Reliability of BRAF mutation detection using plasma sample: A systematic review and meta-analysis

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Testing for B-Raf proto-oncogene (BRAF) mutations is crucial for guiding targeted cancer therapies.
• Plasma samples are frequently utilized for BRAF mutation testing when tumor tissue is inaccessible.
• This study aimed to evaluate the diagnostic accuracy of BRAF mutation testing in plasma samples from cancer patients.

Purpose of the Study:

• To investigate the diagnostic accuracy of BRAF mutation testing using plasma samples.
• To compare the accuracy of plasma-based testing with traditional tumor tissue analysis.
• To identify factors influencing the accuracy of plasma-based BRAF mutation detection.

Main Methods:

• A systematic literature search was conducted across PubMed, Embase, and Cochrane Library for studies comparing paired tissue and plasma BRAF mutation testing.
• Eligible studies involving cancer patients were screened, and data from 53 studies encompassing 3943 patients were pooled.
• Statistical analysis, including meta-analysis and subgroup analysis, was performed to determine pooled sensitivity, specificity, and diagnostic odds ratio.

Main Results:

• Pooled sensitivity and specificity for plasma-based BRAF mutation testing were 69% and 98%, respectively, with a diagnostic odds ratio of 55.78.
• The area under the summary receiver operating characteristic curve was 0.9435, indicating high diagnostic performance.
• Plasma testing showed higher accuracy in colorectal cancer (diagnostic odds ratio of 89.17) compared to melanoma and thyroid carcinoma. Next-generation sequencing demonstrated superior accuracy over PCR-based methods.

Conclusions:

• BRAF mutation testing using plasma samples exhibits high diagnostic accuracy, serving as a viable alternative to tumor tissue analysis for cancer genotyping.
• Plasma-based testing is particularly effective for guiding targeted therapies when tumor samples are not obtainable.
• Further large-scale prospective studies are recommended to comprehensively validate the accuracy of plasma BRAF mutation testing.