One of the big things that’s going on in cancer right now is these new drugs that stimulate and activate the immune response. Traditionally we’ve had all these drugs that kill the tumour and they poison the tumour and we zap the tumour with radiation but this is kind of a new era right now. We have these drugs that can activate the T-cells and stimulate them and then those immune cells really do the heavy lifting and treat the cancer. We are seeing nice activity, it started off in melanoma and now we’re seeing activity in lung cancer, which I specialise in, and a lot of other tumour types as well.
What we’re now looking at is how to best use these for patients and then what we combine them with. I am a radiation oncologist and one of the areas that we are interested in is to see if we can add radiation to immunotherapy to actually get it to work better. Radiation has been used for about 100 years to treat cancer patients and it’s all been focussed around local control, so we see a tumour, we make a plan and then we hit that tumour and then it controls it there but it does nothing for the disease throughout the body. Now with the combination of immunotherapy we really think we can use radiation to turn the tumour basically into a vaccine so we kill the tumour, it slowly dies, it exposes antigens and then can combine that with immune drugs to stimulate these T-cells. So the two can work better together to treat disease outside of what was irradiated so that’s the topic that we were talking about, a lot of the biology and then the practical ways to implement this.
What stage of development is the research in?
It’s very much being investigated in pre-clinical research in animals, running some of the very first trials. There’s a lot of phase I and II studies studying this right now and some of those are just starting to read out. Ideally, we would like to wait and see what these look like in terms of safety, how safe it is is the first thing that many of these studies look at to make sure we are not causing harm in our patients and more toxicity and then also to get a sense of the best way to do it. What’s the right way to sequence the radiation, what’s the best dose of radiation? Which site is the best, is it best to hit a lung site, a liver site, a bone site? But, what’s actually happening now is a lot of these drugs have gotten approved so now they are standard care approved for melanoma, lung cancer, head and neck and renal cell. So what’s happening is a lot of these patients are getting on these drugs, people are progressing and radiation oncologists are being asked to irradiate certain areas that are progressing while they are on the drugs. So, the radiation oncologists are kind of being put in a spot where they’re sometimes pushed or kind of forced to do radiation even though on those drugs we don’t always have the data. A lot of the trials we are trying to run at MD Andersen are really focussed on trying to answer these questions. Is it safe to treat it in the lung? Is it safe to have the drugs on board? What are the right doses where it is safe? Would there be increased toxicity?
So far we have treated a few hundred patients at MD Anderson doing this. We thought there might be a lot more lung toxicity because the immuno drugs alone can cause some inflammation in the lung. So far, we haven’t seen a lot of that increased toxicity when we irradiate the lung. We’ve started at very small safe doses of radiation which we call stereotactic and we’ve slowly gone up to bigger ones. So far the small doses seem to be quite safe. We have done quite a bit of treatment also in the liver with immunotherapy and that seems to be pretty well tolerated as well but we are very cautious about areas around the heart and we could irritate that lining causing a pericarditis and I am also concerned about doing this in the abdomen area where you could irritate the bowel and colitis and irritation in the bowel is a known side effect of immune drugs and if we irradiate there that could really cause increased problems, so those are some of the sites we want to proceed cautiously in.
Will this treatment progress into treating multiple types of cancer?
That’s a great question. Different areas and different settings where its progressing forward to but I have a feeling that we will have great interest to do this in almost every solid tumour that’s treated by radiation. This won’t just be a melanoma thing, I think there is strong relevance for lung cancer, breast cancer, oesophageal cancer, pancreatic cancer, colorectal, prostate cancer. All those ones we treat with radiation, they generally all need some improvement, either with local control, which immune agents could potentially help with that and the distant control, failing outside the body. And so all those tumour histologies need help with that and so the immuno combinations are a logical thing to put into that so it’s an evolving thing in the different stages and the different tumour types. It’s just one of those things there’s a lot of interest and excitement in it right now but we just want to make sure we don’t harm the patients and we do this cautiously and learn so that we figure out who benefits and who should take this on and where it may not be as helpful.
What is the take-home message?
We published at ASCO a series on doing stereotactic in the lung and in the liver for the first thirty patients and it seemed like it was pretty well tolerated. So you just want to keep an eye on the literature to see what is coming out. Like I said, I get a lot of calls from people all over the world who have people on immunotherapies that are progressing and then they are being kind of forced to treat with it on and just interested in the best way to do it, how safe it is to do it. If in doubt maybe you can stop the immuno agent, let it wash out, particularly if you are doing treatment in an area where you are concerned. If you are irradiating by the bowel, maybe something in the brain and that’s one option, or if you leave it on, watch them cautiously. Work closely with your medical oncologist because the side effects we see are not always the ones we are used to in the radiation world. It’s irritation, it’s inflammation, so the immune system gets revved up and so they are different types of side effects. So watch your patients closely, work closely with your medical oncologist.
One thing that came up from one of the other speakers that’s very helpful is these patients on immunotherapy drugs should have a card or be able to tell doctors in the emergency room what they are on. Because a lot of times if they go to an emergency room they will put them on steroids or things that could keep the immuno treatments from working potentially because they are not sure about the other thing that are going on. So, we want to have good communication for people that might see toxicities and so that they call the cancer doctors to understand what’s going on and keeping us informed.
