BRAF V600E-mutated papillary thyroid cancer shows proinflammatory profile in real-world analysis
A real-world analysis found BRAF V600E-mutated papillary thyroid cancer had a proinflammatory molecular profile, but no significant overall survival difference versus BRAF wild-type disease. Treatment choice among BRAF/MEK inhibitors, tyrosine kinase inhibitors, and immunotherapy was not associated with significant survival differences.
BRAF V600E–mutated papillary thyroid cancer was associated with a proinflammatory tumor microenvironment milieu compared with BRAF wild-type papillary thyroid cancer in a real-world molecular profiling analysis. In a dataset of 1,348 patients with differentiated thyroid cancer, overall survival was not significantly different between patients with BRAF-mut and BRAF-WT papillary thyroid cancer, and systemic treatment choice was not associated with significant differences in overall survival in BRAF-mut disease.
Radioactive iodine–refractory papillary thyroid cancers containing BRAF V600E mutations can be treated with BRAF/MEK inhibitors, but their effectiveness compared with tyrosine kinase inhibitors and immunotherapy remains unclear. Thyroid tumor samples underwent DNA/RNA next-generation sequencing and immunohistochemistry, while tumor microenvironment cell fractions were estimated by RNA deconvolution using quanTIseq. Insurance claims data were used to infer real-world overall survival and time on treatment.
A total of 1,348 patients with differentiated thyroid cancer were identified; 81.8% were classified as papillary thyroid cancer, of which 68.4% harbored a BRAF V600E mutation. TERT promoter mutations were the most common mutation in papillary thyroid cancer at 72% and were more prevalent in BRAF-mut versus BRAF-WT disease. Mutations in NRAS, HRAS, and KRAS, as well as RET, BRAF, and ETV6 gene fusions, were predominantly found in BRAF-WT papillary thyroid cancer.
BRAF-mut papillary thyroid cancer were more often PD-L1+ than BRAF-WT disease (33% vs. 18%, P < 0.001) and had significantly higher IFNγ scores. Overall survival was not significantly different between patients with BRAF-mut versus BRAF-WT papillary thyroid cancer. In BRAF-mut papillary thyroid cancer, systemic treatment with BRAF/MEK inhibitors, tyrosine kinase inhibitors, or immunotherapy was not associated with significant differences in overall survival, although there was a trend for longer overall survival in those treated with tyrosine kinase inhibitors compared with BRAF/MEK inhibitors or immunotherapy.
A separate review of precision thyroid oncology described thyroid cancer as the most prevalent endocrine malignancy worldwide and outlined persistent clinical bottlenecks including the diagnostic ambiguity of Bethesda III/IV nodules, the rising prevalence of radioiodine-refractory differentiated thyroid cancer, and the dismal survival rates of anaplastic thyroid carcinoma. The review said biomarkers including BRAF, RAS, TERT, RET, and NTRK, along with liquid biopsy, single-cell sequencing, and spatial transcriptomics, are contributing to a shift from traditional anatomical-pathological staging to a molecular taxonomy model in thyroid oncology.