D3 | Abstract 13

Annual NUTRIM Symposium 18 November 2020

APPLIED SCIENCE

Detecting Advanced Colorectal Neoplasia by analyzing Volatile Organic Compounds in Exhaled Breath: A Pilot Study

H.R. Cheng1,2,3, R.W.R. van Vorstenbosch4, D.M. Pachen4, L.W.T. Meulen1,3, J.W.A. Straathof1,2, J.W. Dallinga4, D.M.A.E.Jonkers1,5, A.A.M. Masclee1,5, F.J. van Schooten3,4, Z. Mujagic1,5, A. Smolinska4

1Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
2 Department of Gastroenterology and Hepatology, Máxima Medical Center, Veldhoven, The Netherlands
3 GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center+, The Netherlands
4 Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht
5 NUTRIM, School of Nutrition & Translational Research in Metabolism, Maastricht University Medical Center+, The Netherlands

H.R. Cheng and R.W.R. van Vorstenbosch are shared first author; Z. Mujagic and A. Smolinska are shared last author
Colorectal cancer is (CRC) the third most common cancer worldwide and poses an important healthcare issue with significant morbidity, mortality, and economic impact. The 5-year survival rate of CRC is estimated to be around 90% for localized disease and 14 % for distant disease. Therefore, it is crucial to detect CRC in an early stage.

The fecal immunochemical test (FIT) for hemoglobin is the current non-invasive method used for CRC screening programs in the Netherlands. It is cheap, readily available, and easily applicable. However, it suffers from a high number of false positives. A more accurate non-invasive tool is needed.

In this multicenter, prospective pilot study the feasibility of detecting cancer pre-stages through the use of Volatile Organic Compounds (VOCs) in exhaled breath was studied in the Dutch CRC screening program (i.e. n=450 FIT positive patients). Exhaled breath was sampled using 3L Tedlar ® bags (SKC Ltd, Dorset, UK) and subsequently analyzed using Thermal Desorption–Gas Chromatography–Mass Spectrometry. Next, the raw data was preprocessed and batch-corrected to diminish the effects of instrumental variation. Random Forest (RF) was used to find compounds that differentiate between controls (i.e. FIT positive patients without abnormalities; n=77) and advanced adenoma cases (i.e. size ≥1 cm, villous histology, and/or high grade dysplasia, n=128).

RF led to selection of a set of 10 discriminatory VOCs. Here, using an internal validation set and an independent test set a sensitivity and specificity of 78% and 70% were obtained, respectively. Furthermore, using internal validation sets the potential was shown to additionally discriminate between non-advanced adenoma cases. Discriminatory markers were putatively identified and related to biological changes in the colon.

 The current study concludes that exhaled VOCs are a feasible tool to diagnose advanced adenomas with good accuracy using a set of 10 discriminatory VOCs. Further research is needed to validate the obtained results and to investigate the diagnostic potential for non-advanced adenomas and CRC.
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