Risk Factor Stratification of Lung Metastasis in Children and Adolescent Papillary Thyroid Cancer

Abstract Background: Lung metastasis (LM) in pediatric papillary thyroid cancer (pPTC) is significantly higher than in adults. While spare information about pPTC and LM hampers to formulate specific guideline. Hence, we retrospectively analyzed the whole pPTCs in our center to investigate factors associated with LM and therapy outcomes.Materials and Methods: PTCs with age＜20 years who received initial operations in ourcenterfrom December 2008 to December 2018 were retrospectively reviewed. Clinicopathological information, treatment pipelineand outcomes were analyzed retrospectively.Results:Totally, 114 pPTC patients were enrolled in our study, LM was observed in 17 (14.9 %) cases. Significant risk factors associated with LM were age, sex, tumor size, multifocality, extrathyroidal extension, lymph node metastasis, number of metastatic lymph nodes (NMLNs)and postoperative stimulated thyroglobulin (sTg). NMLNs ＞14 was identified as an independent risk factor for LM by multivariate analysis (OR 25.166, 95% CI 2.814 - 225.009, p = 0.004) with a sensitivity of 86.7% and specificity of 81.1% for LM, which was verified by integrated meta-analysis. In terms ofresponse to radioiodine treatment in LM, 2 cases reached ‘‘excellent’’ response. ‘‘Biochemically incomplete’’, ‘‘structurally incomplete’’ and “indeterminate” were in 3,12, 2 of 17 patients respectively. Postoperative sTg was correlated with the response to therapy of LM in pPTCs(p = 0.003).Conclusion: LM was frequently observed in pPTCs. NMLNs ＞14 was an independent risk factor for LM in our study and other cohorts, and postoperative sTg was a potential predictor for the therapy outcome of LM in pPTCs.

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Association of High Iodine Intake with the T1799A BRAF Mutation in Papillary Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-2390 ◽

2009 ◽

Vol 94 (5) ◽

pp. 1612-1617 ◽

Cited By ~ 131

Author(s):

Haixia Guan ◽

Meiju Ji ◽

Rong Bao ◽

Hongyu Yu ◽

Yangang Wang ◽

...

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Braf Mutation ◽

Significant Risk ◽

Iodine Content ◽

Iodine Intake ◽

Papillary Thyroid ◽

High Iodine ◽

Tumor Stages

Abstract Context: Epidemiological studies have indicated that high iodine intake might be a risk factor for papillary thyroid cancer (PTC), which commonly harbors the oncogenic T1799A BRAF mutation. Objective: The objective of the study was to investigate the relationship between BRAF mutation in PTC and iodine intake in patients. Subjects and Methods: We analyzed and compared the prevalences of the T1799A BRAF mutation in classical PTC of 1032 patients from five regions in China that uniquely harbor different iodine contents in natural drinking water, ranging from normal (10–21 μg/liter) to high (104–287 μg/liter). The BRAF mutation was identified by direct DNA sequencing. Results: The prevalence of BRAF mutation was significantly higher in any of the regions with high iodine content than any of the regions with normal iodine content. Overall, BRAF mutation was found in 387 of 559 PTC with high iodine content (69%) vs. 252 of 473 PTC with normal iodine content (53%), with an odds ratio of 1.97 (95% confidence interval 1.53–2.55) for the association of BRAF mutation with high iodine content (P < 0.0001). In addition, clinicopathological correlation analysis, the largest one of its type ever, showed that BRAF mutation was significantly associated with extrathyroidal invasion, lymph node metastasis, and advanced tumor stages of PTC. Conclusions: High iodine intake seems to be a significant risk factor for the occurrence of BRAF mutation in thyroid gland and may therefore be a risk factor for the development of PTC. This large study also confirmed the association of BRAF mutation with poorer clinicopathological outcomes of PTC.

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Association Between the Presence of Female-Specific Tumors and Aggressive Clinicopathological Features in Papillary Thyroid Cancer: A Retrospective Analysis of 9,822 Cases

Frontiers in Oncology ◽

10.3389/fonc.2021.611471 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jiao Zhang ◽

Le Zhou ◽

Gianlorenzo Dionigi ◽

Daqi Zhang ◽

Lina Zhao ◽

...

