Endocrine Abstracts

Objectives: The majority of DTC cases has excellent prognosis; approximately 5% may develop metastatic disease not responding to radioiodine treatment (RAI-R DTC). There are few reports of real-life experience concerning their clinical course.

Methods: We conducted a retrospective study in metastatic RAI-R DTC patients focusing on the clinical characteristics at diagnosis, the location and time interval of the appearance of metastatic lesions, the treatment modalities performed (local therapies and/or systemic treatment), the response to therapy and the disease progression rate.

Results: 95 metastatic RAI-R patients (46.3% men, age-at-diagnosis 55.24±13.6years) were followed up for median 8yrs (2-50). The median time from diagnosis to metastases appearance was 3yrs (0-39); 40% underwent ≥3 cervical surgeries and received median cumulative RAI activity 400mCi (100-1250), 28.4% underwent cervical EBRT, 6.3% cervical RFA. 14.7% had a second neoplasia. Local therapies for distant metastases were performed in 40(42.1%) while stabilization was achieved in 33.7%. TKI was administered in 45(47.4%). The median time interval from metastases appearance to TKI administration was 2.5yrs (0.3-20). 18(40%) underwent local therapies while receiving TKI, 18(40%) received multiple TKIs. Patients not treated with TKI (compared to those treated with TKI) had less frequently soft tissue invasion, mediastinum lymph-nodes, more frequently classical-PTC or FTC and underwent less frequently local procedures (p≤0.03). No significant differences were observed in the outcome between groups. Sorafenib was administered to 30 (29 as first-line therapy), with median-interval from metastases appearance to sorafenib 3years (range 0.2-12). Overall response was PR 2/30(6.7%), SD 3/30(10.0%), PD 22/30(73.3%), 8(26.7%) discontinued due to SAE, 21/30 underwent SAE-related dose reduction. Lenvatinib was administered to 31 (16 as first-line therapy), with median-interval from metastases appearance to lenvatinib 4years (0.1-15). Overall response was PR 8/31(25.8%), SD 8/31(25.8%), PD 14/31(45.2%), 1(3.2%) discontinued due to SAE, 29/31 underwent SAE-related dose reduction. Cabozantinib was administered in 7 patients (2 as second-line TKI, 5 as third-line treatment). Overall, the final outcome was: PR 7/95(7.4%) SD 38(40%) PD 50(52.6%), 34/95(35.8%) died of disease progression, 7/95(7.4%) died of unrelated causes. Twenty-three are still under TKIs treatment. In Cox-proportional-hazard analysis, for the total follow-up period, when age-at-diagnosis, TKI, local therapies, local surgeries, soft-tissue invasion, tumor size and histology were included in analysis, the age-at-diagnosis and the administration of local therapies were predictors of more favorable overall and cancer-specific survival (P < 0.02).

Conclusions: In metastatic RAI-R DTCs younger age at diagnosis and the implementation of local therapies are associated with a more favorable outcome.