Risk Stratification of Differentiated Thyroid Cancer: A Single-Center Study in Basrah.

Background Differentiated thyroid cancer is a common endocrine cancer; most of it has an indolent course and favorable outcomes, with a subset of patients having the risk of disease recurrence, which can be assessed using the fixed American Thyroid Association (ATA) risk stratification system or the dynamic response to therapy risk stratification that can be modified during patients follow-up. Aim The aim of this article is to assess the risk stratification of patients having differentiated thyroid cancer. Methods This is a retrospective cross-sectional study in which we evaluated medical records of 75 patients having differentiated thyroid cancer to assess the baseline ATA risk of recurrence and compared it to the results of dynamic risk stratification in response to therapy at 6-12 months post-surgery and at the last visit. Thyroglobulin level, anti-thyroglobulin antibody, thyroid ultrasound, and cytopathological examination were used to determine dynamic response to therapy and divided subjects into four groups: excellent response (ER), biochemical incomplete response (BIR), structural incomplete response (SIR), and indeterminate response (IR). Results At baseline, 55 patients had low risk, 14 patients had intermediate risk, and six patients had high risk. At 6-12 months post-surgery, in the low-risk group, ER, BIR, and IR responses were observed in 56.4%, 5.5%, and 38.2% of patients, respectively, and none of them exhibited SIR. In the intermediate-risk group, ER, BIR, and IR responses were observed in 57.1%, 21.4%, and 21.4% of patients, respectively, and none exhibited SIR. Among the high-risk group, two patients had ER, two patients had BIR, one patient had IR, and one patient had SIR. At the last visit, ER, BIR, and IR were observed in 65.5%, 9.1%, and 25.5% of low-risk patients, respectively, and no patient developed SIR. In the intermediate-risk group, ER, BIR, and IR were observed in 50%, 21.4%, and 28.6% of patients, respectively, and no patients developed SIR. Among the high-risk group, three patients achieved ER, one had BIR, one had IR, and one had SIR. Conclusion Most of the differentiated thyroid cancers in this study are low-risk. Dynamic risk stratification appears to be an effective tool in the follow-up of this population of patients having differentiated thyroid cancer.

Dynamic Risk Stratification Integrated with ATA Risk System for Predicting Long-Term Outcome in Papillary Thyroid Cancer.

BACKGROUND: In recent years, there has been a renewed interest in thyroid cancer management paradigms that use individualized risk assessments as the basis for treatment and follow-up recommendations. In this study, we assumed that the long-term follow-up of differentiated thyroid cancer patients might be better tailored by integrating the response to initial therapy with the America Thyroid Association (ATA) risk classes. METHODS: This retrospective study included low- and intermediate-risk papillary thyroid cancer (PTC) patients followed up for a median time of 8 years and classified according to the response to initial therapy assessed 6-12 months after initial treatment. RESULTS: After a median follow-up of 8 years, in the initial excellent response subgroup of PTC patients (n = 522), the rate of recurrent disease was significantly higher in intermediate-risk patients than in low-risk PTC patients (6.9% versus 1.2%, p = 0.0005). Similarly, in the initial biochemical incomplete response subgroup (n = 82), the rate of excellent response was significantly higher in low-risk PTC patients (58.0%) than in intermediate-risk PTC patients (33.3%) (p = 0.007). Finally, in the initial structural incomplete response subgroup (n = 66), the rate of excellent response was higher in low-risk patients (80.0%) than in intermediate-risk patients (46.4%) (p = 0.08). Moreover, all patients with initial indeterminate response had an excellent response at the last follow-up visit. ATA risk classes were independently associated with long-term outcome in each subgroup of patients classified dynamically after initial therapy and the overall prognostic performance, defined via ROC curve analysis, of response to initial therapy integrated with the ATA risk system (AUC: 0.89; 95% CI: 0.86-0.92) was significantly higher compared to the ATA risk stratification (AUC 0.69; 95% CI: 0.65-0.74, p < 0.001) or the dynamic risk stratification (DRS) systems alone (AUC: 0.86 95% CI: 0.82-0.90, p = 0.007). CONCLUSIONS: This study of a large cohort of PTC patients showed that the initial ATA risk criteria may be useful for improving the risk-adapted management of PTC patients based on the response to initial therapy.

Appropriateness of 14-year cutoff in pediatric differentiated thyroid cancer: Comparison of clinical characteristics and long-term outcomes in 14 years and younger and 15-18 years age groups.

