Thyroglobulin Values Research Articles

Predictive value of thyroglobulin after radioiodine therapy for excellent response to treatment in postoperative thyroid cancer.

This study aimed to assess the usefulness of thyroglobulin (Tg) after radioiodine (RAI) therapy in predicting excellent response (ER) to therapy in postoperative differentiated thyroid cancer (DTC). A retrospective observational study was conducted on postoperative DTC patients who underwent RAI from August 2018 to December 2022. Various factors were analyzed to predict ER to treatment. This involved Tg under stimulation (sTg) before RAI, Tg immediately (imTg) 112 h post-RAI and imTg/sTg(rTg). Based on the efficacy of RAI, patients were categorized into two groups: ER and non-ER (NER). Univariate logistic analysis was utilized to compare parameters between the two groups, followed by binary logistic regression analysis on factors associated with ER. Receiver operating characteristic (ROC) curves were employed to evaluate the sensitivity, specificity, and optimal diagnostic cutoff points for parameters affecting ER. The analysis included 45 ER patients and 56 NER patients. Statistical significance was found in the binary logistic regression analysis for the number of lymph nodes in the lateral cervical region (P = 0.016), sTg (P = 0.021), and rTg (P ≤ 0.001) concerning ER. ROC curve analysis revealed that the rTg area under the curve was 0.845, with an optimal cutoff value of 11.78, sensitivity of 82.6%, and specificity of 74.5%. Post-RAI therapy, significant value is demonstrated by rTg with high sensitivity and specificity. This provides a foundation for the evaluation and decisions about DTC treatment in advance.

8549 A Pre-ablative Stimulated Thyroglobulin Value That Predicts ATA High Risk Patients and Their Treatment Response

Abstract Disclosure: H. Gondaliya: None. N. Nangadda: None. D. Bhat: None. K.S. Khadilkar: None. S. Kumbenahalli Siddegowda: None. B.G. Sooragonda: None. A. Shetty: None. S. Kannan: None. In ATA risk stratification system for differentiated thyroid cancer (DTC), one of the variables placing patients in ATA high risk category is thyroglobulin (Tg) suggestive of distant metastases. However there is no defined cut-off Tg level for guiding the clinicians. We aimed to determine pre-ablative stimulated Tg (psTg) value that predicts ATA high risk patients (based on non-Tg parameters) and their treatment response on follow up. This was an ambispective observational study of 285 patients with DTC treated at our centre from April 2017 to November 2022. psTg was measured in all patients 3-4 weeks after surgery and they were subjected to RAIA depending on clinician’s discretion and followed up using the ATA dynamic risk stratification every 6 months. The cohort was divided into two groups: ATA high risk and ATA non-high risk (Low and intermediate risk). Patients among high risk group were divided based on response to treatment into structural incomplete group and non-structural incomplete group (Excellent, Indeterminate and Biochemically incomplete response). The mean age of the study population was 41±15 years and 68% (n=194) were female and 87% (n=249) were papillary thyroid cancer (PTC) and 13% (n=36) were Follicular Thyroid Cancer (FTC). Median duration of follow up was 2.95 years (IQR: 1.42 - 5.12). Among those with PTC, 75% were Classic, 15% Follicular variant and 10% aggressive variants that included tall cell, hobnail, diffuse sclerosing and columnar variant. On ATA risk stratification, 81.75% (n=233) patients were in non-high risk group with median psTg 3.4 ng/ml (IQR 0.5-12.2) and 18.25% (n=52) were in high-risk group with median psTg 150.5 ng/ml (IQR 7.15-439.5). On ROC analysis of all the patients, a psTg value >53.3 ng/ml was predictive of ATA high risk group with PPV of 64%; NPV of 93.5% and AUC 0.81. In ATA high-risk group, there were 73% (n=38) of patients with structural incomplete response on follow up and their median psTg was 287 ng/ml (IQR 95-500) and there were 27% (n=14) with non-structural incomplete response and their median psTg level of 6.2 ng/ml (IQR 2.3-110). A psTg value >53 ng/ml discriminated structural incomplete from non-structural incomplete response with PPV of 77%; NPV 87% and AUC 0.83. A psTg value >53 ng/ml not only predicts ATA high risk patients but also indicates those who are likely to remain with structural residual disease at follow up of 3 years. Presentation: 6/1/2024

Sufficiency of a Single Negative Thyroglobulin Standard for Judging the Success of Ablation in Low- and Intermediate-risk Differentiated Thyroid Cancer: A Retrospective Study.

