An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

Nixon, Iain J.; Wang, Laura Y.; Migliacci, Jocelyn; Eskander, Antoine; Campbell, Michael J.; Aniss, Ahmad; Morris, Lilah F.; Vaisman, Fernanda; Corbo, Rossana; Momesso, Denise; Vaisman, Mário; Carvalho, André Lopes; Learoyd, Diana; Leslie, William D.; Nason, Richard W.; Kuk, Deborah; Wreesmann, Volkert B.; Morris, Luc G.T.; Palmer, Frank L.; Ganly, Ian; Patel, Snehal G.; Singh, Bhuvanesh; Tuttle, R. Michael; Shaha, Ashok R.; Gönen, Mithat; Pathak, Kumar Alok; Shen, Wen T.; Sywak, Mark; Kowalski, Luiz Paulo; Freeman, Jeremy L.; Perrier, Nancy D.; Shah, Jatin P.

doi:10.1089/thy.2015.0315

Cited by 195 publications

(154 citation statements)

References 26 publications

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“…The wider the spread between the different categories is, the better the statistical power of the division between the groups is. As also shown recently by Nixon et al and Kim et al in this respect, some aspects of the new TNM system offer an improvement over version 7. Even though the lower risk category in TNM 8 encompasses a few more fatal cases than that in TNM 7, the dichotomization in two age categories in TNM 8 appears to yield a more powerful division than that in TNM 7.…”

Section: Discussionsupporting

confidence: 61%

The effects of the Union for International Cancer Control/American Joint Committee on Cancer Tumour, Node, Metastasis system version 8 on staging of differentiated thyroid cancer: a comparison to version 7

Verburg

Mäder

Luster

et al. 2018

Clinical Endocrinology

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Summary Objective To assess the changes resulting from the changes from UICC/AJCC TNM version 7 to version 8 and to subsequently determine whether TNM version 8 is an improvement compared to previous iterations of the TNM system and other staging systems for differentiated thyroid cancer (DTC) with regard to prognostic power. Design Database study of DTC patients treated in our centre between 1978 up to and including 1 July 2014. Results were compared to our previous comparison of prognostic systems using the same data set. Patients 2257 DTC patients. Measurements Staging in accordance with TNM 7 and TNM 8. Thyroid cancer‐specific mortality; comparison was based on p‐values of univariate Cox regression analyses as well as analysis of the proportion of variance explained (PVE). Results There is a redistribution from stage 3 to lower stages affecting 206 (9.1%) patients. DTC‐related mortality according to Kaplan‐Meier for younger and older patients in TNM 7 had a slightly lower prognostic power than that in accordance with TNM 8 (P = 8.0 10−16 and P = 1.5 10−21, respectively). Overall staging is lower in 627/2257 (27.8%) patients. PVE (TNM 7: 0.29; TNM 8: 0.28) and the P‐value of Cox regressions (TNM 7: P = 7.1*10−52; TNM 8: P = 3.9*10−49) for TNM version 8 are marginally lower than that for TNM version 7, but still better than for any other DTC staging system. Conclusion TNM 8 results in a marked downstaging of patients compared to TNM 7. Although some changes, like the change in age boundary, appear to be associated with an improvement in prognostic power, the overall effect of the changes does not improve the predictive power compared to TNM 7.

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Section: Discussionsupporting

confidence: 61%

The effects of the Union for International Cancer Control/American Joint Committee on Cancer Tumour, Node, Metastasis system version 8 on staging of differentiated thyroid cancer: a comparison to version 7

Verburg

Mäder

Luster

et al. 2018

Clinical Endocrinology

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“…Functional enrichment analysis of identified PTC progression associated genes was performed using Enrichr [22, 23]. We analyzed protein-protein interaction using STRING [78] networks based on protein association knowledge from databases of physical interaction and databases of curated biological pathway knowledge (MINT, HPRD, BIND, DIP, BioGRID, KEGG, Reactome, IntAct, EcoCyc, NCI-Nature Pathway Interaction Database, GO) and predicted associations between genes based on observed patterns of simultaneous expression of genes [78].…”

