Correlation of PET images of metabolism, proliferation and hypoxia to characterize tumor phenotype in patients with cancer of the oropharynx

Spatial organization of tumor phenotype is of great interest to radiotherapy target definition and outcome prediction. We characterized tumor phenotype in patients with cancers of the oropharynx through voxel-based correlation of PET images of metabolism, proliferation, and hypoxia. Methods: Patients with oropharyngeal cancer received F-18-fluorodeoxyglucose (FDG) PET/CT, F-18-fluorothymidine (FLT) PET/CT, and Cu-61-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) PET/CT. Images were co-registered and standardized uptake values (SUV) were calculated for all modalities. Voxel-based correlation was evaluated With Pearson's correlation coefficient in tumor regions. Additionally, sensitivity studies were performed to quantify the effects of image segmentation, registration, noise, and segmentation on R. Results: On average, FDG PET and FLT PET images were most highly correlated (R-FDG:FLT = 0.76, range 0.53-0.85), while Cu-ATSM PET showed greater heterogeneity in correlation to other tracers (RFDG:Cu-ATSM = 0.64, range 0.51-0.79; RFLT:Cu-ATSM = 0.61, range 0.21-0.80). Of the tested parameters, correlation was most sensitive to image registration. Misregistration of one voxel lead to Delta R-FDG = 0.25, Delta R-FLT = 0.39, and Delta RCu-ATSM = 0.27. Image noise and reconstruction also had quantitative effects on correlation. No significant quantitative differences were found between GTV, expanded GTV, or CTV regions. Conclusions: Voxel-based correlation represents a first step into understanding spatial organization of tumor phenotype. These results have implications for radiotherapy target definition and provide a framework to test outcome prediction based on pretherapy distribution of phenotype. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 105 (2012) 36-40