Volatile Markers in Digestive Cancer (VOLGACORE)

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Colorectal Cancer; Colorectal Adenoma; Intestinal Metaplasia; Atrophic Gastritis; H.Pylori Infection; Peptic Ulcer Disease; Normal Control; Average-risk General Population
• Intervention / Treatment: Procedure: Faecal sample acquisition; Procedure: Upper endoscopy with biopsies; Procedure: Breath sampling for volatile marker detection; Procedure: Colonoscopy with biopsies or lesion removal when required; Procedure: Plasma/serum sampling; Procedure: Histological evaluation of the surgery material

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 2022

Contacts and Locations

Study Locations

• Latvia
  • Riga, Latvia, LV 1586
    • University of Latvia
• Lithuania
  • Kaunas, Lithuania, LT 44307
    • Lithuanian University of Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cancer patients (Group 1 and 5) will be predominantly enrolled at the time scheduled for surgery, however also patients undergoing diagnostic procedures (endoscopy) will be eligible

Patients without malignant disease but defined colorectal (Groups 2-4) status will be predominantly enrolled prior colonoscopy in out-patient settings. Sampling starting from 1 week after colonoscopy will be allowed if the lesions will not get removed during the index endoscopy

Patients without malignant disease but defined gastric mucosal status (Groups 6-8) status will be predominantly enrolled prior upper endoscopy in out-patient settings. Sampling starting from 2 days after upper endoscopy will be allowed if the lesions will not get removed during the index endoscopy

Average cancer risk subjects (Group 9) will get enrolled by inviting individuals predominantly selected from the lists of general practitioners.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

9

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1. Colorectal cancer; Patients with histologically confirmed colorectal cancer (adenocarcinoma)	Procedure: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Colonoscopy with biopsies or lesion removal when required; 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; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination; Procedure: Histological evaluation of the surgery material; 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)
2. Colorectal high-risk lesions; 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: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Colonoscopy with biopsies or lesion removal when required; 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; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination
3. Colorectal low-risk adenoma; Patients without colorectal adenocarcinoma and without colorectal high-risk lesions as described under Group 2 criteria	Procedure: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Colonoscopy with biopsies or lesion removal when required; 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; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination
4. Group of control (colorectal); 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: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Colonoscopy with biopsies or lesion removal when required; 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; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination
5. Gastric cancer; Patients with histologically confirmed gastric cancer (adenocarcinoma)	Procedure: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Upper endoscopy with biopsies; 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; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination; Procedure: Histological evaluation of the surgery material; 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)
6. Gastric dysplasia; Patients without gastric adenocarcinoma but with histologically confirmed dysplasia (either high- or low-grade) of the stomach	Procedure: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Upper endoscopy with biopsies; 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; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination
7. High-risk gastric lesions; 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: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Upper endoscopy with biopsies; 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; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination
8. Normal and low-risk gastric lesions; Staged 0-III according to OLGIM. Dysplasia should be excluded	Procedure: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Upper endoscopy with biopsies; 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; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination
9. Average risk population; Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer.	Procedure: Faecal sample acquisition; Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis; Procedure: Breath sampling for volatile marker detection; Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology; Procedure: Plasma/serum sampling; Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination

What is the study measuring?

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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
VOC pattern changes following intervention to microbiota	Significant change in VOC content before and following intervention upon microbiome (antibiotic intake, colon cleansing)	At baseline and following the intervention (1 week, 1 month)
Gastric microbiome changes following intervention to microbiota	Significant change in gastric microbiome (phyla, genera) before and following intervention upon microbiome (antibiotic intake)	At baseline and 3 years after intervention
Gastrointestinal microbiome in cancer patients	Significant differences in the composition of gastric and colonic microbiome (phyla, genera) in cancer patients, patients with precancerous lesions and controls	At the time of sampling

Collaborators and Investigators

• Sponsor: University of Latvia
• Collaborators: Karolinska Institutet; Lithuanian University of Health Sciences; Technion, Israel Institute of Technology; German Cancer Research Center; Digestive Diseases Centre GASTRO; Riga East Clinical University Hospital; Academic Histology Laboratory (Latvia); JLM Innovation GmbH (Germany)
• Investigators: Principal Investigator: Hossam Haick, Ph.D., Technion, Israel Institute for Technology (Israel)

Publications and helpful links

General Publications

• Amal H, Leja M, Broza YY, Tisch U, Funka K, Liepniece-Karele I, Skapars R, Xu ZQ, Liu H, Haick H. Geographical variation in the exhaled volatile organic compounds. J Breath Res. 2013 Dec;7(4):047102. doi: 10.1088/1752-7155/7/4/047102. Epub 2013 Nov 1.
• Xu ZQ, Broza YY, Ionsecu R, Tisch U, Ding L, Liu H, Song Q, Pan YY, Xiong FX, Gu KS, Sun GP, Chen ZD, Leja M, Haick H. A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions. Br J Cancer. 2013 Mar 5;108(4):941-50. doi: 10.1038/bjc.2013.44.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: December 30, 2014
• First Submitted That Met QC Criteria: January 2, 2015
• First Posted (Estimate): January 6, 2015

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: August 20, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Colorectal cancer; Gastric cancer; Adenoma; GC-MS; Digestive cancer; Volatile organic compounds; Atrophic gastritis; Precancerous lesions; Nanosensor technology; OLGIM; Breath-testing
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Intestinal Neoplasms; Rectal Diseases; Duodenal Diseases; Stomach Neoplasms; Gastritis; Colorectal Neoplasms; Adenoma; Atrophy; Peptic Ulcer; Metaplasia; Gastritis, Atrophic
• Other Study ID Numbers: 2914; LZP Nr. 2014.10-5 (Other Identifier: Latvian Research Council)