Associations Between Cardiac Radiation Dose-Volume Metrics and Health-Related Quality of Life for Patients With...

Relationships between radiation therapy (RT) dose to cardiac substructures and patient-reported outcomes, as assessed by health-related quality of life (HRQOL), remain unknown. We sought to: (1) compare RT dose to cardiac substructures in patients treated with proton versus photon RT on the Radiotherapy Comparative Effectiveness (RadComp) pragmatic randomized clinical trial, which compared proton versus photon RT in breast cancer; (2) evaluate whether there were changes in HRQOL outcomes from baseline to 6 months following RT; and (3) determine the potential associations between radiation dose-volume histogram (DVH) parameters and changes in cardiac-related HRQOL.

This analysis included 1160 RadComp participants with available radiation DVH metrics for all cardiac substructures who completed baseline and ≥1 follow-up HRQOL over the 6 months post-RT. Cardiac substructures included the whole heart, left ventricle, right ventricle, left atrium, right atrium, and left anterior descending artery; exposures of interest included dose to 0.03 cm³, maximum dose, mean dose, and percent volume receiving a specified dose. HRQOL measures that we hypothesized could provide some insights into cardiac symptoms included Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) shortness of breath and chest pain, chest tightness, and angina.

The mean dose to the whole heart was lower with protons, 0.89 Gy(relative biological effectiveness (RBE)) (Q1-Q3, 0.49-1.39), compared with photons 2.99 Gy (Q1-Q3, 1.60-4.61) (P< .001), as was the mean dose to the left ventricle, left atrium, and left anterior descending artery (P < .001). PRO-CTCAE measures were favorable at all time points with only modest changes observed, and grade ≥3 toxicity was uncommon (≤5.5%) for all measures. No DVH metrics were significantly associated with any cardiac-related HRQOL outcomes over the 6 months post-RT when evaluated by treatment arm or laterality.

Proton RT generally conferred significantly lower doses to the heart and cardiac substructures compared with photon RT. PRO-CTCAE measures were favorable overall. No cardiac DVH parameters were associated with early HRQOL outcomes.