NAVIGATE: Clinical Evaluation of superDimension™ Navigation System for Electromagnetic Navigation Bronchoscopy™

The primary endpoint is the incidence of pneumothorax related to the ENB™ index procedure rated as Grade 2 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE) scale.

Pneumothorax is a disorder characterized by abnormal presence of air in the pleural cavity resulting in the collapse of the lung.

Severity increases as grade increases. Grade 1: Asymptomatic; clinical or diagnostic observations only; intervention not indicated; Grade 2: Symptomatic; intervention indicated (e.g., tube placement without sclerosis); Grade 3: Sclerosis and/or operative intervention indicated; hospitalization indicated; Grade 4: Life-threatening consequences; urgent intervention indicated; Grade 5: Death

The incidence of pneumothorax related to all ENB™ index procedures will be evaluated.

The incidence of bronchopulmonary hemorrhage (rated as Grade 2 or higher according to th CTCAE scale) related to all ENB™ index procedures will be evaluated.

Bronchopulmonary hemorrhage is a disorder characterized by bleeding from the bronchial wall and/or lung parenchyma.

Severity increases as grade increases. Grade 1: Mild symptoms; intervention not indicated; Grade 2: Moderate symptoms; medical intervention indicated; Grade 3: Transfusion, radiologic, endoscopic, or operative intervention indicated (e.g., hemostasis of bleeding site); Grade 4: Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention indicated; Grade 5: Death

The incidence of respiratory failure (rated as Grade 4 or higher according to the CTCAE scale) related to all ENB™ index procedures will be evaluated.

A respiratory failure is a disorder characterized by impaired gas exchange by the respiratory system resulting in hypoxemia and a decrease in oxygenation of the tissues that may be associated with an increase in arterial levels of carbon dioxide.

Severity increases as grade increases. Within CTCAE, there are no grades 1, 2, or 3 for Respiratory Failure.

Grade 4: Life-threatening consequences; urgent intervention, intubation, or ventilatory support indicated; Grade 5: Death

Subject health status evaluated by EuroQol-5d (EQ-5D) questionnaire at all visits. (Mobility, Self-care, Activities, Pain/Discomfort, Anxiety/Depression, Health state) Questionnaire from EuroQol Group. Outcome reported on overall health state over time. 0 = worst imaginable health state, 100 = best imaginable health state.

Subject satisfaction evaluation at the 1 month visit.

The question was "overall, how satisfied were you with the ENB procedure". Options were:

• Totally Dissatisfied
• Dissatisfied
• Neutral
• Satisfied
• Extremely Satisfied

Electromagnetic Navigation Bronchoscopy (ENB) procedure effect on subject productivity and activity using the ENB Productivity and Activity Questionnaire (ENB-PAQ) will be evaluated.

The outcome measurement is the effect of ENB on their regular daily activities on a scale of 0-10 (0=no effect, 10=completely prevented).

Diagnostic yield will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other lung diseases in a lung lesion.

Diagnostic yield was calculated per subject as the rate of true positives (TP) (for malignancy) plus true negatives (TN) (for malignancy) out of all subjects with attempted lung lesion biopsies (the denominator included subjects with no tissue obtained due to unsuccessful navigation).

Sensitivity will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other lung diseases in a lung lesion. [True Positives =TP, False Negatives = FN].

(TP / [TP+FN])

Specificity will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other diseases in a lung lesion. [True Negatives = TN, False Positives = FN] (TN / [FP+TN])

Positive predictive value (PPV) will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other diseases in a lung lesion. [True Positives = TP, False Positives = FP] (TP / [TP+FP])

Negative Predictive Value (NPV) will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other diseases in a lung lesion. [True Negatives = TN, False Negatives = FN] (TN / [FN+TN])

Repeat biopsy rate due to lack of diagnosis during the ENB™ index procedure will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other diseases in a lung lesion.

Tissue adequacy for molecular genetic testing (if applicable).

Diagnosis will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other diseases in a lung lesion (per subject)

Stage at diagnosis (if applicable) will be evaluated for all ENB™ index procedures performed for suspicion of cancer or other diseases in a lung lesion. (Diagnosis worsens as stage number increases).

Refer to the American Joint Committee on Cancer, 7th edition on Lung Cancer Staging. A brief description is provided here.

Stage I = small lesions, no lymph node involvement Stage II = larger lesions and/or lymph nodes on sides of lung involved Stage III = larger lesions and/or lymph nodes in middle of chest involved Stage IV = metastases to other organs

The success rate of accurate placement of fiducial markers demonstrated through follow up imaging will be evaluated for all ENB™ index procedures conducted for placement of fiducial markers.

The success rate of dye marking demonstrated by successful surgical resection will be evaluated for all ENB™ index procedures conducted for dye marking in preparation for surgical resection.

The success rate of obtaining a lymph node biopsy to provide the stage of diagnosis will be evaluated for all ENB™ index procedures conducted for a lymph node biopsy.