ESPE Abstracts

PLR-DTC patients defined as having a tumor grossly confined to the thyroid with minimal or no central lymph nodes comprises 40% of all pediatric DTC followed-up in our center. High-invasive molecular alterations (HIMA) have been reported recently in around 57% of these patients with a still not clear explanation on their influence in outcome.

Objective: To report the characterization of a small group of PLR-DTC patients who were positive for HIMA.

Material and Methods: Medical records of patients with PLR-DTC (n:19) were analyzed retrospectively considering their molecular findings. All patients underwent total thyroidectomy. Radioiodine therapy (RAIT) was indicated only in those patients with positive serum stimulated thyroglobulin (sTG, >2 ng/ml) or TG antibodies (TGAb). Disease status was assessed annually using the ATA-dynamic risk stratification for adults; an excellent response (ER) was considered as remission. Immunohistochemistry, fluorescence in situ hybridization and Sanger sequencing were performed on histological samples. Initial treatment and outcome were compared between patients harboring HIMA (G1, n:7) and those who didn’t (G2, n:12). Statistical differences were analyzed with Chi-square test (p ≤ 0.05).

Results: 7/19 (36.8%) patients presented HIMA (G1): 2 BRAF V600E and 5 gene fusions (2 ALK, 1 RET, 1 MET, 1 NTRK3). All G1 were papillary DTC, 71.4% T1, 43% N0, 6/7 (85.7%) had +sTG, 3/7 (43%) had +TGAb and 7/7 (100%) received RAIT. Disease persisted in 43% at 1 year (y) and 29% at last visit (median follow-up (FU): 5.3 y, range: 2.2 - 6.9 y). G2 included 10 papillary and 2 minimmally invasive follicular DTC, 75% T1,100% N0 and 7/12 (58%) received RAIT. Disease persisted in 17% at 1 y and all reached ER at last visit (median FU: 3.2 y, r: 1.2 - 7.3 y). G2 patients showed a significant lower N staging (P < 0.05) and lower sTG (p 0.05) but outcome was not statistically different.

Conclusion: Our preliminary analysis shows that patients with HIMA presented with more extended N staging and higher sTG and accordingly all were selected to receive RAIT. Although outcome was not different in this small group, those harboring HIMA respond more slowly to initial treatment. Further prospective studies are needed to confirm these observations. The availability of molecular studies at diagnosis could guide the initial treatment approach for PLR-DTC patients.