27 Review on cardiac toxicity Not only treatment related factors were significant related to cardiac toxicity, older age and female sex gave a significantly higher risk in two[3,7] and one[12] of the reviewed papers. However, patient numbers are low and these non-treatment related risk factors should be confirmed in larger patient groups. The challenge for the future will be to decide which clinical endpoints are relevant and should be incorporated into an NTCP model for esophageal cancer patients. Pericardial effusion was the most frequently observed complication, with an actuarial rate of 48%. [6] The biological mechanism behind PE is considered inflammatory. [22] In most cases, pericardial effusion is self-limiting and asymptomatic, but may progress into heart failure and death.[2–4] The observed incidence depends heavily on the use of routine imaging techniques, such as CT scans. Although it is the easiest clinical endpoint to incorporate into a model (high rate and objective), pericarditis is not expected to have a significant impact on the quality of life of the surviving patients. Secondary ischemic events occur frequently in esophageal cancer patients treated with radiotherapy or CRT, not only as a very late side effect, but also during the first 2 years after completion of treatment. However, radiotherapy may not be the only risk factor for this cardiac event. Esophageal cancer patients generally have a number of risk factors for ischemic heart disease, including older age, histories of tobacco use and/or obesity.[23] All patients were irradiated combined with chemotherapy, most often with cisplatinum and 5-FU, which are both associated with increased risks of thrombus formation. [24–26] Based on the available data, it was impossible to correct for these potential confounding factors. Heart failure, the third most frequently observed complication after radiotherapy or chemoradiation, may be the result of other cardiac events, including myocardial infarction, pericarditis and valvular disorders. It may very well be possible that these different cardiac events with different underlying mechanisms relate to different dose-volume response relationships and as such may result in secondary cardiac events. These kind of relationships should be adjusted for in multivariable prediction models. Clinical research on functional imaging and other cardiac function parameters is necessary to better understand the mechanisms of radiation induced-cardiac toxicity and to identify the most critical parts of the heart for each of the aforementioned clinical endpoints. 2
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