This Small Business Innovation Research Phase I project aims to develop and commercialize a technology that can screen patients who are at risk for lung cancer by means of a simple buccal swab of the cheek epithelium. Lung cancer is the leading cause of cancer deaths in the U.S. The reason for the lethality of lung cancer relates to its tendency to be diagnosed at a late stage, given that the potentially curable stages of disease are often clinically silent. Survival rates for lung cancer depend dramatically on the stage at which it is diagnosed. However, existing screening approaches have been inadequate from either a sensitivity or efficacy/cost-effectiveness perspective. Thus, finding a screening method to identify patients at risk would be critical. In Phase I, a high-throughput partial wave spectroscopic (HT-PWS) microscope that can quantify the statistical properties of cellular nanoscale organization and identify early cancerous changes in buccal epithelial cells, which are associated with lung cancer, will be developed. This test will be simple, inexpensive, minimally invasive, and highly accurate and will be based on the well-validated biological phenomena of field carcinogenesis.
The broader impact/commercialization potential of this project is that the partial wave spectroscopic (PWS) microscope-based testing would significantly improve the accuracy of lung cancer screening and allow diagnosis of the disease at an early, curable stage. The vision is for this technology to become a primary font-line screening method for lung cancer which is a $5B market, with an estimated 46M smokers in the United States. The PWS microscopy-based screening technique would be performed on smokers by a primary care physician or dentist as part of an annual exam (like an annual Pap smear test). If the result is negative (not at risk), then the patient would be retested at their next annual physical. However, if the result is positive then the patient will be sent for other more expensive/invasive tests such as Computed tomography (CT) and bronchoscopy. Because significantly more at-risk patients would likely be screened for lung cancer than today, this would have a major impact on healthcare in the United States by both reducing the cost of healthcare and by saving valuable human life.
The overall goal of the SBIR Phase I grant was to develop a technology that can screen patients who are at risk for lung cancer by means of a simple buccal swab of the cheek epithelium. Lung cancer is the leading cause of cancer deaths in the U.S. The reason for the lethality of lung cancer relates to its tendency to be diagnosed at a late stage, given that potentially curable stages of disease are often clinically silent. This underscores the need for effective screening of patients who are risk for lung cancer (current/former smokers). Currently, no low-cost, minimally-invasive and accurate test is available for lung cancer screening. A recently developed nanocytology technique, PWS microscopy, has the potential to become the first low-cost, minimally invasive test to screen patients who are at risk for developing lung cancer. However, the first generation PWS system was extremely slow and it often required ~5-6 hours diagnosing a patient specimen making the translation of PWS nanocytology to clinic virtually impossible. The rationale behind this SBIR phase I project was to develop a radically new lung cancer screening technique based on PWS nanocytology that can acquire data from patient samples in a clinically acceptable time. We accomplished all the primary objectives that were proposed in the Phase I grant: (a) We developed a high throughput PWS (HT-PWS) imaging system that will reduce the time to obtain the final diagnosis of the patient sample to less than 5 minutes (b) We tested the nanoscale sensitivity and diagnostic ability of the HT-PWS system using nanostructured phantoms and human colon cancer cell lines (c) In addition to these primary objectives of Phase I, we also performed a limited clinical trial of the HT-PWS instrument on smokers (control patients) and patients with lung cancer (n = 23) and the results showed a statistically significant difference in buccal PWS. With the successful demonstration of this promising technology in Phase I, we plan to translate the current bench top system to a clinical grade instrument in Phase II. In additional, we plan to refine the sample preparation/collection protocol and expand the clinical evaluation of the HT-PWS system in Phase II. The long term vision is that the nanocytological analysis of cell brushed from the buccal mucosa may become a pre-screen tool that can be performed by a primary care physician or dentist as part of an annual exam to identify the subset of patients who may benefit from further screening. If the buccal nanocytology is positive, the patients will be offered more expensive/invasive tests such as CT scan or bronchoscopy. In the long-term, PWS based nanocytology would significantly improve the accuracy of lung cancer screening and allow diagnosis of the disease at an early, curable stage.
