Radioactive Iodine Remnant Research Articles

7478 Effects of RAI on Papillary Thyroid Carcinoma with Positive Lymph Nodes

Abstract Disclosure: K.N. Rachmasari: None. A. Osman: None. D. Toro Tobon: None. S.B. Lund: None. D.J. Merlino: None. A.R. Hsu: None. M.M. Ryder: None. Background: In low-risk papillary thyroid cancer (PTC), radioactive iodine (RAI) remnant ablation has shown no impact on disease recurrence rates, which are overall low. The role of adjuvant RAI in intermediate risk disease (i.e. T3, N1) remains unproven with no randomized clinical trials to objectively assess efficacy. Thus, in our institution, its use is highly heterogenous. We retrospectively investigated the effects of adjuvant RAI on recurrence and recurrence free survival (RFS) in patients with PTC and positive cervical lymph nodes (CLN). Methods: We performed a retrospective review of patients who underwent surgery at Mayo Clinic Rochester, MN for PTC between January 2007 and December 2016. Adult patients with Tx-T3 disease according to the 8th edition of American Joint Committee on Cancer (AJCC) were identified. Patients with positive CLN (N1) and a minimum follow up of 36 months were included. Demographics, clinicopathologic characteristics, use of RAI therapy and recurrence were analyzed. Results: A total of 367 patients with PTC, Tx-3, N1, M0 were identified, of which 187 received adjuvant RAI and 180 did not. Most patients were female (63.8%), with a median age of 44 years (IQR 34-54), and a median follow up of 77 months (IQR 58.5-101.5). There were no differences in age, type of surgery, histology, multifocality, and follow up period between the RAI and no RAI subgroups. Adjuvant Thyrogen-stimulated or thyroid hormone withdrawal-based RAI was recommended at the discretion of the treating provider and/or per patient preference. Diagnostic I-123 whole body scans were performed in all patients and mostly demonstrated remnant uptake. The median dose of I-131 was 75 mCi (range 50-100). Recurrence was defined by new occurrence of disease after at least a year of absence of clinical, biochemical, and imaging evidence of disease since initial surgery. Within the entire cohort, 35 (9.5%) developed recurrence with a median time of 41 months (28-59.5). Overall, recurrence rate and RFS were not significantly different between both subgroups (p = 0.2). A subanalysis was performed in patients with clinically detectable nodal disease (n = 161), defined by abnormal cervical lymph node on preoperative neck ultrasound with or without positive fine needle aspiration biopsy. Overall recurrence rates were 17 (10.6%) in this group. There were no differences in recurrence rates and RFS in those that received RAI versus those that did not (p = 0.8). Conclusions: In patients with intermediate risk PTC defined by nodal disease and/or T3 disease, recurrences were not different between patients that did or did not receive adjuvant I-131 therapy postoperatively. A randomized, noninferiority study of adjuvant I-131 compared to no I-131 postoperatively for N1 disease is needed to determine the benefit of near total thyroidectomy and adjuvant I-131 for this cohort. Presentation: 6/3/2024

Prognostic value of postoperative anti-thyroglobulin antibody in patients with differentiated thyroid cancer.

Postoperative thyroglobulin (Tg) generally serves as a biomarker to monitor the recurrence or persistence of differentiated thyroid cancer (DTC), whereas it constrains to interference from anti-thyroglobulin antibody (TgAb). This study aimed to determine the value of postoperative TgAb as a surrogate for monitoring tumor status in DTCs with positive TgAb after successful radioactive iodine (RAI) remnant ablation. We retrospectively enrolled DTC patients with positive (≥40 IU/mL, Roche) postoperative TgAb measurements. An index of TgAb change (ΔTgAb) was defined to describe the TgAb decrease rate. DTC status was defined as either no evidence of disease (NED) or persistent/recurrent disease (PRD). Univariate and multivariate binary logistic analyses were used to identify the independent risk factors of PRD. Receiver operating characteristic (ROC) curves were performed to determine the optimal cutoff values of each risk factor, and DeLong's test was conducted to compare their predictive powers. Kaplan-Meier curves were used to assess the impact of different TgAb trends in the first year on progression-free survival. Of the 232 patients enrolled, the median diagnosis age was 34 years (range, 18-62 years), with a male-to-female ratio of 1:4.66 (41/191). Among them, after a median follow-up of 44 months (range, 4-128 months),183 (78.87%) patients were evaluated as NED, while the other 49 (21.12%) had either persistent (n = 25) or recurrent disease (n = 24). Multivariate regression showed that ΔTgAb (P < 0.001) and lymph node metastasis (LNM) rate (P = 0.009) were independently relevant to the presence of PRD, with optimal cutoff values of 47.0% and 35.1%, respectively. It is important to note that there is a high negative predictive value (96.93%) of ΔTgAb with the cutoff of 47.0%. DeLong's test showed that ΔTgAb alone and the combination of ΔTgAb and LNM rate were significantly greater than the isolated LNM rate (both P < 0.001) in predicting NED, while there was no statistical difference of the predictive power between ΔTgAb and the combination (P = 0.203). Additionally, patients with ΔTgAb >47.0% had longer progression-free survival than those with ΔTgAb ≤47.0% (not reached vs. 50 months, P < 0.001), and those with ΔTgAb >47.0% or negative conversion within the first year after RAI ablation had longer progression-free survival. Our study suggested that ΔTgAb could serve as a valuable indicator of disease status in DTC patients with positive TgAb. A ΔTgAb of >47.0% is conducive to identify those with NED and may help to obviate their overtreatment. The decrease rate and negative conversion of TgAb in the first year were good predictors of disease-free survival in patients.

