NCRI 2015

Using circulating tumour DNA to inform treatment strategy

Dr Nitzan Rosenfeld - Cancer Research UK Cambridge Institute, Cambridge, UK

The session we have this afternoon about circulating biomarkers with a twist, focussing on circulating DNA and circulating tumour cells, is going to bring together some speakers from around the world and the UK to look at what’s new and upcoming in these fields which are the subject of very hot research and very fast moving fields these days.

Why is this an important topic?

It’s the coming together of technologies and the applications and these are fields of research which rely heavily on genomic analysis and the methods of genomic analysis now make it possible to really study with the kind of resolution that allows us to pick up mutations coming from cancer even in complex fluids such as plasma DNA that contains a lot of background DNA in addition to DNA coming from cancer as well as the methods that are required to look at single circulating tumour cells which require sophisticated technology and are now really developing to the point where these are becoming much more useful and practical.

What is your presentation about?

My talk will present an overview of progress and a review of where we see things lying, where the field has developed to and where we think it’s developing to. We won’t be presenting any ground-breaking combination of big studies in today’s talk, rather an accumulation of incremental steps that are slowly progressing us towards better understanding of this phenomenon and what we can do with this for cancer analysis and cancer applications.

What have you been doing and what’s your progress so far?

We’re looking at how we can use circulating tumour DNA to monitor cancer response to therapy, looking at circulating tumour DNA as a quantitative measure of tumour burden and how we see that changing over the course of treatment and response to therapy as the patients are initially responding. Unfortunately if the patients relapse we can see that reflected in increasing levels of circulating tumour DNA. I’ll be reviewing some of the data that will be presented and some of it has been published by the other speakers of today, looking at how circulating tumour DNA could be a marker for the risk of relapse after potentially curative surgery or treatment. We’ll be looking at how circulating tumour DNA could be used to reflect and to analyse the heterogeneity of cancer where you have multi-clonal metastatic disease. In addition, I’ll be looking at potential new ways where we can develop circulating tumour DNA further; how we can increase the sensitivity for analysis of low volume disease, for example by pulling together multiple patient-specific mutations as a more sensitive way to analyse the amounts of circulating tumour DNA in the blood;  thinking about how this can lead on to future applications in earlier cancer stages for minimal residual disease and potentially in the future to help in earlier diagnosis of cancer, initially in cases where there are suspected symptoms and eventually in the future possibly towards screening applications.

This is from a simple blood test?

The analysis is based on material we collect from a single blood test although at the moment many of these applications are still in the research phase so we try to get the best information we can by triangulating the data we get from the blood test with data that’s obtained from tumour sampling, using that to learn both about what we can do with this circulating tumour DNA, helping us to develop the methods further. The idea is that as we become more proficient with these then we can collect better information on the cancer without the use of the tumour DNA, both as a research tool to look at new resistance mechanisms, for example, to therapies and also as a diagnostic tool to help identify what’s happening to the patients and what might be the optimal care for them down the line.

Does this prevent over-treatment?

It can go in many different ways. It’s a piece of information that oncologists can use and again we’re working together with oncologists and with any technology that we can bring to see what is the optimal way to use that. One possible way to use that is to see if patients are progressing and to change therapy earlier. That kind of change in standard of care would require quite a significant level of evidence if you want to change while the patient doesn’t have increasing symptoms, for example. An easier place to apply this is when you already know that you want to make a change in therapy and you can use circulating tumour DNA or circulating tumour cells in the future to inform about what might be the best next course of action by getting a picture of what the tumour looks like from the DNA that’s in circulation. Oftentimes you’d like to get a repeat biopsy of the cancer if you are able to because cancer evolves and changes over therapy, but if you are unable to obtain that due to complications, cost, logistics then you might be able to get information from the blood that will still be of informative value.

How widely used is this in the UK?

It’s not yet entered into clinical practice. It’s now starting to enter into select clinical trials which would use this initially as a comparator. Eventually I expect and hope that in the near future this will already start to be used to guide some of the upcoming clinical trials where this kind of information can be used to select treatment within the context of a clinical trial and these clinical trials will help us see how much this information is really helpful to guide these treatments.

What are the conclusions of your talk?

The conclusion of my talk would be really that the technology is now here, we know enough about cancer to know that we do want to get serial sampling of the cancer over time. Technology now allows us to do that and this now opens up the possibility to do these kinds of clinical trials which the community is just now starting to put together. These are significant investments requiring putting together the possible therapies that you need to use as a next step, putting together all the infrastructure that you need in order to obtain the data and the samples, patient consents, all in time in order to undertake this exercise.