Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)diacetyl- bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUVmax; SUVmean) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R-2. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P = .011), midtreatment FLT SUVmean (P = .018), and midtreatment FLT SUVmax (P = .006). Large decreases in FLT SUVmean from pretreatment to midtreatment were associated with worse clinical outcome (P = .013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUVmax (P = .022) in combination with large FLT response from pretreatment to midtreatment (P = .041). Conclusions: In addition to tumor volume, pronounced tumor proliferative response quantified using FLT PET, especially when associated with high residual FLT PET at midtreatment, is a negative prognostic biomarker of outcome in canine tumors following radiation therapy. Neither FDG PET nor Cu-ATSM PET were predictive of outcome. (C) 2015 Elsevier Inc. All rights reserved.