## 4 Discussion
In the current study, K(trans)\({}_{\text{post/pre/muscle}}\) values less than 0.85 suggested post-CRT fibrosis, whereas K(trans)\({}_{\text{post/pre/muscle}}\) values more than 1.20 indicated inflammatory edema. Vascular changes associated with residual cancer represent neoangiogenesis; on the contrary, post-treatment non-tumoral alterations show vascular changes of continued successful therapy and fibrosis [48]. Post-treatment changes may lead to significant variations in DCE-PWI parameter values since K(trans) is sensitive to angiogenic modifications [49]. Therefore, although with some degrees of overlap, little or no change in AUC\({}_{\text{post/pre/muscle}}\) and mean K(trans)\({}_{\text{post/pre/muscle}}\) values, i.e., tumoral neoangiogenesis, may be considered a post-treatment indicator of tumor persistence/recurrence (Figure 5). Some limitations need to be mentioned. The relationship among MRI and HNSCC stage, lymph node, distant metastasis, histological tumor grading, histopathological parameters, progression-free survival, HPV status, intravoxel incoherent motion, or tumoral 18F-FDG PET/CT standard uptake values were not performed. Moreover, we compared tissue changes between pre- and post-CRT without taking into account pre-treatment MRI features only as predictors of treatment response. Another limitation of the present study was the relatively low sample size. Nevertheless, most papers regarding HNSCC and functional MRI did not consider both DWI and DCE-PWI for therapy assessment or did not include both pre- and post-treatment MRI examinations. Moreover, few papers exclusively recruited patients with pharyngeal cancer [11; 28; 50; 51], and only two of these were performed with both DWI and DCE-PWI [11; 51]. In addition, the small number of patients with tumor persistence/recurrence (5 individuals) needed to be related to the well-known excellent response to CRT treatment of oropharyngeal--especially when HPV positive--and nasopharyngeal carcinomas. Furthermore, HPV+ and HPV\(-\) HNSCC generally differ in radiological imaging and prognosis [52], thus representing a possible bias in the current study. Moreover, our single-center results cannot be generalized until more evidence is gathered. Finally, the study design did not allow the calculation of the outcome incidence. For this reason, a discussion of the appropriateness of the cut-off values with respect to the rate of false positives was not possible. Future studies with a different design should help in choosing appropriate cut-off values that balance the benefits to true positives (e.g., increased survival) versus the costs to false positives (e.g., unnecessary procedures). To date, MRI evaluation in strictly morphologic terms represented by the SI on T1 and T2 images and grade of enhancement is still mandatory in HNSCC. Considering the relative complexity of DWI and DCE-PWI parameters that have been used and the low number of retrieved patients, the results obtained in our study are currently available for research purposes only. Further studies will be needed to establish whether or not multiparametric MRI examinations can be successfully used in clinical daily practice.