BACKGROUND: Pediatric differentiated thyroid cancers (DTCs) differ in pathophysiology, presentation, and clinical outcomes from adult DTCs. However, the cutoff age for defining pediatric DTCs remains debatable, with the American Thyroid Association (ATA) and International Incidence of Childhood Cancer (IICC) report recommending different cutoffs of 18 and 14 years, respectively. In this study, we investigated the appropriateness of 14-year cutoff by comparing the clinical characteristics and long-term outcomes in the 14 years and younger and 15-18 years age groups. METHODS: Data of DTC patients, aged 18 years and older, from 1981 to 2016, were sequentially extracted and compared between two age groups: ≤14 and 15-18 years. RESULTS: Total of 176 pediatric DTC patients were included (age group ≤14 years: n = 75; age group 15-18 years: n = 101). None of the baseline clinical characteristics were significantly different between the two age groups. At 2-year follow-up, patients in the age group ≤14 years had significantly higher incomplete response rate compared to those in the age group 15-18 years (69% vs. 42%, respectively, p < .001). However, over a median follow-up of 10.6 years (interquartile range: 7.7-15.5), the 5- and 10-year Disease-free survival (DFS) probabilities were not significantly different (p = .406). On multivariate analysis, incomplete response at 2-year follow-up was the sole independent predictor of poor DFS (hazard ratio: 5.85, 95% confidence interval: 1.69-20.23). CONCLUSIONS: Subdivision of pediatric DTCs into less than or equal to 14 years and 15-18 years age groups did not have any long-term predictive value. The cutoff of 18 years as recommended by ATA is reasonable and should be uniformly followed to avoid inconsistencies and confusion.

Differentiated Thyroid Cancer in a Pediatric Population: Estimating the Risk of Recurrence and Evolution Over Time.

Background Differentiated thyroid cancer (DTC) is the most common endocrine cancer during childhood, and the prognosis is usually good. The 2015 American Thyroid Association (ATA) pediatric guidelines for DTC classify patients into three categories (low, intermediate, and high) that represent the risk for persistent/recurrent disease. The "Dynamic Risk Stratification" (DRS) System showed that, in adults, reassessment of disease status during follow-up was a better predictor of disease status at the end of follow-up when compared to ATA risk stratification. This system is still not validated for the pediatric population with DTC. Our aim was to evaluate the usefulness of the DRS system in predicting DTC disease behaviour in this specific population. We also aimed to evaluate potential clinical-pathological factors associated with persistent disease at the end of follow-up. Methods A retrospective analysis of 39 pediatric patients (≤18 years) with DTC was conducted in our institution between 2007 and 2018, including 33 patients who had follow-up ≥ 12 months; these were classified into ATA risk groups and re-stratified according to their response to treatment at 12-24 months of follow-up. The associations between the ordinal variables of the baseline ATA risk group and the disease status re-evaluated 12-24 months after diagnosis (as per the DRS system) and at the end of follow-up were evaluated using a linear-by-linear association test. Gender, age at diagnosis, tumor size, multicentricity, extrathyroid extension, vascular invasion, lymph node metastasis, distant metastasis, and stimulated thyroglobulin (sTg) during the first RAI administration were evaluated as potential factors associated with persistent disease at 27 months after diagnosis using Firth's bias-reduced penalized-likelihood logistic regression. Results In this study, 39 patients were retrospectively analyzed, including 33 patients who had follow-ups ≥ 12 months with a median time of 56 (27-139) months who were classified in ATA risk groups and then re-stratified depending on their response to treatment between 12 and 24 months of follow-up. There was a statistically significant association between ATA risk groups and re-evaluation at 12 and 24 months (p=0.001) and between these two stratifications and the state of disease at final follow-up (p<0.001 for both). Factors with a statistically significant association with persistent disease at 27 months of follow-up were male sex, lymph node metastases at diagnosis, distant metastasis, extrathyroidal extension, and stimulated Tg values. Conclusions The assessment of the response to treatment between 12 and 24 months and at the end of follow-up refines the initial ATA risk stratification, confirming that dynamic risk evaluation is also helpful in the pediatric population.

Risk Reassessment of Differentiated Thyroid Cancer in Ahvaz, Iran: A Cross-sectional Retrospective Study.

