OR32-06 Disease-related Outcomes In Patients With Thyroid Cancer On Long Term Follow-up: Analysis Of 1487 Patients
Authors: Doerfler William R , Morariu Elena , Carty Sally Elizabeth , Nikiforova Marina , Nikiforov Yuri E , Yip Linwah 
Published: October 2023

Abstract
Disclosure: W.R. Doerfler: None. E. Morariu: None. S.E. Carty: None. M. Nikiforova: Other; Self; Thyroseq. Y.E. Nikiforov: Other; Self; Thyroseq. L. Yip: None.
Introduction: Molecular genotype of differentiated thyroid cancer (DTC) has been shown to be associated with histology and disease-related outcomes including local recurrence and distant metastatic disease. In an updated analysis with long follow-up of a large cohort of thyroid cancer patients with prospective 7-gene molecular testing results, we aim to identify the risk of long-term recurrence and associated factors to guide optimal surveillance strategies.
Methods: We reviewed a consecutive series of 1487 patients with DTC who had index thyroidectomy performed from 2007-2013 and routine molecular testing to detect alterations in 7 genes: BRAF, NRAS, HRAS, and KRAS genes, and RET/PTC1, RET/PTC3, and PAX8/PPARG fusions. We assessed for disease recurrence at latest follow-up which was defined as date of thyroglobulin measurement or neck ultrasound. Recurrence (occurring &gt; 6 months after initial treatment) was defined per 2015 ATA guidelines as disease confirmed on histology, a rise in unstimulated thyroglobulin to &gt;1 ng/mL without clear structural recurrence, or structural recurrence on imaging without confirmed biopsy.
Results:98% of patients were diagnosed with papillary thyroid carcinoma (PTC). BRAFV600E was the most common mutation identified (43%). At least 5 years of follow-up occurred in 966 (64.9%) patients. Median follow up was 7.3 years ± 4.1 years. Of 1390 patients for whom recurrence could be assessed, 93 (6.4%) recurred including 55 (59%) recurrences &lt; 2 years after surgery, 25 (27%) between 2-5 years, and 13 (14%) who were diagnosed &gt;5 years. Of those who recurred between 2 to 5 years, 16 had BRAFV600E, 1 had NRAS, and 1 had RET/PTC1 cancer. Of those who recurred &gt;5 years, 7 had BRAFV600E-positive DTC, 5 were 7-gene negative, and 1 had a complex BRAF mutation. Of the late recurrences (diagnosed &gt;5 years), 9 were structural including 6 locoregional which were biopsy-confirmed, and 4 were biochemical. Metachronous distant metastatic disease occurred in 1 of 13 with late recurrence and was a patient with pulmonary metastasis whose tumor was positive for complex BRAF mutation. Disease-free survival at 5 years for patients with RAS, PAX8PPARG, and BRAFK601E positive cancer (99-100%)was higher than for patients with cancers positive for RET/PTC (87%) or BRAFV600E (88.7%)(p&lt;0.001), and remained higher at 10 years (99-100% vs 87%, p&lt;0.001).
Conclusion: In this large cohort of consecutive DTC patients with prospective 7-gene molecular testing and long-term follow-up, 5- and 10-year DFS was higher in patients with RAS-like TC compared to those with BRAF-like TC. ∼60% of recurrences occurred in the first 2 years, while most recurrences &gt;5 years were locoregional or biochemical and only one patient developed distant metastatic disease. Further analysis with additional comprehensive genetic variables is ongoing to better identify patients who are at risk for long-term recurrence.
Presentation: Sunday, June 18, 2023