Current practice in intermediate risk differentiated thyroid cancer - a review.

Although the overall prognosis for differentiated thyroid cancer (DTC) is excellent, a subset of patients will experience disease recurrence or may not respond to standard treatments. In recent years, DTC management has become more personalized in order to enhance treatment efficacy and avoid unnecessary interventions.In this context, major guidelines recommend post-surgery staging to assess the risk of disease persistence, recurrence, and mortality. Consequently, risk stratification becomes pivotal in determining the necessity of postoperative adjuvant therapy, which may include radioiodine therapy (RIT), the degree of TSH suppression, additional imaging studies, and the frequency of follow-up.However, the intermediate risk of recurrence is a highly heterogeneous category that encompasses various risk criteria, often combined, resulting in varying degrees of aggressiveness and a recurrence risk ranging from 5 to 20%. Furthermore, there is not enough long-term prognosis data for these patients. Unlike low- and high-risk DTC, the available literature is contradictory, and there is no consensus regarding adjuvant therapy.We aim to provide an overview of intermediate-risk differentiated thyroid cancer, focusing on criteria to consider when deciding on adjuvant therapy in the current context of personalized approach, including molecular analysis to enhance the accuracy of patient management.

Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma.

BACKGROUND: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. METHODS: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. RESULTS: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001. CONCLUSION: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.

The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients.

PURPOSE: To introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine 131I therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by 124I PET. METHODS: Patients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUVmax > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-124I to determine the individual lesion radiation-absorbed dose. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion radiation dose metrics, with candidate biomarkers ("predictors") such as SUVmax and activity in microcurie per gram, from a single imaging timepoint. RESULTS: In the 169 lesions (in 15 patients) that received 131I therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming wide heterogeneity of lesion radiation dose. Initial findings from the prediction curve on all 208 lesions confirmed that a 48-h SUVmax was the best predictor of lesion radiation dose and permitted calculation of the 131I activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals. CONCLUSIONS: Based on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint 124I-PET-based dosimetry biomarker for RAI in patients with mDTC. The approach provides clinicians with a tool to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed dose (cGy) for selected index lesions based on a single 48-h measurement 124I-PET image, provided the selected activity does not exceed the maximum tolerated activity (MTA) of < 2 Gy to blood, as is standard of care at Memorial Sloan Kettering Cancer Center. TRIAL REGISTRATION: NCT04462471, Registered July 8, 2020. NCT03647358, Registered Aug 27, 2018.

Gut microbiota is associated with response to 131I therapy in patients with papillary thyroid carcinoma.

PURPOSE: Radioactive iodine (131I) therapy is a conventional post-surgery treatment widely used for papillary thyroid carcinoma (PTC). Since 131I is orally administered, we hypothesize that it may affect gut microbiome. This study aims to investigate alterations of intestinal microbiome caused by 131I therapy in PTC patients and explore its association with response to 131I therapy. METHODS: Fecal samples of 60 PTC patients pre- and post-131I therapy were collected to characterize the 131I therapy-induced gut microbiota alterations using 16S rRNA gene sequencing. According to the inclusion criteria, sequence data of 40 out of the 60 patients, divided into excellent response (ER) group and non-excellent response (NER) group, were recruited to investigate the possible connection between gut microbiota and response to 131I therapy. Multivariate binary logistic regression was employed to construct a predictive model for response to 131I therapy. RESULTS: Microbial richness, diversity, and composition were tremendously altered by 131I therapy. A significant decline of Firmicutes to Bacteroides (F/B) ratio was observed post-131I therapy. 131I therapy also led to changes of gut microbiome-related metabolic pathways. Discrepancies in ß diversity were found between ER and NER groups both pre- and post-131I therapy. Furthermore, a predictive model for response to 131I therapy with a p value of 0.003 and an overall percentage correct of 80.0% was established, with three variables including lymph node metastasis, relative abundance of g_Bifidobacterium and g_Dorea. Among them, g_Dorea was identified to be an in independent predictor of response to 131I therapy (p = 0.04). CONCLUSION: For the first time, the present study demonstrates the gut microbial dysbiosis caused by 131I therapy in post-surgery PTC patients and reveals a previously undefined role of gut microbiome as predictor for 131I ablation response. G_Dorea and g_Bifidobacterium may be potential targets for clinical intervention to improve response to 131I in post-operative PTC patients. TRIAL REGISTRATION: ChiCTR2100048000. Registered 28 June 2021.