Recurrence Risk Evaluation in Patients with Papillary Thyroid Carcinoma: Multicenter Machine Learning Evaluation of Lymph Node Variables.

Lymph node (LN)-related risk factors have been updated to predict long-term outcomes in patients with papillary thyroid carcinoma (PTC). However, those factors' analytic appropriateness and general applicability must be validated. This study aimed to assess LN-related risk factors, and suggest new LN-related risk categories. This multicenter observational cohort study included 1232 patients with PTC with N1 disease treated with a total thyroidectomy and neck dissection followed by radioactive iodine remnant ablation. The median follow-up duration was 117 months. In the follow-up period, structural recurrence occurred in 225 patients (18.3%). Among LN-related variables, the presence of extranodal extension (p &lt; 0.001), the maximal diameter of metastatic LN foci (p = 0.029), the number of retrieved LNs (p = 0.003), the number of metastatic LNs (p = 0.003), and the metastatic LN ratio (p &lt; 0.001) were independent risk factors for structural recurrence. Since these factors showed a nonlinear association with the hazard ratio of recurrence-free survival (RFS) rates, we calculated their optimal cutoff values using the K-means clustering algorithm, selecting 0.2 cm and 1.1 cm for the maximal diameter of metastatic LN foci, 4 and 13 for the number of metastatic LN, and 0.28 and 0.58 for the metastatic LN ratio. The RFS curves of each subgroup classified by these newly determined cutoff values showed significant differences (p &lt; 0.001). Each LN risk group also showed significantly different RFS rates from the others (p &lt; 0.001). In PTC patients with an N1 classification, our novel LN-related risk estimates may help predict long-term outcomes and design postoperative management and follow-up strategies. After further validation studies based on independent datasets, these risk categories might be considered when redefining risk stratification or staging systems.

PSAT296 Graves’ Disease and Hurthle Cell Carcinoma: A Rare Presentation

Abstract Introduction Hurthle cell carcinoma is a rare thyroid malignancy, only accounting for 3-5% of all thyroid malignancies. Thyroid tumors are classified as Hurthle cell carcinomas when they contain more than 75% Hurthle cells. Hurthle cells are oncocytic cells with an acidic cytoplasm and can contain up to 5,000 mitochondria. In the thyroid, oncocytic changes are associated with conditions such as cell-mediated autoimmune thyroiditis, humoral-mediated hyperthyroidism (Graves’ disease), and hyperplastic nodules seen in multinodular goiters. Case Presentation A 64-year-old Polish female with a medical history of hypertension, hyperlipidemia, and smoking presented with fatigue, weight loss of 18kg in 6 months, palpitations, tremors, anxiety, heat intolerance, and diarrhea. Family history was pertinent for thyroid lobectomy in older sister and thyroidectomy in niece with reportedly benign pathology. She denied any family history of thyroid cancer. She resided 1,000 kilometers away from Chernobyl at the time of the nuclear accident. Diagnosis and Treatment Hyperthyroidism was attributed to Graves’ disease, and she was started on methimazole with improvement in symptoms. Fine needle aspiration of 3.4cm right thyroid nodule showed moderate to high cellularity with abundant discohesive Hurthle cells with granular cytoplasm, large nuclei with prominent nucleoli and mild nuclear atypia consistent with Hurthle cell carcinoma with a 25-40% risk of malignancy. She had a total thyroidectomy that revealed a 3cm minimally invasive Hurthle cell carcinoma with a benign lymph node. She was started on levothyroxine 100mcg. Post-surgery labs showed thyroglobulin 3 ng/mL [1.3-31.8], undetectable thyroglobulin antibody, suppressed TSH and normal calcium levels. Further course was complicated by Graves’ orbitopathy, worsened by smoking. She was started on teprotumumab and tapered dexamethasone before receiving 30 mCi radioactive iodine for remnant ablation. Discussion and Conclusion Graves’ disease is the most common cause of hyperthyroidism accounting for 60%- 80% of hyperthyroid cases. Graves’ disease has been reported to be associated with aggressive thyroid carcinomas, 88%being papillary thyroid cancers. Some studies note an increased mortality in patients with differentiated thyroid cancer associated with Graves’ disease when compared to euthyroid controls. Hurthle cell carcinoma is a rare thyroid malignancy and is uncommonly seen in conjunction with Graves’ disease. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Second Adjuvant Radioiodine Therapy after Reoperation for Locoregionally Persistent or Recurrent Papillary Thyroid Carcinoma.

