Abstract and Introduction
Abstract
Context: Serum thyroglobulin (Tg) is a highly sensitive and specific tumor marker, employed in post-operative management of patients with differentiated thyroid carcinomas. Tumor shrinkage of radioiodine-refractory thyroid cancer (RAIR-DTC) treated with multitarget kinase inhibitors as lenvatinib, expressed according to the Response Evaluation Criteria in Solid Tumors (RECIST), is also associated with a drastic reduction of Tg levels. However, interference caused by circulating thyroglobulin autoantibodies (TgAb) represents the main limitation in the clinical use of Tg.
Objective: To evaluate if in RAIR-DTC TgAb could be considered a surrogate marker of Tg in monitoring response to treatment with lenvatinib.
Design: We retrospectively evaluated patients who had started lenvatinib and correlated serum Tg and TgAb with the radiological response across visits.
Setting: University of Pisa, Italy.
Patients: We selected 9/97 RAIR-DTC patients with detectable TgAb.
Intervention: None.
Main Outcome Measure(s): None.
Results: Tg values correlated neither with TgAb title nor with radiological response across visits. Greater decreases in TgAb titer correlated with favorable radiological response to lenvatinib after 1 month (Spearman's correlation = 0.74, P = .021) and 6 months (correlation = 0.61, P = .079). According to RECIST, patients with partial response showed a ~10-fold greater decrease in TgAb compared to those with stable disease at 1 month (median TgAb decrease: −142 vs −14 IU/mL, P = .01) and those with progressive disease at 6 months (median TgAb decrease: −264 vs−24 IU/mL, P = .04).
Conclusion: TgAb evaluation may represent a reliable surrogate marker for Tg trend in evaluating response of RAIR-DTC to treatment with lenvatinib. A multicentric study would be useful to confirm our results.
Introduction
Serum thyroglobulin (Tg) is a highly sensitive and specific tumor marker employed in the post-operative management of patients with differentiated thyroid carcinomas (DTC).[1] There is a close correlation between Tg levels and tumor burden before and after TSH stimulation.[2,3] After total thyroid ablation for DTC, detectable values of Tg are typically associated with the recurrence or persistence of neoplastic disease.[4] Interference caused by circulating thyroglobulin autoantibodies (TgAb) represents the main limitation in the clinical use of Tg measurement, inducing falsely negative or positive results.[1,4,5] Indeed, the presence of TgAb makes Tg measurements unreliable because it either underestimates Tg levels when common Tg-immunometric assays are used or overestimates Tg levels when less common Tg-radioimmunoassay methods are employed.[6–9] Indeed, the current guidelines for the management of DTC patients strongly recommend the measurement of TgAb with every measurement of Tg, ideally in the same laboratory and using the same assay.[1,10,11] TgAb are detected in approximately 7.5% to 25% of DTC patients[10,12,13] and in only 10% of the general population.[14] In patients who are in complete remission after total thyroid ablation and in absence of any further treatment, serum TgAb gradually decline and disappear after a median time of 3 years.[13] Particularly, TgAb decline approximately by 50% in the first 6 month after thyroidectomy (due to the reduction of circulating thyroid antigens and the half-life of pre-existing TgAb) while they increase in the first 6 months after administration of radioactive iodine therapy because of the release of Tg antigens following tissue destruction.[15–17] Persistence, increase, or reappearance of TgAb during follow-up is highly suspicious for recurrence or persistence of thyroid disease.[18] Thus, TgAb should be quantitatively assessed when Tg is measured.[1,11,19] In patients with DTC refractory to RAI (RAIR-DTC) and treated with new multitarget kinase inhibitors (TKI) such as sorafenib, lenvatinb, and cabozantinib, response to therapy in terms of radiological tumor shrinkage is associated with a drastic reduction in Tg value while the progression of disease correlates with higher Tg levels.[20–24] No data about TgAb trend in these patients are available. The aim of this study was to evaluate if TgAb trend could be useful as a surrogate marker for Tg in monitoring response to TKI therapy for patients affected by RAIR-DTC.
J Endo Soc. 2023;7(8) © 2023 Endocrine Society
