2022 ETA Consensus Statement: What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer?

Modern use of post-operative radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) should be implemented in line with patients’ risk stratification. Although beneficial effects of radioiodine are undisputed in high-risk patients, controversy remains in intermediate-risk and some low-risk patients. Since the last consensus on post-surgical use of RAI in DTC patients, new retrospective data and results of prospective randomized trials have been published, which have allowed the development of a new European Thyroid Association (ETA) statement for the indications of post-surgical RAI therapy in DTC. Questions about which patients are candidates for RAI therapy, which activities of RAI can be used, and which modalities of pre-treatment patient preparation should be used are addressed in the present guidelines.

Clinical Outcomes After Radioiodine Therapy, According to the Method of Preparation by Recombinant TSH vs. Endogenous Hypothyroidism, in Thyroid Cancer Patients at Intermediate-High Risk of Recurrence

Background: To effectively treat differentiated thyroid carcinoma (DTC) with radioiodine therapy (RAI), it is necessary to raise serum thyrotropin levels, either by thyroid hormone withdrawal (THW) or by administration of recombinant human TSH (rhTSH). The use of rh-TSH is controversial in DTC patients at intermediate to high risk of recurrence. Even more controversial is the question of whether is alters progression-free survival rates and overall survival in more aggressive patients.Objective: The primary objective of this study was comparing clinical outcomes according to the method of preparation of RAI in intermediate to high DTC patients who presented progression of structural disease.Methods: This retrospective study included 81 patients with initial intermediate to high DTC and progression of structural disease at the end of follow-up. In 21 patients, all RAI treatments were done with only rhTSH stimulation. In 11, RAI treatments were done either with thyroid hormone withdrawal (THW) or rhTSH. In 49 patients, all RAI treatments were done only THW.Results: After a median follow-up time of 83 months, there were no statistical differences in the clinical outcomes (status of structural disease at the end of the follow-up, death rate, overall survival curve, and progression-free survival curve).Conclusions: Preparation for RAI therapy using either rhTSH stimulation or THW was associated with no inferiority in the clinical outcomes in progressive DTC patients at higher risk of recurrence.

Radioiodine Ablation for Thyroid Cancer. Historical and Modern Aspects. Literature Review

Thyroid cancer is the most common oncological pathology of the endocrine system organs with a continuing trend towards an increase in the incidence. Radioiodine therapy (RIT) is the second stage of combined treatment, it is carried out only as an adjuvant treatment, it is an uncontested method of radio-targeted therapy for distant metastases of differentiated thyroid cancer (DTC). The method of radioiodine therapy is based on the unique natural affinity of iodine atoms for the follicular epithelium of the thyroid gland and DTC cells. Determination of indications for RIT is based on stratification of recurrence risk, persistence, and disease prevalence. Over the past 15 years, the world’s leading professional communities have repeatedly revised approaches to risk stratification. Consideration of the mutational profile of the tumor and the theranostic approach have become significant innovations.Radioiodine therapy can be presented in the form of three modes: ablation of residual thyroid tissue, treatment of residual tumor and treatment of distant metastases. These regimens differ in the administered therapeutic activity of 131I, which looks logical from the point of view of the necessary personalization of the treatment. At the same time, in scientific circles, disputes about the absence of significant differences in the used therapeutic activities of 131I prescribed for radioiodine ablation outside the personalized approach do not subside.

Variations in Radioiodine Therapy in Europe – Decision-Making after Total Thyroidectomy

