Cardiac dose-volume analysis of 9,411 patients with registry data for cardiovascular disease and overall survival.

Abstract

Abstract Background and purpose Radiation therapy (RT) to the thorax poses risks of radiation-induced cardiotoxicity, potentially increasing cardiovascular diseases (CVD) incidence. Advances in RT strive to minimize these risks by reducing heart radiation dose exposure. This study integrates detailed 3D dosimetry on individually delineated hearts with registry-based outcome data to assess the impact of radiation dose on cardiovascular morbidity and overall survival (OS) across multiple cancer types. It also examined the influence of patient-specific factors on cardiotoxicity risk and survival outcomes. Materials and methods We analyzed data from 9,411 patients receiving RT at Rigshospitalet between 2009 and 2020 for breast, esophageal, lymphoma, and lung cancers. Cumulative incidence of CVD and death in the presence of competing risks was calculated with the Aalen-Johansen estimator. The impact of radiation dose and patient characteristics on ischemic heart disease (IHD) onset and OS were assessed using Kaplan-Meier and Cox Proportional-Hazards Models. Results Higher mean heart dose (MHD) was associated with poorer OS in breast and lung cancer patients (Hazard ratio 2.8 and 1.2), but no significant relationship was found between MHD and IHD. Established cardiac risk factors (age, sex, and existing IHD) outweighed cardiac dose as a risk factor for subsequent cardiac events for all diagnoses. The risk of death was greater than subsequent CVD, especially in esophageal and lung cancers (cumulative incidence 60% versus 17% and 60% versus 14%), despite comparatively high heart doses. Conclusion The study demonstrates that risk of death from primary cancer is of far greater concern than risk of subsequent cardiac events from cardiac radiation dose exposure in the range achievable with contemporary RT techniques, especially for lung and esophageal cancer patients. Further sparing of the heart should not be prioritized at the expense of adequate treatment of the index cancer. Highlights - Age and existing heart disease far outweighed heart dose as predictors of ischemic heart disease - Overall survival is not a useful surrogate for cardiac toxicity in dose-response studies due to confounding by disease stage - With modern RT techniques, the excess absolute risk attributable to radiotherapy is so small that a statistically significant dose-response could not be observed even in 9,411 patients - For most patients, good quality contemporary radiotherapy is sufficient to limit heart toxicity as a clinically relevant concern