Abstract
Colorectal cancer (CRC) is a worldwide diffused pathology for both men and women and it is the third most common cancer for both genders, in the United States[1] However, if promptly diagnosed, CRC is also one of the most curable tumor types (90% curability rate at stage I), therefore prevention is fundamental to avoid degeneration. Here the clinical validation outcomes of a preventive screening method based on a patented device, SCENT A1, composed by a core of nanostructured MOX sensors [2]. SCENT A1 is capable of detecting the presence of CRC 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 membrane peroxidation and metabolic alterations [3,4]. The screening analysis adopted by NHS of Italy and of other countries is fecal occult blood test (FOBT). In Italy, FOBT 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 data). FOBT-positives are then invited to undergo colonoscopy. SCENT A1 is capable of reducing FOBT false positives and so the total number of non-operative colonoscopies with related risks (e.g. bowel perforation). The device, presently undergoing instrumental certification, is composed by a core of two chemoresistive MOX sensors, chosen and calibrated for this specific aim [5-11]. Sensors (Figure 1) have been synthesized at Sensor Laboratory of the University of Ferrara and are composed by a nanostructured semiconductor film screen-printed onto an alumina substrate and a platinum heater to modulate operating temperature. The first sensor is composed by Iron and Samarium oxides while the second one by Tin and Titanium oxides. The data collection and analysis software employs support vector machine (SVM) [9]. The clinical validation protocol of this device started in May 2016 and ended in July 2019, in collaboration with Hospital St. Anna of Ferrara 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: 260 healthy subjects (negative to colonoscopy); 138 colorectal adenomas and carcinomas (positive to colonoscopy), 54 low-risk adenomas and 84 high-risk adenomas and carcinomas. The system has been capable of distinguishing among these two categories with a sensitivity (TPR: true positive rate) and specificity (TNR: true negative rate) respectively 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 simplified the test and ensured greater doctor protection, despite a small loss in specificity. Low-risk adenomas are, in fact, often similar to healthy tissues and have a risk of evolving into cancer comparable to the risk of colonoscopy complications. As already emerging from a previous study [10-11], in fact, the major error of classification (only 57%) concerned just low-risk tumors that emit gases halfway between healthy and tumoral samples. 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 collaboration, involving private clinic Quisisana, started in 2020 with some laboratory tests on sensors reproducibility [12] will continue in January 2021 with tests on patients directly inside the clinic, in order to test the new shape of the device under certification. Moreover, if employed by the NHS of countries without screening system, this method will significantly reduce CRC-mortality rate.
[1] [https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html
[2] Italian #: RM2014A000595, European #: 3210013 (Germany, UK);
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[12] G. Zonta et al., Ceramics International Volume 46, Issue 5, 1 April 2020, Pages 6847-6855.
Figure 1: a) external view of the patented prototype SCENT A1, composed by flowmeters, a flow diverter and a sample box; b) one of the chemoresistive sensors composing the core of the instrument; c) magnificated scheme of the sensor.
Figure 1