Recurrent Differentiated Thyroid Cancer Research Articles

Abstract 5284: Recurrent Middle Eastern differentiated thyroid carcinoma has worse outcome than persistent disease

Abstract Background: Differentiated Thyroid Cancer (DTC) is the most common endocrine malignancy. Despite its excellent prognosis, recurrent and persistent disease remain major challenges after initial treatment. Although most studies have considered persistence and recurrent as a single entity, emerging studies to differentiate recurrent and persistent disease are controversial and study on recurrent and persistent DTC from Middle Eastern ethnicity is lacking. Methods: We retrospectively analyzed 1822 patients who underwent surgery ± I131 treatment for DTC with a median age of 38.9 years and median follow-up of 90 months. Results: We found a similar prevalence rate of persistent and recurrent disease (16.4% vs. 16.6%) in Middle Eastern DTC patients. Relative to patients with persistent disease, patients with recurrent disease were significantly older (median age 36.1 vs. 45.8 years; p < 0.0001), were more likely to have ATA high risk tumors (p < 0.0001) and had a higher rate of distant metastasis (p < 0.0001). However, structural disease had an almost similar frequency in both recurrent and persistent disease (72.2% vs 73.3%). On multivariant logistic regression analysis, both T status and N status are independent predictors for both recurrent and persistent disease. However, older age, extrathyroidal extension and the presence of distant metastasis were independent predictors of only recurrent disease. In addition, patients with recurrent disease had significantly worse overall survival (OS; p < 0.0001) and cancer specific survival (CSS; p < 0.0001), which remained significant in multivariate Cox proportional hazard model (Hazard ratio = 2.72; 95% confidence interval = 1.20 - 7.01; p = 0.0153 for OS and Hazard ratio = 5.09; 95% confidence interval = 2.10 - 15.24; p = 0.0001 for CSS). Conclusion: Although persistent and recurrent disease in Middle Eastern DTC have similar frequencies, recurrent disease had worse outcome compared to persistent disease. This has great potential clinical relevance to differentiate recurrene from persistence for therapeutic and follow-up approach for improving outcomes of DTC patients from Middle Eastern ethnicity. Citation Format: Sandeep K. Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Nabil Siraj, Saeeda O. Ahmed, Zeeshan Qadri, Saud Azam, Khawla S. Al-Kuraya. Recurrent Middle Eastern differentiated thyroid carcinoma has worse outcome than persistent disease. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5284.

Comparison of staging and recurrence predictors in patients with differentiated thyroid cancer between the 7th and 8th editions of the American Joint Committee on Cancer staging systems.

The predictive value of American Joint Committee on Cancer (AJCC) 8 for recurrence in differentiated thyroid cancer (DTC) is not known. We aimed to compare AJCC 7 and 8 regarding the differences in staging and recurrence predictors in DTC. Demographic, clinical (duration of disease and follow-up, the extent of surgery), laboratory (TSH, fT4, thyroglobulin, and antithyroglobulin), pathological (type of thyroid cancer, localization, multifocality, diameter, extrathyroidal extension [ETE], and lymph node [LN] metastasis), and imaging findings (sonography, and whole-body scan), and follow-up features (metastases, recurrence and/or persistence, and RAI need) were retrospectively analyzed in adult patients with DTC followed-up for at least six months. Staging was determined in accordance with AJCC 7 and AJCC 8, prediction of recurrence and persistence by ATA risk stratification, and death risk by AMES systems. The alterations in staging and recurrence predictors were analyzed. A majority of study patients (N.=524) were female (N.=424) and diagnosed with papillary cancer (N.=511), the median age at diagnosis was 44. 97.89% (N.=93) of stage 2-4 patients (N.=95) in AJCC 7 were down-staged in AJCC 8. We down-staged 41 patients of 45-55 years of age into stage 1 in AJCC 8 independent of LN status. A percentage of 26.71% of patients (N.=140) did have persistence, 9.54% (N.=50) persistence at the last follow-up, and 9.54% (N.=50) had recurrence. According to AJCC 8, T4 and AMES high risk were predictors for recurrence (hazard ratio: 3.053, P=0.023; hazard ratio:2.465, and P=0.005; respectively). Both AJCC 7 and 8 were associated with recurrence (P=0.008 and P<0.001, respectively). Stage 4 in AJCC 7, and stages 3 and 4 in AJCC 8 better predicted the probability of recurrence. Our findings suggest that AJCC 8 better predicted the recurrence in DTC than AJCC 7. In AJCC 8, T4 tumor, AMES high risk, stages 3 and 4 predicted recurrence. The vast majority of patients with stages 2-4 in AJCC 7 were down-staged in AJCC 8.

