This study aims to investigate proof of principle of utilizing nCLE during CBCT-NB navigation bronchoscopy. A confirmatory CBCT spin is considered the gold standard for tool-in-lesion but is associated with additional radiation exposure. We aim to…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
CBCT-NB navigation success: tool-in-lesion OR unsuccessful navigation
nCLE tool-in-lesion confirmation: in-lesion nCLE criteria seen
Secondary outcome
1. Technical feasibility: proportion of nCLE imaging that are successful
(meaning that the preloaded needle can be advanced through the working channel,
puncture the nodule, advance the CLE probe and start imaging) resulting good
quality images (feasibility meaning >90% good quality interpretable images).
This is based on previous nCLE studies where nCLE was employed during
conventional bronchoscopy and >85% of images were of good quality.
2. Safety: number of (severe) adverse events ((S)AEs) and investigational
proce-dure-related adverse events (AEs) (<4% severe adverse events (1/25) will
be con-sidered acceptable). Pneumothorax is one of the most common reported
compli-cation of endobronchial procedures with transbronchial needle aspiration
and biop-sies and occurs between 1-6% of CBCT-NB procedures. Often, medical
interven-tional such as chest tube placement is not needed. Intraproce-dural
haemorrhage requiring medical intervention will also be reported based on the
CTCAE and is also reported in ~4-5% of cases.
3. Diagnostic yield: the proportion of patients in whom the bronchoscopic
procedure results in a definitive diagnosis out of the total number of patients
that have re-ceived the diagnostic bronchoscopic procedure.
4. Diagnostic sensitivity for malignancy: defined as the proportion of patients
that have malignancy diagnosed by bronchoscopic tissue sampling, relative to
the total number of patients with a final diagnosis of malignancy as determined
by the ref-erence standard.
5. Sensitivity, specificity and accuracy of real-time nCLE imaging assessment,
meaning identification of the known nCLE criteria (malignancy, granuloma,
air-way/lung parenchyma)
6. Sensitivity, specificity and accuracy of post-procedure nCLE image
assessment, meaning identification of the known nCLE criteria (malignancy,
granuloma, air-way/lung parenchyma)
7. Interobserver agreement (IOA) and intraobserver reliability (IOR) or the
post-procedure nCLE image assessment
8. Total procedure duration: from introduction of the scope to removal of the
scope
9. Navigation time: from start of navigation modality until decision to start
biopsy
10. Cumulative radiation exposure of the procedure: dose area product and
effective dose of entire procedure
11. Number of cone beam spins
12. Fluoroscopy time in minutes
Background summary
Lung cancer remains a significant problem in current society with one of the
higher cancer related mortality rates. The increased use of chest computed
tomography (CT) and the poten-tial future lung cancer screening result in an
increased detection of early-stage peripheral lung cancer. Bronchoscopies are
often indicated to collect tissue for diagnosis and to aid treatment decision
making.
Diagnostic bronchoscopy for peripheral lung nodules remains challenging despite
many tech-nological innovations. The procedure comprises three essential
pillars needed for a diagnostic success: navigation to the lesion,
tool-in-lesion confirmation and adequate tissue retrieval.
Cone beam computed tomography navigation bronchoscopy (CBCT-NB) is a fairly new
technique that provides coarse navigation to the pulmonary lesion with
real-time guidance us-ing augmented fluoroscopy (AF). An initial CBCT scan
allows for segmentation of the target lesion and selecting the optimal pathway.
Repeated CBCT scanning allows for confirmation that the target has been reached
(navigation success) or if repositioning is needed.
Although the technique is very promising, an often discussed disadvantage of
CBCT is the inherent use of ionizing radiation, limited availability and
challenges with small nodules located in the basal and posterior fields due to
respiratory motion. Most procedures ask for multiple CBCT spins both for
trajectory planning, tool adjustments and tool-in-lesion confirmation. This,
combined with extensive use of fluoroscopy is associated with radiation
exposure for both patients and the investigation team. Additionally, CBCT-NB
with AF provides information from a global perspective rather than a local
perspective. In experienced centers, coarse naviga-tion guidance seems of
lesser concern and fine positioning and optimal tissue sampling are the biggest
problems to be overcome. The persistently low diagnostic yield of navigation
bronchoscopies can for the majority be attributed mispositioning of the tools
in *the last centi-meter*. Therefore there is a need for complementary
techniques providing real-time infor-mation for fine-tuning the needle position
such as needle-based confocal laser endomicros-copy (nCLE) also called the
*smart needle*.
