Breathomics in mesothelioma detection: volatile organic compounds-based approach for rapid and non-invasive diagnosis: a systematic review and meta analysis

Abstract

Malignant pleural mesothelioma (MPM) is a rare but fatal cancer linked to asbestos exposure, accounting for over 30,000 deaths annually with a median survival of less than 12 months. Its prolonged latency (30 – 40 years) and non-specific symptoms, early diagnosis challenging. Breath analysis of volatile organic compounds (VOCs) offers a non-invasive method potentially capable of detecting MPM before radiologic signs appear. This meta-analysis evaluates the diagnostic accuracy of VOC-based breathomics in MPM detection from healthy controls (HC), asbestos-exposed individuals (AE), and other asbestos-related diseases (ARD). A systematic search of PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect identified 2,956 articles, of which six cross-sectional studies (n=618) met PRISMA-based inclusion criteria: (1) VOC-based breath analysis using GC–MS, MCC/IMS, CDA–PCA, or e-nose; (2) reporting diagnostic accuracy metrics (Sn, Sp, AUC, PPV, NPV); (3) including MPM, HC, and AE groups; and (4) comparison with standard diagnostic references. Risk of bias was assessed via QUADAS-2; publication bias with funnel plots and Egger’s test; and bivariate meta-analysis conducted using REML in R. Compared to HC, VOC-breathomics yielded a sensitivity of 0.830, specificity of 0.686, and AUC of 0.786 (I² ≈ 29.1%). Against AE and ARD, sensitivity was 0.877 and 0.807; specificity was 0.850 and 0.723; AUC was 0.860 and 0.815 (I² ≈ 0%). LogDORs were 2.86 [1.75-3.96] (HC), 3.42 [2.33-4.52] (AE), and 2.72 [1.90-3.53] (ARD). Publication bias was detected for HC (p=0.0464) but not AE/ARD. VOCs such as cyclohexane, benzonitrile, and a-pinene have been identified as markers for MPM and lung cancer. While cyclopentane, methyl-octane, and dimethyl-nonane are good indicators for long-term asbestos exposure. VOCs from breath analysis show strong potential for early and non-invasive MPM diagnosis. VOC-based breath analysis has great potential as a non-invasive method for early detection of MPM, although large-scale validation studies are still needed.