Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with¹⁸F-FDG PET,¹⁸F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Abstract

The purpose of this work was to evaluate the potential of functional imaging with 18 F-FDG PET, 18 F-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 ( 18 F-FDG and 18 F-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 18 F-fluoromisonidazole ratio (T/B max ) on the baseline 18 F-fluoromisonidazole scan (P 5 0.04), with the size of the initial hypoxic volume (P 5 0.04), and with T/B max on the 18 F-fluoromisonidazole scan during treatment (P 5 0.02). All locoregional recurrences were within the 18 F-FDGavid regions on baseline 18 F-FDG PET; 3 recurrences mapped outside the hypoxic volume on baseline 18 F-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 5 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 5 0.03) than did lesions that remained controlled. Conclusion: These results confirm the added value of 18 F-FDG PET and 18 F-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.

High Reproducibility of Tumor Hypoxia Evaluated by 18F-Fluoromisonidazole PET for Head and Neck Cancer

“…The images with short time intervals included 18 F-FMISO accumulation in the blood pool (17,18). We considered 18 F-FMISO imaging at 4 h after injection to be more suitable than imaging in less than 3 h, as used in several other studies (3)(4)(5)(7)(8)(9)(10)(11), for the following reasons. Because blood clearance of 18 F-FMISO is rather slow, residual blood pool activity at 1-3 h remains relatively high.…”

“…18 F-fluoromisonidazole ( 18 F-FMISO) PET has been used for noninvasive evaluation of hypoxia, and 18 F-FMISO uptake is related to patient prognosis (3)(4)(5)(6). Quantitative evaluation of 18 F-FMISO uptake is expected to play an important role in the planning of dose escalation radiotherapy (7)(8)(9). However, the reproducibility of 18 F-FMISO uptake has remained unclarified.…”

Positron emission tomography to assess hypoxia and perfusion in lung cancer

“…Koh et al [221] , Liu et al [222] , Yeh et al [223] , Rischin et al [224] , Bentzen et al [125] , Rajendran et al [225] , Gagel et al [126] , Rajendran et al [226] , Hicks et al [227] , Lawrentschuk et al [200] , Loi et al [228] , Thorwarth et al [229] , Rajendran et al [230] , Rischin et al [231] , Thorwarth et al [232] , Zimny et al [124] , Eschmann et al [233] , Gagel et al [202] , Thorwarth et al [234] , Thorwarth et al [235] , Lee et al [236] , Lin et al [237] , Nehmeh et al [238] , Roels et al [239] , Dirix et al [240] , Lee et al [241] , Mortensen et al [127] , Wang et al [56] , Abolmaali et al [242] , Bowen et al [138] , Eary et al [243] , Kikuchi et al [244] , Hugonnet et al [131] , Yamane et al [245] , Mammar et al [246] , Zips et al [247] , Cheng et al [217] , Henriques de Figueiredo et al [248] , Okamoto et al [249] , Sato et al [218] , Segard et al [250] , Tachibana et al [251] , Norikane et al [219] [ Dubois et al …”

PET/CT significance for planning radiotherapy of head and neck cancer

“…This can help us to target predominantly specific hypermetabolic areas as well as potentially radio-resistant hypoxic tumor areas suitable for IMRT treatment [28,29].…”