The study we presented here was called SCORAD and it’s a study into the optimal form of radiotherapy for metastatic spinal cord compression. Metastatic spinal cord compression is a common complication of cancer and has devastating effects on patients because they lose the use of their lower limbs, they become dependent and unable to move without help. The study was to evaluate the best way of giving radiotherapy which is the most common treatment used for this condition. Currently there is wide variation across the world, ranging from single doses to multiple doses given over three or four weeks. The duration of treatment is particularly important in this group of patients because their survival is relatively short and the median survival in our population that we studied was only thirteen weeks which is not untypical of that group of patients. So taking up two or three or four weeks of their time with radiotherapy when it’s not necessary is a critical issue.
We therefore set out to see whether a single dose of radiation was adequate for these patients. We undertook a prospective randomised trial, a non-inferiority design, randomising between a single dose of 8Gy to a multi-fraction schedule which in this case was 20Gy given over five days, so over one week. There were altogether 697 patients randomised and randomisation was from 47 centres. It was carried out primarily in the United Kingdom where there were 43 centres and there were four centres also from Australia. Of those 687 were evaluable and they took part in the final analysis. The primary endpoint was ambulatory status, so the ability to walk at eight weeks. We measured ambulatory status on a four point scale: points 1 and 2 meant the patient was ambulant, either with or without walking aids; point 3 meant the patient couldn’t walk although they still had some motor power in their lower limbs and point 4 was a patient who was paraplegic with flaccid limbs.
The headline result was that there was no difference between the two treatment schedules in terms of ambulatory status, whether that was measured at eight weeks or, indeed, at the other time points we looked at – 2 weeks, 4 weeks and 12 weeks. Similarly the secondary endpoints were all the same across both arms of the radiotherapy. Secondary endpoints included bowel and bladder function, quality of life, retreatment rates and, of course, survival which was identical across the two arms.
The conclusions of the study were that a single dose of 8Gy is adequate and effective for these patients. It’s not detrimental to the likelihood of them being successfully treated in terms of retaining mobility and also in terms of other functions and quality of life. We would propose that this should be seriously considered for all these patients as a standard of care now.
I’m glad to hear the inclusion of quality of life as a measure there because that has been something of a theme from today’s press releases – we are treating people not disease. In the time that you’ve had, as we’ve mentioned, there have been many questions of how will this affect care going forwards and the obvious savings in terms of costs. Where do you think this could be applied most readily? You mentioned the global variation, is anyone ahead of the curve already in terms of this?
In the United Kingdom we are very much so because we are much more familiar with giving large single doses in the palliative setting. So for painful bones, for example, it’s standard treatment and in many other settings. So the precedent is already there in the United Kingdom; it’s similar in some other countries – Canada and Australasia have very much followed our lead in that approach and Canada is very strong in advocating single dose radiotherapy with a very strong palliative lobby there. So in those three areas it will certainly very readily be taken up. In mainland Europe it will also be used although perhaps not quite as commonly. In the United States it has been a much bigger challenge to get American radiation oncologists to take on board single dose treatments and there are all sorts of complex issues around that which are partly cultural, partly hearts and minds. So I think it will be harder but there is a very real group in the United States now of active palliative care radiation oncologists who are promoting the use of single doses and with time it will be taken forward.
When it comes to possibly using this with other diseases, indications that have metastasised to the back of spinal column, would you see that as useful there for alleviating some of the disease as well?
Yes, it’s already used routinely for painful bones that haven’t impinged on the spinal cord. It’s also used routinely for painful bones with cancer in them that are causing pain because the cancer, the tumour lump, is pressing on the exiting nerves, the nerve roots of the spinal column. So in that case that is already fairly standard practice, this is really perhaps the last bit of the jigsaw puzzle in terms of spinal radiation. There are, of course, other issues – we did have toxicity. There was no difference in toxicity between the two arms but about 30% or so of patients get some degree of toxicity. It may be that we need to think about the techniques we use for treating the spine, there are certainly more complex modern techniques which allow us to give radiation to the spine without giving radiation to the organs in front of the spine such as the bowel which is particularly sensitive and causes a lot of the side effects. So there are still questions to be answered, certainly in terms of radiation technique, certainly in terms of those patients who may benefit from more active treatment, more radical treatment, the patients with what are called oligometastasis where this may be the only site of disease, and indeed those patients may well be selected for surgery. So it’s not applicable to all patients but the vast majority who sadly come to us with multi-site disease, those are the patients for whom it is particularly applicable.
I’m sure all the people putting the work in for the new proton centre in Cardiff, the ones in London and Manchester are coming along as well, will be very happy to hear that there is even more work for them with targeted radiotherapy. I don’t suppose there are any plans to investigate even further reductions with a single dose of, say, 4-6Gy rather than the full 8Gy?
Yes, we did that in metastatic bone pain and there are three large randomised trials looking at 4Gy and one of those looked at 6Gy as well. They all showed consistently that although 4Gy was effective in some patients it was not as effective as 8Gy. So there’s an implication there that we are close to a dose threshold and it doesn’t actually take any longer to deliver 8Gy than 4Gy, within a matter of a few seconds, so there’s probably no great benefit unless that were to reduce toxicity. But I don’t think we’ve got that evidence so I suspect that we’ve gone as far as we can with spinal cord compression. In bone pain 4Gy is certainly a useful dose, particularly for patients who need retreatment. So it’s a much more comfortable dose to give after previous radiation to a bone.