Faecal Volatile Organic Compounds to Detect Colorectal Neoplasia in Lynch Syndrome-A Prospective Longitudinal...

Area of Science:

• Gastroenterology
• Oncology
• Biomarker Discovery

Background:

• Lynch syndrome patients require regular colonoscopies to detect colorectal cancer (CRC) and advanced neoplasia.
• Non-invasive biomarkers like fecal volatile organic compounds (VOCs) could optimize surveillance by reducing colonoscopy frequency and overuse.
• Fecal immunochemical tests (FIT) have limitations in detecting non-advanced colorectal neoplasia.

Purpose of the Study:

• To assess the efficacy of fecal VOCs, alone and combined with FIT, in determining optimal colonoscopy intervals for individuals with Lynch syndrome.
• To evaluate VOC patterns for detecting colorectal neoplasia and guiding post-polypectomy surveillance.

Main Methods:

• Prospective, longitudinal, multicenter study involving 200 Lynch syndrome participants.
• Fecal samples analyzed using Field Asymmetric Ion Mobility Spectrometry (FAIMS) and Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) with machine learning.
• Combined VOC analysis with FIT (2.55 μg Hb/g faeces) and Gas Chromatography-Time-of-Flight Mass Spectrometry for individual VOC abundance.

Main Results:

• FAIMS demonstrated 100% sensitivity and 100% negative predictive value for CRC and advanced adenoma (AA).
• GC-IMS showed 89% sensitivity and 99% negative predictive value for CRC and AA.
• VOC-FIT combination did not significantly improve accuracy over VOCs alone for detecting any relevant neoplasia (88% sensitivity, 44% specificity with FAIMS).
• Distinct VOC patterns were observed before and after polypectomy (AUC 0.70).

Conclusions:

• Fecal VOCs represent a promising non-invasive biomarker strategy for postponing colonoscopies in Lynch syndrome surveillance.
• VOC analysis may also be valuable for follow-up after polypectomy in this population.
• Further large-scale validation studies are warranted to confirm these findings.