Background: Accurate evaluation of response to treatment in differentiated thyroid cancer (DTC) is the sine qua non of preventing over-treatment in low-risk patients and implementing appropriate interventions in high-risk individuals. Objectives: This study aimed to assess the response to therapy in DTC patients based on dynamic stratification method. Methods: In this cross-sectional study, 154 medical records of subjects with DTC (with at least 6 months after total thyroidectomy) and referred to endocrinology clinics in Ahvaz, Iran, from April 2020 to May 2021 were examined. Patients were stratified according to a dynamic risk stratification system (informed by their specific clinical, histopathological, and ultrasonography findings, and other diagnostic imagines) into four groups: Excellent response (ER), indeterminate response (IR), biochemical incomplete response (BIR), and structural incomplete response (SIR). Results: For a mean follow-up period of 28.59 months, excellent response to treatment was observed in 92 patients (59.7%), indeterminate response to treatment was found in 32 patients (20.8%), biochemical incomplete response was detected in 2 patients (1.3%), and structural incomplete response was seen in 28 patients (18.2%). In the group with low risk of recurrence, ER and IR were observed in 79.2% and 15.6% of the patients, respectively (P < 0.0001). In the group with an intermediate risk of recurrence, ER was found in 32% of the patients, while IR and SIR + BIR were seen in 34% and 34% of the patients, respectively (P < 0.0001). No cases of ER or IR were observed in the group with high risk (P = 0.001). Conclusions: In sum, response to treatment significantly varied based on dynamic risk stratification, with ER being highest in the low-risk group, less likely in moderate risk group, and undetected in the high-risk group.

Predictive value and dynamic risk stratification of high sensitive basal or stimulated thyroglobulin assay in a long-term thyroid carcinoma cohort.

PURPOSE: To evaluate the predictive value of the rhTSH thyroglobulin stimulation test (rhTSH-Tg) compared to basal high-sensitive thyroglobulin (hs-Tg) under TSH suppressive therapy at 12 months after the completion of initial treatment to predict the long-term response and Dynamic Risk Stratification (DRS) at the last follow-up visit in a long-term DTC cohort. METHODS: Prospective study in 114 DTC patients (77.2% women, mean age 46.4 ± 14.1 years old, median/IQR evolution 6.7[3.1-8.0] years) from 2013 to 2020 undergoing total thyroidectomy and radioiodine ablation in whom hs-Tg and rhTSH-Tg was performed 12 months after completing initial treatment. Pearson correlation, receiving operating characteristics (ROC) and DRS at initial and last follow-up visit were analyzed. RESULTS: hs-Tg and rhTSH-Tg show a strong positive linear correlation (r = 0.864, p < 0.001). The diagnostic performance of initial hs-Tg and rhTSH-Tg levels were evaluated via ROC-AUC as a predictor of excellent response (ER) in the last follow-up visit. Hs-Tg showed a better AUC (0.969, 95%CI = 0.941-0.997) than rhTSH-Tg (0.944, 95%IC = 0.905-0.984; p < 0.001). The hs-Tg and rhTSH-Tg cutoff point of highest sensitivity (S) and specificity (E) was 0.110 and 0.815 ng/dl, respectively. Hs-Tg showed a higher diagnostic accuracy than rhTSH-Tg (S = 100% vs 96.8%, E = 84.3% vs 84.3%, NPV = 100% vs 98.6%, PPV = 70.5% vs 69.7%; p < 0.05). The DRS based on initial hs-Tg showed better ability to predict ER (93.3% vs 86.7%) and biochemical incomplete response (53.3%vs13.3%) in the last follow-up visit compared to rhTSH-Tg. CONCLUSIONS: Both initial hs-Th and rhTSH-Tg were good predictors of long-term ER. In patients with hs-Tg, the rhTSH-test did not provide relevant prognosis information. An ER after initial treatment was associated with a very high NPV at subsequent follow-up.

The prognostic utility of dynamic risk stratification at disease progression in patients with multiple myeloma.

OBJECTIVES: There may be a shift in risk stratification at progression compared to that at diagnosis in patients with multiple myeloma (MM). We aimed to evaluate whether re-staging and stage migration is of prognostic impact. METHODS: Real-world data from the National Longitudinal Cohort of Hematologic Diseases-multiple myeloma were collected; 263 consecutive patients demonstrating disease progression were finally included. Staging at diagnosis and re-staging at progression were performed using the International Staging System (ISS) and Revised International Staging System (RISS). RESULTS: Based on ISS re-staging, the median post-progression survival (mPPS) of patients with stage I, II, and III was 44.2, 21.7, and 11.6 months, respectively (P < 0.0001). Based on RISS re-staging, the mPPS of patients with stage I, II, and III was 50.3, 22.2, and 11.4 months, respectively (P < 0.0001). The mPPS in patients with improved, maintained, and deteriorated ISS stage migration from diagnosis was 33.6, 20.9, and 16 months, respectively (P = 0.0051) and that with improved, maintained, and deteriorated RISS stage migration was 48.4, 23.1, and 13.9 months, respectively (P < 0.001). Compared to patients with maintained or improved disease stage, those with deteriorated ISS/RISS migration showed significantly higher incidence of Del(17P) at progression and worse PPS. Multivariate analyses indicated both re-staging and stage migration by ISS/RISS at progression were independent predictors for PPS. CONCLUSIONS: We demonstrated that ISS/RISS re-staging showed superior prognostic utility over ISS/RISS staging in predicting PPS. Patients with deteriorated stage migration or maintained advanced stage at progression may need more individualized treatment.

