Protective effects of Panax Ginseng against 131I-induced genotoxicity in patients with differentiated thyroid cancer.

BACKGROUND: Radioiodine (131I) therapy (RAIT) is associated with oxidative stress (OS)-induced DNA damage in patients with differentiated thyroid cancer (DTC). The goal of this study was to evaluate the possible ameliorating effects of Panax Ginseng (PG) on RAIT-induced genotoxicity in patients with DTC. MATERIALS AND METHODS: Forty DTC patients who had received 131I (100 to 175 mCi) were enrolled in this study. The patients were randomly classified (n = 10) into control, placebo, PG1 groups (receiving 500 mg/day of PG for 2 days before RAIT), and PG2 group (receiving 500 mg/day of PG for 2 days before to 1 day after RAIT). Blood samples were collected before and 2 days after RAIT. Lymphocyte micronuclei (MN) frequency was measured using the MN assay. Serum total antioxidant capacity (TAC) and ischemia-modified albumin (IMA) were measured using colorimetric assays. Serum albumin, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using commercial kits. RESULTS: The mean of baseline MN frequency was the same in the four groups. RAIT increased the MN frequencies to at least three times the baseline values in the control (39 ± 5) and placebo groups (38 ± 6) (P < 0.001). PG caused a significant decrease in the MN frequencies in the treated groups compared to the control and placebo groups (P < 0.001). RAIT and PG administration had no significant effects on the serum IMA, TAC, and markers of liver and kidney toxicity. CONCLUSION: PG could be considered a useful remedy for the protection against RAIT-induced chromosomal damage in DCT patients.

Does Radioactive Iodine Treatment Damage the Lacrimal System?

PURPOSE: In this prospective study, we aimed to make a quantitative assessment of the lacrimal glands before and after radioactive iodine (RAI) treatment in patients with hyperthyroidism and thyroid cancer. METHODS: The study included 80 eyes of 40 patients. There were 25 patients in group 1 (hyperthyroid group) and 15 patients in group 2 (thyroid cancer group). Group 1 has received low dose ( 131 I) and group 2 high dose ( 131 I). Before, and at the first and sixth month after RAI treatment, all patients underwent ophthalmological examinations, Schirmer tests, TBUT tests, tear osmolarity (TO), and ocular surface examinations. RESULTS: The age and sex characteristics of both groups were similar. Although no significant change was observed in tear film tests before and after treatment in group 1, a significant decrease in Schirmer and TBUT values and a significant increase in TO were observed in group 2 in the first month after treatment. These values returned to normal in the sixth month. Although no Schirmer test was observed lower than 10 mm in any patient before RAI treatment, the Schirmer test was measured 5 to 10 mm in 4 (10%) patients in group 2 in the first month after treatment. Again, in these patients, TBUT was below 10 seconds and TO was greater than 308 mOsm/L. CONCLUSIONS: In this study, although no change was observed in tear function tests in patients receiving low doses of RAI, a decrease in tear secretion and an increase in TO were detected in patients receiving high doses in the early period.

A Pilot Nonrandomized Controlled Trial Examining the Use of Artificial Tears on the Radioactivity of Tears After Radioactive Iodine Treatment for Thyroid Cancer.

Background: Nasolacrimal duct obstruction (NLDO) is an adverse effect of high dose radioactive iodine (RAI) therapy for thyroid carcinoma. There are currently no established preventive measures. This study assesses whether preservative free artificial tears (PFATs) can decrease the 131I sodium iodide (131I) activity in the tears of patients following RAI therapy for thyroid carcinoma, and potentially serve as a preventive measure for RAI-associated NLDO. Methods: This non-randomized prospective pilot clinical trial recruited contact-lens wearing patients undergoing RAI therapy for thyroid cancer to self-administer PFATs into the right eye for four days starting on the day of RAI ingestion. Left eyes were the controls. While wearing contacts, patients self-administered PFATs per the following-Day 1: every 15 minutes for 2 hours, then every 30 minutes until bedtime, day 2: every hour for at least 12 hours, day 3: four times a day, and day 4: two times a day. Contact lenses were changed daily, and all lenses were collected one week later. Levels of 131I activity were measured by a well counter, decay-corrected, and converted to units of becquerel. Statistical analyses were performed to compare the 131I activities of the experimental and control eyes. Results: Sixteen eyes of eight patients treated with an average of 145.7 mCi (range 108-159) of 131I for papillary thyroid cancer were included. On day 1, artificial tears decreased the geometric mean 131I activity by 26% in the experimental eyes (p = 0.008). Artificial tears also decreased the geometric mean area under the curve over four days by 23% (p = 0.002). Conclusions: 131I is present in the tears following RAI therapy for thyroid carcinoma. Frequent PFATs starting on the day of RAI ingestion may decrease the level of 131I in the tears. This finding could have implications for lowering the risk of NLDO. Future multi-center clinical trials are needed to determine whether the use of artificial tears after RAI therapy may decrease the risk of NLDO. Clinical Trial Registration: NCT04327999.

