With the routine use of intensity modulated radiation therapy for the treatment of head-and-neck squamous cell carcinoma allowing highly conformed dose distribution, there is an increasing need for refining both the selection and the delineation of gross tumor volumes (GTV). In this framework, molecular imaging with positron emission tomography and magnetic resonance imaging offers the opportunity to improve diagnostic accuracy and to integrate tumor biology mainly related to the assessment of tumor cell density, tumor hypoxia, and tumor proliferation into the treatment planning equation. Such integration, however, requires a deep comprehension of the technical and methodological issues related to image acquisition, reconstruction, and segmentation. Until now, molecular imaging has had a limited value for the selection of nodal GTV, but there are increasing evidences that both FDG positron emission tomography and diffusion-weighted magnetic resonance imaging has a potential value for the delineation of the primary tumor GTV, effecting on dose distribution. With the apprehension of the heterogeneity in tumor biology through molecular imaging, growing evidences have been collected over the years to support the concept of dose escalation/dose redistribution using a planned heterogeneous dose prescription, the so-called "dose painting" approach. Validation trials are ongoing, and in the coming years, one may expect to position the dose painting approach in the armamentarium for the treatment of patients with head-and-neck squamous cell carcinoma.
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