Modified dynamic risk stratification system further predicts individual outcome in patients with intermediate-risk papillary thyroid cancer.

OBJECTIVE: We assessed the contribution of initial treatment response to further refining prediction of individual outcomes in intermediate-risk papillary thyroid cancer (PTC) on the American Thyroid Association (ATA) risk stratification system. Dynamic risk stratification (DRS) as originally proposed by Tuttle et al. in 2010 was modified to also include serum antithyroglobulin antibodies (TgAb) as a surrogate marker of the likelihood of persistent disease, specifically in patients with thyroglobulin assay interference by TgAb. METHODS: Three hundred and seventy-three patients with ATA intermediate-risk PTC were enrolled retrospectively upon reviewing medical records. Patients were followed at the National Cancer Institute in Bogota, Colombia after being treated with total thyroidectomy and I-131 therapy between 2009 and 2013. Best response to initial therapy was classified as excellent, indeterminate, biochemically incomplete or structurally incomplete. Final disease status after a median follow-up of 7.1 years was classified as no evidence of disease (NED), indeterminate, or persistent disease (either biochemically or structurally). The rate of recurrence was determined in excellent responders. RESULTS: Excellent response was achieved by 164 patients (43.9%). At a median follow-up of 42 months, 19 (11.6%) had experienced recurrence. 87.4% of initially excellent responders available at the final checkpoint were NED, compared to 28% of those with biochemically or structurally incomplete response and to 60.2% of all ATA intermediate-risk PTC patients in our cohort. CONCLUSIONS: Modified DRS further predicted individual outcomes in intermediate-risk PTC, potentially allowing ongoing management to be tailored accordingly.

Dynamic Risk Stratification for Predicting Long-term Outcomes in Pediatric Differentiated Thyroid Cancers.

CONTEXT: The American Thyroid Association (ATA) guidelines recommend Dynamic Risk Stratification (DRS) for predicting long-term outcomes and personalizing management in adult differentiated thyroid cancers (DTCs). However, its applicability in pediatric DTCs needs to be validated. OBJECTIVE: We have attempted a validation study concerning the use of DRS in pediatric DTCs. METHODS: Data of children (age ≤18 years) with DTCs and follow-up of ≥5 years were extracted. All patients were classified according to DRS (excellent biochemical or structural incomplete responses). Univariate and multivariate analyses were done to identify factor(s) affecting disease-free survival (DFS). RESULTS: We included 176 pediatric patients with DTC (median age at diagnosis 15 years). All patients underwent thyroidectomy and received radioiodine as part of initial management. On the basis of clinical, biochemical, and imaging findings acquired during the first 2 years of follow-up, the DRS system divided patients into 3 response categories: excellent response in 82/176 (46.6%), biochemical incomplete response in 56/176 (31.8%), and structural incomplete response in 38/176 (21.6%) patients. The median follow-up was 10.6 years (interquartile range 7.7-15.5). Ten-year overall survival and DFS rates were 100% and 88.7%, respectively. In univariate analysis, DFS was significantly affected by extrathyroidal extension (P = .002), lymph node metastasis (P = .018), ATA initial risk stratification (P = .033), and DRS (P = .004). However, in multivariate analysis, DRS alone showed a significant association with DFS (P = .016). CONCLUSION: Like adults, DRS correctly predicts long-term outcomes in pediatric DTC. In addition to ATA initial risk stratification, DRS could further refine risk in pediatric DTCs and help in planning more personalized treatment and follow-up strategies.

Applicability of Adults 2015 American Thyroid Association Differentiated Thyroid Cancer Guidelines for Postoperative Risk Stratification and Postradioiodine Treatment Dynamic Risk Stratification in Pediatric Population.

