Moving beyond mean heart dose: The importance of cardiac substructures in radiation therapy toxicity.

Normal tissue tolerance dose limits to the heart have been established to reduce the risk of radiation-induced cardiac disease (RICD). Dose constraints have been developed based on either the mean dose delivered to the whole heart (MHD) or the dose delivered to a specific volume, for example, volume of heart receiving equal to or greater than 30 Gy (V30). There is increasing evidence that the impact of thoracic radiation on cardiac morbidity and mortality has been underestimated. Consequently, there is a need to reduce the dose delivered to the heart in radical radiotherapy treatment planning. The pathophysiology of RICD may relate to dose to specific cardiac substructures (CS) rather than the traditionally observed MHD for common toxicities. The MHD or V30 Gy threshold dose rarely represents the true dose delivered to individual CS. Studies have shown the dose to specific areas may be more strongly correlated with overall survival (OS). With advances in modern radiotherapy techniques, it is vital that we develop robust, evidence-based dose limits for CS, to fully understand and reduce the risk of RICD, particularly in high-risk populations with cardiac risk factors. The following review will summarise the existing evidence of dose limits to CS, explain how dose limits may vary according to different disease sites or radiation techniques and propose how radiotherapy plans can be optimised to reduce the dose to these CS in clinical practice.