Thyroid Association Risk Stratification System Research Articles

Partial Thyroidectomy With Incidental Metastatic Lymph Nodes

The need for completion thyroidectomy in patients with incidental metastatic lymph nodes after partial thyroidectomy is unclear. To investigate the outcomes of patients with incidental metastatic lymph nodes following partial thyroidectomy. A retrospective review of a prospectively maintained thyroid cancer database from 1985 to 2015 was carried out at a head and neck surgery practice at a tertiary referral cancer center. A total of 74 patients who underwent thyroid lobectomy or thyroid isthmusectomy between 1985 and 2015 and were found to have incidental metastatic lymph nodes on final pathologic analysis and were selected to be observed without immediate completion thyroidectomy were included. A separate group of additional 11 patients who underwent immediate completion thyroidectomy was also identified and reviewed. Analysis took place from February to May 2022. Recurrence-free survival outcomes of patients found to have incidental metastatic lymph nodes on final pathologic analysis following partial thyroidectomy with no immediate completion thyroidectomy. A total of 74 patients were observed, with a median (IQR) age of 39 (28-49) years; 44 (59%) were women. Sixty-four patients underwent thyroid lobectomy and 10 patients had isthmusectomy. Classic papillary thyroid carcinoma was the most common histologic type (34 [46%]). Vascular invasion and microscopic extrathyroidal extension were present in 11 patients (16%) and 22 patients (30%), respectively. Positive margins were identified in 5 patients (7.8%). Size of metastatic lymph nodes ranged between 0.07 cm and 1.2 cm. No extranodal extension was reported. A total of 52 patients (70%) were classified as intermediate risk for recurrence based on the American Thyroid Association risk stratification system. The median (IQR) follow up was 48.15 (15.4-86.1) months, during which only 1 patient had a regional recurrence. Another patient underwent delayed completion thyroidectomy for a contralateral lobe malignant abnormality. Recurrence-free survival, disease-specific survival, and overall survival were 97.4%, 100%, and 96.2%, respectively. A separate group of 11 patients who underwent immediate completion thyroidectomy were reviewed. These patients were more likely to have tall-cell papillary thyroid carcinoma (6 [55%] vs 13 [18%]), multifocality (9 [82%] vs 28 [41%]), microscopic extrathyroidal extension (8 [73%] vs 22 [30%]), and positive margins (3 [30%] vs 5 [7.8%]) compared with patients who were under observation only. Completion thyroidectomy may not be necessary in appropriately selected patients who are found to have incidental metastatic lymph nodes (N1a) after partial thyroidectomy for localized well-differentiated thyroid cancer.

ATA risk stratification in papillary thyroid microcarcinoma has low positive predictive value when identifying recurrence

BackgroundRising incidence of papillary thyroid microcarcinomas (PTMC) has raised concerns for overdiagnosis. Utility of the American Thyroid Association Risk Stratification System (ATA-RSS) 2015 in predicting risk of disease recurrence in patients with PTMC was assessed. MethodsElectronic health records of patients who underwent total thyroidectomy were queried. ATA-RSS 2015 risk stratification was performed on those with PTMC, and validity for predicting disease recurrence was calculated. ResultsWith 10-year median follow up, recurrence was higher in PTMC patients with high/intermediate vs low ATA risk (33 % vs 4 %, p = 0.002). Sensitivity of ATA-RSS for detecting recurrence was 60 %, specificity 90 %, PPV 33.3 %, NPV 96.6 %, and accuracy 88 %. When microscopic extrathyroidal extension (ETE) was excluded as an intermediate risk criterion, PPV improved to 50 % and accuracy improved to 92.5 % ConclusionsATA-RSS 2015 predicts recurrence in PTMC with high NPV but low PPV. Exclusion of microscopic ETE improved PPV, which may help prevent overtreatment.

Lymph Node Ratio Predicts Recurrence in Patients with Papillary Thyroid Carcinoma with Low Lymph Node Yield.

The American Thyroid Association risk stratification system suggests that having >5 metastatic lymph nodes (LNs) increase the recurrence risk in patients with papillary thyroid carcinoma (PTC). However, little is known about PTC with <5 harvested LNs. This study aimed to stratify patients with low-LN-yield (low-LNY) PTC based on lymph node ratios (LNRs). From 2007 to 2017, 6317 patients who underwent thyroidectomies were diagnosed with PTC at Seoul St. Mary's Hospital, and 909 patients with low LNYs were included in the study. Tumor recurrence was compared based on LNR. The LNR cutoff was determined using a receiver operating characteristic curve. Forty-six patients (5.1%) experienced recurrences over a mean follow-up period of 127.24 ± 33.6 months (range, 5-190 months). The cutoff for the low-LNR (n = 675) and high-LNR (n = 234) groups was 0.29 (AUC = 0.676, 95% CI = 0.591-0.761, p < 0.001). The recurrence rate was significantly higher in the high-LNR group compared to the rate in the low-LNR group (12.4% vs. 2.5%, p < 0.001). Multivariate analysis using Cox regression revealed that tumor size and LNR ≥ 0.29 were independent prognostic factors for recurrence. Therefore, LNR can be utilized to stratify the risk of recurrence in patients with low-LNY PTC.

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study

ObjectiveAlthough the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up. MethodsIn this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons. ResultsThis study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease. ConclusionApplying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.

Improving the prediction of persistent and recurrent differentiated thyroid cancer using the American Thyroid Association 2015 risk stratification system.

The 2015 American Thyroid Association risk stratification system (ATA RSS) is used in patients with differentiated thyroid carcinoma (DTC) to assess their risk of persistent/recurrent disease. Our aims were to validate the 2015 ATA RSS in a registry of DTC patients and to examine whether the addition of factors not included in it, such as pre-radioactive iodine therapy stimulated thyroglobulin (pre-RAI sTg), gender, and age could increase its predictive ability. We studied 403 patients with DTC, treated at a tertiary center from 1990 to 2018 and subjected to total thyroidectomy. All patients had received RAI therapy, except those with low-risk papillary microcarcinoma. Of our patients, 81.9% were women and 91.1% had papillary thyroid carcinoma. After a median follow-up of 5.0years, 53 cases of persistent and 21 cases of recurrent disease were recorded. The proportion of variance explained (PVE) regarding the outcome (presence or absence of recurrent/persistent disease) using the 2015 ATA RSS alone was 18.3% (persistence) and 16.9% (recurrence), increasing to 74.4% and 52.0%, respectively, when pre-RAI sTg was added to the logistic regression model. Gender and age were not associated with the disease outcome. In ROC analysis, pre-RAI sTg had a high predictive value for persistent (AUC 0.983, 95% CI 0.962-1.000) and recurrent disease (AUC 0.856, 95% CI 0.715-0.997). The optimal cut-offs and sensitivity, specificity, and positive and negative predictive value for pre-RAI sTg were the following: for persistence 12.75ng/ml, 100%, 90.5%, 64%, and 100%, and for recurrence 8.05ng/ml, 77.8%, 85.5%, 36.8%, and 97%. The 2015 ATA RSS displayed moderate performance in predicting recurrent/persistent disease in patients with DTC, which improved with the inclusion of pre-RAI sTg values; pre-RAI sTg was an independent predictor of the disease outcome, with high negative prognostic value.

Progression Risk Assessment of Post-surgical Papillary Thyroid Carcinoma Based on Circular RNA-Associated Competing Endogenous RNA Mechanisms.

Background: Accurate risk assessment of post-surgical progression in papillary thyroid carcinoma (PTC) patients is critical. Exploring key differentially expressed mRNAs (DE-mRNAs) regulated by differentially expressed circular RNAs (circRNAs) via the ceRNA mechanism could help establish a novel assessment tool.Methods: ceRNA network was established based on differentially expressed RNAs and correlation analysis. DE-mRNAs within the ceRNA network associated with progression-free interval (PFI) of PTC were identified to construct a prognostic ceRNA regulatory subnetwork. least absolute shrinkage and selection operator (LASSO)–Cox regression was applied to identify hub DE-mRNAs and establish a novel DE-mRNA signature in predicting PFI of PTC.Results: Six hub DE-mRNAs, namely, CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the PFI of PTC, and a prognostic DE-mRNA signature was proposed. A nomogram incorporating the DE-mRNA signature and clinical parameters was established to improve the progression risk assessment in post-surgical PTC, which was superior to the American Thyroid Association risk stratification system and distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size (MACIS) score American Joint Committee on Cancer staging system.Conclusions: Based on the circRNA-associated ceRNA RNA mechanism, a DE-mRNA signature and prognostic nomogram was established, which may improve the progression risk assessment in post-surgical PTC.

Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma.

Simple SummaryThyroid cancer incidence is increasing, with overdiagnosis being the major driver of the thyroid cancer “epidemic”. Papillary thyroid carcinoma, usually with excellent prognosis, sometimes has an aggressive metastatic pattern. This heterogeneity in progression makes it difficult to tailor treatment strategies for an individual patient. We aimed to identify clinicopathological factors associated with papillary thyroid carcinoma recurrence, persistence, and specific mortality. Our study supports that both pre-surgical factors, such as male gender, presence of psammoma bodies, gross extra-thyroidal extension, and lateral compartment lymph node metastases, as well as lymph vessel invasion, venous invasion, presence of necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of PTC patients. The same is true when analysis is restricted to stage I patients. The importance of this report is to emphasize clinical and imaging pre-surgical thyroid cancer patients’ evaluation for an appropriate surgical treatment and patient prognosis.Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients’ outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients’ files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient’s surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.

Stratification of papillary thyroid cancer relapse risk based on the results of molecular genetic studies

Introduction. Post-transcriptional mechanisms play a crucial role in the biological course and clinical manifestations of papillary thyroid cancer (PTC). Recent studies show that an increased content of oncogenic or reduced content of oncosuppressive microRNAs increases the aggressiveness of the tumor and correlates with an unfavorable prognosis of treatment, which allows them to be used in personalizing the treatment tactics of patients with PTC. The study objective is to compare the level of expression of 12 PTC-specific microRNAs and the frequency of V600E mutation of the BRAF gene in patients with different risk of relapse. Materials and methods. The study included 175 patients with PTC. For quantitative analysis of microRNA expression, a reverse transcription reaction followed by a real-time polymerase chain reaction in formalin-fixed paraffin blocks was used. Correlations between 12 microRNA expression and BRAF mutation with different clinical and anatomical features of PTC the risk of relapse according to the American Thyroid Association Risk Stratification System (2009) were analyzed. Results. We demonstrated that miR-146b, miR-221, miR-144, miR-451a, and miR-7 expression correlated with features such as extrathyroid tumor growth, larger size, multifocus, lymph node metastasis, and the presence of distant metastases of the PTC. Most importantly, miR-221, miR-144, miR-451a, and miR-7 expression correlated with risk levels, suggesting their potential significance in stratifying the risk of relapsing PTC. The dependence of the clinical behavior of PTC on the BRAF mutation has not been established.Conclusion. The result of the study will contribute to the individual choice of preoperative treatment tactics for patients with PTC.

Isthmusectomy in selected patients with well-differentiated thyroid carcinoma.

Isthmusectomy in the treatment of well-differentiated thyroid carcinoma (WDTC) is controversial. In this study, we analyze the outcomes of WDTC managed by isthmusectomy alone. Forty-three patients treated with isthmusectomy alone were identified from an institutional database of 6259 surgically treated patients with WDTC. Patient and tumor characteristics were analyzed. Disease-specific survival (DSS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. The pT classification was T1 for 41 and T2 for two patients. All were clinical N0, but 10 pts were pN1a. Using the American Thyroid Association risk stratification system, 9 patients were low-risk and 22 were intermediate-risk. One patient developed local recurrence, and two developed regional lymph node metastases; the 5- and 10-year DSS was 100.0%. The 5- and 10-year RFS was 93.1%. Isthmusectomy alone is an acceptable procedure in selected patients with low- and intermediate-risk WDTC limited to the isthmus.

Evaluating the 2015 American Thyroid Association Risk Stratification System in High-Risk Papillary and Follicular Thyroid Cancer Patients.

