[18F]-Fluorodeoxyglucose Uptake as a Marker of Residual Anaplastic and Poorly Differentiated Thyroid Carcinoma Following BRAF-Targeted Therapy

Samir A Dagher; Kim O Learned; Richard Dagher; Jennifer Rui Wang; Xiao Zhao; S Mohsen Hosseini; Anastasios Maniakas; Maria E Cabanillas; Naifa L Busaidy; Ramona Dadu; Priyanka Iyer; Mark E Zafereo; Alexander M Khalaf

doi:10.3174/ajnr.A8588

[18F]-Fluorodeoxyglucose Uptake as a Marker of Residual Anaplastic and Poorly Differentiated Thyroid Carcinoma Following BRAF-Targeted Therapy

AJNR Am J Neuroradiol. 2024 Nov 21:ajnr.A8588. doi: 10.3174/ajnr.A8588. Online ahead of print.

Affiliation

¹ From the Department of Neuroradiology / Head and Neck Imaging (S.A.D., K.O.L., R.D., A.M.K.), Department of Head and Neck Surgery (J.R.W., X.Z., A.M., M.E.Z.), Department of Pathology (S.M.H.), and Department of Endocrine Neoplasia and Hormonal Disorders (M.E.C., N.L.B., R.D., P.I.), The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 39572200
DOI: 10.3174/ajnr.A8588

Abstract

Background and purpose: Neoadjuvant BRAF-directed therapy and immunotherapy followed by surgery improves survival in patients with BRAF^V600E-mutant anaplastic thyroid carcinoma (ATC), more so in those who have complete ATC pathologic response. This study assesses the ability of FDG-PET to non-invasively detect residual high-risk pathologies including ATC and poorly differentiated thyroid carcinoma (PDTC) in the preoperative setting.

Materials and methods: This retrospective, single-center study included consecutive BRAF^V600E-mutant ATC patients treated with at least 30 days of neoadjuvant BRAF-directed therapy and who underwent FDG-PET/CT within 30 days prior to surgery. The highest pathologic grade observed for every head and neck lesion resected was recorded. Each lesion on pre-operative PET/CT was retrospectively characterized. The primary endpoint was to contrast the standardized uptake normalized by lean body mass (SULmax) for lesions with residual high-risk (ATC, PDTC) versus low-risk pathologies (papillary thyroid carcinoma, negative). An optimal SULmax threshold was then identified using a ROC analysis, and the ability of this threshold to non-invasively and preoperatively risk-stratify patients by overall survival was then evaluated with a Kaplan-Meier plot.

Results: 30 patients (mean age 66.5±9.0; 17 males) were included in this study, with 94 surgically sampled lesions. Of these lesions, 57 (60.6%) were low-risk (39 negative, 18 papillary thyroid carcinoma) and 37 (39.4%) were high-risk (29 ATC, 8 PDTC). FDG uptake was higher for high-risk compared to low-risk pathologies: median SULmax 5.01 [IQR 2.81 - 10.95] versus 1.29 [IQR 1.06 - 3.1] (P<.001, Mann-Whitney U test). The sensitivity, specificity, and accuracy for detecting high-risk pathologies at the optimal threshold of SULmax ≥ 2.75 were 0.784 [95% CI 0.628-0.886], 0.702 [95% CI 0.573-0.805], and 0.734 [95% CI 0.637-0.813], respectively. Patients with at least 1 high-risk lesion identified with the aforementioned cut-off had a worse prognosis compared to patients without high-risk lesions in the head and neck: median OS for the former group was 259 days and was not attained for the latter (P=.038, log-rank test).

Conclusions: Preoperative FDG-PET non-invasively identifies lesions with residual high-risk pathologies following neoadjuvant BRAF-directed targeted therapy and immunotherapy for BRAF-mutated ATC. FDG-PET avidity may serve as an early prognostic marker which correlates with residual high-risk pathology in BRAF-mutated ATC following neoadjuvant therapy.

Abbreviations: ATC = anaplastic thyroid carcinoma; IQR = interquartile range; OS = overall survival; PDTC = poorly differentiated thyroid carcinoma; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic; SUL= standardized uptake value normalized by lean body mass.