We investigated how reduced successful ablation criteria may be used to evaluate radioiodine remnant ablation in patients with low- and intermediate-differentiated thyroid carcinoma (DTC). Overall, 254 low- and intermediate-risk patients with DTC were categorized into three groups (positive, weak, positive, and negative) on the basis of a visual study of thyroid imaging performed before postoperative iodine treatment. Semi-quantitative analysis parameters were incorporated into the positive Tc-99m pertechnetate scanning to further examine the clinical use of thyroid imaging. We investigated the value of successful judgment criteria and the influencing factors of radioiodine ablation. At the same time, the predictive value of thyroglobulin (Tg) for radioiodine treatment and the overall clinical efficacy were assessed. A total of 250 (98.43%) patients were identified as having functional thyroid tissue residue on the Rx-whole-body scan, and 137 (53.94%) patients had positive Tc-99m pertechnetate scans using semi-quantitative analysis. The single Tg standard could not substitute the double standard (χ2c=22.042, p<0.001) for patients with residual thyroid weight by a semiquantitative analysis. However, the semi-quantitative analysis revealed no association between 99mTcO4-thyroid scan and ablation treatment using semi-quantitative analysis; only preablation sTg levels were related with success in the multivariate logistic regression analysis, with a cut-off value of 2.88 ng/mL. The pre-ablation stimulated Tg level was also the primary factor of satisfactory response following follow-up with an optimal cut-off of 6.506 ng/mL. Even in low- and intermediate-risk patients with DTC, a single negative Tg standard also requires receiving some restrictions in the evaluation of ablation success and is inadequate. Conventional 99mTcO4 thyroid imaging combined with a quantitative analysis program can improve the clinical practice of single negative Tg standard.

A retrospective analysis thyroid function and ultrasonography in a group of subjects with lepramatous leprosy in Turkey.

There are several studies on thyroid functions and thyroid gland features in patients with leprosy in the literature. The relationship between them have not been clarified yet. These studies are time-expired and don't contain ultrasonography examination. The purpose of the study is to investigate thyroid functions and gland characteristics in leprosy patients by ultrasonography (US) and current laboratory techniques. This retrospective study was conducted by collecting the data of patients with lepramatous leprosy. Serum thyroid-stimulating hormone, free triiodothyronine, free thyroxine, anti-thyroid peroxidase, antithyroglobulin, and thyroglobulin values and thyroid ultrasonography reports were collected from previous records. The mean age is 75.12±9.89 years of total 17 subjects and 10 patients (58.8%) were male. Thyroid US was performed on 14 of the patients, nodules were detected in a total of 7 (50%) patients. The mean FT3, FT4, TSH, Anti-Tpo, Anti-TG, and TG values of the patients were found to be within normal limits. In the present study, no changes were detected in the thyroid functions and structures of the patients with Lepromatous Leprosy. We consider that prospective randomized studies that will include larger sample sizes are needed to determine whether there is a relationship between leprosy and thyroid disease.

125I seed implantation for lymph node metastasis from radioactive iodine-refractory differentiated thyroid carcinoma: a study on short-term efficacy and dosimetry.

To investigate the feasibility and evaluate the safety and effectiveness of Computed Tomography (CT) guided125I radioactive particle implantation for treating lymph node metastases in radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). To verify the accuracy of the computerized three-dimensional treatment planning system (TPS) in treating lymph node metastasis using125I particle implantation at the dosimetric level. A retrospective analysis was conducted on 42 patients with RAIR-DTC and lymph node metastases who were admitted to the General Hospital of the Northern Theater Command between December 2016 and January 2019. During this analysis, physicians utilized preoperative CT images to design an intraoperative plan using TPS. The dosimetric parameters of the postoperative plan were then compared to the preoperative plan. Additionally, this study examined the changes in tumor size and tumor-related marker Thyroglobulin (Tg) values in patients at 2, 6, and 12 months after the operation. The number of125I radioactive particles implanted in 42 patients was 226, with an average of 14.5 (range 2.0-30.0) particles implanted per lesion. The local remission rates were 97.62% (41/42), 88.10% (37/42), and 85.71% (36/42) at 2, 6, and 12 months postoperatively, respectively. The volume of the lesions was (4.44 ± 1.57) cm3, (4.20 ± 1.70) cm3, and (4.23 ± 1.77) cm3at 2, 6, and 12 months after treatment, respectively, which significantly decreased from the preoperative baseline level of (6.87 ± 1.67) cm3(t-values: 9.466, 9.923, 7.566, all P<0.05). The Tg levels were 15.95 (5.45, 73.93) μg/L, 8.90 (2.20, 39.21) μg/L, and 6.00 (1.93, 14.18) μg/L at 2, 6, and 12 months after treatment, respectively, which were significantly lower than the preoperative baseline levels of 53.50 (20.94, 222.92) μg/L (Z values: -5.258, -5.009, -4.987, all P < 0.001). Postoperatively, Delivered to 90% of the GTV(D90) was slightly lower than the prescribed dose in 95.23% (40/42) of patients, but the difference was not statistically significant [(12,378.8 ± 3,182.0), (12,497.8 ± 1,686.4) cGy; t=0.251, P>0.05], and postoperative dose parameters delivered to 100% of the gross tumor volume (GTV)(D100) (6,881.5 ± 1,381.8) cGy, the volume percentages of GTV receiving 150% of the prescribed dose(V150) (58.5 ± 18.40)%) were lower than the preoperative plan D100 (8,085.8 ± 2,330.0) cGy, V150 (66.5 ± 17.70)%; t-value=8.913 and 3.032, both P<0.05; the remaining indicators were not significantly different from the preoperative plan (the differences in the number of implanted particles, Planning Target Volume(PTV), the volume percentages of GTV receiving 100% of the prescribed dose(V100), Homogeneity Index(HI)were not statistically significant (t/Z = -0.593, -1.604, 1.493, -0.663, all P>0.05). Referring to the TPS preoperative plan, the125I particle implantation therapy for RAIR-DTC lymph node metastasis can achieve the expected dose distribution, ensuring precise short-term local tumor control efficacy.