Background: The 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC) is designed to predict recurring/persisting disease but not survival. Earlier studies evaluating this system evaluated the 2009 edition, comprised a low number of patients with ATA high-risk, had low numbers of patients with follicular thyroid cancer (FTC), or did not distinguish between papillary and FTC. Therefore, we evaluated the prognostic value of the 2015 ATA Risk Stratification System in a large population of high-risk thyroid cancer patients, which included a substantial proportion of FTC patients. Methods: We retrospectively studied adult patients with DTC who were diagnosed and/or treated at a Dutch university hospital between January 2002 and December 2015. All patients fulfilled the 2015 ATA high-risk criteria. Overall survival and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method. Logistic regression and Cox proportional hazards models were used to estimate the effects of DTC subtype and ATA high-risk criteria on response to therapy, recurrence, as well as survival. Results: We included 236 patients with high-risk DTC (32% FTC) with a mean age of 56 years. Median follow-up was 6 years. At final follow-up, 69 patients (29%) had excellent response, while 120 (51%) had structural disease. All high-risk criteria, except large pathologic lymph nodes, were inversely related to excellent response and positively related to structural disease at final follow-up. During follow-up, 14% of the 79 patients who achieved excellent response developed a recurrence. Finally, 10-year DSS was much higher in the initial excellent response than in the initial structural disease group (100% vs. 61%, respectively). Conclusions: In a population of high-risk DTC patients harboring a large subset of FTC patients, the 2015 ATA Risk Stratification System is not only an excellent predictor of persisting disease but also of survival. As much as 14% of the high-risk patients who had an excellent response upon dynamic risk stratification experienced a recurrence during follow-up. Clinicians should thus be aware of the relatively high recurrence risk in these patients, even after an excellent response to therapy.

Impact of Extranodal Extension on Risk Stratification in Papillary Thyroid Carcinoma.

Background: The current American Thyroid Association risk-stratification system for papillary thyroid carcinoma (PTC) incorporates the number and size of positive lymph nodes (LNs) but places less weight on extranodal extension (ENE). This study investigated how to incorporate ENE into the current system to predict recurrence better in PTC N1 patients.Methods: A total of 369 N1 PTC patients without distant metastasis were enrolled. The combination of number of positive LNs and LNs with ENE that had the highest C-index were identified with multivariable Cox proportional hazards models. ENE number was incorporated into the current system considering the recurrence rate and unadjusted and adjusted hazard ratios (HRs) of the subgroups. Kaplan–Meier curves for recurrence based on current and alternative systems were compared by log-rank test.Results: The recurrence rate for the subgroup with five or fewer positive LNs and one to three ENEs (7/61; 11.5%) was higher than that of the subgroup with five or fewer positive LNs without ENE (5/129; 3.9%; adjusted HR = 3.42 [confidence interval (CI) 0.99–11.75]; p = 0.050). In contrast, adjusted HRs of the subgroup with more than five positive LNs and one to three ENEs (2.33 [CI 0.52–10.35]) or with four or more ENEs (3.86 [CI 1.05–14.17]) were not higher than those of the subgroup with more than five LNs without ENE (4.47 [1.16–17.19]). Incorporating ENE into the current system as an intermediate-risk group yielded a lower log-rank p-value (0.05 vs. 0.01) than the current system.Conclusions: The presence of ENE in low volume LN metastasis confers an intermediate risk of recurrence. Incorporating ENE into the current system allows more accurate decisions regarding further management of PTC N1 patients.

MON-549 How Does the 2015 American Thyroid Association Risk Stratification System Perform in High Risk Thyroid Cancer Patients?

Background The 2015 American Thyroid Association (ATA) risk stratification system for differentiated thyroid cancer (DTC) is designed to predict recurring/persisting disease but not survival. Previous studies evaluating this system comprised relatively few patients with High Risk and/or follicular thyroid carcinoma (FTC). Therefore, we evaluated response to therapy, risk of recurrence as well as survival in a large population of High Risk DTC patients with a substantial proportion of FTC patients. Methods Adult patients, who fulfilled the 2015 ATA High Risk criteria and were diagnosed and/or treated for DTC at a Dutch university hospital between January 2002 and December 2015, were retrospectively included. Response to therapy, recurrence, and mortality characteristics were obtained from patient records. Logistic regression and cox proportional hazards models were used to estimate the effects of ATA High Risk factors on response to therapy, recurrence and survival. Further, disease specific survival (DSS) was analyzed using the Kaplan-Meier method. Results We included 236 patients (63% women; 32% FTC) with mean age of 56 years. During follow-up, 49 patients (21%) died due to thyroid cancer. After initial therapy, 38 patients (16%) had excellent response, while 117 (50%) had structural disease. At final follow-up (median 72 months), 69 patients (29%) had excellent response, while 120 (51%) had structural disease. All risk factors, except large pathologic lymph nodes, were inversely related to excellent response at final follow-up. Recurrence occurred in 14% of the patients, and gross extra thyroidal extension at diagnosis increased the chance of recurrence significantly. Ten-year DSS was higher in the initial excellent response than in the structural disease group (100% vs. 61%). Conclusion In patients with High Risk DTC, the ATA risk stratification system is not only an excellent predictor of recurring/persisting disease, but also of survival. At final follow-up, half of the patients had persistent disease while one-third showed excellent response. Recurrence rates were higher than expected.

The impact of ipsilateral central neck dissection on the 2015 American thyroid association risk stratification system and TNM staging in papillary thyroid carcinoma

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; In patients with classic papillary thyroid carcinoma (PTC) and no clinical evidence of lymph node metastasis (cN0), elective central neck dissection remains controversial. This study evaluates whether elective ipsilateral central neck dissection (eICND) along with total thyroidectomy could modify the staging of these patients. Additionally, we aim to assess pN1 risk factors, the incidence of post-operative complications, and the correlation between pN1 and change in tumor classification according to the risk stratification score of the American thyroid association 2015 (ATA 2015-RSS) and the TNM Score.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This is a prospective, observational study, involving 46 patients with cN0 PTC who underwent eICND along with total thyroidectomy. The number of metastatic lymph nodes, the largest lymph node metastasis, and the extra-nodal extension were assessed. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; 22 out of 46 patients (47.8%; CI 32.9–63.1) presented lymph node metastasis. Seventeen out of the 45 patients initially classified as low or intermediate ATA 2015-RSS upgraded their risk staging (37.8%; CI 23.8–53.5). Fourteen out of these reclassified patients had their initial ATA 2015-RSS changed due to lymph node metastasis larger than 2 mm (mostly between 3 mm and 4 mm). Ten out of 46 (21.7%; CI 10.49–36.4) patients had their TNM staging reviewed. General complication rate was 17.4% (8/46).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Elective dissection of levels VI ipsilateral and VII showed the ability to upgrade the initial ATA 2015-RSS and TNM staging in patients with cN0 PTC. However, further studies are necessary to evaluate the clinical impact of lymph node micro-metastasis.&lt;/p&gt;

In Brief

In Brief

Using the American Thyroid Association Risk-Stratification System to Refine and Individualize the American Joint Committee on Cancer Eighth Edition Disease-Specific Survival Estimates in Differentiated Thyroid Cancer.

The eighth edition of the American Joint Committee on Cancer (AJCC) staging system has reclassified up to one third of differentiated thyroid cancer patients into one of the younger prognostic stage groups (<55 years of age at diagnosis, stage I or stage II). This reclassification widens the spectrum of disease in these lower stages without significantly impacting overall disease-specific survival (DSS) for the entire stage group. However, the optimistic DSS estimates in the <55-year-old stage groups may not accurately reflect the prognosis of individual patients with American Thyroid Association (ATA) high-risk features. Therefore, the aim of this study was to integrate the ATA risk classification system into the eighth edition AJCC staging system to refine and individualize DSS estimates for differentiated thyroid cancer patients aged <55 years at diagnosis. Using the Memorial Sloan Kettering Cancer Center tumor registry, 4881 adult DTC patients aged <55 years at diagnosis receiving initial therapy between 1980 and 2016 were retrospectively analyzed. Using Memorial Sloan Kettering Cancer Center registry coded data, all patients were assigned an eighth edition AJCC stage (I or II), ATA risk of recurrence (low, intermediate, or high), and age group at diagnosis (younger patients defined as ≤45 years old, older patients defined as 45-55 years old). The primary outcome was 10-year DSS. A total of 122 (2.5%) disease-related deaths were observed in the cohort of 4881 patients during a median follow-up of 6.6 years. Integration of the AJCC stage, ATA risk, and age groups identified six subgroups with differing outcomes: (i) stage I/ATA low risk, younger and older, 100% DSS; (ii) stage I/ATA intermediate risk, younger and older, 98% DSS; (iii) stage I/ATA high risk, younger, 95% DSS; (iv) stage I/ATA high risk, older, 89% DSS; (v) stage II/ATA high risk, younger, 78% DSS; and (vi) stage II/ATA high risk, older, 61% DSS. Integration of AJCC stage, ATA risk, and age group (i) identifies six subgroups of patients with progressively worse DSS as AJCC stage, ATA risk, and age increases, and (ii) provides a more individualized estimate of DSS, especially in ATA high-risk patients.

