Safety and efficacy of a flexible endobronchial sampling instrument that obtains a CORe sample from KeY suspected areas of pulmonary and mediastinal lesions.

Early diagnosis of lung cancer can improve treatment options and consequently
improve survival and prognosis. Navigation bronchoscopy (NB) is a minimal
invasive diagnostic procedure with a low complication rate and a relatively
high diagnostic yield. It uses a flexible bronchoscope in combination with
extended working catheters and imaging techniques to accurately reach and
sample small peripheral pulmonary nodules. Using NB we are able to accurately
reach the lesion in ± 90% of all cases, but despite that, the average
diagnostic yield is approximately 75% (Kops et al., Lung Cancer 2023). This
discrepancy between getting there and obtaining a diagnosis might be explained
by the manner in which we sample the lesion. The biopsy techniques currently in
use are fine needle aspiration, forceps biopsy and cryobiopsy. These tools are
used in combination with one another, and multiple samples per tool are taken
in routine clinical practice as they do not allow a tru-cut sample from the
suspected lesion in a single go. Due to motion as a consequence of tool in
catheter insertion, lesion stiffness, breathing and or intermittent catheter
movement in-between samples, repeated sampling is required. The discrepancy
between getting there and getting a diagnosis in even the most recent
literature shows there is considerable margin of error. There seems to be high
demand for a sampling tool which might bridge this gap between navigation
success and an accurate diagnostic outcome. The COReKEY investigational device
(hereafter named Investigational Device) is a new biopsy instrument that
provides a cross-sectional sample of the nodule. The design is based on the
spirotome technique, which is widely implemented and the preferred sampling
tool in other forms of biopsy, such as CT guided transthoracic biopsy (TTNB), a
procedure with a high diagnostic yield of approximately 90% [1]. This new
sampling tool only needs 1 or 2 samples to obtain a core biopsy of the
suspected lesion and can potentially increase the diagnostic yield of the
navigation bronchoscopy procedure. This clinical feasibility study aims to
assess the safety and efficacy of the Investigational Device in the navigation
bronchoscopy procedure compared to the conventional sampling strategy

The primary objective of this clinical feasibility study is to assess the
overall diagnostic yield of the Investigational Device in comparison to
standard care. The secondary objective is to assess the safety issues that
possibly occur while using the Investigational Device. Other secondary
objectives include the assessment of tool-in-lesion confirmation of the
Investigational Device on cone-beam CT (CBCT) as compared to conventional
sampling tools, sampling tool characteristics (duration and counts),
ease-of-use of the Investigational Device during tissue sampling, pathology
outcome of samples analysed during rapid onsite evaluation (ROSE), and if
sufficient tissue is present for later full molecular analysis.

This is a prospective, single-center, interventional feasibility study at the
Radboud UMC in Nijmegen. The safety and efficacy of the Investigational Device
in the navigation bronchoscopy procedure as performed per routine clinical
practice will be assessed.

The navigation bronchoscopy procedure consists of three phases: (1) navigation,
(2) confirmation of the correct position and (3) tissue acquisition of the
pulmonary nodule. The navigation and confirmation phases are performed
according to standard practice, with the Investigational Device being used only
during the tissue acquisition phase. All included patients will undergo
sampling with both conventional tools (conventional sampling strategy) and the
Investigational Device (Investigational Device Strategy). The conventional
sampling strategy will be standardized for optimized comparison: For every
patient, 3 samples with transbronchial needle (TBNA) will be taken, followed by
a minimum of 3 samples with forceps. If these samples do not provided a
preliminary diagnosis suspicious of malignancy, as determined by rapid onsite
evaluation (ROSE), additional cryobiopsy sampling will be obtained. Samples
will be collected in separate containers per sampling tool. This will allow
diagnostic yield comparison between different sampling strategies, while
maintaining standard practice quality of care. The Investigation Device
strategy will include sampling with the investigational device at least once,
as per manufacturer*s instructions by *screwing* the tool into place and
sliding over the secondary cutting cannula to extract the sampling tissue from
the peripheral pulmonary lesion.

Patients will be randomized for sampling order. 1) sampling with the
Investigational Device first followed by conventional tools. 2) sampling with
conventional tools first followed by the Investigational Device. This will
minimize the bias that previous sampling might have on subsequent sampling
(e.g. because of limited bleeding around the lesion obscuring vision on image
guidance). The obtained samples (both conventional and Investigational Device
samples) are analyzed for ROSE and pathological assessment.

The expected potential risks of including the Investigational Device in the
navigation bronchoscopy procedure are low. During the conventional NB
procedure, a pneumothorax and/or a bleeding may occur. The pneumothorax rate
during the conventional NB procedure in the Radboudumc was 2.6%, while the
incidence of bleeding was 1.0% based on all performed procedures between July
2020 and december 2021 (Kops et al. 2023, submitted). During this clinical
study the currently used sampling tools will be compared with the
Investigational Device in an intrapatient analysis, which means that per
patient both sampling techniques will be used. This could potentially increase
the amount of complications, because more samples are taken from the lung
nodule. The complication rates should, however, not increase by 5% in this
investigation study when compared to our previous findings.

The expected benefit from the Investigational Device is the increase in
diagnostic accuracy because a cross-sectional sample is provided by the
Investigational Device instead of a small area of the nodule.