Well-differentiated Thyroid Cancer Patients Research Articles

Determination of Possible Biomarkers for Predicting Well-Differentiated Thyroid Cancer Recurrence by Different Ensemble Machine Learning Methods

Objective: Well-differentiated thyroid cancer (WDTC) is the most common thyroid malignancy and although it is curable, the risk of recurrence is high. In this study, classification algorithms based on clinicopathologic features of WDTC patients were used to determine the possible of recurrence in WDTC and to evaluate potential predictive factors, and possible biomarkers based on the optimal model were identified. Method: In this study, open access data on 383 patients with WDTC, 108 with recurrence and 275 without recurrence, were used. In order to predict recurrence in WDTC patients, features were selected using recursive feature elimination variable selection method among features and classification was performed with two ensemble learning methods (Random Forest, Adaboost). Results: Two different ensemble learning models used to classify recurrence in WDTC were Random Forest with an accuracy of 0.957, sensitivity of 0.889, specificity of 0.978, positive predictive value of 0.923, negative predictive value of 0.967, Matthews correlation coefficient of 0.878, G-mean of 0.945, F1-score of 0.906, and accuracy of 0.940, sensitivity of 0.889, specificity of 0.955, positive predictive value of 0.857, negative predictive value of 0.966, Matthews correlation coefficient of 0.833, G-mean of 0.910, F1-score of 0.873. Conclusion: According to variable importance based on the Random Forest, the 5 possible clinical biomarkers for predicting WDTC recurrence are Response, Risk, Node, Tumor, and age. In the light of these findings, patient management and treatment planning can be organized.

STRATIFICATION OF WELL-DIFFERENTIATED THYROID CANCER BASED ON MOLECULAR GENETIC TESTING: A LITERATURE REVIEW

Relevance: Thyroid cancer (TC) is among the most significant malignant diseases of the head and neck, with a steadily growing number of newly diagnosed cases throughout the world. Despite a relatively modest 17th place of TC in the structure of cancer incidence, its treatment in recent decades has seriously worried scientists and physicians due to a very rapid increase in TC incidence among young and middle-aged people. Iodine deficiency decreases immune function, and the effects of ionizing radiation play a role in the development of thyroid cancer. This leads to the development of a stratification system for well-differentiated thyroid cancer (WDTC) at the molecular genetic level. This system is necessary to select patients at risk of progression and to apply aggressive radionuclide therapy and suppressive hormone therapy only to those patients who need it. The study aimed to systematize data from the current literature to assess the need to develop a prognostic stratification of patients with WDTC based on molecular genetic testing. Methods: A literature review of scientific publications was conducted from the PubMed search database from September 2017 to December 2023. Inclusion criteria: publication date from 2017 to present for the main keywords: ‘High differentiated thyroid cancer”, “ prognostic stratification of WDTC based on molecular tests, ‘WDTC mutation markers.’ Some clinical studies of domestic and foreign specialists were also considered. Results: Based on a meta-review of literature data on prognostic stratification of WDTC patients, the rationale for expanding the panel of genetic markers associated with aggressive forms of WDTC is presented, the importance of gene mutation in the occurrence of disease recurrence, and the choice of adequate treatment is proven. Conclusions: Research efforts are underway to find genetic and pathomorphologic predictors of the prognosis of the disease. Knowledge of molecular and genetic mechanisms of tumorigenesis provides a wide range of opportunities for applying molecular diagnostics in differential diagnosis, prognosis of the course of the disease, and treatment of aggressive forms of tumors.

Association of Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio with Clinicopathological Features and Short-Term Outcome in Well-Differentiated Thyroid Cancer.

