Screening of Gastric Cancer Via Breath Volatile Organic Compounds by Hybrid Sensing Approach

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 gastric cancer screening. 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 (gastric 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, Ukraine) and Latin America (Colombia, Chile, Brazil). In addition, group of persons from general population at average risk for developing the target disease and individuals being referred for upper endoscopy according to clinical indications 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) sensor technology. Various sensors will be used and evaluated for the purpose. The potential sources of volatile organic compounds (VOCs) in the breath will be addressed by studying VOC emission by using headspace analysis from cancer tissue, gastric contents, cancer cell cultures and H.pylori. The potential role of gastric and faecal microbiota in the origin of VOCs in the breath will be addressed. Metabolome in the circulation will also get correlated to VOCs in the breath and with microbiome.

Official Title
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Screening of Gastric Cancer Via Breath Volatile Organic Compounds by Hybrid Sensing Approach

Conditions
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Gastric Cancer, Atrophic Gastritis, Gastric Dysplasia, H.Pylori Infection

Intervention / Treatment
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* Device: Breath sampling for VOC detection
* Procedure: Surgery material collection for VOC headspace analysis
* Diagnostic Test: Upper endoscopy
* Diagnostic Test: Microbiota testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with verified gastric cancer (Group 1 & 2) Patients undergoing or having undergone upper endoscopy according to clinical indications (Group 3 & 5) Average-risk population group aged 40-64 at inclusion without alarm symptoms (Group 4) 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

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gastric cancer patients undergoing surgery<br>Patients with histologically confirmed gastric cancer (adenocarcinoma) planned for surgical management | Device: Breath sampling for VOC detection<br>* Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy<br>* Other names: Serum, plasma sampling for group description and stratification;Procedure: Surgery material collection for VOC headspace analysis<br>* Only for gastric cancer patients undergoing surgery (Group 1)<br>Diagnostic Test: Upper endoscopy<br>* Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests)<br>* Other names: Histological and microbial evaluation of biopsy samples and gastric content;Diagnostic Test: Microbiota testing<br>* Faecal and gastric contents and biopsy samples for microbiota testing<br>|
| Gastric cancer patients<br>Patients with histologically confirmed gastric cancer (adenocarcinoma) | Device: Breath sampling for VOC detection<br>* Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy<br>* Other names: Serum, plasma sampling for group description and stratification;Diagnostic Test: Upper endoscopy<br>* Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests)<br>* Other names: Histological and microbial evaluation of biopsy samples and gastric content;Diagnostic Test: Microbiota testing<br>* Faecal and gastric contents and biopsy samples for microbiota testing<br>|
| Control group patients without gastric cancer<br>Patients without gastric malignant disease according to data obtained in upper endoscopy | Device: Breath sampling for VOC detection<br>* Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy<br>* Other names: Serum, plasma sampling for group description and stratification;Diagnostic Test: Upper endoscopy<br>* Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests)<br>* Other names: Histological and microbial evaluation of biopsy samples and gastric content;Diagnostic Test: Microbiota testing<br>* Faecal and gastric contents and biopsy samples for microbiota testing<br>|
| Average risk population<br>Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer | Device: Breath sampling for VOC detection<br>* Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy<br>* Other names: Serum, plasma sampling for group description and stratification;Diagnostic Test: Upper endoscopy<br>* Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests)<br>* Other names: Histological and microbial evaluation of biopsy samples and gastric content;Diagnostic Test: Microbiota testing<br>* Faecal and gastric contents and biopsy samples for microbiota testing<br>|
| Patients with dyspeptic symptoms<br>Patients with dyspeptic symptoms or other complains being referred for upper endoscopy (Chile) | Device: Breath sampling for VOC detection<br>* Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy<br>* Other names: Serum, plasma sampling for group description and stratification;Diagnostic Test: Upper endoscopy<br>* Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests)<br>* Other names: Histological and microbial evaluation of biopsy samples and gastric content;Diagnostic Test: Microbiota testing<br>* Faecal and gastric contents and biopsy samples for microbiota testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristic VOC pattern identification for gastric cancer detection | The characteristic VOC pattern based on sensor analysis and its performance indicators will be detected | 2 years following initiation of patient recruitment | 
| Specific chemistry identification in the exhaled breath | Identification of specific chemistries (GC-MS analysis) originating from gastric cancer | 2 years following initiation of patient recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristic VOC pattern identification for gastric precancerous lesion detection | The characteristic VOC pattern based on sensor analysis and its performance indicators will be detected | 2.5 years following initiation of patient recruitment | 
| Identification of the best-performing sensors | Comparative analysis between the performance of different sensor performance in target disease identification | 3 years following initiation of patient recruitment | 
| Gut microbiota analysis in relation to breath VOCs | Analysis of the role of gastric and faecal microbiota in the origin of VOCs in the exhaled breath | 3 years following initiation of patient recruitment | 

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