Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors

Russo, Marco; Malandrino, Pasqualino; Moleti, Mariacarla; Vermiglio, Francesco; D’Angelo, Antonio; Rosa, Giuliana La; Sapuppo, Giulia; Calaciura, Francesca; Regalbuto, Concetto; Belfiore, Antonino; Vigneri, Riccardo; Pellegriti, Gabriella

doi:10.1002/pbc.27226

Cited by 15 publications

(13 citation statements)

References 37 publications

(85 reference statements)

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“…Male gender coincides with more aggressive tumor features in terms of the extent of the primary tumor at diagnosis, dissemination outside the thyroid and to distant sites. On the other hand, males did not have significantly larger tumors, nor did they differ from females in terms of final outcome (26–28). Younger patients had a more aggressive tumor at diagnosis in terms of extent, lymph node involvement and distant metastases than older pediatric patients although, here again, age did not affect final outcome in our sample.…”

Section: Discussionmentioning

confidence: 71%

Differentiated Thyroid Carcinoma in Pediatric Age: Genetic and Clinical Scenario

et al. 2019

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Introduction: Follicular-derived differentiated thyroid carcinoma (DTC) is the most common endocrine and epithelial malignancy in children. The differences in the clinical and pathological features of pediatric vs. adult DTC could relate to a different genetic profile. Few studies are currently available in this issue, however, and most of them involved a limited number of patients and focused mainly on radiation-exposed populations. Materials and Methods: We considered 59 pediatric patients who underwent surgery for DTC between 2000 and 2017. RET/PTC rearrangement was investigated with fluorescent in situ hybridization and real-time polymerase chain reaction. Sequencing was used to analyze mutations in the BRAF, NRAS, PTEN, PIK3CA genes, and the TERT promoter. The pediatric patients' clinical and molecular features were compared with those of 178 adult patients. Results: In our pediatric sample, male gender and age <15 years coincided with more extensive disease and more frequent lymph node and distant metastases. Compared with adults, the pediatric patients were more likely to have lymph node and distant metastasis, and to need second treatments ( p < 0.01). In all, 44% of the pediatric patients were found to carry molecular alterations. RET/PTC rearrangement was confirmed as the most frequent genetic alteration in childhood DTC (24.6%) and correlated with aggressive features. BRAFV600E was only identified in 16% of the pediatric DTCs, while NRASQ61R, NRASQ61K, and TERTC250T mutations were very rare. Conclusions: Pediatric DTC is more aggressive at diagnosis and more likely to recur than its adult counterpart. Unlike the adult disease, point mutations have no key genetic role.

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Section: Discussionmentioning

confidence: 71%

Differentiated Thyroid Carcinoma in Pediatric Age: Genetic and Clinical Scenario

et al. 2019

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“…In our study, we did not find that the presence of lymph node metastasis was associated with a higher risk for persistent/recurrent disease; however our sample size was small. A recent Italian study [23] found that N1b lymph node status was a strong predictor for persistent/recurrent disease.…”

Section: Discussionmentioning

confidence: 99%

Performance of the American Thyroid Association Risk Classification in a Single Center Cohort of Pediatric Patients with Differentiated Thyroid Cancer: A Retrospective Study

