Validating Treatment Options for Lung Cancer Patients: Automated Rapid EGFR
Pearl Huey, Cellular Pathology, Betsi Cadwaladr University Health Board
Alison Finall, Suzie Howarth, Chris Bowden, Gareth Davies, Cellular Pathology Department, Swansea Bay University Health Board
Gwion Emlyn, Alison Davies, Soraia Ribeiro, Alex Makanga, Cellular Pathology Department, Betsi Cadwaladr University Health Board
Andrew Hall, Life Science Hub
Anna Mullard, Melisa Van Der Bijk, Kelly Andrews, Betsi Cadwaladr University Health Board
This exciting project brought together teams from Betsi Cadwaladr University Health Board, Swansea Bay University Health Board, and the Life Science Hub to evaluate the possibility of using a fully automated platform to deliver rapid EGFR tests locally in order to help optimise treatment options for very ill patients with late-stage lung cancer. These patients may currently miss out on the opportunity to benefit from targeted therapy as they are too ill to wait for a full molecular profile from Cardiff before initiating life prolonging treatment. The AWMGS kindly provided advice as required.
While lung cancer is still the most common cause of cancer deaths in the UK, considerable progress has been made over the last few years in the treatment of advanced Non Small Cell Lung Cancer (NSCLC), especially in the rollout of targeted therapies which can improve survival rates by as much as 50% in some cases.
Molecular testing for patients with NSCLC is necessary to select appropriate targeted therapies; however, genotyping by gold standard Next Generation Sequencing (NGS) methods requires specialist facilities, expert knowledge and access to bioinformatics and can take two weeks or more to arrive at a diagnosis. Unfortunately some lung cancer patients initially present with widespread metastatic disease and deteriorate rapidly from presentation. Patients need to be suitably fit for an oncologist to prescribe tyrosine kinase inhibitors. Some patients who deteriorate rapidly miss out on this treatment opportunity because they deteriorate so quickly. We found that this was statistically significantly most likely to happen in patients with stage 4 disease, hence the reason for targeting this group for testing for EGFR mutation on the Idylla platform.
Our aim was to work as a multi disciplinary team across Wales to firstly identify and then evaluate an alternative rapid testing method to NGS for urgent cases. We specified that we required – an automated platform that required no specialist clean premises or additional expensive equipment. A platform that was CE approved and well established and tested in other labs in the UK. It had to be easy to use and provide clear, easily interpreted results with built in quality control. We needed minimal manual intervention so as not to impact on the workload of already busy laboratories. The system had to be cost effective and have the ability to deliver a reliable, clinically actionable result within just a few hours of a diagnosis of NSCLC in individual cases.
The team began work with:
- An audit of turnaround times from receipt of specimen by the lab to issuing the final report
- A full review of alternative methods for molecular sequencing currently available was undertaken by an independent researcher.
- The Idylla platform was identified as the only platform currently available to meet all the criteria.
- 93 retrospective samples from patients with NSCLC were tested on the Idylla platform and the results matched to the NGS results.
- Development of an agreed standard Operating Procedure (SOP) which was critically scrutinised and critiqued by the clinical team in the AWMGS in Cardiff before final draft was agreed.
- An overview of external quality control results and concerns raised by AWMGS.
- A review of published data on Idylla testing
- A review of National recommendations for improving testing for lung cancer NICE, National Optimal Lund Cancer Pathway.
- Culturing relationships across two scientific disciplines and three different Health Boards
- Not letting the established pathway become an obstacle for improvement
- Evidencing that Idylla was a safe and clinically useful option that would benefit patients
- Ensuring every weakness in the Standard Operating Procedure was identified and addressed to ensure consistently safe results.
One of the most positive outcomes of this work was the establishment of good working relationships between the sites involved and the consolidation of the ambition to establish a hub and spoke model for the future, where Cardiff AWMGS would work in partnership for spoke sites across Wales.
The need for improved turnaround times for all results was apparent, especially a need for rapid tests in patients with late stage lung cancer which could influence treatment options.
Turnaround time audit showed the average turnaround for an end to end result to be around 25 days in January 2020. By June 2021 the end to end turnaround times have improved to average 20 days. The AWMGS are meeting their key target of 95% of cases reported within 14 days. The improvement is largely due to the improvements in awareness for an urgent report, improved testing and reporting times both in Histology and AWMGS, and improvements in communication of results. Reflex cutting of sections and weekend working in BCU had already reduced delays in sending samples to Cardiff. During this project, work was undertaken to enable molecular tests to be transcribed directly in Cardiff into the patients file on the Welsh Clinical portal. A message is sent to the clinician to notify them that a clinically actionable result needs attention. Further work is ongoing to raise awareness of the need for urgency. It was highlighted that AWMGS can deliver an urgent test result within 3-5 days of receipt of the sample using Droplet digital tests, this service has been available since 2017 for liquid biopsy and tissue biopsy targeted EGFR analysis for lung cancers.
The validation exercise showed the Idylla to be 97% concordant with the NGS findings. In our study 18 out of the 21 positive cases showed one of the two “common EGFR mutations”. This is in line with 85% of cases showing a common EGRF mutation indicating the patient would probably benefit from TKI therapy. None of the 93 cases showed false positive results. Three of the 93 cases showed a negative discrepancy, however, the screening panel in the Idylla cartridge was not set up to detect these mutations. All three discordant results related to rare mutations which are of no known clinical significance at present (see results).
There were 3 mutations out of the 21 positive concordant cases that were more complex and outside the well-recognised “common mutations”. These cases with either double mutations or mutations that required additional investigation and would benefit from the expertise of a Clinical Scientist to advise best treatment options. To ensure patient safety it was agreed that the Idylla would only be used to report defined positive mutations in Exon 19 DEL and L858R, both of which are likely to respond well to TKI targeted therapy.
It is important to note that while the AWMGS team were happy to assist in supporting this work to deliver urgent tests locally in a histology laboratory. They do not endorse use of the Idylla Platform as they harbour significant concerns relating to the Idylla technology, its validation and the reporting of results. All cases will still be sent for full NGS sequencing to ensure a gold standard service delivering truly personalised medicine.
The review of alternatives available to deliver a rapid molecular tests concluded:
his project helps drive prudent health care in that it ensures all patients with NSCLC will get the right tests, at the right time, in the right place to direct personalised care.
- Establish costings (each cartridge costs £150, there is no cost for the testing platform and two platforms are supplied at each site to ensure continuity.)
- Submit SBAR and business case to Health Board
- Enroll in National quality control scheme
- Identify staff in BCU and SB with suitable qualifications and competencies (need to look at equivalence pathways) Establish training routes for staff to gain necessary training to meet future service needs.
- Communicate with clinicians to ensure testing is limited to the intended group of patients.
- Ongoing monitor of the quality of results and turnaround times.
- Continue to work with the AWMGS to develop a hub and spoke model for molecular testing in the future .
Our Exemplar Experience
The Bevan experience for me has helped build valuable new relationships, develop self-awareness as well as understand better the value of tenacity and perseverance needed to ascend problems encountered when trying to implement improvement and change.
This project is important as it has put a spotlight on a small group of patients who may currently be denied an opportunity to access life changing personalised treatment.
For more information, please contact: