Prediction of Cervical Lymph Node Metastasis in Clinically Node-Negative T1 and T2 Papillary Thyroid Carcinoma Using Supervised Machine Learning Approach

Papillary thyroid carcinoma (PTC) is generally considered an indolent cancer. However, patients with cervical lymph node metastasis (LNM) have a higher risk of local recurrence. This study evaluated and compared four machine learning (ML)-based classifiers to predict the presence of cervical LNM in clinically node-negative (cN0) T1 and T2 PTC patients. The algorithm was developed using clinicopathological data from 288 patients who underwent total thyroidectomy and prophylactic central neck dissection, with sentinel lymph node biopsy performed to identify lateral LNM. The final ML classifier was selected based on the highest specificity and the lowest degree of overfitting while maintaining a sensitivity of 95%. Among the models evaluated, the k-Nearest Neighbor (k-NN) classifier was found to be the best fit, with an area under the receiver operating characteristic curve of 0.72, and sensitivity, specificity, positive and negative predictive values, F1 and F2 scores of 98%, 27%, 56%, 93%, 72%, and 85%, respectively. A web application based on a sensitivity-optimized kNN classifier was also created to predict the potential of cervical LNM, allowing users to explore and potentially build upon the model. These findings suggest that ML can improve the prediction of LNM in cN0 T1 and T2 PTC patients, thereby aiding in individual treatment planning

Measuring thyroglobulin concentrations in patients with differentiated thyroid carcinoma

Thyroid carcinomas are the most common malignant endocrine tumors. Thyroglobulin (Tg), a specific thyroid protein, is the most important tumor marker in thyroid oncology. After total thyroidectomy or radioiodine therapy, detectable or increasing serum Tg levels in patients with differentiated thyroid carcinoma indicate persistence of active thyroid tissue or cancer recurrence. Serum Tg concentration primarily reflects three variables: the mass of differentiated thyroid tissue present; the degree of thyrotropin receptor stimulation and the intrinsic ability of the tumor to synthesize and secrete Tg. Measurement of serum Tg by current immunometric (IMA) and radioimmunological (RIA) assays encounters some methodological problems which can diminish its clinical importance. Discrepancy between the results for Tg using different methods may be caused by: different reference materials, specific properties of the primary and secondary antibodies for antigenic determinants on Tg and diverse binding affinities of these epitopes, together with interference by serum factors (usually antibodies to Tg (TgAb)) with the primary and secondary Tg antibodies from the diagnostic set. In the presence of endogenous TgAb, Tg values measured by immunoradiometric assay (IRMA) and similar assays are usually lower than the real concentrations, while in RIA apparently lower or higher results can be obtained. Falsely low values may lead to delay in necessary treatment, while an inappropriately high Tg value can cause patient anxiety and unnecessary scans. Despite current methodological limitations, serum Tg measurement is a useful test for determining worsening disease and monitoring the effects of therapy in patients who have undergone surgery for differentiated thyroid carcinoma

Concentration of thyroglobulin and thyroglobulin-specific autoantibodies in patients with differentiated thyroid cancer after treatment with radioactive iodine 131

Background: Measurement of serum thyroglobulin (Tg) is primarily used as a tumor marker in the postoperative management of patients with differentiated thyroid cancer (DTC), while thyroglobulin autoantibodies (TgAbs) are elevated in some patients as well. The aim f this study was to evaluate the concentrations of Tg and TgAbs in DTC patients 3 and 6 months after radioiodine therapy and to analyze whether the development and course of TgAbs is related to the clinical status of DTC patients or Tg levels before and after radioiodine therapy. Methods: Pre-treatment measurements were made in conditions of stimulation of Tg secretion with endogenous thyroid-stimulating hormone (TSH) (TSH>25 mIU/L), while the measurements after the treatment were obtained in conditions of suppression of Tg secretion (TSH<0.15 mIU/L). Results: Concentrations of Tg were decreased in the sera of all patients with DTC 6 months after radioiodine treatment, as well as the mean concentration TgAbs. Thyroglobulin autoantibody concentrations in sera of patients without metastasis were higher than in those with DTC metastases. Individual values of TgAbs in patients without metastases after the radioiodine treatment were decreased, increased, or unchanged. Conclusion: The development and course of TgAbs in DTC patients cannot be predicted by Tg levels before and after radioiodine therapy

