Jessica Garcia1,2,3,4, Anne‐Sophie Wozny1,4, Florence Geiguer1,3,4, Aurélia Delherme1,3,4, David Barthélémy1,2,3,4, P. Merle5, Claire Tissot6, Frederick S. Jones7, Chassidy Johnson8, Xiaobin Xing9, Zhenyu Xu9, Daniel L. Edelstein7, Marie Brevet1,2,10, Pierre‐Jean Souquet11, Claire Rodriguez‐Lafrasse4,12, Léa Payen1,2,3,4, S. Couraud1,13,11
1CIRculating CANcer (CIRCAN) program Hospices Civils de Lyon Cancer institute Lyon France
2Cancer Research Center of Lyon, INSERM U1052, CNRS UMR5286, Claude Bernard University, University of Lyon, Lyon, France
3Laboratoire Commun de Recherche Hospices Civils de Lyon – BioMérieux, Centre Hospitalier Lyon Sud Hospices Civils de Lyon Lyon France
4Laboratoire de Biochimie et Biologie Moléculaire, Groupe Hospitalier Sud Hospices Civils de Lyon Lyon France
5Service de Pneumologie et oncologie thoracique, CHU G Montpied, Clermont-Ferrand, France
6Service de Pneumologie et Cancérologie Thoracique CHU Saint Etienne Saint‐Priest‐en‐Jarez France
7Medical Scientific Affairs, Sysmex Inostics, GmBH, Hamburg, Germany
8Biolidics Limited, Singapore, Singapore
9SOPHiA GENETICS SA, Headquarters, Saint Sulpice, Switzerland
10Institut de pathologie multisites des HCL-Site Est, Hospices Civils de Lyon, Lyon, France
11Service de Pneumologie aigue spécialisée et cancérologie thoracique Groupement hospitalier sud, Institut de Cancérologie des Hospices Civils de Lyon Lyon France
12UMR CNRS 5822/IN2P3, IPNL, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon‐Sud Université Lyon 1 Lyon France
13EMR 3738 Ciblage Thérapeutique en Oncologie, Faculté de médecine Lyon Sud Université Lyon 1, Université de Lyon Lyon France
Tóm tắt
AbstractCell‐free plasma DNA (cfDNA) and mimicking circulating tumor cells (mCTCs) have demonstrated tremendous potential for molecular diagnosis of cancer and have been rapidly implemented in specific settings. However, widespread clinical adoption still faces some obstacles. The purpose was to compare the performance of a BEAMing (beads, emulsion, amplification, and magnetics) assay (OncoBEAM™‐epidermal growth factor receptor [EGFR] [Sysmex Inostics]) and a next‐generation sequencing assay (NGS; 56G Oncology panel kit, Swift Bioscience) to detect the p.T790M EGFR mutation in cfDNA of non‐small cell lung cancer (NSCLC) patients. CfDNA samples (n = 183) were collected within our hospital from patients having a known EGFR sensitizing mutation, and presenting disease progression while under first‐line therapy. EGFR mutations were detected using NGS in 42.1% of samples during progression in cfDNA. Testing using the OncoBEAM™‐EGFR assay enabled detection of the p.T790M EGFR mutation in 40/183 NSCLC patients (21.8%) versus 20/183 (10.9%), using the NGS assay. Samples that were only positive with the OncoBEAM™‐EGFR assay had lower mutant allelic fractions (Mean = 0.1304%; SD ± 0.1463%). In addition, we investigated the detection of p.T790M in mCTCs using H1975 cells. These cells spiked into whole blood were enriched using the ClearCellFX1 microfluidic device. Using the OncoBEAM™‐EGFR assay, p.T790M was detected in as few as 1.33 tumoral cells/mL. Overall, these findings highlight the value of using the OncoBEAM™‐EGFR to optimize detection of the p.T790M mutation, as well as the complementary clinical value that each of the mutation detection assay offers: NGS enabled the detection of mutations in other oncogenes that may be relevant to secondary resistance mechanisms, whereas the OncoBEAM™‐EGFR assay achieved higher sensitivity for detection of clinically actionable mutations.
