Impact of 18F-FDG PET/CT on Clinical Management of Suspected Radio-Iodine Refractory Differentiated Thyroid Cancer (RAI-R-DTC)

Abstract

Background: As reported in the literature, [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) provides useful qualitative and semi-quantitative data for the prognosis of advanced differentiated thyroid cancer. Instead, there is a lack of data about the real clinical impact of 18F-FDG PET/CT on the choice of the more effective therapeutic approach for advanced differentiated thyroid cancer (DTC) that starts to lose iodine avidity. The primary aim of this retrospective study was to assess how 18F-FDG PET/CT can guide the choice of the best therapeutic approach to RAI-refractory DTC (RAI-R-DTC) in patients with a doubtful iodine uptake/negative 18F-FDG PET/CT I whole-body scan after several radioactive iodine therapies (RAIT). The secondary aim was to assess the prognostic role of clinical and semi-quantitative metabolic 18F-FDG PET/CT parameters in comparison to published data. Materials and methods: A monocentric retrospective observational study was performed, reviewing the medical records of 53 patients recruited from a database of 208 patients treated at our Institution between 2011 and 2019, with advanced DTC that underwent FDG PET/CT scan for a suspected RAI-R-DTC. Selected patients had to perform a 18F-FDG PET/CT scan after the second RAIT based on a doubtful iodine uptake/negative 131 I whole-body scan and/or persistent elevated thyroglobulin levels. Metabolic response was defined according to positron emission tomography response criteria in solid tumors (PERCIST) guidelines. Standardized uptake value (SUV)max, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The association between metabolic features, clinical parameters and progression free survival (PFS) was assessed applying Kruskal–Wallis, chi-square-Pearson correlation tests, and Cox regression analyses when appropriate. Results: Among our sample of 53 patients (mean age 52.0 ± 19.9 years; 31 women and 22 men), 27 (51.0%) presented a positive 18F-FDG PET/CT scan: 16 (59.0%) underwent watchful waiting, 4 (15.0%) received external-beam radiation therapy (EBRT), 4 (15.0%) underwent surgery, 2 (7.4%) received another course of RAI therapy, and 1 underwent surgery + EBRT. PERCIST response was evaluated in 14/27 patients. Median follow-up was 5.8 ± 3.9 years and median PFS was 38.0 ± 21.8 months. At the last follow-up assessment, 14/53 (26.4%) demonstrated disease progression, 13/53 (24.5) persistence of structural disease, 25/53 (47%) persistence of biochemical disease, and 15/53 (28%) had an excellent response. A significant association was found between therapeutic approach, metabolic response, and final disease response evaluation, as well as a linear correlation between MTV and TLG with thyroglobulin level. Conclusions: Our Institutional experience confirmed the role of 18F-FDG PET/CT as a useful guide in the clinical management of RAI-R-DTC and obviated further unnecessary RAIT.

Prognostic Role of 2-[18F]FDG PET/CT Metabolic Volume Parameters in Patients Affected by Differentiated Thyroid Carcinoma with High Thyroglobulin Level, Negative 131I WBS and Positive 2-[18F]-FDG PET/CT

“…Moreover, the potential impact of PET/CT metabolic metric parameters has not been clearly investigated. SUV was the first metabolic index investigated with controversial results [ 19 , 28 ]. In this scenario the introduction of alternative PET/CT parameters, expressing at the same time the metabolic and volumetric characteristics of 2-[ 18 F]FDG-positive lesions, showed a significant role in several solid tumors.…”

“…Until now, no method seems to be superior to others, even if EANM guidelines [ 23 ] have suggested an isocounter threshold method based on 41% of the SUVmax. In addition, Manohar et al [ 19 ] in a smaller population ( n = 62) demonstrated a prognostic role of MTV and TLG both for OS and PFS. They dichotomized MTV and TLG according to the median values and then analyzed the log-MTV and log-TLG.…”

“…Instead, in our paper we preferred to apply ROC curve analysis to find the point with the best compromise between sensitivity and specificity. Rizzini et al [ 19 ] showed a positive correlation between MTV and TLG and Tg level and the final disease status, but they did not focus on the outcome survival. Surely the cutoffs derived by this work (6.6 for tMTV and 119.4 for tTLG) are not reproducible at the moment because they are strictly related to the population analyzed and the center’s features; however, they could be used as starting points for future analysis on large multicentric populations.…”

“…In these papers, PET/CT was analyzed by a qualitative point of view dichotomizing the PET/CT scans as positive or negative according to the presence of increased FDG localizations. Instead, a clear evaluation of semi-quantitative PET parameters related to the volume is not yet available; only initial promising findings in small samples of patients seem to underline a potential usefulness of these variables [ 19 , 20 , 21 ].…”

Advances in Functional Imaging of Differentiated Thyroid Cancer

“…The integration of SPECT with computed tomography (CT) in SPECT/CT tools improved the quality and accuracy of 131 I imaging and allows a quantitation of any uptake and potentially a lesion dosimetry evaluation before and after RAI treatment. PET/CT has become an integral part of DTC management using the non-specific 18 F-fluorodeoxyglucose ( 18 F-FDG) tracer both for diagnostic and prognostic purposes and, where available, using 124 I that is a highly performing radiopharmaceutical to evaluate in vivo iodine avid lesions [12,13]. Unfortunately, most evidence concerning the use of these tracers relies on retrospective data or on expert opinion or consensus statements.…”