Chemotherapy for children

Chemotherapy is as good a treatment as radiotherapy for children with brain tumours reported BBC News. The article went on to comment that “using chemotherapy instead of radiotherapy in children with brain tumours reduces the risk of long-term brain damage”.

The story is based on a study in young children with intracranial ependymoma, a form of brain tumour. The aim of the study was to investigate if radiotherapy, thought to be the most effective therapy but also prone to detrimental side effects, could be avoided or delayed by using chemotherapy first.

One interpretation of the BBC story is that chemotherapy was found to be as effective as radiotherapy for treating brain tumours in children, and as it has fewer side effects, is the preferable form of treatment.

This study does seem to confirm that chemotherapy can be used to avoid or delay radiotherapy without adverse effects on survival; whether this reduced the side effects of radiotherapy (short- term memory loss and a reduced IQ) was not tested.

However, the NHS Knowledge Service concludes that as the study was not designed to perform a comparison between radiotherapy and chemotherapy and was neither controlled  or randomised, it is not possible to reliably compare the two.

Finally, the study is in very young children with a specific form of brain tumour, and as such, the findings cannot be directly inferred to other age groups and diseases.

Where did the story come from?

The research was conducted by Professor Grundy and colleagues of the Children’s Cancer and Leukaemia Group. This research was co-ordinated by the University of Leicester and funded by Cancer Research UK and the Samantha Dickson Brain Tumour Trust. It was published in a peer-reviewed medical journal, the Lancet .

The study was a case series, which means that it did not have a control group, with which to compare the survival rates. The aim was to see if radiotherapy could be avoided or delayed by using chemotherapy first.

The study enrolled 89 children between 1992 and 2003. These children were under the age of 3 when they were diagnosed with a particular type of brain tumour (ependymoma). All of the children were given chemotherapy four weeks after their surgery using four different chemotherapy regimens. Treatment was given every 14 days (using carboplatin, cyclophosphamide, cisplatin or high-dose methotrexate). This means that one cycle lasted 56 days. In total children were given seven cycles of chemotherapy, or about a year of the treatment.

The chemotherapy was discontinued if there were severe side effects or the cancer progressed. If the disease did progress, children were given radiotherapy. The dose of radiation depended on whether the disease was localised or spread and on the age of the child. Children were assessed using routine scans during their chemotherapy treatment.

What were the results of the study?

The researchers report that "42% of the children with localised disease did not need radiotherapy in the five years following surgery" and that 79% of these children were still alive three years after treatment and 63% were still alive after five years. The researchers also state that children with localised disease who “achieved the highest relative dose intensity of chemotherapy had the highest” five-year survival rates (surviving at least five years after treatment) compared with those who had the lowest dose.

What interpretations did the researchers draw from these results?

The researchers conclude that “primary chemotherapy strategies have an important role in the treatment of very young children with intracranial ependymoma”.

What does the NHS Knowledge Service make of this study?

This is an interesting study with exciting findings that should form the basis for future research into the use of chemotherapy for children with intracranial ependymoma.

It is important to note that this was a case series. This is an appropriate study design for a rare condition where the recommended treatments change rapidly, however as it was not controlled or randomised, we are unable to directly or reliably compare chemotherapy with radiotherapy.

Though the researchers do compare their survival results with those of other cohort studies in children with cancer, the absence of a control group drawn from a similar population and followed up in the same way means that it is not possible from this study to say that chemotherapy is better than radiotherapy.

The study is in very young children with a rare type of brain tumour. It may not be possible to generalise the results from the study with regard to older children or children with other, more common, types of tumour.

The fact that chemotherapy can be used to avoid or delay radiotherapy without adverse effects on survival, seems to be confirmed, by this study. Whether this benefit translates into long term improvements in IQ was not tested.The researchers suggest studies of this and the development of agreement over how to grade children for treatment, as useful next steps.

Sir Muir Gray adds...

There is no part of healthcare which has a stronger evidence base than the management of leukaemia and other cancers in childhood. This study strengthens the evidence base, but it is important to remember that the treatment for individual children is not chosen by a cookbook approach. It requires careful appraisal of the needs of the individual, courage on the part of the parents and child and good clinical skills of the doctors and nurses involved.

Medicine is still full of uncertainty and we should welcome the fact there is now a library of uncertainties called the Database of Uncertainties about the Effects of Treatments where our ignorance can be filed and presented not only to researchers, but also to patients.

If the medical profession is ignorant and we are uncertain about what to do for a particular disease, the patient has a right to know.

The patient faced with uncertainty has a number of choices. One would be to ask the doctor what they would do and doctors will give advice based on their experience and values.

However, another option is to enter an ethically approved research study where treatment or a placebo will be given under tightly controlled conditions. This is what the parents of children with cancer have chosen and the results have been amazing. What is more, the involvement of children in research has in no way diminished the humanity and personalisation of the care given; no service does it better.

If faced with a major decision when there was uncertainty, I would ask if there is any research study in which I could be included.