Raphael Thys
The All Wales Medical Genomics Service (AWMGS) recently announced the launch of a new service that aims to lead the way in the implementation of state-of-the-art genomic testing services into routine clinical practice for National Health Service (NHS) patients. CYmru Service for Genomic Oncology DIagnoses (CYSGODI) will enable oncologists, hematologists and other healthcare professionals to undertake rapid and extensive genomic analysis of cancer samples on an unprecedented scale in the UK.
To learn more about the technologies being employed and the impact CYSGODI will have on patient treatment and outcomes, Technology Networks spoke to three members of the team.
Ash Board (AB): How is genomics research leading to more targeted therapies for cancer treatment? Rhian White (RW): Next-generation sequencing has facilitated the detection of multiple genetic variants in a single test in a more cost-efficient and time-efficient manner. The variants that are detected are the cause of the cancer and therefore the ability of pharma companies to develop drugs that target these genetic variants results in a highly effective treatment for the patient’s cancer with minimal side effects.
Sian Morgan (SM): For our genomic laboratory and other genomic laboratories across the UK the major driver at the moment is the incorporation of emerging new technologies and the ability to detect a comprehensive list of genetic biomarkers or variants from very often small amounts of formalin-fixed paraffin-embedded (FFPE) tissue biopsy material, which is then used to match a patient to the ever-increasing list of targeted therapy options for improved outcomes. The concept of personalized medicines is not new, and the risk for laboratories is that if we don’t keep up with the increased demand for biomarker testing for patients then clinicians will not have access to the information they require for appropriate treatment care. Personalized medicine is a key strategic approach to cancer care ensuring that expensive treatments are evidenced-based, whilst also giving the best value and outcomes for patients.
Sam Cox (SC): Advances in high-throughput sequencing techniques have significantly contributed to both our understanding of the genetic changes which may be responsible for the development of cancer and the identification of patients whose tumors harbour such variants. This is in turn leading to an ever-increasing number of clinical trials investigating the effectiveness of drugs which specifically target the altered genetic pathways. This represents a significant shift in how cancers are treated; historically anti-cancer treatments have been chosen using a “one size fits all” approach according to where the cancer originally developed within the body. Genomics research offers the opportunity to tailor treatment based on specific genetic changes within an individual patient’s tumour with improved outcomes. There has also been a drive to reduce the time taken for effective novel targeted therapies to be authorized for routine clinical use which will maximize the benefits to patients.
AB: Can you discuss the background work and development that has led to the launch of CYSGODI RW: The launch of CYSGODI has taken place over the course of the last year and involved the team at AWMGS to appraise the needs of cancer patients in Wales in order that we could implement a test that will offer them the best chance of receiving the optimal treatment for their cancer. Once the best test had been identified, the team of clinical scientists, genetic technologists and bioinformaticians at AWMGS validated the test to ensure it meets strict quality control parameters.
SM: CYSGODI was launched because the unprecedented increase in new targeted molecular therapies (including tumor agnostic therapies) and immunotherapies is driving the requirement to continue to develop even more extensive and more timely genomic testing for cancer patients using FFPE (and/or eventually fresh frozen tissue).
The service utilizes the Illumina TruSight Oncology 500 HT DNA/RNA panel and in due course will incorporate the current hemato-oncology next-generation sequencing multi-gene panel (TruSight Myeloid Sequencing Panel).
Using this new technology harnessed from increased investment through the Welsh Government Genomics for Precision Medicine Strategy, our laboratory is the first in the UK to benefit from greater flexibility in the numbers of samples we can sequence using our NovaSeq 6000 that will allow Welsh patients and clinicians access to appropriate clinical trials and treatments.
AB: Why is the TruSight Oncology 500 High-Throughput assay a “pioneering” technology? RW: The TruSight Oncology 500 High-Throughput assay is a “pioneering” technology because it enables the laboratory to detect genomic variants in 500 genes for multiple different tumor types. We are one of the first laboratories in the UK to use this technology for diagnostic purposes. It means that as new precision medicine drugs become available, the AWMGS will be able to rapidly offer genomic testing to enable patients access to a new therapy.
