Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers.

2022

JCO2101861

2022 Jan 11

1527-7755

<p><strong>PURPOSE: </strong>In 2014, data from a comprehensive multiplatform analysis of 496 adult papillary thyroid cancer samples reported by The Cancer Genome Atlas project suggested that reclassification of thyroid cancer into molecular subtypes, -like and -like, better reflects clinical behavior than sole reliance on pathologic classification. The aim of this study was to categorize the common oncogenic variants in pediatric differentiated thyroid cancer (DTC) and investigate whether mutation subtype classification correlated with the risk of metastasis and response to initial therapy in pediatric DTC.</p>

<p><strong>METHODS: </strong>Somatic cancer gene panel analysis was completed on DTC from 131 pediatric patients. DTC were categorized into -mutant (), -mutant ( p.V600E), and / fusion (, , and fusions) to determine differences between subtype classification in regard to pathologic data (American Joint Committee on Cancer TNM) as well as response to therapy 1 year after initial treatment had been completed.</p>

<p><strong>RESULTS: </strong>Mutation-based subtype categories were significant in most variables, including age at diagnosis, metastatic behavior, and the likelihood of remission at 1 year. Patients with / fusions were significantly more likely to have advanced lymph node and distant metastasis and less likely to achieve remission at 1 year than patients within or -mut subgroups.</p>

<p><strong>CONCLUSION: </strong>Our data support that genetic subtyping of pediatric DTC more accurately reflects clinical behavior than sole reliance on pathologic classification with patients with / fusions having worse outcomes than those with -mutant disease. Future trials should consider inclusion of molecular subtype into risk stratification.</p>

10.1200/JCO.21.01861

J Clin Oncol

35015563

Extrathyroidal Extension is an Important Predictor of Regional Lymph Node Metastasis in Pediatric Differentiated Thyroid Cancer.

2019

2019 Oct 01

1557-9077

<p>The American Joint Committee Cancer (AJCC) TNM system predicts survival in patients with differentiated thyroid cancer (DTC). In the eighth edition of the AJCC TNM, microscopic extrathyroidal extension (microETE) was removed and tumor size &gt;4 cm was maintained in the definition of T3 disease to reduce unnecessarily aggressive therapy for adults at low risk of death from DTC. In pediatric patients where DTC survival rates are high, the AJCC TNM is used to identify patients at increased risk of persistent, postsurgical disease, to identify patients who benefit from radioactive iodine therapy. The aim of this study was to assess the correlation of microETE with cervical lymph node (LN) metastasis in pediatric patients and to determine if tumor size or microETE is more informative in predicting regional LN disease. Patients with DTC &lt;19 years of age at the time of thyroidectomy with AJCC T3 tumors (seventh edition) and the presence of LNs on the surgical specimen were included in this retrospective chart review. Pathological findings were confirmed by pathologist review. Forty-five patients with AJCC T3 designation were included, 34 with microETE and 11 without microETE. Of those with microETE, 32 (94.1%) demonstrated regional LN metastasis compared with 5/11 patients (45.5%) without microETE ( = 0.001). In addition, microETE was associated with lateral neck LN metastasis ( = 0.004), bilateral disease ( = 0.001), and tumor multifocality ( = 0.003). Patients with microETE had smaller tumors (median = 2.5 cm, interquartile range [IQR]: 1.6-4.5) compared with patients without microETE (median = 5 cm, IQR: 4.2-5.4;  = 0.02). No increased association was found between microETE and vascular invasion, distant metastasis, or persistent/recurrent disease. In pediatric patients with DTC, microETE is a strong predictor of LN metastasis when compared with tumor size. For patients who do not undergo prophylactic central neck LN dissection, the presence of microETE predicts an increased risk of postsurgical disease and should be included in future revisions of the American Thyroid Association pediatric risk stratification categories.</p>

10.1089/thy.2019.0229

Thyroid

31573414