Purpose This retrospective study aimed to study the applicability of 2015 adult American Thyroid Association (ATA) differentiated thyroid cancer (DTC) postoperative risk stratification and guidelines in the pediatric population for evaluating the number of metastatic lymph nodes in the postoperative risk stratification and postradioactive iodine (RAI) treatment dynamic risk stratification (DRS) using response to treatment (RTT) reclassification. In addition, the effect of pubertal status and gender was assessed on disease presentation and prognosis. Methods Data of 63 DTC patients aged 20 years or less, stratified into prepubertal, pubertal, and postpubertal age groups, was divided into low, intermediate, and high-risk groups using pediatric ATA recurrence risk stratification. Forty-seven patients were classified as responders (excellent and indeterminate responses) and incomplete responders (biochemical and structurally incomplete responses) by assessing the RTT at 1.5 years follow-up similar to recommendation of 2015 adult DTC ATA guidelines. Results Female-to-male ratio showed a trend of gradual increase with increasing age. Significantly more responders were observed in low- and intermediate-risk groups than in high-risk group ( p = 0.0013; p = 0.017, respectively), while prepubertal group had more extensive (N1b) disease. Using DRS at follow-up of 1.5 year, pubertal and postpubertal groups showed significantly better response to RAI. More female than male patients showed response and took significantly less time to respond to RAI ( p = 0.003). Conclusion RAI response in pediatric DTC depends on pubertal status, gender, and number of malignant nodes. DRS using RTT classification may be applicable early at 1.5 years after initial therapy in different pubertal age and risk groups.

The Role of American Thyroid Association Pediatric Thyroid Cancer Risk Stratification and BRAFV600E Mutation in Predicting the Response to Treatment in Papillary Thyroid Cancer Patients ≤18 Years Old

Objective: This study aimed to evaluate the role of risk stratification by the American Thyroid Association (ATA) pediatric thyroid cancer risk levels and BRAFV600E mutation to predict the response to treatment in papillary thyroid cancer (PTC) patients ≤18 years old. Methods: Clinical outcomes during a median period of 6 (2-21.8) years were assessed in 70 patients, according to ATA pediatric risk stratification, BRAFV600E mutation status, and dynamic risk stratification (DRS) at final follow-up. Results: Of 70 patients, 44 (63%), 14 (20%), and 12 (17%) were classified initially as low-, intermediate-, and high-risk, respectively. BRAFV600E mutation analysis data was available in 55 (78.6%) patients, of whom 18 (32.7%) had the BRAFV600E mutation. According to the final DRS, 61 (87%), two (3%), six (9%), and one (1%) patients were classified as an excellent, incomplete biochemical, incomplete structural, and indeterminate response, respectively. All ATA low-risk patients showed excellent response to treatment, whereas the rate of excellent response was 65.4% in intermediate- and high-risk levels (p<0.001). The rates of excellent response in BRAFV600E positive and negative patients were 83% and 92%, respectively (p=0.339). The rate of locoregional recurrence was significantly higher in BRAFV600E positive vs negative patients (33.3% vs 2.7% respectively, p=0.001). Conclusion: ATA pediatric risk stratification is effective in predicting response to treatment in PTC patients ≤18 years old. The presence of BRAFV600E mutation was highly predictive for recurrence but had no significant impact on the rate of excellent response to treatment at final follow-up.

Negative Histopathological Prognostic Factors Affecting Morbidity in T1 Differentiated Thyroid Carcinoma.

Background: The aim was to evaluate: (i) if multifocality is a negative prognostic factor; and (ii) the association of diameter of the largest tumor, total tumor diameter, and the ratio of the largest tumor diameter to total tumor diameter (DR) with histopathological and clinical outcome parameters in T1 differentiated thyroid carcinoma (DTC). Materials and Methods: In 1014 T1N0/1Mx patients, correlation between multifocality, contralateral lobe involvement, capsular-vascular invasion, diameter of the largest tumor, total tumor diameter, DR, and follow-up results were investigated. Results: Persistent/recurrent disease and necessity for additional radioiodine treatment (RAIT) were more frequent in cases with multifocality and contralateral lobe involvement (p = 0.035, p = 0.015, p = 0.021, and p = 0.04). Persistence/recurrence, reoperation in the neck, and additional RAIT were more frequent in patients with the size of the largest tumor focus >1 cm (p = 0.024, p < 0.001, and p = 0.002) and N1 status (p < 0.001, p < 0.001, and p < 0.001). Mean total tumor diameter was higher in patients with capsular invasion, contralateral lobe, and lymph node involvement (p = 0.001, p = 0.003, and p = 0.013). Conclusion: Multifocality, contralateral lobe involvement, diameter of the largest tumor >1 cm, and N1 status are related with increased risk of disease persistence, recurrence, reoperation, and additional RAIT. Sum of diameter of all tumor foci are associated with capsular invasion.

Validation of dynamic risk stratification and impact of BRAF in risk assessment of thyroid cancer, a nation-wide multicenter study.

Introduction: The dynamic risk stratification (DRS) is a relatively new system in thyroid cancer that considers the response to primary treatment to improve the initial risk of recurrence. We wanted to validate DRS system in a nationwide multicenter study and explore if the incorporation of BRAFV600E into DRS helps to better categorize and predict outcomes. Materials and methods: Retrospective study of 685 patients from seven centers between 1991 and 2016, with a mean age of 48 years and a median follow-up time of 45 months (range 23-77). The overall BRAFV600E prevalence was 53.4%. We classified patients into four categories based on DRS ('excellent', 'indeterminate', 'biochemical incomplete', and 'structural incomplete' response). Cox regression was used to calculate adjusted hazard ratios (AHR) and proportions of variance explained (PVEs). Results: We found 21.6% recurrences and 2.3% cancer-related deaths. The proportion of patients that developed recurrence in excellent, indeterminate, biochemical incomplete and structural incomplete response to therapy was 1.8%, 54%, 91.7% and 96.2% respectively. Considering the outcome at the end of the follow up, patients showed no evidence of disease (NED) in 98.2, 52, 33.3 and 25.6% respectively. Patients in the structural incomplete category were the only who died (17.7%). Because they have similar outcomes in terms of NED and survival, we integrated the indeterminate and biochemical incomplete response into one unique category creating the 3-tiered DRS system. The PVEs of the AJCC/TNM staging, ATA risk classification, 4-tiered DRS, and 3-tiered DRS to predict recurrence at five years were 21%, 25%, 57% and 59% respectively. BRAFV600E was significantly associated with biochemical incomplete response (71.1 vs 28.9%) (HR 2.43; 95% CI, 1.21 to 5.23; p=0.016), but not with structural incomplete response or distant metastases. BRAF status slightly changes the AHR values of the DRS categories but is not useful for different risk grouping. Conclusions: This is the first multicenter study to validate the 4-tiered DRS system. Our results also show that the 3-tiered DRS system, by integrating indeterminate and biochemical incomplete response into one unique category, may simplify response to therapy keeping the system accurate. BRAF status does not provide any additional benefit to DRS.

Comparison of the abilities of staging and risk stratification systems to predict the long-term structural recurrence in patients with differentiated thyroid carcinoma after total thyroidectomy and radioactive iodine remnant ablation.

BACKGROUND: In patients with differentiated thyroid carcinoma (DTC), various staging and risk stratification systems have been applied to estimate long-term recurrence, which is a major issue during the postoperative follow-up period. However, the efficacy of these systems remains unclear in this context. METHODS: The present historical cohort study included 510 patients with DTC who underwent a total thyroidectomy followed by radioactive iodine (RAI) remnant ablation. Enrolled patients were categorized according to the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) Tumor Node Metastasis (TNM) staging system, the 2015 American Thyroid Association (ATA) initial risk stratification system, and the dynamic risk stratification (DRS) system. The ability of each system to predict long-term structural recurrence was compared using proportion of variance explained (PVE) by logistic regression models. RESULTS: The median follow-up period was 108 months. Structural recurrence occurred in 7.6% of the patients (n=39/510). Disease-free survival (DFS) curves of the patients within each category in the TNM staging system, the ATA initial risk stratification system, and the DRS system were significantly different (P<0.001). The PVE of the DRS system (20.7%) was higher than those of the TNM staging system and the ATA initial risk estimates. CONCLUSIONS: The DRS system may effectively predict long-term structural recurrence and guide long-term management and follow-up strategies in patients with DTC undergoing total thyroidectomy and RAI remnant ablation.

Nomogram for the Prediction of Biochemical Incomplete Response in Papillary Thyroid Cancer Patients.

PURPOSE: To develop a nomogram for predicting biochemical incomplete response (BIR) in the dynamic risk stratification (DRS) of papillary thyroid carcinoma (PTC) patients without structural recurrence, and to investigate its validity. PATIENTS AND METHODS: Overall, 1705 (1005 and 700 in the training and validation cohorts, respectively) PTC patients treated with total thyroidectomy without structural recurrence were included. multivariate logistic regression analyses were performed to determine the significant predictors of BIR in the training cohort. A nomogram was subsequently constructed for BIR risk prediction. Assessments for the predictive accuracy, discrimination, and calibration of the nomogram were performed. Subsequently, internal and external validations were conducted. RESULTS: In the multivariate analysis, age, sex, lymph node metastasis site, extrathyroidal extension, and lymphovascular invasion showed significant predictive value; using these predictive factors and tumor size, a nomogram for BIR risk prediction was constructed. In the training cohort, the nomogram showed good predictive performance and discrimination in the receiver operating characteristic (ROC) curve analysis, with an area under the curve (AUC) of 0.765. In internal validation, the bootstrap-corrected AUC was 0.76. The calibration plot showed good agreement between the predicted and actual observation. The Hosmer-Lemeshow (HL) test did not suggest a lack of fit (p=0.1613). In the external validation, the AUC was 0.828 in the ROC curve analysis; the calibration plot showed good quality, and the HL test did not suggest a lack of fit (p=0.2161). CONCLUSION: The constructed nomogram may effectively predict the risk of BIR in DRS in PTC patients without structural recurrence. LEVEL OF EVIDENCE: Level 4.

Thyroid lobectomy in patients with differentiated thyroid cancer: an analysis of the clinical outcomes in a nationwide multicenter study.

BACKGROUND: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcinoma (DTC), but the extent of the thyroidectomy remains controversial. Thyroid lobectomy (TL) has been widely used in eastern countries; however, its use has not been generalized in western countries, including Spain. Our aims were to analyse the clinical outcome of a multicentre nation-wide cohort of DTC patients treated by TL and to assess the proportion of patients who required completion of the thyroidectomy and who presented disease recurrence. METHODS: We retrospectively analyzed patients who underwent TL for DTC and were followed-up for ≥12 months. We collected demographic, clinical, and histopathological data. Dynamic risk stratification (DRS) was performed at 12 months and at last visit. RESULTS: One hundred and sixty-four patients (128 women, mean age 50.8 years, median follow-up 45.4 months) from 9 hospitals were included. There were 158 cases of papillary and 6 of follicular thyroid carcinoma (FTC). Remission of the disease (excellent response) was shown in 71.6% of the patients at 12 months and in 74.4% at the end of follow-up. At that time, there were 34 patients (20.7%) with indeterminate response, 6 (3.7%) with biochemical incomplete response, and 2 (1.2%) with structural incomplete response. Completion of the thyroidectomy was necessary in 8 patients (4.9%), but only 3 of them (1.8%) had disease recurrence. CONCLUSIONS: These results, obtained in real clinical practice, suggest that TL is a safe operative option for selected patients with DTC and that the intensity of the treatment must be tailored according to the presurgical tumor-associated risk, in line with a personalized medicine.

Value of thyroglobulin post hemithyroidectomy for cancer: a literature review.

BACKGROUND: An increasing number of patients with low and moderate risk differentiated thyroid cancer (DTC) are now managed with lobectomy alone. The value of serum thyroglobulin (Tg) in the follow up of these patients remains poorly defined. METHODS: A review of the MEDLINE and EMBASE databases was performed to assess the utility of Tg in the follow up of patients undergoing thyroid lobectomy for DTC. RESULTS: A total of five retrospective reviews were identified including 1136 patients undergoing hemithyroidectomy with or without prophylactic central neck dissection. The overall locoregional recurrence rate was 3.7%. Changes in serum Tg following hemithyroidectomy for cancer were found to be clinically useful in one study only. The proposed cut-off value of 30 ng/mL following hemithyroidectomy as a predictor of recurrent disease was not validated by any study. CONCLUSION: Serum Tg values are not useful in the follow up of DTC patients managed with lobectomy alone. Good quality neck ultrasound appears to be an effective modality in the detection of locoregional recurrence in these patients while research efforts continue to identify and validate novel biomarkers.

Dynamic Risk Stratification for Predicting Treatment Response in Differentiated Thyroid Cancer.

