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.

The modern landscape of radiotherapy in thyroid malignancies.

Thyroid carcinoma is the most common malignancy of the endocrine system and accounts for nearly 1.5% of all new cancer cases in India. The incidence of thyroid cancers is on the rise secondary to multiple factors including the widespread use of radiological imaging. Surgery remains the cornerstone of treatment, and radioactive iodine therapy plays a pivotal role in differentiated thyroid cancer. Radiation therapy appears to be an underutilized treatment modality. In this review, we have summarized the role of radiation in the treatment of thyroid cancer.

Dosimetry during iodine-131 therapy - a technical point of view from a single centre's own experience.

BACKGROUND: Nuclear medicine uses radionuclides in medicine for diagnosis, staging, therapy, and monitoring the response to therapy. The application of radiopharmaceutical therapy for the treatment of certain diseases is well-established, and the field is expanding. Internal dosimetry is multifaceted and includes different workflows, as well as various calculations based on patient- specific dosimetry. AIM: The objective of this study was to introduce the technical issues which might occur during iodine-131 (¹³¹I) dosimetry performed in nuclear medicine departments. MATERIAL AND METHODS: Retrospective analysis was performed on a group of 44 patients with papillary thyroid cancer who between May 2021 and October 2021 underwent a 131I treatment: 80-100 mCi (2200-3700 MBq, based on the previous medical history and stage of the disease). Patients underwent a series of ¹³¹I therapy scans using gamma camera Discovery NM 670 CT. Whole body scan (WBS) was performed 2, 4, 24 and 48 hours after ¹³¹I administration. Additionally, after 24 hours of single photon emission computed tomography/ computed tomography, two fields of view (SPECT/CT 2-FOV) were performed from the mid-head to the bladder. RESULTS: During the dosimetry procedure, several issues arise. Firstly, after receiving therapeutic doses of ¹³¹I, patients should remain in their rooms until the appropriate activity is achieved before being transported to the diagnostic room. Secondly, the walls between examination rooms meet the requirements for accurate diagnosis but not for therapy, leading to the occurrence of artefacts in patients examined behind the wall, potentially influencing the examination results. Thirdly, personnel in the control room also experience additional exposure (10 times greater than in the case of standard diagnostic procedure). CONCLUSIONS: The dosimetry in patients in whom therapeutic procedures are performed with the use of isotopes is mandatory according to Polish and European law, technical issues which occur during the dosimetry procedures might influence the organization of the work in departments.

Current approach to pediatric differentiated thyroid cancer.

Differentiated thyroid cancers (DTC) is a rare cancer in children and adolescents, having features of different clinical presentation, biological behavior, and treatment from adult population. Most of the patient management guidelines are based on literature on adult population and the literature on children and adolescents still limited. There are still unsettled issues regarding both patient management and the therapy. However, the current approach for treatment of DTC includes thyroidectomy, lymph node dissection in patients with nodal metastases and possible use of Iodine-131 radiotherapy. The incidence of DTC is low in pediatric population, and the characteristics of the disease vary among different age groups within this population. Therefore, the literature depends on small cohorts and heterogeneous retrospective studies. This paper aims to review the current literature and give an overview to the approach in the management of DTC in pediatric population. DTC in pediatric population, has an aggressive nature, however the patient's overall survival is excellent. A multidisciplinary approach in the management of pediatric DTC patients would yield fewer side effects and a better life quality.

Comparison of body iodine pool assessment methods before radioiodine therapy.

