Left Ventricular Systolic Dysfunction Is a Possible Independent Risk Factor of Radiation Pneumonitis in Locally Advanced Lung Cancer Patients

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.

New developments in locally advanced nonsmall cell lung cancer

“…Chemoradiotherapy can have side-effects that can interfere with the effects of immune-checkpoint inhibition. There can be direct cardiac toxicity, [17][18][19] but radiotherapy of immune-relevant body systems may also induce immunosuppression, which can negatively influence patient outcomes [96,97]. Concurrent chemoradiotherapy may dynamically alter PD-L1 expression and numbers of CD8 + tumour infiltrating lymphocytes [98,99].…”

“…Right ventricular function seems to be correlated with prognosis after chemoradiotherapy [17,18]. A pre-therapeutic reduced left ventricular ejection fraction may increase the risk of radiation pneumonitis [19]. Pulmonary and cardiac toxicities can be increased by chemo-and immunotherapy [20][21][22][23][24].…”