18F-FLT PET/CT Adds Value to 18F-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 ¹⁸F-FDG PET/CT is low because of radiation-induced changes. 3'-deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT) PET has previously demonstrated higher specificity for malignancy than ¹⁸F-FDG PET. We investigated the value of ¹⁸F-FLT PET/CT for diagnosing relapse in irradiated lung cancer. Methods: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. Results: Sixty-three patients who had received radiotherapy in 70 HDVs (34 cRT; 36 SBRT) were included. The specificity of ¹⁸F-FLT PET/CT was higher than that of ¹⁸F-FDG PET/CT (HDV, 96% [95% CI, 87-100] vs. 71% [95% CI, 57-83] [P = 0.0039]; patient-based, 90% [95% CI, 73-98] vs. 55% [95% CI, 36-74] [P = 0.0020]). The difference in specificity between ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT was higher after cRT than after SBRT. The sensitivity of ¹⁸F-FLT PET/CT was lower than that of ¹⁸F-FDG PET/CT (HDV, 69% [95% CI, 41-89] vs. 94% [95% CI, 70-100] [P = 0.1250]; patient-based, 70% [95% CI, 51-84] vs. 94% [95% CI, 80-99] [P = 0.0078]). Adding ¹⁸F-FLT PET/CT when ¹⁸F-FDG PET/CT was positive or inconclusive improved the diagnostic value compared with ¹⁸F-FDG PET/CT alone. In cRT HDVs, the probability of malignancy increased from 67% for ¹⁸F-FDG PET/CT alone to 100% when both tracers were positive. Conclusion:¹⁸F-FLT PET/CT adds diagnostic value to ¹⁸F-FDG PET/CT in patients with suspected relapse. The diagnostic impact of ¹⁸F-FLT PET/CT was highest after cRT. We suggest adding ¹⁸F-FLT PET/CT when ¹⁸F-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.