Mina Gaga1, Joanna Chorostowska-Wynimko2, Ildikó Horváth3, Martin C Tammemagi4, David Shitrit5, Vered H Eisenberg6, Hao Liang7, David Stav8, Dan Levy Faber9,10, Maarten Jansen11, Yael Raviv12, Vasileios Panagoulias13, Piotr Rudzinski2, Gabriel Izbicki14, Ohad Ronen15, Adiv Goldhaber16, Rawia Moalem17, Nadir Arber18, Ilana Haas19, Qinghua Zhou7. 1. 7th Respiratory Medicine Dept, Athens Chest Hospital, Athens, Greece. 2. National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. 3. National Korányi Institute of Pulmonology, Budapest, Hungary. 4. Brock University, St Catharines, ON, Canada. 5. Pulmonary Dept, Meir Medical Center, Kfar Saba, Israel. 6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 7. Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, China. 8. Lung Institute, Maccabi Health Services Hashalom, Tel-Aviv, Israel. 9. Dept of Cardiothoracic Surgery, Lady Davis Carmel Medical Center, Haifa, Israel. 10. Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. 11. Pulmonary Dept, Ziekenhuisgroep Twente, Hengelo, The Netherlands. 12. Dept of Medicine, Pulmonology Institute, Soroka Medical Center, Ben-Gurion University, Beer-Sheva, Israel. 13. 2nd Respiratory Medicine Dept, Athens Chest Hospital, Athens, Greece. 14. Pulmonary Institute, Shaare Zedek Medical Center, Jerusalem, Israel. 15. Dept of Otolaryngology - Head and Neck Surgery, Galilee Medical Center affiliated with Azrieli Faculty of Medicine, Safed, Israel. 16. Clalit Health Services, Raanana, Israel. 17. Gastroenterology Institute, The Holy Family Hospital, Nazareth, Israel. 18. Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel. 19. Breast Unit, Meir Medical Center, Kfar Saba, Israel.
Abstract
AIM: Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck, a six-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. METHODS: A case-control European training set (n=102 lung cancer cases, n=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, respectively). RESULTS: The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The sensitivities/specificities with LCO were 87.2%/64.2% and 76.7%/93.3%, and with HCO they were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I nonsmall cell lung cancer (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. Small cell lung cancer (SCLC) was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%, respectively. 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.
AIM: Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck, a six-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. METHODS: A case-control European training set (n=102 lung cancer cases, n=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, respectively). RESULTS: The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The sensitivities/specificities with LCO were 87.2%/64.2% and 76.7%/93.3%, and with HCO they were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I nonsmall cell lung cancer (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. Small cell lung cancer (SCLC) was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%, respectively. 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.
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