F-FLT PET/CT Adds Value to F-FDG PET/CT for Diagnosing Relapse After Definitive Radiotherapy in Patients with Lung Cancer: Results of a Prospective Clinical Trial.

Diagnosing relapse after radiotherapy for lung cancer is challenging. The specificity of both CT and F-FDG PET/CT is low because of radiation-induced changes. 3'-deoxy-3'-F-fluorothymidine (F-FLT) PET has previously demonstrated higher specificity for malignancy than F-FDG PET. We investigated the value of F-FLT PET/CT for diagnosing relapse in irradiated lung cancer. Patients suspected of relapse of lung cancer after definitive radiotherapy (conventional fractionated radiotherapy [cRT] or stereotactic body radiotherapy [SBRT]) were included. Sensitivity and specificity were analyzed both within the irradiated high-dose volume (HDV) and on a patient basis. Marginal differences and interobserver agreement were assessed. Sixty-three patients who had received radiotherapy in 70 HDVs (34 cRT; 36 SBRT) were included. The specificity of F-FLT PET/CT was higher than that of F-FDG PET/CT (HDV, 96% [95% CI, 87-100] vs. 71% [95% CI, 57-83] [ = 0.0039]; patient-based, 90% [95% CI, 73-98] vs. 55% [95% CI, 36-74] [ = 0.0020]). The difference in specificity between F-FLT PET/CT and F-FDG PET/CT was higher after cRT than after SBRT. The sensitivity of F-FLT PET/CT was lower than that of F-FDG PET/CT (HDV, 69% [95% CI, 41-89] vs. 94% [95% CI, 70-100] [ = 0.1250]; patient-based, 70% [95% CI, 51-84] vs. 94% [95% CI, 80-99] [ = 0.0078]). Adding F-FLT PET/CT when F-FDG PET/CT was positive or inconclusive improved the diagnostic value compared with F-FDG PET/CT alone. In cRT HDVs, the probability of malignancy increased from 67% for F-FDG PET/CT alone to 100% when both tracers were positive. F-FLT PET/CT adds diagnostic value to F-FDG PET/CT in patients with suspected relapse. The diagnostic impact of F-FLT PET/CT was highest after cRT. We suggest adding F-FLT PET/CT when F-FDG PET/CT is inconclusive or positive within the previously irradiated volume to improve diagnostic value in patients for whom histologic confirmation is not easily obtained.