INTRODUCTION AND OBJECTIVES: Radioactive iodine therapy (RAIT) is recommended to reduce the risk of recurrence and metastasis in patients with intermediate-high risk differentiated thyroid cancer (DTC). In preparation for RAIT, stimulation of thyroid-stimulating hormone and reduction of body iodine pool are important for treatment success. For this purpose, patients are asked to reduce their iodine intake before RAIT, and the body iodine pool can be evaluated by measuring iodine excretion in urine before treatment. The aim of our study is to compare the methods used to measure the body iodine pool in the evaluation of the restricted iodine diet (RID) effectiveness applied in the RAIT preparation. PATIENTS AND METHODS: Eighty DTC patients discontinued levothyroxine three weeks before RAIT and followed up with a RID two weeks before treatment. After two weeks of RID, all patients collected their 24-h urine the day before the RAIT date. Patients completed 24-h urine samples on the morning of the RAIT date and also provided a spot urine sample. The estimated 24-h creatinine excretion of the patients was calculated. Estimated 24-h urinary iodine excretion (UIE) was calculated using the spot urine iodine/creatinine (I/C) ratio of the patients. 24-h UIE, iodine concentration in spot urine, I/C ratios in spot urine and estimated 24-h UIE of the patients were analyzed by comparing with each other. RESULTS: In 99% of the patients, RID efficiency was sufficient according to 24-h UIE before RAIT. The mean 24-h UIE was 48.81 micrograms/day (mcg/day) in 24-h urine samples taken from the patients to evaluate the body iodine pool. The patients' iodine concentrations in spot urine, I/C ratios in spot urine, and estimated 24-h UIE were all statistically significantly lower than actual 24-h UIE, which was the reference method (p: 0.026 vs <0.001 vs 0.041). Moderate positive correlation between 24-h UIE and iodine concentration in spot urine (r: 0.440), I/C ratio in spot urine (r: 0.493), and estimated 24-h UIE (r: 0.560) found. The strongest correlation was obtained with the estimated 24-h UIE. CONCLUSION: The estimated 24-h UIE obtained by using the I/C ratio in spot urine can be used practically and safely as an alternative to UIE in 24-h urine, which is the gold standard method for evaluating body iodine pool.

Effects of postoperative antioxidants on the salivary glands in patients with thyroid cancer undergoing radioactive iodine-131 treatment.

OBJECTIVE: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.

Diffuse Bone Uptake of 131 I and Effect on Blood Counts in a Patient With Papillary Thyroid Carcinoma and Chronic Lymphocytic Leukemia.

ABSTRACT: A 57-year-old woman with history of chronic lymphocytic leukemia was referred to our center for adjuvant 131 I therapy following complete thyroidectomy for differentiated thyroid cancer. Posttherapeutic scintigraphy revealed atypical diffuse osteomedullar uptake. A major drop in lymphocyte count was observed, from 117.7 g/L to 4.8 g/L 8 weeks after 131 I therapy. Bone marrow uptake is presumed to be related to tracer sequestration in leukemic cells. White blood cell count normalization suggests a high sensitivity of leukemic cells to beta emission. This scintigraphic pattern may act as a pitfall for nuclear medicine physician.

Combined clinical variable and radiomics of post-treatment total body scan for prediction of successful I-131 ablation in low-risk papillary thyroid carcinoma patients.

To explore the feasibility of combined radiomics of post-treatment I-131 total body scan (TBS) and clinical parameter to predict successful ablation in low-risk papillary thyroid carcinoma (PTC) patients. Data of low-risk PTC patients who underwent total/near total thyroidectomy and I-131 ablation 30 mCi between April 2015 and July 2021 were retrospectively reviewed. The clinical factors studied included age, sex, and pre-ablative serum thyroglobulin (Tg). Radiomic features were extracted via PyRadiomics, and radiomic feature selection was performed. The predictive performance for successful ablation of the clinical parameter, radiomic, and combined models (radiomics combined with clinical parameter) was calculated using the area under the receiver operating characteristic curve (AUC). One hundred and thirty patients were included. Successful ablation was achieved in 77 patients (59.2%). The mean pre-ablative Tg in the unsuccessful group (15.50 ± 18.04 ng/ml) was statistically significantly higher than those in the successful ablation group (7.12 ± 7.15 ng/ml). The clinical parameter, radiomic, and combined models produced AUCs of 0.66, 0.77, and 0.87 in the training sets, and 0.65, 0.69, and 0.78 in the validation sets, respectively. The combined model produced a significantly higher AUC than that of the clinical parameter (p < 0.05). Radiomic analysis of the post-treatment TBS combined with pre-ablative serum Tg showed a significant improvement in the predictive performance of successful ablation in low-risk PTC patients compared to the use of clinical parameter alone.Thai Clinical Trials Registry TCTR identification number is TCTR20230816004 ( https://www.thaiclinicaltrials.org/show/TCTR20230816004 ).

Effect of cognitive behavior therapy based on the health education pathway on psychology of papillary thyroid carcinoma patients: a randomized controlled trial.

