Periodic Reporting for period 3 - ESOTRAC (Hybrid optical and optoacoustic endoscope for esophageal tracking.)
Período documentado: 2019-09-01 hasta 2021-12-31
More than 450,000 people are diagnosed with esophageal cancer (EC) each year and around 400,000 die annually from the disease. In the past three decades, EC incidence rates increased by six fold, making EC the fastest rising cancer in the Western World. This severe increase is closely associated with modern lifestyle and its concomitants such as alcohol consumption, higher age, obesity, and, in particular, a pre-cancerous condition called Barrett’s esophagus (BE), affecting around 10 million people in the Western countries. All these predispositions may lead to EC if not detected and treated early on.
Unfortunately, EC is often detected late leading to the high mortality rates mentioned above. In fact, the 5-year survival rate is only 10% if detected late while it significantly increases to 90% upon early diagnosis. The current situation of late EC detection is largely based on the lack of adequate detection methods.
In recent times, EC detection typically relies on white-light endoscopy (WLE), i.e. the visual inspection of the esophagus through an optical system (endoscope) and subsequent pathological analysis of biopsied samples. Human vision, however, is insensitive to detecting early disease and lacks specificity and staging ability, compromising disease prognosis and thus, is often inaccurate and may miss lesions.
The interdisciplinary research team of ESOTRAC developed an innovative endoscope that combines sensing of pathophysiological tissue signatures resolved by multi-spectral optoacoustic tomography (MSOT) with morphological disease parameters provided by optical coherence tomography (OCT). The novel endoscope has superior qualities in detecting early stages of EC compared to WLE, e.g. by not only inspecting the esophageal surface but screening for abnormalities hidden inside the tissue. The hybrid endoscope generates three dimensional images of the esophagus at high resolution, allowing physicians to inspect the entire esophagus wall and to detect early onset of cancer within the mucosa/submucosa, which in turn, will reduce unnecessary biopsies.
Moreover, the socio-economic impact of our hybrid endoscope can become immense. Treating late disease incurs average costs of €130,000 per patient putting esophageal cancer amongst the most expensive treatments in oncology today. A 5% shift from late-detections to early-detections would result in €2.7 billion savings; with a 10% shift, this number would rise to €5.4 billion.
Unfortunately, EC is often detected late leading to the high mortality rates mentioned above. In fact, the 5-year survival rate is only 10% if detected late while it significantly increases to 90% upon early diagnosis. The current situation of late EC detection is largely based on the lack of adequate detection methods.
In recent times, EC detection typically relies on white-light endoscopy (WLE), i.e. the visual inspection of the esophagus through an optical system (endoscope) and subsequent pathological analysis of biopsied samples. Human vision, however, is insensitive to detecting early disease and lacks specificity and staging ability, compromising disease prognosis and thus, is often inaccurate and may miss lesions.
The interdisciplinary research team of ESOTRAC developed an innovative endoscope that combines sensing of pathophysiological tissue signatures resolved by multi-spectral optoacoustic tomography (MSOT) with morphological disease parameters provided by optical coherence tomography (OCT). The novel endoscope has superior qualities in detecting early stages of EC compared to WLE, e.g. by not only inspecting the esophageal surface but screening for abnormalities hidden inside the tissue. The hybrid endoscope generates three dimensional images of the esophagus at high resolution, allowing physicians to inspect the entire esophagus wall and to detect early onset of cancer within the mucosa/submucosa, which in turn, will reduce unnecessary biopsies.
Moreover, the socio-economic impact of our hybrid endoscope can become immense. Treating late disease incurs average costs of €130,000 per patient putting esophageal cancer amongst the most expensive treatments in oncology today. A 5% shift from late-detections to early-detections would result in €2.7 billion savings; with a 10% shift, this number would rise to €5.4 billion.
ESOTRAC had an ambitious goal: the development of a completely new hybrid endoscope which has never been designed in this way before. Major challenges that the consortium always had to keep in mind were, on the one hand, the perfect alignment of two technologies with their very unique requirements, materials and speed of operation, and on the other hand, the miniaturization of the whole set-up from benchtop to a portable rack system. While the ESOTRAC partners discussed various biocompatible materials as well as alternate configurations of hardware and already tested their suitability for incorporation into the hybrid endoscope, a key factor for coming up with a final miniaturized capsule endoscope were custom-made components. From the first laboratory-based prototype it took several iterations of design revisions to decrease the size of the capsule endoscope constantly. Finally, the capsule reached the desirable size of the cap of a pen which can pass through the human esophagus. The consortium managed to apply precision alignments of the micro components in a way that optical and acoustic signals reached excellent performance and synchronized signals of OCT and optoacoustics could be acquired in high speed and in fast rotation never reached before. Requirements of physicians experienced in esophageal screening were taken into consideration when designing the user interface of the custom-made ESOTRAC software, as well as safety measures and the synchronization of both imaging modalities.
