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

SIMPLE SUMMARY: Dyspnea is a common symptomatic side-effect of thoracic radiation therapy. The aim of this study is to build a predictive model of any-grade radiation-induced dyspnea within six months after stereotactic body radiation therapy in patients treated for non-small cell lung cancer. The occurrence of pre-treatment chronic obstructive pulmonary disease and higher relative lungs volume receiving more than 15 Gy as well as heart volume were shown to be risk factors for dyspnea. The obtained results encourage further studies on the topic, which could validate the present organ-based findings and explore the voxel-based landscape of radiation dose sensitivity in the development of dyspnea. ABSTRACT: 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.