Diagnostic, Theranostic and Prognostic Value of Thyroglobulin in Thyroid Cancer.

Thyroglobulin (Tg) is an iodinated glycoprotein, which is normally stored in the follicular colloid of the thyroid, being a substrate for thyroid hormone production. Since it is produced by well-differentiated thyroid cells, it is considered a reliable tumor marker for patients with differentiated thyroid carcinoma (DTC) during their follow-up after total thyroidectomy and radioiodine ablation. It is used to monitor residual disease and to detect recurrent disease. After total thyroid ablation, unstimulated highly sensitive Tg measurements are sufficiently accurate to avoid exogenous or endogenous thyrotropin (TSH) stimulation and provide accurate diagnostic and prognostic information in the great majority of DTC patients. Adopting sophisticated statistical analysis, i.e., decision tree models, the use of Tg before radioiodine theranostic administration was demonstrated to be useful in refining conventional, pathology-based risk stratification and providing personalized adjuvant or therapeutic radioiodine administrations. The follow-up of DTC patients aims to promptly identify patients with residual or recurrent disease following primary treatment. Our review paper covers the diagnostic, theranostic and prognostic value of thyroglobulin in DTC patients.

Detection of thyroglobulin for diagnosis of metastatic lateral cervical lymph nodes in papillary thyroid carcinoma: accuracy and application in clinical practice.

Accurate assessment of lateral cervical lymph node metastasis (LLNM) involvement is important for treating papillary thyroid carcinoma (PTC). Thyroglobulin is associated with LLNM, but there may be differences in the diagnostic value of serum thyroglobulin (sTg) and fine needle aspiration washout fluid thyroglobulin (FNA-Tg). Herein, we investigated the optimal cutoff value (OCV) of sTg and FNA-Tg and their diagnostic performance. We enrolled 116 PTC patients who underwent radical resection of thyroid carcinoma with lateral cervical lymph node dissection at the Affiliated Hospital of Zunyi Medical University from June 2018 to July 2022. We used the receiver operating characteristic (ROC) curve analysis to determine the OCV for sTg and FNA-Tg to diagnose LLNM in PTC patients. We also evaluated the performance of FNA-Tg, sTg, fine needle aspiration cytology (FNAC), and their combinations for diagnosis. Pathological results were the gold standard. We performed 125 lymph node dissections, 106 had metastasis, and 19 did not. The OCV for sTg was 17.31 ng/mL [area under the curve (AUC) =0.760, sensitivity =78.30%, specificity =73.68%, and accuracy =77.60%]. Meanwhile, the OCV for FNA-Tg was 4.565 ng/mL (AUC =0.948, sensitivity =89.62%, specificity =100%, and accuracy =91.20%). The combination of FNAC and FNA-Tg presented the greatest diagnostic performance for LLNM detection in PTC patients. Moreover, serum antithyroglobulin antibody (TgAb) was not correlated with sTg or FNA-Tg levels. The cutoff value for the diagnosis of LLNM in PTC are sTg >17.31 ng/mL or FNA-Tg >4.565 ng/mL. The combination method of FNA-Tg and FNAC is the most optimal choice for the diagnosis of LLNM and is highly recommended for further clinical application.

Serum Thyroglobulin (Tg) assay by immunoradiometric methods (IRMA): comparison of concentrations obtained with Cisbio Bioassays vs Beckman Coulter kit in patients with differentiated thyroid cancer.