The effect of radioiodine therapy on blood cell count in patients with differentiated thyroid cancer.

PURPOSE: This study aimed to investigate the long-term effects of radioiodine treatment (RAI) on blood cell counts in patients with differentiated thyroid cancer (DTC) and to describe the characteristics of patients at high risk for blood cell count abnormalities. METHODS: The study included patients with DTC who underwent RAI treatment between 2007 and 2017. Patients with regular complete blood counts for at least 5 years were included, while those with diseases or treatments that could influence blood count parameters were excluded. Blood cell count abnormalities were defined according to the Common Terminology Criteria for Adverse Events version 5.0, and factors influencing these abnormalities were examined. RESULTS: A total of 225 patients were analyzed. The mean age at diagnosis was 45.8 ± 13.9 years, and 76.5% of patients were female. In the first year after RAI, leukocyte, neutrophil, and lymphocyte counts were significantly reduced compared with baseline values. The leukocyte and neutrophil counts returned to baseline values by the third year, while the decrease in lymphocytes continued until the fifth year. Blood cell count abnormalities developed in 16 patients (7.1%) within the first year after RAI. Risk factors for blood cell count abnormalities within the first year after RAI included male sex, older age, T4, N1, and M1 disease, as well as higher RAI doses. In logistic regression analysis, only RAI dose remained independently associated with blood cell count abnormalities. CONCLUSION: These results suggest an association between RAI dose and blood cell count abnormalities, characterized by mild lymphopenia, and indicate that the risk of mild lymphopenia persists over time. Careful consideration should be given when planning high-dose RAI for patients at a high risk of blood cell count abnormalities, such as males with metastatic disease and of advanced age.

The effect of selenium supplementation on sonographic findings of salivary glands in papillary thyroid cancer (PTC) patients treated with radioactive iodine: study protocol for a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Thyroid cancer is a very damaging disease. The most common treatment for this disease includes thyroidectomy and then using radioactive iodine (RAI). RAI has many side effects, including a decrease in salivary secretions, followed by dry mouth and oral and dental injuries, as well as increased inflammation and oxidative stress. Selenium can be effective in these patients by improving inflammation and oxidative stress and by modulating salivary secretions. So far, only one clinical trial has investigated the effect of selenium on thyroid cancer patients treated with radioiodine therapy (RIT) conducted on 16 patients; considering the importance of this issue, to show the potential efficacy of selenium in these patients, more high-quality trials with a larger sample size are warranted. METHODS: This is a parallel double-blind randomized controlled clinical trial that includes 60 patients aged 20 to 65 years with papillary thyroid cancer (PTC) treated with RAI and will be conducted in Seyyed al-Shohada Center, an academic center for referral of patients to receive iodine, Isfahan, Iran. Thirty patients will receive 200 µg of selenium for 10 days (3 days before to 6 days after RAI treatment) and another 30 patients will receive a placebo for the same period. Sonographic findings of major salivary glands, salivary secretions, and sense of taste will be evaluated before and 6 months after 10-day supplementation. DISCUSSION: Due to its anti-inflammatory and antioxidant effects, as well as improving salivary secretions, selenium may improve the symptoms of thyroid cancer treated with radioactive iodine. In past studies, selenium consumption has not reduced the therapeutic effects of radiation therapy, and at a dose of 300 to 500 µg/day, it has not had any significant side effects in many types of cancer under radiation therapy. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201129049534N6 . Registered on 16 September 2021.

Effects of apitherapy against salivary gland disorder after radioactive iodine therapy for differentiated thyroid cancer.

