Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Role of TSH Inhibition Therapy in the Postoperative Management of Patients with Differentiated Thyroid Cancer

Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.

Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for persistent/recurrent and metastatic differentiated thyroid cancer 2018 (English version)

Contents1. Diagnosis and dynamic assessment of persistent/recurrent and metastatic differentiated thyroid cancer (prmDTC)1.1 Basic principles of diagnosis1.2 Diagnostic methods1.3 Ongoing assessment of response to therapy2. Multidisciplinary treatment of prmDTC2.1 Basic principles of treatment2.2 Surgical management2.2.1 Preoperative clinical assessment2.2.2 Principles of surgical treatment for prmDTC.

ANALYSIS OF EFFICACY IN TREATMENT OF LOW-RISK WELL-DIFFERENTIATED THYROID CANCER WITHOUT CERVICAL LYMPH NODE INVOLVEMENT: 42 CASES REPORT

Objective To assess the more appropriate surgical treatment for low-risk group differentiated thyroid cancer. Methods A total of 42 low-risk patients with DTC, according to the AMES system (male, n = 6; female, n = 36) , were chosen for total thyroidectomy or subtotal thyroidectomy with center compartment lympha-dectomy. Results Nineteen patients had cervical lymph node involvement. Two patients had recurrent nerve injured. One patient had hypoparathyroidism. There were no mortality or local lymph recurrent up to present. Conclusion Total thyroidectomy or subtotal thyroidectomy with prophylactic center compartment lymphadectomy is an appropriate approach for the treatment of low-risk group differentiated thyroed cancer, to prevent recurrent and improve life quality.

Serial stimulated thyroglobulin measurements are more specific for detecting distant metastatic differentiated thyroid cancer before radioiodine therapy

Objective: Preablative stimulated thyroglobulin (ps-Tg) has the potential to be used in identifying distant metastatic differentiated thyroid carcinoma (DM-DTC), but its single level can be affected by remnant thyroid tissue and thyrotropin (TSH). The objective of this retrospective study was to evaluate the value of serial ps-Tg measurements in identifying DM-DTC specifically. Methods: A total of 317 DTC patients with serial measurements of ps-Tg, TSH and anti-Tg antibody were divided into M1 (n=72) and M0 (n=245) according to the presence of distant metastasis (DM) or not. The initial psTg measurement, with a corresponding TSH exceeding 30 mu IU/mL, was marked as Tg1, and ps-Tg measured right before radioactive iodine (RAI) therapy was defined as Tg2, with a median interval of 8 days. Delta Tg denotes Tg2-Tg1, and Delta TSH denotes TSH2-TSH1. Tg1, Tg2, Delta Tg, and Delta Tg/Delta TSH were tested for efficacy in identifying DM-DTC using receiver operating characteristic (ROC) curve analysis, and further compared with chest computed tomography (CT) and posttreatment whole-body RAI scan (RxWBS). Results: Compared with single ps-Tg measurement (Tg1 or Tg2), both Delta Tg and Delta Tg/Delta TSH were more narrowly distributed around zero in the M0 group, which made their distribution in the M1 group more distinguished in a relatively dispersed way. Delta Tg/Delta TSH manifested a higher accuracy (88.64%) and specificity (90.20%) in identifying DM-DTC than Tg1 or Tg2 measurements, with a much higher specificity than chest CT (90.20% vs. 66.00%) and a much higher sensitivity than RxWBS (83.33% vs. 61.11%). Conclusions: Serial ps-Tg measurements even over as short an interval as 8 days hold incremental value in identifying DM-DTC. Delta Tg/Delta TSH is a specific early biochemical marker for DM-DTC.

