold greater mortality hazard, whereas none of the cardiac dose metrics independently predicted overall mortality.
- Interpretation requires caution: the cohort contained only 86 patients, the cardiovascular endpoint combined heterogeneous events, and 13 of 15 pericardial events were asymptomatic effusions found on surveillance imaging. Chemotherapy, immunotherapy, smoking and substantial baseline cardiovascular disease also make it impossible to attribute the observed morbidity specifically to radiation exposure.
CLINICAL TAKEAWAY
Cardiovascular morbidity after definitive lung cancer chemoradiotherapy may be substantial in patients who already carry a high cardiovascular-risk burden, and minimizing heart V20/V30 remains a sensible planning priority when target coverage permits. The study also supports continued cardiovascular surveillance after treatment, but the 59% event rate should not be interpreted as radiation-induced cardiac toxicity alone because the composite endpoint and population were highly heterogeneous.