Whole-Body Radioiodine Effective Half-Life in Patients with Differentiated Thyroid Cancer

Background: Radioactive 131I (RAI) therapy is used in patients with differentiated thyroid cancer (DTC) after total thyroidectomy for remnant ablation, adjuvant treatment or treatment of persistent disease. 131I retention data, which are used to indicate the time at which a 131I treated DTC patient can be released from the hospital, may bring some insights regarding clinical factors that prolong the length of hospitalization. The aim of this study was to investigate the 131I whole-body retention in DTC patients during 131I therapy. Methods: We monitored 166 DTC patients to follow the 131I whole-body retention during 131I therapy with a radioactivity detector fixed on the ceiling of each protected room. A linear regression fit permitted us to estimate the whole-body 131I effective half-life in each patient, and a relationship was sought between patients’ clinical characteristics and whole-body effective 131I half-life. Results: The effective 131I half-life ranged from 4.08 to 56.4 h. At multivariable analysis, longer effective 131I half-life was related to older age and extensive extra-thyroid disease. Conclusions: 131I effective half-life during 131I treatment in DTC patients is highly variable among patients and is significantly longer in older and in patients with RAI uptake in large thyroid remnants or in extrathyroidal disease that significantly prolongs the whole-body retention of 131I.

Cytomorphological features of papillary thyroid carcinomas with the development of radioiodine-resistance

Background. The problem of diagnosis and treatment of papillary thyroid cancer (PTC) are radioiodine resistant metastases (RIRM). An urgent issue is the possibility of their early prediction and diagnosis based on the detection of cytomorphological features of the PTC and its metastases, which correlate with the development of radioiodine (RI) resistance. Purpose – detection of cytomorphological features of primary PTC and its metastases in patients who subsequently showed resistance to 131I therapy, compared with the control group of patients who achieved a positive effect of 131I therapy. Materials and Methods. A comparative analysis of morphological features in histological conclusions and the study of cytological characteristics in the fine-needle aspiration (FNA) smears of primary PTC and their primary metastases, as well RIRM оf experimental and control groups of patients were conducted. The experimental group consisted of 152 patients who showed resistance to RI therapy, the control group – 161 patients who achieved a positive effect of RI therapy. Statistical processing was done in Statistica 12. Results and discussion. It is shown that the frequency of follicular structures in the material of primary PTC of patients with a positive effect of 131I therapy is significantly higher, and the frequency of necrotic changes is significantly lower than in patients with the development of RIRM (p <0.05 by criterion χ2). The frequency of follicular structures in the histological material and FNA smears of primary metastases of patients with a positive effect of 131I therapy is significantly higher, and oxyphilic changes are significantly lower than in patients with the development of RIRM (p <0.05 by criterion χ2). Oxyphilic changes were observed significantly more often in the RIRM compared with primary metastases of the control group (p = 0.03). It was proved that cystic changes are significantly more common in FNA smears and histological material of RIRM in comparison with primary metastases of experimental and control groups of patients (p <0.05). Conclusions. TThe use of the presence of oxyphilic and cystic changes in the FNA smears and histological material of metastases of the PTC as prognostic factors of RI resistance is proposed. The presence of follicular structures in the materials of primary PTC and metastases can be a prognostic factor of effective RI therapy.

Low iodine diet of four days is sufficient preparation for 131I therapy in differentiated thyroid cancer patients

Context No consensus exists about the optimal duration of the low iodine diet (LID) in preparation of 131I therapy in differentiated thyroid cancer (DTC) patients. Objective This work aimed to investigate if a LID of four days is enough to achieve adequate iodine depletion in preparation for 131I therapy. In addition, the nutritional status of the LID was evaluated. Methods In this prospective study, 65 DTC patients treated in two University Medical Centers were included between 2018 and 2021. The patients collected 24-h urine on day four and seven of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-h urinary iodine excretion (UIE) on both days. Results The median 24-h UIE on day four and day seven of the LID were not significantly different (36.1[IQR 25.4 – 51.2]mcg and 36.5[IQR 23.9 – 47.7]mcg, respectively, P=0.43). On day four of the LID, 72.1% of the DTC patients were adequately prepared (24-h UIE&lt;50 mcg), and 82.0% of the DTC patients on day seven(P=0.18). Compared to the self-reported regular diet, DTC patients showed a significantly(P&lt;0.01) lower percentage of nutrient intake (calories, protein, calcium, iodine, and water) during the LID. Conclusions The 24-h UIE on day four of the LID did not differ from day seven, and therefore shortening the LID from seven to four days seems justified to prepare DTC patients for 131I therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment.

