Radioiodine Therapy Reduces the Frequency of Circulating Tumour Cells in Patients With Differentiated Thyroid Cancer

Mathias Schmidt; Christina Antke; Katalin Mattes-György; Hubertus Hautzel; Stephanie Allelein; Matthias Haase; Till Dringenberg; Matthias Schott; Margret Ehlers


Clin Endocrinol. 2021;94(6):1004-1011. 

In This Article

Abstract and Introduction


Objective: The aim of the study was the quantification of circulating tumour cells (CTCs) in differentiated thyroid cancer (DTC) patients before and 6 weeks after radioiodine therapy (RIT).

Context: Circulating tumour cells (CTCs) were described more recently in cancer patients, mostly correlating with poor outcome and advanced metastases.

Design: Peripheral blood for identification and quantification of CTC before RIT or/and 6 weeks after RIT was provided by 55 DTC patients that received RIT for remnant tissue ablation.

Patients: 13 follicular thyroid cancer (FTC) patients, 31 papillary thyroid cancer (PTC) patients and 11 patients having the follicular variant PTC (FV-PTC) were included.

Measurements: Peripheral blood mononuclear cells (PBMCs) were isolated and EpCAM-positive CTCs were counted by immune fluorescent staining.

Results: A CTC positivity of 31.8% before RIT could be observed. Six weeks after RIT, the CTC positivity was reduced to 13.6%. Paired data at both time points of blood sampling could be gathered for n = 33 DTC patients. These patients had significantly higher CTC numbers before RIT than 6 weeks afterwards (0.27 ± 0.47 vs 0.05 ± 0.15, P = .0215). Additionally, significantly reduced CTC numbers were also demonstrated in pre-RIT CTC-positive patients (0.88 ± 0.43 vs 0.05 ± 0.16, P = .0039).

Conclusion: Our results indicate a reducing effect on the number of CTCs by RIT. Therefore, CTC enumeration should be considered as efficient tool for treatment monitoring during RIT.


Thyroid cancer (TC) is the most common endocrine cancer. Differentiated thyroid cancer (DTC) arises in the majority of all TC cases, including papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC).[1] Usually, DTC has a good prognosis, if tumour spread did not yet occur at time of diagnosis.[2]

PTC is the most common type of differentiated thyroid cancer (85% of all DTC cases) with an excellent survival rate of 98% over 5 years for low-risk PTC and 89% for PTC categorized as high risk.[3] While PTC is growing slowly and restricted to the thyroid gland at time of diagnosis, FTC tends to be more aggressive. However, if metastatic spread occurs, PTC typically spreads to the cervical lymph nodes and FTC to the lung.[4] Fortunately, FTC and PTC can mostly be treated by tumour resection and adjuvant radioiodine therapy (RIT) with I-131, leading to the ablation of residual tissue after surgery.[5] After initial therapy, patients are followed by serum thyroglobulin (Tg) measurement and neck ultrasound (US).

Notably, serum Tg is established as sensitive tumour marker in DTC, with a distinct prognostic value for patients undergoing total thyroidectomy.[6] Characteristically, in patients treated with thyroidectomy followed by RIT, stimulated serum Tg levels < 1 ng/mL are highly predictive of an excellent response to therapy, while higher levels indicate tumour activity and recurrence.[7] Although serum Tg measurement displays the standard sensitive mainstay for patients' follow-up, this method can be limited by the potential concomitant existence of serum anti-Tg-antibodies. These antibodies may interfere with Tg assays, leading to false-negative or false-positive results.[8]

Hence, a new additional diagnostic tool for clinical monitoring of TC patients may be the enumeration of circulating tumour cells (CTC).[9] CTCs usually dispatch from the primary tumour. Their detection in the peripheral blood of different kind of cancers, including breast cancer, melanoma and thyroid cancer, is already validated.[10–12] Furthermore, CTCs are supposed to play a role in the development of distant metastases.[13,14] Like divers malignant solid tumours, CTCs express the epithelial cell adhesion molecule (EpCAM), proving their epithelial origin.[15,16] Importantly, Ensinger et al and Xu et al confirmed these observations for thyroid cancer tissue, underlining the benefit of EpCAM based CTC staining for DTC.[17,18]

CTCs became a common biomarker for tumour activity, cancer regression as well as progression and therapeutic effectiveness for other malignancies.[9,10,12] Different groups already described the existence of CTCs in DTC.[17–19]

Therefore, we analysed the CTCs' frequency in more detail. We examined CTCs' frequency in radioactive iodine (RAI) treated DTC patients before and 6 weeks after RAI therapy, to investigate the possibility of CTC measurement as additional diagnostic tool during treatment.