To assess the association of inflammatory markers with known risk factors and short-term outcome of well-differentiated thyroid cancer. Well-differentiated nonmetastatic thyroid cancer patients diagnosed and treated between September 2015 and December 2019 at Kasturba Hospital, Manipal, India, were retrieved for the study. Patients' presurgical blood parameters were noted, and neurtrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were calculated. Clinicopathological details along with tumor markers at baseline and at 6 months' follow-up were tabulated. Patients were categorized as complete disease clearance if their clinical examination was normal, stimulated thyroglobulin (Tg) was <1 ng/ml, Anti-thyroglobulin antibodies <65 IU/L or showing a decreasing trend, and follow-up I-131 whole-body scan was negative. The association of the inflammatory markers with known risk factors and short-term outcomes were compared. A total of 272 patients were analyzed in the study. The median NLR in our study cohort was 2.55 (mean = 3.96 with standard deviation [SD] =4.20) and the median LMR was 3.72 (mean = 3.79 with SD = 1.94). The disease clearance rate of our study cohort was 73.9%. The median NLR (2.4 vs. 3.1) and LMR (3.13 vs. 3.93) were significantly different among the patients with complete disease clearance and those with persistent disease (P = 0.008 and P = 0.003, respectively). The known risk factors such as multifocality (P = 0.04), tumor size (P = 0.013), lymph node metastases (P = 0.001), and baseline Tg (P ≤ 0.001) were significantly associated with persistent disease at 6 months. The NLR showed a positive correlation and LMR had a negative correlation with the known risk factors, however, the associations were not statistically significant. The NLR and LMR are simple yet potential prognostic tools in well-differentiated thyroid cancer.

The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients

PurposeTo introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine 131I therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by 124I PET.MethodsPatients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUVmax > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-124I to determine the individual lesion radiation-absorbed dose. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion radiation dose metrics, with candidate biomarkers (“predictors”) such as SUVmax and activity in microcurie per gram, from a single imaging timepoint.ResultsIn the 169 lesions (in 15 patients) that received 131I therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming wide heterogeneity of lesion radiation dose. Initial findings from the prediction curve on all 208 lesions confirmed that a 48-h SUVmax was the best predictor of lesion radiation dose and permitted calculation of the 131I activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals.ConclusionsBased on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint 124I-PET-based dosimetry biomarker for RAI in patients with mDTC. The approach provides clinicians with a tool to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed dose (cGy) for selected index lesions based on a single 48-h measurement 124I-PET image, provided the selected activity does not exceed the maximum tolerated activity (MTA) of < 2 Gy to blood, as is standard of care at Memorial Sloan Kettering Cancer Center.Trial registrationNCT04462471, Registered July 8, 2020.NCT03647358, Registered Aug 27, 2018.

Relationship between the Expression of BRAF V600E and Ki-67 with the Recurrence of Well-Differentiated Thyroid Cancer.

This study aims to determine the relationship between BRAF V600E and Ki-67 expression with the recurrence of well-differentiated thyroid cancers. The design of this study is a case-control and survival analysis. The data was taken from the thyroid cancer registry in Padang, Indonesia, where samples were taken from well-differentiated thyroid cancer patients who underwent therapy according to the protocol between 2015 and 2020. During this period, 396 well-differentiated thyroid cancer cases were obtained, of which 24 cases experienced recurrence. Of the cases that recurred, we found as many as 20 cases with complete tissue preservation documents later designated as cases. Calculating the expression of BRAF V600E and Ki-67 was performed semi-quantitatively per 100 tumor cells at random. For statistical tests, chi-square and survival analysis were performed using Kaplan-Meier and Cox regression analysis using a computer program with a determined significance level of p < 0.05. BRAF V600E expression was found in all cases and controls in which 85% of cases had vigorous intensity and 15% had moderate intensity. Ki-67 expression was found positive in 35% of the recurrent cases, while in control, there was no expression of Ki-67. Patients with positive Ki-67 expression had shorter median survival than patients with negative Ki-67 expression of 40 months (95% CI 35-45 months) to 60 months (95% CI 53-67 months). An association was obtained between Ki-67 expression and thyroid cancer recurrence based on disease-free survival (p<0.05) with HR 1.34 (95% CI 1.13-1.92). This study confirms the association between Ki-67 expression and thyroid cancer recurrence based on disease-free survival and can be used as alternative to support the significance of Ki-67 as a predictor of thyroid cancer recurrence. In addition, Ki-67 can complement other molecular markers such as the BRAF V600E, to increase its prognostic strength.