Introduction: In clinical practice, Thyroglobulin is a tumor marker for the post-operative follow-up of differentiated thyroid cancer, provided that any thyroid residual remains are eliminated beforehand, either by simple total thyroidectomy, or most often supplemented by isotopic totalization with Iode131. The aim of this study were to compare serum Tg values measured with 02 kit manufacturers of immunoradiometric type (IRMA) and to evaluate their cost/effectiveness ratio. Methods: We included patients followed for differentiated thyroid cancer operated and irradiated with Iodine 131 at the nuclear medicine department of Tlemcen University Hospital. Their serum Thyroglobulin was dosed in the laboratory of the department with the Tg-IRMA kit of Cisbio Bioassays taken in this study as «Gold standard» and the Tg-IRMA kit of Beckman Coulter. Results: Ninety-nine (99) serums of patients with CDT were measured for Thyroglobulin. The correlation of the Thyroglobulin values obtained with the 02 kits is positive and significant (r= 0.98; p &lt; 0.01). The equation of the regression line of Passing- Bablok is of type y = 0.7 x + 0 (with Y = Tg-IRMA Cisbio Bioassays and X = Tg-IRMA Beckman Coulter). The difference in the averages analyzed with the Bland-Altman diagram is = 0 (p &gt; 0.05), indicating that there is no difference in the mean of Tg between the 02 kits. The analysis by ROC curve of the Tg-IRMA Beckman Coulter kit Thyroglobulin values at the threshold of 0.7 and 1 ng/mL finds respectively a sensitivity and a specificity of 100% and 93% with an area under the curve = 0.99. Conclusion: There is a strong correlation between Thyroglobulin concentrations obtained with the 02 kits, so a budget reduction in the management of our patients with diffrentiated thyroid cancer is possible, in favor of the Tg-IRMA kit of Beckman Coulter with a good cost/ efficiency ratio.

Comparison and Analysis of Clinical Features of Papillary Thyroid Cancer Complicated With Hashimoto's Thyroiditis.

Hashimoto thyroiditis (HT) combined with papillary thyroid cancer (PTC) is more common in clinical practice, maybe posing a serious threat to the health of patients. It is uncertain whether HT is a risk factor or protective factor for PTC. The aim of the study was to retrospectively explore the effect of HT on the biological behavior of PTC. A total of 200 patients were included in the study. Among them, 100 patients with PTC without HT were in the control group (PTC group), and 100 cases diagnosed as PTC with HT were in the experimental group (HT + PTC group). The following data were counted and analyzed, respectively: (1) the basic clinicopathologic characteristics of patients; (2) postoperative thyroid function indicators; (3) blood biochemical indicators; (4) liver function indicators; and (5) histopathological report. Compared with the PTC group, women were predominant in the PTC + HT group (P < .05). In addition, the central lymph node metastasis rate, the number of cervical lymph node metastases, and the lateral cervical lymph node metastasis rate were significantly decreased (P < .05). Thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone (TSH), and thyroglobulin antibody (TGAb) of the thyroid function index were significantly increased, while the thyroglobulin (TG) value was significantly decreased (P < .05). The alkaline phosphatase (ALP) level of the liver function index was significantly decreased, while the lactate dehydrogenase (LDH) level was significantly increased (P < .05). In the pathological examination, a large number of mononuclear cells infiltrated in the lymphocyte follicular stroma. In an ultrasound examination, the boundary definition rate is lower. Women may be more susceptible to PTC or PTC and HT than men. Patients under 55 years old accounted for a larger proportion in PTC + HT than PTC. Hashimoto thyroiditis may play an inhibitory role in the occurrence of PTC, and the presence of HT is a protective factor for PTC.

Chapter 6: Risk Stratification and Surveillance in Differentiated Thyroid Cancers

ABSTRACT Surveillance strategies in differentiated thyroid cancers (DTCs) differ from other head-and-neck subsites by virtue of their excellent prognosis. Guidelines in this chapter are based on a comprehensive literature review, particularly in the Indian setting concurred upon by experts in the field. Key recommendations include serial measurement of thyroglobulin values, thyroglobulin antibodies, and risk-based suppression of thyroid-stimulating hormone during follow-up of treated DTCs, with radioactive iodine scan and structural imaging based on dynamic risk stratification. These recommendations take into consideration prevailing Indian scenario related to reliability of follow-up, insurance coverage, as well as burden on health-care systems.

Minimally Invasive Open Bilateral Total Thyroidectomy Using Unilateral Neck Incision in Thyroid Cancer: Preliminary Surgical and Quality of Life Outcomes.

