Journal article
Molecular Profiling and Real-World Outcomes of BRAF V600E-Mutated Papillary Thyroid Cancer
Clinical cancer research
01/16/2026
DOI: 10.1158/1078-0432.CCR-25-3932
PMID: 41543354
Abstract
Radioactive iodine refractory papillary thyroid cancers (PTC) containing BRAF-V600E mutations can be treated with BRAF/MEK inhibitors (BRAF/MEKi), but their effectiveness compared to tyrosine kinase inhibitors (TKI) and immunotherapy (IO) remains unclear. Therefore, we compared real-world survival and molecular/transcriptional signatures in patients with BRAF-mut and BRAF-wildtype (wt) PTC.
Thyroid tumor samples underwent DNA/RNA next-gen sequencing and immunohistochemistry at Caris Life Sciences. Tumor microenvironment (TME) cell fractions were estimated by RNA deconvolution using QuanTIseq. Insurance claims data was used to infer real-world overall survival (OS) and time on treatment.
A total of 1348 patients with differentiated thyroid cancer were identified; 81.8% were classified as PTC, of which 68.4% harbored a BRAF-V600E mutation. TERT promoter mutations were the most common mutation in PTC (72%), and more prevalent in BRAF-mut versus (vs) BRAF-wt. Mutations in NRAS, HRAS, and KRAS, as well as RET, BRAF, and ETV6 gene fusions, were predominantly found in BRAF-wt PTC. BRAF-mut PTC were more often PD-L1+ (33% vs. 18%, p<0.001) and had significantly higher IFNγ scores. OS was not significantly different between patients with BRAF-mut vs wt PTC. Systemic treatment (BRAF/MEKi, TKI or IO) was not associated with significant differences in OS in BRAF-mut PTC, although there was a trend for longer OS in those treated with TKI compared to BRAF/MEKi or IO.
BRAF-mut PTC is associated with a pro-inflammatory TME milieu compared to BRAF-wt PTC. However, in this limited data set, treatment choice was not associated with differences in OS in BRAF-mut PTC.
Details
- Title: Subtitle
- Molecular Profiling and Real-World Outcomes of BRAF V600E-Mutated Papillary Thyroid Cancer
- Creators
- Martina Chirra - University of CincinnatiAndrew Elliott - Caris Life SciencesHira Shaikh - University of IowaJulie McGrath - Phoenix Children's HospitalDalia El-Gamal - University of CincinnatiAnthony Nicholas Karnezis - University of California, DavisFarah R Abdulla - Caris Life SciencesChukwuemeka Ikpeazu - Sylvester Comprehensive Cancer CenterJennifer Leddon - Cincinnati VA Medical CenterAmmar Sukari - The Barbara Ann Karmanos Cancer InstituteDan P Zandberg - UPMC Hillman Cancer CenterJennifer Maria Johnson - Thomas Jefferson UniversityLova Sun - Hospital of the University of PennsylvaniaTrisha M Wise-Draper - University of Cincinnati
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research
- DOI
- 10.1158/1078-0432.CCR-25-3932
- PMID
- 41543354
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Publisher
- American Association for Cancer Research
- Language
- English
- Electronic publication date
- 01/16/2026
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985121590702771
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