Factors influencing the presence of circulating differentiated thyroid cancer cells in the thyroidectomy perioperative period

Objective The aim of the study was to detect circulating differentiated thyroid cancer （DTC） micrometas-tasis and to investigate the factors influencing their presence in the perioperative thyroiclectomy period. Methods DTC micrometastases in the peripheral blood were detected with flow cytometry, and patient clinical and pathological factors were analyzed in 327 DTC patients. Results Circulating blood micrometastases were present in the peripheral circulation at a higher rate 1 week postoperatively than preoperatively and at 4 weeks postoperatively （P 〈 0.05）. The preoperative pres- ence of circulating micrometastasis was associated with the size of the tumor and the presence of lymph node metastasis （P 〈 0.05）, but was not related to the degree of tumor differentiation （P 〉 0.05）. At 4 weeks postoperatively, the presence of circulating micrometastasis was not associated with tumor size or lymph node stage （P 〉 0.05）, but was associated with poorly differentiated tumors （P 〈 0.05）. Conclusion The presence of circulating DTC micrometastases correlates to tumor size, lymph node stage, and operative manipulation. The differentiation degree of the tumors were associated with the persistent presence of micrometastasis in the circulating blood.

Characteristics of Persistent or Recurrent Differentiated Thyroid Cancer

Introduction: The differentiated thyroid cancer has generally an excellent prognosis after the treatment. The aim of this study is to describe the characteristics of persistent or recurrent differentiated thyroid cancers. Patients/ Methods: It is about a descriptive and retrospective study conducted from 392 patients followed for differentiated thyroid cancer. The data concerning the persistent or recurrent differentiated thyroid cancer have been collected from 1986 to 2015 in endocrinology service in Ibn Rochd CHU. Results: In total, twenty-four patients have shown the relapse or the persistency of their tumor, corresponding to the prevalence of 6.12 percent. The papillary carcinoma was dominant in 79 percent of cases and the follicular carcinoma in 21 percent of cases. The metastases were cerebral (two cases), lung (3 cases), bones (3 cases, Figure 1), and lymph nodes (9 cases). In our series, eighteen cases of persistent differentiated thyroid cancer have been found against six cases of recurrent differentiated thyroid cancer. Two cases of death at least three years of followed in our series and concerned the two cases of cerebral metastasis. Conclusion: The persistent or recurrent differentiated thyroid cancer rate is low in our series. The discovery of the relapse t is late.

Impact of Thyroglobulin on Survival and Prognosis of Differentiated Thyroid Cancer

Proper assessment of risk factors contributes to the principle management of differentiated thyroid carcinoma post operatively. Aim of the study: to investigate the effect of Thyroglobulin (Tg) levels on prognosis together with other risk factors for Differentiated Thyroid Cancer (DTC). Patients and methods: Medical records of all patients with DTC presented to Clinical Oncology and Nuclear Medicine Department referred from Diabetes & Endocrine unit (Internal Medicine Hospital) and Surgery Department Mansoura University from 2011-2016 were retrospectively reviewed. Patients with distant metastasis or who lost follow-up were excluded. So data of 220 patients were analyzed. Data collected included pre-surgical assessment, also surgical interference either total or near total thyroidectomy with or without lymph node neck dissection were reviewed. Different prognostic factors that affect progression free survival (PFS) include age, umorsize, ymph node status, ex, multifocality, capsular infiltration, vascular invasion and Tg level were evaluated through multivariate analysis. Results: Most of the patients included were <45 years (69.1%). Incidence of the disease was higher in female (80%) with papillary type predominance (80.9%). About 59.5% of cases presented with tumor size ≤ 2 cm and multifocality was reported in 13.6%. While 30% had lymph node metastasis, 11% had vascular invasion. Capsular infiltration was observed in 15% and most of them showed Tg level ≤ 10 ng/ml (68.2%). About 70% received ablative radioiodine. The 5-year Progression Free Survival (PFS) was 85%. On multivariate analysis of variable prognostic factors on PFS, we found that tumor size, age, lymph node status, capsular infiltration, Tg level and vascular invasion significantly affected PFS (P = 0.01, 0.005, 0.004, 0.005, 0.02, 0.003) respectively. While sex, pathological type and multifocality were not (P = 0.9, 0.4, 0.6) respectively. Conclusion: Postoperative Tg level is a statistically significant prognostic factor together with other risk factors.

