Abstract
Aim Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck®, a 6-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples.
Methods A case-control European training set (102 lung cancer cases/265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case-control European and Chinese validation sets (cases/controls: 179/137 and 30/15).
Results The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The respective sensitivity/specificity with LCO were 87.2%/64.2% and 76.7%/93.3% and with HCO were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I NSCLC sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. SCLC was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942.
Conclusions Lung EpiCheck demonstrated strong performance in lung cancer prediction in case-control European and Chinese samples, detecting high proportions of early stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Yan reports grants from National Institutes of Health, during the conduct of the study;.
Conflict of interest: Dr. Gaga has nothing to disclose.
Conflict of interest: Dr. Chorostowska-Wynimko reports grants, personal fees and non-financial support from Grifols, grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Pfizer, personal fees and non-financial support from MSD, personal fees and non-financial support from BMS, personal fees from GSK, personal fees from Novartis, personal fees from Chiesi, personal fees from Roche, grants and personal fees from Boehringer-Ingelheim, grants, personal fees and non-financial support from CSL Behring, grants, personal fees and non-financial support from CelonPharma, personal fees from Amgen, personal fees from Lekam, outside the submitted work;.
Conflict of interest: Dr. Horvath reports personal fees from AstraZeneca, personal fees from Novartis, personal fees from CSL Behring, personal fees from Boeringer-Ingelheim, personal fees from GSK, personal fees from Berlin-Chemie, from null, outside the submitted work;.
Conflict of interest: As of January 2019, Tammemagi has served as consultant to Johnson & Johnson/Janssen, Medial EarlySign, Nucleix, bioAffinity Technologies, AstraZeneca. Dr Tammemagi has serve as consultant for these companies providing advice on the design and analysis of biomarker or lung cancer screening studies or on cancer risk prediction modelling.
Conflict of interest: Dr. shitrit has nothing to disclose.
Conflict of interest: Dr. Eisenberg has nothing to disclose.
Conflict of interest: Dr. liang has nothing to disclose.
Conflict of interest: Dr. Levy Faber has nothing to disclose.
Conflict of interest: Dr. Jansen has nothing to disclose.
Conflict of interest: Dr. Raviv has nothing to disclose.
Conflict of interest: Dr. Panagoulias has nothing to disclose.
Conflict of interest: Dr. Rudzinski has nothing to disclose.
Conflict of interest: Dr. Izbicki has nothing to disclose.
Conflict of interest: Dr. Ronen has nothing to disclose.
Conflict of interest: Dr. Goldhaber has nothing to disclose.
Conflict of interest: Dr. Arber has nothing to disclose.
Conflict of interest: Dr. Haas Hamish has nothing to disclose.
Conflict of interest: Dr. Zhou has nothing to disclose.
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- Received July 9, 2020.
- Accepted October 7, 2020.
- Copyright ©ERS 2020
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