With the final miniaturized capsule endoscope at hand, the consortium performed experiments to test its suitability for esophageal screening and to obtain images for biomarker quantification. A successful in-vivo screening of pig was achieved as well as the imaging of human esophageal resection samples from patients at the University of Cambridge hospital. These experiments lay an important foundation for the next steps to validate the endoscope in patient screenings.
As raising awareness is of outmost importance, the ESOTRAC consortium created a website (https://www.esotrac2020.eu/) to inform the general public, scientists and clinicians about the project goals and most recent developments. ESOTRAC distributed a press release, flyers, and brochures to relevant stakeholders and created a YouTube video entitled “Future of Biomedical Imaging: ESOTRAC”. An article about ESOTRAC was published in the Physics World Magazine and ESOTRAC took part in an exhibition to inform the general public. Further outreach activities to the scientific community included, for instance, a workshop, oral and poster presentations at international conferences, and pitch events. To top it off, ESOTRAC members published 18 scientific publications in high-ranking journals.
With the final miniaturized capsule endoscope at hand, the consortium performed experiments to test its suitability for esophageal screening and to obtain images for biomarker quantification. A successful in-vivo screening of pig was achieved as well as the imaging of human esophageal resection samples from patients at the University of Cambridge hospital. These experiments lay an important foundation for the next steps to validate the endoscope in patient screenings.
As raising awareness is of outmost importance, the ESOTRAC consortium created a website (https://www.esotrac2020.eu/) to inform the general public, scientists and clinicians about the project goals and most recent developments. ESOTRAC distributed a press release, flyers, and brochures to relevant stakeholders and created a YouTube video entitled “Future of Biomedical Imaging: ESOTRAC”. An article about ESOTRAC was published in the Physics World Magazine and ESOTRAC took part in an exhibition to inform the general public. Further outreach activities to the scientific community included, for instance, a workshop, oral and poster presentations at international conferences, and pitch events. To top it off, ESOTRAC members published 18 scientific publications in high-ranking journals.
Now that this challenging project has come to an end, the ESOTRAC consortium presents a hybrid endoscope with unparalleled capabilities for the detection of early stages of esophageal cancer. Since the key technologies have never been combined before in an endoscopic setting, a number of technical components were developed and miniaturized within ESOTRAC. These innovations bear a potential not only for ESOTRAC per se but also for other clinical applications and as such represents enormous progress beyond the state of the art.
With a pre-clinical validation at hand and important documentation for regulatory approval already prepared, the next steps will be to validate the ESOTRAC hybrid endoscope in a clinical setting. This will be a major step towards the market entry of the novel system, to the benefits of patients and the healthcare system as well. From a medical point of view, white-light endoscopy examinations are done by the visionary inspection of the esophageal wall by the operator and identification of lesions is fairly subjective. By offering cross-sectional imaging and quantification, the novel endoscope can improve upon objective metrics for disease detection, enabling precision medicine and standardizing the quality of healthcare in esophageal cancer and other diseases.
Economically, the costs of the novel endoscope will be comparable to currently existing systems, which can be amortized after ~ 1300 examinations. Most importantly, the implementation of the endoscope will reduce healthcare costs by cutting the 5-year average treatment costs of late stage EC of €130,000 down to around €12,000 upon early detection of disease. In turn, this means that for every 1% of the world population that can be shifted from late to early detection, i.e. ~ 4,500 patients, the healthcare savings are €541 million.
The consortium developed several exploitation strategies with the ESOTRAC market experts to allow for a quick introduction of the hybrid endoscope to the market once the clinical validation of the system is performed as a next step. In conclusion, in the long-term ESOTRAC will save costs, boost innovation in the European community, and – most importantly – save lives!
With a pre-clinical validation at hand and important documentation for regulatory approval already prepared, the next steps will be to validate the ESOTRAC hybrid endoscope in a clinical setting. This will be a major step towards the market entry of the novel system, to the benefits of patients and the healthcare system as well. From a medical point of view, white-light endoscopy examinations are done by the visionary inspection of the esophageal wall by the operator and identification of lesions is fairly subjective. By offering cross-sectional imaging and quantification, the novel endoscope can improve upon objective metrics for disease detection, enabling precision medicine and standardizing the quality of healthcare in esophageal cancer and other diseases.
Economically, the costs of the novel endoscope will be comparable to currently existing systems, which can be amortized after ~ 1300 examinations. Most importantly, the implementation of the endoscope will reduce healthcare costs by cutting the 5-year average treatment costs of late stage EC of €130,000 down to around €12,000 upon early detection of disease. In turn, this means that for every 1% of the world population that can be shifted from late to early detection, i.e. ~ 4,500 patients, the healthcare savings are €541 million.
The consortium developed several exploitation strategies with the ESOTRAC market experts to allow for a quick introduction of the hybrid endoscope to the market once the clinical validation of the system is performed as a next step. In conclusion, in the long-term ESOTRAC will save costs, boost innovation in the European community, and – most importantly – save lives!