The role of radioiodine therapy (RIT) (used as ablation therapy or adjuvant therapy) following total thyroidectomy for differentiated thyroid cancer (DTC) changed. Major revisions of the American Thyroid Association (ATA) Guidelines in 2015 resulted in significant differences in treatment recommendations in comparison to the European Association of Nuclear Medicine (EANM) 2008 guidelines. Recently, we presented the effects on daily practice for RIT among Swiss Nuclear Medicine centers. We now performed a study at the European level and hypothesized that there is also considerable variability among European experts. We performed a decision-tree based analysis of management strategies from all members of the EANM thyroid committee to map current practice among experts. We collected data on whether or not RIT is administered, on which criteria these decision are based, and collected details on treatment-activities and patient preparation. Our study shows discrepancies for low-risk DTC, where “follow-up only” is recommended by some experts while RIT with significant doses is used by other experts. E.g. for pT1b tumors without evidence of metastases the level of agreement for the use of RIT is as low as 50%. If RIT is administered, activities of I-131 range from 1.1 GBq to 3.0 GBq. In other constellations (e.g. pT1a) experts diverge from current clinical guidelines as up to 75% administer RIT in certain cases. For intermediate and high-risk patients, RIT is generally recommended. However, dosing and treatment preparation (rhTSH vs. THW) vary distinctly. In comparison to the Swiss study, the general level of agreement is higher among the European experts. The recently proposed approach on the use of RIT, based on integrated post-surgery assessment (Martinique paper) and results of ongoing prospective randomized studies are likely to reduce uncertainty in approaching RIT treatment. In certain constellations, consensus identified among European experts might be helpful in formulating future guidelines.

DNA damage and repair in peripheral blood mononuclear cells after internal ex vivo irradiation of patient blood with 131I

Aim The aim of this study was to provide a systematic approach to characterize DNA damage induction and repair in isolated peripheral blood mononuclear cells (PBMCs) after internal ex vivo irradiation with [131I]NaI. In this approach, we tried to mimic ex vivo the irradiation of patient blood in the first hours after radioiodine therapy. Material and methods Blood of 33 patients of two centres was collected immediately before radioiodine therapy of differentiated thyroid cancer (DTC) and split into two samples. One sample served as non-irradiated control. The second sample was exposed to ionizing radiation by adding 1 ml of [131I]NaI solution to 7 ml of blood, followed by incubation at 37 °C for 1 h. PBMCs of both samples were isolated, split in three parts each and (i) fixed in 70% ethanol and stored at − 20 °C directly (0 h) after irradiation, (ii) after 4 h and (iii) 24 h after irradiation and culture in RPMI medium. After immunofluorescence staining microscopically visible co-localizing γ-H2AX + 53BP1 foci were scored in 100 cells per sample as biomarkers for radiation-induced double-strand breaks (DSBs). Results Thirty-two of 33 blood samples could be analysed. The mean absorbed dose to the blood in all irradiated samples was 50.1 ± 2.3 mGy. For all time points (0 h, 4 h, 24 h), the average number of γ-H2AX + 53BP1 foci per cell was significantly different when compared to baseline and the other time points. The average number of radiation-induced foci (RIF) per cell after irradiation was 0.72 ± 0.16 at t = 0 h, 0.26 ± 0.09 at t = 4 h and 0.04 ± 0.09 at t = 24 h. A monoexponential fit of the mean values of the three time points provided a decay rate of 0.25 ± 0.05 h−1, which is in good agreement with data obtained from external irradiation with γ- or X-rays. Conclusion This study provides novel data about the ex vivo DSB repair in internally irradiated PBMCs of patients before radionuclide therapy. Our findings show, in a large patient sample, that efficient repair occurs after internal irradiation with 50 mGy absorbed dose, and that the induction and repair rate after 131I exposure is comparable to that of external irradiation with γ- or X-rays.

Clinical pharmaceutical screening in critical situations in a radioiodine therapy management service

Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to evaluate all health problems and medications used in the pre-radioiodine therapy period and comprehensive medication managementservices can serve as a screening tool in this context. The present study aims to describe critical clinical situations identified during the initial assessments of a comprehensive medication management service offered to differentiated thyroid carcinoma patients pre-radioiodine therapy, and the pharmaceutical interventions performed to solve them. A descriptive study with regard to the initial ten months of a comprehensive medication management service was carried out in a large oncology hospital (Rio de Janeiro, Brazil). Descriptive analysis was used to describe the critical clinical situations identified, as well as the correspondent drug therapy problems and the type, acceptability, and outcomes of the pharmaceutical interventions performed to solve them. Thirty patients with an average of 45.8 years and 5.1 medications were evaluated. Five critical clinical situations were identified; corresponding to drug therapy problems two(needs additional drug therapy – n = 4) and drug therapy problems four (dosage too low – n = 1). All pharmaceutical interventions were accepted. The comprehensive medication management service provision pre-radioiodine therapy is feasible and represents an important screening strategy.