Unilateral Multifocality Is Not a Risk Factor for Recurrence After Thyroid Lobectomy: A Study of 1,684 Patients With Differentiated Thyroid Cancer.

Many studies indicate that multifocality is associated with high-risk features of differentiated thyroid cancer (DTC). Herein, we evaluated the impact of the unilateral multifocality on post-lobectomy recurrence in patients with DTC. We retrospectively analyzed 1,684 patients with DTC who underwent thyroid lobectomy from 2008 to 2015 using logistic regression models to calculate the relative risk on post-lobectomy recurrence. Tumor diameter increased from 4.9 mm to 8.1 mm and the proportion of extrathyroidal extension (ETE) and unilateral multifocality progressively increased from 2008 to 2015 (2.1% to 24.3% and 4.2% to 22.8%, respectively). During the 88.6-month follow-up period, 67 (3.98%) recurrences and 2 (0.12%) deaths were observed. There were 269 (16.0%) multifocal DTC cases. There was no significant difference between the multifocal and unifocal groups in terms of the proportion of recurrences (5.2% vs. 3.7%) and distant metastasis (0.4% vs. 0.1%). Logistic regression analysis revealed age <42.5 years (OR=1.83), tumor diameter greater than 7.5 mm (OR=1.89), and N1a (OR=2.04) were potent risk factors for post-lobectomy recurrence. Conversely, male sex (OR=0.77; p=0.407), ETE (OR=1.16; p=0.698) and multifocality (OR=1.23; p=0.526) were not risk factors for recurrence after thyroid lobectomy. A positive node ratio (PNR) ≥42.0%, N1a stage, a tumor diameter ≥7.5mm and age <42.5 years were significant risk factors for recurrence (Log-rank p=0.001, p=0.001, p=0.004 and p=0.009, respectively). Contrariwise, multifocality and ETE were proven to not be risk factors for DTC recurrence after thyroid lobectomy (Log-rank p=0.099 and p=0.126, respectively). Unilateral multifocality was not a risk factor for DTC recurrence after thyroid lobectomy and could not be considered an indication for immediate completion or total thyroidectomy.

PSAT380 Characteristics and prognosis of Differentiated Thyroid Cancer in patients with Graves Disease

Abstract Background The incidence of thyroid cancer in the United States and worldwide has increased 300% over the last three decades.1 Graves’ disease (GD) is the most common cause of hyperthyroidism. GD occurs due to activating antibodies to the TSH receptor. Thyroid-stimulating antibodies can result in intrinsic and genetic factors to favor the tumor growth process.2 Recent studies show that the incidence of thyroid cancer is higher among patients with GD when compared to toxic multinodular goiter.3 The current study compares the outcomes of Differentiated Thyroid Cancer (DTC) in patients with GD with non-GD patients. Objective The aim of the study was to compare demographics, pathology, stage, and prognosis of DTC in patients with GD with non-GD patients. Methods This was a retrospective chart review of 42 patients with a diagnosis of DTC with or without GD. Patients were selected using HERON (Healthcare Enterprise Repository Ontological Narration) software. We compared age at diagnosis, type and size of the tumor, radioactive iodine (RAI) use, and DTC recurrence amongst patients with GD with non-GD patients. We used the Chi-square to test for independence among the categorical variables at a nominal level of 0.05. The comparison of continuous variables was based on the t-test. Results The mean age of patients was 50 years (range 23–86). Out of 42 patients, 29 patients had GD and 13 patients did not have GD. 92% had papillary thyroid cancer and the mean tumor size was 1.3 cm (range 0.09–7.5). 86% of the patients had Stage 1 and 2 DTC. Patients with GD were diagnosed with DTC at a younger age (mean age 46 years) when compared to the patients without GD (mean age 59 years) with a p-value of 0.013. There was no difference in patients with GD in regard to the type of DTC (P = 0.54) and the stage of DTC (p-value 0.139). Both groups of patients had a similar rate of recurrence and RAI use (Table). Conclusion The current study concludes that patients with GD were diagnosed with DTC at an earlier age when compared to patients without GD. The stage of DTC and recurrence rate were similar in the two groups. The study was limited to a small number of patients. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Results of surgical treatment for recurrent differentiated thyroid cancer at National Hospital of Endocrinology

