Colorectal Adenocarcinoma, Colorectal Cancer, Colorectal Polyps
Conditions
Keywords
Volatile organic compounds, Mass spectrometry, Early detection
Brief summary
This study aims to determine whether a breath test could be used for early detection of colorectal cancer and colorectal polyps. Patients who are attending for a planned colonoscopy or who are scheduled to undergo elective resection of histologically confirmed colorectal cancer (adenocarcinoma) will be approached to provide a breath sample. Multi platform mass spectrometry analysis will be performed to establish volatile biomarkers that can discriminate between colorectal cancer, benign colorectal disease (e.g. polyps) and healthy controls.
Detailed description
Colorectal cancer is the 2nd most common cause of cancer death in the UK where survival rates are among the lowest in Europe. If diagnosed early survival may exceed 90%. The proposed breath test is a non-invasive investigation that can detect the presence of volatile organic compounds (VOCs) in breath and their relative abundance in disease states including colorectal cancer. This test has potential to be used in a primary care setting to identify patients at high risk of colorectal cancer, supporting earlier referral for definitive investigation. A negative test may provide reassurance to patients and prevent unnecessary tests in this group. The test could also have an application for colorectal cancer screening. In this study the investigators will determine the diagnostic accuracy of an exhaled breath test for the detection of colorectal adenocarcinoma and colonic polyps. To determine the accuracy of the breath test a multicentre cross-sectional study will be conducted to analyse single breath samples from patients attending hospital for planned colonoscopy or elective resection of histologically confirmed colorectal cancer. The target for the study is 1463 patients. Breath collection will be conducted using a previously validated method. Samples of breath (500ml) collected using a CE-marked handheld ReCIVA sampling device (Owlstone Medical Ltd., Cambridge, UK) during a period of tidal breathing (approximately 5minutes) will be absorbed onto thermal desorption tubes (Markes International, Llantrisant, UK). All patients will have received bowel preparation and will be fasted for a minimum of 6 hours prior to the breath sample. Breath samples collected within thermal desorption tubes will be transferred to a central laboratory for analysis by gas chromatography mass spectrometry (GC-MS) and proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS). Raw data files will be extracted and analysed in accordance with established protocols. Quality assurance measures will be formally assessed at each stage of sample handling.
Interventions
DIAGNOSTIC_TESTBreath sample
Patients will be asked to give a sample of their breath, using the ReCIVA breath testing device. This involves performing tidal breathing whilst wearing a face mask for approximately 5 minutes. Breath (500mls at a flow rate of 200mls/min) is passed over thermal desorption tubes which absorb compounds of interest.
Sponsors
Imperial Health Charity
Rosetrees Trust
National Institute for Health Research, United Kingdom
Imperial College London
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* ≥18 years and ≤90 years of age * Undergoing planned colonoscopy or elective resection of histologically confirmed colorectal adenocarcinoma * Fasted \>6 hours * Able to provide informed written consent
Exclusion criteria
* Any patient \<18 years or \>90 years of age. * Lacks capacity or is unable to provide informed written consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Diagnostic Accuracy of the Proposed Breath Test for Detection of Colorectal Cancer in All Patients | 30 minutes | Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of colorectal cancer, as diagnosed on colonoscopy, using 14 specific VOCs plus BMI as prediction variables. |
| Determine the Diagnostic Accuracy of Using VOCs Present in Breath for the Detection of Colorectal Cancer in Symptomatic Patients | 30 minutes | Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of colorectal cancer, as diagnosed on colonoscopy, using 14 specific VOCs plus BMI as prediction variables. |
Countries
United Kingdom
Participant flow
Recruitment details
1855 total patients were enrolled in the study between 5/6/2017 and 21/2/2020.
Pre-assignment details
The cancer/non cancer diagnosis was not known for the majority of excluded participants, because the exclusion was based upon data corruption/failure of quality control of breath sample, hence no further clinical details were recorded. Exclusions have been arbitrarily divided between both study groups for the purposes of this table.
Participants by arm
| Arm | Count |
|---|---|
| Colorectal Cancer 162 patients of the included total had a diagnosis of colorectal cancer | 162 |
| Non-cancer Controls 1270 patients had a non-cancer diagnosis | 1,270 |
| Total | 1,432 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | failed QC measures | 205 | 206 |
| Overall Study | Physician Decision | 12 | 0 |
Baseline characteristics
| Characteristic | Colorectal Cancer | Non-cancer Controls | Total |
|---|---|---|---|
| Age, Continuous | 66.5 years | 63 years | 64 years |
| Race/Ethnicity, Customized Arab | 5 Participants | 40 Participants | 45 Participants |
| Race/Ethnicity, Customized Asian/Asian British | 22 Participants | 198 Participants | 220 Participants |
| Race/Ethnicity, Customized Black / African / Caribbean / Black British | 19 Participants | 106 Participants | 125 Participants |
| Race/Ethnicity, Customized Other ethnicity | 8 Participants | 38 Participants | 46 Participants |
| Race/Ethnicity, Customized Unrecorded | 4 Participants | 30 Participants | 34 Participants |
| Race/Ethnicity, Customized White British/ European | 104 Participants | 858 Participants | 962 Participants |
| Sex: Female, Male Female | 61 Participants | 540 Participants | 601 Participants |
| Sex: Female, Male Male | 101 Participants | 730 Participants | 831 Participants |
| Time fasted | 22 Hours | 24 Hours | 24 Hours |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1,270 | 0 / 162 |
| other Total, other adverse events | 0 / 1,270 | 0 / 162 |
| serious Total, serious adverse events | 0 / 1,270 | 0 / 162 |
Outcome results
Primary
Determine the Diagnostic Accuracy of the Proposed Breath Test for Detection of Colorectal Cancer in All Patients
Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of colorectal cancer, as diagnosed on colonoscopy, using 14 specific VOCs plus BMI as prediction variables.
Time frame: 30 minutes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Detection of Colorectal Cancer in Breath in All Patients | Determine the Diagnostic Accuracy of the Proposed Breath Test for Detection of Colorectal Cancer in All Patients | Sensitivity | 79 percentage of true cases |
| Detection of Colorectal Cancer in Breath in All Patients | Determine the Diagnostic Accuracy of the Proposed Breath Test for Detection of Colorectal Cancer in All Patients | Specificity | 86 percentage of true cases |
Primary
Determine the Diagnostic Accuracy of Using VOCs Present in Breath for the Detection of Colorectal Cancer in Symptomatic Patients
Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of colorectal cancer, as diagnosed on colonoscopy, using 14 specific VOCs plus BMI as prediction variables.
Time frame: 30 minutes
Population: This a subgroup or 855 symptomatic patients taken from within the total cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Detection of Colorectal Cancer in Breath in All Patients | Determine the Diagnostic Accuracy of Using VOCs Present in Breath for the Detection of Colorectal Cancer in Symptomatic Patients | Sensitivity | 83 Percentage of true cases |
| Detection of Colorectal Cancer in Breath in All Patients | Determine the Diagnostic Accuracy of Using VOCs Present in Breath for the Detection of Colorectal Cancer in Symptomatic Patients | Specificity | 88 Percentage of true cases |