Use of chemotherapy to treat children with intracranial ependymoma avoids or delays the need for use of radiotherapy which can potentially cause serious damage to the child’s nervous system, without compromising chances of survival. Intracranial ependymomas are tumours which mostly develop around the lining of the cerebral ventricles.
Over half of childhood intracranial ependymomas occur in the children under five-years, and effective treatments are limited. Further, the success of any treatment strategy in this age group has to be measured not only in terms of event-free or overall survival, but also by the potential for serious and/or irreversible damage to the brain. Radiotherapy causes multiple problems in many long-term survivors, including a reduction in intelligence quotient (IQ) and other cognitive defects such as short-term memory loss.
Professor Richard Grundy, Children’s Brain Tumour Research Centre, The Queen’s Medical Centre and University of Nottingham, Nottingham, UK and colleagues did a study of 89 children with ependymoma in the period 1992-2003. Of these, nine had secondary cancers at pre-operative imaging, while in the other 80, the disease had not spread. All had as much of their tumours surgically removed as possible, then received alternating blocks of myelosuppressive* and non-myelosuppressive* chemotherapy for an intended duration of one year. Radiotherapy was withheld unless their disease progressed.
For the 80 patients who did not have secondary cancers, 42% avoided radiotherapy, while the average of delay of radiotherapy to children who did require it was 20.3 months. With six years median follow-up, at three years overall survival of these 80 patients was 79.3% while event-free survival was 47.6%. At five years, overall survival was 63.4% and event-free survival was 41.8%. For the 50 patients that relapsed, 90% did so because of the tumours re-appeared in the brain rather than elsewhere.
There was no significant difference in event-free or overall survival between patients with complete and incomplete surgical resection, nor did survival differ according to histological grade, age at diagnosis, or site of disease. A later analysis of nine children from the study who had avoided radiotherapy showed they had normal IQs.
The authors believe there could be several reasons their treatment protocol avoided the need for radiotherapy. The intensity of the chemotherapy programme might have been essential. The effect of non-chemotherapy events, such as postsurgical neurotoxicity, intercurrent infections, shunt malfunction and treatment, could also have been important, suggesting that enhanced supportive and preventative care might benefit patients by allowing optimal chemotherapy to be achieved in a higher proportion of patients.
The authors conclude: “The original aim of avoiding or delaying radiotherapy in children without compromising outcome has been achieved. Our results confirm a role for primary chemotherapy in children with intracranial ependymoma. The results reported here will contribute further to the impetus for collaborative studies in Europe and the US in this very young age group.
“Despite these advances, the long-term outlook for children with ependymoma remains unacceptably poor and further therapeutic advances will only come through a better understanding of the underlying tumour biology.”
The findings are reported in a recent article published online and in the The Lancet Oncology special edition on paediatric oncology.
Myelosuppressive chemotherapy is chemotherapy a treatment which inhibits blood cell production.
Non-myelosuppresive chemotherapy targets cancerous cells without specifically inhibiting blood cell production
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