Diagnostics
highly likely to have cancer who had no way of progressing to the next step of starting treatment.” By the end of March, UK endoscopic activity had collapsed to 5% of pre-pandemic levels, only crawling back up to 20% by the end of May. Over that period, endoscopic cancer detection fell by 58% overall, and by 72% for colorectal cancer. The backlog of procedures has been climbing ever since, reaching an estimated 476,000 in January 2021, according to figures in a Lancet Gastroenterology and Hepatology paper. The meaning of those numbers will become palpable in many families over the years to come. A recent modelling study in Annals of Oncology indicated that a surgical delay of three months across all solid tumours in the UK would lead to 4,755 excess deaths, escalating to 10,760 after six months. The earlier a cancer is caught, the easier it is to stop. Those that aren’t stopped kill. With that in mind, the Royal Marsden Trust looked at its options. Together with its academic partner, the Institute of Cancer Research, it has established itself as a leading centre for research into the use of non- invasive fluid samples, or liquid biopsies, for monitoring cancers through the circulating tumour cells (CTCs) and scraps of cell-free circulating tumour DNA (ctDNA) they leak into the bloodstream. Staff have even developed a number of their own clinically- validated liquid biopsy assays for everything from monitoring how breast cancers respond to treatment to investigating what ctDNA can tell us about the likelihood that bowel cancer might return after surgery. “We put our heads together and said, ‘What can we do to support the cancer effort in this exceptional situation, where our diagnostics are switched off?’” recalls Starling. In record time, they devised and launched the PREVAIL-ctDNA study to explore the possibility of replacing invasive tissue biopsies for patients presenting with symptoms of pancreatic, lung, bladder, colorectal and gastrointestinal cancers. Preliminary results are encouraging, and Starling, a gut cancer specialist as well as the coordinating investigator for the protocol, is particularly excited by the potential she sees for liquid biopsies to shorten diagnostic pathways for conditions like pancreatic and bile duct cancer, which are hard to detect with endoscopes and other existing diagnostic tools. “One in four patients has a difficult, protracted diagnostic pathway, with even invasive diagnostics not quite clinching the diagnosis and having to be repeated, and seeing various specialists on and off,” she explains. “That can take a few months – but we’ve made a diagnosis with liquid biopsies much sooner for a number of patients.”
For the lung cancer cohort, there’s a dual benefit. As well as simplifying the diagnostic process for a cancer that’s often difficult to reach and identify with a bronchoscopy, liquid biopsies also provide the molecular information needed to guide precision
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therapeutics. “It’s two for the price of one,” says Starling – and at a cost patients are far more willing to pay, given the alternative is inhaling several feet of electrical cable.
The next step for the PREVAIL-ctDNA study is a
larger-scale protocol across more diagnostic units. “This was very much a feasibility programme, to deploy the test in a setting that we thought was very important because of the pandemic,” continues Starling, “but actually it just makes sense in the future in terms of supporting the diagnostic pathway, and to really to put a stop to the more protracted, difficult diagnostic cases, and potentially to even reduce the burden on these pressurised resources in endoscopy.”
Given the international endoscopy backlog – and the capacity limits caused by greater cleaning and PPE requirements, not to mention the lingering possibility of another surge in the virus – those resources will be stretched for a long time to come. It’s revealing that invisible particles should have brought us to this point. Cancer is defined as much by its ability to escape and spread imperceptibly through the bloodstream as the fact it agglomerates into the solid tumours we seek out and sample with endoscopes. The future of cancer diagnosis will be defined by tools that reflect that.
Galleri quest Late last year, the NHS announced a 165,000- patient pilot of a test capable of detecting and pinpointing more than 50 types of cancer through a single blood draw. The Galleri multi-cancer early detection (MCED) blood test, as it’s called, combines liquid biopsy technology with sophisticated machine learning capabilities to both identify the presence of ctDNA in a blood sample, and determine its tissue of origin through methylation analysis.
“We’ve made a diagnosis with liquid biopsies much sooner [than a few months] for a number of patients.”
Naureen Starling
As Dr Joshua Ofman, chief medical officer and head of external affairs for GRAIL, the company behind the Galleri, points out, there are currently only five guideline-recommended screening tests in the US, each of which only screens for a single cancer at a time. Meanwhile, cancers responsible for 71% of all cancer deaths have no available early detection screening. “The most pressing unmet need in early cancer detection,” he stresses, “is to identify cancers for which there are no existing recommended screening tests.”
11 5% The UK’s
mid-pandemic endoscopic activity low compared with pre-pandemic. It only climbed back up to 20% by the end of May last year. The BMJ
10,760
Estimated excess cancer deaths in the UK if all solid tumour surgeries were delayed by six months. Annals of Oncology
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