Evaluation of Quality of Life Related to I-131 Therapy in Patients with Well-Differentiated Thyroid Cancer and Emphasis in Salivary Morbidity: A Follow up Study after Treatment

Goal: To evaluate the impact of iodine-131 therapy received during childhood and adolescence and correlate it with the quality of life in these patients. Methods: We studied 19 patients diagnosed with cancer in childhood or adolescence who underwent thyroidectomy and supplemental therapy with I-131. We also recruited a control group of healthy subjects with the same demographic parameters. All patients were subjected to a scintigraphy examination of the salivary glands, and were also asked to complete a questionnaire in order to assess their overall quality of life. In addition, a more specific questionnaire for patients with head and neck cancer was also given to all study participants. Results: The quantitative and qualitative analyses of the salivary glands showed functional deficits with greater involvement of the parotid gland for volume, concentration and excretion. The right submandibular gland showed significant changes for volume in the patient group. The questionnaires made it possible to observe significant differences between the patient and control groups for symptoms such as thick saliva, dry mouth and speech problems. Conclusion: In spite of being very effective and widely used, iodine radionuclide therapy is correlated with a lower quality of life in young people.

Differentiated Thyroid Cancer with Thyroglobulin Elevation and Negative Iodine Scintigraphy (TENIS Syndrome)

Background and Objectives: Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and Negative Iodine Scintigraphy. The predisposing factors and outcome of this condition are unclear. In this study, our objectives were to analyze the characteristics of patients with high Tg level and negative Iodine scintigraphy and to determine the predictive factors for development of high Tg and negative scintigraphy. Patients and Methods: Retrospective study of 34 patients undergoing treatment for DTC, followed in the Nuclear Medicine department of the University Hospital—Sahloul Sousse between 1990 and 2006 and having a high Tg and negative Iodine scintigraphy. Fourteen patients had Tg between 2 and 10 ng/ml, 16 had Tg between 11 and 100 ng/ml and 4 patients had Tg more than 100 ng/ml. Results: There were 25 women and 9 men. The mean age was 51.65 years. In 94.1% of cases, the tumor was papillary carcinoma. Follicular tumors accounted for only 5.9%. The mean nodule size was3.26 cm. Capsular invasion was seen in 47.1% cases. The locoregional invasion was found in 35.3%. The lymph node extension was found in 84.8% of patients having lymph node surgery. Lymph node involvement was observed in 92.8% of patients with papillary cancer but it was found in 7.2% of patients with follicular cancers. Lymph node invasion was unilateral in 28.6% (N1a) and bilateral, contralateral or mediastinal in 71.4% (N1b). Initial level of Tg was as follows: 7 patients had Tg between 2 and 10 ng/ml, 14 patients had Tg between 11 and 100 ng/ml and 12 had Tg more than 100 ng/ml. The mean number of radioactive Iodine cure was 11.08 for patients with Tg more than 100 ng/ml with a significant difference (P = 0.001). Conclusion: Among epidemiological, pathological and clinical characteristics, lymph node invasion is the most frequent parameter found in patients with a DTC with high Tg level and negative Iodine scintigraphy.

Prevalence and Clinical Significance of Preoperative Thyroglobulin Antibodies in Differentiated Thyroid Cancer Patients