Introduction Differentiated thyroid carcinoma (DTC) has increased incidence. Intermediate- and high-risk patients have lymph node relapse rate ranging from 10 to 50%, and receive multiple reinterventions, increasing the morbidity of the disease. Currently, there are no established guidelines for the use of second radioactive iodine (RAI) therapy after the reintervention for local recurrence. Materials and Methods This is a retrospective review of the medical records of 1,299 patients treated from January 2016 to July 2019 with DTC. We included 48 patients who received total thyroidectomy, RAI remnant ablation, surgery to remove the locally recurrent/persistent papillary thyroid carcinoma (PTC), and received a second RAI therapy. Results There were no significant differences between thyroglobulin (Tg) levels before reoperation (Tg0), Tg levels postoperatively (Tg1), and Tg levels after 6 months of second adjuvant RAI therapy (Tg2). However, we evidenced a 69.79% drop in first Tg levels (Tg0: 24.7 vs. Tg1: 7.56, p =0.851) and 44.4% decrease in second Tg levels (Tg1: 7.56 vs. Tg2: 4.20, p =0.544). Also, 77.1% of the patients did not have another documented recurrence. The median relapse-free time was 10.9 months (range: 1.3-58.2 months). Conclusion The results of the study cannot assess that a second RAI treatment after reoperation for locoregionally persistent or recurrent disease have a significant impact on treatment outcomes in intermediate- or high-risk patients with PTC. However, the 77.1% of patients have not presented a second documented recurrence and the median values of Tg and TgAb levels showed a substantial decrease after surgery and second RAI treatment.

Comparison of the abilities of staging and risk stratification systems to predict the long-term structural recurrence in patients with differentiated thyroid carcinoma after total thyroidectomy and radioactive iodine remnant ablation.

In patients with differentiated thyroid carcinoma (DTC), various staging and risk stratification systems have been applied to estimate long-term recurrence, which is a major issue during the postoperative follow-up period. However, the efficacy of these systems remains unclear in this context. The present historical cohort study included 510 patients with DTC who underwent a total thyroidectomy followed by radioactive iodine (RAI) remnant ablation. Enrolled patients were categorized according to the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) Tumor Node Metastasis (TNM) staging system, the 2015 American Thyroid Association (ATA) initial risk stratification system, and the dynamic risk stratification (DRS) system. The ability of each system to predict long-term structural recurrence was compared using proportion of variance explained (PVE) by logistic regression models. The median follow-up period was 108 months. Structural recurrence occurred in 7.6% of the patients (n=39/510). Disease-free survival (DFS) curves of the patients within each category in the TNM staging system, the ATA initial risk stratification system, and the DRS system were significantly different (P<0.001). The PVE of the DRS system (20.7%) was higher than those of the TNM staging system and the ATA initial risk estimates. The DRS system may effectively predict long-term structural recurrence and guide long-term management and follow-up strategies in patients with DTC undergoing total thyroidectomy and RAI remnant ablation.