OBJECTIVE: Sialadenitis and salivary gland disorders are complications of radioactive iodine therapy (RAIT) that affect the quality of life of patients with differentiated thyroid cancer (DTC). The current study aimed to provide evidence on the protective effect of apitherapy on salivary gland function during RAIT in patients with DTC. METHODS: In total, 120 patients with DTC who underwent total thyroidectomy were divided into the apitherapy group (group A, n = 60) and the control group (group B, n = 60). Group A received 2.5 g of acacia honey three times daily after each meal during admission for RAIT. Statistical analyses were performed using the Saxon test (which is used to evaluate saliva volume) and salivary gland scintigraphy (which is applied to assess maximum uptake ratio and washout ratio). RESULTS: Compared with group B, group A presented with a more significantly positive change in the rate of amount of saliva before and after treatment (P < 0.01). Group B presented a significant decrease in the maximum uptake ratio of the bilateral parotid and submandibular glands on salivary gland scintigraphy (P < 0.05) and washout ratio of all salivary glands (P < 0.05). Group A did not present significant differences in the maximum uptake ratio and washout ratio. CONCLUSIONS: Apitherapy can have protective effects against salivary gland disorder associated with RAIT in patients with DTC.

Safety and efficacy of CT-guided radioactive iodine-125 seed implantation as a salvage treatment for recurrent head and neck cancer after two or more courses of radiotherapy.

BACKGROUND: In the past, patients with recurrent head and neck cancer (rHNC) who had previously received a high dose of radiation and were unable to undergo surgery were mainly treated with palliative chemotherapy due to the high incidence of side effects from re-irradiation. With the development of radiotherapy technology, re-irradiation of recurrent lesions by radioactive iodine-125 seed implantation (RISI) has been proposed as a feasible therapeutic approach. This study aimed to investigate the safety and efficacy of computed tomography (CT)-guided RISI in the treatment of rHNC after two or more courses of radiotherapy, and to analyze the prognostic factors. METHODS: Data of 33 patients with rHNC who received CT-guided RISI after two or more courses of radiotherapy were collected and statistically analyzed. The median cumulative dose of the previous radiotherapy was 110 Gy. Short-term efficacy was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1) criteria, while adverse events were evaluated by Common Terminology Criteria for Adverse Events (version 5.0) criteria. RESULTS: The median gross tumor volume (GTV) was 29.5 cc, and the postoperative median dose to 90% of target volume (D90) was 136.8 Gy. For adverse reactions, enhanced pain was found in 3 (9.1%) patients, followed by grade 1 to 2 acute skin reactions in 3 (9.1%) patients, grade 2 to 3 late skin reactions in 2 (6.1%) patients, grade 1 to 2 early mucosal reactions in 4 (12.1%) patients, and mandibular osteonecrosis in 1 (3.0%) patient. Regarding the treatment efficacy, the 1- and 2-year local control (LC) rates were 47.8% and 36.4% (median LC time, 10 months), and the 1- and 2-year overall survival (OS) rates were 41.3% and 32.2% (median OS time, 8 months). The absence of adverse events was associated with better LC. CONCLUSIONS: CT-guided RISI, as a salvage therapy, demonstrated acceptable safety and efficacy in the treatment of rHNC after two or more courses of radiotherapy. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Register database (Registration No. ChiCTR2200063261 ) in September 2, 2022.

Life-threatening Airway Complication After Radioactive Iodine Treatment: A Case Report and Review of the Literature.

BACKGROUND/AIM: Radioactive iodine (RAI) treatment is a cornerstone of treatment of differentiated thyroid carcinoma. Although serious RAI-related complications are uncommon, there have been reports of airway emergencies. Here, a life-threatening airway complication after RAI treatment is reported and previously reported cases are reviewed. CASE REPORT: A 79-year old man with Hürthle cell carcinoma and a remnant thyroid lobe after surgery developed an edema compromising the airway two days after receiving radioactive iodine treatment. An emergency awake intubation and tracheostomy were performed. He could be successfully de-cannulated 17 days later with no long-term complications. CONCLUSION: Although rare, life-threatening airway complications after radioactive iodine treatment, especially with high dose treatment in patients with remaining thyroid tissue, can occur and these patients should be supervised where these complications can be managed.

Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK.

