35 Editorial on relevance of cardiac toxicity In imaging studies during follow up, myocardial wall motion disorders and changes in the metabolism of the myocardium were observed. These changes are in line with animal and autopsy studies showing damage to microvasculature, focal ischemia and fibrosis of the myocardium [7]. The problem with cardiac events after radiotherapy is that it is not possible to determine in individual patients whether such an event is actually related to radiation treatment itself. However, there are strong arguments to conclude that at least part of cardiac events after radiotherapy are radiation-induced, such as the significant association between cardiac radiation dose and the incidence of cardiac events [8,9]. Based on the current literature, however, it remains difficult to define a clear cut threshold for the radiation dose that can be given without any risk. In this regard, it is important to mention that Darby et al. did not find a threshold dose and concluded that every Gray on the heart matters. Furthermore, the heart is a complex organ containing numerous different sub volumes leading to a variety of different biological changes when irradiated. E.g., coronary artery events are most probably related to high radiation dose levels on small sub volumes, while the risk of heart failure may be more related to a lower dose on large volumes of the heart. Therefore, it is unlikely that one threshold dose can be defined that covers all late toxicities related to different parts of the heart. Given that there are many other risk factors for cardiac events, multivariable prediction models are needed that take into account not only dose volume metrics but also patient and other treatment-related factors. Current modern radiation treatment techniques can be used to modify the radiation dose to the heart. However, attempts to reduce the dose to the heart will generally increase the low to intermediate dose to the lungs[10], resulting in an increased risk of radiation pneumonitis and pulmonary fibrosis. Reducing the total dose or even omitting the radiotherapy treatment will certainly reduce toxicity rates but this will certainly jeopardize local control rated and tumor specific survival rates, as recent studies showed worse results with lower radiation dose [11]. In fact, proton therapy is the only radiation delivery technique that can reduce the dose to the heart without increasing the lung dose [12]. At present, however, the capacity for proton therapy is limited and only few proton therapy facilities are actually treating patients. The benefit in terms of dose reduction that can be obtained with protons varies widely among individual patients, meaning that proton therapy will not result in a clinical benefit in terms of a clinically relevant reduction 3
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