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Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis.

ABSTRACT: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned.This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer.A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R(2)). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination.The best five alternate papillary cancer systems had age cut-points of 45-50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p?=?0.200). The best five alternate follicular cancer systems had age cut-points of 50-55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p?=?0.003-0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p?=?0.197).No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation.

SUBMITTER: McLeod DS

PROVIDER: S-EPMC4589102 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis.

McLeod Donald S A DS Jonklaas Jacqueline J Brierley James D JD Ain Kenneth B KB Cooper David S DS Fein Henry G HG Haugen Bryan R BR Ladenson Paul W PW Magner James J Ross Douglas S DS Skarulis Monica C MC Steward David L DL Xing Mingzhao M Litofsky Danielle R DR Maxon Harry R HR Sherman Steven I SI

Thyroid : official journal of the American Thyroid Association 20150824 10

<h4>Background</h4>Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned.<h4>Objective</h4>This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer.<h4>Methods</h4>A total of 4721 patients with differentiated thyroid cancer were assessed. ...[more]

PMID: 26203804

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Project description:Differentiated thyroid cancer (DTC) is a common type of cancer among women with an increasing worldwide incidence rate. However, there are no specific and sensitive molecular biomarkers for DTC diagnosis or prognosis. Angiopoietin-like protein 1 (ANGPTL1) may be a novel tumor suppressor in lung, breast, colorectal and hepatocellular carcinoma. However, little is known about the influence of ANGPTL1 on the malignant properties of thyroid cancer cells or DTC recurrence in patients. Thus, the present study aimed to investigate the effects of ANGPTL1 on thyroid cancer malignancy or recurrence. The present study examined the mRNA levels of ANGPTL1 in thyroid cancer and paracancerous tissues using RNA sequencing data from The Cancer Genome Atlas. The present study also determined the effects of ANGPTL1 on thyroid cancer cell proliferation using the Cell Counting Kit-8 assay. Associations were identified among ANGPTL1 expression levels and thyroid cancer proliferation, migration and metastasis using The Cancer Genome Atlas data set and by Gene Set Enrichment Analysis. The expression of ANGPTL1 in patients with DTC and without recurrence was compared in order to assess its potential as a prognostic biomarker for DTC. In addition, ANGPTL1 concentrations in the serum of patients with DTC and individuals with benign thyroid nodules were compared to evaluate the sensitivity and specificity of ANGPTL1 as a predictive biomarker for DTC. The results of the present study demonstrated that ANGPTL1 expression levels were lower in thyroid cancer compared with those in adjacent normal thyroid tissues. ANGPTL1 expression was observed to decrease with thyroid cancer progression. In addition, ANGPTL1 was demonstrated to inhibit thyroid cancer cell proliferation, migration and invasion and ANGPTL1 expression levels were reduced in patients with DTC with recurrence compared with those in patients with non-recurrent DTC. Additionally, serum concentrations of ANGPTL1 in patients with DTC were decreased compared with those in individuals with benign thyroid nodules. In conclusion, ANGPTL1 may be a novel predictive biomarker for DTC diagnosis and recurrence in patients with DTC.

Project description:BackgroundIn most staging systems, 45 years of age is used to differentiate low risk thyroid cancer from high risk thyroid cancer. However, recent studies have questioned both the precise 45 year age point and the concept of using a binary cut off as accurate predictors of disease specific mortality.MethodsA cohort of 3664 thyroid cancer patients that received surgery and adjuvant treatment at Memorial Sloan Kettering Cancer Center (MSKCC) from the years 1985 to 2010 were analyzed to determine the significance of age at diagnosis as a categorical variable at a variety of age cutoffs (5 year intervals between 30 and 70 years of age). The unadjusted and adjusted hazard ratio for the association between disease-specific survival and age was determined using a Cox proportional hazards model adjusted for other predictive variables sex, histology, and pathological T, N, and M status. Furthermore, predictive nomograms of disease-specific mortality were created and validated on an external dataset of 4551 patients to evaluate the impact of age at diagnosis as both a categorical and continuous variable.ResultsIn the MSKCC cohort, with a median follow-up time of 54 months (range 1-332), there were 59 deaths from thyroid cancer with a 10 year disease-specific survival of 96%. Adjusted hazard ratios for all age cutoffs from age 30 to age 70 years were significant. There was no specific cutoff age which risk stratifies patients with differentiated thyroid cancer (DTC). Categorizing age into five strata (<40, 40-49, 50-59, 60-69 and >70 years) showed a 37-fold increase in hazard ratio from age <40 years to age >70 years. A predictive nomogram using age as a continuous variable with other predictive variables had a high concordance index of 96%. Validation on the external cohort had a concordance index of 73%.ConclusionsMortality from DTC increases progressively with advancing age. There is no specific cutoff age which risk stratifies patients with DTC. A predictive nomogram using age as a continuous variable may be a more appropriate tool for stratifying patients with DTC and for predicting outcome.

Dataset Information

Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis.

Publications

Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis.

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