126 Chapter 8 Figure 3 dose distribution of an esophageal cancer versus a breast cancer patient differences in MHD vs dose in subregions of the heart Two papers published by Atkins et all and Prunaretti ea. indeed confirmed this. Looking at the mean dose to the heart was not representative for the dose in a specific subregion (figure 3), especially when using more modern techniques [29,30]. This effect is visualized in figure 1 in EC patients, whereas the mean heart dose was about half using a proton therapy plan compared to the photon plan , the dose difference in the left atrium was much smaller Another advantage of using dose distributions to cardiac substructures instead of the dose distributions to the whole organ is that this will probably give more insight in the possible mechanisms behind these toxicities, which could guide new optimization strategies in preventing these side effects. However, there are drawbacks in delineating substructures. Some of these substructures are small and more difficult to delineate, leading to an increase in contouring variabilities between centres and physicians and this more uncertainties in interpreting the results of studies on dose-effect relationships. Both may introduce a potential bias in NTCP modelling. Moreover, in smaller organs, it is more likely to have smaller difference in dose distributions within this organ. Especially when located closely to the target volume, it will be difficult to find a dose response relationship but merely an on-off relationship (within or without your target volume) as a toxicity endpoint. A second drawback is history, as many of the current knowledge and validated models are based on the mean heart dose. Introducing these newer models, using subregions of the heart, will require time, both for generating and validating these new models.
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