Impact of [18F]FDG-PET and [18F]FLT-PET-Parameters in Patients with Suspected Relapse of Irradiated Lung Cancer

Tine N Christensen, Seppo W Langer, Gitte Persson, Klaus Richter Larsen, Annemarie G Amtoft, Sune H Keller, Andreas Kjaer, Barbara Malene Fischer, Tine N Christensen, Seppo W Langer, Gitte Persson, Klaus Richter Larsen, Annemarie G Amtoft, Sune H Keller, Andreas Kjaer, Barbara Malene Fischer

Abstract

Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-uptake. The 3'-deoxy-3'-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01-1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.

Keywords: FDG-PET/CT; FLT-PET/CT; MTV; PTV; SUVmax; lung cancer; prognosis; relapse diagnosis.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient with relapse in the irradiated high-dose volume (HDV). (a) HDV defined as the volume irradiated with >50% of max from the radiotherapy plan. The patient received two Gy × 33 for a T3N1M0 tumor in the left upper lobe. FDG-PET/CT (b) and FLT-PET/CT (c) 7 months after the end of radiotherapy both showed a high tracer uptake. SUV: Standardized uptake value.
Figure 2
Figure 2
Patient with radiation-induced changes in HDV. (a) HDV defined as volume irradiated with >50% of max from the radiotherapy plan. The patient received SBRT (22 Gy × 3) for a T1N0M0 tumor in the right lower lobe. (b) FDG-PET/CT and (c) FLT-PET/CT 13 months after the end of radiotherapy showed only a faint shadow of FDG- and FLT-uptake in the HDV.
Figure 3
Figure 3
Correlation of (a) FDG-SUVmax and FLT-SUVmax with linear fit (R = 0.804; p < 0.001; spearman’s correlation), and (b) FDG-SUVpeak and FLT-SUVpeak with linear fit (R = 0.770; p < 0.001; spearman’s correlation).
Figure 4
Figure 4
Scatter plot of SUVmax in HDV vs. time from the end of radiotherapy to the suspicion of relapse with a linear fit stratified by the relapse status. (a) FDG-SUVmax; (b) FLT-SUVmax.
Figure 5
Figure 5
Boxplots of FDG- and FLT-SUVmax in HDV with relapse vs. HDV without relapse in patients with irradiated lung cancer.
Figure 6
Figure 6
Receiver operating characteristic (ROC) curves for the relapse diagnosis with FDG-SUVmax (a) and FLT-SUVmax (b).
Figure 7
Figure 7
Scatter plot of sensitivity and specificity of FDG-SUVmax (a) and FLT-SUVmax (b) in HDV with variable cutoffs.

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