Trial Information

High Definition Bronchoscopy; an Exploratory Study of Diagnostic Value in Comparison to Standard White Light Bronchoscopy and Autofluorescence Bronchoscopy

Rationale Bronchoscopy is one of the most important procedures in diagnosis of lung cancer
and other pulmonary diseases. This procedures renders important anatomical information and
subtle changes in the epithelium or vascularity of the bronchial tree are clues to guide the
endoscopist in this procedure, especially in case of centrally located lung cancer. These
subtle changes may influence the choice of treatment, site of biopsy and resectability of
cancers when determining resection margins but also in case of multifocal premalignant
disease. A recently published meta-analysis has shown diagnostic superiority of
autofluorescence bronchoscopy (AFB) over routine white light bronchoscopy (WLB).
Furthermore, patients with a head and neck cancer have an increased risk of developing lung
cancer given their smoking habits. Through technological improvement a new technique has
become available in the form of high-definition (HD-) bronchoscopy. Current normal video
white light bronchoscopy is the standard, and video-autofluorescence bronchoscopy (AFB) is
offered by specialized centers only. The impact of this development with high-definition
videobronchoscopy using a 1.1 megapixel chip on the diagnostic performance of bronchoscopy
is however unknown.

Objective (primary and secondary outcome)

(1) Investigate sensitivity of HD bronchoscopy, with or without surface enhancement or tone
enhancement in comparison to AFB (the 'gold standard') and standard WLB for detecting
abnormalities of the tracheobronchial tree. Furthermore we aim to investigate determination
of resection margins of (suspected) malignancies in the glottic and supraglottic area or
centrally located lung cancer in comparison to autofluorescence bronchoscopy (SAFE 3000 dual
video mode) in a high risk population with biopsies from all suspect lesions identified by
either technique. (2) When the sensitivity and specificity of HD videobronchoscopy in either
mode in the abovementioned study is in the vicinity of the reported sensitivity and
specificity of SAFE3000 dual mode videobronchoscopy we suggest to use the results of this
study perform a power analysis. With this information it may then be possible to design a
new future study to compare sensitivity for detecting premalignant lesions in a high risk
population in a prospective study.

Study design This study is a descriptive exploratory randomized observational study with a
blinded post procedure analysis of the diagnostic performance of HD bronchoscopy in
comparison to WLB and AFB.

Study population Patients scheduled for diagnostic or therapeutic procedure under general
anesthesia by the cardiothoracic or thoracic surgeon or ear-, nose- and throat (ENT) surgeon
with suspected or proven lung cancer or head and neck cancer are eligible for this
exploratory study. Eligible are patients with ASA physical status 1-3 patients aged 18 years
or older. Ineligibility criteria are all known contraindications for diagnostic bronchoscopy
(bleeding disorders, indication for use of anticoagulant therapy (acenocoumarol, warfarins,
therapeutic dose of low molecular weight heparins or clopidogrel), known allergy for
lidocaine, known pulmonary hypertension, recent and/or uncontrolled cardiac disease).
Presence of contraindications for the use of laryngeal mask (anatomical abnormalities,
increased risk for intubation (mallampati score 4), ASA classification greater than or equal
to 4.

Study procedure Prior to surgery by the ENT surgeon or cardiothoracic surgeon bronchoscopy
will be performed by an experienced chest physician through a laryngeal mask under general
anaesthesia. Bronchoscopy will be performed in a standardized order using five different
imaging modes. The order of the different modes will be randomized. High-definition digital
videos will be made from all procedures without in screen indications of date, time or
reference to study site or patient identification. The five imaging modes used in this
study are: Standard white light videobronchoscopy (WLB); High Definition (HD-) bronchoscopy;
HD-bronchoscopy + surface enhancement; HD-bronchoscopy + tone enhancement and Auto
Fluorescence Bronchoscopy (AFB - SAFE3000) in dual video mode. All visible abnormalities
suspected for malignancy or pre-malignancy will be biopsied afterwards. The HD-digital
video's will be reviewed by the experienced bronchoscopists in random order and blinded for
patient, study site and date and scored using a predefined scoring system to describe
surface, vascularity and tumours. Premalignant lesions identified by multiple techniques are
considered as non-inferior. From each patient 5 HD- films will be generated. These films
will be reviewed in a blinded fashion and random order by two experienced pulmonologists and
an independent equally experienced third pulmonologist. When new clinically relevant
abnormalities are found the normally indicated diagnostic procedures will be followed and
performed immediately after completion of the videoregistration. All findings will be
disclosed to the patient and the physician in charge by the investigator and the impact of
these findings on the planned diagnostic or therapeutic procedure will be registered.

Main study parameter / endpoints The bronchoscopy videos will be scored by blinded
experienced endoscopists on epithelial changes, vascularity changes, presence or suspicion
of dysplasia, presence of suspicion of carcinoma in situ, and tumor margins. The study is a
descriptive exploratory study of diagnostic performance of HD-bronchoscopy using different
imaging techniques in comparison to standard white light bronchoscopy and autofluorescence
bronchoscopy in determining epithelial changes, changes in vascularity and tumour margins.
As a secondary outcome we aim, when differences are established between the different
bronchoscopy modes, to perform a power analysis to determine the feasibility of a
prospectively designed study to investigate the diagnostic performance of HD bronchoscopy.

Nature and extent of the burden and risks associated with participation, benefit and group
relatedness After start of the general anaesthesia for the planned operation a laryngeal
mask airway is inserted by the anesthesiologist. Bronchoscopy is then performed by a very
experienced pulmonologist using routine topical anesthesics. In this way the burden for the
patient and the risk of complications is very low. These patients have an indication for the
planned surgical procedure and have been evaluated by an anesthesiologist prior to the
procedure and are considered fit for surgery. The total anesthesia time for the planned
procedure will be increased by 10 to 15 minutes.

Bronchoscopy is a very safe diagnostic procedure, the reported complications are in general
attributable to te more invasive diagnostic procedures performed during that diagnostic
bronchoscopy like biopsy, lavage and needle aspirations. This is not the aim of this study,
invasive diagnostic procedures will only be performed in case of a clinically relevant new
finding. In general we expect that the vast majority of the patients involved will not have
any benefit of participating in this study