Alwithenani

DeBrabandere

Rachinsky

et al. 2019

Journal of Thyroid Research

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Introduction. Differentiated thyroid cancer (DTC) is the most common endocrine malignancy in children. Retrospective studies show conflicting results regarding predictors of persistent and recurrent disease after initial therapy. In 2015, the American Thyroid Association (ATA) proposed a clinical classification system to identify pediatric thyroid cancer patients at risk for persistent/recurrent disease. Material and Methods. We retrospectively included all patients in our registry diagnosed with papillary DTC at ≤ 18 years of age. We analyzed the prognostic performance of the ATA classification and other risk factors for predicting response to initial treatment and final outcome in pediatric DTC. Results. We included 41 patients, 34 females and 7 males, diagnosed with papillary DTC at a mean (SD) age of 16.2 (1.8) years. Based on the ATA pediatric risk classification, patients were categorized as low (61%), intermediate (10%), or high risk (29%). The median follow-up period was 7.3 (1-41) years. After initial treatment, disease free status was achieved in 92%, 50%, and 42% of the low, intermediate, and high risk groups, respectively (P <0.01). At the last visit, persistent disease was present in 12%, 25%, and 33% (P=0.27). Assessing other risk factors, only the presence of distant metastases at diagnosis resulted in increased presence of persistent disease at last follow-up (P=0.03). Conclusion. This study supports the clinical relevance of the ATA risk classification for predicting the response to initial treatment. There was no clear prediction of long-term outcome, but this may be due to limited power caused by the small number of patients.

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“…For example, the recognition of metastasizing into lymph nodes and male sex as prognostic factors found in one-factorial analysis have not been confirmed by the multifactorial analysis [28]. At the same time multi-focal tumor growth as well as the presence of category N1b tumor are thought to be important factors of WDTC relapse risk [29,30]. According to some other data, tumor belonging to the N1b category as well as the level of post-operative thyreoglobulin is also relapse development predictors, while it is not true for clinical and biological properties of thyroid carcinomas [31].…”

Section: Groupsmentioning

confidence: 97%

Main Prognostic Factors for Well Differentiated Thyroid Cancer: Analis of Combined Patients Treatment Results during 20 Years after Surgery

Bb¹,

Ae²,

My³

et al. 2018

Thyroid Disorders Ther

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Background: In general, the prognosis in patients with well differentiated thyroid carcinoma (WDTC) is excellent. However, there are small cohorts of patients who experience a more aggressive form of disease which is often associated with certain poor prognostic factors. Identifying these patients at an early stage is imperative for guiding treatment decisions. The purpose of the work is to study the cumulative survival of patients with WDTC, depending on a number of clinical and biological characteristics of tumors. Methods: A retrospective cohort study of patients operated on WDTC in the period from 1995 to 2015 (5526 people). Each patient was analyzed according to age, gender, tumor size and characteristics of the TNM (7 editions), clinical stage, volume of surgery, number of points on the MACIS scale, risk group, number of courses of radioiodine treatment, result treatment and the term of postoperative observation. The construction of cumulative survival curves was made according to the Kaplan-Meier approach. To compare the cumulative survival index value in groups, the non-parametric Log-rank test was used. Results: The most unfavorable factors of the prognosis for patients with WDTC are such integrated indicators as the stage of disease IVb and IVc, as well as tumors of the T4b category. It is also unfavorable to recognize the age of patients over 60 years, the presence of distant metastases, the stage of disease IVa, the category of carcinomas T4a and the size of the tumor more than 40 mm. Other prognostic factors (invasion, multifocal tumor growth, metastasis of carcinoma to the lymph nodes, male sex, post-operative relapse), although they are probable predictive factors, but have somewhat less significance in analyzing the prognosis of survival of patients. Conclusion: Understanding the importance of certain prognostic factors of survival is extremely necessary, since they are the only indicators of the effectiveness of the diagnostic, medical and organizational work will reduce the number of patients who require aggressive treatments and, consequently, increase the duration and quality of their postoperative life.

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Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors

Cited by 15 publications

References 37 publications

Differentiated Thyroid Carcinoma in Pediatric Age: Genetic and Clinical Scenario

Differentiated Thyroid Carcinoma in Pediatric Age: Genetic and Clinical Scenario

Performance of the American Thyroid Association Risk Classification in a Single Center Cohort of Pediatric Patients with Differentiated Thyroid Cancer: A Retrospective Study

Main Prognostic Factors for Well Differentiated Thyroid Cancer: Analis of Combined Patients Treatment Results during 20 Years after Surgery

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