To evaluate diffusion-weighted (DW) magnetic resonance (MR) imaging, as compared with turbo spin-echo MR imaging, for the detection of nodal metastases in head and neck squamous cell carcinoma (HNSCC). The study was approved by the ethics committee, and patients gave written informed consent. Before undergoing surgery, 33 consecutive patients underwent 1.5-T MR imaging, including DW imaging performed with a wide range of b values (0-1000 sec/mm(2)). The apparent diffusion coefficients (ADCs) of lymph nodes 4 mm or greater in short-axis diameter depicted on images obtained with b values of 0 and 1000 sec/mm(2) were calculated. After topographic correlation, the lymph nodes were evaluated microscopically with prekeratin immunostaining. The optimal ADC thresholds for discriminating between metastatic and benign lymph nodes were determined. The sensitivity, specificity, and accuracy of DW imaging were calculated separately-on per-lymph-node and per-neck-level bases-for all lymph nodes and for supracentimeter and subcentimeter lymph nodes and were compared with corresponding turbo spin-echo MR imaging values. Correlation of histopathologic and radiologic findings was possible for 301 lymph nodes. The ADC derived from the signal intensity averaged across images obtained with b values of 0 and 1000 sec/mm(2) (ADC(b0-1000)) was 1.19 x 10(-3) mm(2)/sec +/- 0.22 (standard deviation) for benign lymph nodes and 0.85 x 10(-3) mm(2)/sec +/- 0.27 for malignant lymph nodes (P < .0001). With an optimal ADC(b0-1000) threshold of 0.94 x 10(-3) mm(2)/sec, 84% sensitivity, 94% specificity, and 91% accuracy for differentiation of malignant versus benign status of each lymph node and 94% sensitivity, 97% specificity, and 97% accuracy for differentiation at each neck level were achieved. Compared with turbo spin-echo imaging, DW imaging had higher sensitivity (76% vs 7%) but slightly lower specificity (94.0% vs 99.5%) for detection of subcentimeter nodal metastases. DW imaging performed with ADC(b0-1000) values had higher accuracy than turbo spin-echo MR imaging in nodal staging, providing added value in the detection of subcentimeter nodal metastases.

Over the last few decades, significant improvements have been made in the radiotherapy (RT) treatment of head and neck malignancies. The progressive introduction of intensity-modulated RT and the use of multimodality imaging for target volume and organs at risk delineation, together with the use of altered fractionation regimens and concomitant administration of chemotherapy or targeted agents, have accompanied efficacy improvements in RT. Altogether, such improvements have translated into improvement in locoregional control and overall survival probability, with a decrease in the long-term adverse effects of RT and an improvement in quality of life. Further progress in the treatment of head and neck malignancies may come from a better integration of molecular imaging to identify tumor subvolumes that may require additional radiation doses (ie, dose painting) and from treatment adaptation tracing changes in patient anatomy during treatment. Proton therapy generates even more exquisite dose distribution in some patients, thus potentially further improving patient outcomes. However, the clinical benefit of these approaches, although promising, for patients with head and neck cancer need to be demonstrated in prospective randomized studies. In this context, our article will review some of these advances, with special emphasis on target volume and organ-at-risk delineation, use of molecular imaging for tumor delineation, dose painting for dose escalation, dose adaptation throughout treatment, and potential benefit of proton therapy.

The purpose of this work was to evaluate the potential of functional imaging with ¹⁸F-FDG PET, ¹⁸F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI to provide an appropriate and reliable biologic target for dose painting in radiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods: Fifteen patients with locally advanced HNSCC, treated with concomitant chemoradiotherapy, were prospectively enrolled in a bioimaging protocol. Sequential PET (¹⁸F-FDG and ¹⁸F-fluoromisonidazole) and MRI (T1, T2, dynamic enhanced, and diffusion-weighted sequences) were performed before, during, and after radiotherapy. Results: Median follow-up was 30.7 mo (range, 6.3–56.3 mo); in 7 patients, disease recurred. Disease-free survival correlated negatively with the maximum tissue-to-blood ¹⁸F-fluoromisonidazole ratio (T/B_max) on the baseline ¹⁸F-fluoromisonidazole scan (P = 0.04), with the size of the initial hypoxic volume (P = 0.04), and with T/B_max on the ¹⁸F-fluoromisonidazole scan during treatment (P = 0.02). All locoregional recurrences were within the ¹⁸F-FDG–avid regions on baseline ¹⁸F-FDG PET; 3 recurrences mapped outside the hypoxic volume on baseline ¹⁸F-fluoromisonidazole PET. Lesions (primary tumor and lymph nodes) where a locoregional recurrence developed during follow-up had significantly lower apparent diffusion coefficients on diffusion-weighted MRI during week 4 of radiotherapy (0.0013 vs. 0.0018 mm²/s, P = 0.01) and at 3 wk after treatment (0.0014 vs. 0.0018 mm²/s, P = 0.01) and a significantly higher initial slope on baseline dynamic enhanced MRI (26.2 vs. 17.5/s, P = 0.03) than did lesions that remained controlled. Conclusion: These results confirm the added value of ¹⁸F-FDG PET and ¹⁸F-fluoromisonidazole PET for radiotherapy planning of HNSCC and suggest the potential of diffusion-weighted and dynamic enhanced MRI for dose painting and early response assessment.