Radioactive iodine is a highly effective treatment for thyroid cancer and has now been used in clinical practice for more than 80 years. In general, the treatment is well tolerated. However, it can be logistically quite complex for patients due to the need to reduce iodine intake and achieve high levels of thyroid-stimulating hormone prior to treatment. Radiation protection precautions must also be taken to protect others from unnecessary radiation exposure following treatment. It has been well documented by thyroid cancer patient support groups that there is significant variation in practice across the UK. It is clear that some patients are being asked to observe unnecessarily burdensome restrictions that make it more difficult for them to tolerate the treatment. At the instigation of these support groups, a multidisciplinary group was assembled to examine the evidence and generate guidance on best practice for the preparation of patients for this treatment and the management of subsequent radiation protection precautions, with a focus on personalising the advice given to individual patients. The guidance includes advice about managing particularly challenging situations, for example treating patients who require haemodialysis. We have also worked together to produce a patient information leaflet covering these issues. We hope that the guidance document and patient information leaflet will assist centres in improving our patients' experience of receiving radioactive iodine. The patient information sheet is available as Supplementary Material to this article.

68Ga-DOTA-FAPI-04 PET/CT Imaging in a Case of Radioactive Iodine-Induced Chronic Parotitis.

ABSTRACT: 68Ga-DOTA-FAPI-04 is a promising PET agent for tumor imaging. However, inflammatory lesions can also show increased FAPI uptake. Herein, we reported a 52-year-old woman who underwent total thyroidectomy for thyroid papillary carcinoma 1 year ago and underwent adjuvant radioiodine therapy 1 month later. After 131I therapy, she began to develop pain and swelling in bilateral cheeks, which developed into oral dryness. The patient was diagnosed with radioactive iodine-induced parotitis. 68Ga-DOTA-FAPI-04 PET/CT showed the density of bilateral parotid glands increased, and the volume decreased with intense tracer uptake. 99mTcO4- salivary gland scintigraphy showed decreased tracer uptake in the bilateral parotid glands.

Prevention of salivary gland dysfunction in patients treated with radioiodine for differentiated thyroid cancer: A systematic review of randomized controlled trials.

Introduction: Salivary gland dysfunction (e.g., sialadenitis and xerostomia) is the most common complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC). Several methods have been used to reduce/prevent this adverse effect. We aimed to systematically review the effectiveness of non-pharmacological and pharmacological interventions in preventing RAI-induced salivary gland dysfunction in patients with DTC. Methods: A systematic review was conducted, according to PRISMA guidelines. The protocol was registered (PROSPERO: CRD42022295229). PubMed, Embase, Scopus, and the Cochrane Library electronic databases were searched from inception to November 2021. Inclusion criteria were randomized controlled trials of DTC patients who were older than 18 years and underwent RAI after thyroidectomy in which at least one studied group received an intervention to prevent salivary gland dysfunction. Results: Twelve studies (a total of 667 participants) were included. Among DTC patients who were treated with RAI, nonpharmacological treatment such as parotid gland massage and aromatherapy ameliorated salivary gland dysfunction. Antioxidants such as vitamin E and selenium demonstrated radioprotective effects on the salivary gland, while other antioxidants did not show radioprotective benefits. Vitamin C showed no significant effects on preventing salivary gland dysfunction. Amifostine had inconsistent outcomes among studies. Among cholinergic agonists, pilocarpine did not demonstrate the radioprotective effect on parotid glands, while bethanechol lowered salivary gland dysfunction. However, the negative results from pilocarpine may be explained by the strong sialorrheic effect of the Cincinnati regimen in both study arms. Conclusion: Among non-pharmacological and pharmacological methods, parotid gland massage, aromatherapy, vitamin E, selenium, amifostine, and bethanechol may have benefits in minimizing RAI-induced salivary gland dysfunction in patients with DTC. The results are limited by a small number of patients and should be confirmed in future larger randomized controlled trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=295229, PROSPERO, identifier CRD42022295229.

The Iodine Rush: Over- or Under-Iodination Risk in the Prophylactic Use of Iodine for Thyroid Blocking in the Event of a Nuclear Disaster.