Section: Methodsmentioning

confidence: 99%

A novel integrative risk index of papillary thyroid cancer progression combining genomic alterations and clinical factors

Cheng

Acharya

et al. 2017

Oncotarget

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Although the majority of papillary thyroid cancer (PTC) is indolent, a subset of PTC behaves aggressively despite the best available treatment. A major clinical challenge is to reliably distinguish early on between those patients who need aggressive treatment from those who do not. Using a large cohort of PTC samples obtained from The Cancer Genome Atlas (TCGA), we analyzed the association between disease progression and multiple forms of genomic data, such as transcriptome, somatic mutations, and somatic copy number alterations, and found that genes related to FOXM1 signaling pathway were significantly associated with PTC progression. Integrative genomic modeling was performed, controlling for demographic and clinical characteristics, which included patient age, gender, TNM stages, histological subtypes, and history of other malignancy, using a leave-one-out elastic net model and 10-fold cross validation. For each subject, the model from the remaining subjects was used to determine the risk index, defined as a linear combination of the clinical and genomic variables from the elastic net model, and the stability of the risk index distribution was assessed through 2,000 bootstrap resampling. We developed a novel approach to combine genomic alterations and patient-related clinical factors that delineates the subset of patients who have more aggressive disease from those whose tumors are indolent and likely will require less aggressive treatment and surveillance (p = 4.62 × 10–10, log-rank test). Our results suggest that risk index modeling that combines genomic alterations with current staging systems provides an opportunity for more effective anticipation of disease prognosis and therefore enhanced precision management of PTC.

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“…The vast majority of the downstaged patients (97%) were then considered as having stage I disease, and the disease-specific survival rate of this newly defined group of patients was 98% at 10 years of follow-up [13]. This analysis suggested that using an age cutoff of 45 years would lead to a significant number of patients who are at very low risk of death being inappropriately assigned an advanced disease stage [14]. The American Thyroid Association (ATA), the Latin American Thyroid Society (LATS), and the European Thyroid Association (ETA) guidelines for the follow-up and treatment of DTC have recommended the use of the TNM staging system mainly to predict the probability of DTC-related death [15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Should Age at Diagnosis Be Included as an Additional Variable in the Risk of Recurrence Classification System in Patients with Differentiated Thyroid Cancer

et al. 2017

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Objective: To evaluate the influence of age at diagnosis on the frequency of structural incomplete response (SIR) according to the modified risk of recurrence (RR) staging system from the American Thyroid Association guidelines. Patients and Methods: We performed a retrospective analysis of 268 patients with differentiated thyroid cancer (DTC) followed up for at least 3 years after initial treatment (total thyroidectomy and remnant ablation). The median follow-up in the whole cohort was 74.3 months (range: 36.1-317.9) and the median age at diagnosis was 45.9 years (range: 18-87). The association between age at diagnosis and the initial and final response to treatment was assessed with analysis of variance (ANOVA). Patients were also divided into several groups considering age younger and older than 40, 50, and 60 years. Results: Age at diagnosis was not associated with either an initial or final statistically significant different SIR to treatment (p = 0.14 and p = 0.58, respectively). Additionally, we did not find any statistically significant differences when the percentages of SIR considering the classification of RR were compared between different groups of patients by using several age cutoffs. Conclusions: When patients are correctly risk stratified, it seems that age at diagnosis is not involved in the frequency of having a SIR at the initial evaluation or at the final follow-up, so it should not be included as an additional variable to be considered in the RR classifications.

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An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

Cited by 195 publications

References 26 publications

The effects of the Union for International Cancer Control/American Joint Committee on Cancer Tumour, Node, Metastasis system version 8 on staging of differentiated thyroid cancer: a comparison to version 7

The effects of the Union for International Cancer Control/American Joint Committee on Cancer Tumour, Node, Metastasis system version 8 on staging of differentiated thyroid cancer: a comparison to version 7

A novel integrative risk index of papillary thyroid cancer progression combining genomic alterations and clinical factors

Should Age at Diagnosis Be Included as an Additional Variable in the Risk of Recurrence Classification System in Patients with Differentiated Thyroid Cancer

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