Locally Advanced, pT4 Well-Differentiated Thyroid Cancer in Young Patients – A Population-Based Study

<h3>Purpose/Objective(s)</h3> Locally advanced, non-metastatic pT4 well-differentiated thyroid cancer (WDTC) diagnosed at age <55 years is considered to be Stage I disease by the American Joint Committee on Cancer (AJCC) 8^th edition staging system implying excellent cause-specific survival (CSS) outcomes of ≥95% at 10 years. There are no published outcomes however on this specific cohort of patients, and they may be underrepresented in published outcome series as they comprise of <5% of all WDTC patients. Thus, the objective was to determine the recurrence and survival outcomes of this cohort. <h3>Materials/Methods</h3> We conducted a population-based retrospective study of all patients with pT4 WDTC diagnosed at age <55 years, treated in our province from 1985 to 2013 were extracted. Demographic and treatment factors were extracted. The primary endpoints were cumulative incidence of locoregional recurrence (LRR), cause-specific survival (CSS) and overall survival (OS). Competing risk Fine-Grays analysis and Cox-proportional hazards model was used. <h3>Results</h3> There were 218 patients (median follow up 18.2 years) with 137 under the age of 45. Patients were all treated with thyroidectomy. Most patients had papillary histology (95.9%). Adjuvant radioactive iodine was administered in 88% of cases, and 43% received adjuvant external-beam radiotherapy (EBRT). The 15-year LRR was 21%. On multivariate analysis, there was a trend towards EBRT receipt and lower LRR (HR:0.47, p=0.06). Of the patients who did not receive EBRT, but had a LRR (n=19), 11 were salvaged (with RAI, EBRT, and surgery) and only two died of WDTC (both from LRR). For the cohort as a whole, the 15-year CSS was 96%. There were four deaths secondary to LRR and seven deaths from distant disease. Advanced age, larger tumor size, higher T stage, and presence of LVI were associated with worse CSS (all p<0.05), though we note the limited number of events limit the conclusions from our multivariate analysis. The 15-year OS was 93%. Older age, tumor size, and lymphovascular invasion were significantly associated with worse OS (all p<0.05). On multivariate analysis, EBRT receipt was not associated with improved CSS or OS. <h3>Conclusion</h3> Despite very locally advanced disease, patients with non-metastatic pT4 WDTC, <55 years at diagnosis, have favorable long-term outcomes. Further prospective studies of adjuvant EBRT are needed in this population.

Surgeon Thyroidectomy Case Volume Impacts Disease-free Survival in the Management of Thyroid Cancer.

To assess the association between surgeons thyroidectomy case volume and disease-free survival (DFS) for patients with well-differentiated thyroid cancer (WDTC). A secondary objective was to assess a surgeon volume cutoff to optimize outcomes in those with WDTC. We hypothesized that surgeon volume will be an important predictor of DFS in patients with WDTC after adjusting for hospital volume and sociodemographic and clinical factors. In this retrospective population-based cohort study, we identified WDTC patients in Ontario, Canada, who underwent thyroidectomy confirmed by both hospital-level and surgeon-level administrative data between 1993 and 2017 (N=37,233). Surgeon and hospital volumes were calculated based on number of cases performed in the year prior by the physician and at an institution performing each case, respectively and divided into quartiles. A multilevel hierarchical Cox regression model was used to estimate the effect of volume on DFS. A crude model without patient or treatment characteristics demonstrated that both higher surgeon volume quartiles (p < 0.001) and higher hospital volume quartiles (p < 0.001) were associated with DFS. After controlling for clustering and patient/treatment covariates and hospital volume, moderately low (18-39/year) and low (0-17/year) volume surgeons (hazard ratios [HR]: 1.23, 95% confidence interval [CI]: 1.09-1.39 and HR: 1.34, 95% CI: 1.17-1.53 respectively) remained an independent statistically significant negative predictor of DFS. Both high-volume surgeons and hospitals are predictors of better DFS in patients with WDTC. DFS is higher among surgeons performing more than 40 thyroidectomies a year. 3 Laryngoscope, 133:S1-S15, 2023.

