The Impact of the BRAFV600E Mutation on Radioiodine Sensitivity and Prognosis of Papillary Thyroid Cancer with Lung Metastases

Introduction: BRAFV600E is the most frequent genetic aberration in papillary thyroid carcinoma (PTC). Studies revealed BRAFV600E mutation is associated with non-radioiodine avid status. Our previous study found BRAFV600E mutation has no effect on radioiodine ablation and adjuvant therapy for PTC without distant metastases. But the impact of BRAFV600E mutation status on patients with distant metastases was still unknown. So, in this study we aimed to evaluate the relationship between BRAFV600E mutation status and the ability of trapping iodine in lung metastases (LM) and further evaluate the impact of the BRAFV600E mutation on the prognosis of PTC patients with LM.

Methods: 93 PTC patients with LM after post-total thyroidectomy and central or lateral lymph node dissection between January 2012 and September 2021 were respectively included. All of them received BRAFV600E mutation examination of primary tumors and radioiodine therapy (RAI). Patients were divided into progress disease (PD) and non-progress disease (NPD) according to chest CT of follow-up each 6 to 12months. Progression free survival (PFS) was defined as the time from lung metastases first discovered to PD or the latest follow-up. Overall survival (OS) was defined as the time from lung metastases first discovered to dead. 

Results: 35.5% (33/93) PTC patients had BRAFV600E mutation, and 64.5% (60/93) patients had wild type BRAFV600E. In patients with BRAFV600E mutation, 21.2% (7/33) patients had radioiodine-avid LM and 78.8% (26/33) patients had non-radioiodine-avid LM. 63.3% (38/60) patients with radioiodine-avid LM and 36.7% (22/60) patients with non-radioiodine-avid LM in patients with wild type BRAFV600E (χ2=15.125, P=0.000). In univariate analysis, age and the status of iodine-uptake were associated with PFS while there were no statistical differences in BRAFV600E mutation status (54.0 vs 93.0, P=0.122). However, in multivariate cox regression analysis, the status of iodine-uptake was the only factor associated with PFS (HR=9.262, 95%CI 2.750-31.194, P=0.000). 5 patients with non-radioiodine-avid LM including 4 patients with wild type BRAFV600E and 1patients with BRAFV600E mutation dead at the end of follow-up. BRAFV600E mutation status also was independent with OS while gender and the status of iodine-uptake were associated with OS in univariate analysis. However, there were no significant factors associated with OS in multivariate cox regression analysis.

Conclusions: Although patients with BRAFV600E mutation of primary tumors do have lower percentage of radioiodine-avid LM than those patients with wild type BRAFV600E, the status of BRAFV600E mutation did not affect the PFS and OS of PTC patients with LM. And the iodine uptake status of LM was the independent prognosis factor of PFS.

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