Radioiodine Remnant Ablation for Differentiated Thyroid Cancer

Postoperative radioactive iodine (RAI) remnant ablation for differentiated thyroid cancer (DTC) facilitates the early detection of recurrence and represents an adjuvant therapy that targets persistent microscopic disease. The optimal activity of RAI in low- and intermediate-risk DTC remains controversial. To evaluate the long-term cure rate of different RAI activities in low- and intermediate-risk DTC. Secondary outcomes included successful remnant ablation, adverse effects, and hospital length of stay. A systematic search of the databases PubMed, Cochrane Collaboration, Embase, Scopus, and Web of Science was performed to identify randomized clinical trials (RCTs) and observational studies that compared long-term outcomes (>12 months) for American Thyroid Association-classified low- and intermediate-risk DTC based on receipt of either low-activity or high-activity RAI postoperatively. All RCTs or observational studies evaluating patients with low- and intermediate-risk DTC who were treated initially with total/near-total thyroidectomy, followed by remnant RAI ablation with either low or high activities. Eligible studies had to present odds ratio, relative risk (RR), or hazard ratio estimates (with 95% CIs), standard errors, or the number of events necessary to calculate these for the outcome of interest rate. Two investigators reviewed the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Dichotomous variables were pooled as risk ratios and continuous data as weighted-mean differences. Quality assessment of the included studies was performed using the Newcastle-Ottawa and Jadad scales. Disease recurrence was the primary outcome. Secondary outcomes included successful ablation, adverse effects, and length of stay. Ten studies that included 3821 patients met inclusion criteria, including 6 RCTs and 4 observational studies. There was no difference in long-term cure recurrence rates (RR, 0.88; 95% CI, 0.62-1.27, P = .50) or successful remnant ablation (RR, 0.95; 95% CI, 0.87-1.03; P = .20) between low-activity and high-activity RAI. In this systematic review and meta-analysis, low-activity RAI was comparable with high-activity RAI regarding successful ablation and recurrence rates. This suggests that low-activity RAI is preferable to high-activity in low- and intermediate-risk DTC because of its similar efficacy but reduced morbidity. PROSPERO Identifier: CRD42020166780.

Optimal Timing of Initiating Dynamic Risk Stratification During the Early Postoperative Period in Patients with Differentiated Thyroid Carcinoma After Thyroidectomy and Radioactive Iodine Remnant Ablation.

This study investigated the optimal timing to initiate assessment of the response to initial therapy during the early postoperative period in patients with differentiated thyroid carcinoma (DTC) using dynamic risk stratification (DRS). This historical cohort study included 510 patients with DTC who underwent a total thyroidectomy followed by radioactive iodine (RAI) remnant ablation. DRS for these patients was categorized into subgroups according to the time into the follow-up period at which the response to initial therapy was assessed. The ability of each DRS subgroup to predict the long-term structural recurrence of cancer was compared using the proportion of variance explained (PVE) from logistic regression models. The median follow-up period was 108 months. Structural recurrence occurred in 7.6% of patients (n=39/510). The PVE for long-term structural recurrence was higher among DRS subgroups (28.8-34.19%) compared with the American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis staging system (both the 7th and 8th editions; 4.01% and 6.13%, respectively) and the American Thyroid Association initial risk estimate (4.59%). Among the DRS subgroups, DRS assessed between 2 and 3years after the initial surgery was associated with the highest PVE (34.19%). The first assessment of DRS optimally predicts long-term structural recurrence in patients with DTC who underwent a total thyroidectomy and subsequent RAI remnant ablation at that 2- to 3-year postoperative period.

The Optimal Activity of Radioactive Iodine for Remnant Ablation in Low/Intermediate Risk Differentiated Thyroid Carcinoma: A Continuous Controversy and Meta-Analysis.

Radioactive iodine (RAI) is widely used for remnant ablation in low/intermediate differentiated thyroid carcinoma (DTC). However, the optimal effective dose that overweighs the benefits over unwanted side effects is a matter of controversy. This meta-analysis aimed to assess low versus high doses of RAI activity for DTC remnant ablation. Two authors independently searched PubMed and Cochrane Library using the keywords low dose radioactive iodine, high dose radioactive iodine, low-risk/intermediate risk, differentiated thyroid carcinoma, and remnant ablation. Two hundred and twenty references were identified when limiting the engine to controlled trials in English and during the period from January 2010 to December 2020. Nine trials (five from Europe and four from Asia) including 3137 patients fulfilled the inclusion and exclusion criteria. The data were then entered in an extraction sheet detailing the trial information including the author's name, year of publication, country, and type of surgery, preparation for RAI, the patients and control number in the low and high-dose groups, follow-up period, and the results. Out of 220 articles retrieved, nine controlled trials were included (follow-up period range, six months to 12 years, 3137 patients, and low risk of bias). The analysis favored the high dose for remnants ablation, odd ratio, 0.73, 95% CI, 0.50-1.07; P-value for the overall effect was 0.10. However, the results were limited due to the significant heterogeneity observed (56%, P-value 0.03). High-dose RAI was better for DTC remnants ablation. Further studies focusing on intermediate-risk DTC and adjusting for preoperative and postoperative factors are recommended.