Thyroid cancer incidence has increased in recent decades, and thyroid surgery is continuously evolving in response to demands for postoperative comfort and cosmesis. This study aimed to introduce a new surgical method for minimally invasive open bilateral total thyroidectomy (MI-BTT) using a unilateral 2.5-3.0 cm neck incision. Furthermore, we reported the surgical outcomes and postoperative quality of life (QoL) using a validated Korean translated Dermatology Life Quality Index (DLQI) questionnaire. We retrospectively evaluated 41 Asian patients who underwent MI-BTT for low-risk papillary thyroid cancer by a single surgeon from March 2019 to December 2021. A total of 4 male and 37 female patients were included. The mean age and body mass index were 46.2±10.1 years and 23.3±3.3 kg/m², respectively. The average tumor size was 1.1±0.6 cm, and 36 patients (87.8%) had bilateral cancer. Twenty-three (56.1%) patients had occult central lymph node (CLN) metastasis in the final pathologic report, with the mean number of dissected CLNs being 7.2±6.5. Gross capsular extension was found in 6 patients (14.6%). Moreover, 28 patients (68.3%) received additional treatment after surgery with low or high doses of radioactive iodine. The average serum-stimulated thyroglobulin value identified during treatment was 1.57±2.30 ng/mL. The mean operation time was 78.0±13.9 minutes, and postoperative complications included transient hypocalcemia (36.6%), transient hoarseness (24.4%), and seroma (2.4%). The mean total DLQI score was 2.73±0.78, indicating a small effect on QoL. MI-BTT is a novel, safe, and feasible technique to improve patient satisfaction for surgical scars and QoL.

Analysis of the clinical factors affecting excellent response of Iodine-131 treatment for pulmonary metastases from differentiated thyroid cancer

BackgroundIodiene-131 (131I) treatment is the primary therapeutic approach for imaging 131I-avid pulmonary metastases. The response to radioiodine (RAI) treatment is an important prognostic factor in patients with pulmonary metastases from differentiated thyroid cancer (DTC). Patients who achieve an excellent response (ER) to 131I treatment show significantly reduced disease-related mortality. This study aimed to retrospectively analyse the clinical data and therapeutic effects of 131I treatment in patients with DTC and pulmonary metastases and to screen out the clinical factors affecting ER. Materials and methodsThe study included a total of 75 patients with exclusively Iodine-131 avid (131I-avid) pulmonary metastases who underwent 131I treatment. Relevant clinical data for these patients were collected. Following treatment, the status of DTC metastatic lesions was categorized as follows: excellent response (ER), biochemical incomplete response (BIR), structural incomplete response (SIR), or indeterminate response (IDR). Gender, age at diagnosis, pathological type, stages (TNM), stimulated thyroglobulin (sTg) value before initial 131I treatment, metastatic nodule size, and type of post-treatment whole body scan (Rx-WBS) were recorded. Mono-factor analysis and binary logistic regression analyses were used to identify the factors that might affect the ER in DTC pulmonary metastases. The receiver operating characteristic (ROC) curve of the sTg value was used to predict the ER of 131I treatment. ResultsAll 75 patients with exclusively 131I-avid pulmonary metastases received 131I treatment and underwent follow-up. Out of the 75 patients, 26 achieved ER, resulting in an excellent response rate of 34.7 % (26/75). Among them, 25 (25/26, 96.2 %) achieved an ER after undergoing two rounds of 131I treatment. Binary logistic regression analysis showed that the factors influencing DTC pulmonary metastases excellent response were lower sTg levels [odds ratio (OR) = 0.998, P < 0.001], micronodular metastases (OR = 0.349, P = 0.001) and focal distribution on Rx-WBS imaging (OR = 0.113, P = 0.001). The area under the ROC curve for sTg value predicting ER was 0.876, and the cut-off value was 26.84 ng/mL, with a sensitivity and specificity of 87.9 % and 80.3 %, respectively. Conclusions131I treatment is effective for 131I-avid pulmonary metastases of DTC. Some patients who underwent 131I treatment achieved ER. Most patients with ER were obtained after two rounds of 131I treatments. Patients with sTg values before initial 131I treatment lower than 26.84 ng/mL, micronodular metastases, and focal distribution on Rx-WBS imaging were more likely to achieve ER.

Usefulness of second 131I treatment in biochemical persistent differentiated thyroid cancer patients.

Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment. The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR). One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated. After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment. Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

Tumor Microenvironment Features as Predictive Biomarkers in Metastatic Differentiated Thyroid Cancer and Their Relationship With 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Metabolic Parameters.

