Radiation-Induced Dyspnea in Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

In this study, we investigated the prognostic factors for radiation-induced dyspnea after hypo-fractionated radiation therapy (RT) in 106 patients treated with Stereotactic Body RT for Non-Small-Cell Lung Cancer (NSCLC). The median prescription dose was 50 Gy (range: 40-54 Gy), delivered in a median of four fractions (range: 3-12). Dyspnea within six months after SBRT was scored according to CTCAE v.4.0. Biologically Effective Dose (α/β = 3 Gy) volume histograms for lungs and heart were extracted. Dosimetric parameters along with patient-specific and treatment-related factors were analyzed, multivariable logistic regression method with Leave-One-Out (LOO) internal validation applied. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot parameters. Fifty-seven patients (53.8%) out of 106 developed dyspnea of any grade after SBRT (25/57 grade ≥ 2 cases). A three-variable predictive model including patient comorbidity (COPD), heart volume and the relative lungs volume receiving more than 15 Gy was selected. The model displays an encouraging performance given by a training ROC-AUC = 0.71 [95%CI 0.61-0.80] and a LOO-ROC-AUC = 0.64 [95%CI 0.53-0.74]. Further modeling efforts are needed for dyspnea prediction in hypo-fractionated treatments in order to identify patients at high risk for developing lung toxicity more accurately.