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 F-18-FDG PET/CT is low because of radiation-induced changes. 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT) PET has previously demonstrated higher specificity for malignancy than F-18-FDG PET. We investigated the value of F-18-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 F-18-FLT PET/CT was higher than that of F-18-FDG PET/CT (HDV, 96% [95% CI, 87-100] vs. 71% [95% CI, 57-83] [P 5 0.0039]; patient-based, 90% [95% CI, 73-98] vs. 55% [95% CI, 36-74] [P = 0.0020]). The difference in specificity between F-18-FLT PET/CT and F-18-FDG PET/CT was higher after cRT than after SBRT. The sensitivity of F-18-FLT PET/CT was lower than that of F-18-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 F-18-FLT PET/CT when F-18-FDG PET/CT was positive or inconclusive improved the diagnostic value compared with F-18-FDG PET/CT alone. In cRT HDVs, the probability of malignancy increased from 67% for F-18-FDG PET/CT alone to 100% when both tracers were positive. Conclusion: F-18-FLT PET/CT adds diagnostic value to F-18-FDG PET/CT in patients with suspected relapse. The diagnostic impact of F-18-FLT PET/CT was highest after cRT. We suggest adding F-18-FLT PET/CT when F-18-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.

Automated summary

Diagnosing relapse after radiotherapy for lung cancer is challenging. While F-18-FLT PET/CT demonstrated higher specificity for malignancy than F-18-FDG PET, the sensitivity was lower. The addition of F-18-FLT PET/CT improved diagnostic value, particularly after conventional fractionated radiotherapy.