Volatile Markers in Digestive Cancer

Study Overview
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Brief Summary
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The study is aimed to determine the potential of volatile marker testing for identification of gastrointestinal cancers (in particular - colorectal and gastric cancers), the related precancerous lesions in the stomach and colon. The study will be addressing the role of confounding factors, including lifestyle factors, diet, smoking as well as addressing the potential role of microbiota in the composition of exhaled volatile markers.

Detailed Description
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Patients with established disease (cancer, precancerous lesions) as well as patients investigated for the lesions and having been documented lack of the lesions will be enrolled to the study at clinical sites in Europe (Latvia, Lithuania). In addition, group of persons from general population at average risk for developing the target disease will be also enrolled. Testing of volatile markers will be conducted by one of two methods: 1) gas chromatography coupled to mass spectroscopy (GS-MS) and 2) nanosensor technology. Volunteers (including patients with established disease) will be enrolled prior the removal of the target lesion (e.g. surgery for cancer or polypectomy in the case of a polyp). The study will be conducted by utilizing the experience of institutions in the European Union and Israel.

Official Title
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Volatile Marker Testing for Digestive Cancer and Precancerous Lesion Detection, Evaluation of Confounding Factors

Conditions
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Gastric Cancer, Colorectal Cancer, Colorectal Adenoma, Peptic Ulcer Disease, Atrophic Gastritis, Intestinal Metaplasia, H.Pylori Infection, Normal Control, Average-risk General Population

Intervention / Treatment
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* Procedure: Breath sampling for volatile marker detection
* Procedure: Upper endoscopy with biopsies
* Procedure: Colonoscopy with biopsies or lesion removal when required
* Procedure: Plasma/serum sampling
* Procedure: Faecal sample acquisition
* Procedure: Histological evaluation of the surgery material


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with verifies colorectal cancer (Group 1) Patients with verified gastric cancer (Group 5) Patients undergoing colonoscopy due to clinical indications (group 2-4) Patients undergoing upper endoscopy due to clinical indications (Group 6-8) Average-risk population group aged 40-64 at inclusion without alarm symptoms (Group 9) Motivation to participate in the study Physical status allowing volatile marker sampling and other procedures within the protocol Signed consent Exclusion Criteria: Known other active cancer Ventilation problems, airway obstruction Unwillingness or inability to co-operate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1. Colorectal cancer<br>Patients with histologically confirmed colorectal cancer (adenocarcinoma) | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Colonoscopy with biopsies or lesion removal when required<br>* Colonoscopy with proper biopsy or polypectomy material work-up will be used for identification and stratification of colorectal lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>Procedure: Histological evaluation of the surgery material<br>* The material obtained during surgery (stomach or colorectal) will be used for confirmation of the diagnosis in cancer groups. Surgery itself will be performed according to the clinical indications, and will not be extended (i.e. cannot be considered a study intervention)<br>|
| 2. Colorectal high-risk lesions<br>Patients without colorectal adenocarcinoma, but carrying high-risk adenomatous polyps being described by one of the following: 1) size≥1 cm; 2) high-grade dysplasia; 3) villous component. Prior to removal of the lesions. | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Colonoscopy with biopsies or lesion removal when required<br>* Colonoscopy with proper biopsy or polypectomy material work-up will be used for identification and stratification of colorectal lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>|
| 3. Colorectal low-risk adenoma<br>Patients without colorectal adenocarcinoma and without colorectal high-risk lesions as described under Group 2 criteria | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Colonoscopy with biopsies or lesion removal when required<br>* Colonoscopy with proper biopsy or polypectomy material work-up will be used for identification and stratification of colorectal lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>|
| 4. Group of control (colorectal)<br>Patients having undergone colonoscopy without an evidence for colorectal lesions fulfilling Group 1 or Group 2 or Group 3 criteria. Prior to removal of the lesions. | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Colonoscopy with biopsies or lesion removal when required<br>* Colonoscopy with proper biopsy or polypectomy material work-up will be used for identification and stratification of colorectal lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>|
| 5. Gastric cancer<br>Patients with histologically confirmed gastric cancer (adenocarcinoma) | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Upper endoscopy with biopsies<br>* Upper endoscopy with proper biopsy work-up will be used for identification and stratification of gastric lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>Procedure: Histological evaluation of the surgery material<br>* The material obtained during surgery (stomach or colorectal) will be used for confirmation of the diagnosis in cancer groups. Surgery itself will be performed according to the clinical indications, and will not be extended (i.e. cannot be considered a study intervention)<br>|
| 6. Gastric dysplasia<br>Patients without gastric adenocarcinoma but with histologically confirmed dysplasia (either high- or low-grade) of the stomach | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Upper endoscopy with biopsies<br>* Upper endoscopy with proper biopsy work-up will be used for identification and stratification of gastric lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>|
| 7. High-risk gastric lesions<br>Patients graded Stage III-IV according to OLGIM (Operative Link of Gastric Intestinal Metaplasia Assessment) staging system, but excluding those with dysplasia (Group 5) | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Upper endoscopy with biopsies<br>* Upper endoscopy with proper biopsy work-up will be used for identification and stratification of gastric lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>|
| 8. Normal and low-risk gastric lesions<br>Staged 0-III according to OLGIM. Dysplasia should be excluded | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Upper endoscopy with biopsies<br>* Upper endoscopy with proper biopsy work-up will be used for identification and stratification of gastric lesions as well as acquisition of biopsies for microbiota testing<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>|
| 9. Average risk population<br>Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer. | Procedure: Breath sampling for volatile marker detection<br>* Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology<br>Procedure: Plasma/serum sampling<br>* Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination<br>Procedure: Faecal sample acquisition<br>* Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance of nanoarray sensor testing to detect target lesions | Sensitivity, specificity, overall accuracy of nanoarray sensor testing for VOCs to detect the target lesions in the blinded analysis | At the time of breath sampling | 
| VOCs differentiating the study groups | List of VOCs assayed by GC-MS with statistical difference between the study groups | At the time of breath sampling | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of characteristic VOC pattern in risk age groups | List of characteristic VOCs in general population at risk for developing gastrointestinal cancer, including analysis of confounding factors, e.g. dietary habits, smoking, and profession. | At the time of sampling | 
| VOC pattern changes following treatment | Significant change in VOC content before and following treatment (surgery, medical therapy, combined) | At baseline and every 6 months within 3 year period | 
| Groups of gastrointestinal microbiota correlating to VOCs | List of gastrointestinal microbiota groups (phylum/genus level) with positive correlation to particular VOCs | At the time of sampling | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Volatile organic compounds, Nanosensor technology, GC-MS, Breath-testing, Digestive cancer, Precancerous lesions, Colorectal cancer, Adenoma, Gastric cancer, Atrophic gastritis, OLGIM