OBJECTIVES: Our main aim was to explore whether cognitive behavior therapy based on the health education pathway (CBT-HEP) can effectively alleviate the distress, anxiety, and depression of papillary thyroid carcinoma (PTC) patients after 131 I treatment. In addition, we investigated the critical factors that can significantly affect the distress and quality of life in PTC patients before 131 I treatment. METHODS: In total, 496 people were screened and 357 were enrolled, followed by randomization of those with a distress thermometer (DT) ≥4. Patients in the experimental group received CBT-HEP intervention, and patients in the control group were given casual conversation. RESULTS: The scores of DT, Hamilton Anxiety Scale (HAMA) and Patient Health Questionnaire-9 (PHQ-9) in CBT-HEP group decreased gradually after intervention. In control group, DT scores decreased significantly, while HAMA and PHQ-9 scores did not change significantly. CONCLUSION: CBT-HEP is effective in relieving distress, anxiety and depression in PTC patients. In addition, female sex, lifestyle, hypothyroidism, negative emotions, related symptoms, fear of tumor recurrence and radiation safety are the critical factors affecting mental health and quality of life.

Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

A New Twist on a Classic: Enhancing Radioiodine Uptake in Advanced Thyroid Cancer.

Advanced differentiated thyroid cancer that is resistant to radioactive iodine therapy may become responsive with a unique treatment combination of chloroquine and vorinostat. This treatment was demonstrated in cellular and animal models of thyroid cancer to inhibit endocytosis of the plasma membrane-bound iodine transporter, NIS, and restore iodine uptake. See related article by Read et al., p. 1352.

Ablation Rates and Long-Term Outcome Following Low-Dose Radioiodine for Differentiated Thyroid Cancer in the West of Scotland: A Retrospective Analysis.

OBJECTIVE: Low-dose radioiodine is an accepted means of remnant ablation in patients with low- to intermediate-risk differentiated thyroid cancer (DTC) based on the results of several phase III trials. We evaluated the rate of ablation success and long-term recurrence outcomes in the first 3 years of implementing this practice at our institution. METHODS: Patients who received 1.1 to 1.2 gigabecquerel (30 millicurie) were identified retrospectively from the radionuclide database, January 1, 2012, to December 31, 2014, inclusive. Successful ablation was defined as Iodine-131uptake <0.1% on diagnostic scan and Tg level <2.0 ng/mL at 6 to 8 months after treatment. Follow-up was conducted annually for 10 years and relapse rates were determined based on the available clinical, radiological, and biochemical information. RESULTS: We identified 114 patients, 109 of whom had dual response assessment. The median age was 43 years (range, 14 to 80 years). Almost 70% had T1 or T2 tumors, with T3 and T4 tumors recorded in 27% and 2.5% of patients, respectively. Nodal staging was performed in just over 30% and involved lymph nodes were detected in 21% (N1a 8% and N1b 13%). Ablation success based on diagnostic scan alone was 94.7% (108/114), Tg alone 94.7% (108/114), and on both modalities was 90.4% (103/114). CONCLUSION: Remnant ablation was achieved in >90%, and the corresponding clinical recurrence rate was only 1.8% despite the inclusion of patients with locally advanced disease. Low-dose radioiodine is effective and may be suitable for a proportion of patients with higher-risk DTC.

Correlation between remnant thyroid gland I-131 uptake and serum thyroglobulin levels: can we rely on I-131 whole body scans?

BACKGROUND: I-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake. METHODS: From March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation. RESULTS: Thyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success. CONCLUSION: I-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation.

Prophylactic effect of pilocarpine on acute sialadenitis following radioactive iodine therapy in thyroid cancer patients.

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.

Retrospective case-control study examining the relationship between recurrence-free survival and changes in pre- and post-radioiodine therapy serum thyroglobulin levels in patients with differentiated thyroid cancer.

