Abstract
Objectives: To assess the association between left ventricular (LV) systolic and diastolic dysfunction and grade ≥2 radiation pneumonitis (RP) for locally advanced lung cancer patients receiving definitive radiotherapy.Materials and Methods: A retrospective analysis was carried out for 260 lung cancer patients treated with definitive radiotherapy between 2015 and 2017. RP was evaluated according to Radiation Therapy Oncology Group (RTOG) toxicity criteria. Logistic regression analysis, 10-fold cross validation, and external validation were performed. The prediction model's discriminative performance was evaluated using the area under the receiver operating characteristic curve (AUC), and calibration of the model was assessed by the Hosmer-Lemeshow test and the calibration curve.Results: Within the first 6 months after radiotherapy, 70 patients (26.9%) developed grade ≥2 RP. Reduced left ventricular ejection fraction (LVEF) before radiotherapy was detected in 53 patients (20.4%). The odds ratio (OR) of developing RP for patients with LVEF <50% was 3.42 [p < 0.001, 95% confidence interval (CI), 1.85–6.32]. Multivariate analysis showed that forced expiratory volume in the first second/forced vital capacity (FEV1/FVC), LVEF, Eastern Cooperative Oncology Group (ECOG) performance status, chemotherapy, and mean lung dose (MLD) were significantly associated with grade ≥2 RP. The AUC of a model including the above five variables was 0.835 (95% CI, 0.778–0.891) on 10-fold cross validation and 0.742 (95% CI, 0.633–0.851) on the external validation set. The p-value for the Hosmer-Lemeshow test was 0.656 on 10-fold cross validation and 0.534 on the external validation set.Conclusion: LV systolic dysfunction is a possible independent risk factor for RP in locally advanced lung cancer patients receiving definitive radiotherapy.
Highlights
Concurrent chemoradiotherapy is a standard treatment regimen for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) [1] or small cell lung cancer [2]
Reduced left ventricular ejection fraction (LVEF) before radiotherapy was detected in 53 patients (20.4%)
The odds ratio (OR) of developing Radiation pneumonitis (RP) for patients with LVEF
Summary
Concurrent chemoradiotherapy is a standard treatment regimen for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) [1] or small cell lung cancer [2]. Previous preclinical [10,11,12] and clinical [13] studies have demonstrated that heart irradiation increases the risk of radiation-induced pulmonary dysfunction. The possible mechanism is that heart radiation directly leads to perivascular fibrosis and myocardial damage and increases enddiastolic pressure, contributing to left ventricular (LV) diastolic dysfunction, which further leads to pulmonary interstitial edema [12], suggesting a detrimental effect of reduced ventricular function on lung tissue. Nalbantov et al [14] demonstrated cardiac comorbidity was an independent risk factor for developing radiation-induced lung toxicity in lung cancer patients receiving definitive radiotherapy. Semrau et al [15] found that for patients with inoperable NSCLC receiving concurrent chemoradiotherapy, left ventricular ejection fraction (LVEF) ≤50% had no significant association with grades III and IV RP according to the Common Toxicity Criteria. The overall incidence of RP was fairly low: only three out of 130 patients (2.3%), it couldn’t accurately reflect the association between baseline cardiac function and RP
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