Postoperative Radioiodine Therapy Research Articles

Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Impact of radioiodine therapy on recurrence and survival outcomes in intermediate-risk papillary thyroid carcinoma -A systematic review and meta-analysis.

The utility of radioiodine (RAI) therapy in intermediate-risk papillary thyroid carcinoma (PTC) remains a topic of ongoing discussion. This systematic review and meta-analysis aimed to consolidate existing evidence on the impact of postoperative RAI therapy on recurrence and survival outcomes in intermediate-risk PTC. A literature search was performed using relevant keywords in PubMed, Scopus, and EMBASE. Articles from January 2008 to March 2023 were included. Odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates were generated using meta-analysis. Eleven articles comprising 56,266 intermediate-risk PTC patients were included. 41,530 (73.8%) patients underwent postoperative RAI therapy, while 14,736 (26.2%) patients were kept on no-RAI (NOI) follow-up. No significant reduction in rates of structural disease recurrence was noted with RAI therapy in comparison to NOI follow-up (pooled univariate OR, 0.73, 95% confidence interval [CI], 0.29-1.87, I2 = 75%). RAI therapy was not a significant predictor of better recurrence-free survival (pooled multivariate HR, 0.21; 95% CI, 0.01-3.74, I2 = 94%). Interestingly, RAI therapy was associated with an overall survival benefit compared to NOI follow-up (pooled multivariate HR, 0.63; 95% CI, 0.48-0.82, I2 = 79%). This meta-analysis did not establish a conclusive benefit of RAI therapy in preventing structural disease recurrence or improving recurrence-free survival in intermediate-risk PTC. However, these results need to be interpreted with caution owing to significant heterogeneity in the existing literature. A prospective, randomised clinical trial is the need of the hour to better understand the effect of RAI therapy on long-term outcomes.

Efficacy of ethanol ablation in the long-term local control of recurrent neck nodal metastases occurring after bilateral thyroidectomy, extensive nodal resection and postoperative radioiodine therapy in adult patients presenting with node-positive UICC/AJCC ptnm stage i papillary thyroid carcinoma.

Efficacy of ethanol ablation in the long-term local control of recurrent neck nodal metastases occurring after bilateral thyroidectomy, extensive nodal resection and postoperative radioiodine therapy in adult patients presenting with node-positive UICC/AJCC ptnm stage i papillary thyroid carcinoma.

Long-term prognostic analysis of children and adolescents with differentiated thyroid carcinoma based on therapeutic response to initial radioiodine therapy.

The clinical features and prognosis of children and adolescents with differentiated thyroid carcinoma (caDTC) are different from that of adults. Postoperative radioiodine therapy (RIT) was recommended for some intermediate and high risk caDTC patients. The objective of this study was to evaluate the long-term prognosis of pediatric caDTC patients with different responses to initial RIT and to explore the related influencing factors. All subjects were assigned to no clinical evidence of disease (NED) group, biochemical persistent disease (BPD) group, or structural/functional persistent disease (S/FPD) group based on the therapeutic response to initial RIT. Then, disease status was evaluated in all three groups at the last follow-up using ATA guidelines. Meanwhile, disease-free survival (DFS) for NED group and the progression-free survival (PFS) for the BPD and S/FPD groups were also assessed. 117 subjects were divided into NED group (n=29), BPD group (n=48) and S/FPD group (n=34) after initial RIT. At the last follow-up, excellent response (ER), indeterminate response (IDR), biochemically incomplete response (BIR) and structurally incomplete response (SIR) rates were 93.10%, 6.90%, 0% and 0% in NED group; 29.17%, 25.00%, 43.75% and 2.08% in BPD group; and 11.77%, 2.94%, 0%, and 85.29% in S/FPD group. The 5-year DFS rate in NED group was 95.5%. The 5-year PFS rates in BPD and S/FPD groups were 79.2% and 48.6%, respectively. For children with structural or functional lesions, longer PFS were found in male children with 131I-avid lesions, and post-operative stimulated serum thyroglobulin (sti-Tg) < 149.80 ng/ml. The response to initial RIT could be helpful for defining subsequent treatment and follow-up strategies for caDTC patients. Post-operative sti-Tg and 131I-avidity of lesions are correlated with PFS.

Comparison of the initial presentation and long-term outcome of differentiated thyroid carcinoma (DTC) between children and adults: A single institution experience in Taiwan.

