Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer.

PURPOSE: The outcome of locally advanced head-and-neck cancer often is poor. An important determinant of treatment failure is tumor hypoxia arising from an inappropriate blood supply. Quantitation of the hypoxic fraction and blood flow in vivo may provide prognostic information and a means to target specifically tumor cells resistant to conventional treatment. METHODS AND MATERIALS: Twenty-one patients with head-and-neck cancer underwent multitracer positron emission tomography (PET) before the start of preoperative or definitive radiotherapy (RT). Tumor blood flow was measured using the [(15)O]H(2)O autoradiographic technique followed by evaluation of oxygenation status using [(18)F]fluoroerythronitroimidazole ([(18)F]FETNIM). [(18)F]fluorodeoxyglucose PET was performed on a separate day to calculate the metabolically active tumor volume. The definition of the fractional hypoxic volume (FHV) in the tumor was determined by multiple voxel-wise measurements of the uptake of [(18)F]FETNIM in well-oxygenated tissues and tumor. PET findings were then correlated with the RT outcome and survival. RESULTS: High blood flow was associated with poor local control after RT (p = 0.021) and with poor survival (p = 0.018). Patients with a FHV greater or equal to the median had significantly worse survival than those with a FHV less than the median (p = 0.036). The relationship between tumor hypoxia and FHV was supported in 3 patients who underwent invasive measurement of the tissue O(2) partial pressure. CONCLUSION: High tumor blood flow predicted for a poor response to RT in head-and-neck cancer. The use of [(18)F]FETNIM for assessment of radiobiologic hypoxia requires a study with greater statistical power. PET with [(15)O]H(2)O or [(18)F]FETNIM may become useful in clinical trials in which novel therapeutic agents targeting tumor vasculature or hypoxia are evaluated.