PURPOSE: Thyroglobulin assay is important to assess the residual or recurrence of differentiated thyroid cancer (DTC). Patients with positive serum thyroglobulin levels after radioactive iodine (RAI) adjuvant therapy could achieve long-term recurrence-free survival (RFS). The patient's prognosis could not be confidently estimated based solely on the evaluation of thyroglobulin levels. We investigated the recurrence rate and RFS of patients who received adjuvant RAI therapy after surgery for DTC to clarify the relationship between changes in pre- and post-therapy serum thyroglobulin levels and RFS. MATERIALS AND METHODS: Patients who underwent adjuvant RAI therapy between May 2007 and March 2021 were included in this study, whereas those with positive anti-thyroglobulin antibodies, distant metastases, or gross residual tumors were excluded. The change in pre- and post-treatment serum thyroglobulin levels under thyroid-stimulating hormone stimulation was calculated and classified as follows: group A, thyroglobulin levels decreased by ˃10%; group B, thyroglobulin levels within a range of 10% or less; and group C, thyroglobulin levels increased by ˃10%. RFS outcomes were analyzed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: A total of 74 patients were included. Relapse was seen in 13 of 46 patients in group A, 9 of 15 in group B, and 10 of 13 in group C. Median RFS was 129.00 (95% confidence interval CI 77.79-180.21), 113.00 (95% CI 86.83-139.17), and 33 months (95% CI 6.026-59.974) in groups A, B, and C, respectively. Patients in group C exhibited significantly shorter RFS than those in groups A and B (P = 0.001). CONCLUSIONS: Changes in thyroglobulin levels pre- and post-therapy were associated with RFS. Patients with decreased post-therapy thyroglobulin levels had a favorable prognosis, even if their thyroglobulin levels were positive after RAI therapy.

Radiofrequency ablation for papillary thyroid microcarcinoma with a trachea-adjacent versus trachea-distant location.

OBJECTIVE: To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea. METHODS: Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated. RESULTS: A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73). CONCLUSION: For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.

HIF-1α regulates the cell viability in radioiodine-resistant papillary thyroid carcinoma cells induced by hypoxia through PKM2/NF-κB signaling pathway.

The curative treatment options for papillary thyroid cancer (PTC) encompass surgical intervention, radioactive iodine administration, and chemotherapy. However, the challenges of radioiodine (RAI) resistance, metastasis, and chemotherapy resistance remain inadequately addressed. The objective of this study was to investigate the protective role of hypoxia-inducible factor-1α (HIF-1α) in 131 I-resistant cells and a xenograft model under hypoxic conditions, as well as to explore potential mechanisms. The effects of HIF-1α on 131 I-resistant BCPAP and TPC-1 cells, as well as the xenograft model, were assessed in this study. Cell viability, migration, invasion, and apoptosis rates were measured using Cell Counting Kit-8, wound-healing, Transwell, and flow cytometry assays. Additionally, the expressions of Ki67, matrix metalloproteinase-9 (MMP-9), and pyruvate kinase M2 (PKM2) were examined using immunofluorescence or immunohistochemistry assays. Sodium iodide symporter and PKM2/NF-κBp65 relative protein levels were detected by western blot analysis. The findings of our study indicate that siHIF-1α effectively inhibits cell proliferation, cell migration, and invasion in 131 I-resistant cells under hypoxic conditions. Additionally, the treatment of siHIF-1α leads to alterations in the relative protein levels of Ki67, MMP-9, PKM2, and PKM2/NF-κBp65, both in vivo and in vitro. Notably, the effects of siHIF-1α are modified when DASA-58, an activator of PKM2, is administered. These results collectively demonstrate that siHIF-1α reduces cell viability in PTC cells and rat models, while also mediating the nuclear factor-κB (NF-κB)/PKM2 signaling pathway. Our findings provide a new rationale for further academic and clinical research on RAI-resistant PTC.

Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance.

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.

Decreasing utilization for postoperative radiation therapy in locoregionally advanced medullary thyroid cancer.

BACKGROUND: Use of postoperative radiation therapy (PORT) in locoregionally advanced medullary thyroid cancer (MTC) remains controversial. The objective was to evaluate the effect of PORT on locoregional control (LRC) and overall survival (OS). METHODS: Retrospective cohort study of 346 MTC patients separated into PORT and no-PORT cohorts. Relative indications for PORT, as well as changes in patterns of treatment, were recorded. RESULTS: 49/346 (14%) received PORT. PORT was associated with worse OS; adjusted HR = 2.0 (95%CI 1.3-3.3). PORT was not associated with improved LRC, even when adjusting for advanced stage (Stage III p = 0.892; Stage IV p = 0.101). PORT and targeted therapy were not associated with improved OS compared to targeted therapy alone; adjusted HR = 1.2 (95%CI 0.3-4.1). CONCLUSIONS: Use of PORT in MTC has decreased and its indications have become more selective, coinciding with the advent of effective targeted therapies. Overall, PORT was not associated with improved LRC or OS.