Confocal laser endomicroscopy (CLE) is a high-resolution microscopic technique
that visual-izes individual cells in real-time at the tip of the biopsy needle,
allowing for real-time micro-scopic feedback for fine tuning needle positioning
and tool-in-lesion confirmation. Currently, it is unknown which (combination
of) techniques are the most optimal (i.e., leading to a high di-agnostic yield
and cost-effective). Therefore, research is needed to investigate the potential
of new (combinations of) techniques. To date, there are no reports on the
combination of CBCT-NB with nCLE.
Study objective
This study aims to investigate proof of principle of utilizing nCLE during
CBCT-NB navigation bronchoscopy. A confirmatory CBCT spin is considered the
gold standard for tool-in-lesion but is associated with additional radiation
exposure. We aim to investigate the concordance between CBCT navigation success
(tool-in-lesion on CBCT spin) and nCLE tool-in-lesion confirmation
(tool-in-lesion nCLE criteria observed). We also hypothesize that nCLE could
reduce or replace the need for additional confirmatory CBCT scans and limit
fluoroscopy use.
Study design
Investigator-initiated proof of principle medical device study
Study burden and risks
A participating patient who enters the study and will not benefit from study
participation, how-ever risks related to this study are negligible.
Additionally, future patients might benefit from improved lung cancer
diagnostics based on study findings. Only patients that have a clinical
indication for CBCT-NB will participate in this study. Risks related to CBCT-NB
(such as radi-ation exposure) are not extra for the study but part of clinical
practice.
From experience we know that the risks of study participation are negligible as
previous study publications showed that nCLE-imaging and IV fluorescein
administration are safe. In the prior bronchoscopic nCLE studies in Amsterdam
UMC, including over 50 patients, no study proce-dure or device related adverse
events occurred. Right before nCLE-imaging, fluorescein will be administered
intravenously through an existing venous entrance. Fluorescein is a com-monly
used dye in hospitals (e.g. in ophthalmology) and adverse reactions are rare
(1.1%) and mild in character. In 2010, Wallace et al. published a retrospective
study of all confocal laser endomicroscopy procedures performed between January
2003 and November 2008, with in total 2,272 procedures and no serious adverse
events related to fluorescein injection were identified. nCLE measurements will
be performed during bronchoscopic work-up and is followed by conventional
cytological aspirations (routine work up), without the need for addi-tional
aspirations or biopsies for research purposes. Estimated prolonged endoscopy
time due to study participation is approximately 10 minutes. Patient will not
be aware of this as patients are already deeply sedated for the procedure. In
conclusion we believe that the burden and risks associated with study
participation (up to 10 minutes additional sedation time and appli-cation of
fluorescein) are negligible.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
• 18 years or older
• Suspected pulmonary nodule with an indication for CBCT-NB (decided by
multidisciplinary tumour board)
• Nodule must be solid or partially solid
• Solid part of the nodule must be at least 8 mm
• Largest dimension of the nodule on CT equal or less than 30 mm
• Ability to understand and willingness to sign a written informed consent
Exclusion criteria
• Inability or non-willingness to provide informed consent
• Patients with an endobronchial visible lung tumor on bronchoscopic inspection
• Patients in which the target lesion is within reach of the linear EBUS scope
• Lung nodules that resolved at the time of index intraprocedural CBCT
• Failure to comply with the study protocol
• Patients with known allergy for fluorescein or risk factors for an allergic
reaction
• Pregnant or breastfeeding women
• Patients with hemodynamic instability
• Patients with refractory hypoxemia
• Patients with a therapeutic anticoagulant that cannot be held for an
appropriate interval before the procedure
• Patients who are unable to tolerate general anesthesia according to the
anesthesiologist
• Patient undergoing chemotherapy as several chemotherapies have fluorescent
properties at the same wavelength (e.g. doxorubicin)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL86502.018.24 |