Clinical trials good for child cancer patients

Increased participation in clinical trials since the late 1970s has dramatically improved survival rates among child cancer patients according to an analytical study published in the journal Annals of Oncology this week.

The United Kingdom Children’s Cancer Study Group (UKCCSG) was set up in 1977 with the aim of establishing a range of national and international clinical trials for most children’s cancers. As a result, national or international trials were open on the cancer types with which more than 60 per cent of children between 1978 and 2005 were diagnosed.

An increasing level of participation in trials during this time was accompanied by a rise in the percentage of children surviving for five years or more after diagnosis from 28 per cent in the period 1966-1970 to 79 per cent by 2005. The study related for the first time population-based survival rates to the number of trials open to entry, analysing data on 25,853 children diagnosed before the age of 15.

I spoke to Charles Stiller, Registry Director at the Childhood Cancer Research Group (CCRG), University of Oxford, and lead author of the paper to find out more about the remarkable progress made and the importance of clinical trials.

What were the aims of your analysis and what were you expecting to find?
The main aim of the analysis was to look formally at how the progress that has been reported in the outcomes of a large number of clinical trials for children with different types of cancer has translated into improvements for the totality of children with those types of cancer in the general population.

Broadly speaking, I suppose we expected to find what we did, namely that the improvements in the population as a whole followed those reported from the trials. It would have been surprising if they didn’t, simply because a lot of the trials recruited a very high proportion of the children who were eligible for them.

Do you think that other factors than participation in clinical trials could be behind the dramatic increase in survival rate?
Clearly for the children who were not involved in trials, participation could not have been a factor. During the period we were looking at, there was a steady increase in the concentration of childhood cancer treatment into principal treatment centres affiliated to what is now the Children’s Cancer and Leukaemia Group. In earlier decades going back to the 1970s many children were simply treated in general paediatric departments, but that hardly ever happens nowadays.

There has certainly been a concentration of expertise. There are many more doctors than there used to be who specialise in paediatric oncology and they all communicate with each other. There is a good network between them, and they all keep up-to-date with current developments.

And I suppose the treatments themselves have got better?
Of course, and that brings us back to the trials, which have a crucial role in the development of those treatments. One should not forget either that it is not simply a matter of anti-cancer treatments improving – improved supportive care must also have had an effect.

Why do you think the increased survival rate has been more pronounced in some types of cancer, such as hepatoblastoma and acute lymphoblastic leukaemia (ALL), than others?
Hepatoblastoma was starting from a rather low base, so there was greater scope for improvement. It has gone from being one of the childhood tumours with the least good prognosis to being a disease with quite a good outcome. Undoubtedly the trials that have taken place for that particular tumour, which is very rare, have been very important. In particular I think the first one of the series – which was probably the first example of a truly global childhood cancer trial – was a remarkable success.

ALL is the most frequent type of childhood cancer so the numbers of children affected are larger than for any other type. Of course that means that there is a much larger patient population for conducting trials and also it is the disease type which clinicians have most experience in treating.

In what ways does the study illustrate the importance of international and even global collaboration in clinical trials?
I began to answer that question with the example of hepatoblastoma. In the period covered by this study the other diagnostic groups for which there were international trials was neuroblastoma – where there was a succession of European studies – and the sarcomas. In fact, the increases in survival for some of the sarcomas are not as great as for some of the other diagnostic groups, but on neuroblastoma very respectable progress was made.

For ALL, you can now expect to get five year survival rates in 90 per cent of children aged one to 14. Infants traditionally had a much poorer prognosis, but in the last part of the study from 1999 onwards, which is the era of an international infant ALL study, there was again a striking increase in survival.

What lessons do you think can be taken from the work of the CCRG so far and this study in particular about the importance of clinical trials more generally?
I should say I’m speaking from the epidemiologist’s and statistician’s point of view; I’m not a clinician. The gains that have been seen in the trials, which have been well-reported in the literature, are reflected in the general population partly because of the way in which there have often been very high accrual rates for the trials. Most of the children not in the trials have been treated according to something very like the trial protocols anyway. The diffusion of progress into the population as a whole has been extraordinarily rapid compared to what has been found with some adult cancers. I think this is certainly something that is of crucial importance. The trials are the recognised, scientifically sound way in which treatment developments can be evaluated. Each trial also lays the groundwork for maintaining survival at a higher level in the future.