Abstract Introduction: To evaluate the results of surgical treatment for recurrent differentiated thyroid cancer. Patients and methods: Descriptive study of 82 recurrent differentiated thyroid cancer patients underwent re-operated at National Hospital of Endocrinology from 2017 to 2020. Results: Mean age 44.2 ± 12.6 years, female/male = 3.3 / 1. Median recurrence times was 25 months. Patients detected the disease through regular health check was 82.9%. Physical examination revealed lesions 31,7%. Ultrasound revealed lesions 97.6%. Tg positive 81.7%, median 33.2; Anti-Tg positive 20.7%, median 22.6. Whole-body Scintigraphy was positive 47.6%. PET/CT positive 100%. Surgical techniques: Total thyroidectomy + cervical lymph nodes dissection accounted for 9.8%; cervical lymph nodes dissection only accounted for 90.2%. Location of cervical lymph node dissection: Central dissection 18.3%; lateral dissection 51.2%; Central &amp; lateral lymph nodes dissection accounted for 30.5%. The rate of invasion of recurrent block accounted for 23.2%. Complications that occurred during surgery including: major vascular injury 2.4%; laryngeal nerve injury 2.4%, tracheal injury 1.2%, parathyroid glands injury 3.6%, lymphatic vascular injury 6.1% were managed immediately during surgery. Post-surgical complications: bleeding 1.2%; respiratory failure 1.2%; hoarseness 3.6%; Hypocalcemia 11.0%; Hematoma 3.6%; Chyle leak 7.3%, in which 1 case (1.2%) had to have stitches sutured. Vocal fold paralysis after in 3 months later (2.4%) and 1 case hypoparathyroidism (1.2%); Tg positive 70.7%, median 14.3. Anti–Tg positive 13.4%, median 16.2. 18.3% of patients treated with hormone only; 81.7% of patients treated with I131. Conclusion: Surgery is a safe and effective treatment for recurrent differentiated thyroid cancer. Keywords: Recurrent differentiated thyroid cancer, lymph node neck dissection

Use of multikinase inhibitors/lenvatinib concomitant with locoregional therapies for the treatment of radioiodine-refractory differentiated thyroid cancer.

Locoregional recurrence of differentiated thyroid cancer (DTC) occurs in 20% of thyroid cancer patients. Currently, there are many strategies for management of locoregional recurrence of DTC that lead to local control of the disease. The introduction of lenvatinib into the therapeutic armamentarium provides a new option for the treatment of radioiodine‐refractory DTC (RR‐DTC). However, results for simultaneous treatment with lenvatinib and locoregional therapies are unknown in patients with RR‐DTC. This paper reviews the current status of this approach and gives recommendations on the management of lenvatinib during concomitant locoregional procedures.

New PET Tracer [68Ga]FAPI-004 Outperforms [18F] FDG in a Series of 34 Patients with Recurrent Differentiated Thyroid Cancer

New PET Tracer [⁶⁸Ga]FAPI-004 Outperforms [¹⁸F] FDG in a Series of 34 Patients with Recurrent Differentiated Thyroid Cancer

A Retrospective Cohort Study with Validation of Predictors of Differentiated Thyroid Cancer Outcomes.