The place of radioactive iodine remnant ablation in papillary thyroid microcarcinoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Experiences of low iodine diets in the treatment of differentiated thyroid cancer with radioactive iodine ablation therapy.

International guidelines on the treatment of differentiated thyroid cancers (DTC) promote the use of low iodine diets (LID) prior to radioactive iodine remnant ablation (RIA), as high iodine status may interfere with radioiodine uptake. Most UK treatment centres adhere to these guidelines and advise people to consume a LID. There is limited research as to how people cope with the LID or its impact on daily life and wellbeing, and no studies have been conducted in the UK. This study explored peoples' views and experiences in relation to consuming a LID during treatment for DTC with RIA. Twenty-eight semi-structured interviews were conducted with people from across three treatment centres where differing advice had been delivered regarding a LID. Interviews were recorded, transcribed verbatim and key themes were developed through inductive thematic analyses. Individuals advised to consume a LID believed that adhering to the diet would help their treatment. Most restricted their diets beyond what was recommended and there was confusion surrounding what they could eat as part of the diet. Food selection and preparation were important which included substitution of foods and ingredient checking. Being on the diet was considered to have both a physical and psychological impact. The findings of this study provide a qualitative insight into the lived experiences of people with DTC in relation to consuming a LID. The results have relevance for professionals providing dietary guidance at oncology centres treating patients with RIA therapy in the UK.

MON-494 Quality of Life in Patients with Papillary Thyroid Microcarcinoma According to the Treatment: Total Thyroidectomy Versus Total Thyroidectomy with Radioactive Iodine Remnant Ablation

Background: Recently, the role of radioactive iodine (RAI) ablation in the treatment of low risk differentiated thyroid carcinoma (DTC), especially for papillary thyroid microcarcinoma (PTMC), is controversial. This study aims to compare quality of life (QoL) parameters in patients with PTMC underwent total thyroidectomy (TT) versus TT with RAI ablation. Methods: In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: 12-item short-form health survey (SF-12), thyroid cancer specific quality of life (THYCA-QOL), and fear of progression (FoP). Results: The TT and TT with RAI groups comprised 107 and 183 patients, respectively. The TT with RAI group had significantly lower serum TSH level than TT group. However, after matching of TSH level between the groups (TT with RAI = 100, TT = 100), there was no significant difference in baseline characteristics. According to the SF-12, the score for general health showed significantly lower in TT with RAI group than TT group (p = 0.047). The THYCA-QOL also showed statistically significant difference in felt chilly score between the groups (p = 0.023). No significant differences in FoP scores were seen between the groups. Conclusion: Patients with PTMC underwent TT with RAI ablation experienced more health-related problems than those managed by TT alone. These findings support RAI ablation should be carefully determined in patients with low-risk DTCs.

Complex management decisions in a woman with concurrent primary hyperparathyroidism and metastatic papillary thyroid carcinoma, both presenting during pregnancy.

SummaryA 40-year-old woman was hospitalised at 25-week gestation following a diagnosis of severe symptomatic hypercalcaemia (adjusted serum calcium 3.02 mmol/L). A diagnosis of primary hyperparathyroidism (PHP) was made on the basis of elevated parathyroid hormone (PTH) 11.2 pmol/L (reference range 1.5–6.9) and exclusion of familial hypocalciuric hypercalcaemia. Ultrasound examination of the neck did not convincingly demonstrate an abnormal or enlarged parathyroid gland and parathyroid scintigraphy was not performed due to maternal choice relating to perceived radiation risk to the foetus. At neck exploration during the 28th week of pregnancy a right lower pole parathyroid lesion was excised together with two abnormal lymph nodes (largest 1.6 cm). Histology confirmed a parathyroid adenoma and also papillary thyroid carcinoma deposits in the two resected lymph nodes. Post-operatively, levels of adjusted serum calcium normalised and pregnancy progressed uneventfully to term. Total thyroidectomy was performed 2 weeks after delivery revealing two small foci of papillary micro-carcinoma (largest 2.3 mm, one in each thyroid lobe) with no evidence of further metastatic tumour in lymph nodes removed during functional neck dissection. Radioiodine remnant ablation (RRA) was performed 2 months post thyroidectomy to allow for breast involution. The patient remains in full clinical and biochemical remission 9 years later. We present and review the difficult management decisions faced in relation to the investigation and treatment of PHP in pregnancy, further complicated by incidentally discovered locally metastatic pT1aN1aM0 papillary thyroid carcinoma.Learning points:PHP may have serious consequences during pregnancy and usually requires surgical management during pregnancy to reduce the risk of maternal and foetal complications. The indications for and optimal timing of surgical management are discussed.Localisation by parathyroid scintigraphy is controversial during pregnancy: modified dose regimes may be considered in preference as an alternative to unguided neck exploration.Breastfeeding is contraindicated for 6–8 weeks before radioactive-iodine remnant ablation (RRA) to prevent increased breast uptake. Breastfeeding is further contra-indicated until after a subsequent pregnancy.Incidentally discovered differentiated thyroid carcinoma (DTC) in cervical lymph nodes in some cases may be managed expectantly because in one quarter of thyroidectomies the primary tumour remains occult.

