Is Stimulated Thyroglobulin Before Radioiodine Therapy a Useful Tool in Predicting Response to Initial Therapy in Patients with Differentiated Thyroid Carcinoma?

Abstract

Thyroglobulin (Tg) is an important tool to evaluate the persistence and recurrence risk in differentiated thyroid cancer (DTC). We aimed to evaluate the correlation between pre-radioiodine therapy stimulated Tg (pre-RAI Tg) levels and the first response to treatment evaluation, and to establish a cut-off pre-RAI Tg threshold for predicting an initial excellent response. Retrospective cohort study of DTC patients who underwent total thyroidectomy and radioiodine therapy. Response to therapy was evaluated 6 to 24 months after initial therapy, and patients were classified as: excellent response (ER); indeterminate response (IndR) and incomplete response (IncR). Total patients: 166 among which 85.5% female with mean age of 47.6 ± 13 years. The ER had a significantly lower pre-RAI Tg in comparison to IndR (p<0.001) and IncR (p<0.001), and pre-RAI Tg were different between the IndR and IncR (p=0.02). A cut-off pre-RAI Tg value at 7.55ng/ml was obtained by receiver operating characteristics curve for differentiating ER from IndR and IncR. The area under curve was 0.832 (95% CI 0.76–0.91). In multivariate analysis, ATA low-risk (RR 1.61, 95% CI 1.06–2.43, p=0.025) and Tg below 7.55ng/ml (RR 2.17, 95% CI 1.52–3.10, p<0.001) were associated with ER. After a median of 7.4-year follow-up, 124 (74.7%) patients were allocated into ER, 22 (13.2%) into IndR, and 20 (12%) into IncR. In conclusion, pre-RAI Tg predicts first evaluation of treatment response. Pre-RAI Tg cut-off was a key predictor of initial excellent response to therapy and may be an important tool in the follow-up of DTC patients.

