29 Review on cardiac toxicity Esophageal cancer patients are different from breast cancer and lymphoma patients, as their prognosis is poorer and the radiation doses to the heart are much higher. In current routine clinical practice, radiation oncologists consider the spinal cord and lungs as the most important critical organs. Although the results of our review confirm that the heart should also be considered to be a critical organ, the optimal distribution of the dose between the various OARs remains to be determined. In general, a reduction of the dose to the heart, even with advanced radiation delivery techniques such as IMRT or VMAT, will result in a higher lung dose with an increased risk of radiation pneumonitis and fibrosis. Proton therapy may overcome this problem, but is not widely available and relatively expensive. Therefore, selection of the patients who will benefit most from proton therapy will be essential.[34] However, if the precise association between radiation-induced side effects and the dose-volume parameters is not clear, the translation of observed differences in dose distributions between protons and photons into clinical benefits remains difficult. Accurate multivariable prediction models on radiation-induced toxicity are necessary to estimate the potential added benefits of various techniques. Although we showed that cardiac toxicity is a relevant problem in the treatment of esophageal cancer, we will obviously need more esophageal cancer patients with strict follow up data and dose distributions on critical organs as current data are insufficient to make prediction models for radiation-induced cardiac toxicity in these patients. As causes of death are often hard to identify, overall survival in addition to disease specific survival is very important to avoid underestimation of cardiac toxicity. Imaging studies and cardiac function parameters during follow up will help us identifying the most relevant clinical endpoints and critical parts of the heart. 2
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