New cancer blood test up to ten times more sensitive

A new method of analysing cancer patients’ blood for evidence of the disease could be up to ten times more sensitive than previous methods according to research funded by Cancer Research UK and published in Science Translational Medicine.

In the coming years, this method and others based on this approach could lead to tests that more accurately determine if a patient is likely to relapse after having treatment and could pave the way for the development of pinprick home blood tests to monitor patients. The technique uses personalised genetic testing of a patient’s tumour to search blood samples for hundreds of different genetic mutations in circulating tumour DNA (ctDNA); DNA released by cancer cells into the bloodstream.

Combined with new methods to analyse this data to remove background noise and enhance the signal, the team were able to reach a level of sensitivity that in some cases could find one mutant DNA molecule among a million pieces of DNA – approximately ten times more sensitive than previous methods. Dr. Nitzan Rosenfeld, senior group leader at the Cancer Research UK Cambridge Institute, who led the team at the University of Cambridge that conducted this research, said: “Personalised tests that can detect if

hospitals. Thanks to such advances, PBT can hopefully become part of a toolkit for many more hospitals in the near future. CSJ

References 1 American Society of Clinical Oncology, accessed at: cancer-treated/radiation-therapy/proton-therapy

2 National Association for Proton Therapy Annual Survey 2018 accessed at:

cancer patients, particularly after they’ve received treatment, as it can be an indicator of whether the treatment was successful and if the patient might relapse. In some situations, other types of tests can be used to detect some cancers before they display any symptoms or show up on a scan.

cancer is still present, or find it early if it is returning, are now being tested in clinical trials. “While this may be several years away from clinical use, our research shows what is possible when we push such approaches to an extreme. It demonstrates that the levels of sensitivity we’ve come to accept in recent years in relation to testing for ctDNA can be dramatically improved. At present this is still experimental, but technology is advancing rapidly, and in the near future tests with such sensitivity could make a real difference to patients.”

Detecting ctDNA in blood samples is what is known as a ‘liquid biopsy’. It allows doctors to find out more about a patient’s cancer without the need for invasive surgery. The technique is important for monitoring release/2018/03/26/1453021/0/en/Annual-Survey- Shows-Surge-in-Cancer-Patients-Treated-With- Proton-Therapy-in-Number-of-Indications.html

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3 Cone beam CT provides three-dimensional anatomical images of patients, immediately prior to being treated. Information on the location of bone is obtained from traditional orthogonal x-rays and the motion of tumours is captured by RGPT. These are then combined with the ability to identify healthy

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Currently, however, the sensitivity of the methods depends on having a high enough number of mutant pieces of DNA, either relative to background DNA or in absolute numbers. When the amount of ctDNA is low, a test can produce a negative result even if a patient has residual cancer in their body that could lead to relapse. A single tumour will contain many different mutations that caused the cancer to form. While some of them are commonly known across certain cancer types, such as EGFR in lung cancer, the overall set of mutations for a tumour varies from person to person. By analysing the genetic makeup of an individual’s tumour and targeting a set of mutations in a personalised way, liquid biopsies to monitor cancer can become much more sensitive. Until recently, these personalised liquid biopsies have searched for around 10-20 mutations in the blood and up to around 100 at most. In the material from a tube of blood, these would be able to detect ctDNA to levels on the range of 1 mutant molecule among 30,000 pieces of DNA.

tissue surrounding a tumour, particularly the location and shape of soft tissue via Cone beam CT.

4 RGPT allows real-time beam irradiation to the tumour while compensating for movement associated with respiration. It is the technology collaboratively developed between Hokkaido University and Hitachi, supported by Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST) of Japan Society for the Promotion of Science.

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