Zhongguo aizheng zazhi (May 2022)
The relationship between genetic characteristics and clinical characteristics and the efficacy of 131I therapy in children and adolescents with locally advanced or metastatic differentiated thyroid cancer
Abstract
Background and purpose: The molecular characteristics of differentiated thyroid cancer (DTC) in children and adolescents and its role in clinical practice remain unclear. This study intended to explore the genetic characteristics and its relationship with clinical characteristics and efficacy of 131I therapy in locally advanced or metastatic pediatric and adolescent DTC patients. Methods: A thyroid cancer-related gene panel (ThyroLead®) was used to test the primary tumors from children and adolescents with DTC treated in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from December 2020 to July 2021. The samples were sequenced, the clinicopathological characteristics and 131I treatment history were retrospectively collected, and the relationship between their genetic characteristics and clinicopathological characteristics and the efficacy of 131I therapy was analyzed. Results: All the 39 children present locally advanced or metastatic disease. All the children with accessible data had lymph node metastasis, 91.4% (32/35) of whom had lateral lymph node metastasis, and 61.5% (24/39) patients had distant metastasis. Thyroid cancer-related gene variants were detected in 61.5% (24/39) of the patients, among which RET fusion (38.5%, 15/39) and BRAF V600E point mutation (12.8%, 5/39) were the most common. No statistically significant differences were found in clinical characteristics between the mutation group and the non-mutation group (P>0.05). Most of the children (91.7%, 22/24) with distant metastases remained structural incomplete response (SIR) status after 131I treatment. Nine patients were considered radioactive iodine-refractory (RAIR) status, and 8 of them had thyroid cancer driver mutations, among which NCOA4/RET accounted for 62.5% (5/8). Among cases with RET genetic variations, NCOA4/RET fusion-positive patients tended to present more distant metastasis than those with other forms of RET fusion (33.3% vs 88.9%, P=0.089). Conclusion: Compared with point mutations, fusion gene mutations, especially RET fusions, are more common in locally advanced or metastatic pediatric and adolescent DTC patients. NCOA4/RET fusion-positive tumor has more aggressive behaviors and are more likely to become RAIR.
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