Banking on biomarkers – improving the diagnosis of early stage NSCLC
Dr Harvey Pass - New York University Langone Medical Center, New York, USA
BOOSTER is a new trial that’s going to be performed by an international collaboration known as the WIN Consortium in which we’re going to take patients who have stage 1 lung cancer and make an archive. Now, why would you do that? Well, you make an archive so that you can study the differences between stage 1 lung cancers from one country to the next but also because these patients will have an operation they will have a situation in which their stage 1 is present and their stage 1 is gone. By collecting different materials, including blood, urine, you’re able to look in the blood and the urine and those biofluids and see whether you have certain proteins or DNA or RNA that disappears once you do a complete resection on those patients.
How does it differ from the BATTLE trials that looked at biomarkers in NSCLC?
A very different concept, with the BATTLE trial that’s really a therapeutic sort of trial in which you are looking for biomarkers that are going to tell you that a specific targeted therapy matches a mutation or some other aberration that’s going to be specific for that patient. This BOOSTER trial is not going to be really for therapeutics, it’s going to be for diagnostics because if you’re able to find a biomarker that goes along with lung cancer, meaning it goes away if you take the lung cancer away, then that may be a diagnostic marker for lung cancer but also it may be a biomarker that if you follow the patient’s blood or urine, wherever it’s found, and the biomarker stays low then that patient is still cancer free. However, if you find the biomarker comes back or is rising, as in a PSA for what it’s worth, you would think that the cancer is coming back and you’d need to do some sort of investigation to try to find it.
We will also have matching tumour from these patients. So the tumour and the normal tissue will be present from these patients that can be studied to be able to verify that these biomarkers that we find in the blood or in the urine actually are coming from the tumour or may even be coming from things within the blood like white blood cells. So it’s very important to be able to query all these to find out where is the biomarker coming from, is it cancer related or is it non-cancer related?
How many patients will be involved?
The number of patients roughly is a thousand patients that could be accrued potentially over a three year period considering that we will have institutions in Asia, in the UK, in the United States, in Europe that are going to be contributing to these trials. You only have to have a small number of patients per institution if you have a large number of institutions. But the importance of having a thousand patients like this is that these are a thousand patients from different geographies that may actually show differences in lung cancer from one country to another. That’s very important because we’ve learned that there are different mutational patterns based on geography and we need to know that even more for determining what biomarkers are going to be appropriate for a population.
So what stage is the programme at?
It’s just starting. Essentially a protocol has been written; essentially a committee is being formed and we hope that over the summer we’re going to be able to finalise a number of different things. First of all we have to decide are we going to use simply paraffin embedded tissue for our biomarker discovery in the tissues. That saves a lot of expense as well as a lot of manpower or labour if you don’t have to worry about fresh frozen tissue. Second, you have to decide how much blood or urine you’re going to take. We envision that we’re going to take probably 100cc of blood from the patients before they get operated on and then 2-3 months, maybe 3-6 months which also has to be finalised, on the postoperative visit another 100cc so then you can compare those two. Then you have to decide what are you actually going to do in the future with that. It’s not that you have to define right now what are the tests you’re going to do but you have to have an idea of how much material you need to provide for tests in the future. Certain tests require more serum or more plasma than others so you have to make sure that your archives are set up so that you have enough for those tests that may require more reagent.
What may be some of the challenges that may be faced?
The challenge is really just getting interested surgeons. This is really driven by the patients who are resectable so you need to reach out to your surgeons at institutions who will most likely be very willing to provide the tissue as well as have the blood draws. But everything comes down to funding and you need to be able to have somebody who is going to run the trial, that would probably be done for nothing, but you need to have the people who would help to get the trial done at that particular institution. Who is going to pick up the bloods from the operating room or the clinic? Who is going to then process the bloods? Who is going to store the bloods? Who is going to keep track of where the bloods are? Who is going to be the person that’s going to send the bloods to the central repository so that the testing can be done? So all of those personnel costs, as well as reagent costs, add up; it’s not that much but at the same time you need to be able to have that in place before you have a trial like this started.
How does the WIN Consortium plan on encouraging participation in the trial?
I think it’s going to depend upon philanthropy, I think it’s going to depend upon grants. I think that the individual patients’ personal experience, since I’ve been doing this for twenty years, patients are very happy to donate a portion of their tumour as well as have the bloods drawn before and after surgery. So that’s not an issue, getting patients to be on the trial, the only barriers are to be able to get it done and having the finances to be able to do everything that you want to do. You don’t have to have the finances to do the actual testing, you want to have the finances set up so that you can get the specimens and store them in a way that they will be able to be distributed to the scientists that are going to work with them.
What do you hope the BOOSTER programme will achieve?
I think we’re going to try to be one of the first consortiums that has a very, very standard way of having the blood taken, the blood processed, the urine taken, the urine processed, the processing of the white blood cells, as well as how we’re going to use the tissue. Because many of these archives do not have standard operating procedures so that everybody has preserved the tissue or the blood in the same way. Therefore if you don’t do that or if you have degradation of certain nucleic acids you don’t get consistent results. So this will be an archive that will be a resource for the whole scientific community in lung cancer that can then get information from this. Obviously what we’d love to be able to find is targets, meaning biomarkers of diagnosis, so that if we have something on a CAT scan that’s a nodule and a biomarker specific for lung cancer we’ll know what that is and we’ll know it’s a lung cancer and not something else. Plus, we’ll also know whether the patient is recurring and the sooner we can find out that a patient is recurring, in stage 1 lung cancer approximately 30% of the patients will recur and most of them recur within the first 2-3 years, the sooner we find that they’re recurring, the sooner they can get treated and then use the tissue that we have for the SEMS [?] algorithm to be able to then treat them going forward with the WIN Consortium.
Do you have a final take home message from your presentation?
I think that the only take home message is that consortiums like this, where you have people that are really committed to getting the tissue and doing the work, are the only way in which we’re going to make progress. Because individual siloed academic centres that are doing it will never have the power of the number of specimens and also won’t be able to network as well as something like the WIN Consortium to be able to use the tissue the way it needs to be used.
