Background
Distinguishing between malignant and benign thyroid nodules remains a significant challenge for clinicians and researchers globally. The use of volatile organic compounds (VOCs) has emerged as a novel approach in cancer diagnosis. This prospective pilot study aims to identify VOCs in exhaled breath, blood, and urine that can differentiate benign from malignant thyroid nodules using gas chromatography-ion mobility spectrometry (GC-IMS).
Methods
Patients with thyroid nodules scheduled for surgery were enrolled at the Maastricht University Medical Center (MUMC+). Breath samples were analyzed using a BreathSpec GC-IMS machine (G.A.S. Dortmund, Germany), specifically designed for breath analysis. All blood and urine samples were analyzed with a separate GC-IMS device, the FlavourSpec® (G.A.S., Dortmund, Germany).
Results 
In this proof-of-concept study, 70 patients undergoing thyroid surgery at MUMC+ were consecutively included. Of these patients, 29 were confirmed to have thyroid cancer after surgical resection. The overall analysis did not reveal statistically significant differences in VOCs in breath, urine and blood, between patients with benign and malignant thyroid cancer. 
Conclusion
This proof-of-concept study demonstrated that GC-IMS was unable to adequately distinguish between the VOC profiles of malignant and benign thyroid nodules. However, this study had a small sample size and future larger studies are needed to investigate the potential of using VOCs to distinguish between benign and malignant thyroid nodules. Furthermore, future research should focus on investigating potential confounders that affect patient VOC profiles.
(NCT04883294)
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