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

Time frame: index procedure visit

Population: All subjects included in this analysis

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

Time frame: up to 24 months

Population: Number of subjects where navigation was complete and tissue was obtained for a diagnosis. Subjects with multiple lesion diagnoses may be represented more than once in all subcategories.

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).

Time frame: up to 24 months

Population: Per subject including all those with attempted lung lesion biopsies. This includes any with unsuccessful navigation, but excludes subjects with insufficient follow-up where True Positive, True Negative, False Positive and False Negative could not be determined by 24 months.

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

Time frame: index procedure visit

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

Time frame: index procedure visit

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

Time frame: index procedure visit

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 / \[FN+TN\])

Time frame: up to 24 months

Population: Number of subjects with a False Negative (FN) for Malignancy or True Negative (TN) for Malignancy diagnosis by 24-months.

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 / \[TP+FP\])

Time frame: up to 24 months

Population: Number of subjects with a True Positive (TP) for Malignancy or False Positive (FP) for Malignancy diagnosis by 24-months.

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.

Time frame: Baseline, 1 month, 12 month, and 24 month follow up visits

Population: Number of subjects who completed the EQ-5D at the baseline visit.

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.

Time frame: up to 24 months

Population: Number of subjects with navigation complete and tissue obtained

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 / \[TP+FN\])

Time frame: up to 24 months

Population: Number of subjects with a True Positive (TP) for Malignancy or False Negative (FN) for Malignancy diagnosis by 24-months.

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 / \[FP+TN\])

Time frame: up to 24 months

Population: Number of subjects with a False Positive (FP) for Malignancy or True Negative (TN) for Malignancy diagnosis by 24-months.

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

Time frame: up to 24 months

Population: Number of subjects diagnosed with primary lung cancer.

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).

Time frame: at the 1 month follow up visit

Population: Number of subjects who completed the ENB-PAQ at 1-month

Subject satisfaction evaluation at the 1 month visit. The question was overall, how satisfied were you with the ENB procedure. Options were: 1. Totally Dissatisfied 2. Dissatisfied 3. Neutral 4. Satisfied 5. Extremely Satisfied

Time frame: at the 1 month follow up visit

Population: Subjects who completed the 1-month subject satisfaction questionnaire (How satisfied are you with ENB on a scale of 1-5)

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.

Time frame: at index procedure visit

Population: Number of subjects where ENB was used to aid in placement of fiducial markers, and follow-up imaging data was available.

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.

Time frame: at index procedure visit

Population: Number of subjects where ENB was used to aid in pleural dye marking.

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.

Time frame: at index procedure visit

Population: Number of subjects where ENB was used to aid in lymph node biopsy.

Tissue adequacy for molecular genetic testing (if applicable).

Time frame: at index procedure visit

Population: This is the number of lesions diagnosed with primary lung adenocarcinoma or non-small-cell lung cancer not otherwise specified, where molecular genetic testing was attempted. This does not include all lesions biopsied as not all lesions had one of these specific diagnoses, nor did all these with these specific diagnoses have molecular testing attempted.