Detection of Colorectal Cancer in Patients With a Positive Fecal Immunochemical Test Using an Electronic Nose Device (AeoNoseTM)
Condition: Colorectal Cancer; Polyps of Colon
MeSH terms: Colorectal Neoplasms; Colonic Polyps
Study type: Interventional

Summary: 
      The present study aims to investigate the diagnostic accuracy of exhaled breath analysis with
      the Aeonose (the eNose Company, Zutphen, the Netherlands) to distinguish the breath of
      patients suspected for CRC (based on a positive fecal immunochemical test), who are truly
      diagnosed with CRC, from patients suspected for CRC in whom this diagnosis is rejected after
      colonoscopy.
    

Detailed description: 
      Study rationale:

      Colonoscopy plays a key role in all colorectal cancer (CRC) screening modalities. An
      important limitation of colonoscopy remains that the diagnostic accuracy and therapeutic
      safety of colonoscopy both depend on several physician and patient-related factors.
      Significant amounts of polyps are missed during colonoscopy and severe untoward effects still
      occur in 0.1%-0.3% of all colonoscopy procedures, even among expert examiners. Moreover, the
      burdensome nature of the procedure and the necessity of full bowel preparation negatively
      influences participation rates and the use of colonoscopy as a CRC screening test is limited
      by healthcare costs and the expertise needed to perform the screening. These disadvantages of
      colonoscopy warrant the development of a new, non-invasive, accurate CRC screening test.

      An electronic nose device is an artificial olfactory system that analyses volate organic
      compounds (VOCs) in exhaled breath. The use of electronic noses has already been assessed as
      a potential non-invasive diagnostic biomarker test for lung cancer, breast cancer and
      malignant melanomas. The present study aims to investigate the diagnostic accuracy of exhaled
      breath analysis with the AeonoseTM (The eNose Company, Zutphen, the Netherlands) to
      distinguish the breath of patients suspected for CRC (based on a positive fecal
      immunochemical test (FIT)), who are truly diagnosed with CRC, from patients suspected for CRC
      in whom this diagnosis is rejected after colonoscopy.

      Objectives:

        -  To investigate the diagnostic accuracy of exhaled breath analysis with the AeonoseTM to
           distinguish the breath of patients suspected for CRC based on a positive FIT test, who
           are truly diagnosed with CRC, from patients suspected for CRC in whom this diagnosis is
           rejected after colonoscopy.

        -  To investigate the diagnostic accuracy of exhaled breath analysis with the AeonoseTM for
           other (pre-)malignant colon lesions (e.g. advanced adenomas, non-advanced adenomas, and
           sessile serrated lesions).

        -  To assess the acceptance rate of using the AeonoseTM device.

      Study design: The present multicenter study will include 1950 FIT-positive patients. The
      study will be conducted in seven hospitals in the Netherlands. First a database of breath
      prints will be developed to detect CRC. In this study phase the AeonoseTM will be trained and
      the database of breath prints will be verified using "leave 10% out" cross validation. After
      the calibration phase the diagnostic accuracy of AeonoseTM will be assessed in new study
      patients (external validation).

      Study population: Patients between the ages of 55 and 75 years old with a positive FIT-test
      referred for a colonoscopy procedure.

      Main study parameters/endpoints:

        -  The ability of AeonoseTM to distinguish between patients with and without CRC in a
           FIT-positive population in terms of sensitivity and specificity.

        -  The diagnostic accuracy of AeonoseTM for other (pre-)malignant colon lesions.

        -  Acceptance rate of AeonoseTM

      Statistical analysis:

      Data on demographic and baseline characteristics will be summarized for continuous variables,
      in case of normal distribution by mean and standard deviation, and in case of non-normal
      distribution by median and interquartile range. For discrete variables (eg, race and sex)
      data will be summarized by proportions (percentages). Differences in baseline characteristics
      will be determined using independent sample t test, Fisher's exact test or Chi-square test,
      when appropriate. A 2-sided p-value <0.05 will be considered statistically significant.

      The data will be analyzed by an artificial neural network (ANN) to identify data classifiers
      to extract differences between the patterns in patients by the presence or absence of CRC in
      biopsies. By analyzing a group of breath prints from patients with and without CRC,
      individual differences of diet, medications, co-morbidities, and other factors can be
      filtered out to identify features that distinguish the compounds of patients with CRC. This
      process continues until a selected level of discrimination is met. Data compression and ANN
      have been integrated in a proprietary software package (Aethena) of the eNose Company
      (Zutphen, the Netherlands).

      The binary results will be presented in a scatterplot and a receiver operating
      characteristics curve (ROC-curve). Matthews correlation coefficients will be calculated to
      measure the quality of binary classifications. Cross-validation of the data will be performed
      using a leave-10%-out method. A portion of the data is left out to predict the most optimal
      model.
    

Intervention name(s): Aeonose
Intervention type(s): Device
Intervention description(s): An electronic nose device is an artificial olfactory system that analyses volate organic compounds (VOCs) in exhaled breath. The AeonoseTM is a handheld device of 650 gram. A nose clip will be used to prevent the entry of non-filtered air and patients will be instructed to enclose the mouthpiece with their mouth at all times. A measurement cycle lasts for about 15 minutes, of which 5 minutes of in-and exhalation by the patient takes place.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic