Table 2 Definitions and overview of study endpoints

- Primary endpoints will be calculated separately for needle aspiration, forceps biopsy, and the combination of the two. For initially negative results, the final diagnosis will be confirmed based on the 12 months of clinical follow-up

- Diagnostic accuracy:

Proportion of subjects in whom the ENB-guided biopsy yielded a definite diagnosis

 = (malignant and benign diagnosis by modality)/(biopsied lung lesions)

- Sensitivity:

 = (Malignancy confirmed by modality)/(Number of malignancies confirmed at 12-month follow-up)

- Specificity:

 = (Benign confirmed by modality)/(Number of benign lesions confirmed at 12-month follow-up)

- Positive predictive value:

 = (True malignant lesions)/(Number of malignant lesions by modality)

- Negative predictive value:

 = (True benign lesions)/(Number of benign lesions by modality)

Secondary endpoints

- Secondary outcomes will be calculated separately for needle aspiration and forceps biopsy

- Navigation success:

Target lesion successfully reached with the biopsy tool; identified by the dedicated navigation software

- Procedure time:

Duration from the initial introduction of the tool to the final removal of the biopsy tool

- Time per biopsy attempt:

Procedure time divided by the number of biopsy attempts

- Successful acquisition of core tissue:

Acquisition of a fresh tissue available for histological examination

Procedure-related adverse events

-Pneumothorax

Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated

Grade 2: symptomatic; intervention indicated (e.g., thoracic tube insertion without pleurodesis)

Grade 3: pleurodesis and/or operative intervention indicated; hospitalization indicated

Grade 4: life-threatening consequences; urgent intervention indicated

Grade 5: death

Bronchopulmonary hemorrhage

Grade 1: mild symptoms: intervention not indicated

Grade 2: moderate symptoms: invasive intervention not indicated

Grade 3: transfusion indicated; invasive intervention indicated; hospitalization

Grade 4: life-threatening consequences; intubation or urgent intervention indicated

Grade 5: death

Respiratory failure:

Life-threatening situations with urgent intubation or ventilator support indicated