SM: TruSight Oncology 500 can analyze DNA and RNA from the same sample, detecting single nucleotide variants (SNVs), indels, amplifications, splice variants and fusions, in a single sequencing run. TruSight Oncology 500 also allows for the determination of tumor mutational burden (TMB) and microsatellite instability (MSI) in DNA samples, which are currently being developed as biomarkers for immunotherapy.
SC: From a clinical perspective, this technology will futureproof the genomic testing service for patients in Wales. As the number of targeted therapies increases, we will be able to quickly and effectively expand the number of genes which are routinely tested for.
AB: How does it differ from genomic technologies that are currently available? RW: The previous genomic technology that was utilized in the laboratory was only able to detect variants in 30 genes. We have therefore massively increased our testing capabilities.
SM: There are a number of differences, highlights include:
- A consolidated, comprehensive assayEnabling analysis of multiple tumor variant types (both solid tumor and hemato-oncology) in 523 genes, across DNA and RNA, from guidelines and clinical trials in a single assay.
- A fast, integrated workflowWe can go from sample to results in 4-5 days using automation-friendly library prep kits and optimized data analysis solutions.
- Proven, reliable resultsWe generate accurate data using an assay shown to meet demanding performance specifications.
- Value-adding in-house solution for the medium to long termIt is possible to keep samples and obtain extensive data that should be relevant in the medium and long term as new biomarkers emerge for standard of care or new emerging trials.
AB: How will the data generated by CYSGODI be used to inform clinical decisions? RW: The data will be used to inform the clinician of the best treatment for the patient. It will also inform the eligibility of clinical trials which may offer patients even more treatment options.
SM: The concept of personalized medicines is not new, and the risk for laboratories is that if we don’t keep up with the increased demand for biomarker testing for patients then clinicians will not have access to the information they require for appropriate treatment care. Personalized medicine is a key strategic approach to cancer care ensuring that expensive treatments are evidenced-based, whilst also giving the best value and outcomes for patients.
SC: The clinical interpretation provided by the genomics service is vital to ensuring clinicians are alerted to the presence of clinically relevant genetic variants and what the implications of these results will be for individual patients and their treatment options. There is also a pressing need to capture, store and interrogate genomics data so that patients can be identified and offered the opportunity to take part in clinical trials.
AB: What challenges exist when implementing genomic testing services at a large scale in clinical practice? RW: A current challenge is the ability to have enough tumor biopsy material to detect the large number of genetic variants. Next-generation sequencing overcomes this because all relevant variants can be detected in a single test. The time a test takes is also critical and, again, because next-generation sequencing is a single test, the time taken to acquire all the genetic information required to make a treatment decision is reduced.
SM: Trained workforce, IT infrastructure and sample quality (FFPE) – requirement to move towards fresh from frozen.
SC: It is vital that NHS patients have equitable access to genetic testing services regardless of where they live and that we maximize the opportunity to identify patients who may benefit from novel targeted therapies. This requires clear channels of communication at the early stages of service developments to ensure clinical teams are aware of the service and when to access it, and that the testing pathway is appropriate for everyday clinical use.
And timing is everything – we need to be performing testing at agreed time points in the diagnostic pathway, but more importantly, genomic results need to be available in a timely manner. This will be key to ensuring suitable patients start treatment as soon as possible and will require ongoing investment in both diagnostic services and the healthcare workforce.
Ash Board, Editorial Director at Technology Networks was speaking to:
Rhian White, FRCPath, Consultant Clinical Scientist,
Sian Morgan, Head of All Wales Medical Genomics Laboratory,
Dr. Samantha Cox, Consultant Clinical Oncologist and Chair of All Wales Genomics Oncology Group.
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