Radioactive iodine refractoriness in Middle Eastern differentiated thyroid cancer: clinical outcome and risk factor analysis

Radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has received increasing attention due to its poor prognosis. However, outcomes may vary among patients with RAIR-DTC. The role of clinico-pathological and molecular prognostic factors in survival remains controversial, resulting in difficulty in selecting patients for new targeted therapies. We assessed mortality rate and DTC-specific survival in Middle Eastern RAIR-DTC to identify prognostic factors associated with survival. This single center, retrospective study enrolled 268 patients with RAIR-DTC. Mortality rate and DTC-specific survival were analyzed to identify prognostic factors related to survival. Univariate and multivariate analysis were performed using Cox proportional hazards model. Of the 268 cases of RAIR-DTC, 40.3% (108/268) had absent 131I uptake (either on diagnostic or post-therapy whole body scan), 15.3% (41/268) had progressive disease (PD) despite I, 7.5% (20/268) had persistent disease despite cumulative activity of I of >600 mCi and 36.9% (n=99/268) developed distant metastasis. On multivariate analysis, age (more than 45 years), presence of metastatic disease and tumors harboring ( ) promoter mutations were independent prognostic factors for poor DTC-specific survival. Subjects were divided into 3 groups according to the number of risk factors; low risk (no risk factors); intermediate (≤ 2 risk factors); and high risk (all the 3 risk factors). Ten-year DTC-specific survival rates in low, intermediate and high-risk groups were 100.0%, 92.9% and 53.6%, respectively. The contribution of age greater than 45 years to RAIR-DTC mortality is impactful. Older age, presence of distant metastasis and mutations could be used as early predictors of RAIR-DTC cases. The identification of prognostic factors for poor survival in RAIR-DTC may improve the selection of patients for more personalized surveillance and therapeutic modalities.