Radioiodine remnant ablation in papillary thyroid microcarcinoma: a meta-analysis.

The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing sharply, the current statement about whether PTMC patients should undergo radioactive iodine (RAI) remnant ablation is still controversial, mainly because it is uncertain whether RAI treatment can reduce the recurrence rate. To evaluate the effectiveness of RAI remnant ablation for thyroid cancer-related outcomes of PTMC patients. We comprehensively searched PubMed, Cochrane Library, Scopus and Science Direct for studies that compared the effectiveness after total-thyroidectomy or near total-thyroidectomy, with or without RAI remnant ablation treatment. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. Twenty-two studies, which included 8724 patients, met our search criteria and were assessed. For PTMC patients treated by total thyroidectomy or near-total thyroidectomy, the locoregional recurrence rates were 1.92 and 7.36% [risk ratio (RR)=0.45; 95% confidence interval (CI)=0.18-1.11; P=0.08] for patients with or without RAI treatment respectively, the distant metastasis rates were 1.39 and 2.46% (RR=0.64; 95% CI=0.28-1.48; P=0.30), and the thyroid cancer-related mortality rates were 0.98 and 1.76% (RR=0.68; 95% CI=0.22-2.09; P=0.50). For PTMC patients who have already treated by total thyroidectomy or near-total thyroidectomy, incremental RAI remnant ablation may significantly improve thyroid cancer-related outcomes.

Lobectomy in patients with differentiated thyroid cancer: indications and follow-up.

The extent of thyroid surgery for patients with low- and intermediate-risk differentiated thyroid carcinoma (DTC), with a primary tumour <4 cm and no extrathyroidal extension (ETE) or lymph node (LN) metastases, has shifted in a more conservative direction. However, clinicopathological risk factors, including microscopic ETE, aggressive histology, vascular invasion in papillary thyroid carcinoma (PTC) and intermediate volume of LN metastases, can only be identified after completing thyroid lobectomy. It is controversial whether patients with these risk factors should immediately undergo complete thyroidectomy and/or radioactive iodine remnant ablation or should be monitored without further treatments. Data are conflicting about the prognostic impact of these risk factors on clinical DTC outcomes. Notably, the recurrence rate in patients who underwent thyroid lobectomy is low and the few recurrences that develop during long-term follow-up can readily be detected by neck ultrasonography and treated by salvage surgery with no impact on survival. These findings suggest that a more conservative approach may be a preferred management strategy over immediate completion surgery, despite a slightly higher risk of structural recurrence. Regarding follow-up of post-lobectomy DTC patients, it is reasonable that an initial risk stratification system based on clinicohistological findings be used to guide the short-term follow-up prior to evaluating the response to initial therapy and that the dynamic risk stratification system based on the response to initial therapy be used to guide long-term follow-up.

SUN-621 Lessons from beyond the Graves'