163 Background: Differentiated thyroid carcinoma (DTC) in children is known to be more aggressive than in adults. However, there are no cohort studies in Asia that have compared the presentation and long-term outcomes of pediatric DTC with adult DTC. In this study, we aimed to compare the clinical characteristics and outcomes of pediatric DTC with a comparison cohort of adult DTC patients. Methods: We reviewed the data of 46 pediatric DTC patients who underwent total thyroidectomy from January 1991 to December 2021, along with a comparison cohort of 350 adult DTC patients at our hospital. All patients received postoperative radioiodine therapy. Clinicopathologic features and surgical outcomes were analyzed retrospectively, and patients were stratified according to the American Thyroid Association (ATA) risk stratification system. Clinical outcomes were classified according to Dynamic Risk Stratification (DRS) at the end of follow-up. Results: Children with DTC had less common papillary thyroid carcinoma (80 vs. 93%) but had larger primary tumors, more multifocal disease, and more lymph node and distant metastasis at presentation compared to adults. Thus, at initial risk stratification, more children had intermediate-to-high risk (62 vs. 49%) than adults. At the end of follow-up, fewer children were classified as having excellent response (no evidence of disease) than adults (48 vs. 79%). Based on the ATA risk stratification system, a higher percentage of high-risk children had structural-persistent disease (60%) compared to high-risk adults (29%), and a lower percentage of low-risk children became no evidence of disease (76%) compared to low-risk adults (93%). Conclusions: Children with DTC present with more extensive disease and have worse outcomes compared to adults. The ATA initial risk stratification system can predict long-term outcomes in both children and adult DTC patients and guide personalized management and follow-up strategies.

A tribute to Ernest L. Mazzaferri, MD and the lasting impact that he had on thyroid cancer care ten years after his death.

This viewpoint highlights the contributions of Dr. Ernest Mazzaferri, a prominent figure in the field of thyroid cancer care, who made significant contributions to the diagnosis and treatment of this disease. Dr. Mazzaferri's first paper on thyroid cancer, published in 1977, established fundamental principles that remain fundamental to differentiated thyroid cancer management. He was an advocate of total thyroidectomy and of postoperative radioiodine therapy and contributed to improving thyroid fine needle aspiration techniques. Dr. Mazzaferri's leadership in developing guidelines for the management of thyroid cancer and thyroid nodules has been influential and widely accepted. His groundbreaking work established a systematic and data-driven approach to the diagnosis and treatment of thyroid cancer that continues to shape the field of thyroid cancer care today. This Viewpoint reflects on his lasting impact ten years after his death.

Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature

BackgroundHürthle cell carcinoma (HCC) of the thyroid is rare. There are contrasting data on its clinical behavior. The aim of this study was to describe clinic-pathological features and outcomes of HCC patients at our institution, in order to adapt our surgical management.MethodsWe retrospectively studied 51 cases of HCC treated at the interdisciplinary endocrine center of the University Hospital of Cologne, Germany between 2005 and 2020.ResultsPatients median age was 63 years (range 29-78) with 64.7% of cases being female. Primary treatment included surgery and postoperative radioiodine therapy with 3.7 GBq in all patients. Surgery consisted of total thyroidectomy in all cases and additional central lymphadenectomy in 90.2% of cases. The median number of harvested lymph nodes was 11 (range 2-31). Lymph node involvement was found in two (4.3%) pT4a tumors. In all other cases (95.7%), central lymphadenectomy was prophylactic and lymph nodes were free of metastasis in final histopathology. Twelve (23.5%) patients with incomplete biochemical response to primary treatment were diagnosed with structural relapse during the course of disease, for which seven (58.4%) underwent resection of isolated cervical metastasis. Histopathology revealed soft tissue implants in all cases and cervical surgery led to biochemical and radiologic cure in only two (28.5%) cases. Five (41.6%) patients developed metastatic disease, followed by systemic therapy in two patients. Vascular invasion of the primary tumor was significantly associated with relapse (p<0.01).ConclusionsRecurrence of HCC was common in this study. Given the low rate of lymph node metastases both in this study and in recent literature and the nature of relapse (soft tissue instead of nodal metastasis), the benefit of routine prophylactic central lymph node dissection for HCC remains unclear, especially in the absence of vascular invasion from the primary tumor.

