Brief Title
The Detection of EGFR Mutations in Liquid Based Cytology Samples
Official Title
Use of the Idylla Platform for the Detection of EGFR Mutations in Liquid- Based Cytology Specimens of Lung Adenocarcinoma
Brief Summary
This study will investigate whether liquid based cytology specimens are a feasible
alternative to formalin-fixed paraffin embedded histology samples for detection of epidermal
growth factor receptor (EGFR) mutations in lung adenocarcinoma using the Biocartis Idylla
platform. The Biocartis Idylla is a fully automated, real-time PCR based molecular
diagnostics system. The Idylla carries out the entire analytical process from sample to
result.
This study will be based in the cytology department at Royal Cornwall Hospital as part of a
service improvement. It will use residual material from existing samples sent to the
laboratory as part of the routine service. It will use existing material from patients
diagnosed with lung adenocarcinoma by cytology using the current, validated procedure which
uses formalin-fixed paraffin embedded (FFPE) samples over a 10 month period. EGFR mutation
results obtained using the validated procedure (formalin fixed paraffin embedded) will be
compared to those produced using liquid based cytology samples.
Detailed Description
The presence of activating epidermal growth factor receptor (EGFR) mutations identifies
patients with lung adenocarcinoma in which EGFR tyrosine kinase inhibitors (TKI) can be a
potential first-line treatment. The TKIs currently available are erlotinib, gefitinib and
afatinib, which work by blocking receptor tyrosine kinase activity, thereby halting cell
proliferation and causing cell death. Several studies have found that first-line TKI
treatment prolongs progression free survival in comparison to standard chemotherapy, and is
also associated with a more favourable tolerability and less adverse effects.
Samples for EGFR mutation analysis are collected from patients by endobronchial
ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and bronchial brushings and
washings. EBUS-TBNA provides a minimally invasive method for tissue sampling from
radiologically suspicious lymph nodes in the chest using a fine-gauge needle. Samples
obtained are collected and sent to the laboratory for processing. At present, laboratories
rely on the use of formalin-fixed paraffin embedded (FFPE) samples for EGFR testing,
therefore clots are produced in the laboratory using the collected tissue fragments. The
clotted sample must then be fixed in formalin before being processed in the histology
laboratory to produce slides for microscopic examination by the consultant pathologist. Once
adenocarcinoma is diagnosed, FFPE samples are then sent for EGFR mutation analysis. The
current laboratory process takes approximately 5 days.
Liquid based cytology (LBC) specimens obtained through the same sampling procedures are also
prepared in the laboratory and fixed using a methanol based solution (PreservCyt). Previous
research has been carried out to determine whether LBC samples can be used instead of FFPE
samples for the detection of EGFR mutations with favourable results. Examples of this include
research by Zhao et al (2017), Satouchi et al (2017), De Luca et al (2017) and Malapelle et
al (2016). A switch to the use of LBC samples for EGFR testing would remove multiple
processing steps in the sample pathway to mutation testing. Immunocytochemistry will be
required in the majority of cases for confirmation of adenocarcinoma. This faster pathway
would be beneficial in cases of already confirmed adenocarcinoma for second line EGFR
treatment testing (T790M) and in cases where the residual cytology sample, that would
normally be discarded, can be utilised for testing, optimising the potential of the sampling.
This study will investigate whether LBC specimens are a feasible alternative to FFPE samples
for detection of EGFR mutations using the Biocartis Idylla platform.
If liquid based cytology samples are found to be a feasible alternative this could result in:
- Quicker turnaround time of results in cases of unequivocal adenocarcinoma. This would
provide earlier access to TKIs allowing for optimal patient management.
- Easier sample preparation within the laboratory
- Would allow for efficient use of all material acquired from the sampling procedures. For
example additional testing could be performed on the FFPE tissue in place of EGFR
testing which could aid in diagnosis. Increase in efficient use of material could also
prevent repeats of the EBUS procedure on patients.
- Methanol has been found to be a superior fixative than formalin. Use of liquid based
cytology samples may allow for better results from molecular testing.
- Would provide support to the idea that molecular testing for other cancers may be able
to be carried out on liquid based cytology samples for example BRAF mutation testing for
melanoma. Also provides support of the use of other liquid samples for molecular testing
such as blood samples which could be tested for circulating tumour cells (less invasive
sampling).
Study Type
Observational
Primary Outcome
Significance of using liquid based cytology samples for EGFR mutation detection using the Idylla platform (in comparison to the use of FFPE samples)
Condition
Adenocarcinoma of Lung
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
13
Start Date
May 7, 2019
Completion Date
February 24, 2020
Primary Completion Date
February 24, 2020
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of lung adenocarcinoma by the cytology laboratory at Royal Cornwall Hospital
Trust using the current, validated method on formalin-fixed paraffin embedded samples
within the time period of the study. This will include both patients with wild type
lung adenocarcinoma and also patients with lung adenocarcinoma with EGFR mutations.
Exclusion Criteria:
- Samples received by the cytology laboratory following the sampling procedures that are
not diagnosed as lung adenocarcinoma during the time period of the study.
Gender
All
Ages
18 Years - 100 Years
Accepts Healthy Volunteers
No
Contacts
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Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT04086680
Organization ID
2019.RCHT.24
Responsible Party
Sponsor
Study Sponsor
Royal Cornwall Hospitals Trust
Collaborators
Biocartis
Study Sponsor
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Verification Date
June 2019