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The progress and technological development of functional and molecular techniques for imaging the tumours has offered the possibility of defining the target in radiation therapy and devising the treatment in an innovative manner. The concept of Biological Target Volume (BTV) encompassing the multi-dimensional physiological and functional information provided by the new imaging techniques has been proposed many years ago and since then it has been a continuous challenge for the clinical community to define and apply it. There are several questions that arise: what are the key tumour features that could be derived from functional and molecular imaging, how should they be used for defining the BTV, what dose should be prescribed to the BTV to account for these features and, finally, how to deliver this dose in a safe and robust manner. The ultimate challenge would therefore be to use molecular and biological information from advanced imaging modalities for the individualisation and the adaptation of the treatment according to the key features of the patient taking into account the response of both tumours and normal tissues. A simplified approach would be to determine the critical radiobiological parameters influencing the radiation sensitivity of individual tumours before treatment, such as tumour metabolism, hypoxia, proliferation and density of clonogenic cells, based on PET-CT imaging using suitable tracers (e.g., FDG, FMISO, and FLT) and to include this biological information into the treatment planning. This approach therefore includes the critical step of deciding what dose should be prescribed and subsequently delivered based on the acquired knowledge about the tumour features derived from imaging - in other words the biologically-guided dose prescription.
This talk would therefore focus on the current approaches for prescribing the dose after the definition of the BTV, starting from the empirical dose escalations to developing quantitative methods for incorporating PET-CT information on tumour clonogenic cell density, hypoxia and proliferation into the treatment planning and optimisation. The controversial approach of dose re-distribution will also be discussed. Particular attention will be paid to presenting the potential implications of not taking into account the intrinsic dynamic character of the features defining the BTV on the dose escalation in the typical dose painting by numbers or contours approaches. The mathematical formalism and the computational approach will be presented in detail as well as the pipeline for the implementation into a treatment planning system. Clinical examples for dose prescription based on tumour hypoxia and clonogen density for H&N carcinoma patients will be included.