Postoperative radioiodine therapy impact on survival in poorly differentiated thyroid carcinoma: a population-based study.

PurposeThe true impact of postoperative radioiodine therapy on survival has been controversial for patients with poorly differentiated thyroid carcinoma (PDTC). We aimed to determine the impact of postoperative radioiodine on survival in PDTC through a population-based study.MethodsData on patients with PDTC were collected from the US SEER database (2004 to 2015). Patients were divided into the radioiodine group and nonradioiodine group. Survival comparison between groups was evaluated by Kaplan–Meier curves, log-rank test and multivariate Cox regression analysis. Akaike information criterion was used to select variables in the nomogram. The performance of the nomogram was assessed by discrimination (C-index) and calibration plots.ResultsThe radioiodine group had more aggressive features, such as advanced tumor node metastasis stage and radical surgery, compared to the nonradioiodine group. PDTC patients receiving radioiodine therapy had a significant survival advantage in terms of overall survival (OS) (P = 0.001) but not in terms of cancer-specific survival (P = 0.083). Multivariate analysis revealed radioiodine therapy was an independent favorable factor for OS in PDTC patients (hazard ratio = 0.57; 95% CI, 0.44–0.75, P < 0.001). Subgroup analysis identified patients’ characteristics favoring radioiodine therapy. The nomogram (age, tumor size, extension, neck lymph nodes metastasis and radioiodine therapy) of OS for predicting 3-, 5- and 10-year OS probability showed good discrimination (C-index, 0.797) and calibration power.ConclusionPostoperative radioiodine therapy can prolong the long-term OS in patients with PDTC, and is an independent favorable prognostic factor for those patients. Further prospective studies are warranted.

Progressive changes in the major salivary gland after radioiodine therapy for differentiated thyroid cancer: a single-center retrospective ultrasound cohort study

This study aimed to determine the prevalence of radioiodine-induced salivary gland damage by evaluating progressive changes in salivary glands using ultrasound. Four hundred forty-six patients with differentiated thyroid carcinoma who underwent total or near-total thyroidectomy and postoperative radioiodine therapy were retrospectively reviewed. From the first to the fifth follow-up visits, the positive rate of major salivary gland changes on ultrasound gradually increased from 2.0% to 33.0% (P<0.001) and possibly stabilized at the fifth visit (approximately 36 months). The first positive result was detected at an average of 20.78±8.72 months. Only 21 of the 161 positive cases eventually achieved negative ultrasound results (Fisher's test, P<0.001), and the 21 cases simply showed a coarse echotexure. In conclusion, ultrasound changes appeared late, and most of these changes were not reversed.

Applying postoperative radioiodine therapy before 3months seems to decrease ablation success in patients with differentiated thyroid carcinoma.

Radioiodine can be applied for remnant ablation in low and low to intermediate-risk patients with differentiated thyroid cancer (DTC). A controversy still exists about the application time interval of radioiodine following total thyroidectomy. In this study, we investigated the effect of radioiodine (RAI) therapy timing on the success rates of the ablation. We retrospectively reviewed the data of DTC patients who underwent total thyroidectomy and were treated with radioiodine remnant ablation during 2013-2017. Because the objective of this study was to determine the success of ablation according to the postoperative RAI therapy timing, any patients with a pathologic uptake outside the thyroid bed as well as high-risk patients determined before and at RAI therapy were excluded from the study. Finally, 503 patients with low and low to intermediate-risk groups were included in the study. Successful ablation was defined as no visible focal uptake on the neck on I-131 whole body scan with stimulated thyroglobulin (Tg) level of < 1ng/mL and a normal or undetectable antithyroglobulin antibody (ATG). The time interval from total thyroidectomy to RAI therapy (titRAI) was calculated as months for each patient. A total of 115 (22.9%) patients were in the low to intermediate-risk group whereas most of the patients were at the low-risk group according to the American Thyroid Association (ATA) 2015. Successful ablation was observed in 388 (77.1%) patients. The titRAI was ≤ 3months in 151 (30.0%) patients and > 3months in 352 (70.0%) patients. The ratio of successful ablation was statistically higher in patients with a titRAI > 3months (81.2% of patients) than in patients with ≤ 3months (67.5% of patients) (χ2 11.247, p 0.001). The rate of successful ablation was 20.3% higher in patients treated after 3months. There was no statistical difference when titRAI cut off was reduced to 2months (p > 0.5). Investigated the effect of radioiodine therapy initiated before 3months after total thyroidectomy and it seems to decrease ablation success.

