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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

¹ Department of Radiation Oncology, Leuvens Kankerinstituut, University Hospitals Leuven, Leuven, Belgium; ² Department of Radiology, Leuvens Kankerinstituut, University Hospitals Leuven, Leuven, Belgium; and ³ Department of Nuclear Medicine, Leuvens Kankerinstituut, University Hospitals Leuven, Leuven, Belgium

Correspondence: For correspondence or reprints contact: Piet Dirix, Department of Radiation Oncology, Leuvens Kankerinstituut (LKI), University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49 B-3000, Leuven, Belgium. E-mail: piet.dirix{at}uzleuven.be

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.

Key Words: head and neck cancer • radiotherapy • PET • MRI

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