Background: The goal of radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is to treat metastasis and reduce recurrence risk. International guidelines provide broad risk stratification to aid treatment decisions, but a more nuanced approach to individualize care is warranted. We developed a predictive risk model for DTC. Methods: We performed a retrospective multivariable analysis of 899 patients who received RAI after thyroidectomy at a quaternary center in Australia between 2008 and 2016. Collected data included age, gender, histology, stimulated thyroglobulin (sTg), and 8th American Joint Committee Cancer (AJCC) staging. The ATA Modified Initial Risk (ATA) was calculated retrospectively. Recurrence was defined as clinically significant progression requiring either surgical intervention or administration of a second activity of RAI. Synchronous metastasis was defined as distant metastasis (i.e., outside of the neck) that was present at the time of diagnosis on structural imaging or initial post-iodine treatment scan. The features significantly associated with synchronous metastasis or recurrence were employed in the generation of a predictive risk model. A separate cohort of 393 patients who received RAI in 2017-2021 was used for validation. Results: On multivariate analysis, sTg ≥10 μg/L, extrathyroidal extension (ETE) and lymph node involvement predicted recurrence. Independent of ATA, patients with sTg ≥10 μg/L had a shorter disease-free survival (DFS) than those with sTg <10 μg/L (p < 0.001). The ETE stratified by four histological categories was significantly associated with worse DFS (p < 0.001). In a subset of patients, the presence of thyroglobulin antibody (TgAb) did not influence recurrence in patients with sTg <10 μg/L. On multivariate analysis, widespread ETE, sTg ≥10 μg/L, multifocal papillary thyroid cancer and follicular thyroid cancer were positively associated with synchronous metastasis. A predictive risk model was developed to estimate synchronous metastasis/recurrence risk and validated successfully in the second cohort. Conclusions: Our novel predictive risk model modifies and extends ATA stratification by including sTg and ETE, which we found to be independent predictors of both recurrence and synchronous metastasis in DTC.

Prognostic Value of Hybrid PET/MR Imaging in Patients with Differentiated Thyroid Cancer.

Simple SummaryHybrid positron emission tomography (PET)/magnetic resonance (MR) is an emerging imaging modality with great potential to provide complementary data acquired at the same time, under the same physiological conditions. We evaluated the prognostic value of hybrid 18F-fluorodeoxyglucose (FDG) PET/MR in patients with differentiated thyroid cancer (DTC) who underwent total thyroidectomy and radioactive iodine therapy for suspicion of disease relapse. Our findings suggest that hybrid PET/MR imaging may have the potential to improve the information content of one modality with the other and would offer new opportunities in patients with DTC. However, there is need of more clinical studies to understand the additional value of 18F-FDG PET/MR in patients with DTC.Background: Hybrid positron emission tomography (PET)/magnetic resonance (MR) is an emerging imaging modality with great potential to provide complementary data acquired at the same time, under the same physiological conditions. The aim of this study was to evaluate the prognostic value of hybrid 18F-fluorodeoxyglucose (FDG) PET/MR in patients with differentiated thyroid cancer (DTC) who underwent total thyroidectomy and radioactive iodine therapy for suspicion of disease relapse. Methods: Between November 2015 and February 2017, 55 patients underwent hybrid 18F-FDG PET/MR. Assessment of positive MR was made considering all sequences in terms of malignancy based on the morphological T2-weighted features and the presence of restricted diffusivity on diffusion-weighted imaging images and both needed to be positive on the same lesion. Both foci with abnormal 18F-FDG uptake, which corresponded to tissue abnormalities on the MR, and tracer accumulation, which did not correspond to normal morphological structures, were considered positive. Results: During follow-up (mean 42 ± 27 months), 29 patients (53%) had disease recurrence. In the Cox univariate regression analysis age, serum Tg level ≥ 2 ng/mL, positive short tau inversion recovery (STIR), and positive PET were significant predictors of DTC recurrence. Kaplan–Meier survival analyses showed that patients with Tg ≥ 2 ng/mL had poorer outcomes compared to those with serum Tg level < 2 ng/mL (p < 0.05). Similarly, patients with positive STIR and positive PET had a worst outcome compared to those with negative STIR (p < 0.05) and negative PET (p < 0.005). Survival analysis performed in the subgroup of 36 subjects with Tg level ≥ 2 ng/mL revealed that patients with positive PET had a worst outcome compared to those with negative PET (p < 0.05). Conclusions: Age, serum Tg level ≥ 2 ng/mL, positive STIR, and positive 18F-FDG PET were significant predictors of DTC recurrence. However, the serum Tg level was the only independent predictor of DTC. Hybrid PET/MR imaging may have the potential to improve the information content of one modality with the other and would offer new opportunities in patients with DTC. Thus, further studies in a larger patient population are needed to understand the additional value of 18F-FDG PET/MR in patients with DTC.

FDG PET/CT in differentiated thyroid cancer patients with low thyroglobulin levels.

