Use of the Biocartis Idylla ™ Platform for the Detection of Epidermal Growth Factor Receptor, B-RAF and K-RAS Proto-oncogene Mutations in Liquid Based Cytology Specimens and Blood Plasma Samples From Patients With Non Small Cell Lung Carcinoma and Pancreatic Adenocarcinoma

Advances in medicine have resulted in the development of specific drugs to treat cancers that express certain mutations. The detection of epidermal growth factor receptor (EGFR), BRAF and KRAS mutations (10-30%, 1-2%, 25% respectively) in lung cancers and KRAS mutations in 94% of pancreatic cancers allows these patients to be treated with a wider cohort of drugs, potentially resulting in progression free, prolonged survival, with a more favourable tolerability and less adverse effects compared with chemotherapy.

NHS England has a test directory which lists the molecular tests that trusts should provide for cancer patients. EGRF, KRAS and BRAF are listed in this directory. Verification of the use of the Idylla would enable this trust to provide all of these molecular tests effectively. Lung and pancreatic cancers both present at advanced disease states and therefore a rapid turnaround of test results is vital. Currently laboratories rely on the use of formalin-fixed paraffin embedded (FFPE) samples for EGFR testing.

Clots are produced in the laboratory to congeal all of the tissue fragments and cells into one solid mass. The clotted sample is then fixed in formalin and processed. The current processing and reporting time is 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 fixative called Preservcyt. Previous research has been conducted to determine whether LBC samples can be used instead of FFPE samples for mutation detection with favourable results. A switch to the use of LBC samples for mutation analysis on the Idylla would remove multiple processing steps and make use of residual samples that are currently discarded, which optimises the amount of testing that we can run on small cytology samples, reducing the likelihood of repeat procedures for patients. Alcohol fixation is regarded as a superior method of DNA and RNA preservation, therefore better molecular results will be seen.

Detection of circulating tumour cell mutations could in the future negate the need for invasive procedures, with patients requiring a simple blood test for diagnosis.

The aim of the study is to determine whether LBC samples are a feasible and reliable alternative to FFPE samples for detecting mutations in LBC samples and blood using the Idylla platform.