Blood cells in thyroid cancer patients: A possible influence of apoptosis

© 2016 Olgica B. Vrndic. The side effects of radioactive iodine (131-I) treatment of differentiated thyroid cancer (DTC) patients include reduction of peripheral blood cell counts. The aim of this study was to analyze some potential changes in blood cell counts of DTC patients after 131-I therapy, especially CD3-positive, CD19-positive, and CD56-positive peripheral blood lymphocytes (PBL), as well as the possible role of apoptosis in selected lymphocyte populations. The study group included 24 thyroid cancer patients and 24 control subjects. Peripheral blood samples from patients and controls were analyzed using 5-color flow cytometry. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. There was a statistically significant decrease of all blood cells after the 131-I therapy. The CD19+ B lymphocyte population was the most affected (5.82 ± 3.21% before therapy vs. 3.93 ± 2.60% after therapy, p = 0.008). This decrease was correlated with the degree of apoptosis of peripheral blood lymphocytes (Spearman's r = 0.563, p = 0.013). We concluded that 131-I therapy of DTC patients led to a decrease of all peripheral blood cells, especially CD19+ B lymphocytes. This directly correlated with apoptosis of PBLs, indicating that radiation damage to B cells leads to subsequent elimination by apoptosis

Protein and lipid concentrations in patients with differentiated thyroid cancer treated with radioactive iodine-131

© 2014 University of Kragujevac, Faculty of Science. All rights reserved. Short-term, overt hypothyroidism in patients with differentiated thyroid cancer (DTC) before radioiodine (131-I) therapy might be accompanied by a number of metabolic changes, including altered protein and lipid metabolism. Protein concentrations and their relationship to lipids in the serum of DTC patients have not been fully elucidated. Th e aim of our study was to evaluate the protein and lipid concentrations in 24 DTC patients before and 3 and 7 days after 131-I therapy compared with those of 20 healthy control subjects. After radioiodine therapy, the mean protein concentration (78.71 -} 6.71 g/L vs. 87.16 -} 6.04 g/L; p = 0.003) and cholesterol level (8.12 ±} 2.13 mmol/L vs. 8.84 -} 2.09 mmol/L; p = 0.001) were lower 3 days after therapy; this persisted up to 7 days after therapy, whereas triglyceride concentrations were higher 3 days after therapy (2.44 -} 1.07 mmol/L vs. 2.26 -} 1.08 mmol/L; p = 0.041) and returned towards the pretreatment values at 7 days after 131-I therapy. Th ere was an indirect correlation between the protein and triglyceride concentrations 3 days after 131-I therapy in patients over 50 years old (Spearman’s r =-0.583, p = 0.048) but not in patients under 50 years old (Pearson’s r =-0.277, p = 0.384). Radioiodine therapy of DTC patients led to decreased serum protein and cholesterol concentrations, accompanied by increased triglyceride levels; these changes were especially evident in older subjects with metastases

Protein and Lipid Concentrations in Patients with Differentiated Thyroid Cancer Treated with Radioactive Iodine-131 / Koncentracija Proteina I Lipida Kod Pacijenata Sa Diferentovanim Karcinomom Štitaste Žlezde Koji Su Lečeni Radioaktivnim Jodom-131

Prolazna, manifestna hipotireoza koja se javlja kod pacijenata sa diferentovanim karcinomom štitaste žlezde (DTC) pre terapije radioaktivnim jodom (131-I) može biti udružena sa brojnim metaboličkim promenama, uključujući i promene u metabolizmu proteina i lipida. Koncentracija proteina i njihov odnos sa lipidima u serumu pacijenata sa DTC nakon terapije 131-I nedovoljno su ispitani. Cilj našeg istraživanja bio je da se ispita serumska koncentracija proteina i lipida kod pacijenata sa DTC pre, kao i tri i sedam dana posle terapije 131-I. Studijom je obuhvaćeno 24 DTC pacijenata i 20 zdravih ispitanika. Pokazano je značajno, progresivno smanjenje koncentracije proteina (78.71±6.71 g/L vs. 87.16±6.04 g/L; p=0.003) i holesterola (8.12±2.13 mmol/L vs. 8.84±2.09 mmol/L; p=0.001) tri dana nakon terapije 131-I, uz statistički značajno povećanje koncentracije triglicerida tri dana nakon terapije (2.44±1.07 mmol/L vs. 2.26±1.08 mmol/L; p=0.041) i povratkom na preterapijske vrednosti 7 dana posle terapije. Pri tom, indirektna korelacija između koncentracije proteina i triglicerida tri dana posle 131-I pokazana je u grupi pacijenata starijih od 50 godina (Spearman r=- 0.583, p=0.048), što nije bio slučaj sa ispitanicima mlađim od 50 godina (Pearson r=- 0.277, p=0.384). U zaključku, terapija radioaktivnim jodom prouzrokuje smanjenje koncentracije serumskih proteina i holesterola, koje je udruženo sa povećanjem koncentracije triglicerida i posebno je izraženo kod starijih pacijenata sa metastazama

Radioiodine therapy accelerates apoptosis in peripheral blood lymphocytes of patients with differentiated thyroid cancer