To evaluate the usefulness of [18F]fluorodeoxyglucose (FDG) positron emissive tomography (PET)/CT in patients with low detectable thyroglobulin levels suspicious for persistent or recurrent differentiated thyroid cancer (DTC). A retrospective case series study evaluating FDG PET/CT in patients with detectable thyroglobulin (Tg) levels (≥0.20 and <10.00 ng/mL) after initial treatment with total thyroidectomy and I-131 thyroid remnant ablation for pT1-3aN0-1bM0 DTC. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of FDG PET/CT were calculated. Twenty-seven patients underwent FDG PET/CT. Median Tg level at FDG PET/CT was 2.00 ng/mL (range 0.30-9.00). FDG PET/CT was positive in 14 patients (51.9%): lesions suspicious for lymph node metastases were depicted in 12 patients, and lung metastases in 2. DTC was confirmed in 13/14 FDG PET/CT-positive patients. In 9/13 patients with a negative FDG PET/CT, DTC was confirmed ≤3 months after FDG PET/CT. The sensitivity, PPV, specificity and NPV were 59.1, 92.9, 80.0 and 30.8%, respectively. This case series shows that FDG PET/CT might be useful to detect persistent or recurrent DTC in patients with low detectable Tg. However, when FDG PET/CT is negative, this does not rule out DTC and further investigations are necessary.

Additive value of 18FDG-PET/CT to positive 131I whole body scan in recurrent differentiated thyroid cancer patients with potential influence on treatment strategy: single Egyptian center experience

BackgroundYears ago the utility of of18F-fluorodeoxyglucose-positron emission tomography/computerized tomography (18FDG-PET/CT) in differentiated thyroid cancer was confined mainly to cases with elevated serum thyroglobulin and negative 131I whole body scan. In this study, we try to assess the diagnostic performance of 18FDG-PET/CT in recurrent differentiated thyroid cancer patients with positive 131I whole body scan and in addition to evaluate the impact of 18FDG-PET/CT on the treatment strategy.ResultsThe 18FDG PET/CT detected tumor recurrence in 35 (81.3%) patients most of them (91.4%) were in stage IV, while the rest 8.5% was in stage III. No recurrence was detected among patients in stage II and III by 18FDG PET/CT.Regarding lesion-based analysis, sensitivity of 18FDG-PET/CT was superior to that of 131I post-therapeutic whole body scan (TxWBS) (78.2% vs. 69.4%, respectively), while both modalities had the same specificity (50%). 18FDG-PET/CT changed the treatment plan in 18 (41.6%) patients.Conclusion18FDG-PET/CT may be complementary to 131ITxWBS in high-risk DTC with impact on treatment strategy.

Methylation-Driven Gene PLAU as a Potential Prognostic Marker for Differential Thyroid Carcinoma.

Purpose: Aberrant DNA methylation plays a crucial role in the tumorigenesis of differentiated thyroid cancer (DTC); nevertheless, the factors leading to the local and regional recurrence of DTC are not well understood. This study aimed to establish the connection between DNA methylation-driven genes and the recurrence of DTC. Methods: RNA sequencing profiles and DNA methylation profiles of DTC were downloaded from The Cancer Genome Atlas (TCGA) database. Combined application of the methylmix R package and univariate Cox regression analyses were used to screen and distinguish prognosis-related methylation-driven genes. Multivariate Cox regression analyses were utilized to identify the target genes that were closely associated with the recurrence of DTC. Then, correlations between the expression levels of the target genes and the clinicopathological features were verified, as well as their potential biological functions. Results: A total of 168 Methylation-driven genes were differentially expressed in thyroid cancer, among which 10 genes (GSTO2, GSTM5, GSTM1, GPX7, FGF2, LIF, PLAU, BCL10, SHARPIN and TNFRSF1A) were identified as Hub genes. We selected PLAU for further analysis because PLAU was most strongly correlated with DTC recurrence and the DNA methylation levels of PLAU were closely associated with multiple clinicopathological features of DTC. PLAU was significantly upregulated in DTC, and patients with a high expression level of PLAU had a higher risk of recurrence (p < 0.05). Functional predictions suggested that PLAU-related genes were mainly involved in the regulation of immune-related signaling pathways. Moreover, the mRNA level of PLAU was found to be positively correlated with the cell markers of neutrophils and dendritic cells. In addition, we found that two DNA methylation sites (cg06829584, cg19399285) were associated with abnormal expression of PLAU in DTC. Conclusion: The methylation-driven gene PLAU is an independent risk factor for the recurrence of DTC and it functions as an oncogene through the regulation of immune-related signaling pathways, which offers new insight into the molecular mechanisms of thyroid cancer and provides new possibilities for individualized treatment of thyroid cancer patients.