Mutational analysis using next generation sequencing in pediatric thyroid cancer reveals BRAF and fusion oncogenes are common

BackgroundWe previously described mutation rates of BRAFV600E, RAS, RET-PTC and PAX8-PPARγ in pediatric subjects with well-differentiated thyroid cancer (WDTC). We expanded the cohort adding next-generation sequencing (NGS) and assessed genotype-phenotype correlations. MethodsSingle-center retrospective cohort examining thyroidectomy tissue blocks from consecutive pediatric WDTC patients between 2001 and 2015. Tissues were analyzed at Quest Diagnostics for BRAF, RAS mutations, RET-PTC and PAX8-PPARγ, and additional fusions, using standalone and NGS tests. WDTC included papillary (PTC), follicular (FTC) and follicular-variant PTC (FVPTC). ResultsWe genotyped 46 samples (36 females). Mean age at diagnosis was 14.7 years and the cohort comprised of mostly Hispanic (60.9%) and Caucasian (26.1%) patients. Mean follow-up was 3.5 years. Genetic alterations (GA) were noted in 69.6%, with BRAFV600E (n = 11), and RET-PTC (n = 8) detected only in PTC. GA were detected in 2/7 FTC (1 PAX8-PPARγ, 1 NRAS) and 6/10 FVPTC (3 PAX8-PPARγ, 1 STRN-ALK, 1 BRAFK601E, 1 NRAS). Patients with BRAFV600E were predominantly Hispanic (81.8%) and >15 years (81.8%), whereas 87.5% RET-PTC and 50% other-fusions occurred in patients ≤15 years (p = 0.044). Of the 29 PTC patients, 82.8% had GA: BRAFV600E (37.9%), RET-PTC (27.6%), 17.2% other fusion-oncogenes (2 -ALK, 3 -NTRK). Non-RET fusions had the highest vascular invasion (100%, p = 0.042 vs RET-PTC) and frequent lymphatic invasion (80%). GA were most common in PTC with cervical metastasis. ConclusionsBRAFV600E was the most common single mutation, especially in older and Hispanic adolescents. All fusions combined are more common than BRAFV600E. NGS reveals a genetic basis in most pediatric WDTC, which may have implications for the role of molecular testing and systemic therapy.

Prognostic Value of Serum Thyroglobulin and Anti-Thyroglobulin Antibody in Thyroid Carcinoma Patients following Thyroidectomy.

Well-differentiated thyroid cancer (WDTC) is a malignant head and neck tumor with a very high incidence. Thyroidectomized WDTC patients have been referred to nuclear medicine for radioactive iodine (RAI) ablation therapy and/or annual follow-up with diagnostic whole-body imaging. Serum thyroglobulin (TG) and thyroglobulin antibodies (TGAb) are biochemical tumor markers used to monitor WDTC. A global rise in the prevalence of WDTC is increasing the number of thyroidectomized patients requiring lifelong monitoring for persistent or recurrent diseases. The present study aimed to identify the most successful prognostic factors in well-defined thyroid carcinoma patients following total thyroidectomy and RAI therapy, followed by an estimation of the cutoff value of TG and TGAb. In this context, a total of 100 subjects were recruited and classified as follows: 60 thyroid carcinoma patients underwent total thyroidectomy and successful RAI therapy, while 40 normal healthy individuals matched for age, sex, and socioeconomic status constituted the control group. Interestingly, the levels of TG did not differ significantly between the relapsed and non-relapsed cases, but the levels of TGAb differed significantly between the relapsed and non-relapsed cases. Collectively, TG and TGAb are considered the most successful prognostic factors in well-defined thyroid carcinoma patients after total thyroidectomy and RAI therapy. The present study also concluded that the TGAb determination was better than that of the TG level, with a cutoff value of 10 ng/mL. These findings provide baseline information for follow-up and lifelong monitoring of thyroidectomized WDTC patients. Further research is warranted to explore more about serum TG and TGAb in thyroid carcinoma patients on a larger scale.

Surgical Case Volume has an Impact on Outcomes for Patients with Lateral Neck Disease in Thyroid Cancer.

