Abstract
Lung cancer, malignant pleural mesothelioma, and esophageal cancer are the most common thoracic malignancies and are responsible for substantial cancer-related morbidity and mortality worldwide. Early cancer identification prompts earlier intervention and can therefore improve patient survival. Traditional diagnostics are costly and invasive, however, creating an urgent need for alternative methods. Over the past 30 years, breath analysis has emerged as a rapid, minimally invasive, and cost-effective approach. Metabolites in exhaled breath, known as volatile organic compounds (VOCs), reflect internal biomolecular processes and their composition has been shown to vary in association with numerous pathological states. This review provides an overview on the use of VOCs in exhaled breath for the early screening and diagnosis of thoracic malignancies. Study design, methodology, and significant results from over sixty studies published since 1990 are specified and summarized. A total of 439 significant VOCs are reported in the literature, mainly consisting of aromatic compounds, aldehydes, alkanes, lipids, ketones, and sulfur-containing compounds. Diagnostic sensitivities and specificities range from 51-100% and 68.8 – 100%, respectively. Cancer-specific VOC profiles and associations of clinical interest (e.g., comorbidities, histology, and staging) are emphasized and discussed. While there is considerable evidence to support the diagnostic utility of VOCs, the lack of standardization and external validation in large independent cohorts remain key barriers to clinical translation. However, efforts to address these limitations are currently underway.
Highlights
Thoracic malignancies are aggressive neoplasms of uncontrolled cell growth that originate within the chest cavity
Diagnostic accuracy and specificity for Malignant pleural mesothelioma (MPM) appears to increase given a history of asbestos exposure. These results suggest that volatile organic compounds (VOCs) screening may yield lower false positive rates in patients with a history of asbestos exposure
Electronic sensor accounts for the majority of lung cancer studies published within the same time period and are gaining popularity over Gas chromatography-mass spectrometry (GC-MS) as the VOC detection method of choice
Summary
Thoracic malignancies are aggressive neoplasms of uncontrolled cell growth that originate within the chest cavity. Malignant pleural mesothelioma, and esophageal cancer are the most common thoracic malignancies. Screening and detection can reduce mortality in all three cancers [1,2,3]. Over the past few decades, volatile organic compounds (VOCs) in exhaled breath have emerged as a potentially quick, safe, noninvasive biomarker for detecting lung cancer, esophageal cancer, and malignant pleural mesothelioma. Prior reviews have considered these three malignancies separately; overall VOC patterns between lung cancer, esophageal cancer, and malignant pleural mesothelioma have not been explored. Lung Cancer Lung cancer (LC) is a tumor of lung tissue most commonly caused by smoking cigarettes [9]. Lung cancer is the leading cause of cancer mortality in the United States and worldwide, accounting for 2.1 million new cases and 1.8 million deaths in 2018 [10]. Over 50% of patients with lung cancer die within one year following diagnosis and have a five-year survival rate of less than 20% [9]
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