The study was looking at brain metastases that were undergoing surgical resection. The standard of care is based on a 2017 study that we completed at MD Anderson showing that after post-total resection of a metastatic brain tumour that if you do stereotactic radiation to the cavity it actually provides a benefit over just observation alone. That formed the new standard of care after 2017. So what we did with the current trial is say how could we improve upon that and we used a new FDA-cleared brachytherapy implant that’s a 2x2cm tile containing radiation seeds that we put in the walls of the cavity. So the trial was comparing this new treatment, placing the tiles to deliver radiation at the time of surgery, and compare it to that historical standard of care which was giving the stereotactic radiation after the operation.

Could you outline the methodology?

It was a randomisation, 1:1 randomisation, across 32 centres in the US, 1:1 to each arm. We would randomise patients based on a number of factors to either the experimental arm or the control arm. So patients then were randomised pre-surgery and you either went on to receive the tiles at surgery, after the resection took place but all within that same surgery, or you came back 21 +/- 7 days after the surgery to get your stereotactic radiation. Patients could have up to five additional lesions not requiring surgery and those lesions could be treated with stereotactic radiation at that same timepoint, 21 +/- 7 days.

What did you find?

The findings show that we had two primary endpoints, one was surgical bed recurrence and one was surgical bed recurrence free survival. Both of those were significantly improved with the tiles. We also showed as a secondary endpoint that there was an overall survival benefit which was fascinating, given that this was a local control process for the tiles and for the postoperative stereotactic radiation which you wouldn’t normally expect to give an overall survival benefit. But yet we achieved a statistically significant difference in overall survival.

In order to control for this, we used a certain modified intent to treat population to do this analysis and we examined those two groups to try to understand and make sure that when we were doing overall survival analysis that it was true. So, for example, it was a non-inferiority design trial. When we did the statistics we had to prove not only non-inferiority but, in a hierarchical order, prove that it was then superior and only at that point did we jump to the secondary endpoint. So when we got to the secondary endpoint we had already passed considerable statistical barriers to get to be able to study that secondary endpoint. At that point we were able to show that there was an overall survival advantage.

What impact could these findings have?

It’s a great question. The impact from a patient perspective, we think, is pretty significant. There was already a good benefit with the stereotactic radiation but the tiles seem to, number one, there was a prolonged benefit so your ability to stay disease free where we gave the radiation in the tiles is significantly longer. Number two, the delays that patients might experience after surgery, so they might have rehabilitation needs after an operation, there’s wound healing, there are logistical issues and we found that a lot of patients actually complained of weather being a big issue that would prevent them from getting their postoperative stereotactic radiation. So that delay is gone because you get the tiles at the time of the surgery.

We also know that at four weeks after surgery, if that’s when you’re getting your radiation, that four-week cut-off is a cut-off where the local control is worse with postoperative stereotactic radiation greater than four weeks. So, because of that, if you’re getting the tiles early you’re getting your radiation right out of the operating room and for a longer period of time you go without recurrent disease.

The one other thing that we looked at is time to any adverse imaging change. So patients who on their MRI scan either had radiation necrosis or recurrent disease was a much longer time period. So we think that that longer timepoint gives patients a longer time to stay on their systemic therapy and go from time of surgery and be treated with systemic therapy for much longer because their time is not being interrupted by imaging changes from radiation necrosis or recurrent disease.

So the benefit outside of the numbers are logistical issues – you get your tiles right away; the benefit on long-term control and the benefit of not potentially having your systemic therapy interrupted, needs for steroids and other treatments.