This study aimed to assess whether surgical case volume for lateral neck dissection has an impact on the survival of patients who have well-differentiated thyroid cancer (WDTC) with lateral cervical node metastases. The authors used a population-based cohort study design. The study cohort consisted of WDTC patients in Ontario Canada who underwent thyroidectomy and lateral neck dissection. These patients were identified using both hospital- and surgeon-level administrative data between 1993 and 2017 (n = 1832). Surgeon and hospital volumes were calculated based on the number of cases managed in the year before the procedure by the physician and at the institution managing each case, respectively, and divided into tertiles. Multilevel Cox regression models were used to estimate the effect of volume on disease-free survival (DFS). A crude model without patient or treatment characteristics demonstrated that DFS was associated with both higher surgeon volume tertiles (p < 0.01) and higher hospital volume tertiles (p < 0.01). After control for clustering, patient/treatment covariates, and hospital volume, the lowest surgeon volume tertile (range, 0-20/year; mean, 6.5/year) remained an independent statistically significant negative predictor of DFS (hazard ratio, 1.71; 95 % confidence interval, 1.22-2.4; p < 0.01). Surgeon lateral neck dissection case volume is a predictor of better DFS for thyroid cancer patients, with the lowest surgeon volume tertile (<20 neck dissections per year) demonstrating poorer DFS.

MicroRNA-Based Risk Score for Predicting Tumor Progression Following Radioactive Iodine Ablation in Well-Differentiated Thyroid Cancer Patients: A Propensity-Score Matched Analysis.

Simple SummaryThe three-tiered American Thyroid Association (ATA) risk stratification helps clinicians tailor decisions regarding follow-up modalities and the need for postoperative radioactive iodine (RAI) ablation and radiotherapy. However, a significant number of well-differentiated thyroid cancers (DTC) progress after treatment. Current follow-up modalities have also been proposed to detect disease relapse and recurrence but have failed to be sufficiently sensitive or specific to detect, monitor, or determine progression. Therefore, we assessed the predictive accuracy of the microRNA-based risk score in DTC with and without postoperative RAI. We confirm the prognostic role of triad biomarkers (miR-2f04, miR-221, and miR-222) with higher sensitivity and specificity for predicting disease progression than the ATA risk score. Compared to indolent tumors, a higher risk score was found in progressive samples and was associated with shorter survival. Consequently, our prognostic microRNA signature and nomogram provide a clinically practical and reliable ancillary measure to determine the prognosis of DTC patients.To identify molecular markers that can accurately predict aggressive tumor behavior at the time of surgery, a propensity-matching score analysis of archived specimens yielded two similar datasets of DTC patients (with and without RAI). Bioinformatically selected microRNAs were quantified by qRT-PCR. The risk score was generated using Cox regression and assessed using ROC, C-statistic, and Brier-score. A predictive Bayesian nomogram was established. External validation was performed, and causal network analysis was generated. Within the eight-year follow-up period, progression was reported in 51.5% of cases; of these, 48.6% had the T1a/b stage. Analysis showed upregulation of miR-221-3p and miR-222-3p and downregulation of miR-204-5p in 68 paired cancer tissues (p < 0.001). These three miRNAs were not differentially expressed in RAI and non-RAI groups. The ATA risk score showed poor discriminative ability (AUC = 0.518, p = 0.80). In contrast, the microRNA-based risk score showed high accuracy in predicting tumor progression in the whole cohorts (median = 1.87 vs. 0.39, AUC = 0.944) and RAI group (2.23 vs. 0.37, AUC = 0.979) at the cutoff >0.86 (92.6% accuracy, 88.6% sensitivity, 97% specificity) in the whole cohorts (C-statistics = 0.943/Brier = 0.083) and RAI subgroup (C-statistic = 0.978/Brier = 0.049). The high-score group had a three-fold increased progression risk (hazard ratio = 2.71, 95%CI = 1.86–3.96, p < 0.001) and shorter survival times (17.3 vs. 70.79 months, p < 0.001). Our prognostic microRNA signature and nomogram showed excellent predictive accuracy for progression-free survival in DTC.

Clinical predictors of I-131 therapy failure in differentiated thyroid cancer by machine learning: A single-center experience.

