Liquid Biopsies in LFS – First Results


Early cancer detection is the primary aim in the management of Li Fraumeni Syndrome – early detection is key to successful cancer treatment. Currently the main mechanisms for this early detection are regular surveillance using whole-body MRI (WBMRI), physical checkups and so on. However, access to WBMRI is problematic for many LFS patients, and of course it can only pick up cancers once they reach a certain size – too small and they don’t show up in the scanned images. An alternative mechanism that is being intensely researched is the use of liquid biopsy. The idea here is to pick up cancer-associated chemical signals from blood samples. Not only is this easier and more convenient than having to undergo WBMRI, but there is also the potential to pick up cancers before they are big enough to show up on a scan. That’s the theory, and currently there are two studies on-going in the UK looking at this for LFS – the ICED study at the Royal Marsden and ATLAS in Manchester. A new paper, published in the journal Cancer Discovery, reports on the first results of a liquid biopsy in LFS study from Toronto.

While the idea of liquid biopsy is simple enough, in practice this is a really difficult thing to do – especially in LFS. If you are looking for one type of cancer things are a bit more straightforward, you can look for chemical signals just for that one cancer type. But people with LFS can develop all kinds of cancers – there is not just one possible signal, there are many. There are risks of false positives – picking up non-cancer signals and saying they are cancer, and false negatives – giving someone the all-clear when there is actually a cancer present. The authors try and address these issues by using a combination of three different techniques rather than relying only on one.

What’s more they compare three groups of people – those with LFS and currently healthy (no cancer), those with LFS and currently with cancer and then people without LFS. They also include a mix of adults and children with LFS rather than just using adult samples. It’s a really thorough approach. And the results are very encouraging.

First, they show that it is possible to actually perform this kind of liquid biopsy for the majority of LFS patients – there were a few cases in children when the researchers were not able to perform the tests from the amount of blood available (they used blood previously collected, so not enough was stored). Showing that such studies are feasible is an import finding in itself – and allows future studies to learn how to maximise the chances of successfully performing these tests. The good news is that the amount of blood needed is consistent with current practice – it doesn’t take pints, just a single standard blood draw is enough.

In terms of proving that liquid biopsies can successfully detect cancer the answers are mixed. The study did identify a cancer signal, later confirmed by imaging, in 26 of 73 cases in people who were cancer-free. However, this has to be balanced by the fact that there were also 22 of 73 where there was a cancer signal that was not confirmed by imaging – most likely false positives, but deeply worrying for those individuals getting that news. For those who want the technical terms – the study “was able to detect cancer-associated signal in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%)”. These results are proof of principle that liquid biopsies can be effective in detecting cancer in people with LFS prior to the cancer showing up on scans. It’s an incredibly important result and we owe a huge vote of thanks to the team in Toronto who carried out this study.

Of course, this is only a first set of results and there’s clearly lots more to do. The false positive rate is a major concern – this has to be brought down. Perhaps adding additional tests can help, or else having more LFS samples will allow better differentiation between what is a cancer signal and what isn’t. The data already shows that there are differences between LFS samples and non-LFS samples regardless of whether there’s a cancer present or not. What we can see is that initially it’s likely that liquid biopsies will be added to routine imaging surveillance rather than replace it – a belt and braces approach to maximise the chances of detecting cancers early. However, in the longer term, once the techniques have improved sufficiently, we would want to see liquid biopsies as a regular and routine LFS management tool, with MRI and other imaging used just to confirm findings.

For those who want the full paper, it is available here.

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