Factors Affecting Central Node Metastasis and Metastatic Lymph Node Ratio in Papillary Thyroid Cancer.

OBJECTIVE: Despite the growing evidence that metastatic lymph node ratio (MLNR) is a valuable predictor for the prognosis of papillary thyroid carcinoma, it has not yet been fully determined which factors give the ratio predictive value independent of the number of metastatic lymph nodes (MLNs). STUDY DESIGN: Retrospective cohort study. SETTING: A comprehensive cancer center. METHODS: Recurrence and clinicopathologic factors were analyzed in 2409 patients with papillary thyroid carcinoma who underwent total thyroidectomy and central node dissection. RESULTS: Cutoff values of MLNs ≥2 and MLNR ≥28.2% increased the recurrence risk (hazard ratio [95% CI], 9.97 [4.73-21.0] and 11.4 [5.53-23.3], respectively). Younger age, male sex, multifocality, tumor size, lymphatic and vascular invasion, and gross extrathyroidal extension positively correlated with MLN and MLNR (all P < .05). Meanwhile, lymphocytic thyroiditis negatively correlated with MLNR in female patients (P < .001), by increasing total lymph node yields as compared with papillary thyroid carcinoma without lymphocytic thyroiditis. In multivariate analysis, younger age, tumor size, and lymphatic invasion remained significant in male and female patients for MLN and MLNR; lymphocytic thyroiditis was also significantly correlated with MLNR in female patients. CONCLUSION: Our study demonstrates that MLN and MLNR are independently observed prognostic markers for tumor recurrence. However, lymphocytic thyroiditis in female patients seems to have lower MLNR by increasing total lymph node yields. In light of their association, a different cutoff for MLNR needs to be applied according to the presence or absence of underlying lymphocytic thyroiditis in the use of MLNR for predicting the recurrence. LEVEL OF EVIDENCE: 4.

Tumor doubling time predicts response to sorafenib in radioactive iodine-refractory differentiated thyroid cancer.

Sorafenib has emerged as an effective therapeutic option for radioactive iodine (RAI)-refractory, locally advanced or metastatic differentiated thyroid cancer (DTC). We investigated the efficacy and safety of sorafenib treatment in a real-world setting and unveil predictive markers of responsiveness to sorafenib. The treatment response, progression-free survival (PFS), overall survival, and adverse events (AEs) of sorafenib-treated RAI-refractory, locally advanced or metastatic DTC patients at three institutes were retrospectively reviewed, and their tumor doubling time was calculated by three investigators. Total eighty-five patients were treated with sorafenib, and seven patients discontinued sorafenib due to AEs before the first tumor assessment. The median PFS was 14.4 months, and the objective response rate was 10.3% in 78 patients who were able to evaluate the tumor response. Age, sex, histologic type, tumor location, RAI avidity, or the presence of FDG-PET uptake did not affect PFS. However, smaller tumor size (≤1.5 cm) of the target lesions in lung showed better PFS (hazard ratio [HR] 0.39, p = 0.01), and tumors with the shortest doubling time (≤6 months) had worse outcome (HR 2.70, p < 0.01). Because of AEs, dose reductions or drug interruptions were required in 64% of patients, and eventually, 23% of patients discontinued sorafenib permanently. The most common AE was hand-foot skin reaction (HFSR). Patients with severe HFSR showed better PFS, but there were no statistical significance (HR 0.65, p = 0.05). In conclusion, small tumor size and long doubling time of each target lesion can be a prognostic marker to predict the responsiveness to sorafenib in RAI-refractory DTC patients.