Iodine is an essential element for the production of thyroid hormones (THs). Both deficient and excess iodine intakes may precipitate in adverse thyroidal events. Radioactive iodine (RI) is a common byproduct of nuclear fission processes. During nuclear emergencies RI may be released in a plume, or cloud, contaminating the environment. If inhaled or ingested, it may lead to internal radiation exposure and the uptake of RI mainly by the thyroid gland that absorbs stable iodine (SI) and RI in the same way. A dose of radiation delivered to the thyroid gland is a main risk factor for the thyroid cancer development. The SI prophylaxis helps prevent childhood thyroid cancer. The thyroid gland saturation with prophylactic SI ingestion, reduces the internal exposure of the thyroid by blocking the uptake of RI and inhibiting iodide organification. However, negative impact of inadequate SI intake must be considered. We provide an overview on the recommended iodine intake and the impact of SI and RI on thyroid in children and adolescents, discussing the benefits and adverse effects of the prophylactic SI for thyroid blocking during a nuclear accident. The use of SI for protection against RI may be recommended in cases of radiological or nuclear emergencies, moreover the administration of iodine for prophylactic purposes should be cautious. Benefits and risks should also be considered according to age. Adverse effects from iodine administration cannot be excluded. Precise indications are mandatory to use the iodine for thyroid blocking. Due to this natural adaption mechanism it's possible to tolerate large doses of iodine without clinical effects, however, a prolonged assumption of the iodine when not needed can be dangerous and may precipitate in severe thyroidal and non-thyroidal negative effects.

Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA).

PURPOSE: Selumetinib can increase radioactive iodine (RAI) avidity in RAI-refractory tumors. We investigated whether selumetinib plus adjuvant RAI improves complete remission (CR) rates in patients with differentiated thyroid cancer (DTC) at high risk of primary treatment failure versus RAI alone. METHODS: ASTRA (ClinicalTrials.gov identifier: NCT01843062) is an international, phase III, randomized, placebo-controlled, double-blind trial. Patients with DTC at high risk of primary treatment failure (primary tumor > 4 cm; gross extrathyroidal extension outside the thyroid gland [T4 disease]; or N1a/N1b disease with ≥ 1 metastatic lymph node(s) ≥ 1 cm or ≥ 5 lymph nodes [any size]) were randomly assigned 2:1 to selumetinib 75 mg orally twice daily or placebo for approximately 5 weeks (no stratification). On treatment days 29-31, recombinant human thyroid-stimulating hormone (0.9 mg)-stimulated RAI (131I; 100 mCi/3.7 GBq) was administered, followed by 5 days of selumetinib/placebo. The primary end point (CR rate 18 months after RAI) was assessed in the intention-to-treat population. RESULTS: Four hundred patients were enrolled (August 27, 2013-March 23, 2016) and 233 randomly assigned (selumetinib, n = 155 [67%]; placebo, n = 78 [33%]). No statistically significant difference in CR rate 18 months after RAI was observed (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI, 0.61 to 1.87]; P = .8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo. The most common adverse event with selumetinib was dermatitis acneiform (n = 11 [7%]). No treatment-related deaths were reported. CONCLUSION: Postoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients. Future strategies should focus on tumor genotype-tailored drug selection and maintaining drug dosing to optimize RAI efficacy.

Optimal Thyroid Hormone Replacement Dose in Immune Checkpoint Inhibitor-Associated Hypothyroidism Is Distinct from Hashimoto's Thyroiditis.

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many advanced cancers but are recognized to cause treatment-limiting immune-related adverse events (IrAE). ICI-associated thyroiditis is the most common endocrine IrAE and usually resolves to permanent hypothyroidism. Optimal thyroid hormone replacement in these patients remains unclear. We report the levothyroxine (LT4) dose needed to achieve stable euthyroid state in patients with hypothyroidism from ICI-associated thyroiditis, with comparison to patients with Hashimoto's thyroiditis (HT) and athyreotic state. Methods: We conducted a retrospective study of adults with ICI-associated hypothyroidism treated with LT4 at an academic medical center. Patient data were collected from the electronic medical record. Cases had ICI exposure followed first by hyperthyroidism and then subsequent hypothyroidism. Controls were HT (positive thyroid autoantibodies, requiring LT4) and athyreotic (total thyroidectomy or radioiodine ablation, requiring LT4) patients. Patients with central hypothyroidism, thyroid cancer, pregnancy, gastrointestinal stromal tumors, and use of L-triiodothyronine were excluded. Our primary outcome compared LT4 dose needed to achieve euthyroid state (thyrotropin 0.3-4.7 mIU/L over >6 consecutive weeks) for ICI-associated hypothyroidism, HT, and athyreotic patients, considering the impact of age and possible interfering medications by linear regression modeling. Secondary analysis considered the impact of endocrine specialty care on the time to euthyroid state. Results: One hundred three patients with ICI-associated thyroiditis were identified. Sixty-six of the 103 patients achieved euthyroid state; 2 with intrinsic thyroid gland function recovery and 64 on LT4. The mean LT4 dose achieving stable euthyroid state was 1.45 ± standard deviation (SD) 0.47 mcg/[kg·day] in ICI-associated hypothyroidism, 1.25 ± SD 0.49 mcg/[kg·day] in HT, and 1.54 ± SD 0.38 mcg/[kg·day] in athyreotic patients, using actual body weight. The difference in dose between ICI-associated hypothyroidism and HT was statistically significant (p = 0.0093). Dosing differences were not explained by age or use of interfering medications. Conclusions: ICI-associated thyroiditis represents an increasingly recognized cause of hypothyroidism. Our study demonstrates that patients with ICI-associated hypothyroidism have different thyroid hormone dosing requirements than patients with HT. Based on our findings and prior reports, we recommend that in patients with ICI-associated thyroiditis LT4 therapy be started at an initial weight-based dose of 1.45 mcg/[kg·day] once serum free thyroxine levels fall below the reference range.

