ASTRO 2015

Stereotactic radiation therapy for oligmetastases

Dr David Palma – London Health Sciences Centre, London, Canada

What will you be talking about at the joint ASTRO/ESTRO session?

Today at ASTRO/ESTRO we’re talking about the concept of oligometastases and that concept is a relatively new one in oncology. It used to be thought that if a patient had metastases, meaning that they had a cancer that had spread to other parts of the body, then unfortunately that patient would be incurable and they would be treated with palliative treatments only, trying to improve quality of life, maybe extend survival but not to get rid of the cancer. Now we’re recognising that there may be some patients who have a limited number of metastases and that is called oligo, meaning just a few, oligometastases. The hypothesis is that if patients only have a limited number of metastases and you can treat them, you can ablate them with radiation or some other types of treatments, then maybe in some situations the cancer might not come back and in theory some patients could be cured and that’s the topic of our session today.

What are some of the issues in treating patients with oligometastases?

One of the big issues is that it’s very hard for us to determine right now how much benefit patients get if we treat them aggressively with types of radiation such as stereotactic radiation. We know that some patients go a long time without their cancer coming back but there has never been a randomised trial to prove that we can extend the survival in patients with oligometastases in several parts of the body. For patients with a single brain metastasis we know we can improve survival but for every other situation, such as a lung metastasis or a liver metastasis, that has not been proven. So oncologists are struggling a bit, we have to use the best available evidence but it’s not the best possible evidence until we have randomised trials. The difficulty is that in any treatment in medicine we always have to balance the risks with the benefits and we only give a treatment if the benefits outweigh the risks. The problem is that the benefits are not quantified: we don’t know how many patients we have to treat to cure one so it’s hard to weigh that against the possible risks. Even though treatments like stereotactic radiation are very safe there is a small risk of a serious injury and sometimes patients can be hospitalised, it’s not common, but if it happens to your patient it’s unfortunate. So what we’re calling for is we’re calling for better evidence to help physicians decide who to treat aggressively when they have oligometastases and which patients would be best served instead with a palliative approach focussing more on quality of life.

So are there randomised trials already in progress?

There are several trials running at the moment. The one that’s furthest along is a collaboration between my centre in London, Canada and the VU University in Amsterdam where we are randomising patients with up to five oligometastases either to have stereotactic radiation to all of the metastases, and that’s the experimental arm, or in the standard arm to have palliative radiation, palliative chemotherapy. That trial is about two-thirds complete and we expect to finish it in about 2017. It’s currently open in Amsterdam, also in Scotland, across Canada and in Australia, so it’s truly an international effort.

So you have any indication of the findings, or is the trial still closed down?

Yes, it’s still closed down; we won’t know until the final results. All there was was an interim analysis with a go/no-go decision but we don’t get the data, we just get told, ‘Continue the trial.’ The data that we do have is data such as single arm observational trials where patients are treated and we follow them to see how they do. Those trials can be quite helpful; we see that in some cases you still have more than half the patients alive at two years, even though they have metastatic disease. But there is no control arm in those trials so we don’t know for sure is the better than expected survival because of the treatment or is it because we’re choosing patients with more indolent cancers. In medicine we’ve been down this road before, sometimes we’ve been fooled by observational data without adequate controls. That happened in the ‘80s and ‘90s when people were doing stem cell transplants for breast cancer – they would get high dose chemotherapy and stem cell transplants, there was a lot of enthusiasm because of better than expected outcomes in uncontrolled trials but when they did the randomised trials the benefit wasn’t there. So we have to be careful making sure that we learn from our past. Nonetheless we are very excited about this paradigm and our hope is that these trials will be positive when they’re done but we have to do the work and find out.

From a practical perspective how can stereotactic radiation therapy currently be used in patients with oligometastases?

What we know right now is we know which patients do well when they have oligometastases and which do poorly. If patients are known to do poorly it’s probably not worthwhile treating them aggressively. There’s a colloquial term for how we identify these patients who do very well and it’s the four aces, like a good poker hand. The four aces are patients who are young, patients who are fit, patients who have slow growing cancers and a low disease burden. So an example of that might be a 35 year old with no medical problems who has a cancer come back with a single metastasis, maybe five years after the original tumour was diagnosed. That would be all four of those aces; that patient is going to do very well. We don’t know for sure if it’s from the treatment but that’s a lot different than somebody who is 70 and has multiple comorbidities, multiple illnesses and they have numerous metastases and the primary tumour is still in place. That’s a bad prognostic factor. So we know how to select people and until we wait for the trials we have to be judicious about offering this treatment to the right population.