Circulating MicroRNA Profiles as Potential Biomarkers for Differentiated Thyroid Cancer Recurrence.

Circulating microRNAs (miRNAs) are emerging biomarkers of thyroid cancer. This study sought to identify the profile of circulating miRNAs and its response to human recombinant TSH (rhTSH) in thyroid cancer patients with recurrent/persistent disease. We obtained serum samples from 30 patients with differentiated thyroid cancer, 14 with recurrent/persistent disease and 16 with complete remission. We used next-generation sequencing to define the miRnomes along with a comprehensive quantitative PCR (qPCR) validation using 2 different platforms. We made a transversal study by comparing serum miRNA profiles of patients with or without recurrent/persistent disease and a longitudinal study looking at differences before and after rhTSH stimulation. Selected miRNAs were then studied in human thyroid cancer cell lines TPC-1, FTC-133, and OCUT-2 in response to TSH stimulation. We could not demonstrate any consistent differences in serum profiles of known miRNAs between patients with and without recurrent/persistent disease or before and after rhTSH stimulation. However, our sequencing data revealed 2 putative novel miRNAs that rise with rhTSH stimulation in the serums of patients with recurrent/persistent disease. We further confirmed by qPCR the upregulation of these putative miRNAs both in serums and in TSH-stimulated cells. We also show miRNAs that are good candidates for housekeeping genes in the serum of patients independently of the levels of TSH. The present study does not provide evidence that known miRNAs can be used as circulating markers for recurrence of thyroid cancer. However, we suggest that novel miRNA molecules may be related to thyroid cancer pathogenesis.

Interesting False Positive Radioiodine Uptake on I-131 Whole Body Scintigraphy with Different Mechanisms in Two Patients Diagnosed Differentiated Thyroid Carcinoma: A Review of Literature

Introduction: Radioiodine total body scan is used to detect recurrent differentiated thyroid cancer in neck and metastatic lesions. We recently encounter cases of false positive in two veteran: one suffered from shrapnel wound 45 years ago in the back; while another veteran had focal contamination underneath his Dutch beard. Cases Report: The first case was a 69-years-old Vietnam War male veteran with paraplegia and a history of papillary thyroid carcinoma, he was s/p total thyroidectomy 5/2013 (T3, N1). He received 143 mCi following the surgery. Ultrasound examination revealed recurrence, which was treated with left neck dissection and followed with a dose of 254 mCi of I-131 on 8/2014. A postRAI treatment scan revealed a focal uptake in the posterior component of T10/T11 vertebra, which, in retrospect, was present in the prior post-ablation scan in 7/2013 without any interval change. A chest CT in 9/2014 revealed a sub-centimeter metallic density in the same site; likely shrapnel deposited 45 years ago. Thus, focal radioiodine uptake likely relates to inflammatory/ benign etiology. Suppressed Tg was 3.9 in 8/2015, decreased from 5.3 ng/mL in 2/2015. The second case was a 41-years-old male veteran s/p total thyroidectomy with central neck dissection in 10/2018 and found one positive LN on left. Final path report was papillary thyroid cancer - staging T1a, N1. The patient received 75.9 mCi of I-131 for remnant ablation in 12/2018 and followed with a total body scan, which showed a focal activity subjacent to left submandibular gland. The activity persisted in a repeat scan after the patient claiming had thoroughly washed his Dutch-style beard. The SPECT/CT revealed the focal activity was not in the left submandibular area and might represent a contamination in the adjacent mustache. This was confirmed by a repeat planar image performed after the beard was shaved off. Discussion: Focal radioiodine uptake is a sensitive marker for detection of recurrence of differentiated thyroid cancer, s/p total thyroidectomy and RAI ablation. However, radioiodine ptake is not specific for thyroid tissue. It can also be seen in healthy tissue, including thymus, breast, liver, and gastrointestinal tract, or in benign diseases, such as cysts and inflammation, or in a variety of benign and malignant non-thyroidal tumors, which could be mistaken for thyroid cancer. These case studies provide examples of potential false-positive uptake of radioiodine in the whole-body scan and illustrate how such unexpected findings can be appropriately evaluated. Chronic trauma may recruit leukocytes that known to induce iodide organification by means of a myeloperoxidase. Therefore, retention of radioiodine in leukocytes of posttraumatic tissues may also explain various reports of false-positive uptake in sites of inflammation. Secretion of mucin containing iodide salts has also been suggested as another possible mechanism of iodine accumulation associated with chronic inflammatory conditions. Since radioiodine, normally concentrates in saliva, in-patient with beard should always watch for hidden contamination. Conclusion: Wounds caused by shrapnel fragments could be a common problem for veterans returning from overseas. Recognizing that false positive results could occur in RAI total body scan is clinically important.

