Neurotoxicity of cancer treatment: Neurocognitive dysfunction and underlying mechanisms

Due to improved treatment, over 80% of children with acute lymphoblastic
leukaemia (ALL) are now long term survivors. Central nervous system prophylaxis
is an essential part of current ALL treatment. Cranial radiation treatment
(CRT) has been reported to cause long term neurocognitive and academic deficits
among survivors. The literature suggests that also treatment with chemotherapy
exclusively * since 1984 the standard type of treatment in The Netherlands * is
associated with neuropsychological sequelae, in particular in the domain of
executive functions.
Much of the information on long term sequelae of treatment, also from our
previous study*, relates to outcomes within the first 5 * 10 years following
treatment. Data on long term consequences beyond this time frame are
insufficient. In addition, the greatest gap in our knowledge regarding
treatment-related cognitive changes is a lack of understanding of the
mechanism(s) that account for these sequelae. So far, abnormalities detected by
structural (conventional) MRI have not consistently been found to correlate
with clinical findings and neurocognitive status. More sensitive imaging
measures that have recently been developed, are considered necessary.
As in other countries cranial radiation is still an important option in the
treatment of childhood ALL, and because in other diseases CRT is unavoidable,
the study of CRT-related consequences may provide important information.
We hypothesize that long-term unfavourable effects of treatment of childhood
ALL are reflected in a neuropsychological profile emphasizing executive
function (EF) deficits. This deficit profile may be more outspoken in survivors
treated with chemotherapy and cranial radiation (vs. treated with chemotherapy
only). As the quality of executive functions is, above all, dependent on the
integrity of functional networks of the brain, it is hypothesized that EF
deficits are associated with disruptions of neural networks. These disruptions
may be more severe in survivors treated with cranial radiation in addition to
chemotherapy.

* Effects of Chemotherapy on Attention and Information Processing in Survivors
of Childhood Cancer (KWF, project number: AZVU 2001 - 2390). De Sonneville LMJ,
Veerman AJP (principal investigators), Buizer AI (research physician)

With this information we hope to be able provide ex-patients with more detailed
information about late effects of treatment. Also it is a very important step
towards ajusting current treatment protocol to prevent late effects as much as
possible.

The study will be purely observational. It will include a neuropsychological
assessment to determine the neuropsychological deficit profile of long-term
survivors of childhood ALL, neuroimaging of the brain to bring out disruptions
in the functional integrity of neural networks (MEG, (f)MRI, DTI) and
questionnaires on quality of life.

Patients will be requested to visit the VUmc twice: the first time for
neuropsychological assessment (2 h) and MEG acquisition (1 h 45 min), the
second time for an MRI scan (1 h). Furthermore they will be asked to complete a
questionnaire at home and bring it on their first visit.
Subjects will be consulted about a convenient time for the appointments.