Thyroglobulin antibody (TgAb) has been used as a surrogate tumor marker of differentiated thyroid carcinoma (DTC) patients. Preoperative TgAb (PreopTgAb) is thought to affect the prevalence, disease severity, and outcome of DTC. The objective of the present study was to retrospectively analyze the prevalence of PreopTgAb in patients diagnosed with DTC and its relation to thyroid cancer characteristics, staging, and disease outcome. A retrospective analysis of 109 DTC patients with reports of PreopTgAb was carried out. Clinicopathological parameters, including patient demographics (age and gender), TNM staging, histopathologic characteristics (type of pathology, vascular invasion, extrathyroid extension, carcinoma variant, multifocality), treatment (surgery, radioactive iodine), and outcome were recorded. The association of PreopTgAb was compared with the study variables and outcome of the disease using the Chi-square test and Mann-Whitney tests. The prevalence of PreopTgAb was 59.6%. Among the 54 PreopTgAb positive patients, 34 patients had an excellent response and 15 patients had an indeterminate response, while biochemically and structurally incomplete response was observed in 3 and 2 patients, respectively. PreopTgAb was not significantly associated with age (p = 0.919), sex (p = 0.650), pathology (p = 0.079), stage at diagnosis (p = 0.513), vascular invasion (p = 0.211), extra thyroid extension (p = 0.734), histologic variant (p = 0.877), multifocality (p = 0.361), and outcome (p = 0.360). Although we did not find a significant association between positive PreopTgAb and clinical characteristics and outcome of DTC, it can still be considered as a surrogate marker of DTC during follow-up.

EFFECTS OF LEVOTHYROXINE ON BONE METABOLISM IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AFTER OPERATION AND ^(131)I ABLATION

Objective To investigate the effects of substitutive and suppressive doses of levothyroxine on bone metabolism in patients with differentiated thyroid carcinoma after surgery and 131I ablation. Methods The patients, who had received levothyroxine(L-T4) for at least 3 years for treating their differentiated thyroid carcinoma after surgery and 131I therapy, were classified into substitutive group and suppressive group according to the levels of serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH). We compared the levels of FT3, FT4, TSH, serum parathyroid hormone (PTH), serum calcium (Ca), serum phosphate (P), serum alkaline phosphates (ALP) and Bone mineral density (BMD) to those of healthy volunteers well matched for sex, age, menopausal status, and body mass index (BMI). Results No significant differences were found in the bone density and biochemical parameters of bone metabolism of the subjects treated with substitutive or suppressive doses of L-T4 compared with the control subgroup. No significant differences were observed among the subgroups according to accumulative doses of 131I. No bone fracture was found in all the patients. Conclusion The substitutive and suppressive doses of L-T4 are safe and necessary for patients with differentiated thyroid carcinoma after surgery and 131I therapy. Such treatment for 3 years is not associated with increased risk of osteoporosis. Much longer term of follow up is still needed in patients receiving substitutive and suppressive doses of L-T4.

Changes in percentage of lymphocyte subsets after ^(131)I treatment in patients with differentiated thyroid cancer

To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node me-tastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduc-tion compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The re-sults show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.

Interaction between tumor stage and age on survival outcomes of patients with anaplastic thyroid cancer

BACKGROUND Anaplastic thyroid cancer(ATC)is an aggressive,rare malignancy associated with rapid growth and metastasis,and a very poor prognosis.We investigated the clinical characteristics,survival outcomes and independent prognostic factors associated with anaplastic thyroid cancer.AIM To assess to what extent the interaction between age and tumor stage affects mortality.METHODS A total of 622 patients diagnosed with anaplastic thyroid cancer,between 2010 and 2017 were enrolled in our study by retrieving data from the Surveillance,Epidemiology and End Results(SEER)database.We analyzed demographics,clinical characteristics,overall mortality(OM)and cancer specific mortality(CSM)of ATC.Variables with a P value<0.1 were incorporated into the multivariate cox model to determine the independent prognostic factors.Furthermore,we analyzed the interaction between age and tumor stage on mortality.RESULTS In the multivariate analyses,the divorced/separated population had a lower OM[hazard ratio(HR)=0.63,95%CI:0.42-0.94,P<0.05]and CSM(HR=0.61,95%CI:0.40-0.92,P<0.05).OM was higher in tumors with direct extension only(HR=6.26,95%CI:1.29-30.42,P<0.05)and tumors with distant spread(HR=5.73,95%CI:1.34-24.51,P<0.05).CSM was also higher in tumors with direct extension(HR=5.05,95%CI:1.05-24.19,P<0.05)and tumors with distant spread(HR=4.57,95%CI:1.08-19.29,P<0.05).Mortality was not adversely affected by lymph node involvement.OM was lower in patients who received radiation(HR=0.66,95%CI:0.53-0.83,P<0.01),chemotherapy(HR=0.63,95%CI:0.50-0.79,P<0.01)or surgery(HR=0.53,95%CI:0.43-0.66,P<0.01).CSM was also lower in patient who received radiation(HR=0.64,95%CI:0.51-0.81,P<0.01),chemotherapy(HR=0.62,95%CI:0.50-0.78,P<0.01)or surgery(HR=0.51,95%CI:0.41-0.63,P<0.01).There was no significant interaction between age and tumor stage that affected mortality.CONCLUSION In this large US SEER database retrospective study,we found the mortality to be higher in advanced stage tumors with direct extension and distant metastasis.However,patients who received aggressive therapy showed a better overall survival.The aim of our study is to emphasize the importance of detecting ATC at an early stage and provide aggressive therapy to these patients.Since advanced stage ATC is associated with a dismal prognosis,we emphasize the need for randomized control trials and development of novel therapies that will be used to treat ATC.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway

Objectives:Thyroid cancer(THCA)is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide.And the number of patients dying from THCA has also gradually risen because the incidence continues to increase,so the mechanisms related to effective targets is necessary to improve the survival.This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer(THCA)cell proliferation and the associated pathways.Methods:Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development.COL4A2 expression in THCA tissues was analyzed using immunohistochemistry,and survival information was determined via Kaplan-Meier curves.The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses.Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity,respectively.Downstream of COL4A2 was identified by Gene set enrichment analysis(GSEA).The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model.Results:Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2.THCA patients with high COL4A2 expression had shorter recurrence-free survival.Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity.The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines.The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival.Conclusions:COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

A Study on the Explainability of Thyroid Cancer Prediction:SHAP Values and Association-Rule Based Feature Integration Framework

In the era of advanced machine learning techniques,the development of accurate predictive models for complex medical conditions,such as thyroid cancer,has shown remarkable progress.Accurate predictivemodels for thyroid cancer enhance early detection,improve resource allocation,and reduce overtreatment.However,the widespread adoption of these models in clinical practice demands predictive performance along with interpretability and transparency.This paper proposes a novel association-rule based feature-integratedmachine learning model which shows better classification and prediction accuracy than present state-of-the-artmodels.Our study also focuses on the application of SHapley Additive exPlanations(SHAP)values as a powerful tool for explaining thyroid cancer prediction models.In the proposed method,the association-rule based feature integration framework identifies frequently occurring attribute combinations in the dataset.The original dataset is used in trainingmachine learning models,and further used in generating SHAP values fromthesemodels.In the next phase,the dataset is integrated with the dominant feature sets identified through association-rule based analysis.This new integrated dataset is used in re-training the machine learning models.The new SHAP values generated from these models help in validating the contributions of feature sets in predicting malignancy.The conventional machine learning models lack interpretability,which can hinder their integration into clinical decision-making systems.In this study,the SHAP values are introduced along with association-rule based feature integration as a comprehensive framework for understanding the contributions of feature sets inmodelling the predictions.The study discusses the importance of reliable predictive models for early diagnosis of thyroid cancer,and a validation framework of explainability.The proposed model shows an accuracy of 93.48%.Performance metrics such as precision,recall,F1-score,and the area under the receiver operating characteristic(AUROC)are also higher than the baseline models.The results of the proposed model help us identify the dominant feature sets that impact thyroid cancer classification and prediction.The features{calcification}and{shape}consistently emerged as the top-ranked features associated with thyroid malignancy,in both association-rule based interestingnessmetric values and SHAPmethods.The paper highlights the potential of the rule-based integrated models with SHAP in bridging the gap between the machine learning predictions and the interpretability of this prediction which is required for real-world medical applications.

