Abstract Disclosure: E. Chuki: None. N. Behairy: None. S. Auh: None. A. Makarewicz: None. N. Uttarkar Vikram: None. P. Padmasree: None. C. Cochran: None. S. Gubbi: None. J. Klubo-Gwiezdzinska: None. Background: There is conflicting data on the disease aggressiveness in patients with Familial Non-medullary Thyroid Cancer (FNMTC) as compared with sporadic differentiated thyroid cancer (sDTC). Moreover, limited evidence exists comparing FNMTC and sDTC responsiveness to treatment. Therefore, the goal of this study was to compare response to standard therapy, defined as progression-free survival (PFS), in patients with FNMTC and sDTC. Methods: This was a single-center Institutional Review Board-approved cohort study, including patients diagnosed with FNMTC or sDTC, subjected to standard therapy with a median follow-up of 4.8 years (range 2.1-10 years). Patients with FNMTC were matched to patients with sDTC in a 1:2 ratio using the Ccoptimalmatch package in R based on age, sex, and American Thyroid Association (ATA) risk stratification at presentation. PFS was defined from the date of initial thyroid surgery to the first evidence of progression, assessed by RECIST 1.1 criteria. Demographics, cancer characteristics, and treatment modalities were collected and compared. Kaplan-Meier curves and log-rank tests were employed to assess differences in PFS. SAS 9.4 software was used for analyses, with a p-value set at 0.05. Results: The study consisted of 198 subjects, with 66 patients affected by FNMTC and 132 sDTC cases, aged 43.1±14.3, 69.7% female, 47% low, 45.5% intermediate and 7.6% high ATA risk for recurrence. Within the FNMTC cohort 26 (39.4%) cancer cases were detected by screening. There were no differences in age, sex and ATA risk stratification between the study groups due to exact matching (±1 year for age). No significant differences were observed in histology type (p = 0.49), multifocality (p = 0.59), gross extrathyroidal extension (p = 0.76), or presence of distant metastases (p = 0.09). FNMTC exhibited smaller tumor size at diagnosis (mean 1.2±0.96 vs 1.8±1.5 cm, p < 0.01), and fewer positive lymph nodes (p = 0.02). Initial surgery extent favored more total thyroidectomies in the FNMTC group (p < 0.01), and there was a higher prevalence of repeat neck surgeries in the sDTC group (p = 0.045). There was no difference in utilization of RAI therapy between the groups (p = 0.68). During follow up 15.2% of FNMTC and 12.9% of sDTC patients presented with disease progression. PFS probabilities at 5, 10, 15, 20, and 25 years were similar between both groups (0.8 and 0.85 at 5 years, 0.8 and 0.78 for subsequent years) (p = 0.99). Conclusions: The initial surgical treatment for FNMTC tends to be more extensive than applied in sDTC, despite a smaller tumor size and lower number of metastatic lymph nodes at diagnosis. This strategy could lead to a lower need for repeat neck surgeries. The smaller tumor size at diagnosis of FNMTC might be a result of an active screening of affected families. The similar PFS in patients with FNMTC and sDTC suggests a comparable tumor biology and similar responsiveness to standard therapy. Presentation: 6/3/2024
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