Thyroglobulin doubling time offers a better threshold than thyroglobulin level for selecting optimal candidates to undergo localizing [18F]FDG PET/CT in non-iodine avid differentiated thyroid carcinoma.

PURPOSE: To investigate the potential role of serum thyroglobulin doubling time (TgDT) in predicting 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT results in patients affected by differentiated thyroid carcinoma (DTC) who demonstrated a combination of positive Tg but a negative [131I] whole-body scan ([131I]-WBS). MATERIALS AND METHODS: Inclusion criteria were (1) prior [131I] treatment for DTC, (2) negative subsequent [131I]-WBS, (3) no interfering anti-Tg antibodies, (4) three consecutive Tg measurements under the thyroid hormone replacement therapy to calculate TgDT before 2-[18F]FDG PET/CT, and (5) at least 6 months of clinical and/or imaging follow-up to ascertain the diagnosis. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to identify the optimal cutoff point for the last stimulated Tg and TgDT prior to [18F]FDG PET/CT. RESULTS: One hundred and thirteen patients were included. Seventy-four (65%) patients had positive [18F]FDG PET/CT for DTC recurrence, while the remaining 39 (35%) negative. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of [18F]FDG PET/CT were 92%, 94%, 97%, 87%, and 93%. Patients with positive [18F]FDG PET/CT had higher Tg and TgDT than those with negative PET/CT. ROC curve analysis revealed an optimal Tg cutoff of 19 ng/mL (sensitivity 78%, specificity 85%, AUC = 0.844) and TgDT of 2.5 years (sensitivity 93%, specificity 87%, AUC = 0.911). TgDT threshold of 2.5 years predicted significantly (p = 0.023) better than Tg level PET/CT results. CONCLUSIONS: The diagnostic performance of [18F]FDG PET/CT could be significantly improved when TgDT is less than or equal to 2.5 years, as compared with using the absolute Tg level.

The role of Tg kinetics in predicting 2-[18F]-FDG PET/CT results and overall survival in patients affected by differentiated thyroid carcinoma with detectable Tg and negative 131I-scan.

PURPOSE: The aim of this study was to assess the potential role of thyroglobulin (Tg) kinetics in predicting 2-[18F]-FDG-PET/CT results and overall survival (OS) in patients affected by differentiated thyroid carcinoma (DTC) and suspected recurrence. METHODS: On hundred and thirty-nine patients were retrospectively included. All patients underwent 2-[18F]-FDG-PET/CT due to detectable Tg levels and negative [131I] whole-body scan. The last two consecutive serum Tg measurements before PET/CT were used for Tg-doubling time (TgDT) and Tg-velocity (Tg-vel) calculation. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for Tg, TgDT and Tg-vel for predicting PET/CT results. RESULTS: One hundred and fifteen (83%) patients had positive PET/CT for DTC recurrence, while the remaining 24 (17%) negative. Stimulated Tg before PET and Tg-vel were significantly higher in patients with a positive PET/CT scan than negative scan (average Tg 190 vs 14 ng/mL, p = 0.006; average Tg-vel 4.2 vs 1.7 ng/mL/y, p < 0.001). Instead, TgDT was significantly shorter in positive scan (average TgDT 1.4 vs 4.4 years, p < 0.001). ROC curve analysis revealed the best Tg, TgDT and Tg-vel cutoff of 18 ng/mL,1.36 years and 1.95 ng/mL/y. In patients with Tg<18 ng/mL, the PET/CT detection rate was significantly lower in patients with low Tg-vel (p = 0.018) and with long TgDT (p = 0.001). ATA class risk, PET/CT results and Tg before PET were confirmed to be independent prognostic variables for OS. CONCLUSIONS: Tg kinetics may help to predict 2-[18F]-FDG-PET/CT results in DTC patients with negative [131I]WBS and detectable Tg, especially in case of low-moderate Tg.

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors.

