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

NCT04883294 | Unknown DMC

• 1 other identifier: NL76036.068.21
• Study Type: observational
• Target: 1,500
• Locations: 0 countries
• Sites: N/A

Brief Summary

Patients with a suspected thyroid nodule face an invasive and patient unfriendly diagnostic work-up to determine the risk of malignancy. Typically, patients undergo ultrasound of the thyroid gland followed by fine-needle aspiration cytology (FNAC). FNAC has been considered as a gold standard diagnostic procedure in suspected thyroid nodules. Unfortunately, both the negative- and positive predictive value of FNAC is poor, often resulting in the need for a diagnostic hemithyroidectomy for definite diagnosis . Approximately 40-94% of the suspected thyroid nodules appear to be benign after resection and thus exposes patients to unnecessary surgery with unnecessary risks. Therefore, a quick, non-invasive assessment of the risk of malignancy of thyroid nodules is of paramount importance. Such a novel test could fasten the diagnostic process for patients with malignancies and reduce the amount of 'unnecessary' surgeries for benign conditions. 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 with 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. We hypothesize that the high negative predictive value of the pilot study will be confirmed in the validation study and expect that implementation of the Aeonose™ in clinical practice will subsequently reduce the number of unnecessary surgeries below 10% for patients with Bethesda ≥ III nodules and may provide an important role in non-invasive detection of recurrent disease.

Conditions

Thyroid Neoplasm

Keywords

Electronic Nose; Thyroid Neoplasm; Volatile Organic Compounds; Thyroid Cancer; Thyroid Nodule; Diagnosis

Outcome Measures

Primary Outcomes (5)

• Sensitivity

  4 months

• Specificity

  4 months

• Positive Predictive Value

  4 months

• Negative Predictive Value

  4 months

• Area Under the Curve of the Receiver Operating Characteristics Curve

  4 months

Secondary Outcomes (6)

• Quality of Life

  4 months

• Burden Thermometer/Problem List

  4 months

• Surgical Complications

  4-6 months

• Number of unnecessary surgeries

  4 years

• Ease of use of electronic nose

  4 months

Study Arms (2)

Disease Group

A disease group including patients older than 18 years old with any kind of histopathologically proven malignancy of the thyroid gland (including Papillary thyroid cancer (PTC), Follicular thyroid cancer (FTC), Medullary thyroid cancer (MTC), and Anaplastic thyroid cancer);

Diagnostic Test: Electronic Nose

Control

A control group including patients older than 18 years old with any kind of histopathologically proven benign thyroid gland disease (including adenoma, hyperplasia).

Diagnostic Test: Electronic Nose

Interventions

Electronic Nose DIAGNOSTIC_TEST

All participants breathed through the Aeonose for five minutes. This device contains metal-oxide sensors that change in conductivity upon reaction with VOCs in exhaled breath. These conductivity changes are input data for machine-learning and used for pattern recognition. A nose clip was placed on the nose of each participant to avoid entry of non-filtered air in the device. Before measuring, the Aeonose was flushed with room air, guided through a carbon filter as well. Failed breath tests were excluded from analysis; the reason for failure was documented.

Also known as: AeonoseTM

Control; Disease Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All adult patients who have a scheduled visit in the outpatient clinic of the departments of endocrinology or endocrine surgery for an thyroid nodule needing further diagnostic follow- up will be asked to participate in this study. Patients will be recruited among those visiting the outpatient clinic of the participating hospital.

You may qualify if:

• Thyroid nodule requiring additional diagnostic follow-up (TI-RADS/Bethesda)
• Patients with thyroid problems requiring surgery (e.g. goiter)
• AeonoseTM measurement before undergoing cytological puncture or at least 3 days after cytological puncture pre-operatively.
• \> 18 year.
• Signed informed consent

You may not qualify if:

• Other underlying malignancy, (less than 5 years ago), basal cell carcinoma not included - Unable to participate due to comorbidities (e.g. COPD)
• Not able to understand the information

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Related Publications (10)

• Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013;2013:965212. doi: 10.1155/2013/965212. Epub 2013 May 7.