Can ultrasensitive thyroglobulin immunoassays avoid the need for ultrasound in thyroid cancer follow-up?

Differentiated thyroid cancer (DTC) is the most common endocrine neoplasm, with a rising incidence and a long life expectancy. It has recently been suggested that patients with low- and intermediate-risk DTC with a good response to treatment at one year could be followed up using only highly sensitive immunoassays for thyroglobulin (Tg). The aim of this study was to examine the serum Tg levels in a series of DTC patients with histologically proven persistent or recurrent diseases. The study involved 50 consecutive patients being routinely followed up at our center, whose clinical, histological, and biochemical data were retrospectively collected. The false-negative rate of ultrasensitive serum Tg assay was 14.3% (5/35) overall, and limited to anti-thyroglobulin autoantibodies (TgAb)-negative patients. Among them, only one patient had an excellent response to treatment at one-year follow-up and was diagnosed with a 4 mm recurrence, after more than seven years of periodic ultrasounds. The size of the neck lesion documented in the histological report was slightly larger in patients with detectable as opposed to negative Tg values (P < 0.05). Serum highly sensitive Tg is undetectable in a proportion of patients with a proven persistent or recurrent DTC. The reasons behind this phenomenon are still unknown. However, in low/intermediate-risk patients cured at one-year follow-up, highly sensitive Tg without neck US seems an appropriate strategy for patients' management.

Postoperative Radiotherapy in the Management of Advanced or Recurrent Differentiated Thyroid Cancer

To evaluate outcome and prognostic factors of postoperative radiotherapy for differentiated thyroid cancer (DTC).In this retrospective study, 80 patients who received postoperative radiotherapy for DTC from January 2000 to December 2019 were analyzed. The median follow-up duration was 7.5 years (range, 0.6-18.7 years).Thirty-three (41.3%) patients had recurrent tumor and 21 (26.3%) patients still had gross disease even after radical surgery. Cervical node metastasis was present in 54 (67.5%) patients, while 7 (8.75%) patients were presented with distant metastasis. The median total dose and fraction size were 63.0 Gy and 2.0 Gy, respectively. The 5-year locoregional recurrence free survival (LRFS) was 80.7% and the five-year overall survival (OS) was 89.1%. Multivariate analysis showed age ≥ 55 (HR 6.11; 95% CI 1.51-25.25), male (HR 3.22; 95% CI 1.02-11.11), gross residual disease after surgery (HR 2.80; 95% CI 1.01-7.77) and esophageal invasion (HR 5.50; 95% CI 1.38-21.93) were significantly associated with worse LRFS. However, only the age ≥ 55 (HR, 1.10; 95% CI, 1.03-1.18) and the presence of gross residual disease (HR, 4.56; 95% CI, 1.02-20.31) were significant prognostic factors for OS. No severe toxicity was reported.Postoperative radiotherapy can be one of the feasible and safe modalities for advanced or recurrent DTC, since the locoregional control was comparable to other studies despite unfavorable clinicopathologic elements of the study population. The age ≥55 and gross residual disease significantly affect both locoregional control and overall survival. However, due to the lack of a control in this study, there is a limitation to definitely confirm the efficacy of adjuvant RT and therefore a further study is necessary to find those who can benefit from it.

The Use of 18F-FDG PET/CT in Patients with Recurrent Differentiated Thyroid Cancer