Current surgical management of follicular thyroid carcinoma

: Follicular thyroid carcinoma (FTC) comprises a heterogenous group of tumors, which divides into subtypes with different malignant potential: minimally invasive (excellent prognosis), encapsulated angioinvasive and widely invasive FTC (higher risk metastasis and recurrence). Numerous clinical risk factors (presence of metastases, advanced patient age, tumor size and others), which can be used to assess FTC aggressiveness, are discussed with regard to the present literature. The definitive characterization of follicular neoplasms depends on postoperative histology, due to the incapability of preoperative imaging, fine-needle aspiration cytology or molecular analysis to clearly distinguish between FTC and benign follicular thyroid adenoma. In this review, treatment strategies for FTC (according to the WHO 2017 classification of endocrine neoplasms) are presented, as recommended by the leading expert societies American Thyroid Association (ATA), British Thyroid Association (BTA), German Society of Endocrine Surgery (CAEK) and European Society of Endocrine Surgery (ESES). Hemithyroidectomy is sufficient in low-risk FTC (capsular invasion only). Thyroidectomy with postoperative radioiodine therapy is recommended for high-risk FTCs (angioinvasion; widely invasive histology). Prophylactic lymphadenectomy is not necessary. Considering clinical risk factors, an individual surgical approach should be chosen, following a stepwise, escalating surgical management with restricted primary resection (hemithyroidectomy) and, if necessary, completion surgery based on the definitive histopathology.

Controversies in Radioiodine Treatment of Low- and Intermediate-risk Thyroid Cancer

In differentiated thyroid cancer, radioiodine therapy (RIT) is usually carried out after thyroidectomy. Although the potent beneficial effects of radioiodine are undisputed in high-risk patients, much controversy remains surrounding many aspects of RIT in low- and intermediate-risk patients. Other than the indication for postoperative RIT, controversies also include, among others, the intent of RIT and the choice of activity for RIT or the mode of thyroid stimulating hormone stimulation. Furthermore, there is even controversy on the definition of what constitutes low- or intermediate-risk patients. Here the various issues will be discussed and an overview of the different points of view in a number of more prominent national and international guidelines and current literature is presented.

Early Diagnosis of Low-Risk Papillary Thyroid Cancer Results Rather in Overtreatment Than a Better Survival.

We are witnessing a rapid worldwide increase in the incidence of papillary thyroid carcinoma (PTC) in the last thirty years. Extensive implementation of cancer screening and wide availability of neck ultrasound or other imaging studies is the main reason responsible for this phenomenon. It resulted in a detection of a growing number of clinically asymptomatic PTCs, mainly low-risk tumors, without any beneficial impact on survival. An indolent nature of low-risk PTC, particularly papillary thyroid microcarcinoma (PTMC), and the excellent outcomes raise an ongoing discussion regarding the adequacy of treatment applied. The question of whether PTMC is overtreated or not is currently completed by another, whether PTMC requires any treatment. Current ATA guidelines propose less extensive preoperative diagnostics and, if differentiated thyroid cancer is diagnosed, less aggressive surgical approach and limit indications for postoperative radioiodine therapy. However, in intrathyroidal PTMCs in the absence of lymph node or distant metastases, active surveillance may constitute alternative management with a low progression rate of 1%–5% and without any increase in the risk of poorer outcomes related to delayed surgery in patients, in whom it was necessary. This review summarizes the current knowledge and future perspectives of active surveillance in low-risk PTC.

Personalized management of differentiated thyroid cancer in real life \u2013 practical guidance from a multidisciplinary panel of experts