  PMID: 23737785 BACKGROUND

• Tessler FN, Middleton WD, Grant EG. Thyroid Imaging Reporting and Data System (TI-RADS): A User's Guide. Radiology. 2018 Apr;287(1):29-36. doi: 10.1148/radiol.2017171240.

  PMID: 29558300 BACKGROUND

• Tamhane S, Gharib H. Thyroid nodule update on diagnosis and management. Clin Diabetes Endocrinol. 2016 Oct 3;2:17. doi: 10.1186/s40842-016-0035-7. eCollection 2016.

  PMID: 28702251 BACKGROUND

• Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009 Nov;132(5):658-65. doi: 10.1309/AJCPPHLWMI3JV4LA.

  PMID: 19846805 BACKGROUND

• Haick H, Broza YY, Mochalski P, Ruzsanyi V, Amann A. Assessment, origin, and implementation of breath volatile cancer markers. Chem Soc Rev. 2014 Mar 7;43(5):1423-49. doi: 10.1039/c3cs60329f. Epub 2013 Dec 4.

  PMID: 24305596 BACKGROUND

• de Lacy Costello B, Amann A, Al-Kateb H, Flynn C, Filipiak W, Khalid T, Osborne D, Ratcliffe NM. A review of the volatiles from the healthy human body. J Breath Res. 2014 Mar;8(1):014001. doi: 10.1088/1752-7155/8/1/014001. Epub 2014 Jan 13.

  PMID: 24421258 BACKGROUND

• Guo L, Wang C, Chi C, Wang X, Liu S, Zhao W, Ke C, Xu G, Li E. Exhaled breath volatile biomarker analysis for thyroid cancer. Transl Res. 2015 Aug;166(2):188-95. doi: 10.1016/j.trsl.2015.01.005. Epub 2015 Jan 20.

  PMID: 25666355 BACKGROUND

• Hoftijzer HC, Heemstra KA, Corssmit EP, van der Klaauw AA, Romijn JA, Smit JW. Quality of life in cured patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2008 Jan;93(1):200-3. doi: 10.1210/jc.2007-1203. Epub 2007 Oct 23.

  PMID: 17956954 BACKGROUND

• Barbus E, Pestean C, Larg MI, Piciu D. Quality of life in thyroid cancer patients: a literature review. Clujul Med. 2017;90(2):147-153. doi: 10.15386/cjmed-703. Epub 2017 Apr 25.

  PMID: 28559697 BACKGROUND

• Al-Difaie ZJJ, Scheepers MHMC, Engelen SME, Lubbers T, Havekes B, Bouvy ND. Volatile organic compounds in exhaled breath, blood, and urine detected in patients with thyroid carcinoma using gas chromatography-ion mobility spectrometry-a pilot study. J Breath Res. 2024 Nov 26;19(1). doi: 10.1088/1752-7163/ad89ef.

  PMID: 39437815 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood, Histology and Post-operative thyroid specimen

MeSH Terms

Conditions

Thyroid Neoplasms; Thyroid Nodule; Disease

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nicole Bouvy, Prof,MD,PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole Bouvy, Prof, MD, PhD

CONTACT

+31 43 3876543; n.bouvy@mumc.nl

Zaid Al-Difaie, Dr.

CONTACT

+31640075718; z.al-difaie@maastrichtuniversity.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: May 12, 2021
• Study Start: May 1, 2021
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2025
• Last Updated: May 12, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Once the associated article is published and/or the project has ended, (part of) the data will be accessible for further research and verification. A possible embargo period is yet to be defined in conjunction with the research team and the eNose company.
• Access Criteria: Once the project has ended, the data collection will be publicly accessible without any restrictions.