Taking bloods.  A healthcare activity so everyday and undistinguished as to be essentially invisible.

Yet rapid advances in genomic technologies mean that the insights gained from this simple act could be signalling a new dawn for cancer diagnostics.

Although only at the beginning of the journey research is increasingly showing that a blood sample (liquid biopsy) can not only reveal the presence of disease-causing mutations in circulating tumour DNA (ctDNA), but allow for the possibility of real-time ctDNA-directed treatment.


The Shedding – Where ctDNA Originates

Cancer begins when a normal cell’s DNA mutates. From that point on, the cell multiplies too often and a mass / tumour of abnormal cells forms. As with all cells, a proportion of the cancerous cells inevitably die and shed genetic material (ctDNA) into the bloodstream. These mix with larger amounts of circulating free DNA (cfDNA) fragments coming from the death of normal cells.


The Search

The blood test allows these DNA fragments to be searched for, and if present, examined, creating a personalised genomic blueprint for each patient by analysing the patchwork of genetic faults in the tumour cells.  In doing so it can help reveal the stage of a tumour, and potentially its weaknesses.

Because scans won’t pick up tiny quantities of cancer cells known as minimal residual disease (MRD) which could still regrow into further tumours, the liquid biopsy may allow a clinician to track a patients disease status earlier, more accurately, and select the most effective medications and interventions.

TRACC – Bowel Cancer Trial

One of the areas the technology is currently being trialled in the UK is in the field of bowel cancer where the test is being used to establish whether surgery has removed all of a tumour.

Doctors estimate that half of all patients with stage 3 bowel cancer are cured by surgery alone. However, the gold standard treatment is to give intravenous chemotherapy after surgery to reduce the risk of the cancer returning. But the chemotherapy used in bowel cancer, Oxaliplatin, can come with significant potential side-effects, such as long-term nerve damage.

In the trial, if the test shows the patients are clear of the microscopic traces of ctDNA in their bloodstream, they are given an oral chemotherapy tablet which tends to have less side-effects.

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The Health Economics of Tailored Treatment

The beauty of a liquid biopsy is not only that it is quicker and less invasive than taking a tissue sample – no small benefit at a tremendously stressful time for a patient – but that it is also available to those unable to tolerate surgical procedures, or in cases where a tumour is difficult to access.

Ease of sampling also opens up the possibility of continuous monitoring which can provide information on the success of curative surgery, reveal whether chemotherapy is working, if the disease has developed resistance, or for relapse monitoring.

Crucially, it also provides the possibility of detecting disease presence, or progression, earlier than an imaging scan, or than symptoms would present themselves, because these tiny fragments would be invisible on a scan.

The information gleaned from the procedure allows doctors to make more informed decisions on earlier medical interventions, which could provide potentially better long-term outcomes for patients

This would be the case with TRACC trial which, if successful, could affect the way in which thousands of bowel cancer patients are treated each year through not unnecessarily being given chemotherapy. Not only sparing patients from toxicity, but also providing the potential for huge cost savings for the NHS.

However, whilst liquid biopsies are currently seen as a complementary tool to be used alongside tissue biopsy, particularly in situations where there simply isn’t enough tissue, ongoing developments in the field are opening the door to an exciting future.

NEY GMS & ctDNA – Piloting Circulating Tumour DNA (ctDNA) Testing in Lung Cancer Patients for Earlier Diagnosis & Personalised Treatment

Regionally led by Dr Alastair Greystoke & Dr Jackie Cook, this project aims to provide evidence, including the health economics, for the expansion of ctDNA testing in the NHS.

This will support tumour genotyping from blood to allow rapid personalised drug treatment selection, and speed up time to treatment for patients with advanced lung cancer

“We know that analysis of DNA in the blood can give us extra information over the traditional method of taking a biopsy. For patients newly diagnosed with lung cancer we are now fully assessing the potential benefits to patients, and the national health service, of getting this extra information as early as possible, with the view of hopefully making this available to all patients presenting with advanced lung cancer in England” (Dr Alastair Greystoke)

Nationally, the project is being led by NHS North Thames Genomic Medicine Service Alliance (GMSA).

NEY GMS, in collaboration with the four Cancer Alliances in the region, are working with clinicians to identify patients in our region with suspected Non-Small Cell Lung Cancer (NSCLC).  The ctDNA in their blood will be sequenced to help diagnose their condition and inform their treatment plan.

In parallel, the team will monitor the quality and scope of the testing, turnaround times, onward management of patients and the impact it has on speed of treatment and treatment selection.