To evaluate the added value of nCLE-imaging to conventional bronchoscopic peripheral lung lesion analysis on the diagnostic yield.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine if the addition of nCLE-imaging to conventional bronchoscopic
peripheral lung lesion analysis results in an improved diagnostic yield.
Secondary outcome
1. 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 reference standard).
2. Procedure duration (from bronchoscope insertion until removal)
3. Amount and proportion of needle repositionings (defined as the selection of
a different distal airway for tissue sampling) and needle fine-tuning tuned
(defined as moving the needle within the same distal airway) per arm
4. To assess the diagnostic yield for several lesion and procedural
characteristics (lesion size, bronchus sign, eccentric vs concentric vs absent
radial EBUS image, location)
5. Fluoroscopy time and radiation dose
6. To extend the nCLE image atlas for malignant and benign pathologies
7. To assess the yield of ROSE for a classifying diagnosis
8. To assess the ability of ROSE to provide tool-in-lesion-confirmation (the
acquisition of tissue not related to airway/lung parenchyma sampling such as
bronchus epithelium/blood contamination including tissue not suitable for a
specific diagnosis such as atypical cells)
9. Complication rate (defined as any complication occurring during or directly
after the bronchoscopic procedure or any procedure-related complication in the
follow-up period).
10. Proportion of patients per arm that need additional diagnostic procedures
(CT-guided transthoracic biopsies, surgical diagnostics and/or additional
bronchoscopy) after the bronchoscopy during the 6-month follow-up period.
11. Create an algorithm for automated nCLE criteria recognition (for example
machine learning)
Background summary
Lung cancer screening and the increasing use of chest-computed tomography (CT)
has led to an increase in the number of (incidental) found suspected malignant
lung lesions. Since tissue acquisition for pathological analysis is
prerequisite for diagnosis and optimal treatment, a drastic increase in the
number of patients that need to undergo bronchoscopy is expected.
Over 70% of the suspected lesions develop in the periphery of the lung and are
therefore not visible during conventional bronchoscopy. Although several
bronchoscopic navigational techniques demonstrated an improved navigation
towards the target lesion, the diagnostic yield remains suboptimal due to a
substantial near-miss rate. As a result, the need for complementary
bronchoscopic guidance that provides real-time feedback on the correct
positioning of the biopsy instruments is urgent.
Needle-based Confocal laser endomicroscopy (nCLE) is a novel high-resolution
imaging technique that uses an excitation laser light to create 'real-time'
microscopic images of tissues. nCLE can be integrated into the biopsy needle,
allowing real-time cancer detection at the tip of the biopsy needle during
bronchoscopy. The confocal microscope captures autofluorescence of tissues or,
combined with intravenously (IV) infused fluorophores (such as fluorescein)
allows imaging of individual tumor cells. Recent studies on nCLE-imaging in
lung tumors and metastatic lymph nodes have identified and validated nCLE
criteria for malignancy (enlarged pleomorphic cells, dark clumps and
directional streaming) and airway/lung parenchyma (alveoli, elastin fibres of
the conducting airway, bronchial epithelium and still image) and granuloma.
Preliminary results of an ongoingstudy in our center demonstrate that these
nCLE-criteria can be used in real-time to fine-tune the needle positioning
during ongoing bronchoscopy and thereby potentially improve the diagnostic
yield.
In the present study, we aim to evaluate the added value of nCLE-imaging (smart
needle) to the conventional used bronchoscopic approach for peripheral lung
lesion analysis.
Study objective
To evaluate the added value of nCLE-imaging to conventional bronchoscopic
peripheral lung lesion analysis on the diagnostic yield.
Study design
Investigator-initiated, international, multi-center randomized controlled trial
including university and general hospitals.
Intervention
Bronchoscopy will be performed as usual, including radial endobronchial
ultrasound (r-EBUS) and optionally fluoroscopy, followed by transbronchial
needle aspiration (TBNA and (cryo-)biopsies (control arm). In the study arm,
nCLE-imaging will be added prior to tissue acquisition to fine-tune the
sampling area. Cytology staining for rapid onsite evaluation (ROSE) and
cellblock will be performed according to local practice (ROSE mandatory for
first pass).
Study burden and risks
A participating patient who enters the study and will be randomized to the
interventional arm might benefit from improved diagnostic accuracy, however
this has yet to be proven and is subject of the study. However, future patients
might benefit from improved lung cancer diagnostics based on study findings.
The risks of study participation is neglectable 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 related adverse events occurred. Right before nCLE-imaging,
fluorescein will be administered intravenously through an existing venous
entrance. Fluorescein is a commonly 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 (1). nCLE measurements will be performed
during bronchoscopic work-up and is followed by conventional cytological
aspirations (routine work up), without the need for additional 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 sedated for the bronchoscopic procedure. In conclusion we
believe that the burden and risks associated with study participation (up to 10
minutes additional sedation time and application of fluorescein) are
neglectable.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
• >=18 years of age
• Suspected malignant peripheral lung lesion with an indication for a
bronchoscopic diagnostic work-up
• Solid part of the lesion must be >10 mm
• Largest dimension of lesion size on CT equal to or less than 30 mm
• Bronchus sign on pre-procedural CT or estimated confidence for successful
navigation to the nodule resulting in a r-EBUS signal
• 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
• 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)
• Inability to follow-up
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 |
|---|---|
| ClinicalTrials.gov | NCT06079970 |
| CCMO | NL83267.018.22 |