Both apoptosis and micronuclei formation reflect cytogenetic damage in cells and could contribute to cell homeostasis. The aim of this study was to evaluate apoptosis in peripheral blood lymphocytes (PBLs) of patients with differentiated thyroid cancer (DTC) before and after 131-iodine (131-I)-therapy and its correlation with micronuclei (MN) frequency. The study population included 18 DTC patients and 18 healthy donors. Apoptotic cells were detected using the Annexin V-FITC/7-AAD kit and MN frequency by cytokinesis-block MN assay. The difference between early apoptosis in PBLs of DTC patients before therapy and controls (9.88 ± 4.99% vs. 6.64 ± 2.07%, p = 0.003) was significant, as well as between early apoptosis in PBLs of DTC patients before and after 131-I-therapy (9.88 ± 4.99% vs. 13.53 ± 6.57%, p = 0.008). The MN frequency and early apoptosis in PBLs of DTC patients was positively correlated before (r = 0.540, p = 0.021) and after 131-I-therapy (r = 0.585, p = 0.014). Thyroid cancer patients had a significantly increased early apoptosis in PBLs, which further increased after 131-I-therapy in association with MN frequency

Cytokine profile in patients with differentiated thyroid cancer

291-299Multiple cytokines released in tumor microenvironment can promote anticancer effects, or carcinogenesis and tumor growth. Although cytokines mainly act locally, the changes in their circulating levels may reflect the interactions between tumor and inflammatory cells during the disease course. The aim of this study was to analyze the serum cytokine profile in patients with differentiated thyroid cancer (DTC) and to identify cytokines those could be associated with tumor progression/metastasis. Serum concentrations of thirteen cytokines were measured in control subjects and DTC patients before, three and seven days after radioactive iodine therapy, using multiplex cytokine detection systems for Th1/Th2/Th9/Th17/Th22 cell-related cytokines Most cytokines were not detected in serum samples from control subjects, while detectable levels of the cytokines were measured in some, but not all DTC patients. The serum levels of the following cytokines: interleukin IL-17A, IL-10 and IL-13 were significantly increased in DTC patients with metastasis. At the same time, the concentrations of several cytokines (IL-12p70, IL-17A, IL-5, IL-1β and tumor necrosis factor (TNF-α) were positively correlated with thyroglobulin (Tg) levels. The histological type of tumor, hypothyroidism, and intensity of oxidative stress were not associated with cytokine levels in patients’ sera. Radioactive 131-I therapy reduced serum levels of the majority of examined cytokines, but these differences did not reach statistical significance. In conclusion, the study indicates that the increase of the levels of several Th2/Th17 cells and proinflammatory cytokines in the serum of patients with DTC is associated with tumor progression/metastasis. Thus, the increase in this specific cytokine constellation might be an indicator of the malignant disease progression

Correlation between micronuclei frequency in peripheral blood lymphocytes and retention of 131-I in thyroid cancer patients

Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50 ± 6.90 vs. 27.10 ± 19.50 MN) and significantly decreased the CBPI (1.52 ± 0.20 vs. 1.38 ± 0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined. © 2013 Tohoku University Medical Press

Oxidative stress in patients with differentiated thyroid cancer: Early effects of radioiodine therapy

223-229Ionizing radiation in <span style="mso-ansi-language: SR" lang="SR">differentiated thyroid cancer (DTC) patients treated with radioiodine (131-I) produces reactive oxygen species (ROS), which could induce oxidative stress with disturbance of redox balance. The aim of this study was to evaluate oxidative stress in DTC patients treated with 3.7 or 5.5 GBq of 131-I using values for serum malondialdehyde (MDA, a marker of oxidative stress), uric acid (to determine antioxidant status) and total antioxidative status (TAS). The study population included 20 DTC patients and 20 healthy controls. Significant differences in MDA concentrations were found between DTC patients before 131-I therapy and control subjects (p = 0.001), while TAS values were similar in both populations (p&gt;0.05). There was a negative correlation between MDA concentrations and TAS in the DTC group before therapy (R2 = 0.2973, p = 0.013). Three days after 131-I therapy, MDA concentrations were higher than the pretreatment values (<span style="mso-ansi-language: SR" lang="SR">3.36 ± 1.69 nmol/mL vs. 2.93 ± 1.31 nmol/mL; p = 0.006), while serum uric acid concentrations declined progressively from 341.0 ± 80.39 μmol/L to 304.25 ± 77.25 μmol/L (p = 0.026) in 3 days and 291.2 ± 88.86 μmol/L (p = 0.009) in 7 days after 131-I therapy. There was no dose-dependent effect on MDA, or uric acid concentrations and TAS. Thus, <span style="mso-ansi-language: SR" lang="SR">131-I therapy in DTC patients induced oxidative stress, which was accompanied by a simultaneous and extended reduction in uric acid concentration, but without significant disturbances in TAS. This is the first study that evaluated TAS capacity in DTC patients before and 7 days after 131-I therapy. The relatively stabile TAS values in these patients indicated a good protection from oxidative stress induced by high doses of ionizing radiation. </span