Breath Volatile Organic Compound Profiling of Colorectal Cancer Using Selected Ion Flow-tube Mass Spectrometry

Objective: (1) Identify changes in volatile organic compounds (VOCs) concentration within exhaled breath observed with colorectal cancer (CRCa) relative to control groups. (2) Validate the presence of discriminative VOCs in a prospective cohort. (3) Identify VOC changes related to CRCa recurrence following surgical resection. Background: Breath VOCs have the potential to noninvasively diagnose cancer. Methods: Exhaled breath samples were collected using 2-L double-layered Nalophan bags, and were analyzed using selected-ion-flow-tube mass-spectrometry. Gold-standard test for comparison was endoscopy for luminal inspection and computed tomography (CT) to confirm cancer recurrence. Three studies were conducted: (1) Profiling study: 150 patients; 50 CRCa and 100 controls; (2) Independent diagnostic validation: 79 patients; 25 CRCa and 54 controls; (3) Independent clinical validation with tumor recurrence: 40 patients; 19 postoperative (no recurrence), and 21 CRCa recurrences. Results: (1) In multivariate analysis, propanal was significantly elevated in the cancer cohort compared with control patients. Using a threshold of 28 ppbv, this gave a sensitivity of 96% and specificity of 76% for CRCa diagnosis. (2) In a prospective cohort, using a propanal threshold of 28 ppbv, this gave a sensitivity of 83.3% and specificity of 84.7%. (3) Following surgery, propanal reduced to levels expected in control patients, and with recurrence, levels increased significantly. Using a threshold of 28 ppbv, the sensitivity for identification of CRCa recurrence was 71.4% and specificity was 90.9%. Conclusion: This study suggests the association of a single breath biomarker with the primary presence and recurrence of CRCa. Further multicenter validation studies are required to validate these findings.