paediatrics Brussels 17

1447 / 1708

696 Vol 8 August 2007
Articles
Primary postoperative chemotherapy without radiotherapy
for intracranial ependymoma in children: the UKCCSG/SIOP
prospective study
Richard G Grundy, Sophie AWilne, Claire LWeston, Kath Robinson, Linda S Lashford, James Ironside, Tim Cox, W Kling Chong,
Richard H A Campbell, Cliff C Bailey, Rao Gattamaneni, Sue Picton, Nicky Thorpe, Conor Mallucci, MartinW English, Jonathan A G Punt,
David AWalker, DavidW Ellison, David Machin, for the Children’s Cancer and Leukaemia Group (formerly UKCCSG) Brain Tumour Committee
Summary
Background Over half of childhood intracranial ependymomas occur in children younger than 5 years. As an adjuvant
treatment, radiotherapy can be effective, but has the potential to damage the child’s developing nervous system at a
crucial time—with a resultant reduction in IQ and cognitive impairment, endocrinopathy, and risk of second
malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in
children younger than 3 years with intracranial ependymoma.
Methods BetweenDecember, 1992, and April, 2003, we enrolled 89 childrenwith ependymoma whowere aged 3 years or
younger at diagnosis, of whom nine had metastatic disease on pre-operative imaging. After maximal surgical
resection, children received alternating blocks of myelosuppressive and non-myelosuppressive chemotherapy every
14 days for an intended duration of 1 year. Radiotherapy was withheld unless local imaging (ie, from the child’s
treatment centre) showed progressive disease.
Findings 50 of the 80 patients with non-metastatic disease progressed, 34 of whom were irradiated for progression.
The 5-year cumulative incidence of freedom from radiotherapy for the 80 non-metastatic patients was 42% (95% CI
32–53). With a median follow-up of 6 years (range 1·5–11·3), overall survival for the non-metastatic patients at 3 years
was 79·3% (95% CI 68·5–86·8) and at 5 years 63·4% (51·2–73·4). The corresponding values for event-free survival
were 47·6% (36·2–58·1) and 41·8% (30·7–52·6). There was no significant difference in event-free or overall survival
between complete and incomplete surgical resection, nor did survival differ according to histological grade, age at
diagnosis, or site of disease. In 47 of 59 (80%) patients who progressed, relapse resulted from local control only. The
median time to progression for the 59 patients who progressed was 1·6 years (range 0·1–10·2 years). The median age
at irradiation of the whole group was 3·6 years (range 1·5–11·9). For the 80 non-metastatic patients, the 23 who
achieved the highest relative dose intensity of chemotherapy had the highest post-chemotherapy 5-year overall survival
of 76% (95% CI 46·6–91·2), compared with 52% (33·3–68·1) for the 32 patients who achieved the lowest relative dose
intensity of chemotherapy.
Interpretation This protocol avoided or delayed radiotherapy in a substantial proportion of children younger than
3 years without compromising survival. These results suggest, therefore, that primary chemotherapy strategies have
an important role in the treatment of very young children with intracranial ependymoma.
Introduction
Over half of childhood intracranial ependymomas occur
in children under 5 years of age, and the effective
treatment of these patients remains one of the more
difficult tasks in paediatric oncology.1 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 in terms of the potential for serious or irreversible
damage to the developing brain.
Most childhood ependymomas arise in the posterior
fossa, are large, and are difficult to resect. There is
general acceptance that adjuvant therapy is required
even when complete resection is achieved.2–7 Choices
over adjuvant therapy are difficult, and to an extent, have
depended on the underlying philosophies of national
groups and institutions. Radiotherapy is effective, but its
delivery is complicated by the vulnerability of an
immature CNS to radiation damage. Although the
degree of functional impairment depends on field size,
radiation dose, and age at treatment, most long-term
survivors have multiple problems including a global
reduction in IQ and more specific cognitive defects such
as short-term memory loss. 8–11 Preliminary studies
suggest that conformal radiotherapy to the posterior
fossa in children older than 12 months might not result
in severe neurocognitive damage, at least in the short
term.4 However, there are other serious delayed effects
from radiotherapy, such as neuroendocrine sequelae and
second cancers which could adversely affect the child’s
quality of life.12–14
The perception of unacceptable side-effects of cranial
radiotherapy in young children led a number of institutions
and national groups to adopt chemotherapy-based
strategies designed to avoid or delay irradiation.2,3,5,6,15
Lancet Oncol 2007; 8: 696–705
Published Online
July 20, 2007
DOI:10.1016/S1470-
2045(07)70208-5
See Reflection and Reaction
page 665
Children’s BrainTumour
Research Centre, University of
Nottingham, Queen’s Medical
Centre, Nottingham, UK
(Prof R G Grundy MBChB,
S AWilne MBBS,
J A G Punt MBBS,
Prof D AWalker MBBS);
Children’s Cancer and
Leukaemia Group, Data Centre,
Leicester, UK(C LWeston MSc,
K Robinson BA,
L S Lashford MBBS,
R H A Campbell MBChB,
Prof C C Bailey MBBS,
R Gattamaneni MBChB,
Prof D Machin PhD);Western
General Hospital NHSTrust,
Edinburgh, UK
(Prof J Ironside MBChB); Great
Ormond Street Hospital for
Children NHSTrust, London,
UK (T Cox MBChB,
W K Chong MBChB) ; St James
Hospital NHSTrust, Leeds, UK
(S Picton MBChB); Alder Hey
Children’s Hospital, Liverpool,
UK (NThorpe MBChB,
C Mallucci MBChB); Birmingham
Children’s Hospital,
Birmingham, UK
(MW English MBChB);
Newcastle General Infirmary
NHSTrust, Newcastle upon
Tyne, UK
(Prof DW Ellison MBChir) ;
National Cancer Centre,
Singapore (D Machin)
Correspondence to:
Prof Richard Grundy, Children’s
BrainTumour Research Centre,
University of Nottingham,The
Medical School, Queen’s Medical
Centre, Nottingham NG7 2UH,
UK
richard.grundy@nottingham.