Smellprints in lung Cancer; the role of ENose in diagnosis and Treatment (SCENT):
part 1. Differences in smellprints between patients with lung cancer and breast cancer

Lung and breast cancer are leading causes of cancer-related death, with a total
of 400,000 new lung and breast cancer cases and more than 200,000 deaths from
these cancers per year in the United States [1]. Although mortality in breast
cancer has been reduced after the introduction of screening programs [2], the 5
years survival in lung cancer remains poor, largely due to the fact that most
patients with lung cancer present already with advanced disease. Given this
poor prognosis, early detection of lung cancer is considered crucial to
decrease mortality, and in particular non-invasive diagnostic strategies aimed
at identifying biomarkers of lung cancer are of great interest.
During the last few years the analysis of exhaled breath has been proposed as a
novel option for early detection of lung cancer. Exhaled breath contains a
complex mixture of several hundreds of volatile organic compounds (VOCs). This
could be established by gas chromatography and mass spectrometry (GC-MS). It
has been shown that distinct biochemical markers have been found in the exhaled
breath of patients with lung and breast cancer that could be discriminated from
those of controls, suggesting that VOC analysis might be used as a non invasive
marker of these cancers. However, the requirement of elaborative offline GC-MS
analysis limited the further development of this diagnostic potential.
After the introduction of electronic noses, the sampling of exhaled breath and
its VOC-pattern has become readily available, due to their ability to allow
on-board analysis and discrimination of *smellprints* by composite nano-sensors
arrays (*breatheomics*). This is 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 recently Dragonieri and colleagues showed
that VOC patterns analysed by an electronic nose discriminated patients with
lung cancer from COPD patients as well as healthy controls, further emphasizing
the importance of prospective studies focussing on the diagnostic value of
electronic noses in lung cancer.
Although most of previous mentioned studies were able to discriminate between
patients with and without a specific type of cancer (mainly lung and breast
cancer), until now studies comparing markers in exhaled breath in patients with
different cancer types are lacking. So, the question remains whether the
discrimination that can be made by an electronic nose is based on changes in
VOCs due to an organ-specific malignancy or might be related to metabolic
changes due to cancer in general.
In the present study, we hypothesize that an electronic nose can discriminate
the VOC pattern in exhaled breath between patients with lung cancer and breast
cancer. Furthermore it is very interesting to investigate whether the VOC
pattern changes after resection of the (lung)malignancy.

Primairy objective: we will examine the difference in VOC pattern of exhaled
air between patients with histology-confirmed diagnoses of non small cell lung
cancer vs breast cancer.
Secundairy objective:
a. to confirm the potential of the electronic nose to distinguish the VOC
patterns between patients with NSCLC and healthy controls and to assess its
capacity to discriminate between women with and without breast cancer.
b. when the eNose demonstrates to be capable to distinguish the VOC patterns of
patients with NSCLC and breast cancer, we will try to identify the distinct
biomarkers in the exhaled breath samples of both groups by using
gaschromatography and mass spectrometry (GC MS)
c. to investigate whether the VOC pattern changes when resection of the lung
cancer has been performed.

open observational, case-control study.
for the lung cancer resection group in addition a short longitudinal
observatory study.

All persons, patients and controls, will visit the pulmonary function
department once. They first will complete a questionnaire obtaining information
about medical history, smoking history en actual medical condition. Then
exhaled breath collection will take place after 5 min tidal breathing VOC
filtered room air. Finally spirometry will be performed. Total time will not
exceed 20 min.

Both groups (breast cancer and lung cancer) are chosen, because they are
leading causes of death and both have much better perspectives when diagnosed
at early stage. eNose technology might be of great value in the screening and
monitoring of these two cancers.

Patients with lung cancer treated with surgical resection, also if they are
candidates for adjuvant chemotherapy or radiotherapy, will perform two
additional measurements: at the end of their post-operative period in the
hospital (about 7-14 days post operation) and at 6 weeks (before other adjuvant
therapy modalities if needed) at the outpatient department. These measurements
will be performed as much as possible during the regular hospital visits.