Comparing the efficacy of thyroglobulin and thyroglobulin/ thyroid-stimulating hormone ratio models in predicting a successful response to radioactive iodine therapy.

BACKGROUND: The thyroglobulin (Tg)/ thyroid-stimulating hormone (TSH) ratio has manifested to be a reliable marker for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The objective of this study was to compare the efficacy of Tg and Tg/TSH ratio models in predicting a successful response to radioactive iodine therapy. METHODS: One thousand six hundred forty-two DTC patients receiving 131I radiotherapy were finally enrolled in this retrospective study. The patients were divided into a training set (n = 973) and a validation set (n = 669) by the patient consultation time (July 2019). A receiver-operating characteristic curve was constructed for Tg and the Tg/TSH ratio to establish their cutoffs. Then, the variables were screened by univariate logistic regression and incorporated into logistic prediction models by stepwise regression, where Tg/TSH was excluded from model 1 and Tg was excluded from model 2. RESULTS: In 1642 enrolled DTC patients, the first 131I radiotherapy had an excellent response in 855 patients. The cut-offs for Tg level and Tg/TSH ratio were 3.40 ng/ mL [area under the curve (AUC): 0.789] and 36.03 ng/mIU (AUC: 0.788), respectively. In addition, the AUC of the model including Tg was higher than that of the model including Tg/TSH in both the training set (0.837 vs 0.833) and the testing set (0.854 vs 0.836). CONCLUSIONS: Both Tg and Tg/TSH ratios could be considered predictors of the effects of the first 131I ablative therapy. However, the prediction model including Tg performed better than the model including Tg/TSH.

Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Is Related to a Poor Outcome: A Comparison Study Using Propensity Score Matching.

OBJECTIVE: The clinical outcome of diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) remains controversial. We aimed to determine whether DSV-PTC is associated with an increased risk of persistent/recurrent disease. METHODS: We performed a retrospective cohort study of DSV-PTC and classic variant of papillary thyroid carcinoma (CV-PTC) after postoperative radioactive iodine therapy. We used propensity score matching (1:3 matching ratio) to account for differences between the recipients of DSV-PTC and CV-PTC. Univariate and multivariate analyses were performed to assess the independent factors for persistent/recurrent disease. The Kaplan-Meier curve analyses were used to compare disease-free survival (DFS). RESULTS: In total, 35 (12.7%) patients with DSV-PTC and 240 (87.3%) patients with CV-PTC were included. After propensity score matching, 35 pairs of patients were selected (DSV-PTC, n = 35; CV-PTC, n = 105). In the matched analysis, a higher proportion of patients with DSV-PTC experienced persistent/recurrent disease than that of those with CV-PTC (25.7% vs 5.7%, P = .003). In the multivariate analyses of clinical and tumor characteristics, only the histologic type of DSV-PTC (odds ratio, 6.288; 95% confidence interval, 1.900-20.811; P = .003) was associated with an increased risk of persistent/recurrent disease. The 5-year DFS rates for the DSV-PTC and CV-PTC groups were 69.2% and 93.6%, respectively. The Kaplan-Meier analysis indicated that the DSV-PTC group (P= .001) had shorter DFS. CONCLUSION: This propensity score-matched analysis found that the histologic type of DSV-PTC may increase the risk of persistent/recurrent disease.

Urinary iodine excretion after using povidone iodine or chlorhexidine gluconate for topical disinfectant in patients undergoing thyroidectomy due to thyroid carcinoma: When to do radio active iodine therapy?