PurposeThe standard of care for differentiated thyroid carcinoma (DTC) includes surgery, risk-adapted postoperative radioiodine therapy (RaIT), individualized thyroid hormone therapy, and follow-up for detection of patients with persistent or recurrent disease. In 2019, the nine Martinique Principles for managing thyroid cancer were developed by the American Thyroid Association, European Association of Nuclear Medicine, Society of Nuclear Medicine and Molecular Imaging, and European Thyroid Association. In this review, we present our clinical practice recommendations with regard to implementing these principles in the diagnosis, treatment, and long-term follow-up of patients with DTC.MethodsA multidisciplinary panel of five thyroid cancer experts addressed the implementation of the Martinique Principles in routine clinical practice based on clinical experience and evidence from the literature.ResultsWe provide a suggested approach for the assessment and diagnosis of DTC in routine clinical practice, including the use of neck ultrasound, measurement of serum thyroid-stimulating hormone and calcitonin, fine-needle aspiration, cytology, and molecular imaging. Recommendations for the use of surgery (lobectomy vs. total thyroidectomy) and postoperative RaIT are also provided. Long-term follow-up with neck ultrasound and measurement of serum anti-thyroglobulin antibody and basal/stimulated thyroglobulin is standard, with 123/131I radioiodine diagnostic whole-body scans and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography suggested in selected patients. Management of metastatic DTC should involve a multidisciplinary team.ConclusionsIn routine clinical practice, the Martinique Principles should be implemented in order to optimize clinical management/outcomes of patients with DTC.

Aberrant DNA repair as a potential contributor for the clonal evolution in subsets of anaplastic thyroid carcinomas arising through dedifferentiation: implications for future therapeutic algorithms?

Well-differentiated thyroid carcinoma (WDTC, including papillary thyroid carcinoma and follicular thyroid carcinoma) are fairly slow-growing tumors with an overall low mortality due to the efficacy of combinatory surgery and postoperative radioiodine therapy. Subsets of WDTCs may dedifferentiate into poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC), of which especially the latter has an exceptionally poor patient outcome. The underlying genetics responsible for this tumor progression is only partly understood, and is complicated by the fact that subgroups of ATCs are thought to arise de novo without a demonstrable, pre-existing WDTC. Even so, recent advances using next generation sequencing (NGS) techniques have identified a genetic link between WDTCs and ATCs, suggesting a step-wise accumulation of mutations driving the loss of differentiation for most cases. In this Commentary, recent findings from an NGS study on synchronous FTC, PDTC, and ATC tumor components from the same patient are highlighted. By using whole-genome data, clonality analyses identified a chief ancestral clone carrying mutations in TP53-associated signaling networks regulating genes involved in DNA repair, with sub-clones in each tumor component that were identified also in the less differentiated, neighboring tumor. Moreover, mutational signatures suggested a general mismatch repair (MMR) deficiency along with microsatellite instability. These findings support the chained progression model of dedifferentiation in thyroid cancer, and pinpoint a central role for defective DNA repair. Since effective treatment modalities for ATCs are urgently needed, studies regarding therapeutic agents specifically targeting defective MMR in dedifferentiated thyroid carcinoma could be pursued.

Postoperative Radioiodine Treatment within 9\xa0Months from Diagnosis Significantly Reduces the Risk of Relapse in Low-Risk Differentiated Thyroid Carcinoma

PurposeAlthough postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC.MaterialThe analyzed group involved 701 DTC patients staged pT1b-T4N0-N1M0, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months (N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228). Median follow-up was 12.1 years (1.5–15.2).ResultsBased on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant.ConclusionIf postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes.

European Perspective on 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: Proceedings of an Interactive International Symposium.

The American Thyroid Association (ATA) management guidelines for patients with thyroid nodules and differentiated thyroid cancer (DTC) are highly influential practice recommendations. The latest revision appeared in 2015 ("ATA 2015"). These guidelines were developed predominantly by North American experts. European experts frequently have different perspectives, given epidemiological, technological/methodological, practice organization, and medicolegal differences between the respective regions. Divergent viewpoints were the focus of an invited symposium organized by the European Association of Nuclear Medicine involving 17 European thyroidologists, four ATA Guidelines Taskforce members, and an audience of 200 international experts. The group discussed the preoperative assessment of thyroid nodules, surgery and the role of pathology, radioiodine (RAI) therapy (RAIT), the assessment of initial therapy and dynamic risk stratification, and the treatment of persistent disease, recurrences, and advanced thyroid cancer. The dialogue resulted in this position paper contrasting European and ATA 2015 perspectives on key issues. One difference pertains to the permissiveness of ATA 2015 regarding lobectomy for primary tumors ≤4 cm. European panelists cited preclusion of RAIT, potential need for completion thyroidectomy, frequent inability to avoid chronic thyroid hormone replacement, and limitations of supportive evidence as arguments against widely applying lobectomy. Significant divergence involved ATA 2015's guidance regarding RAIT. European panelists favored wider use of postoperative RAIT than does ATA 2015. Rationales included the modality's association with favorable patient outcomes and generally limited toxicity, and lack of high-quality evidence supporting withholding RAIT. Additionally, European panelists favored recombinant human thyrotropin (rhTSH) in more settings than does ATA 2015, citing avoidance of hypothyroid morbidity and quality-of-life impairment, without apparent sacrifice in oncologic outcomes. Based on clinical evidence plus theoretical advantages, European experts advocated dosimetric versus fixed-activity RAIT approaches for advanced DTC. European panelists noted that the ATA 2015 risk-stratification system requires information sometimes unavailable in everyday practice. ATA 2015 recommendations regarding RAI-refractory DTC should consider potential palliative benefits of RAIT in patients who also have RAI-susceptible lesions. European panelists suggested modifications to approximately one-third of ATA 2015 recommendations. Varying European and ATA 2015 perspectives can stimulate analysis and discussion of the literature and performance of primary research to resolve discrepant recommendations and potentially improve patient outcomes.

