To explore the significance of serum thyroglobulin (Tg) in the decision-making of response to ¹³¹I therapy and subsequent treatment for distant metastatic differentiated thyroid cancer (DM-DTC).

Between January 2018 and December 2019, a total of 62 papillary thyroid cancer (PTC) patients (20 males and 42 females, age: (38.1±15.9) years) with pulmonary metastasis from Peking Union Medical College Hospital were retrospectively analyzed. Patients were divided into two groups (non-radioactive iodine (RAI)-avid group and RAI-avid group) according to the post-treatment whole body scan (Rx-WBS). The serum Tg response to ¹³¹I therapy including Tg change and Tg change speed was compared between two groups, and the relationship between serum Tg change speed and structural progression was explored by binary logistic regression analysis. The Tg response to different treatment schemes (¹³¹I treatment or follow-up) was compared in non-RAI-avid group. χ² test and Mann-Whitney U test were used to compare data between different groups. Receiver operating characteristic (ROC) curve analysis was used to find the best threshold of Tg change speed to predict the structural progress.

After ¹³¹I treatment, increased Tg level was found in 60.0% (15/25) patients in non-RAI-avid group (n=25), while only 21.6%(8/37) patients in RAI-avid group (n=37; χ²=9.417, P=0.002). Non-RAI-avid group showed an overall increased Tg trend, with a speed of 0.05(-0.16, 0.15) μg·L ^-1·month^-1, while RAI-avid group showed a general decreased Tg trend, with a speed of -0.18(-1.95, 0.01) μg·L ^-1·month^-1 (U=265.000, P=0.005). A significant correlation between Tg change speed and structural response (odds ratio (OR)=53.005, P<0.001) was found. When Tg change speed was more than 0.135 μg·L^-1·month^-1, structural progression could be well predicted with the sensitivity of 87.5% and specificity of 97.1%. In comparison to non-RAI-avid patients with merely follow-up, further ¹³¹I treatment for such patients did not yield significant benefit in terms of Tg change and Tg change speed (χ²=0.071, U=394.000; both P>0.05).

The serum Tg monitoring can be more sensitive in evaluating the therapeutic response to ¹³¹I for DM-DTC patients in whom response evaluation criteria in solid tumors (RECIST) might not be sensitive enough to reflect the minor change. For patients with non-RAI-avidity, Tg evaluation will offer more sensitive evidence to tailor the necessity of further ¹³¹I treatment.

Thyroid neoplasms; Neoplasm metastasis; Radiotherapy; Iodine radioisotopes; Thyroglobulin; Treatment outcome