In recent years, the impressive progress performed in imaging, computational and technological fields have made possible the emergence of image-guided radiation therapy (IGRT) and adaptive radiation therapy (ART). The accuracy in radiation dose delivery reached by IMRT offers the possibility to increase locoregional dose-intensity, potentially overcoming the poor tumor control achieved by standard approaches. However, before implementing such a technique in clinical routine, a particular attention has to be paid at the target volumes definition and delineation procedures to avoid inadequate dosage to TVs/OARs. In head and neck squamous cell carcinoma (HNSCC), the GTV is typically defined on CT acquired prior to treatment. However, providing functional information about the tumor, FDG-PET might advantageously complete the classical CT-Scan to better define the TVs. Similarly, re-imaging the tumor with optimal imaging modality might account for the constantly changing anatomy and tumor shape occurring during the course of fractionated radiotherapy. Integrating this information into the treatment planning might ultimately lead to a much tighter dose distribution. From a methodological point of view, the delineation of TVs on anatomical or functional images is not a trivial task. Firstly, the poor soft tissue contrast provided by CT comes out of large interobserver variability in GTV delineation. In this regard, we showed that the use of consistent delineation guidelines significantly improved consistency between observers, either with CT and with MRI. Secondly, the intrinsic characteristics of PET images, including the blur effect and the high level of noise, make the detection of the tumor edges arduous. In this context, we developed specific image restoration tools, i.e. edge-preserving filters for denoising, and deconvolution algorithms for deblurring. This procedure restores the image quality, allowing the use of gradient-based segmentation techniques. This method was validated on phantom and patient images, and proved to be more accurate and reliable than threshold-based methods. Using these segmentation methods, we proved that GTVs significantly shrunk during radiotherapy in patients with HNSCC, whatever the imaging modality used (MRI, CT, FDG-PET). No clinically significant difference was found between CT and MRI, while FDG-PET provided significantly smaller volumes than those based on anatomical imaging. Refining the target volume delineation by means of functional and sequential imaging ultimately led to more optimal dose distribution to TVs with subsequent soft tissue sparing. In conclusion, we demonstrated that a multi-modality-based adaptive planning is feasible in HN tumors and potentially opens new avenues for dose escalation strategies. As a high level of accuracy is required by such approach, the delineation of TVs however requires a special care.

Positron emission tomography (PET) is a molecular imaging technique that provides a direct and accurate evaluation of tissue function in vivo. PET of the glucose analogue 18F-fluoro-deoxy-glucose, is increasingly in use to aid in gross target volume delineation in radiotherapy treatment planning (RTP) where it shows reduced inter-observer variability. The aim of this thesis was to develop and investigate a new technique for delineating PET-GTV with sufficient accuracy for RTP. A new technique, volume and contrast adjusted thresholding (VCAT), has been developed to automatically determine the optimum threshold value that measures the true volume on PET images. The accuracy was investigated in spherical and irregular lesions in phantoms using both iterative and filtered back-projection reconstructions and different image noise levels. The accuracy of delineation for the irregular lesions was assessed by comparison with CT using the Dice Similarity Coefficient and Euclidean Distance Transformation. A preliminarily investigation of implementing the newly developed technique in patients was carried out. VCAT proved to determine volumes and delineate tumour boundaries on PET/CT well within the acceptable errors for radiotherapy treatment planning irrespective of lesion contrast, image noise level and reconstruction technique.

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