Clinical Trial Details
— Status: Suspended
Administrative data
| NCT number |
NCT05569629 |
| Other study ID # |
PrePostBW |
| Secondary ID |
|
| Status |
Suspended |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2024 |
| Est. completion date |
September 30, 2025 |
Study information
| Verified date |
May 2024 |
| Source |
Chinese University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objective: To identify the optimal position of bronchial washing (BW) in the sequence of
bronchoscopic sampling in order to maximize the ability to confirm malignancy for
endoscopically visible tumours.
Hypothesis to be tested: The investigators hypothesize that the diagnostic yield, with the
incorporation of contemporary cytology processing techniques, of combined BW before and after
endobronchial biopsy (EBBx) / bronchial brushing (BB) is higher than that of single BW after
EBBx / BB.
Design and subjects: This is a prospective, randomized controlled study to be conducted in
the medical department of a tertiary care hospital in Hong Kong involving patients who will
receive bronchoscopy. Patients will be recruited if an endoscopically visible tumour is
suspected.
Study instruments: Patients will be randomized into two groups. The diagnostic yield of
confirming malignancy for endoscopically visible tumours, with the incorporation of
contemporary cytology processing techniques, will be compared between obtaining BW before and
after EBBx / BB, and obtaining single BW after EBBx / BB.
Main outcome measures: Only patients with a definite cytological or histological diagnosis of
lung cancer will be included in further analyses. The diagnostic yield of diagnosing lung
cancer between the pre & post-EBBx/BB group and post-EBBx/BB group will be compared by the
Chi-square test as an intergroup comparison.
Description:
Lung cancer is the most common cancer in Hong Kong, and also ranks first in cancer-related
mortality. Early diagnosis of lung cancer is pivotal to facilitating early treatment and
ensuring a better prognosis. In those centrally located tumours, especially those arising
from the bronchus and endoscopically visible, bronchoscopy with endobronchial biopsy (EBBx),
bronchial brushing (BB) and bronchial washing (BW) are the three major endoscopic techniques
to establish the pathological diagnosis. The diagnostic yield of EBBx is the highest among
the three, ranging from 48% to 79%, but occasionally fails to give the proper diagnosis
because of thick necrotic materials covering the tumours, crushed artefacts and inappropriate
targeting. Supplementing BW, a cost-effective procedure, can increase the overall diagnostic
yield by 2% to 12% beyond EBBx alone. The final diagnostic yield can be as high as up to 97%
for endoscopically visible tumours by combining EBBx, BB and BW in a single bronchoscopy
procedure. Therefore, various guidelines recommend performing these three procedures to
maximize the diagnostic yield and the volume of tissue obtained for phenotyping and
genotyping of advanced non-small cell lung carcinoma.
The sequence of these three endoscopic sampling techniques, especially the relative position
of BW, has been controversial. BW obtains the return of normal saline after instilling over
an endoscopically visible tumour, which contains exfoliated malignant cells from the tumour.
It is logical that the shedding of malignant cells is increased after breaking or ablating
the bronchial mucosa by EBBx and BB (EBBx / BB), but this hypothesis was not supported by
several prospective studies. However, these studies were limited by inconsistent
incorporation of BB, and a majority of them were self-controlled comparative studies. The
only randomized, multi-centre study by Lee et al showed no significant difference in the
diagnostic yield of BB before and after EBBx, but again, BB was not consistently performed in
the study. Instead, the diagnostic yield by combining the BW before and after EBBx, with or
without BB, was higher than a single BW alone. Although the BW obtained after EBBx / BB was
more haemorrhagic in appearance, the interpretation was considered unaffected. Guidelines for
bronchoscopy addressing the sequence of endoscopic sampling are conflicting. BTS guideline
commented that the sequence of sample acquisition is not important, while the Indian
guideline recommends BW should be performed both before and after EBBx / BB. The guideline
issued by the American College of Chest Physicians did not address this issue. Nowadays, more
sophisticated endoscopic sampling techniques, e.g. cryobiopsy, are available with a high
diagnostic yield, but they usually carry higher procedural risk and are only available in
tertiary centres with expertise. Therefore, it is necessary to optimize the sampling sequence
with existing and widely available techniques.
The method of cytological processing plays a critical part in optimizing the diagnostic yield
of BW. Conventional cytology (CC) preparation was employed in the above-mentioned studies,
and the authors did not address the reason for negative BW cytology. Only Van der MA drift et
al identified the problem of poor cellularity in a number of negative BW specimens. In the
past decade, the introduction of liquid-based cytology (LBC) and cell block (CB) preparation
to reduce unsatisfactory cytological results and eliminate obscuring factors such as blood,
inflammation, and mucus has improved the overall diagnostic yield in addition to CC. CB also
serves as another source of diagnostic material for immunohistochemical (IHC) and molecular
studies. The recent developments in whole-slide scanners with increased throughput and
z-stacking three-dimensionally reconstructed images allow for accurate and reproducible
cellular quantification and cytomorphometric analysis. Digital pathology-based quantification
can complement, validate and provide added analysis to the yield, diagnostic accuracy and
cytological effects in different protocols for bronchoscopic sampling. With the incorporation
of LBC and CB techniques and an optimal sequence of bronchoscopic sampling, the diagnostic
accuracy, cellular yield and specimen quality can be further improved and guide personalized
oncological treatment.
The investigators believe that combining EBBx and BB together is important to ablate a larger
area of bronchial mucosa than either procedure alone, and potentially release more malignant
cells during the BW. To date, there is no randomized controlled trial comparing the
diagnostic yield of combined BW before and after EBBx / BB, and BW after EEBx / BB. The
investigators hypothesize that the diagnostic yield, with the incorporation of contemporary
cytology processing techniques, of combined BW before and after EBBx / BB is higher than that
of single BW after EBBx / BB. The aim of this study is to identify the optimal position of BW
in the sequence of bronchoscopic sampling in order to maximize the ability to confirm
malignancy for endoscopically visible tumours.