The role of the tumor microenvironment in tumor progression and treatment response is being investigated for different types of cancer. This study aimed to determine the relationships between tumor microenvironment, histopathology, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based metabolic parameters, treatment response, and overall survival (OS) in metastatic differentiated thyroid cancer (DTC). Methods: Metastatic DTC patients who underwent 18F-FDG PET/CT between 2015-2019 were evaluated. Clinicopathological, histopathological features and PET/CT parameters of patients were recorded. Microenvironmental characteristics of the primary tumor, such as mitosis, intratumoral and peritumoral lymphocytosis, intratumoral and peritumoral fibrosis, were evaluated from the tissue samples. The relationships between these factors were statistically analyzed. Sixty-five patients (38 females, 27 males, age: 49±15 years) were included. Mitosis, intra/peritumoral lymphocytosis, and intra/peritumoral fibrosis were frequent; however, none of them had a statistically significant association with PET-positive metastases, treatment response, or OS. Univariate analysis showed that gender, size, thyroglobulin values, residual thyroid tissue, PET-positive metastases, and maximum standardized uptake value (SUVmax) were significant predictors of OS. At multivariate analysis, PET-positive metastases (HR=-2.65, 95%CI 0.007-0.707, p=0.024) and SUVmax (HR=-2.74, 95%CI 0.006-0.687, p=0.023) were the only independent predictors for OS. Conclusion:Our study revealed that microenvironmental characteristics of the primary tumor did not show prognostic significance in metastatic DTC. PET-positive metastases and SUVmax levels were the only significant factors that predicted overall survival in DTC. Supporting the results of our study with further studies with a larger sample size may be necessary to determine the relationship between the tumor microenvironment and prognosis in DTC.

Establishing a Cutoff Serum Thyroglobulin Value for the Diagnosis and Management of Well-Differentiated Thyroid Cancer.

Objective The aim of this study was to define a cutoff serum thyroglobulin (Tg) level associated with either residual or metastasis that may help decide postoperative radioactive iodine (RAI) scan and treatment in differentiated thyroid cancer (DTC) patients residing in low-income countries like Nepal. Methods We prospectively studied a total of 81 patients (female-to-male ratio of 3.0:1; mean age: 37.3 ± 14.0 years, within age range of 14-88 years) who underwent total thyroidectomy with/without neck dissection and were referred for RAI whole-body scan (WBS) ± RAI ablation or adjuvant treatment in the department of Nuclear Medicine, Chitwan Medical College. We calculated the cutoff value of Tg using receiver operating characteristic (ROC) curve analysis. Results Forty-six of 81 patients (56.7%) had remnants in the thyroid bed, 26/81 (32.1%) had regional lymph node metastasis, 9/81 (11.1%) had distant lymph node metastasis, 3/81 (3.7%) had lung metastases, and only 1/81 (1.2%) had bone metastases. RAI WBS was positive in 61/81 (75.3%) patients and negative in 20/81 (24.7%) patients. Seventeen of 81 (20.9%) patients had negative RAI scans with low serum Tg levels; only 3/81 (3.7%) patients had Tg elevated negative RAI scan (TENIS). Although scan was positive in 61/81 (75.3%) patients, 64/81 (79.0%) patients received treatment with RAI, of which 3/81 (3.7%) patients were TENIS patients. There was a significant difference in serum Tg levels between patients who received or did not receive RAI ablation or treatment ( p < 0.05). On ROC curve analysis, the cutoff value of Tg levels between patients who received and did not receive treatment was 2.9 ng/mL (sensitivity: 85.9%; specificity: 94.1%; positive predictive value [PPV], 98.2%; negative predictive value [NPV]: 64.0%; AUC: 0.938). Conclusion We identified a cutoff value of 2.9 ng/mL between patients who required or did not require treatment with high sensitivity, specificity, and PPVs.

The value of [18F]FDG PET/CT in avoiding overtreatment of 131l avidity pulmonary metastasis of differentiated thyroid cancer.

We usually use 131I-whole body scan (131I-WBS) and serum thyroglobulin (Tg) values to determine whether differentiated thyroid cancer (DTC) patients need to receive 131I treatment, but not all ¹³¹I-avid (functioning) patients have a good response to ¹³¹I therapy. Our study aims to assess the data of [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography ([¹⁸F] FDG PET/CT) to research the status of 131I-avid pulmonary metastases (PMs) and the prognosis of the patients. The 131I-avid PMs of DTC patients who underwent [18F]FDG PET/CT scans were included. The maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were used to estimate [¹⁸F]FDG uptake. The mean follow-up period was 34.14 ± 18.64 months. Progression-free survival (PFS) was estimated by the Kaplan-Meier method. The study was based on per-patient and per-lesion analyses. Among the 42 included patients, 34 (34/42, 81%) showed [¹⁸F]FDG uptake, which was defined as abnormal foci (SUVmax > 1.0) in the lungs. SUVmax, MTV, TLG, and tumour size were the factors that influenced the outcome of 131I treatment based on Tg levels (p = 0.000, 0.016, 0.000, 0.000) in per-lesion analysis. The only independent factor was the size of the lesion. There was a significant difference in response to ¹³¹I therapy between PMs with F-I+ and F+/I+ according to both Tg levels and Response Evaluation Criteria in Solid Tumours (RECIST) (version 1.1) (p = 0.044, 0.001), in the per-lesion analysis. When the changes in size or metabolism of some lesions are inconsistent the prognosis of these patients is poor (p = 0.003). We concluded that higher [18F]FDG uptake and larger tumour size predict poor therapeutic effects and a high risk of disease progression in ¹³¹I-avid PMs of DTC. For evaluating the efficiency of ¹³¹I treatment, per-lesion analyses and assessing the data of [¹⁸F] FDG PET/CT would be more reliable than per-patient evaluation only. And early focal treatment modalities may improve their life span.