Background: Povidone Iodine (PI) is the most frequent antiseptic used as a topical disinfectant in surgery. It has been reported high transcutaneous iodine absorption due to topical PI usage, but there is a lack of data in periods of excess iodine depletion. Materials and Methods: This is a cross-sectional study designed to assess serial urinary iodine concentration (UIC) after topical administration of PI to evaluate the transcutaneous iodine absorption and the proper iodine depletion time for safe administration of Radio Active Iodine (RAI) therapy as ablative or adjuvant therapy. Results: Thirty-seven patients with papillary thyroid carcinoma undergoing total thyroidectomy were assigned to the PI group (n = 20) or chlorhexidine gluconate (CHG) group (n = 17). In the PI group, the UIC levels rose to a maximum of 2 times in the 4th week after administration and returned to pre-operative levels in the 8th week after. In the CHG group, there was a decrease in UIC levels due to a low iodine diet (LID) with a significant P-value of 0.001, <0.001, and 0.001 in the 2nd, 4th, and 8th weeks follow up respectively compared to the PI group. The urinary excretion of excess iodine lasts about 8 weeks after total thyroidectomy until iodine levels turn back to pre-operative values. Conclusion: If the thyroidectomy was prepared with PI, RAI is better to be performed 6-8 weeks after surgery rather than the standard prescription of 4 weeks.

Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves' disease.

Liver dysfunction is a common complication of Graves' disease (GD) that may be caused by excessive thyroid hormone (TH) or anti-thyroid drugs (ATDs). Radioactive iodine (RAI) therapy is one of the first-line treatments for GD, but it is unclear whether it is safe and effective in patients with liver dysfunction. 510 consecutive patients with GD receiving first RAI were enrolled in the study, and followed up at 3-, 6- and 12-month. Liver dysfunction was recorded in 222 (43.5%) patients. GD patients with liver dysfunction had higher serum levels of free triiodothyronine (FT3) (median 27.6 vs. 20.6 pmol/L, p < 0.001) and free thyroxine (FT4) (median 65.4 vs. 53.5 pmol/L, p < 0.001) levels than those with normal liver function. Binary logistic regression analysis showed that duration of disease (OR = 0.951, 95% CI: 0.992-0.980, p = 0.001) and male gender (OR = 1.106, 95% CI: 1.116-2.384; p = 0.011) were significant differential factors for liver dysfunction. Serum TSH levels were higher in patients with liver dysfunction at all 3 follow-up time points (p = 0.014, 0.008, and 0.025 respectively). FT3 level was lower in patients with liver dysfunction at 3-month follow-up (p = 0.047), but the difference disappeared at 6 and 12 months (p = 0.351 and 0.264 respectively). The rate of euthyroidism or hypothyroidism was higher in patients with liver dysfunction than in those with normal liver function at 3 months (74.5% vs 62.5%; p = 0.005) and 6 months (82.1% vs 69.1%; p = 0.002) after RAI treatment, but the difference did not persist at 12-month follow-up (89.6% vs 83.2%, p = 0.081).There were no statistically significant differences in treatment efficacy (94.48% vs 90.31%, p = 0.142), incidence of early-onset hypothyroidism (87.73% vs 83.67%, p = 0.277), and recurrence rate (4.91% vs 7.14%, p = 0.379) between the 2 groups at 12-month follow-up. In conclusion, the efficacy of RAI was comparable in GD patients with liver dysfunction and those with normal liver function.

Anxiety and depression status prior to radioactive iodine therapy among differentiated thyroid cancer patients during the COVID­19 pandemic.

OBJECTION: The psychological health of thyroid cancer patients cannot be ignored; however, few studies have been conducted on the psychological status and influencing factors of thyroid cancer patients before radioactive iodine (RAI) therapy. The aim of this study was to investigate the incidence and risk factors for anxiety and depression in thyroid cancer patients prior to RAI therapy. METHODS: Clinical data were collected from patients with differentiated thyroid cancer (DTC) patients preparing for RAI therapy. Anxiety and depression were measured before RAI therapy using the Generalized Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire (PHQ-9). We used the chi-square test and logistic regression analysis to identify independent risk factors for anxiety and depression. RESULTS: A total of 112 patients with thyroid cancer were included. Of these, 72.32% (n = 81) were female, with a mean age of 41.50 years. Anxiety and depression were reported by 46 (41.08%) and 38 (33.93%) patients, respectively. Based on the chi-square test and univariate logistic regression analysis, being female and having ever-experienced RAI therapy were significant risk factors for anxiety and depression among DTCs prior to RAI therapy. On multivariable analysis, the results of model 2 which included age, sex, education level, and ever suffering radioactive iodine therapy showed that being female was markedly associated with anxiety and depression in these patients, while having ever undergone RAI therapy was significantly related to anxiety but not depression. CONCLUSIONS: The incidence of anxiety and depression among patients with DTC prior to RAI therapy were 41.08% and 33.93%, respectively. Being female and having ever experienced RAI therapy significantly influenced anxiety and depression. Based on these findings, anxiety and depression assessment should be an important part of pre-RAI therapy in patients with DTC, and appropriate psychological nursing intervention can be carried out for key patients.

