The role of BRAF V600E mutation in post-surgical 131I therapy in papillary thyroid carcinoma: a study based on SPECT-CT uptake analysis.

Abstract

The BRAF V600E mutation (BRAF mut) in papillary thyroid cancer (PTC) has been associated with poor response to therapy with 131I in patients with metastases but the results in postsurgical treatment are controversial. Our main objective is to investigate the impact of the mutation on the biokinetics of the administered 131I therapy after surgery. A prospective study was designed, from July 2015 to January 2018 which included patients with PTC receiving 131I therapy after surgical treatment. To study the biokinetics of the radioiodine in postoperative thyroid remnants, SPECT-CT images were acquired so as to obtain the following variables: percentage of remnant uptake at 2 and 7 days post-administration, effective half-life and time-integrated activity coefficient. All of them were compared depending on the mutational diagnosis and other clinical features and pathological variables. Sixty-one patients, and in total 103 thyroid remnants, were included. About 59% of patients were BRAF mutated. The mutation was associated with classic variant (88.5% vs. 11.5%; P=0.0001), desmoplastic reaction (85.7% vs. 14.3%; P=0.002), smaller tumor size (1.5 vs. 2.1 cm; P=0.024), nodal disease (3.3 vs. 1; P=0.001) and advanced stages (76.9% vs. 23%; P=0.014). The BRAFmut group had a lower percentage of 131I uptake at 2 days (0.17% vs. 0.47%; P=0.001) and at 7 days (0.02% vs. 0.1%; P=0.013); and a lower time-integrated activity coefficient (0.05h vs. 0.17 h; P=0.002). In univariate analysis, in addition to the mutation, the histological variant was significant but only for time-integrated activity coefficient (P=0.04). In multivariate analysis, only mutation determined the 2-day uptake (P<0.001) and the time-integrated activity coefficient (P<0.001). The BRAF V600E mutation is associated with lower 131I uptake in thyroid remnants. Furthermore, it is an independent factor that decreases the effect of post-surgical 131I therapy, and therefore, it could be used as a potential tool to optimize the treatment of PTC.