In patients with distant metastasis, treatment for differentiated thyroid cancer (DTC) includes complete total thyroidectomy, followed by radioactive iodine (RAI) therapy for metastatic lesions. Tyrosine kinase inhibitor (TKI) treatment is the final treatment option for metastatic lesions, which is incurable with surgery/RAI therapy. The present study examined whether treatment outcomes for DTC in patients with distant metastasis improved following TKI treatment. This study included 147 patients (median age, 71; range, 33-91 years) who underwent surgery in our hospitals and were diagnosed with distant metastasis. Disease progression was observed in 70 patients, of whom 56 were treated with TKI (TKI group); 14 refused TKI treatment or showed no treatment indication [untreated (UT) group]. Disease progression and treatment outcomes were assessed using imaging evaluations. The present study investigated thyroglobulin doubling time (Tg-DT) and Tg antibody presence/absence and their relation to disease progression. Overall survival following disease progression between the two groups was compared. The study included 22 cases of sorafenib, 49 of lenvatinib, and 15 involving TKIs. The mean dosing period for sorafenib was 153 days and for lenvatinib was 462 days. In the TKI group, 16, 26, and 9 patients exhibited partial responses (PRs), stable disease (SD), and progressive disease (PD), respectively, whereas 5 patients were not evaluable. The disease control rate (DCR) (PR+SD) was 75.0%. A total of 16 patients died in the TKI group, whereas 10/14 patients in the UT group died. Survival curves for the groups were significantly different. TKI treatment improved the prognosis of patients with distant metastasis and PD.

Correlation of Consecutive Serum Thyroglobulin Levels During Hormone Withdrawal and Failure of Initial Radioiodine Ablation in Thyroid Cancer Patients.

OBJECTIVE: The aim of this study was to evaluate the value of thyroglobulin (Tg) kinetics during preparation of radioiodine ablation for prediction of initial radioiodine ablation failure in thyroid cancer patients. METHODS: Thyroid cancer patients after total thyroidectomy who underwent radioiodine ablation with 3-4 weeks of hormone withdrawal between May 2011 and January 2012 were included. Consecutive serum Tg levels 5-10 days before ablation (Tg1) and on the day of ablation (Tg2) were obtained. The difference between Tg1 and Tg2 (ΔTg), daily change rate of Tg (ΔTg/day) and Tg doubling time (Tg-DT) were calculated. Success of initial ablation was determined by the results of the follow-up ultrasonography, diagnostic radioiodine scan and stimulated Tg level after 6 to 20 months. RESULTS: A total of 143 patients were included. Failed ablation was reported in 52 patients. Tg2 higher than 5.6 ng/ml and Tg-DT shorter than 4.2 days were significantly related to a high risk of ablation failure. ΔTg and ΔTg/day did not show significant correlation with ablation failure. CONCLUSIONS: Thyroglobulin kinetics on consecutive blood sampling during hormone withdrawal may be helpful in predicting patients with higher risk of treatment failure of initial radioiodine ablation therapy in thyroid cancer patients.

Ki-67 labeling index is a predictor of postoperative persistent disease and cancer growth and a prognostic indicator in papillary thyroid carcinoma.

BACKGROUND: We previously reported that the Ki-67 labeling index (LI) in primary tumors and the thyroglobulin (Tg)-doubling time (DT) were potent prognostic indicators in patients with papillary thyroid carcinoma (PTC). OBJECTIVES: To elucidate the relationship between these two factors. METHODS: A total of 390 patients with PTC who underwent total thyroidectomy between 1998 and 2004 and in whom the Tg-DT was calculated were enrolled. We determined the Ki-67 LI in primary tumors and compared these values with the patients' clinicopathological factors, postoperative Tg status, Tg-DT, and prognosis. Tg status was categorized by postoperative serum Tg values: biochemically persistent disease (BPD), equivocal state, and biochemical remission. RESULTS: The Ki-67 LI was ≤5% in 312 patients (80%), 5%-10% in 48 patients (12%), and >10% in 30 patients (8%). Ki-67 LI was significantly associated with BPD (p < 0.0001). The proportion of BPD patients increased with the higher Ki-67 LI category: 24, 67, and 87%, respectively. The Ki-67 LI had a significant inverse correlation with the Tg-DT (Spearman's ρ = -0.5267, p < 0.0001). Of the 378 patients without distant metastasis at surgery, 68 patients had recurrence, and 6 of the 390 patients died of PTC during the follow-up (mean 88 months). On multivariate analyses, the Ki-67 LI remained an independent predictor of disease-free survival and disease-specific survival when Tg-DT and Tg status were excluded from the analyses. CONCLUSIONS: Evaluation of the Ki-67 LI in primary tumors may allow the prediction of the postoperative Tg status, Tg-DT and prognosis of patients with PTC. Published by S. Karger AG, Basel.