BRAF V600 Mutation Detection in Plasma Cell-Free DNA: NCCTG N0879 (Alliance)
| Autor: | Jessica A. Slostad, Michael D. Keppen, Svetomir N. Markovic, Robert R. McWilliams, Lori A. Erickson, Minetta C. Liu, Kandelaria M. Rumilla, Matthew S. Block, Jacob B. Allred, David M. King |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Medicine (General) NA not available Phases of clinical research Plasma cell OS overall survival chemistry.chemical_compound R5-920 Internal medicine Lactate dehydrogenase medicine Progression-free survival neoplasms NCCTG North Central Cancer Treatment Group LDH lactate dehydrogenase business.industry Melanoma Hazard ratio cfDNA cell-free DNA medicine.disease HR hazard ratio PFS progression-free survival PPV positive predictive value Clinical trial FFPE formalin-fixed paraffin-embedded medicine.anatomical_structure NPV negative predictive value Cell-free fetal DNA chemistry Original Article ddPCR digital droplet polymerase chain reaction business MAPK mitogen-activated protein kinase |
| Zdroj: | Mayo Clinic Proceedings: Innovations, Quality & Outcomes Mayo Clinic Proceedings: Innovations, Quality & Outcomes, Vol 5, Iss 6, Pp 1012-1020 (2021) |
| ISSN: | 2542-4548 |
| Popis: | Objective To evaluate the prognostic significance of detectable circulating cell-free DNA (cfDNA) BRAF V600E/K mutations in patients with advanced melanoma enrolled in a clinical trial without BRAF-targeted therapy. Patients and Methods BRAF V600E/K mutation status was determined on archived tissue and pretreatment stored plasma from 149 patients with unresectable stage IV melanoma who were enrolled between May 5, 2010 and May 2, 2014 in the North Central Cancer Treatment Group/Alliance N0879 randomized phase 2 clinical trial. Results were reported as presence or absence of cfDNA BRAF V600E/K detection of assay vs tissue. Progression-free survival (PFS) and overall survival (OS) were assessed for patients with and without detectable BRAF mutation. Results In total, 63 of 149 (42.3%) patients had BRAF V600E/K results for tissue and blood, and 20 of 63 (31.7%) patients had tissue-diagnosed mutant BRAF. Of these, 11 of 20 (55.0%) patients had detectable plasma cfDNA BRAF. Among patients with tissue-mutant BRAF V600E/K, PFS and OS were shorter for those with corresponding cfDNA mutations (PFS, 5.8 vs 12.0 months; P=.051; OS, 9.2 vs 27.1 months; P=.054). Our assay demonstrated sensitivity of 55% (95% CI, 0.322 to 0.768), specificity of 97.7% (95% CI, 0.932 to 1.000), positive predictive value of 91.7% (95% CI, 0.760 to 1.000), and negative predictive value of 82.4% (95% CI, 0.719 to 0.928). Conclusion In advanced melanoma, detectable cfDNA BRAF V600E/K mutation is present in about half the patients with stage IV with BRAF-mutant melanoma tumor tissue and appears to confer a poorer prognosis when detectable. Given the poorer prognosis, cfDNA can be used to risk-stratify patients with metastatic melanoma in practice or clinical trials.Trial Registration: clinicaltrials.gov Identifier: NCT00976573 |
| Databáze: | OpenAIRE |
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