Smellprints in lung Cancer; the role of ENose in diagnosis and Treatment (SCENT)
part 5: Diagnostic value of the eNose in Colorectal Cancer

Colorectal cancer (CRC) is an important cancer in terms of incidence and
mortality. There is evidence that screening of CRC improves prognosis and
might eventually reduce incidence by detecting advanced adenomas and therefore
population based screening procedures are currently under investigation.
Screening tests for CRC can be grouped into 2 categories: a. tests that
primarily detect cancer like tests based on fecal occult blood and b. tests
that can detect cancer and advanced lesions, which include flexible
sigmoidoscopy and colonoscopy. Other directions of making a diagnosis might be
of importance since all tests have their shortcomings and no ideal screening
procedure is available at the moment. The metabolic status of the patient could
be of value in this respect. In a case control study colorectal cancer could
be differentiated from healthy subjects with a sensitivity of 95 percent and
specificity of 94 percent based on serum protein analysis. In another pilot
study pre- and post operative groups of CRC could be discriminated based on
serum metabolites with Gas chromatograph-mass spectrometry (GC-MS) in
combination with pattern recognition techniques. So metabolic analysis,
*metabolomics*, might be of value in diagnosis and monitoring in CRC in future.
During the last few years the analysis of exhaled breath has been proposed as a
novel option for early detection of e.g. lung cancer. After the introduction of
electronic noses, the sampling of exhaled breath and its VOC-pattern has become
readily available, *breatheomics* based on pattern recognition without
analyzing the individual molecular components, which potentially suffices for
diagnostic objectives. The first studies by a sensor array in detecting lung
cancer have demonstrated promising diagnostic accuracy and currently. We are
investigating the value of the eNose in lung cancer, breast cancer and head and
neck squamous cell carcinoma (HNSCC) in our other SCENT studies that will give
more insight into the value of electronic nose technology in each of these
cancers. One of the postulated mechanisms for a change in breathprint is a
change in the metabolic status induced by the cancer and it would be
interesting to investigate whether resection of the tumour also changes the
breathprint determined by the electronic nose.
In conclusion good screening procedures are important in CRC, but existing
tests do have their shortcomings and maybe the electronic nose technique could
be that rapid non invasive screening tool in colorectal carcinoma that we need.
Therefore in the present study, we hypothesize that an electronic nose can
discriminate the VOC pattern in exhaled breath between patients with colorectal
cancer and healthy controls. If confirmed, follow up of the breathprint after
tumour resection is interesting.

The primary objective of this study is to examine the difference in VOC pattern
of exhaled air (breathprint) between patients with histology-confirmed
diagnosis of colorectal cancer and healthy controls.
The secondary objectives are to investigate:
a. Whether the eNose can discriminate the breathprint of patients with CRC from
patients with lung cancer, Head Neck Squamous Cell Carcinoma (HNSCC) and mamma
carcinoma, all groups included in SCENT study 1,2 and 4.
b. Whether the eNose can discriminate between the breathprints of patients with
adenocarcinoma (NSCLC, mamma carcinoma, CRC) and squamous cell carcinoma
(NSCLC, HNSCC).
c. Whether the eNose can discriminate between the breathprints of patients
before and 6 weeks after resection of the CRC that is localized proximal to the
rectum.

Open observational, case control study. In addition for the group CRC proximal
to the rectum a (short) longitudinal observational study.

Patient recruitment is based on histologic diagnosis of CRC.

At the Pulmonary function department each participant will follow this sequence:
1. questionnaire
2. exhaled breath collection
3. pulmonary function test: spirometry

Patients and controls will visit the pulmonary function department.
Participants refrain from eating, drinking
and smoking 3 hours prior to the test. They first complete a questionnaire
obtaining information about medical history ,
smoking status and actual medical condition and then proceed with an exhaled
breath collection: exhaled vital capacity
(VC) manoeuvre will be performed after breathing for 5 minutes through a
mouthpiece. Then spirometry will be done.
These investigations are part of the routine pulmonary function testing and are
safe procedures. Total investigation
time will be less than 20 minutes. eNose testing might contribute to a simple
non invasive diagnostic process in future
in patients with CRC.

Patients with CRC with tumour proximal to the rectum shall have a second test 6
weeks post resection (before adjuvant treatment if necessary)