Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry.

Malignant pleural effusions (MPEs) can be utilized as liquid biopsy for phenotyping malignant cells and for precision immunotherapy, yet MPEs are inadequately studied at the single-cell proteomic level. Here we leverage mass cytometry to interrogate immune and epithelial cellular profiles of primary tumors and pleural effusions (PEs) from early and late-stage non-small cell lung cancer (NSCLC) patients, with the goal of assessing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in patient specimens. By using the EMT-MET reference map PHENOSTAMP, we observe a variety of EMT states in cytokeratin positive (CK+) cells, and report for the first time MET-enriched CK+ cells in MPEs. We show that these states may be relevant to disease stage and therapy response. Furthermore, we found that the fraction of CD33+ myeloid cells in PEs was positively correlated to the fraction of CK+ cells. Longitudinal analysis of MPEs drawn 2 months apart from a patient undergoing therapy, revealed that CK+ cells acquired heterogeneous EMT features during treatment. We present this work as a feasibility study that justifies deeper characterization of EMT and MET states in malignant cells found in PEs as a promising clinical platform to better evaluate disease progression and treatment response at a personalized level.

First Human Use of a New Robotic-Assisted Fiber Optic Sensing Navigation System for Small Peripheral Pulmonary Nodules.

BACKGROUND: We tested a new, investigational robotic-assisted bronchoscope system with a remotely controlled catheter to access small peripheral bronchi with real-time driving under live visualization and distal tip articulation of the catheter. The unique catheter remains stationary once located at the biopsy position. OBJECTIVES: The primary objectives of this study were to evaluate the safety and feasibility of a new shape-sensing robotic bronchoscope system to bronchoscopically approach and facilitate the sampling of small peripheral pulmonary nodules of 1-3 cm. Secondary objectives included evaluating procedural characteristics and early performance trends associated with the use of the new robotic bronchoscope system. METHODS: Subjects were enrolled according to study eligibility criteria at a single center. Navigation pathways were semi-automatically created using pre-procedure CT scans. Simultaneous (real-time) viewing of actual and virtual bronchi was used real time during navigation to the displayed target. An endobronchial ultrasound mini-probe was used to confirm lesion location. Flexible 19- to 23-G needles specifically designed to accommodate tight bend radii in transbronchial needle aspiration were used along with conventional biopsy tools. Enrolled subjects completed follow-up visits up to 6 months after the procedure. RESULTS: The study included 29 subjects with a mean lesion size of 12.2 ± 4.2, 12.3 ± 3.3, and 11.7 ± 4.1 mm in the axial, coronal, and sagittal planes, respectively. The CT bronchus sign was absent in 41.4% of cases. In 96.6% of cases, the target was reached, and samples were obtained. No device-related adverse events and no instances of pneumothorax or excessive bleeding were observed during the procedure. Early performance trends demonstrated an overall diagnostic yield of 79.3% and a diagnostic yield for malignancy of 88%. CONCLUSION: This new robotic-assisted bronchoscope system safely navigated to very small peripheral airways under continuous visualization, and through maintenance of a static position, it provides a unique sampling capability for the biopsy of small solitary pulmonary nodules.

Interventional pulmonology approaches in the diagnosis and treatment of early stage non small cell lung cancer.

Lung cancer management is complex and requires a multi-disciplinary approach to provide comprehensive care. Interventional pulmonology (IP) is an evolving field that utilizes minimally invasive modalities for the initial diagnosis and staging of suspected lung cancers. Endobronchial ultrasound guided sampling of mediastinal lymph nodes for staging and detection of driver mutations is instrumental for prognosis and treatment of early and later stage lung cancers. Advances in navigational bronchoscopy allow for histological sampling of suspicious peripheral lesions with minimal complication rates, as well as assisting with fiducial marker placements for stereotactic radiation therapy. Furthermore, IP can also offer palliation for inoperable cancers and those with late stage diseases. As the trend towards early lung cancer detection with low dose computed tomography is developing, it is paramount for the pulmonary physician with expertise in lung nodule management, minimally invasive sampling and staging to integrate into the paradigm of multi-specialty care.