The clinical outcomes of COVID-19 infection in patients with a history of thyroid cancer: A nationwide study.

BACKGROUND: There are scarce published data in differentiated thyroid cancer patients about new coronavirus disease 2019 (COVID-19) disease outcomes and mortality. Here, we evaluated COVID-19 infection outcomes and mortality in thyroid cancer patients with COVID-19 infection. DESIGN AND METHODS: We included a cohort of patients with thyroid cancer with PCR-confirmed COVID-19 disease from 11 March to 30 May 2020 from the Turkish Ministry of Health database in our nationwide, retrospective study. We compared the mortality and morbidity of COVID patients with or without thyroid cancer. Univariate and multivariate analyses were used to assess the independent factors for mortality, length of hospital stay and intensive care unit (ICU) admission and mechanical ventilation. We also analysed the effect of radioiodine treatment on severity and death rate of COVID-19 disease. RESULTS: We evaluated 388 COVID-19 patients with thyroid cancer [median age: 54 years, interquartile range (IQR) 18 years, males: 23%] and age and gender-matched 388 COVID-19 patients without thyroid cancer. Patients with thyroid cancer had a similar mortality ratio compared with the non-cancer group. Among patients with thyroid cancer, age, presence of diabetes mellitus, asthma/COPD, heart failure, chronic kidney disease, prior coronary artery disease, RAS blocker usage and low lymphocyte count were associated with mortality. Radioactive iodine (RAI) treatment and cumulative radioactive iodine dosage did not negatively affect the severity and mortality of COVID-19 disease in our patient group. CONCLUSIONS: Our study indicated that history of thyroid cancer did not have an increased risk of mortality or morbidity in COVID-19 disease. Besides, RAI therapy history and doses of radioactive iodine did not affect mortality or outcome.

Differentiated thyroid carcinoma in children: A retrospective analysis of 125 pediatric cases from a single institution in India.

BACKGROUND: Thyroid carcinoma (TC) is extremely rare in children. We assessed the clinicopathological features, outcomes, recurrence pattern, and associated risk factors of differentiated thyroid carcinoma (DTC). METHODS: Children aged ≤14 years, pathologically diagnosed as DTC at a tertiary cancer institute between January 1998 and December 2015 were retrospectively analyzed. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: During 18 years, 125 children with DTC were treated with a male:female ratio of 1:2.3. The median age was 12 years (2-14 years). Anterior neck swelling was the commonest presentation (72.8%). Histopathology revealed papillary thyroid carcinoma (PTC) in 123 children (98.4%). Extrathyroidal extension was seen in 32 children (25.6%). Sixty-eight children (54.4%) had nodal metastases and seven had distant metastasis. Relapse developed in 12 children. All were salvaged with subsequent surgery and radioiodine therapy. Eight children had persistent disease and one had a second malignant neoplasm. The median follow-up period was 9 years 1 month (1-20 years). Five-year recurrence-free survival (RFS) was 94.8% and 5-year overall survival was 100%. Larger tumors (p-value = .001), extrathyroidal extension (p-value = .001), and nodal metastasis (p-value = .022) were significant predictors for RFS in univariate analysis. CONCLUSIONS: Pediatric DTC showed aggressive behavior characterized by a high rate of extrathyroidal extension and nodal and pulmonary metastasis. Persistent disease should be distinguished from recurrent disease as DTCs with metastatic disease remain stable for long time and usually respond well to radioiodine therapy. Our study reaffirmed favorable prognosis despite aggressive presentation and even after relapse.

Influence of Levothyroxine With Recombinant Human Thyroid-Stimulating Hormone on Urinary Iodine Excretion Before Radioactive Iodine Administration.