Keywords

thyroglobulin - dynamic risk stratification - prognostic

Publication History

Received: 29 November 2023

Accepted after revision: 01 May 2024

Article published online:
21 May 2024

• References

• 1 Haugen BR, Alexander EK, Bible KC. et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016; 26: 1-133
• 2 Mazzaferri EL, Robbins RJ, Spencer CA. et al. A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 2003; 88: 1433-1441
• 3 Tuttle RM, Tala H, Shah J. et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American thyroid association staging system. Thyroid 2010; 20: 1341-1349
• 4 Momesso DP, Vaisman F, Yang SP. et al. Dynamic risk stratification in patients with differentiated thyroid cancer treated without radioactive iodine. J Clin Endocrinol Metab 2016; 101: 2692-2700
• 5 Evans C, Tennant S, Perros P. Thyroglobulin in differentiated thyroid cancer. Clin Chim Acta 2015; 444: 310-317
• 6 Heemstra KA, Liu YY, Stokkel M. et al. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2007; 66: 58-64
• 7 Giovanella L, Ceriani L, Ghelfo A. et al. Thyroglobulin assay 4 weeks after thyroidectomy predicts outcome in low-risk papillary thyroid carcinoma. Clin Chem Lab Med 2005; 43: 843-847
• 8 Webb RC, Howard RS, Stojadinovic A. et al. The utility of serum thyroglobulin measurement at the time of remnant ablation for predicting disease-free status in patients with differentiated thyroid cancer: a meta-analysis involving 3947 patients. J Clin Endocrinol Metab 2012; 97: 2754-2763
• 9 Chou R, Dana T, Brent GA. et al. Serum thyroglobulin measurement following surgery without radioactive iodine for differentiated thyroid cancer: a systematic review. Thyroid 2022; 32: 613-639
• 10 Melo M, Costa G, Ribeiro C, Carrilho F. et al. Stimulated thyroglobulin at recombinant human TSH-aided ablation predicts disease-free status one year later. J Clin Endocrinol Metab 2013; 98: 4364-4372
• 11 Barres B, Kelly A, Kwiatkowski F. et al. Stimulated thyroglobulin and thyroglobulin reduction index predict excellent response in differentiated thyroid cancers. J Clin Endocrinol Metab 2019; 104: 3462-3472
• 12 Pitoia F, Abelleira E, Cross G. Thyroglobulin levels measured at the time of remnant ablation to predict response to treatment in differentiated thyroid cancer after thyroid hormone withdrawal or recombinant human TSH. Endocrine 2017; 55: 200-208
• 13 Tian T, Xu Y, Zhang X. et al. Prognostic implications of preablation stimulated Tg: a retrospective analysis of 2500 thyroid cancer patients. J Clin Endocrinol Metab 2021; 106: e4688-e4697
• 14 Lamartina L, Grani G, Durante C. et al. Follow-up of differentiated thyroid cancer - what should (and what should not) be done. Nat Rev Endocrinol 2018; 14: 538-551
• 15 Aschebrook-Kilfoy B, Schechter RB, Shih YC. et al. The clinical and economic burden of a sustained increase in thyroid cancer incidence. Cancer Epidemiol Biomarkers Prev 2013; 22: 1252-1259
• 16 Pacini F, Fuhrer D, Elisei R. et al. 2022 ETA consensus statement: what are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer?. Eur Thyroid J 2022; 11: e210046
• 17 Mukhtar N, Aljamei H, Aljomaiah A. et al. Natural course of the American thyroid association response to therapy statuses (dynamic risk stratification) in differentiated thyroid cancer. Eur Thyroid J 2021; 10: 198-207
• 18 Brierley J, G. M. W. C. TNM Classification of malignant tumours, 8th Edition. Hoboken: Wiley, 2017
• 19 Malandrino P, Tumino D, Russo M. et al. Surveillance of patients with differentiated thyroid cancer and indeterminate response: a longitudinal study on basal thyroglobulin trend. J Endocrinol Invest 2019; 42: 1223-1230
• 20 Polachek A, Hirsch D, Tzvetov G. et al. Prognostic value of post-thyroidectomy thyroglobulin levels in patients with differentiated thyroid cancer. J Endocrinol Invest 2011; 34: 855-860
• 21 Kim H, Kim SJ, Kim IJ. et al. Limited clinical value of periablative changes of serum markers in the prediction of biochemical remission in patients with papillary thyroid cancer. Nucl Med Mol Imaging 2013; 47: 268-272
• 22 Bandeira L, Padovani RDP, Ticly AL. et al. Thyroglobulin levels before radioactive iodine therapy and dynamic risk stratification after 1 year in patients with differentiated thyroid cancer. Arch Endocrinol Metab 2017; 61: 590-599
• 23 González C, Aulinas A, Colom C. et al. Thyroglobulin as early prognostic marker to predict remission at 18-24 months in differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2014; 80: 301-306
• 24 Campennì A, Ruggeri RM, Siracusa M. et al. Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients. Eur J Nucl Med Mol Imaging 2021; 48: 2466-2475
• 25 Kim TY, Kim WB, Kim ES. et al. Serum thyroglobulin levels at the time of 131I remnant ablation just after thyroidectomy are useful for early prediction of clinical recurrence in low-risk patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 2005; 90: 1440-1445
• 26 Moreno I, Hirsch D, Duskin-Bitan H. et al. Response to therapy assessment in intermediate-risk thyroid cancer patients: is thyroglobulin stimulation required?. Thyroid 2020; 30: 863-870
• 27 Rosario PW, Mourão GF, Calsolari MR. Definition of the response to initial therapy with radioiodine in patients with differentiated thyroid carcinoma: basal or stimulated thyroglobulin?. Horm Metab Res 2019; 51: 634-638
• 28 Scheffel RS, Zanella AB, Antunes D. et al. Low recurrence rates in a cohort of differentiated thyroid carcinoma patients: a referral center experience. Thyroid 2015; 25: 883-889
• 29 Mehanna H, Al-Maqbili T, Carter B. et al. Differences in the recurrence and mortality outcomes rates of incidental and nonincidental papillary thyroid microcarcinoma: a systematic review and meta-analysis of 21 329 person-years of follow-up. J Clin Endocrinol Metab 2014; 99: 2834-2843