Objectives: 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is used to monitor the recurrence in thyroid cancer patients when there is suspicion of metastases. De-differentiated lesions become 18F-FDG avid with a more aggressive clinical course. The aim of this study was to investigate the use of 18F-FDG PET/CT in differentiated thyroid cancer.Methods:Forty-six patients, either with a negative radioiodine scan or clinical progression and suspicions for metastases with differentiated thyroid cancer that were referred to our department for 18F-FDG PET/CT scan and evaluated retrospectively. PET/CT findings were correlated with clinical and histopathological findings, serum thyroglobulin (Tg), and anti-Tg levels.Results:Twenty-six patients (56.2%) were positive for recurrence in 18F-FDG PET/CT images. Positive 18F-FDG PET/CT findings were significantly correlated with the disease stage and Tg levels. Maximum standardized uptake value did not correlate with other findings or patients’ profiles. The cut-off value for Tg was at 52.5 ng/mL having 73.08% sensitivity, 75% specificity, 79.17% positive predictive value, and 68.18% negative predictive value for 18F-FDG PET/CT imaging.Conclusion: 18F-FDG PET/CT is useful for detecting recurrence in differentiated thyroid cancer. Increased Tg levels and stage of the disease were significantly correlated with 18F-FDG positivity. 18F-FDG positivity may also provide information about the de-differentiation process that may support the treatment plan.

Hybrid [18F]FDG PET/MR Has High Sensitivity and Specificity in the Detection of Recurrent Differentiated Thyroid Cancer

Clinical ThyroidologyVol. 33, No. 10 Thyroid CancerHybrid [18F]FDG PET/MR Has High Sensitivity and Specificity in the Detection of Recurrent Differentiated Thyroid CancerGunnar Moen and Martin BiermannGunnar Moen Neuroradiology, Department of Radiology, Haukeland University Hospital, Bergen, NorwaySearch for more papers by this author and Martin Biermann Nuclear Medicine/PET Center, Department of Radiology, Haukeland University Hospital, Bergen, Norway Department of Clinical Medicine, University of Bergen, Bergen, NorwaySearch for more papers by this authorPublished Online:7 Oct 2021https://doi.org/10.1089/ct.2021;33.447-451AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 33Issue 10Oct 2021 InformationCopyright 2021 American Thyroid Association, Inc.To cite this article:Gunnar Moen and Martin Biermann.Hybrid [18F]FDG PET/MR Has High Sensitivity and Specificity in the Detection of Recurrent Differentiated Thyroid Cancer.Clinical Thyroidology.Oct 2021.447-451.http://doi.org/10.1089/ct.2021;33.447-451Published in Volume: 33 Issue 10: October 7, 2021PDF download

Improving the prediction of persistent and recurrent differentiated thyroid cancer using the American Thyroid Association 2015 risk stratification system.

The 2015 American Thyroid Association risk stratification system (ATA RSS) is used in patients with differentiated thyroid carcinoma (DTC) to assess their risk of persistent/recurrent disease. Our aims were to validate the 2015 ATA RSS in a registry of DTC patients and to examine whether the addition of factors not included in it, such as pre-radioactive iodine therapy stimulated thyroglobulin (pre-RAI sTg), gender, and age could increase its predictive ability. We studied 403 patients with DTC, treated at a tertiary center from 1990 to 2018 and subjected to total thyroidectomy. All patients had received RAI therapy, except those with low-risk papillary microcarcinoma. Of our patients, 81.9% were women and 91.1% had papillary thyroid carcinoma. After a median follow-up of 5.0years, 53 cases of persistent and 21 cases of recurrent disease were recorded. The proportion of variance explained (PVE) regarding the outcome (presence or absence of recurrent/persistent disease) using the 2015 ATA RSS alone was 18.3% (persistence) and 16.9% (recurrence), increasing to 74.4% and 52.0%, respectively, when pre-RAI sTg was added to the logistic regression model. Gender and age were not associated with the disease outcome. In ROC analysis, pre-RAI sTg had a high predictive value for persistent (AUC 0.983, 95% CI 0.962-1.000) and recurrent disease (AUC 0.856, 95% CI 0.715-0.997). The optimal cut-offs and sensitivity, specificity, and positive and negative predictive value for pre-RAI sTg were the following: for persistence 12.75ng/ml, 100%, 90.5%, 64%, and 100%, and for recurrence 8.05ng/ml, 77.8%, 85.5%, 36.8%, and 97%. The 2015 ATA RSS displayed moderate performance in predicting recurrent/persistent disease in patients with DTC, which improved with the inclusion of pre-RAI sTg values; pre-RAI sTg was an independent predictor of the disease outcome, with high negative prognostic value.

PO-1021 Postoperative Radiotherapy in the Management of Advanced or Recurrent Differentiated Thyroid Cancer

PO-1021 Postoperative Radiotherapy in the Management of Advanced or Recurrent Differentiated Thyroid Cancer