29 June 2023
Lung cancer patients in Wales are about to get answers faster—and potentially find out if they’re a match for targeted therapies.
In Wales, lung cancer is the third most common cancer for women and the fourth most common for men, and it remains the leading cause of cancer-related deaths. Welsh patients often present late, at stage III or IV lung cancer. Unfortunately, patients diagnosed with stage IV lung cancer face a one-year survival rate of 16%.
In 2017, the Welsh government issued the Genomics for Precision Medicine Strategy, and last December, the Genomics Delivery Plan for Wales 2022-2025, calling for nationwide clinical care based on next-generation sequencing (NGS). “We all agree that there is a critical need to rapidly implement the increased utilization of liquid biopsy within the cancer pathways for patients within the health care system in Wales,” says Sian Morgan, laboratory director of the All Wales Medical Genomic Service (AWMGS).
In collaboration with Illumina and 13 other organizations, AWMGS, the single provider of genetic services in NHS Wales, will make liquid biopsies available to 1260 lung cancer patients consecutively across the country’s seven health boards, under a partnership named QuicDNA. Rather than excising tissue from a patient, a liquid biopsy uses a simple blood draw, since fragments of tumor DNA shed into the bloodstream. The blood samples with circulating tumor DNA (ctDNA) are sequenced on a 500-gene panel. The approach is known as comprehensive genomic profiling (CGP) and it can assess multiple biomarkers in numerous tumor types in a single NGS assay.
In Wales, ctDNA is currently used in a limited fashion to investigate genes associated with targeted therapies (EGFR and KRAS genes), usually when tissue is unavailable in late-stage patients. The standard tissue biopsy can be painful and place patients at risk of complications, and is not always an option. And if the biopsy is of poor quality, or too small, there may not be enough tissue left for genomic testing, which then requires a second or third biopsy, adding to the patient’s discomfort and prolonging the diagnosis.
“We think it is critically important for stage III and IV lung cancer patients, in particular, to receive genomic results as soon as possible,” says Magda Meissner, a medical oncologist at the Velindre Cancer Centre in Cardiff and the clinical lead for Liquid Biopsy for All Wales Medical Genomic Services. She refers to local studies that indicate a potential 25% of lung cancer patients miss out on targeted treatment, either due to becoming too unwell to receive anticancer treatment or passing away before receiving genetic results that could extend their lives. “We need to expedite the process.”
The standard guideline for the pathway to cancer diagnosis in Wales is 62 days or more. Currently it is challenging to meet even this parameter—time that many patients don’t have. First, a patient needs to make an appointment to see a general practitioner, who can then order required investigations and refer them to a rapid-access lung clinic at a hospital. At the clinic, a lung physician will assess the patient and the imaging results. If the physician suspects cancer, a tissue biopsy will be arranged, and the collected tissue will be sent to a pathologist for diagnosis.
In the United Kingdom, every patient with suspected cancer has their case discussed at a multidisciplinary team (MDT) meeting, which includes the oncologist, radiologist, pathologist, respiratory physician, thoracic surgeon, palliative care team, and nursing specialist team. The team reviews the biopsy results and imaging before making a final diagnosis and discussing the best treatment options. Often at this point, the doctors will request genomic testing, which takes another 14 to 28 days before they can get results and potentially offer a targeted therapy.
Meissner says patient health can deteriorate during this multistep process, and the main goal in implementing ctDNA is to offer targeted therapy to patients with an identified genomic target sooner than they would normally receive it.
With the new QuicDNA program, patients will get a blood sample for ctDNA early in the diagnostic pathway when the lung physician suspects stage III or IV lung cancer. The genomic results will be available for the MDT meeting. Because more than 10 genetic biomarkers are associated with an approved therapy for lung cancer, genetic testing can significantly increase treatment options. “When you can identify, for example, an EGFR mutation through sequencing, a patient can potentially start oral therapy (tablets) the next day,” says Meissner.
What they’ll learn
The QuicDNA program will generate an enormous amount of genomic data, which will be used alongside clinical data to evaluate diagnostic efficiency and clinical utility of liquid biopsy. The partnership with Illumina will also further investigate why some patients might show an initial response to a treatment but then progress, or worsen, a few months later.
They will also evaluate the economic costs and effects of liquid biopsy for the Welsh health system. “Invasive tissue biopsies require highly skilled individuals, including clinicians, nurses, and pathologists who examine the tissue under the microscope,” says Meissner. “All of these personnel and resources need to be arranged within a hospital setting, which adds to the overall cost.”
A tool in disease monitoring
The investigators strongly believe that by the end of the study and based on the outcome data, the routine use of this technology can be justified and embedded in NHS practice across Wales. And the team on site is already thinking about further possibilities for ctDNA use. They might also be able to use ctDNA for disease monitoring. Rather than waiting for a regular scan every two to three months, clinicians could change treatment quicker if they learn that the patient isn’t responding well based on a blood test. Taking subsequent samples when a patient progresses on treatment could enable them to discover new mutations.
The potential for ctDNA is great, and Meissner says the medical community is excited: “I think people are realizing that ctDNA is a powerful analyte, not only in lung cancer but other cancers.” She already has oncologists contacting her to do ctDNA testing for other cancers. “As soon as we prove the value in lung cancer, we want to expand liquid-based CGP to other tumor types.”
Morgan adds that, given the rapidly changing landscape of cancer management, the growing number of targeted therapies and types of tumors, and the variety of treatment settings, “I can see liquid biopsy becoming the frontline test for many tumors, due to ease of sampling and time to return genomics profiling results that will impact patient management and outcomes. It is not entirely a question of replacing tissue, but the requirement for a more timely test for patient management.”