Application of thyroglobulin and anti-thyroglobulin antibody combined with emission computed tomography in the adjuvant diagnosis of differentiated thyroid carcinoma

Purpose Thyroid nodules are a kind of common endocrine system disease, with approximately 5% of them developing into malignant lesions, the most common of which belong to differentiated thyroid carcinoma (DTC). Accurate differential diagnosis using reliable methods and targeted treatment of benign and malignant thyroid nodules are of great significance to improve patient outcomes. This study mainly investigates the diagnostic value of thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-TgAb) combined with emission computed tomography (ECT) in the adjuvant diagnosis DTC. Methods All the data of 387 histopathologically diagnosed DTC patients (observation group) and 151 patients with nodular goiter (control group) admitted between June 2019 and June 2021 were collected and retrospectively analyzed. Serum Tg and anti-TgAb levels were detected in all subjects. In addition, all patients in the observation group underwent thyroid ECT, and the results were compared with the pathological findings. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic performance of Tg, TgAb and thyroid ECT, either alone or in combination, in patients with thyroid cancer (TC). Results The consistency test showed that Tg (Kappa-value = 0.370) and anti-TgAb (Kappa-value = 0.393) had generally consistent efficiency with pathological findings in the diagnosis of DTC; ECT (Kappa-value = 0.625) and the combined diagnosis of the three (Kappa-value = 0.757) showed higher consistency than the pathological diagnosis, of which the combined diagnosis contributed to an even higher consistency. The combined diagnosis of Tg, anti-TgAb, and thyroid ECT outperformed either of these alone in DTC diagnosis, with a sensitivity of 91.5%, a specificity of 86.1%, and an accuracy of 90%. Conclusions The combination of Tg. anti-TgAb, and RNI can effectively improve the diagnostic accuracy of DTC and reduce the missed diagnosis rate, which has important reference significance for clinical diagnosis and treatment of TC.

Thyroglobulin immunoassay with a fully automated pretreatment process provides accurate thyroglobulin values in anti-thyroglobulin antibody positive specimens

ObjectivesHuman thyroglobulin (Tg) is widely used as a tumor marker for recurrence and metastasis of differentiated thyroid cancer (DTC). Currently, serum Tg values are measured using second-generation sandwich immunoassays (2nd-IMA). However, interference by endogenous autoantibodies to thyroglobulin (TgAbs) can lead to false-negative results or falsely low Tg values. Here, we describe a new Tg assay using the immunoassay for total antigen including complex via pretreatment (iTACT) method to prevent TgAb interference and compare it with 2nd-IMA. MethodsTg values were evaluated by three assays: iTACT Tg, Elecsys Tg-II, which is a 2nd-IMA, and LC-MS/MS (Liquid chromatography tandem-mass spectrometry). The ratio of Tg values between each assay was then compared to the Tg value by LC-MS/MS and TgAb titer. Tg immunoreactivity was analyzed by size-exclusion chromatography. ResultsCorrelation between iTACT Tg and LC-MS/MS using TgAb-positive specimens was good: Passing–Bablok regression with iTACT Tg = 1.084 × LC-MS/MS + 0.831. Correlation between 2nd-IMA and LC-MS/MS showed a relatively lower slope: 2nd-IMA = 0.747 × LC-MS/MS − 0.518. Thus, Tg values determined by iTACT Tg are equivalent to those of LC-MS/MS regardless of TgAb titer, whereas 2nd-IMA gave lower Tg values due to TgAb interference. Tg-TgAb complexes of various molecular weights were verified by size-exclusion chromatography. Tg values measured by 2nd-IMA fluctuated depending on the molecular weight of the Tg-TgAb complexes, whereas iTACT Tg accurately quantified Tg values regardless of the size of the Tg-TgAb complexes. ConclusionTg values in TgAb-positive specimens were accurately determined by iTACT Tg. TgAb-positive specimens contain Tg-TgAb complexes of various molecular weights that interfere with Tg value determination by 2nd-IMA, whereas iTACT Tg is unaffected by the presence of Tg-TgAb complexes.