Well-differentiated thyroid carcinoma is predominantly a slow-growing malignancy, amendable to treatment, and has an excellent prognosis following thyroidectomy and radioiodine (RAI) therapy. However, patients who fail the initial RAI treatment attempt may require repeated RAI or other treatments and with this, comes an associated impact on patient quality of life. Therefore, the anticipation of patients in whom there is a higher risk of RAI failure may help in patient risk stratification and subsequent management. We conducted a retrospective review to determine the factors associated with initial RAI therapy failure in well-differentiated thyroid cancer patients. Using scikit-learn from Python, we implemented a machine-learning algorithm to determine the clinical patient factors associated with a higher likelihood of treatment resistance. We found that clinical factors such as tumor focality (P = 0.026) and lymph node invasion at surgical resection (P = 0.0135) were significantly associated with initial treatment failure following RAI. Elevated serum thyroglobulin (Tg) and Tg antibody levels following surgery but before RAI were also associated with treatment resistance (P < 0.0001 and P = 0.011 respectively). Less expected factors such as decreased time from surgery to RAI were also associated with treatment failure, however not to a statistically significant degree (P > 0.064). Clinical outcomes following RAI can be stratified by identifying factors that are associated with initial treatment failure. These findings can help restratify patients for RAI treatment and change patient management in certain cases. Such stratification will ultimately help to optimize successful treatment outcomes and improve patient quality of life.

Outcomes of Tracheal Resections in Well-Differentiated Thyroid Cancer-A case series and meta-analysis.

Tracheal invasion in thyroid cancer is a well-known form of advanced disease. There is an ongoing controversy over outcomes of tracheal shaving in this situation. The aim of this study was to compare the results of tracheal shaving to radical resections in patients with low-volume tracheal involvement. An institutional case series and a meta-analysis was conducted. All studies that included patients diagnosed with well-differentiated thyroid cancer (WDTC) and tracheal invasion were analyzed. Patients with low-volume tracheal invasion (according to the Shin classification) were extracted from the various studies and subsequently included in this study. The outcomes of tracheal shaving and radical resection were consolidated and compared. All recurrences and mortality over 10years of follow-up were calculated using the Kaplan-Meier method. Institutional case series included 22 patients diagnosed with WDTC and tracheal invasion that underwent resection. There was one case of recurrence (4.5%) during the follow-up period and no mortality. The meta-analysis yielded a total of 284 patients from six studies who met the inclusion criteria. The 10-year overall survival was 82.4% for the shave group and 80.8% for the resection group. The combined Kaplan-Meier curves revealed no statistically significant difference between the two techniques (hazard ratio [HR] = 0.86, P = .768). The combined 10-year local control rate of the shave group was 90.2%. The outcomes of tracheal shaving in low-volume invasion are similar to more aggressive forms of tracheal resections. Shave resection is oncologically safe in carefully selected WDTC patients demonstrating minimal tracheal invasion.

Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up

ObjectiveThe objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up.MethodsA retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019.ResultsIn total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively).ConclusionsWDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.

Current opportunities of comprehensive therapy for bone metastases from thyroid cancer

Background. Approximately 10 % of patients with well-differentiated thyroid cancer (WDTC) develop distant metastases. Of them, only 23 % have bone metastases. Complications associated with metastatic lesion in the skeleton significantly affect overall condition of patients and their quality of life. Surgery and pharmacotherapy are highly traumatic and toxic. Bisphosphonates are stable structural analogues of pyrophosphate that inhibit osteoclast activity, thereby reducing bone resorption, which increases the time to development of bone complications, improves patient’s quality of life, and reduces pain.The study objective is to assess performance status and pain severity in WDTC patients with distant bone metastases after bisphosphonate therapy.Materials and methods. We analyzed clinical experience in using bisphosphonates in WDTC patients treated in P.A. Herzen Moscow Oncology Research Institute between 2016 and 2020. This study included 41 patients with WDTC and bone metastases of various locations. Pain severity was evaluated using a 5-point verbal scale; performance status was evaluated using the Eastern Cooperative Oncology Group scale.Results. We observed an improvement in patients’ performance status (from score 2 to 0 according to the Eastern Cooperative Oncology Group scale) in response to therapy. We also found a decrease in pain intensity (from score 4 to 1.5).Conclusion. The inclusion of bisphosphonates into the treatment scheme for WDTC patients with bone metastases can reduce pain intensity and improve performance status.