OBJECTIVE: Stimulation with recombinant human thyroid-stimulating hormone (rhTSH) before radioactive iodine administration for patients with thyroid cancer may increase the body iodine pool in the presence of continued levothyroxine; however, the precise significance of its influence remains unclear. METHODS: This was a prospective observational study conducted between March 2017 and August 2020. We measured the 24-hour urinary iodine excretion and urinary iodine-to-creatinine ratio in patients with thyroid cancer stimulated by rhTSH or thyroid hormone withdrawal (THW) before radioactive iodine administration. Oral iodine intake was controlled by a 7-day self-managed low iodine diet, followed by a strict 3-day low iodine diet while in the hospital. RESULTS: Overall, 343 subjects were included (rhTSH: n = 181; THW: n = 162). The mean levothyroxine dose in the rhTSH group was 115.2 µg daily. The median 24-hour urinary iodine and urinary iodine-to-creatinine ratio in the rhTSH group (71.0 [interquartile range, 57.5-88.0] µg/day and 80.0 [59.0-97.5] µg/gCr, respectively) were significantly higher than those in the THW group (42.0 [30.0-59.0] µg/day and 39.0 [28.0-61.3] µg/gCr, respectively; both P < .001). After propensity score matching by age, sex, body weight, and renal function (rhTSH: n = 106; THW: n = 106), consistent results for both values were observed for both methods. The increase in urinary iodine with the rhTSH method was smaller than the expected value calculated from the amount of levothyroxine. CONCLUSION: Urinary iodine excretion was significantly higher among patients with rhTSH stimulation than those with THW, indicating that the rhTSH method slightly increases the body iodine pool.

Favorable outcomes of papillary thyroid microcarcinoma concurrent with Graves' disease after radioactive iodine therapy.

Graves' disease (GD) may coexist with papillary thyroid microcarcinoma (PTMC). The main purpose of this study was to evaluate whether treatment with radioactive iodine (RAI) may cause acute exacerbation of PTMC concurrent with GD or not. From the medical records of 10,257 GD patients who underwent RAI therapy between 2000-2017, 12 subjects with concurrent PTMC were retrieved. Further, 49 patients with concurrent GD and PTMC who underwent no RAI administration throughout their clinical course were enrolled as controls. Size of the PTMC nodules was evaluated based on maximal diameter and tumor volume-doubling rate (TV-DR). Among the 12 subjects who underwent RAI therapy (median dose, 13 mCi), 2 showed tumors >10 mm in maximal diameter with slow growth for more than 10 years, while the other 10 showed tumors with maximal diameter ≤10 mm. No subject showed any clinical findings of nodal or distant metastasis during the follow-up periods (0.4-11.5 years) before surgery or during active surveillance. No significant differences were observed in the TV-DR values (median, 0.044/year; range, -0.81-1.40) between the study subjects and controls (median, 0.025/year; range, -0.70-1.29; p = 0.69). When comparing the TV-DR before and after RAI administration in 3 individuals in particular, in whom PTMC were cytologically confirmed before RAI administration and whose prospective follow-up data were available, tumor progression was observed to be stable or decreased after RAI administration. There were no acute exacerbations or unfavorable outcomes of concurrent PTMC and GD after low-dose RAI administration.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

Radioactive Iodine Therapy in Differentiated Thyroid Cancer: 2020 Update.

OBJECTIVE. The paradigm of theranostics is based on tailoring therapy for the purpose of optimizing outcomes. This principle is being applied to radioactive iodine therapy. Consequently, thyroid cancer therapy protocols are evolving. The purpose of this article is to promote a modern approach to radioiodine therapy. CONCLUSION. This article highlights guidelines and position statements, summarizes the prognostication systems of thyroid cancer, and reviews which prescribed activities of 131I.

Treatment intensity and control rates in combining external-beam radiotherapy and radioactive iodine therapy for metastatic or recurrent differentiated thyroid cancer.

