Sensing Device for Colorectal Cancer Preventive Screening through Fecal Odor Analysis: Clinical Validation Outcomes
Authors: Zonta Giulia , Astolfi Michele , de Togni Aldo , Gaiardo Andrea , Gherardi Sandro , Guidi Vincenzo , Landini Nicolò , Palmonari Caterina , Malagù Cesare 
Published: May 2020

Colorectal cancer (CRC) is a worldwide diffused pathology for both men and women. It showed to be the third most common cancer for both genders, in the United States. [1] On the other hand, if promptly diagnosed, CRC is also one of the most curable tumor types (curability rate of about 90% at stage I), therefore prevention is fundamental to avoid its degeneration. This work shows the clinical validation outcomes of a preventive screening method based on a portable device composed by a core of nanostructured MOX sensors. This patented device, named SCENT A1 [2], is capable of detecting the presence of colorectal adenomas and carcinomas from fecal odor with an in-vitro, inexpensive and non-invasive methodology. Fecal odor can be affected by the presence of CRC-biomarkers produced by cancer cells through mechanisms of membrane peroxidation and metabolic alterations [3,4]. The analysis currently adopted by National Health Service (NHS) of Italy and of other countries as mass population screening is fecal occult blood test (FOBT). In Italy, this test is performed every two years on subjects from 50 to 69 years old and shows a huge percentage of false positives (about 65% according to the analyzed data). FOBT positives are then invited to undergo colonoscopy. SCENT A1 is capable of reducing FOBT-false positives, also diminishing the total number of non-operative colonoscopies, preventing healthy patients, often elderly, from undergoing the related risks (e.g. bowel perforation). The device presented here is composed by a core of five chemoresistive MOX sensors, chosen and calibrated for this specific aim through a study started in 2013 that lead to encouraging results [5-10]. Sensors have been synthesized at Sensor Laboratory on the University of Ferrara and are composed by a nanostructured semiconductor film screen-printed onto an alumina substrate and a platinum heater to modulate the operating temperature. In Figure 1 both the device and a sensor schematization are shown. In the ending phase of the protocol, the chosen sensors have been limited to two, one composed by Iron and Samarium oxides and the other by Tin and Titanium oxides. This choice has been done in order to simplify the device and to facilitate a future large scale reproduction, without any loss in the information carried by the system. The data collection and analysis software has been realized by employing machine learning techniques like support vector machine (SVM) [9] method. The clinical validation protocol of this device started in May 2016, in collaboration with Hospital St. Anna of Ferrara, Delta Hospital of Lagosanto and Department of Public Health of Ferrara. A total of 398 fecal samples of FOBT-positive subjects have been analyzed by SCENT A1 system with the k-fold cross validation method. Samples have been grouped into two macro-categories, depending on the gold-standard (colonoscopy) outcomes:

healthy subjects (negative to colonoscopy), in total 260;

all types of colorectal adenomas and carcinomas (positive to colonoscopy), in total 138 (54 low-risk adenomas and 84 high-risk adenomas and carcinomas).

The system has been capable of distinguishing among these two cathegories with a sensitivity (TPR: true positive rate) and specificity (TNR: true negative rate) respectively of of 84,1% and 82,4%, defined as follows:

TPR=TP/P=TP/(FN+TP);

TN/N=TN/(FP+TN);

where TP, TN, FP and FN are the abbreviations that indicate respectively true positives, true negatives, false positives and false negatives. The choice to group carcinomas, high- and low-risk adenomas into a single class and not into two diverse classes as before [10], has been done in order to simplify the test and to ensure greater doctor protection, despite a small loss in specificity. This is due to the fact that low-risk adenomas are often similar to healthy tissues and they have a risk of evolving into cancer comparable to the risk of colonoscopy complications. As already emerging from a previous study [10], in fact, the major error of classification (only 57%) concerned just low-risk tumors that emit gases halfway between healthy and tumoral samples. By observing these results, what emerges is that, if SCENT A1 test is carried out on FOBT-positives subjects as a second check, it would guarantee a reduction of about two thirds of the colonoscopies performed on healthy patients. A new multicenter protocol, involving also Ospedale Maggiore of Bologna (Italy) and the private clinic Quisisana will start in 2020, in order to test diverse devices of the same type also to subjects resulted negative to FOBT and colonoscopy. This double comparison will be useful to evaluate the possible capability of this method of identifying interval cancers. Moreover, if employed by the NHS of countries where screening systems are not currently carried out on population, this method will significantly reduce the mortality rate related to CRC.

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Figure 1