Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with 18F-FDG PET, 18F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

The purpose of this work was to evaluate the potential of functional imaging with F-18-FDG PET, F-18-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 (F-18-FDG and F-18-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 F-18-fluoromisonidazole ratio (T/B-max) on the baseline F-18-fluoromisonidazole scan (P = 0.04), with the size of the initial hypoxic volume (P = 0.04), and with T/Bmax on the F-18-fluoromisonidazole scan during treatment (P = 0.02). All locoregional recurrences were within the F-18-FDG-avid regions on baseline F-18-FDG PET; 3 recurrences mapped outside the hypoxic volume on baseline F-18-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 mm(2)/s, P = 0.01) and at 3 wk after treatment (0.0014 vs. 0.0018 mm(2)/s, P 5 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 F-18-FDG PET and F-18-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.