Surgical Risk Prediction for Nasolacrimal Duct Obstruction in Radioactive Iodine-Treated Thyroid Cancer: A Nationwide Cohort Study.

Background: To estimate the incident risk of surgical intervention for nasolacrimal duct obstruction after radioactive iodine (RAI) treatment and elucidate the high-risk group of patients with thyroid cancer (TC). Methods: This is a nationwide, population-based cohort study using data from the Korean National Health Claims database. Among the entire South Korean population aged between 20 and 80 years from 2007 to 2019, all patients with TC were included. Among all TC patients, a cohort was established by classifying it into the RAI and non-RAI groups according to whether RAI treatment was performed during the recruitment period. A log-rank analysis was used to evaluate the risk of nasolacrimal duct obstruction surgery in the RAI group compared with that in the non-RAI group. The Cox proportional hazards regression analysis was performed to calculate the adjusted hazard ratio (HR). The analysis was performed stratified by the age group, sex, frequency of RAI treatment, and cumulative dose of 131I. Results: Among 55,371 TC patients, who received RAI treatment, 515 (0.93%) underwent nasolacrimal duct obstruction surgeries, and among 56,950 TC patients, who did not receive RAI treatment, 72 (0.13%) underwent the surgeries. The average timing of incident nasolacrimal duct obstruction surgery was 3.8 ± 2.1 years after the first exposure to RAI. The incidence rate of nasolacrimal duct obstruction surgery was 104.04/100,000 person-years in the RAI group. There was a significantly higher risk of nasolacrimal duct obstruction surgery (HR 7.50 [confidence interval, CI: 5.86-9.60], p < 0.001) in the RAI group than in the non-RAI group. The risks significantly increased in the high-dose group (HR 14.15 [CI: 10.88-18.39]) and those younger than 50 years (HR 15.54 [CI: 9.76-24.72]). Conclusion: We quantified the risk of RAI-induced nasolacrimal duct obstruction surgery through a long-term follow-up of 9 years, which may contribute to estimating the general health care burden related to RAI treatment for TC patients in a practical setting. Great attention should be paid to its risk in patients younger than 50 years, especially in those treated with high doses.

High-dose radiation exposure and hypothyroidism: aetiology, prevention and replacement therapy.

Without any doubt, high dose radiation exposure can induce hypothyroidism. However, there are open questions related to the mechanisms of its induction, corresponding dose thresholds and possible countermeasures. Therefore, this review addresses the aetiology, prevention and therapy of radiation induced hypothyroidism. External beam radiotherapy with several 10 Gy to the head and neck region and radioiodine therapy with several 100 Gy thyroid absorbed dose can destroy the thyroid gland and can induce autoantibodies against thyroid tissue. According to recent literature, clinical hypothyroidism is observed at threshold doses of ∼10 Gy after external beam radiotherapy and of ∼50 Gy after radioiodine therapy, children being more sensitive than adults. In children and adolescents exposed by the Chernobyl accident with mean thyroid absorbed doses of 500-800 mGy, subclinical hypothyroidism has been detected in 3%-6% of the cases with significant correlation to thyroid absorbed doses above 2.5 Gy. In case of nuclear emergencies, iodine thyroid blocking (ITB) is the method of choice to keep thyroid absorbed doses low. Large doses of stable iodine affect two different steps of internalization of radioiodine (transport and organification); perchlorate affecting the transport only may be an alternative to iodine. Administered before radioiodine incorporation, the effect of 100 mg iodide or more is still about 90% after 1 days, 80% after 2 days, and 50% or less after 3 days. If administered (too) late after exposure to radioiodine, the theoretically expected protective effect of ITB is about 50% after 6 h, 25% after 12 h, and about 6% after 24 h. In case of repeated or continuous exposure, repeated administration of 50 mg of iodide daily is indicated. If radiation-induced hypothyroidism cannot be avoided, thyroid hormone replacement therapy with individualized dosing and regular monitoring in order to maintain thyroid-stimulating hormone levels within the normal range ensures normal life expectancy.

