Abstract
PURPOSE: The objective was to assess associations between cardiac substructure dose and changes in patient-reported outcomes (PROs) post-chemoradiotherapy for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: The study population was derived from CLARITY (NCT04305613), a multi-institutional longitudinal prospective cohort study. Patients treated with conventionally fractionated radiotherapy (1.8-2 Gy per fraction) with concurrent chemotherapy completed physical activity (Godin) and quality of life (FACIT-Fatigue and Dyspnea) questionnaires at baseline, completion of radiotherapy, 6 and 12 months post-radiotherapy. Thirty cardiac dosimetric parameters were a priori selected from centrally contoured radiotherapy plans: mean dose, maximum dose, volume receiving ≥ 5 Gy (V5Gy), V15Gy, and V30Gy to the whole heart, left ventricle, right ventricle, left atrium, right atrium, and left anterior descending coronary artery, and applied to a LASSO regression model to further define variable importance. Associations between cardiac radiation dose metrics and changes in PROs were assessed using repeated-measures linear regression via generalized estimating equations with correction for multiple testing. RESULTS: In a subcohort of 122 patients, the median age was 67 years, 57% were male, and 41% had prevalent cardiovascular disease. Median whole heart mean dose was 9 Gy, whole heart maximum dose was 64 Gy, and LAD V15Gy was 1%. Godin physical activity (p = 0.0499), FACIT-Fatigue (p < 0.001), and FACIT-Dyspnea scores (p = 0.0037) worsened from baseline to end of radiotherapy, then recovered to baseline levels thereafter. In multivariable analysis and after adjusting for multiple comparisons, no cardiac dose metric was significantly associated with a worsening in patient-reported physical activity, fatigue or dyspnea (p > 0.05). CONCLUSIONS: PROs worsened from baseline to the end of thoracic chemoradiotherapy, then recovered to baseline levels. Cardiac radiation dose metrics were not associated with these changes.