Anaplastic thyroid cancer: Unveiling advances in diagnosis andmanagement

The review article by Pavlidis et al published in World J Clin Oncol provides a meticulous analysis of the intricacies surrounding anaplastic carcinoma of the thyroid.Thyroid carcinoma encompasses a spectrum of diseases,each charac-terized by distinct behaviors and outcomes.Diagnostic approaches encompass a diverse array of tools.Surgery remains the pivotal treatment for anaplastic thyroid carcinoma.Radiotherapy and chemotherapy offer the best overall sur-vival in aggressive disease.Combinations of immunotherapy with targeted the-rapies,such as dabrafenib-trametinib,demonstrate potential for enhanced effect-iveness and improved survival outcomes.Multifaceted approach fuelled by precision medicine and interdisciplinary collaboration is imperative in charting a course toward improved outcomes in this formidable malignancy.

CircTIAM1 overexpression promotes the progression of papillary thyroid cancer by regulating the miR-338-3p/LASP1 axis

Background:Papillary thyroid cancer(PTC)is the most prevalent histological type of differentiated thyroid malignancy.Circular RNAs(circRNAs)have been implicated in the pathogenesis and progression of various cancers.circTIAM1(hsa_circ_0061406)is a novel circRNA with aberrant expression in PTC.However,its functional roles in PTC progression remain to be investigated.Methods:The expression levels of circTIAM1 in the PTC and the matched para-cancerous tissues were detected by quantitative real-time reverse-transcription PCR(qRT-PCR).The subcellular localization of circTIAM1 was examined by fluorescence in-situ hybridization(FISH).Kaplan-Meier plot was used to analyze the association of clinicopathological features with circTIAM1 expression.Bioinformatics databases were utilized to predict the target miRNAs of circTIAM1 and the downstream target mRNAs.RNA pulldown,RIP assay,and dual-luciferase reporter assay were used to confirm the interactions.Functional experiments,such as CCK-8,EDU staining,and apoptosis assays,as well as in vivo xenograft model were employed to explore the impacts of circTIAM1,miR-338-3p,and LIM/SH3 protein 1(LASP1)on the malignant phenotype of the PTC cells.Results:CircTIAM1 was highly expressed in PTC cells.Moreover,circTIAM1 silencing suppressed the proliferation and invasion of PTC cells in vitro and impaired tumorigenesis in vivo.Furthermore,miR-338-3p was verified as a miRNA target of circTIAM1.LASP1 was also identified as a downstream target of miR-338-3p.The anti-tumorigenic effect of miR-338-3p overexpression and the pro-tumorigenic effect of LASP1 was further explored by functional assays,which demonstrated that circTIAM1 modulated the PTC progression through targeting miR-338-3p/LASP1 axis.Conclusion:The overexpression of circTIAM1 is associated with the malignant progression of PTC.A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.

Pattern of Thyroid Cancer at King Abdulaziz University Hospital, Jeddah: A 10-Year Retrospective Study

Background and objective: Thyroid cancer is the most common endocrine malignancy. This report aims to describe the pattern of thyroid cancer presentations at King Abdulaziz University Hospital, Jeddah. Methods: This was a retrospect chart review of all thyroid cancer cases diagnosed between 2001 and 2010 at King Abdulaziz University Hospital, Jeddah. We documented patients’ demographic and clinical data, including age at diagnosis, tumor type and size, extrathyroidal extension, and metastasis. Results: A total of 114 thyroid cancer cases were diagnosed from 2001 through 2010. Females comprise the majority of cases (female to male ratio of 4:1). The mean ages of patients diagnosed with different thyroid cancers were: papillary thyroid cancer, 39.6 years;follicular thyroid cancer, 43.2 years;medullary thyroid cancer, 55.8 years;and anaplastic thyroid cancer, 46.0 years. Papillary thyroid cancer was diagnosed in 88 cases (77%), follicular thyroid cancer in 19 cases (17%), medullary thyroid cancer in 5 cases (4%), and anaplastic thyroid cancer in 2 cases (2%). Conclusion: Thyroid cancers are more common among females. The disease is diagnosed at a relatively young age among our patients (40 years). Papillary thyroid cancer is the most common type of thyroid cancer.