In the current study, we evaluated various quantitative as well as volumetric parameters of 18F-FDG PET/CT for prediction of response to RAI. Cut-off values with the statistically significant ability of response prediction were found for most of the 18F-FDG PET/CT parameters. However, the maximum SUVmax showed the highest AUC (0.98) with the highest sensitivity of 100% and specificity of 87.5% for predicting RAI response in metastatic DTC patients.
Prediction of treatment response is important in cancer therapies. In the patients with poor response to RAI, especially the RAI-refractory DTC patients, treatment strategies should be switched to other systematic therapies such as kinase inhibitor therapy or other conventional chemotherapy (Haugen et al., 2016; Ito et al., 2014). During recent years, 18F-FDG PET/CT parameters have been well studied in DTC (Marcus et al., 2015). Patients with positive 18F-FDG PET/CT may be considered candidates for surgical intervention or external radiation therapy since FDG-avid lesions have been reported to seldom improve with RAI alone (Bannas et al., 2012). Even high-dose RAI had little or no effect on the viability of metastatic FDG-avid thyroid cancer lesions (Wang et al., 2001). Masson-Deshayes, et al. (Masson-Deshayes et al., 2015) reported that metabolic parameters of 18F-FDG PET/CT were prognostic factors in metastatic DTC, but they did not evaluate the short-term response to RAI. In our study, we focused on the evaluation of treatment response after one cycle of RAI. Compared to the long-term evaluation of survival, short-term evaluation is less likely to be influenced by other factors, such as the difference of treatment strategy, so our results may practically contribute to setting a treatment strategy for metastatic DTC patients (Hou et al., 2017).
To our knowledge, this is the first study to evaluate the quantitative as well as the volumetric parameters in metastatic DTC for response evaluation. Maximum SUVmax showed higher sensitivity, positive predictive value (PPV), and accuracy, compared to MTV and TLG. In our study, one patient with large tumor size showed extremely high values of MTV and TLG, but the maximum SUVmax classified this patient into Non-PD. These results suggested that the intensity of FDG uptake may be more important than the volume of the metastatic tumors for the prediction of treatment response in DTC patients with distant metastases (Lee et al., 2014).
Metastatic DTC is a rapidly progressive disease with an average interval between the first and second metastases of less than 15 months (Wang et al., 2014), as confirmed by our findings. Therefore, RECIST 1.1 may be applied in this clinical setting. One previous study by per lesion analysis showed that both SUVmax/lesion and MTV/lesion were not correlated with 1-year tumor growth rate in metastatic DTC patients (Terroir et al., 2017). In comparison, our study showed all 18F-FDG PET/CT parameters were significantly higher in the PD patients than those in the Non-PD patients. The evaluation of the treatment response was based on RECIST 1.1 in our study, while the previous study evaluated the lesions by calculating tumor growth rate (Terroir et al., 2017). When evaluated by RECIST 1.1, the growth of tumors is not analyzed separately but is calculated as the sum of longest diameters of all target lesions in each patient. Moreover, recurrence and metastasis of the tumor lesions is also considered during the evaluation. Therefore, we suspect that per patient based analysis using RECIST may be more accurate and practical in clinical application.
In the recent guidelines, low serum Tg level of DTC patients after total or near-total thyroidectomy and RAI has been emphasized to indicate an excellent response (Haugen et al., 2016; Cabanillas et al., 2016; Perros et al., 2014). A previous study showed that the serum Tg level correlated with the long-term clinical outcome of 444 patients with metastatic DTC after RAI (Durante et al., 2006). In our study, the Tg level before treatment showed no significant difference between PD and Non-PD patients. However, the change in Tg levels showed a significant difference between the two groups, which may indicate that dynamic Tg assessment may also predict treatment response. Miyauchi et al. recently proposed a new tool, Tg doubling time (Tg-DT), to predict the survival and development of disorders in DTC (Miyauchi et al., 2011). This parameter, reflecting the dynamic change of Tg, was proved as an independent predictor of disease-specific mortality, loco-regional recurrence, and development of newly identified distant metastases in DTC.
There were several limitations to our study. Firstly, various factors can impact the therapeutic response to RAI, such as age, dose of RAI uptake ratio of radioactive iodine, tumor size, metastatic organs, and so on. These factors were not controlled consistently, due to the retrospective nature of this study. Moreover, the serum glucose level can impact the value of FDG-PET parameters. Secondly, the number of patients included was small. Only 29 (11.2%) patients among 259 patients were enrolled in the recent study. The unequal patient number (21 PD versus 8 Non-PD) also led to the intrinsic statistical limits of this study. A larger number for analysis is necessary to confirm our results. Thirdly, since many cases were excluded due to lack of imaging examinations such as 18F-FDG PET/CT before treatment, further studies are encouraged with a larger number of patients. Fourthly, our recent study focused on the metastatic DTC patients. The growth of thyroid cancer is slow, so it is difficult to differentiate between PD and Non-PD patients without metastases.