Abstract 5584: Exhaled breath as diagnostic tool for malignant pleural mesothelioma

Abstract

Abstract Background: Malignant Pleural Mesothelioma (MPM) is an asbestos-related disease with a dismal prognosis due to its late detection at an advanced stage. Hence, a diagnostic test is requisite that allows to screen asbestos-exposed persons for earlier MPM detection. As blood biomarkers have not shown to be clinically useful biomarkers for early non-invasive diagnosis, breath is currently explored. Breath is easy to retrieve by physicians in a clinical environment and contains volatile organic compounds (VOCs) that arise from (patho)physiological processes. Since asbestos causes oxidative stress and cancers are known to up regulate their metabolism, we hypothesize that VOCs and, hence, the exhaled breath of MPM patients will differ from healthy controls. Methods: We compared the breath of 23 MPM patients, 10 asbestos-exposed and 12 non-exposed healthy individuals using a multicapillary column/ion mobility spectrometer (MCC/IMS, B&S Analytik, Dortmund, Germany). After subjects refrained from eating, drinking and smoking for at least 2 hours, 10 ml alveolar air was sampled via a CO2-controlled ultrasonic sensor and subsequently analyzed. Per subject a background sample was taken. Eighty-nine VOC peaks were visually selected via on-board VisualNow 3.7 software. Their intensity was compared between background and breath samples. After calculating the VOCs’ alveolar gradient, we performed a logistic LASSO regression in R (R-Foundation for Statistical Computing, Vienna, Austria). We selected the optimal MPM diagnostic logistic LASSO model by 10-fold cross-validation using age, gender and the alveolar gradient of the peaks and estimated this models’ sensitivity, specificity, AUCROC and positive (PPV) and negative predictive value (NPV). Results: We were able to discriminate MPM patients from the asbestos-exposed and non-exposed controls with 96% sensitivity and 91% specificity. The AUCROC was 0,94 and the PPV and NPV were resp. 92% and 95%. The VOCs P5, P3, and P1 were the significant discriminators. Conclusions: Breath analysis in a clinical setting by MCC/IMS allows to discriminate MPM patients from asbestos-exposed and non-exposed healthy controls. It can help to screen asbestos-exposed persons at risk, switching diagnosis to an early phase and hence, better patient survival. Identification of the underlying VOCs and a further validation in different patient cohorts is being undertaken. Citation Format: Kevin Lamote, Filip Lardon, Joris Van Cleemput, Kristiaan Nackaerts, Olivier Thas, Jan P. van Meerbeeck. Exhaled breath as diagnostic tool for malignant pleural mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5584. doi:10.1158/1538-7445.AM2015-5584