Prognosis in Differentiated Thyroid Cancer (DTC) patients is excellent, but a significant degree of overtreatment still exists because of the inability to accurately identify small patient cohorts who experience a more aggressive form of the disease, often associated with certain poor prognostic factors. Identifying these cohorts at an early stage would allow patients at high risk to receive more aggressive treatment while avoiding unnecessary and invasive treatments in those at low risk. Most risk stratification systems include age, tumor size, grade, presence of local invasion, and regional or distant metastases. Here we discuss these common factors as well as their association with treatment response, but also other upcoming markers including histology and multifocality of primary tumor, dose administered and preparation method for Radioiodine Therapy (RAI), Thyroglobulin (Tg), Anti-thyroglobulin Antibodies (Tg-Ab) levels both at initial management and during follow-up, and the presence of previously existing benign thyroid disease. In addition, we examine the role of remnant size and avidity as well as surgeons' experience in performing thyroidectomies with recurrence rate, discussing its impact on disease prognosis. Our results reveal that treatment response has a statistically significant association with histology, T and M stages, surgeons' experience, Tg levels and remnant score both during RAI and follow up and Tg-Ab levels during follow-up whole body scan (WBS).

A COVID-19 Risk Assessment Decision Support System for General Practitioners: Design and Development Study.

BACKGROUND: The coronavirus disease (COVID-19) has become an urgent and serious global public health crisis. Community engagement is the first line of defense in the fight against infectious diseases, and general practitioners (GPs) play an important role in it. GPs are facing unique challenges from disasters and pandemics in delivering health care. However, there is still no suitable mobile management system that can help GPs collect data, dynamically assess risks, and effectively triage or follow-up with patients with COVID-19. OBJECTIVE: The aim of this study is to design, develop, and deploy a mobile-based decision support system for COVID-19 (DDC19) to assist GPs in collecting data, assessing risk, triaging, managing, and following up with patients during the COVID-19 outbreak. METHODS: Based on the actual scenarios and the process of patients using health care, we analyzed the key issues that need to be solved and designed the main business flowchart of DDC19. We then constructed a COVID-19 dynamic risk stratification model with high recall and clinical interpretability, which was based on a multiclass logistic regression algorithm. Finally, through a 10-fold cross-validation to quantitatively evaluate the risk stratification ability of the model, a total of 2243 clinical data consisting of 36 dimension clinical features from fever clinics were used for training and evaluation of the model. RESULTS: DDC19 is composed of three parts: mobile terminal apps for the patient-end and GP-end, and the database system. All mobile terminal devices were wirelessly connected to the back end data center to implement request sending and data transmission. We used low risk, moderate risk, and high risk as labels, and adopted a 10-fold cross-validation method to evaluate and test the COVID-19 dynamic risk stratification model in different scenarios (different dimensions of personal clinical data accessible at an earlier stage). The data set dimensions were (2243, 15) when only using the data of patients' demographic information, clinical symptoms, and contact history; (2243, 35) when the results of blood tests were added; and (2243, 36) after obtaining the computed tomography imaging results of the patient. The average value of the three classification results of the macro-area under the curve were all above 0.71 in each scenario. CONCLUSIONS: DCC19 is a mobile decision support system designed and developed to assist GPs in providing dynamic risk assessments for patients with suspected COVID-19 during the outbreak, and the model had a good ability to predict risk levels in any scenario it covered.

Assessment of the impact of 2015 American Thyroid Association guidelines in management of differentiated thyroid cancer patients.

The 2015 American Thyroid Association (ATA) guideline have suggested modifications in the risk stratification (RS) for differentiated thyroid cancer (DTC) patients, introduced the concept of dynamic risk stratification (DRS) and redefined the role of radioactive iodine (RAI) in treatment algorithm. The aim of this retrospective audit was to assess the practical implications of these modifications in management of DTC. METHODS: A total of 138 DTC patients were stratified according to ATA 2009 and 2015 guidelines into low (LR), intermediate (IR) and high (HR) risk groups. Change in RS and in intention of RAI use was calculated. Deviation in administered RAI dosage from the guidelines was assessed. 1-year follow-up data was audited to assess how the DRS modified the initial risk estimate. RESULTS: A total of 11.6% of patients changed their RS categories in 2015 guidelines. A total of 10.1% got upstaged to HR, and 1.4% got downstaged to LR. In 2.17% of patients' intention of RAI use changed to remnant ablation from adjuvant therapy and 65% of the LR patients won't require any RAI therapy. A total of 26.7% of patients had received significantly more RAI dosage according to ATA 2015. At 1-year follow-up according to DRS 84% of LR, 75% of IR and 44% of HR patients showed excellent response (ER). CONCLUSION: More patients changed RS to HR than to LR. Intention of RAI use changed in only a small number of patients. Significantly higher dosage of RAI is being administered to patients in current practice. The effect of DRS in modifying the initial RS was most prominent in IR, with most showing ER to initial therapy.