Assessment of Breathomics Testing Using High-Pressure Photon Ionization Time-of-Flight Mass Spectrometry to Detect Esophageal Cancer

Question Could esophageal cancer be detected by testing breathomics using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS)? Findings In this diagnostic study of 675 patients with and without cancer, esophageal cancer was accurately detected by testing breathomics with a sensitivity of 97.83% and specificity of 83.72% in the validation data set. Meaning These findings suggest that testing breathomics could help to improve the diagnosis of esophageal cancer. This diagnostic study investigates whether breathomics can detect esophageal cancer among patients without a previous diagnosis of cancer using high-pressure photon ionization time-of-flight mass spectrometry. Importance A triage test is needed to increase the detection rate for esophageal cancer. Objective To investigate whether breathomics can detect esophageal cancer among patients without a previous diagnosis of cancer using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Design, Setting, and Participants This diagnostic study included participants who planned to receive an upper endoscopy or surgery of the esophagus at a single center in China. Exhaled breath was collected with a self-designed collector and air bags before participants underwent these procedures. Sample collection and analyses were performed by trained researchers following a standardized protocol. Participants were randomly divided into a discovery data set and a validation data set. Data were collected from December 2020 to March 2021. Exposures Breath samples were analyzed by HPPI-TOFMS, and the support vector machine algorithm was used to construct a detection model. Main Outcomes and Measures The accuracy of breathomics was measured by the sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve. Results Exhaled breath samples were obtained from 675 patients (216 [32%] with esophageal cancer; 459 [68%] with noncancer diseases). Of all patients, 206 (31%) were women, and the mean (SD) age was 64.0 (11.9) years. In the validation data set, esophageal cancer was detected with an accuracy of 93.33%, sensitivity of 97.83%, specificity of 83.72%, positive predictive value of 94.74%, negative predictive value of 92.78%, and area under the receiver operating characteristic curve of 0.89. Notably, for 16 patients with high-grade intraepithelial neoplasia, 12 (75%) were predicted to have esophageal cancer. Conclusions and Relevance In this diagnostic study, testing breathomics using HPPI-TOFMS was feasible for esophageal cancer detection and totally noninvasive, which could help to improve the diagnosis of esophageal cancer.