Prognostic Factors for Early and Long-Term Remission in Pediatric Differentiated Thyroid Carcinoma: The Role of Sex, Age, Clinical Presentation, and the Newly Proposed American Thyroid Association Risk Stratification System.

The incidence of pediatric differentiated thyroid carcinoma (DTC) has been rising in recent years, and the main risk factors for recurrence are lymph node and distant metastasis at diagnosis. Other clinical features remain unclear, such as the impact of age, sex, and puberty. Furthermore, until now, this population has been treated using the same strategies used to treat adults. In 2015, the American Thyroid Association (ATA) published the first guidelines targeted at this age group. The aims of this study were to investigate the prognostic factors for early and long-term remission and also to validate the ATA risk stratification proposal in a population outside the United States. Clinical records from 118 patients <18 years old followed in two referral centers were reviewed. The median age was 12 years (range 4-18 years), and 20.3% (24 patients) were <10 years old at diagnosis. The median follow-up was 9.1 years. The majority were female (72%) and received total thyroidectomy and radioiodine therapy (RAI), and 61.8% were treated with more than one dose of RAI. The majority were classified as high risk (48.3%) by the new ATA pediatric guidelines due to distant metastasis (30 patients) or extensive lymph node involvement (27 patients). The remained were classified as low risk (31.3%) and intermediate risk (20.4%). Females with no lymph node or distant metastasis and low ATA pediatric risk were more likely to have no evidence of disease (p < 0.05) within the first year and also in the long term. In this study, age did not significantly predict outcomes. Furthermore, patients also benefitted from multiple doses of RAI, but when the cumulative activity was >400 mCi, this benefit was diminished. This study shows that the ATA risk stratification proposal for pediatric patients is useful in predicting early and long-term outcomes in pediatric patients with DTC. In addition, it shows that sex and metastatic disease are important prognostic factors in pediatric populations.

Implementing the Modified 2009 American Thyroid Association Risk Stratification System in Thyroid Cancer Patients with Low and Intermediate Risk of Recurrence

The primary purpose of this study was to validate the proposed modified 2009 American Thyroid Association Risk Stratification System (M-2009-RSS) in patients with thyroid cancer and to compare the findings with those of the 2009 ATA Risk of Recurrence (2009 ATA-RR) and the Ongoing Risk of recurrence system. The secondary purpose was to assess which risk stratification system had the best predictive value to foresee the probability of structural incomplete response or the no evidence of disease (NED) status at the end of follow-up. This retrospective review included 149 patients with differentiated thyroid cancer who had low and intermediate 2009 ATA-RR and were treated at a single experienced center and followed-up for a median of 6 years (range 3-12 years). Each patient was risk stratified using both the 2009 ATA-RR and the M-2009-RSS. The primary endpoints were 1) the best response to initial therapy defined as either excellent response, biochemical or structural incomplete response, or indeterminate response; 2) clinical status at final follow-up defined as either NED, biochemical incomplete response, structural incomplete response, indeterminate response, or recurrence (biochemical or structural disease identified after a period of NED), and 3) ongoing RR defined as low or high risk according several outcomes after initial treatment. Mean age of included patients was 45.3±13 years. Both the ATA 2009-RR and the M-2009-RSS provided clinically meaningful graded estimates with regard to the status of NED at the end of follow-up in low-risk patients (84% for 2009 ATA-RR and 74% for M-2009-RSS) or the likelihood of having persistent structural disease (0% for 2009 ATA RR and 3.6% for the M-2009-RSS). When patients were classified as low risk, the positive predictive value (PPV) and negative predictive value (NPV) to predict structural disease was 0% and 88.7% for the 2009 ATA-RR, 3.6% and 86.5% for the M-2009-RSS, and 1.6% and 68.2% for the ongoing RR (p=0.022 and 0.055 of chi-square test for PPV and NPV, respectively). Despite expanding the definition of low risk to include small-volume lymph node metastases, minor extrathyroidal extension, and minimally invasive follicular thyroid cancer, the M-2009-RSS predicts clinical outcomes (structural incomplete response and NED at the end of follow-up) that are very similar to the previously validated 2009 ATA RR classification system.