Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma

Abstract

Background In this study, we investigated the relationship between clinicopathologic factors, BRAFV600E mutation status and [18F] F-fluoro-2-deoxyglucose (FDG) avidity in patients with radioiodine (RAI)-negative recurrent or metastatic differentiated thyroid cancer (DTC). Methods From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAFV600E mutation testing by immunohistochemistry and real-time PCR. Tumor size, recurrent versus metastatic disease, histopathologic features including classical type versus aggressive subtypes (poorly differentiated, tall cell, columnar cell, hobnail variants) and BRAFV600E mutation status were correlated with the SUVmax of highest hypermetabolic lesions on FDG PET/CT by the univariate analysis using logistic regression. Results Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17–81) were included. The majority of patients had BRAFV600E mutation and classical subtype, 55/63 (87.3%) and 45/63(71.4%), respectively. Thyroglobulin at the time of suspected recurrence was 262.7 ng/ml (range 16.3–1000) and patients received a median 3 prior RAI treatments. Fifty-four patients (85.7%) had local recurrence. The majority of patients 58/63 (92.1%) had FDG-avid disease on PET/CT. On univariate analysis, tumor size aggressive histopathologic types and distant metastasis are the significant factors for predicting FDG uptake, p = 0.04, p = 0.001 and p = 0.004 respectively. Although FDG uptake of BRAFV600E bearing recurrent/metastatic RAIR DTC lesions was higher than those without the mutation, the difference did not reach statistical significance, SUVmax of 7.11 versus 4.91, respectively, p = 0.2. Conclusion The majority of recurrent or metastatic RAI-negative DTC have BRAFV600E mutation and detectable disease on FDG PET/CT. FDG avidity of the recurrent or metastatic RAI-negative DTC is independently associated with the aggressive histopathologic features.

A Narrative Review of Genetic Alterations in Primary Thyroid Epithelial Cancer

“…Several studies have investigated the role of BRAF-V600E mutations as prognostic markers and have shown a strong correlation with poor clinicopathological outcomes of PTC. In particular, a close association of BRAF mutation with extrathyroidal extension, lymph node metastasis, and advanced TNM stages III/IV of PTC, which are welldocumented risk factors associated with increased rates of recurrence and mortality of thyroid cancer, have been reported [42][43][44][45][46]. The role of the BRAF-V600E mutation as a poor prognostic factor has also been reported in low-risk intrathyroidal tumors [44].…”

Strategies for Radioiodine Treatment: What’s New

“…Refractory tumors have an enhanced expression of glucose transporters, such as GLUT1 [ 188 , 189 ]. This change is reflected in the occurrence of 18 FDG-PET avid-metastases and is associated with iodine refractoriness, aggressive disease, and poor outcome [ 170 , 190 , 191 ].…”

Predictive Value of Clinical and Pathological Characteristics for Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma: A 16-year Retrospective Study

“…In our research, we also focused on whether extrathyroid invasion could lead to RAIR-DTC. Ha's study suggested that aggressive histopathologic subtypes were significantly associated with the recurrent or metastatic lesions in RAI-negative DTC (35). Robertson et al (36) conducted a multivariate analysis of 231 patients with thyroid cancer and found that lymphadenopathy was the only important risk factor for recurrence (p<0.001), and the presence of extrathyroid invasion (p=0.013) leaded to high mortality.…”

“…In our research, we also focused on whether extrathyroid invasion could lead to RAIR-DTC. Ha’s study suggested that aggressive histopathologic subtypes were significantly associated with the recurrent or metastatic lesions in RAI-negative DTC ( 35 ). Robertson et al.…”