A multicenter study evaluating the diagnostic value for vascular abnormalities of High Definition Bronchoscopy when combined with i-scan Imaging Technology compared to High Defintion Bronchoscopy alone

Videobronchoscopy is an essential diagnostic procedure for evaluation of the
central airways and pivotal for the diagnosis and staging of lung cancer.
Through technological improvement new technique have become available in the
form of high-definition (HD+) bronchoscopy. Furthermore, in combination with
improved video processor unit this HD bronchoscope offers post processing real
time image enhancement (i-scan Technology) [Kodoshima WJG 2010]. Our earlier
exploratory study showed that HD+bronchoscopy with i-scan detected
significantly more sites with abnormal and suspicious vascular patterns [van
der Heijden 2014- submitted]. The impact of this visual finding with high
definition videobronchoscopy using a 1.1 megapixel chip on the diagnostic
performance of bronchoscopy is however unknown since in this pilot study no
biopsies were taken.
In this study we therefore aim to investigate the PPV and diagnostic yield of
HD+ bronchoscopy, with or without surface enhancement or tone enhancement in
comparison to biopsy outcome of all sites with abnormal and / or suspicious
vascular patterns in patients with known or suspected lung cancer.

Primary objective:
Determing the positive predictive value and diagnostic yield of HD+ i-scan
bronchoscopy for vascular pattern detection .
Secondary objectives:
1. To investigate the correlation of vascular abnormalities with histology
2. To investigate the impact of i-scan technology on the clinical approach or
follow-up plan
3. To investigate the interobserver variability
4. Investigate diagnostic performance and determing the positive predictive
value of HD+ i-scan bronchoscopy in comparison to normal HD-WL on demarcation
of tumour margins

The study is designed as a randomized controlled, cross-over, multi-centric
investigator initiated study where each patient serves as its own control.
A total of 5 centers in Europe will participate with this study. We aim to
start in October 2014 and complete inclusion to the study within one year, by
October 2015.

Patients will undergo a bronchoscopy with Pentax EB1990i HD-bronchoscope in
combination with Pentax EPKi series videoprocessor investigating the entire
bronchial tree. Three modalities will be used: (1) HD+, (2) HD+ surface
enhancement (SE, i-scan1) and (3) HD+ surface enhancement and tone enhancement
(TE-c, i-scan2).
When sites with abnormal or suspicious vascular patterns are detected the
investigator will change to a normal bronchoscope and take biopsies from each
site and a biopsy from a normal secondary carina on the contralateral site as
control. Changing of scopes is mandatory since the working channel of the
EB1990i bronchoscope does not allow introduction of a biopsy forceps. Finally
any other indicated procedures will be performed at the discretion of the local
investigator.
The local investigator will immediately complete the CRF identifying all
locally identified and biopsied suspicious sites. Furthermore in the CRF will
identify whether this study-bronchoscopy has altered the clinical workup or
treatment of this patient and register any complications.
All videos will be analyzed centrally at RadboudUMC in random order, blinded
for patient outcome and type of bronchoscopy, by two experienced investigators
to determine interobserver variability.
All videos will be reviewed in joined reading at RadboudUMC with disclosure of
the pathology outcome of biopsies taken by the local investigator to correlate
visual scores to pathology and determine preferred modality.

The burden and risks associated with participation are considered low. Patients
that will be approached for study participation have an indication for a
bronchoscopy investigation. When they participate in this study the procedure
will be performed more extensively with a dedicated HD+ bronchoscope followed
by a bronchoscopy using a standard bronchoscope when tissue sampling is
indicated. The entire procedure will take an additional 5-10 minutes to
complete. However after inspection with the HD bronchoscope a regular
bronchoscope is needed to obtain biopsies and perform the indicated other
diagnostic procedures.
Bronchoscopy is a very safe diagnostic procedure, the reported complications
are in general attributable to the more invasive diagnostic procedures
performed during that diagnostic bronchoscopy like biopsy, lavage and needle
aspirations. The chance of complications like bleeding and infection is low (<
1%).
In general we expect that the majority of the patients involved will not have a
clinical relevant benefit of participating in this study other than that the
bronchoscopy will always be performed by very experienced bronchoscopist.