Validation of the Diagnostic Accuracy of the Electronic Nose in the Detection of Thyroid Cancer

Thyroid cancer is the most common endocrine cancer worldwide. In most developed countries, the incidence of thyroid cancer has rapidly increased in the last three decades In the Netherlands, 700 patients are diagnosed with thyroid cancer each year. The most common histological forms are the well-differentiated papillary and follicular cancer, comprising of 80-85% of all thyroid cancers

Patients often present themselves with a thyroid nodule, which can be benign or malignant. Current diagnostic work-up includes ultrasound of the neck, resulting in the Thyroid Imaging Reporting And Data System (TI-RADS). This risk-stratification system for thyroid nodules is based on ultrasound features. When indicated, fine-needle aspiration cytology (FNAC) is performed, resulting in the Bethesda classification to report the risk of malignancy. The FNAC has been considered as gold standard diagnostic procedure in suspected thyroid nodules . Unfortunately, both negative- and positive predictive value of FNAC is poor, often resulting in the need for a diagnostic hemithyroidectomy for definite diagnosis. 40-94% of the suspected thyroid nodules appear to be benign after resection. After surgical removal, patients with differentiated thyroid cancer sometimes receive adjuvant treatment with radioactive-iodine. Thereafter, patients face a long-term follow-up since recurrence of the disease may occur years after removal of the primary tumor. Based on risk stratification, serum thyroglobulin (Tg) levels are determined once or twice per year with or without additional imaging (e.g. thyroid ultrasound or total body scintigraphy). So, both diagnosis and follow-up of thyroid cancer are associated with invasive and unpleasant procedures for the patient.

After surgical removal, patients with differentiated thyroid cancer sometimes receive adjuvant treatment with radioactive-iodine. Thereafter, patients will be subjected to a long-term follow- up since recurrence of the disease may occur years after removal of the primary tumor. Based on risk stratification, serum thyroglobulin (Tg) levels are determined once or twice per year with or without additional imaging (e.g. thyroid ultrasound or total body scintigraphy). So, both diagnosis and follow-up of thyroid cancer are associated with invasive and unpleasant procedures for the patient.

A promising development in cancer detection is based on volatile organic compounds (VOCs), gaseous degradation products of biochemical processes detectable in exhaled breath. During pathophysiological processes related to tumor growth, alterations in cell metabolism lead to a shift in the production of VOCs. The VOCs' patterns can be detected by the Aeonose™ through their reaction to the metal-oxide sensors in this device. A pilot study conducted at the Maastricht University Medical Center+ demonstrated that, by creating an artificial neural network (ANN) from the VOC patterns of numerous patients and their specific histopathological diagnosis, the Aeonose™ has a high diagnostic accuracy to discriminate benign from malignant thyroid nodules.

The purpose of this study is to validate the accuracy of the Aeonose™, to prevent unnecessary surgery and to investigate the use of the Aeonose™ as a surveillance tool in the postoperative follow-up of differentiated thyroid cancer.