Clinical Course from Diagnosis to Death in Patients with Well-Differentiated Thyroid Cancer.

Because of the low mortality rate of well-differentiated thyroid cancer (WDTC), investigation of the clinical course leading to death is limited. We analyzed the cause of death and clinical course from diagnosis to death in patients who died of WDTC. A total of 592 WDTC patients died between 1996 and 2018. After exclusion, 79 patients were enrolled and divided into four groups based on their clinical course; that is, inoperable at the time of diagnosis (inoperable), distant metastasis (DM) detected at the time of diagnosis (initial-DM), DM detected during follow-up (late-DM), and loco-regional disease (L-R). Lung (55.6%) in papillary thyroid carcinoma (PTC) and bone (46.7%) in follicular thyroid carcinoma (FTC) were the most common metastasis locations. The most common causes of death were respiratory failure (32.3%) and airway obstruction (30.6%) in PTC, and complications due to immobilization arising from bone metastasis (35.3%) in FTC. Brain metastasis was found in 13.3% of patients and had the worst prognosis. The overall survival (OS) differed significantly (p = 0.001) according to clinical course; the inoperable had the shortest survival, followed by the initial-DM, L-R, and late-DM. However, OS did not differ significantly between PTC and FTC patients with initial-DM (p = 0.83). Other causes of death were far more common than death resulting from WDTC. In patients dying of WDTC, the major cause of death varied by metastatic site. OS differed according to clinical course, but not histologic type. Timing and DM sites differed between PTC and FTC.

Evaluation of CYFRA 21.1 as a dedifferentiation marker of advanced thyroid cancer

Purpose of the Study:Well-differentiated thyroid carcinomas have good prognosis, but as it de-differentiates, the survival rates go down. Early identification of such patients needs a marker which indicates the dedifferentiation process. CYFRA 21.1 has also shown to be increased in patients with 131I refractory thyroid cancer. We tested whether CYFRA 21.1 can differentiate between 131I avid and refractory tumors.Methodology:Well-differentiated thyroid cancer patients with known distant metastases were accrued and tested for stimulated and unstimulated thyroglobulin and CYFRA 21.1. All patients underwent 131I whole-body scan, 131I post therapy scan, and 18F-Fluorodeoxyglucose positron emission tomography-computed tomography. Those with even a single 131I nonavid lesion were considered 131I refractory disease. CYFRA 21.1 of both 131I avid and nonavid was compared, and CYFRA 21.1 levels against disease extent were analyzed.Results:CYFRA 21.1 levels were significantly elevated in 131I refractory group. A cutoff value of 2.07 ng/ml distinguished between 131I avid and refractory disease with high sensitivity and specificity (88% and 89. 7%, respectively). However, CYFRA 21.1 levels were similar in patients when analyzed based on disease sites.Conclusion:CYFRA 21.1 can be utilized to differentiate between 131I avid and refractory diseases. Further long-term studies are required to use it as a predictive and prognostic marker.

Prognostic risk factors for rare oncocytic variantin 101 cases of papillary thyroid carcinoma.

