2022,
BMC Cancer.
DOI:
10.1186/s12885-022-09849-x
Results of a worldwide external quality assessment of cfDNA testing in lung Cancer
Jennifer A. Fairley
, Melanie H. Cheetham
, Simon J. Patton
, Etienne Rouleau
, Marc Denis
, Elisabeth M. C. Dequeker
, Ed Schuuring
, Kaat van Casteren
, Francesca Fenizia
, Nicola Normanno
, Zandra C. Deans
Abstract:
Abstract
Background
Circulating cell free DNA (cfDNA) testing of plasma for EGFR somatic variants in lung cancer patients is being widely implemented and with any new service, external quality assessment (EQA) is required to ensure patient safety. An international consortium, International Quality Network for Pathology (IQNPath), has delivered a second round of assessment to measure the accuracy of cfDNA testing for lung cancer and the interpretation of the results.
Methods
A collaboration of five EQA provider organisations, all members of IQNPath, have delivered the assessment during 2018–19 to a total of 264 laboratories from 45 countries. Bespoke plasma reference material containing a range of EGFR mutations at varying allelic frequencies were supplied to laboratories for testing and reporting according to routine procedures. The genotyping accuracy and clinical reporting was reviewed against standardised criteria and feedback was provided to participants.
Results
The overall genotyping error rate in the EQA was found to be 11.1%. Low allelic frequency samples were the most challenging and were not detected by some testing methods, resulting in critical genotyping errors. This was reflected in higher false negative rates for samples with variant allele frequencies (VAF) rates less than 1.5% compared to higher frequencies. A sample with two different EGFR mutations gave inconsistent detection of both mutations. However, for one sample, where two variants were present at a VAF of less than 1% then both mutations were correctly detected in 145/263 laboratories. Reports often did not address the risk that tumour DNA may have not been tested and limitations of the methodologies provided by participants were insufficient. This was reflected in the average interpretation score for the EQA being 1.49 out of a maximum of 2.
Conclusions
The variability in the standard of genotyping and reporting highlighted the need for EQA and educational guidance in this field to ensure the delivery of high-quality clinical services where testing of cfDNA is the only option for clinical management.
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2023-08-24 13:14:00
龙海晨:
#paper Fairley JA, Cheetham MH, Patton SJ, Rouleau E, Denis M, Dequeker EMC, Schuuring E, van Casteren K, Fenizia F, Normanno N, Deans ZC. Results of a worldwide external quality assessment of cfDNA testing in lung Cancer. BMC Cancer. 2022 Jul 12;22(1):759. doi: 10.1186/s12885-022-09849-x. PMID: 35820813; PMCID: PMC9275131. 文章是对世界范围内用cfDNA检测肺癌的进行质量评估。45个国家304家注册实验室中有264个实验室提交了结果。排除无法从人造血浆中提取DNA的实验室，大多数实验室获得了准确的结果，对于不同的基因突变采用不同的检测手段准确率不同。实验证明了CFDNA检测肺癌的可行性。