Quantitative thyroglobulin response to radioactive iodine treatment in predicting radioactive iodine-refractory thyroid cancer with pulmonary metastasis

Objective: Current diagnosis of radioactive iodine (RAI)-refractory (RAIR) differentiated thyroid cancer (DTC) is based on the imaging technique, which is of a high cost. Serum thyroglobulin (Tg) is a sensitive and easily obtained biomarker. Hence, we aimed to assess the predicting value of quantitative response of Tg in earlier identifying the RAIR-DTC with pulmonary metastasis. Patients and methods: Pulmonary metastatic DTC patients who underwent total or near-total thyroidectomy and at least two times of RAI therapy were included in this study. The pre-ablative stimulated Tg at the first and second RAI therapy were defined as pstim-Tg1 and pstim-Tg2, while the suppressed Tg before and after the second RAI therapy were designated sup-Tg1 and sup-Tg2. The predicted value of pstim-Tg2/Tg1 and sup-Tg2/Tg1 ratio were detected using the receiver operating characteristic (ROC) curve and logistic regression analyses. Results: Totally 115 patients were involved in this study. ROC curves showed a cut-off value of 0.544 for pstim-Tg2/ pstim-Tg1 in detecting RAIR, with a sensitivity of 0.9 and specificity of 0.477, and an area under the curve (AUC) of 0.744. Similarly, the cut-off of sup-Tg2/ sup-Tg1 was 0.972, with a sensitivity of 0.733 and specificity of 0.935, and AUC of 0.898. Univariate analysis illustrated that age, tumor size, pstim-Tg2/Tg1, sup-Tg2/ sup-Tg1 and BRAFV600E mutation were eligible to predict RAIR. While from multivariate analysis, only age, pstim-Tg2/Tg1, sup-Tg2/ sup-Tg1 and BRAFV600E mutation were verified to be the independent predictive factors. Conclusion: The quantitative Tg response was encouraging in identifying RAIR-DTC with pulmonary metastasis. Age, BRAFV600E mutation and Tg response were independent predictors in predicting RAIR-DTC.