Volatile Organic Compound Assessment in Pancreatic Ductal Adenocarcinoma

Pancreatic Cancer, PDAC - Pancreatic Ductal Adenocarcinoma

Volatile organic compounds (VOCs), Breath analysis, Volatolomics, Metabonomics / Lipidomics, Transcriptomics, Microbiome Analysis, Organoids, Immune profiling

Patients with early pancreatic cancer often have symptoms that could also be caused by many common benign conditions, or no symptoms at all. Jaundice, weight loss and pain are 'red flag' symptoms of pancreatic cancer that are linked to incurable disease. At the moment only patients with 'red flag' symptoms are urgently referred for diagnostic testing to find out if they have the cancer. As a result, late diagnosis is a common feature of pancreatic cancer. This leads to limited treatment options being available to patients by the time they are diagnosed, and ultimately results in poor survival rates. There is a clear need to improve earlier detection of pancreatic cancer so that patients with pancreatic cancer can be identified earlier and faster, enabling them to start treatment more quickly. The study team is developing a non-invasive breath test that detects small molecules called volatile organic compounds (VOCs) that may be altered by pancreatic cancers. For patients with non-specific symptoms, this test would help general practitioners (GPs) to identify those patients that may indeed have an underlying pancreatic cancer, who would benefit from referral for specialised pancreatic cancer tests.

Bioresource study to identify pathways responsible for VOC production: A total of 192 patients will be recruited to provide samples to create a pancreatic biobank. This will be comprised of two groups, each containing 96 patients: (i) patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC); (ii) control patients undergoing pancreatic resection for benign pancreatic disorders (e.g. intraductal papillary mucinous neoplasms, pancreatic mucinous cystic neoplasms, chronic pancreatitis). The following biosamples will be collected from each patient: breath, saliva, blood, urine, pancreatic tissue, duodenal aspirate. Collected samples will be stored in a biobank and will be utilised in a wide range of studies to investigate the mechanisms of VOC production in PDAC. The following analyses will be undertaken: volatolomics, metabonomics / lipidomics, metagenomics / microbiome analysis, transcriptomics, and culture experiments (to establish bacterial, immune and organoid cultures). VAPOR 1 clinical study: Up to 813 patients will be recruited for the development of this non-invasive PDAC detection model. This will be comprised of three groups: (i) patients with PDAC; (ii) control patients with specified benign pancreatic disorders (new-onset diabetes mellitus, or chronic pancreatitis); (iii) control patients with non-specific gastrointestinal symptoms but a radiologically-normal pancreas. Participants will be required to fast for 6 hours prior to breath sampling. After rinsing their mouth with water, patients will be asked to provide breath samples by exhaling into single-use breath collection bags. Breath will be transferred using a precision pump into thermal desorption (TD) storage tubes. Breath samples will be analysed in accordance with existing quality-controlled processes.

United Kingdom