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Screening of Gastric Cancer via Breath volatile organic compounds by Hybrid Sensing Approach

Periodic Reporting for period 2 - VOGAS (Screening of Gastric Cancer via Breath volatile organic compounds by Hybrid Sensing Approach)

Reporting period: 2020-07-01 to 2021-12-31

Screening for different diseases is required to reveal groups of individuals in whom the likelihood of a specific disease is increased and who could benefit from further medical evaluation. These benefits are compounded when considering available treatment upon early detection. The ideal screening test is low-cost, high-accuracy, non-invasive, easily repeatable, effortlessly operated and has minimal impact on daily activities. In the VOGAS project, we aim to tackle these requirements by integrating two very different nanotechnologies into a single device to detect disease markers from exhaled breath. This approach relies on convergence of three different sensing technologies, which are presumably orthogonal in nature. A breath sample is analyzed by a unique Gold Nanoparticles sensor array, a well optimized MOS sensor array and a Hollow Waveguide IR spectrometer all in parallel in a matter of minutes. This device will be placed in different point-of-care locations and the analysis will be done on site. The sensor response will be recorded, stored and pre-processed via the internal software of the device. Subsequently, it will be sent to an external server for elaborated statistical pattern recognition analysis. In general, the different statistical programs compare the responsive pattern of the sensor array as well as the spectral chromatograms to previously known samples. These have been a-priori fed to the program as a training set. This analysis is then translated to a screening result harboring a level of certainty of the particular breath sample, originating from a "Sick" or "Healthy" individual. We develop the VOGAS project with the aim of early detection of Gastric Cancer. However, we believe that the VOGAS concept represents a new approach for addressing major societal challenges in health and well-being of the general population.
The first 36 months evolved according to the plan despite the delays caused by the covid 19 pandemic. That is to say that providing the 9 month extension, we believe that all of the planned activities will be able to actualize.
• The Sensors array was further optimized, and the new design was calibrated with more efficient curing methods. This serves to allow for lower sensor drift and lower sensor to sensor viability. The sensor redundancy approach was adopted from a research group of Prof Denatale in Rome who demonstrated a significant noise reduction and drift compensation due to sensor redundancy. Just recently we were able to initiate a collaborative work with them for the analysis of the Vogas results.
• Device manufacturing - Due to the need to test the VOGAS device by clinical trial including a large number of subjects and a limited time to recruit a sufficient number of Gastric Cancer (GC) patients, it was decided to build six devices of the final format. This decision changes the previous plan of building only three devices of the final format and three devices which only harbor the sensor technology without the IR module. This decision was discovered to be of great importance due to the outbreak of covid-19 which delayed some of the activities, further limiting the actual time to recruit GC patients. Thus, the six devices have been built, distributed and are currently operational in the different clinical centers. We currently measured breath samples of approximately half of the subjects planned to be recruited in the project all together.
• VOC analysis - UOL collected samples of gastric cancer tissue and stomach content form GC patients as well as from heathy volunteers. These were shipped to UIBK for Volatile Organic Compound (VOC) analysis. The analysis by GC and PTR-MS was done along with a tissue culture study comparing VOC emission from normal and gastric cancer cell lines. This study comprising most of the work of work package 1, led to the finding of several unique and novel VOC’s whose levels are altered in malignant tissue relative to normal ones.
• Clinical studies - All five clinical centers, obtained the necessary permits and authorizations to conduct the clinical trials. All Standard Operating Procedures (SOPs) have been agreed upon and the two clinical studies were launched (WP4 and WP5). Two units were sent to Latvia, one unit to Brazil, one unit to Chile and one unit to Ukraine. Despite some technical problems we are now about halfway with the recruitment of the total number of subjects planned for these two studies.
• Obtainment of results – JLM has dedicated a very large storage space in the Vogas cloud for uploading the clinical results. Each center is uploading the Vogas breath sample results to the cloud where it is stored for the statistical analysis. In parallel both Juha and Johannes inspect the results daily to make sure that both the GNP and the IR units are generating meaningful results. This is important to make sure that the different modules are working fine and when technical problems accrue, we can respond in a timely manner.
• Statistical analysis – Breath samples of healthy volunteers and gastric cancer patients obtained in previous projects were analyzed by VTT according to the neural adaptive statistical method. A project data base has been designed and formed and the flow of data storage and analysis was constructed. VTT also provided a safe ICT platform for data transfer and analysis which would maintain the privacy of the users. Lately the collaboration with the Denatale group in Rome who initiated the adaptive neural network method has been established. The partial set of results was shared with the Denatale group in order to initiate the collaboration.
• Ethics – An external ethical board (EEB) was formed, and all informed consent forms were evaluated. Periodic ethical meetings were held, and the ethical summaries of these meetings were included into the periodic report. Finally, a responsible research and innovation (RRI) study and a few filed exercises were performed.
The existing screening methods for cancer suffer from a multitude of disadvantages. Some, such as colonoscopy and sigmoidoscopy are invasive and hence, pose actual risks of medical complications to the screened subjects. Others, such as TEM or mammography for example, require special facilities, are expensive and subject the examined individual to risks of radiation. These caveats are compounded by the discomfort and inconvenience, as well as the involvement of time and money these screening methods impose on the patient. These are all good explanations for the low number of screening methods implemented today. Despite the above, it is widely agreed that one of the most curtail obstacles in screening programs is that a very limited number of diseases currently have an effective screening approach available, e.g. screening for only four cancer types is currently recommended in the EU. The VOGAS project is based on three different and most likely orthogonal analytical methods. Therefore, while maintaining the ease of operation and un invasiveness, VOGAS has a very good chance for improving signal to noise ration and hence it’s predictive value.