Inhibidores multiquinasas en el tratamiento de cáncer diferenciado de tiroides refractario a tratamiento con yodo radioactivo / Multikinase inhibitors in the treatment of differentiated thyroid cancer refractory to treatment with radioactive iodine

ANTECEDENTES Solicitud presentada por el Comité Farmacoterapéutico del Instituto Nacional de Enfermedades Neoplásicas, en relación con la evaluación y aprobación de Lenvatinib y Sorafenib, en el tratamiento de cáncer diferenciado de tiroides irresecable o metastásico, refractario a tratamiento con yodo radioactivo. ESTRATEGIA DE BÚSQUEDA DE INFORMACIÓN: Pregunta Clínica: En los pacientes con cáncer diferenciado de tiroides irresecable o metastásico, refractario a tratamiento con yodo radioactivo, ¿es eficaz y seguro el tratamiento con inhibidores multiquinasas? Recolección de los Manuscritos a Revisar: Tipos de estudios: La estrategia de búsqueda sistemática de información científica para el desarrollo del presente informe se realizó siguiendo las recomendaciones de la Pirámide jerárquica de la evidencia propuesta por Haynes y se consideró los siguientes estudios: Sumarios y guías de práctica clínica. Revisiones sistemáticas y/o meta-análisis. Ensayos Controlados Aleatorizados (ECA) ● Estudios Observacionales (cohortes, caso y control, descriptivos) No hubo limitaciones acerca de la fecha de publicación o el idioma para ningún estudio. Fuentes de información: De acceso libre. Bases de datos: Pubmed, Cochrane. Fecha de búsqueda: La búsqueda sistemática incluyó a todos los estudios publicados sin límite de antigüedad. Términos de Búsqueda: Considerando la pregunta PICO se construyó dos estrategias de búsqueda, sin restricciones en el idioma ni en periodo de publicación. DISCUSIÓN: Tomando los criterios para un marco de valor de la Health Technology Assessment International (2018)28 para la toma de decisiones y formulación de la recomendación, se describe: La calidad de la evidencia es alta. La evidencia analizada ha consistido en revisiones sistemáticas tanto con meta análisis y de red, los cuales encabezan la pirámide de calidad de evidencia, así como ECA, GPC y ETS de agencias reconocidas. Los ensayos clínicos muestran que lenvatinib y sorafenib son efectivos para retrasar la progresión de la enfermedad, pero hay una tasa de respuesta más alta con lenvatinib y puede retrasar la progresión por más tiempo. Evaluación económica en la región no se tiene, sin embargo, en Reino Unido se realizó una, en la cual, las estimaciones de rentabilidad son más altas de lo que NICE normalmente considera aceptable. Pero los tratamientos aumentan la duración de la vida y no hay otros tratamientos disponibles para la afección. Además, las estimaciones de rentabilidad no capturan los beneficios de que las personas tengan una respuesta al tratamiento, es decir, una mejora de los síntomas. CONCLUSIONES: El cáncer de tiroides es una enfermedad oncológica de buen pronóstico en la mayoría de los casos. Existe un porcentaje de pacientes que desarrollará una progresión recurrencia o enfermedad metastásica refractaria a yodo radioactivo, siendo esta, de mal pronóstico. El tratamiento sistémico para los pacientes con CDT - RR se basa en inhibidores multiquinasas: Sorafenib y Lenvatinib. Sorafenib y Lenvatinib, han demostrado eficacia sobre placebo respecto a la SLP, sin embargo, también se ha demostrado la presencia de EA que han llevado a reducción de dosis y/o interrupción del tratamiento. Nuestro análisis para evaluar el beneficio neto de ambas tecnologías en base a los ECAs fase 3, demuestra una superioridad de Lenvatinib sobre Sorafenib. Las RS analizadas han demostrado la eficacia de ambos IMK versus placebo y una mayor eficacia de Lenvatinib sobre Sorafenib, a pesar de la mayor cantidad de eventos adversos. No se cuenta con evaluaciones económicas en la región, sin embargo, en la EE realizada por la NICE, se concluyó que a pesar de no ser costo - efectiva, al tratarse de una enfermedad rara, ambas drogas deben ser aprobadas para el manejo de pacientes con CDT - RR. Por lo expuesto, la UFETS en consenso con el Comité de ETS, concluye que Sorafenib y Lenvatinib, son alternativas de terapia en pacientes con CDT - RR con una preferencia de uso para Lenvatinib sobre Sorafenib.

