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

Abstract

Diagnosing relapse after radiotherapy for lung cancer is challenging. The specificity of both CT and 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG)-PET/CT is low due to radiation-induced changes. 3’-deoxy-3’-[¹⁸F]fluorothymidine (FLT)-PET has previously demonstrated higher specificity for malignancy than FDG-PET. We investigated the value of FLT-PET/CT for diagnosing relapse in irradiated lung cancer. Methods: Patients suspected for relapse of lung cancer after definitive radiotherapy (conventional fractionated radiotherapy (cRT) or stereotactic radiotherapy (SBRT)) were included. Sensitivity and specificity were analysed within the irradiated high-dose volume (HDV) and patient-based. Marginal differences and inter-observer agreement were assessed. Results: Sixty-three patients who had received radiotherapy in 70 HDVs (34 cRT; 36 SBRT) were included. The specificity of FLT-PET/CT was higher than FDG-PET/CT (HDV: 96% [87-100] vs. 71% [57-83]; P = 0.0039; patient-based (90 % [73-98] vs. 55% [36-74]; P = 0.0020)). The difference between specificity of FLT-PET/CT and FDG-PET/CT was higher after cRT compared with SBRT. Sensitivity of FLT-PET/CT was lower than FDG-PET/CT (HDV: 69% [41-89] vs. 94% [70-100]; P = 0.1250; patient-based: 70% [51-84] vs. 94% [80-99]; P = 0.0078). Adding FLT-PET/CT when FDG-PET/CT was positive or inconclusive improved diagnostic value compared with FDG-PET/CT only. In cRT-HDVs, the probability of malignancy increased from 67% for FDG-PET/CT alone to 100% when both PETs were positive. Conclusion: FLT-PET/CT adds diagnostic value to FDG-PET/CT in patients with suspected relapse. The diagnostic impact of FLT-PET/CT was highest after cRT. We suggest adding FLT-PET/CT when FDG-PET/CT is inconclusive or positive within the previously irradiated volume to improve diagnostic value in patients where histological confirmation is not easily obtained.