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

Qi Huang,Shushi Meng,Song Zhao,Qingyun Li,Xiangnan Li,Jianfeng Li,Yu Qi,Shaodong Wang,Hang Li,Mantang Qiu,Yang Yang,Hao Wu,Peiyu Wang

doi:10.1001/jamanetworkopen.2021.27042

Abstract

A triage test is needed to increase the detection rate for esophageal cancer. 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). 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. Breath samples were analyzed by HPPI-TOFMS, and the support vector machine algorithm was used to construct a detection model. 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. 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. 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.

Highlights

Esophageal cancer is the sixth leading cause of cancer-related death worldwide.[1]
Exhaled breath samples were obtained from 675 patients (216 [32%] with esophageal cancer; 459 [68%] with noncancer diseases)
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

Summary

Introduction

Esophageal cancer is the sixth leading cause of cancer-related death worldwide.[1] It is estimated that nearly half of new esophageal cancer cases are in China.[1] Approximately 80% of patients with esophageal cancer are diagnosed at a late stage, resulting in poor 5-year survival.[2] Upper endoscopy is the primary option for esophageal cancer detection and screening; endoscopy is not suitable for population-based screening because it is invasive, expensive, and not sensitive among patients without symptoms.[3] Esophageal cancer may be missed at endoscopy in as many as 7.8% of patients who are subsequently diagnosed with cancer.[4] a sensitive, noninvasive, and inexpensive tool is urgently needed to detect esophageal cancer at an early stage

Methods

Results

Discussion

Conclusion