Introduction: The coexistence of thyrotoxicosis and thyroid carcinoma is a well-recognised clinical phenomenon. Patients with Graves’ disease have an increased risk of developing thyroid carcinomas than in patients with toxic adenoma or toxic multinodular goiter. We report a patient with Graves’ disease who had a ‘silent’ thyroid cancer. Clinical Case: A 20 year-old female was diagnosed with Graves’ disease. She had clinical signs of Graves’ ophthalmopathy, a thyroid goiter, sinus tachycardia and unintentional weight loss. Her TSH level was <0.005 mIU/L [0.40 - 3.50 mIU/L], free T4 level was 40.9 pmol/L [9.0 - 19.0 pmol/L], free T3 level was >46.1 pmol/L [2.6 - 6.0 pmol/L] and TSH receptor antibody (TRAb) level was 27.5 IU/L [<1.0 IU/L]. She denied prior head/neck irradiation or a family history of thyroid disorders. She was commenced on carbimazole. Her initial thyroid ultrasound (January 2016) demonstrated a heterogenous, hypervascular goiter (right lobe measured 65 x 31 x 25 mm and left lobe measured 50 x 21 x 31 mm). On her repeat thyroid ultrasound (April 2017), the heterogeneous hypervascular goiter had increased in size (right lobe 81 x 37 x 36 mm and left lobe 64 x 31 x 36 mm). A thyroid technetium scan identified diffuse radiotracer uptake (82.51%), consistent with Graves’ disease. Due to refractory Graves’ disease and the presence of Graves’ ophthalmopathy, a total thyroidectomy was performed (February 2018). Surprisingly, post-operative histopathology identified a 60 mm papillary thyroid carcinoma in the right lobe and a 36 mm papillary thyroid carcinoma in the left lobe, with lymphovascular and adipose tissue invasion. The tumours were negative for BRAF V600E. The remaining thyroid tissue showed Graves’ thyroiditis. Six weeks post-thyroidectomy, she had a thyroglobulin level at 16.3 μg/L [0 - 28 μg/L], undetectable anti-thyroglobulin antibody and TRAb level at 4.4 IU/L. Radioactive iodine remnant ablation was performed (August 2018) with steroid cover for persisting Graves’ ophthalmopathy. Her whole body I-131 scan identified residual thyroidal type tissue in the thyroid bed and diffuse uptake throughout both lungs, likely secondary to inflammation from a flu-like illness prior to her scan. Her thyroglobulin levels had reduced to 1.1 μg/L, with TSH level of 12 mIU/L, free T4 level of 18 pmol/L and free T3 level of 3.3 pmol/L. Conclusions: Patients with Graves’ disease have an increased risk of thyroid carcinomas, possibly related to TSH receptor antibodies. It is usually either clinically apparent or occult micro-carcinomas. Large papillary thyroid carcinomas in Graves’ disease not detected by thyroid technetium scan or thyroid ultrasound is rare.

Stimulated Thyroglobulin and Thyroglobulin Reduction Index Predict Excellent Response in Differentiated Thyroid Cancers.

Despite its good prognosis, differentiated thyroid cancer (DTC) is characterized by high rates of disease persistence and recurrence. Estimation of long-term remission (excellent response) thanks to specific parameters could help to individualize the active surveillance schedule. Evaluation of the ability of stimulated thyroglobulin (Tg) and Tg reduction index (TRI) to predict long-term remission in patients with DTC managed by thyroidectomy and radioactive iodine (RAI) remnant ablation. Observational retrospective study of 1093 patients treated for DTC between 1995 and 2010. Preablation stimulated thyroglobulin (presTg) was measured under thyroid hormone withdrawal just before RAI. Recombinant human TSH-stimulated thyroglobulin (sTg) was measured at first evaluation of the initial management 6 to 12 months after RAI. TRI was calculated based on pre-Tg and sTg. After univariate and multivariate analyses, lymph node invasion (N1, OR = 2.08; 95% CI, 1.19 to 3.64), presTg (OR = 4.04; 95% CI, 2.56 to 6.38), sTg (OR = 2.62; 95% CI, 2.05 to 3.34), and TRI (OR = 0.43; 95% CI, 0.21 to 0.88) were identified as independent prognostic factors influencing the rate of disease persistence or recurrence after the initial management. Receiver operating characteristic analysis identified presTg cutoff (<10 µg/L) to predict excellent response, with a negative predictive value of 94%, and validated for higher stages (T3/T4, N1). Furthermore, sTg <1 µg/L predicts excellent response. TRI >60% for the entire cohort and 62.5% for locally advanced disease (T3/T4, N1) was sensitive predictor for excellent response. This study identifies presTg, sTg, and TRI as highly sensitive predictors of excellent response in patients with DTC and subsequently disease-free status. The cutoff of such parameters is also adapted for patients with higher tumor stages (T3/T4, N1).

Individualized Follow-Up Strategy for Patients with an Indeterminate Response to Initial Therapy for Papillary Thyroid Carcinoma.

The concept of a dynamic risk-stratification scheme has been suggested for individualized management of patients with papillary thyroid carcinoma (PTC). However, there is no specified follow-up strategy for patients with an indeterminate response. This study evaluated 403 PTC patients who had an indeterminate response during the first 12-24 months after initial therapy. All patients underwent total thyroidectomy with radioactive iodine remnant ablation. Patients were further classified into three groups based on risk of structural persistence/recurrence: a Tg+ group (detectable thyroglobulin [Tg], regardless of antithyroglobulin antibody [TgAb] or imaging findings; 196 patients), a TgAb+ group (positive results for TgAb with undetectable Tg, regardless of imaging findings; 46 patients), and an Image+ group (nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, with undetectable Tg and negative results for TgAb; 161 patients). With a median of 9.6 years (interquartile range 7.7-11.2 years) of follow-up, 56 (14%) PTC patients had structural persistent/recurrent disease: 50 (89%) at locoregional sites and six (11%) at distant sites. The recurrence rate in Tg+, TgAb+, and Image + groups were 26.5%, 8.7%, and 0%, respectively. The median time to detection of structural persistent/recurrent disease from the initial thyroid surgery was 3.7 years (interquartile range 2.5-6.3 years). The optimal cutoff stimulated Tg level to predict structural persistent/recurrent disease was 3.1 ng/mL in the Tg+ group. This classification system revealed higher predictability of structural persistent/recurrent disease than the tumor-node-metastasis staging system and American Thyroid Association risk stratification (proportion of variation explained: 15.7% vs. 2.4% and 0.9%, respectively). Six (3%) patients with distant metastatic disease were all classified in the Tg+ group, and all had lung metastasis. The findings suggest a more individualized follow-up strategy for patients with an indeterminate response. More careful evaluation, including early evaluation of distant metastasis, is necessary in patients with elevated Tg levels. However, for patients testing positive for TgAb or those with only nonspecific imaging findings, regular follow-ups of Tg and TgAb levels and neck ultrasonography are sufficient.

Comparison of short-term oncologic outcome of robotic thyroid surgery using dynamic risk stratification: A propensity score–matched comparison study

The long-term oncologic outcome of robotic surgery for thyroid cancer is not well established. The aim of this study was to predict the long-term oncologic outcome of robotic surgery by using dynamic risk stratification in classic papillary thyroid carcinoma. A total of 444 propensity score-matched pairs of patients with papillary thyroid carcinoma treated with robotic surgery and conventional open surgery were classified into 4 response-to-therapy categories. The results were compared between the robotic surgery and open surgery groups. The median follow-up duration was 60 months. After propensity score matching, the robotic surgery group showed less extensive thyroid surgery and lymph node dissection and a higher proportion of patients who underwent radioactive iodine remnant ablation than the open surgery group; however, the dynamic risk stratification did not differ between the 2 groups (P = .086). The long-term oncologic outcome of robotic surgery is expected to be comparable with that of open surgery based on the dynamic risk stratification.

The predictive value for excellent response to initial therapy in differentiated thyroid cancer: preablation-stimulated thyroglobulin better than the TNM stage.

This study aimed to identify the predictive value of the low preablation-stimulated thyroglobulin (ps-Tg, <2 ng/ml) for excellent response to radioiodine remnant ablation in differentiated thyroid carcinoma. A total of 398 consecutive patients who underwent total thyroidectomy and radioactive iodine remnant ablation therapy were reviewed retrospectively. Each patient was risk-stratified using the American Joint Cancer Committee and risk staging systems and using response to the initial therapy reclassification system. ps-Tg was defined as less than 2 ng/ml with negative thyroglobulin antibody under thyroid-stimulating hormone stimulation. A multivariate analysis was carried out for ps-Tg, TNM stage, and other potential clinical and pathologic factors. We followed the patients for a median of 32.7 months. Overall, an excellent rate of response was achieved in 367 (92.2%) of the 398 patients. The only variable found to be associated with excellent response was ps-Tg (odds ratio=2.530, P=0.009) by multivariate analysis. The subgroups with 0<ps-Tg<1 ng/ml had a higher success ablation rate than the patients with 1≤ps-Tg<2 ng/ml. Overall, 31 patients were not achieving an excellent response, and most of them showed an indeterminate response. Only two patients who achieved an excellent response were confirmed to have developed recurrence in the follow-up, both in the local regional lymph nodes. There is a good probability that most low ps-Tg (<2 ng/ml) patients can achieve an excellent response. ps-Tg is the essential and independent predictor for an excellent response in the patients with ps-Tg less than 2 ng/ml, which is better than TNM stage.