Sialadenitis as a complication of radioiodine therapy in patients with thyroid cancer: where do we stand?

PURPOSE: This study aims to elaborate on the current knowledge concerning the mechanism, frequency, clinical manifestations, diagnostic procedures, prevention, and management of radioactive iodine (RAI)-induced sialadenitis in patients receiving treatment for differentiated thyroid cancer (DTC). METHODS: A review of the literature was carried out through the " www.ncbi.nlm.nih.gov/pubmed " database focusing on the results of the past decade. RESULTS: The high concentration of RAI in the salivary glands results in high beta radiation exposure of the striated duct cells and stem cells. This exposure leads to acute and/or chronic sialadenitis with obstructive symptoms and progressive loss of salivary gland function and xerostomia, with severe impact on patients' quality of life. No standard diagnostic method has been established. As far as prevention is concerned, many approaches have been proposed, such as sialogogues, local massage, vitamin E, and amifostine administration. Although there is no unanimity as to their effectiveness, the use of sialogogues is recommended. Treatment includes conservative drug therapy and sialendoscopy when necessary. CONCLUSION: RAI-induced sialadenitis has a major impact on patients' quality of life. Due to the good prognosis of DTC, the reduction of sialadenitis and its prognosis, prevention, and treatment constitute a priority for the overall treatment of these patients. Further studies that will establish a coherent treatment protocol for this condition are necessary.

Radioiodine therapy induced sialadenitis versus chronic idiopathic sialadenitis-Presentation and outcomes.

BACKGROUND: This study explores the unique characters of high dose radioactive iodine (RAI) induced chronic sialadenitis. METHODS: A retrospective study of patients having received salivary endoscopy and followed in our outpatient clinic. RESULTS: A total of 100 patients met the inclusion criteria, 75 were diagnosed with chronic idiopathic sialoadenitis and 25 with radio-iodine induced sialoadenitis (RIS). The main complaint in both groups was swelling of the parotid gland. Pain, dysphagia, and xerostomia were observed considerably more in the RIS group. During sialo-endoscopy, fibrosis of the Stensen's duct was more common in the RIS group (p = 0.003). RIS patients group generally managed better with interventional endoscopic treatment alone (80% vs. 46%). CONCLUSION: RIS patients have distinct clinical characteristics. There may be a collateral muscular damage to the masticatory muscles. Fibrosis and parenchymal damage are major findings during sialendoscopy. Sialendoscopy is a safe and efficient treatment for RAI induced sialadenitis.

Decline in anti-Müllerian hormone concentrations following radioactive iodine treatment in women with differentiated thyroid cancer: A systematic review and meta-analysis.

AIM: Radioactive iodine (RAI) is frequently used as adjuvant therapy in patients with differentiated thyroid cancer (DTC). However, its effect on ovarian reserve has not been fully elucidated, with studies yielding inconsistent results. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of RAI on ovarian reserve in premenopausal women with DTC. METHODS: A comprehensive literature search was conducted in PubMed, Cochrane and Scopus, through to December 6th, 2020. Data were expressed as weighted mean difference (WMD) with a 95% confidence interval (CI). The I2 index was used to assess heterogeneity. RESULTS: Four prospective studies were included in the qualitative and quantitative analysis. Anti-Müllerian hormone (AMH) concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p<0.0001; I2 0%), six (WMD -1.58, 95% CI -2.63 to -0.52, p=0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p<0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n=104). With respect to follicle-stimulating hormone (FSH) concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to 7.70, p=0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to 1.32, p=0.83; I2 55.2%) post-RAI compared with baseline (two studies; n=83). No data were available for antral follicle count. CONCLUSIONS: AMH concentrations are decreased at three months and remain low at 6 and 12 months following RAI treatment in women with DTC. No difference in FSH concentrations post-RAI is observed.