Influence of age and primary tumor size on the risk for residual/recurrent well‐differentiated thyroid carcinoma

Orlov, Steven; Orlov, David; Shaytzag, Michael; Dowar, Mark; Tabatabaie, Vafa; Dwek, Philip; Yip, Jonathan; Hu, Cindy; Freeman, Jeremy L.; Walfish, Paul G.

doi:10.1002/hed.21020

Cited by 39 publications

(37 citation statements)

References 39 publications

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“…Consistent with the previous recent publications (24,25), our data also demonstrate that the AJCC staging is not the best tool for predicting the risk of recurrent/persistent disease. This is most readily apparent in the high rate of persistent/ recurrent disease seen in stage II patients.…”

Section: Discussionsupporting

confidence: 89%

Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System

Tuttle

Tala

Shah

et al. 2010

Thyroid

814

685

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Background: A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. Methods: This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. Results: Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediaterisk, and 68% of the high-risk patients ( p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. Conclusions: Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.

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Section: Discussionsupporting

confidence: 89%

Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System

Tuttle

Tala

Shah

et al. 2010

Thyroid

814

685

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“…Orlov et al [9], in a study of 246 patients, found that age, primary tumor size, and pTNM staging did not predict the risk of residual/recurrent well-differentiated thyroid cancer, whereas extrathyroidal extension at the initial surgery was a better predictor.…”

Section: Discussionmentioning

confidence: 99%

Follicular Thyroid Carcinoma: Disease Response Evaluation Using American Thyroid Association Risk Assessment Guidelines

et al. 2015

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Objective: To evaluate the overall and progression-free survival for follicular thyroid carcinoma (FTC) based on the American Thyroid Association (ATA) staging system for recurrence risk assessment and the TNM staging system. Methods: A clinical review of FTC patients between 1995 and 2014 was conducted at a single center. The data was classified using the TNM staging system into low, intermediate, and high risk of recurrence as per the ATA risk assessment. Results: Over the course of 19 years, 114 (11.9%) of all of the thyroid cancer patients presenting to our hospital had FTC (i.e. 78 females and 36 males). The age range was 15-80 years. Ninety-four tumors were resectable and 18 were unresectable. Sixteen patients were excluded due to insufficient information on their recurrence risk. Based on the ATA categorization, 36 patients had a low recurrence risk. All patients were alive at the time of categorization, and 1 showed progressive disease. Thirty-eight patients had an intermediate recurrence risk. One patient died and 2 showed progression. Twenty-four had a high recurrence risk. Seven patients died and 6 showed progression. In terms of TNM stages, 2 (3.2%) stage I, 3 (17.6%) stage II, 1 (14%) stage III, and 2 (12.5%) stage IV patients died during follow-up. Both ATA risk classification and TNM staging were significant predictors of disease-free survival. On bivariate analysis, the ATA classification (HR 4.67; 95% CI 1.74-12.5, p = 0.002) was a better predictor of survival compared to the TNM classification (HR 1.26; 95% CI 0.98-1.62, p = 0.063). Conclusion: ATA risk stratification predicts the disease recurrence rate and survival better than TNM staging. Age does not have an association; the risk category with dynamic reassessment effectively better predicts the course of disease in FTC.

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“…Hence, the rate of persistent/recurrent disease and the disease-free status, if survival analyses were performed, represent more feasible parameters to be considered when assessing prognosis in DTC and are used as the primary endpoints in most prognostic studies about this clinical setting. Given that the AJCC/UICC system was able to predict mortality but not persistence/recurrence (Orlov et al 2009, Baek et al 2010, Tuttle et al 2010b, Vaisman et al 2012, a great effort has been made in the last decade to build novel staging systems specifically dedicated to the prediction of persistent/recurrent disease. Particularly, each of the major societies dealing with thyroid diseases (ATA (American Thyroid Association), ETA (European Thyroid Association) and LATS (Latin American Thyroid Society)) has validated a categorical classification identifying subgroups with different risks of persistent/recurrent disease (Pacini et al 2006, Pitoia et al 2009, 2013.…”

Section: Prediction Of Clinical Outcome In Differentiated Thyroid Cancermentioning

confidence: 99%

Application of molecular biology of differentiated thyroid cancer for clinical prognostication

Marotta¹,

Sciammarella²,

Colao³

et al. 2016

Endocrine-Related Cancer

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Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF V600E is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF V600E and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated. 23:11Review V Marotta et al. Molecular prognosis in thyroid cancer

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Influence of age and primary tumor size on the risk for residual/recurrent well‐differentiated thyroid carcinoma

Abstract: Age, primary tumor size, and pTNM staging do not predict risk for residual/recurrent WDTC, whereas extrathyroidal extension at initial surgery is predictive.

Cited by 39 publications

References 39 publications

Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System

Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System

Follicular Thyroid Carcinoma: Disease Response Evaluation Using American Thyroid Association Risk Assessment Guidelines

Application of molecular biology of differentiated thyroid cancer for clinical prognostication

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