Post-operative radioiodine therapy (RaIT) as adjuvant therapy in low–intermediate risk differentiated thyroid cancer

For many years, thyroid surgery and radioiodine therapy for thyroid remnant ablation (i.e. post-operative RaIT) have been the first-line therapeutic approaches in differentiated thyroid carcinoma (DTC). In the latest American Thyroid Association Guidelines (ATA), post-operative RaIT is not indicated in low-risk DTC, while no clear indication is postulated regarding low- to intermediate-risk patients, even if it is discouraged in most of them. The European Association of Nuclear Medicine did not endorse ATA guidelines since the role of nuclear medicine was marginalized in patients affected by low- or low- to intermediate-risk cancers. The present review evaluates the adjuvant role of post-operative RaIT in low and low- to intermediate-risk DTC patients. The terms radioiodine adjuvant therapy, radioiodine adjuvant treatment, thyroid remnant ablation, radioiodine thyroid remnant ablation, radioiodine therapy and radioiodine treatment were used to search MEDLINE for papers published from January 2008 to May 2018. Among 895 papers, we considered 8 in which patients underwent post-operative RaIT and the results of post-therapy whole body scans (pT-WBS) were reported. pT-WBS identified metastases in 282 out of 1622 patients (17.4%). All except 28 metastatic patients were affected by either low- or low- to intermediate-risk DTC. Metastases were confirmed by (targeted)-morphological and/or morphofunctional and/or morphometabolic studies in about 40% of patients. According to the presented data, slightly less than 20% of low- or low- to intermediate-risk DTC patients showed metastases at pT-WBS. Thus, in our opinion post-operative RaIT should be considered as an adjuvant therapy also in low and low- to intermediate-risk DTC patients.

BRAF V600E Mutation in Papillary Thyroid Cancer and Its Effect on Postoperative Radioiodine (131I) Therapy: Should We Modify Our Therapeutic Strategy?

IntroductionThe BRAF V600E mutation in papillary thyroid cancer (PTC) has been associated with resistance to 131I. Our aim was to quantify the response to 131I after surgery in patients who had the mutation (BRAF+) and those who did not have the mutated gene (BRAF−). MethodA prospective cohort study was designed, from September 2015 to February 2016, which included patients with PTC receiving therapy after surgical treatment. Variables were described for age, gender, histology, tumor stage, thyroglobulin values before, 48h after and 6 months after 131I; absorbed dose and % activity on days 2 and 7 and elimination time. Results41 patients giving in total 67 thyroid remnants were included. 61% were BRAF+. In stages III and IV, 80% were BRAF+. In lateral resection, 100% were BRAF+. The number of nodes was higher in BRAF+: 3.4 vs 1.2 (P=.01). The classic variant was predominant in BRAF+ (91.7% vs 8.3%, P=.03). 85.7% vs 14.3% of BRAF+ had desmoplastic reaction (P=.02). The BRAF+ had a lower absorbed dose than the administered activity (5.4Gy/MBq vs 20Gy/MBq, P=.02); lower% activity with respect to the unit of mass at 2 (0.046%/g vs 0.103%/g, P=.02) and at 7 days (0.006%/gr vs 0.034%/gr, P=.04). ConclusionsThe mutation of the BRAF V600E gene is related with greater resistance to postoperative treatment with 131I since the onset of the disease.