Real world outcomes of next generation sequencing (NGS) of progressive RAI resistant metastatic thyroid cancer and treatment of these patients with redifferentiation protocol.

e18088 Background: Patients with papillary and follicular thyroid cancer (PTC and FTC) who are refractory to radioactive iodine treatment (RAIR) have poor prognosis. Frequently these patients are found to have BRAF V600E and NRAS Q61R mutations, which can be targeted using BRAF and MEK inhibitors to promote redifferentiation of thyroid cancer (TC) cells to take up RAI. The aim of this study is to define clinical, pathological, and molecular characteristics associated with response to redifferentiation therapy. Methods: NGS was performed to identify targetable mutations. The protocol consisted of 6 weeks of either dual therapy Trametinib and Dabrafenib (BRAF V600E) or Trametinib alone (NRAS Q61R) followed by dosimetry and therapeutic RAI administration. Interim imaging and biochemical analysis were performed at 3 months and 6 months. Statistical analysis was performed using the Kaplan-Meier survival analysis to estimate the mean time to progression from the protocol finish date. Patients who did not progress were censored at the last date of their clinic visit or at 192 days. Exploratory analysis was conducted to look at the change in trends in thyroglobulin (TG) values. Results: 16 patients met eligibility criteria. Previous RAI dosage ranged from 83mCi to 700mCi of Iodine 131 (I-131). 5 patients were African American, and 1 was Hispanic. Upon molecular analysis, 11 patients were found to have BRAF V600E mutation, 4 patients had NRAS Q61R mutation, and 1 was not identified. All but one patient had RAI uptake and received a dosage of 140 – 357 mCi of I-131 after dosimetry scan calculation. Upon interim analysis, 3 patients progressed at 3 months and an additional 3 patients progressed at 192 days. At 192 days, the mean time to progression from protocol finish date was 170 days (SD=9.7). Interim TG level analysis and images analysis are reflected in the table. There were other mutations identified: 11 patients were PDL1 negative, 5 PDL1 positive with range of 1-50%, 8 with TERT mutation, 4 with TP53, 2 with CHEK 2, other mutations were DNMT3A, FGFR3, BLM, EGFR, GNAS, ARID1, PDGFRA, NFE2L2, ARID2, Exon 17, POT1 Exon 14, and NTRK, were only present in one patient each. Conclusions: All but one patient with RAIR TC with BRAF V600E or NRASQ61R mutation who have undergone redifferentiation protocol have increased uptake of RAI after 6 weeks of targeted therapy with excellent response on interim analysis. Our study is ongoing to further define clinical, pathological, and molecular characteristics that help select patients with advanced TC who benefit most from redifferentiation treatment. Clinical trial information: 00005381 . [Table: see text]

Comparison of Radioactive Iodine Activities in Terms of Short- and Long-term Results in Ablation Therapy in Patients with Low-risk Differentiated Thyroid Cancer.

The aim of this study was to compare the treatment responses after ablation with 30-50 mCi radioactive iodine (RAI) and 100 mCi RAI in patients with differentiated thyroid cancer (DTC) who were in the low-risk group according to 2015 American Thyroid Associations Classification (ATA 2015) criteria. Between February 2016 and August 2018, 100 patients who received RAI treatment in our clinic after total thyroidectomy and who were in the low-risk group DTC were included in this retrospective study. These patients were divided into 2 groups: low-activity (30-50 mCi) (group 1) and high-activity (100 mCi) (group 2). While 54 patients were treated with low activity, 46 patients received high activity RAI. The 2 groups were compared according to the 1st- and 3rd-year treatment response status. According to the first-year follow-up, 15 patients were accepted as indeterminate response and 85 patients as excellent response. Three (5.5%) of the patients who were accepted as indeterminate response were in group 1 and 12 (26%) were in group 2. According to the third year follow-up, 1 patient in group 1 and 3 patients in group 2 were accepted as indeterminate response. No biochemical incomplete response or recurrent disease was detected. In the chi-square analysis performed to investigate the relationship between the first-year treatment response and RAI activities, a significant relationship was found (p=0.004). In the Mann-Whitney U test performed to investigate the parameters that may be effective in the treatment response, only the preablative serum thyroglobulin value was shown to have a significant difference between the two groups (p=0.01). In the long-term follow-up of the patients, based on the third year treatment response data, chi-square analysis was performed to evaluate the two groups in terms of treatment responses, and no statistically significant relationship was found (p=0.73). Ablation with 30-50 mCi can be safely applied in DTC patients who are in the ATA 2015 low-risk group and are planned for RAI ablation treatment.