Non-Iodine-Avid Disease Is Highly Prevalent in Distant Metastatic Differentiated Thyroid Cancer With Papillary Histology

Context Patients with radioactive iodine (RAI) refractory metastatic differentiated thyroid cancer (DTC) have poor prognosis. Early identification of RAI refractoriness may improve care. Objective This work aimed to characterize DTC patients with distant metastases (DM) at diagnosis who presented with non-iodine-avid disease. Methods Retrospective analyses of DTC patients with DM at diagnosis who presented between 2012 and 2020 were performed. Iodine uptake in DM was correlated with tumor histology and mutational profile. The difference in uptake between BRAF (V600E)-like (BVL) and RAS-like (RL) cancers based on insights from The Cancer Genome Atlas was evaluated. Results Among 78 patients, 48.7% had negative uptake in DM on the first posttherapy scan. Negative scans were highly prevalent in papillary thyroid carcinoma (PTC) with papillary architecture, PTC with BRAF (V600E) mutation, and PTC with both BRAF (V600E) and TERT promoter mutations (71.1%, 80.9%, and 100%, respectively). BVL and RL tumors exhibited distinct uptake patterns with negative scan prevalence of 76.9% and 14.3% (P = .005). Multivariate logistical regression confirmed high odds of negative uptake in BVL tumors with either BVL mutations or papillary architecture, 19.8 (95% CI, 2.72-144), and low odds of negative uptake in RL tumors with either RL mutations or follicular architecture, 0.048 (95% CI, 0.006-0.344), after adjusting for age, sex, race, RAI preparation method, bone metastases, and RAI dose. Patients with negative scans were significantly older (62.4 vs 47.0 years, P = .03). Conclusion Among DTC patients with DM at diagnosis, non-iodine-avid disease is highly prevalent in patients with BVL cancers, particularly with BRAF (V600E) and TERT promoter mutations, and is associated with an older age. Better strategies are needed to improve RAI treatment response for these patients.