Dosimetric associations between high-dose cardiac exposure and global longitudinal strain deterioration after definitive radiotherapy for lung cancer

Background Radiation-induced cardiac injury is an important late effect of definitive radiotherapy for lung cancer (1). Global longitudinal strain (GLS) is a sensitive marker of subclinical myocardial dysfunction; however, its relationship with detailed cardiac dosimetry remains incompletely defined (2). Purpose To evaluate associations between cardiac dose–volume parameters and GLS deterioration after definitive radiotherapy for non-metastatic lung cancer, and to assess effect modification by hypertension. Methods Patients with non-metastatic lung cancer treated with definitive radiotherapy or concurrent chemoradiotherapy were identified from a prospective registry with protocol-driven echocardiographic follow-up. Cardiac dose–volume parameters for the whole heart and cardiac substructures were derived using a standardized cardiac atlas. GLS change from baseline to follow-up was analyzed using multivariable linear regression adjusted for baseline GLS and established cardiovascular risk factors, with interaction analyses for hypertension. Results Ninety-eight patients with paired baseline and follow-up echocardiography were included. Median GLS significantly deteriorated from −16.17 at baseline to −14.11 at follow-up, corresponding to a median increase of 1.82% (95% CI, 1.40–2.25; p < 0.001) (Figure 1). In adjusted analyses, higher total prescribed dose was significantly associated with GLS deterioration (β = 0.009 per 10 Gy increase, 95% CI 0.001–0.017, p = 0.032). Among cardiac substructures, ventricular high-dose exposure demonstrated the strongest associations with GLS change. Specifically, both left ventricular (LV) and right ventricular (RV) V45 (percentage volume receiving ≥45 Gy) were significantly associated with GLS deterioration (LV V45: β = 0.351 per 10% increase, 95% CI 0.044–0.658, p = 0.026; RV V45: β = 0.840, 95% CI 0.240–1.439, p = 0.007). In contrast, atrial dose parameters were not associated with GLS change. Hypertension significantly modified the association between LV V45 and GLS deterioration. GLS change per 10% increase in LV V45 was modest among patients without hypertension but markedly greater among patients with hypertension, with a significant interaction (p for interaction = 0.027) (Figure 2). During follow-up, 8 patients (8.2%) experienced CVD events, including arrhythmia, heart failure, and pulmonary thromboembolism. Conclusions High-dose ventricular cardiac exposure during definitive radiotherapy for lung cancer is associated with subclinical myocardial dysfunction as measured by GLS, with a disproportionately greater impact among patients with hypertension. These findings support ventricular dose optimization and hypertension-informed cardiac surveillance strategies in lung cancer radiotherapy.