Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study)
Abstract Background Colorectal cancer (CRC) is the fourth most common cancer in the United Kingdom. The five-year survival rate from CRC is only 10% when discovered at a late stage, but can exceed 90% if diagnosed early. Symptoms related to CRC can be non-specific, and therefore the decision to refe...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14520-2 |
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| author | Michael G. Fadel James Murray Georgia Woodfield Ilaria Belluomo Ivan Laponogov Aaron Parker Valerio Converso James K. Ellis Pete Wheatstone Julie Hepburn Chris Groves Kevin Monahan Brian P. Saunders Patrik Španěl Kirill Veselkov Amanda J. Cross Christos Kontovounisios Linda D. Sharples George B. Hanna COBRA2 Collaborators |
| author_facet | Michael G. Fadel James Murray Georgia Woodfield Ilaria Belluomo Ivan Laponogov Aaron Parker Valerio Converso James K. Ellis Pete Wheatstone Julie Hepburn Chris Groves Kevin Monahan Brian P. Saunders Patrik Španěl Kirill Veselkov Amanda J. Cross Christos Kontovounisios Linda D. Sharples George B. Hanna COBRA2 Collaborators |
| author_sort | Michael G. Fadel |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) is the fourth most common cancer in the United Kingdom. The five-year survival rate from CRC is only 10% when discovered at a late stage, but can exceed 90% if diagnosed early. Symptoms related to CRC can be non-specific, and therefore the decision to refer for a colonoscopy can be challenging. Breath analysis potentially offers a simple and quick method to detect CRC specific volatile organic compounds (VOCs) in breath. This protocol describes the COBRA2 study which aims to develop and validate the clinical prediction model (CPM) in the detection of CRC based on the breath test. An exploratory comparison between the breath test and faecal immunochemical test (FIT) will also be carried out to assess whether combining both tests improves diagnostic performance. Methods The COBRA2 study is a multicentre, case-control development and validation study. Breath samples will be collected from participants attending hospital for a planned colonoscopy (control group) or from participants with histologically confirmed colorectal adenocarcinoma (CRC group). A total of 720 participants (470 controls, 250 CRC) will be recruited. All participants will maintain a clear fluid diet for a minimum of 4–6 h prior to sampling, which will take place at outpatient clinics to avoid bowel preparation. The FIT result will be recorded where available. Breath samples will be analysed using gas chromatography–mass spectrometry to identify the VOCs present. Relationships between VOCs of interest and presence of CRC will be explored, and the CPM will be developed using statistical and machine learning methods. We will also assess whether incorporating FIT into the CPM improves diagnostic performance. The CPM will be subsequently validated in an independent sample of up to 250 participants (125 controls, 125 CRC) using the same case–control design and the potential clinical utility of decision rules for triaging will be assessed. If successful, broad validation in an unselected target population of symptomatic patients is required. Discussion The non-invasive breath test may provide direct patient benefit through earlier and accurate detection of CRC, and higher patient acceptability. It can help ensure timely secondary care referral, potentially translating to improved curative treatment and survival for patients. Trial registration The study is registered with ClinicalTrials.gov (NCT05844514). |
| format | Article |
| id | doaj-art-c557eefdc4d84da9bce73ac364fa2ea9 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-c557eefdc4d84da9bce73ac364fa2ea92025-08-20T03:43:11ZengBMCBMC Cancer1471-24072025-07-012511910.1186/s12885-025-14520-2Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study)Michael G. Fadel0James Murray1Georgia Woodfield2Ilaria Belluomo3Ivan Laponogov4Aaron Parker5Valerio Converso6James K. Ellis7Pete Wheatstone8Julie Hepburn9Chris Groves10Kevin Monahan11Brian P. Saunders12Patrik Španěl13Kirill Veselkov14Amanda J. Cross15Christos Kontovounisios16Linda D. Sharples17George B. Hanna18COBRA2 CollaboratorsDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Medical Statistics, London School of Hygiene and Tropical MedicineDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonPatient and Public Involvement, Clinical Trials Research Unit, University of LeedsPatient and Public Involvement, Health and Care Research Wales Support CentreDepartment of Gastroenterology, St George’s HospitalDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonDepartment of Medical Statistics, London School of Hygiene and Tropical MedicineDepartment of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College LondonAbstract Background Colorectal cancer (CRC) is the fourth most common cancer in the United Kingdom. The five-year survival rate from CRC is only 10% when discovered at a late stage, but can exceed 90% if diagnosed early. Symptoms related to CRC can be non-specific, and therefore the decision to refer for a colonoscopy can be challenging. Breath analysis potentially offers a simple and quick method to detect CRC specific volatile organic compounds (VOCs) in breath. This protocol describes the COBRA2 study which aims to develop and validate the clinical prediction model (CPM) in the detection of CRC based on the breath test. An exploratory comparison between the breath test and faecal immunochemical test (FIT) will also be carried out to assess whether combining both tests improves diagnostic performance. Methods The COBRA2 study is a multicentre, case-control development and validation study. Breath samples will be collected from participants attending hospital for a planned colonoscopy (control group) or from participants with histologically confirmed colorectal adenocarcinoma (CRC group). A total of 720 participants (470 controls, 250 CRC) will be recruited. All participants will maintain a clear fluid diet for a minimum of 4–6 h prior to sampling, which will take place at outpatient clinics to avoid bowel preparation. The FIT result will be recorded where available. Breath samples will be analysed using gas chromatography–mass spectrometry to identify the VOCs present. Relationships between VOCs of interest and presence of CRC will be explored, and the CPM will be developed using statistical and machine learning methods. We will also assess whether incorporating FIT into the CPM improves diagnostic performance. The CPM will be subsequently validated in an independent sample of up to 250 participants (125 controls, 125 CRC) using the same case–control design and the potential clinical utility of decision rules for triaging will be assessed. If successful, broad validation in an unselected target population of symptomatic patients is required. Discussion The non-invasive breath test may provide direct patient benefit through earlier and accurate detection of CRC, and higher patient acceptability. It can help ensure timely secondary care referral, potentially translating to improved curative treatment and survival for patients. Trial registration The study is registered with ClinicalTrials.gov (NCT05844514).https://doi.org/10.1186/s12885-025-14520-2Colorectal cancerBreath testVolatile organic compoundsBiomarkersDetectionDiagnostic model |
| spellingShingle | Michael G. Fadel James Murray Georgia Woodfield Ilaria Belluomo Ivan Laponogov Aaron Parker Valerio Converso James K. Ellis Pete Wheatstone Julie Hepburn Chris Groves Kevin Monahan Brian P. Saunders Patrik Španěl Kirill Veselkov Amanda J. Cross Christos Kontovounisios Linda D. Sharples George B. Hanna COBRA2 Collaborators Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study) BMC Cancer Colorectal cancer Breath test Volatile organic compounds Biomarkers Detection Diagnostic model |
| title | Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study) |
| title_full | Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study) |
| title_fullStr | Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study) |
| title_full_unstemmed | Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study) |
| title_short | Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case–control development and validation study (COBRA2 study) |
| title_sort | non invasive breath testing to detect colorectal cancer protocol for a multicentre case control development and validation study cobra2 study |
| topic | Colorectal cancer Breath test Volatile organic compounds Biomarkers Detection Diagnostic model |
| url | https://doi.org/10.1186/s12885-025-14520-2 |
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