BACKGROUND: To evaluate the treatment outcomes of external-beam radiotherapy (EBRT) with or without radioactive iodine therapy (RAIT) for metastatic or recurrent lesions of differentiated thyroid cancer (DTC). METHODS: Between August 1997 and March 2018, 73 lesions (distant metastases, 50; regional lymph-node metastases, 17; postoperative tumor-bed recurrences, 6) in 36 patients that had received EBRT with or without RAIT were reviewed. Doses of EBRT were 8-70 Gy (median 40 Gy). Seventeen patients received RAIT after EBRT. RESULTS: Median follow-up time of imaging studies was 14 months (range 1-110 months). Two-year overall survival rates and control rates of EBRT sites were 71% and 62%, respectively. Two-year control rates for EBRT of < 30 Gy (n = 7), 30 Gy (n = 13), 31-49 Gy (n = 25), 50 Gy (n = 20), and > 50 Gy (n = 8) were 0%, 56%, 53%, 79%, and 100%, respectively. There were statistically significant differences in control rates between < 30 Gy and 30 Gy (p = 0.003), and between 50 Gy and > 50 Gy (p = 0.037). Control rates of > 50 Gy were significantly better compared to ≤ 50 Gy (p = 0.021). Two-year control rates with (n = 28) and without (n = 45) post-EBRT RAIT were 89% and 45%, respectively (p = 0.009). In multivariate analysis, EBRT of > 50 Gy and post-EBRT RAIT were significant independent factors for favorable control of EBRT sites (hazard ratio [HR], 5.72; 95% confidence interval [CI], 1.21-27.1; p = 0.028 and HR, 2.98; 95% CI, 1.28-6.98; p = 0.012, respectively). CONCLUSION: EBRT of > 50 Gy and post-EBRT RAIT appeared to be useful for long-term control of EBRT sites for metastatic or recurrent lesions of DTC.

Clinical outcomes and risk stratification for papillary thyroid carcinoma presenting with distant metastasis before the era of tyrosine kinase inhibitors.

Radioactive iodine (RAI) therapy has been the mainstay of treatment for papillary thyroid carcinoma (PTC) patients with distant metastasis (DM). Although tyrosine kinase inhibitors (TKIs) were introduced for the treatment of RAI refractory metastatic thyroid carcinoma several years ago, clinical outcomes for PTC patients with DM treated using RAI therapy remain unclear. We retrospectively examined 64 PTC patients (9 men, 55 women) with DM at diagnosis treated using RAI therapy without administration of any kind of chemotherapy or TKIs. Median age of patients was 58 years. Site of DM was the lungs (n = 59), bone (n = 3), and pleural dissemination (n = 2). No patients showed multiple-organ metastases at diagnosis. By the end of the study period, 21 patients had died of PTC. Cause-specific survival rates at 10, 15, and 20 years after initial surgery were 68.2%, 63.6% and 61.1%, respectively. Uni- and multivariate analyses identified age ≥55 years (HR 3.1, p = 0.023), site of DM other than the lungs (HR 13.4, p < 0.0001), and DM with no RAI avidity (HR 5.1, p = 0.0098) as factors independently associated with disease-related death. When analyses were restricted to patients with lung metastasis (n = 59), surgical non-curability was another independent risk factor (HR 5.2, p = 0.0047) in addition to age and RAI avidity. According to risk stratification analysis based on these risk factors, patients with site of DM other than the lungs or with lung metastasis showing ≥2 risk factors among age ≥55 years, DM with no RAI avidity, and surgical non-curability are expected to show higher mortality rates.

Impact on testicular function of a single ablative activity of 3.7 GBq radioactive iodine for differentiated thyroid carcinoma.

STUDY QUESTION: What are the consequences of radioactive iodine (RAI) therapy for testicular function? SUMMARY ANSWER: A single activity of 3.7 GBq RAI for differentiated thyroid carcinoma (DTC) treatment in young men transiently altered Sertoli cell function and induced sperm chromosomal abnormalities. WHAT IS KNOWN ALREADY: Few studies, mainly retrospective, have reported the potential impacts of RAI on endocrine and exocrine testicular function. STUDY DESIGN, SIZE, DURATION: A longitudinal prospective multi-center study on testicular function performed in DTC patients before a single 131I ablative activity of 3.7 GBq (V0) and at 3 months (V3) and 13 months (V13) after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty male patients, aged 18-55 years, with DTC participated. Hormonal analysis included FSH, LH, testosterone and inhibin B serum levels at V0, V3 and V13. Furthermore, sperm parameters, DNA fragmentation and sperm chromosomal abnormalities were evaluated at each time points. The differences in all parameters, between V0-V3, V0-V13 and V3-V13, were analyzed, using a Wilcoxon test. MAIN RESULTS AND THE ROLE OF CHANCE: Prior to RAI administration, all patients had normal gonadal function. At V3, a statistically significant increase in FSH levels and a decrease in inhibin B levels were observed and sperm concentration, as well as the percentage of morphologically normal spermatozoa, were significantly decreased (P < 0.0001). These modifications were transient as both sperm concentration and normal morphology rate returned to baseline values at V13. However, at this later time point, FSH and inhibin B levels were still impacted by RAI administration but remained in the normal range. Although no DNA fragmentation was observed at V3 nor V13, our study revealed a statistically significant increase in the number of sperm chromosomal abnormalities both at V3 (P < 0.001) and V13 (P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Among the 40 patients included in the study, only 24 had all the parameters available at all visits. WIDER IMPLICATIONS OF THE FINDINGS: Prospective studies with longer term follow up would be helpful to determine whether the chromosome abnormalities persist. These studies would be required before sperm banking should be suggested for all patients. However, sperm preservation for DTC patients who require cumulative radioiodine activities higher than 3.7 GBq should be proposed. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Programme Hospitalier de Recherche Clinique, AP-HP (No. P040419). The authors report no conflict of interest in this work. TRIAL REGISTRATION NUMBER: NCT01150318.