Radioiodine-resistant metastases of well-differentiated thyroid cancer, analysis of tumor characteristics and primary surgical intervention

The aim of this article is to assess the initial status, characteristics of the tumor process and initial surgical treatment in patients with well-differentiated thyroid carcinomas who subsequently showed resistance to 131I therapy, comparing with the control group of patients who achieved a positive effect of 131I therapy. Materials and methods. In total, 156 cases of well-differentiated thyroid cancer were analyzed. The control group consisted of 189 patients who showed complete responses to treatment of metastases after 131I therapy and the confirmed relapse-free period. The patients were operated and followed up in the Department of Endocrine Gland Surgery of SI “V. P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine” between 1990 and 2019. Results. Based on our study, in the group of radioiodine-resistant metastases, there was a 3.1:1.0 predominance of women over men; whereas in the control group, this ratio was 1.4:1.0. It was noted that resistance to radioactive iodine in patients under 20 years of age was 4 times significantly lower (10.26 %) comparing with the radiosensitive group (41.90 %). In the age group of 41–60 years, radioiodine resistance was 6.5 times higher than that in the comparison group (39.10 % and 6.35 %), and in the age group over 61 years – 11 times (11.54 % and 1.05 %). The impact analysis of radiation exposure on the radioiodine refractoriness occurrence revealed that among patients living in radiation-contaminated areas of Ukraine in 1986 following the Chornobyl accident, there were no significant differences in the development of resistance to radioactive iodine (resistance to 131I – 51.92 % (n = 81), treatment response 131I – 64.02 % (n = 121)). These differences may be due to the younger age of patients affected by radiation and better sensitivity to radioiodine compared to the main group patients. The maximum number of radioiodine-resistant observations was in the intermediate risk group (71.15 %; n = 111). Worth noting is the significant number of radioiodine-resistant metastases in the group where their absence was initially diagnosed (11.53 %; n = 18) and in the group where the proper assessment of lymph collectors was not performed (29.49 %; n = 46). Radioiodine resistance was significantly more common (33.97 %; n = 53) in observations where the prophylactic central dissection was not performed. Conclusions. The main risk factors in the development of radioiodine-resistant metastases were the age of patients older than 40 years, the limited primary surgery on regional lymphatic collectors of the neck, tumor aggressiveness. Careful pre- and intraoperative assessment of regional collectors of the lymph outflow, preventive central neck dissection and extensive therapeutic dissections can reduce the risk of residual and radioiodine-resistant metastases. Timely diagnosis of metastases can improve the results of primary surgical treatment for patients with differentiated thyroid carcinoma and reduce the incidence of radioiodine resistance.

TNF-α May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis

Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = −0.62, p < 0.001 and r = −0.58, p < 0.001). Our results demonstrate that TNF-α may exert different antitumor effects in response to 131I therapy depending on the patient’s immune profile.

Survey of Practice: The Current Extent of Adjunctive Use of Lithium in the UK During Radioactive Iodine Therapy for Hyperthyroidism

Background: The latest United Kingdom National Institute for Health and Care Excellence (NICE) guideline recommends 131I as first-line definitive treatment for Graves’ disease in patients who are unlikely to achieve remission with antithyroid medication. A small but significant proportion of patients have recurrence of hyperthyroidism after 131I therapy. Lithium enhances thyroidal iodine retention and thus increases radiation dose delivered to the thyroid gland during 131I therapy. While clinical trial findings with adjuvant Lithium have not been universally positive, several studies have demonstrated a favorable effect on cure rate, speed of cure and stabilization of thyroid hormone status during131I therapy. Aim: To determine the extent to which Lithium is used as an adjunct to 131I therapy for hyperthyroidism in the UK. Methods: We conducted a survey of 82 nuclear medicine departments and 236 consultant endocrinologists in National Health Service (NHS) hospitals across the UK. Results: Responses were received from 43 departments and 64 endocrinologists. Ten nuclear medicine departments reported that they do not perform therapeutic procedures. Amongst the remainder, only one department stated that Lithium is considered routinely as an adjunct to 131I for selected patients. Amongst consultant endocrinologists, only two indicated that they use Lithium as an adjunct to 131I therapy. Conclusions: Owing to mixed trial evidence and a lack of guideline support for adjunctive Lithium with 131I, its use is not widespread the UK at present. However, some researchers report that it might offer faster control of hyperthyroidism and reduce the amplitude of post-therapy thyroid function fluctuations. As these could be important determinants not only of quality of life but also of safety of treatment, our findings may be valuable to those planning randomized controlled trials of adjunctive Lithium with 131I therapy for Graves’ disease.