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

Abstract

Background: 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.

Methods: 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.

Results: 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 ¹³¹I, 7.5% (20/268) had persistent disease despite cumulative activity of I¹³¹ 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 telomerase reverse transcriptase (TERT) 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.

Conclusions: The contribution of age greater than 45 years to RAIR-DTC mortality is impactful. Older age, presence of distant metastasis and TERT 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.

Keywords: DTC-specific survival; TERT mutation; differentiated thyroid cancer; radioactive iodine refractory; risk factors.

Figure 1

DTC-specific mortality rate in different age groups. The DTC-specific mortality rates increased with increasing age in the entire cohort.

Figure 2

Relationship between age and DTC-specific mortality rates in the entire cohort. (A) Mortality rate. (B) Accumulated mortality rate.

Figure 3

Determination of the optimal age cut-off point for DTC-specific survival using Contal and O’Quigley’s method. The dashed line demarcates the optimal age cut-off point: 44.0 years.

Figure 4

DTC-specific survival. (A) The 5- and 10-year DTC-specific survival rates in the entire cohort (n = 268) were 93.4% and 89.3%, respectively. (B) The 10-year DTC-specific survival rates in the low-, intermediate-, and high-risk groups are 100.0%, 92.9% and 53.6%, respectively. DTC-specific survival is significantly better in low-risk group patients than in high-risk group patients and intermediate-risk group patients (p < 0.0001).