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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.