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 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.

Keywords: 18F-FDG PET/CT; 18F-FLT PET/CT; lung cancer; radiotherapy; relapse.

© 2021 by the Society of Nuclear Medicine and Molecular Imaging.

Figures

FIGURE 1.

Patient flow in study. Numbers in parentheses refer to subgroups (cRT/SBRT). *One patient was included in both subgroups.

FIGURE 2.

18F-FDG PET/CT and 18F-FLT PET/CT in 3 representative patients with suspected relapse after cRT of lung cancer. (A and B) Relapse 19 mo after end of cRT detected by 18F-FDG PET/CT (A) and 18F-FLT PET/CT (B). (C and D) No relapse 4 mo after end of cRT; 18F-FDG PET/CT was false-positive (C) and 18F-FLT PET/CT true-negative (D). (E and F) Relapse 15 mo after end of cRT; 18F-FDG PET/CT was true-positive (E) and 18F-FLT PET/CT false-negative (F). Relapse was located in lung tissue as confirmed by biopsy, not in lymph node as it may appear on these images.

FIGURE 3.

Location of relapse. In total, 33 patients had relapse; of these, 30 had pulmonary relapse. Numbers in parentheses refer to subgroups (cRT/SBRT). *One patient was included in both subgroups. †Three patients (1/2) had only extrapulmonary relapse.

FIGURE 4.

Suggested diagnostic flow for patients suspected for having relapse within irradiated HDV. Positive predictive value (PPV) and negative predictive value (NPV) are given for HDVs treated with cRT.