Changes in the size of the thyroid in patients with benign non-toxic multinodular goiter after radioactive iodine therapy.

Background: Multinodular goiter (MNG) is regarded as one of the most common causes of hyperthyroidism, particularly in areas of mild-to-moderate iodine deficiency. The present study aims to explore the effects of the radioactive iodine (RAI) therapy on benign non-toxic MNG and evaluate its side effects. Methods: Patients with benign non-toxic MNG entered the study. Ultrasonography was applied to calculate the percentage of the decrease in the size of the thyroid before and six months minimum after the treatment. Chi-square, Mann-Whiteny-U and T-test were done using SPSS v.18.0 (p<0.05). Results: The volumes of the thyroid lobes and nodules decreased significantly due to RAI therapy (p<0.001). The total volume of the thyroid, volume of the right nodule, and volume of the left nodule decreased by 77.8%, 40.7%, and 34.6% respectively. Conclusion: According to the results of the current study, RAI therapy is an effective treatment method although it has short-term side effects. This treatment option is recommended for patients with benign non-toxic MNG, notably those who cannot be a candidate for surgery. This treatment affects the size of the thyroid and its nodules significantly and decreases almost all of the complications.

Noninferior response in BRAF(V600E) mutant nonmetastatic papillary thyroid carcinoma to radioiodine therapy.

PURPOSE: As the most frequent and specific genetic alteration in papillary thyroid carcinoma (PTC), BRAF(V600E) has an intimate relationship with more invasive tumour and higher postoperative recurrence risk in PTC patients. We investigate the effect of radioactive iodine (RAI) therapy on the clinical outcome in PTC patients with the BRAF(V600E) mutation without distant metastases. METHODS: This retrospective study included PTC 228 patients without distant metastases who underwent total or near-total thyroidectomy and RAI treatment in our hospital from January 2011 to July 2014. The BRAF(V600E) status of the primary lesions was determined and the patients were divided into two groups according to the presence of the mutation. Serological and imaging data were collected at a median follow-up of 2.34 years after RAI administration. Suppressed and stimulated thyroglobulin (Tg), Tg antibody, diagnostic whole-body scintigraphy, and other imaging examinations were used to assess clinical outcome, which was defined as excellent response, indeterminate response, biochemical incomplete response and structural incomplete response. RESULTS: The BRAF(V600E) mutation was observed in 153 of the 228 patients (67.1 %). The clinicopathological features did not differ between the BRAF(V600E) mutatation and wild-type groups except age at diagnosis (P = 0.000), tumour size (P = 0.023) and TNM stage (P = 0.003). Older age and more advanced TNM stage were prevalent in the BRAF(V600E) mutatation group, whereas tumours were slightly larger in the BRAF(V600E) wild-type group. The response to RAI therapy was evaluated in both the entire series and the patients with a high recurrence risk, and no significant difference in response was found between the BRAF(V600E) mutatation and the wild-type groups (P = 0.881 and P = 0.851, respectively). CONCLUSION: The clinical response to timely postsurgical RAI therapy is not inferior in BRAF(V600E) mutation PTC patients without distant metastases, which suggests that RAI therapy might improve the general clinical outcome in this patient group.