Early Detection and Diagnosis of Lung Cancer with Endomicroscopy

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PROJECT SUMMARY Early diagnosis of lung cancer is critical to patient survival. Unfortunately the vast majority of cases are detected once symptoms arise and the cancer has spread offering patients little hope for cure (average 5-year survival rate < 15%). The U.S. Preventive Services Task Force recommends individuals at high risk of developing lung cancer undergo yearly screening with low dose computed tomography (LDCT). Screening is highly sensitive at detecting lung nodules and has resulted in a reduction in mortality of these patients, however only 5% of nodules detected are likely to be cancer. Diagnosis of lung cancer must be made on the microscopic level which is traditionally done by obtaining tissue specimens for subsequent histopathology examination. Methods for biopsy generally fall under two categories; high-risk surgical and transthoracic procedures that provide a higher diagnostic yield, and low-risk bronchoscopy based procedures that generally have a lower yield. Given that the vast majority of nodules detected by LDCT screening are benign it is critical that the high-risk procedures for diagnosis are avoided. The low diagnostic yields of bronchoscopy based biopsy procedures can be attributed to insufficiently large, inappropriately located, or non-diagnostic tissue sampling. Therefore there is a critical need to dramatically increase the diagnostic yield of low-risk bronchial biopsy approaches. In our laboratory we have developed novel optical coherence tomography (OCT) imaging approaches to provide high-resolution images of tissue microstructure. We have additionally developed and disseminated OCT interpretation criteria for the diagnosis lung cancer. In this proposal we aim to further develop our endobronchial OCT imaging catheters to provide images with superior resolution and contrast with the goal of microscopically guiding biopsy site selection to increase tumor yield (Aim 2), and to use our endomicroscopy images and previously developed image interpretation criteria to provide a preliminary diagnosis of the lesion within the procedure room (Aim 3). The intra-procedural diagnostic endomicroscopy images could be useful complementary information provided to pathologists in addition to the tiny physical biopsy specimens for diagnosis, or to enable immediate diagnosis and treatment of small lesions without requiring a second procedure.