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Independent Risk Factor ◽

Protective Factor ◽

Extrathyroidal Extension ◽

Clinicopathological Features ◽

Breast Mass ◽

Papillary Thyroid ◽

Female Specific

ObjectiveTo investigate the association between the presence of female-specific tumors and aggressive clinicopathological features in papillary thyroid cancer (PTC).MethodsThis study retrospectively analyzed 9,822 female cases between June 2008 and December 2017. Odds ratios and corresponding 95% confidence intervals were calculated. Findings were stratified by age and body mass index (BMI) in different models.Results1443/9822 (14.7%) patients with PTC had a female-specific tumor. Presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter (adjusted OR = 1.446, 95% CI 1.136–1.840, P = 0.003), but a protective factor against extrathyroidal extension of PTC (adjusted OR = 0.650, 95%CI 0.500–0.845, P = 0.001). Presence of a benign uterine mass was an independent risk factor for multifocal PTC (adjusted OR = 1.305, 95%CI 1.113–1.531, P = 0.001). Analyses stratified by age and BMI revealed the presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter in patients aged <36 years (adjusted OR = 1.711, 95% CI 1.063–2.754, P = 0.027), and a protective factor against extrathyroidal extension of PTC in patients aged ≥36 - <42 years (OR adjusted = 0.533, 95% CI 0.302–0.941, P = 0.030) or with a BMI ≥ 23.4 kg/m2 (BMI ≥ 23.4 to < 25.7 kg/m2, adjusted OR = 0.441, 95% CI 0.246–0.792, P = 0.006; BMI ≥25.7 kg/m2, adjusted OR = 0.558, 95% CI 0.315–0.998, P2 = 0.045). Presence of a benign uterine mass was an independent risk factor for multifocal PTC in patients aged ≥49 years (adjusted OR = 1.397, 95% CI 1.088–1.793, P = 0.009) or with a BMI <21.5 kg/m2 (OR adjusted = 1.745, 95% CI 1.214–2.509, P = 0.003).ConclusionThe presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter and a protective factor against extrathyroidal extension of PTC, while the presence of a benign uterine mass was an independent risk factor for multifocal PTC. Data from this study may help surgeons propose more personalized treatment plans when encountering patients with PTC and female-specific benign tumors.

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Multifocality Is Not an Independent Risk Factor for Recurrence of Papillary Thyroid Cancer

Clinical Thyroidology ◽

10.1089/ct.2017;29.437-439 ◽

2017 ◽

Vol 29 (11) ◽

pp. 437-439 ◽

Cited By ~ 2

Author(s):

Jerome M. Hershman

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Independent Risk Factor ◽

Papillary Thyroid ◽

Risk Factor For Recurrence

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A Fas-Associated via Death Domain Promoter Polymorphism (rs10898853, -16C/T) as a Risk Factor for Papillary Thyroid Cancer

European Surgical Research ◽

10.1159/000355878 ◽

2014 ◽

Vol 52 (1-2) ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Y.G. Eun ◽

D.H. Chung ◽

S.W. Kim ◽

Y.C. Lee ◽

S.K. Kim ◽

...

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Promoter Polymorphism ◽

Death Domain ◽

Papillary Thyroid

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Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy

Journal of Clinical Medicine ◽

10.3390/jcm9082481 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2481

Author(s):

Kirk Jensen ◽

Shilpa Thakur ◽

Aneeta Patel ◽

Maria Cecilia Mendonca-Torres ◽

John Costello ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Liquid Biopsy ◽

Digital Pcr ◽

Response To Therapy ◽

Response To Treatment ◽

Papillary Thyroid ◽

Primary Tumors ◽

Promising Tool ◽

Increased Risk

The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic BRAFV600E mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cfBRAFV600E alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cfBRAFV600E was significantly associated with tumor size (p = 0.03), multifocal patterns of growth (p = 0.03), the presence of extrathyroidal gross extension (p = 0.02) and the presence of pulmonary micrometastases (p = 0.04). In patients with low-, intermediate- and high-risk PTCs, cfBRAFV600E was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable cfBRAFV600E were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cfBRAFV600E (OR (odds ratios), 4.68; 95% CI (confidence intervals)) 1.26–17.32; p = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of BRAFV600E in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment.

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