Oncocytic variant (OV) is an unusual subtype of papillary thyroid cancer whose histopathologic diagnostic criteria, clinicopathologic features and biological behavior are different and have not been comprehensively studied, characterized in literature. Previous studies present conflicting results upon its prognosis. We investigated demographic and clinicopathologic risk factors affecting its prognosis while presenting our clinical experience. This is a retrospective cohort study reviewing 101 patients of OV from an archive of 4500 well-differentiated thyroid cancer patients treated with iodine-131 (131I) between 1991 and 2017. Predefined parameters of age, gender, tumor size (TS), total 131I dose, time to recurrent disease, overall survival, extrathyroidal extension, multifocality, vascular invasion, accompanying other variants, capsular status of thyroid gland, initial cervical lymph node (LN) metastases, preablation stimulated thyroglobulin level, background thyroiditis and stage were evaluated by statistical comparison between metastatic and nonmetastatic groups. Seventeen cases (17%) developed metastases/recurrence, 70% of the recurrences occured before 24 months. Four patients (4%) died during the follow-up. Metastatic sites were usually cervical LN, local recurrence in thyroid bed and lungs. Multivariate analysis revealed stage (IV) and TS were the main parameters impacting recurrence/metastases. In the follow-up, isolated cervical LN metastases were found in 41% of metastatic cases, while 12% had sole recurrence in thyroid bed. Eighty eight percent of the metastatic disease included locoregional (cervical) and/or remote LN. The recurrences were associated with initial thyroid masses greater than 3.5cm in diameter. We found that the prognosis of OV is not poor in our series. Stage (IV) and tumor size are the main risk factors in metastatic development.

The efficacy of radioactive iodine for the treatment of well-differentiated thyroid cancer with distant metastasis.

ObjectiveRadioactive iodine (131I) has been used as a treatment for high-risk well-differentiated thyroid cancer after thyroidectomy. The aim of this study was to evaluate the long-term follow-up results after using high accumulated doses of 131I (>600 mCi) for the treatment of well-differentiated thyroid cancer.Patients and methodsIn this study, we retrospectively evaluated prospectively enrolled patients with well-differentiated thyroid cancer who were treated and followed up in Chang Gung Memorial Hospital in Linkou and Keelung, Taiwan. All the patients underwent thyroidectomy between 1979 and 2016.ResultsFor our study, 228 patients with papillary and follicular thyroid carcinoma with distant metastases were enrolled. Of the 228 patients, 71 (31.1%) received 131I therapy with an accumulated dose of at least 600 mCi. Forty-four died because of disease-specific mortality (DSM) after a mean follow-up of 10.6±6.3 years. Compared with the patients in the DSM group, which included 27 survival cases, patients who were younger, and those with a multifocal tumor, more extensive thyroidectomy, and papillary thyroid carcinoma showed better prognosis. The DSM group included a higher percentage of patients who developed a secondary primary cancer after receiving a diagnosis of thyroid cancer than the survival group (18.2 vs. 3.7%). However, the difference did not reach statistical significance (P=0.075).Conclusion131I provided an effective therapeutic modality for well-differentiated thyroid cancer patients with distant metastasis. After a mean of follow-up 10 years, more than 60% of cases resulted in DSM when high accumulated 131I doses were administered.

Well-differentiated thyroid cancer and robotic transaxillary surgery at a North American institution

BackgroundRecent studies from Asia have reported the safety and feasibility of robotic-assisted thyroid surgery. In the United States, several small series and case reports have been published, mostly regarding treatment of benign disease. The aim of our study is to report the safety and feasibility of robotic surgery for well-differentiated thyroid cancer patients at a North American institution. Materials and MethodsWe performed a retrospective cohort study using a prospectively collected single-center clinical database at Tulane University Medical Center. We included all well-differentiated thyroid cancer patients who underwent robotic-assisted or conventional cervical approach thyroid surgery with or without lymph node dissections at our institution from January 2015 to June 2017. Patient demographics and perioperative data were collected and analyzed. ResultsA total of 144 surgeries for thyroid cancer were performed; 35 (24.3%) were robotic-assisted. There were no significant differences in estimated blood loss, operative times, complication rates, specimen sizes, positive microscopic margins, number of lymph nodes removed with associated lymph node dissections, patient follow-up duration, or clinical recurrence rates between the two groups. Overall length of stay was shorter for robotic-assisted surgery, at 0.6 ± 0.9 d, versus 1.1 ± 1.2 d for conventional open surgery (P = 0.009). For robotic-assisted surgery, 19 patients (54.3%) were discharged on the day of procedure, and only one patient was admitted as inpatient to the hospital (2.9%). ConclusionsRobot-assisted thyroid surgery is a safe, feasible, and oncologically sound approach for a select group of well-differentiated thyroid cancer patients. However, long-term studies are needed.