Cardiac conduction system as anew organ at risk in radiotherapy.

Abstract

Cardiovascular diseases represent the most common non-oncologic cause of death in patients following radiotherapy (RT) in the thoracic region. Radiation-induced heart disease (RIHD) can manifest as various heterogeneous clinical entities. However, the influence of RT on the cardiac conduction system has only recently gained more attention. Arrhythmogenic toxicity, i.e., conduction disorders and arrhythmias, constitutes asignificant part of these adverse effects. The cardiac conduction system is not routinely monitored as an organ at risk (OaR). Its specific histological nature and function suggest different sensitivity and response to radiation. The heart is ahighly heterogeneous organ, and the routinely monitored dose to the whole heart may not adequately characterize the risk of increased arrhythmogenic toxicity from RT. Cardiac structures, including the conduction system, appear to be additional OaRs for which dose distribution should be monitored. For the systematic selection of studies, we utilized the PubMed database with keywords derived from the analysis of existing literature. The search was limited to English-language publications, and the selection criteria included relevance to the topic and the quality of methodology. This article summarizes the impact of RT on the cardiac conduction system. Radiotherapy-induced cardiotoxicity significantly affects morbidity and mortality. The heart exhibits heterogeneity in terms of radiosensitivity. Certain cardiac subregions in the dose distribution show ahigher correlation with poorer overall survival than routinely monitored doses to the whole heart and derived parameters (the volumes irradiated with the doses of 5or 30Gy - V5or V30, respectively). The most radiosensitive subregions appear to be the base of the heart, including the beginning of the conduction system. Higher doses to the conduction system, especially the sinoatrial (SA) node, are associated with ahigher incidence of awide range of arrhythmias and poorer overall survival. However, dose limits (Dmean and Dmax) for the conduction system have not yet been established. Dosimetric studies have identified cutoff doses to the SA node, exceeding which there is asignificant increase in mortality and the occurrence of arrhythmias.