175 Background: In its early stages, gastric cancer symptoms are frequently lacking, resulting in an often late and incurable diagnosis. A non-invasive, cheap, and reliable screening method for gastric cancer could improve outcomes and increase the number of surgically resectable gastric cancers. Breath analysis has emerged as an experimental method of non-invasive screening of gastric cancer and identification of individuals suitable for confirmatory, diagnostic upper gastrointestinal endoscopy. We aimed to evaluate the accuracy and applicability of breath analysis for gastric cancer detection in adults. Methods: This systematic review searched MEDLINE, EMBASE, BIOSIS, CENTRAL, and Compendex until 11 July 2019 for original studies analyzing exhaled breath to detect gastric cancer in patients. Two authors then independently screened the abstracts, titles, and full texts. Summary sensitivity and specificity analyses were obtained using a hierarchical bivariate method. Positive predictive value and number needed to screen (NNS) of breath analysis methods for gastric cancer detection were calculated for each country using gastric cancer prevalence by country obtained from the Global Cancer Observatory. Non-quantitative results were descriptively summarized. Risk of bias was assessed using the QUADAS-2 tool. This study protocol was pre-registered in PROSPERO (CRD42020139422). Results: Twenty studies were included. Together, the studies included 2,976 subjects. The pooled mean age of the subjects in the gastric cancer groups was 60.5 ± 11 years while the pooled mean age for control groups was 55.4 ± 12 years. Within these twenty studies, breath analysis technologies most commonly used were mass spectrometry (MS)-based methods; other methods included volatile organic compound sensors, thermal desorption tubes, and silicon nanowire field effect transistors. Across all included studies, we found and summarized the characteristics of 131 chemical compounds found in the exhaled breath of study subjects. Eleven studies (total n = 1905) involving all technologies reported quantitative results, with sensitivities ranging from 67-100% and specificities from 71-98%. The summary sensitivity across six studies utilizing MS-based breath analysis methods was 85.3% (95% CI: 82-96%); summary specificity was 81.7%. (95% CI: 78-85%). Based on the MS-based values, we estimated that screening with MS-based breath tests could lower the NNS by more than four-fold in the 15 countries with the highest prevalence of gastric cancer. Conclusions: Breath analysis is a promising method for gastric cancer detection with good diagnostic performance and potential to decrease the NNS for endoscopy-based gastric cancer detection. However, due to the heterogeneity of breath analysis technologies, rigorous studies with standardized, reproducible methods are needed to evaluate the clinical applicability of these technologies.
Detection of cancer through exhaled breath: a systematic review