The purposes of this study are to uncover1. Which surgical methods are least likely to cause the CMS and if there is a difference in risk between primary surgery andreoperation2. Which patients may be genetically predisposed to developing the CMS 3…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
- Nervous system, skull and spine therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To explore the relationship between different surgical methods for the removal
of posterior fossa tumours, and relate these to
the incidence and clinical course of the CMS (prospective observational study).
Hypothesis: Methods that spare the dentate nuclei and their efferents and focus
on minimally traumatic techniques lower the
risk of developing the CMS by 50%, and lessen its severity and duration by 40%
when compared to more invasive tumour
removal methods. The risk of getting the CMS is greater after reoperation(
s) when compared to primary surgery.
Secondary outcome
Genetics
To analyze the role of genomic variants on the development, severity and
recovery from the CMS by carrying out a broad genetic profiling of the study
participants (SNP analysis). Hypothesis: Genetic variants in inflammation,
vascularization, neuronal tissues, neurotransmitters, neurotransmitter
transporters, blood-brain-barrier tissues and/or lipoproteins explain at least
50% of the variation in incidence of CMS and explain at least 40% of the
variation in severity, duration and level of recovery from the CMS in those
instances where tumour type, size, location and the surgical approach are
similar.
Corticosteroids
To explore the effect that pre, intra and/or postoperative corticosteroids may
have on the risk and severity of the CMS (prospective observational study).
Hypothesis: Preoperative corticosteroids have a protective effect against the
development of the CMS as they reduce vasogenic (tumour induced) cerebral
oedema and thereby ICP. Intraoperative corticosteroids increase the risk of
getting the CMS as the hyperglycaemia that they induce can cause acute
neurological injury. Postoperative corticosteroids have a negative effect on
the overall outcome of the CMS as earlier studies have shown a negative effect
on the treatment of traumatic head injuries.
Other treatments
To investigate the effect of chemo and radiotherapy on recovery from CMS.
Additionally information will be gathered on any medication specifically given
to treat the symptoms of the CMS , with the aim of documenting what helps and
does not help (prospective observational study). Hypothesis: Chemo and
radiotherapy delay recovery from CMS.
Tumour type
To document the incidence of the CMS according to histological tumour type
(prospective observational study). Hypothesis: The risk of CMS depends on
tumour type.
Handedness
To determine whether the risk of the CMS varies according to handedness
(prospective observational study). Hypothesis: The risk of CMS is increased in
lefthanded compared to righthanded and even more so in cases of
medulloblastomas.
Comorbidities
To determine whether the presence of any comorbidities influences the risk of
the CMS (prospective observational study). Hypothesis: The risk of CMS is
increased in patients suffering from chronic comorbidities such as NF1,
diabetes, heart diseases etc.
Language and speech
To analyze the speech and language deficits associated with CMS on shortas well
as longterm basis, and to explore how preoperative language status affects the
risk of developing CMS. Both have been done before, although in significantly
smaller cohorts (prospective observational study). Hypothesis: Poor
preoperative speech and language status increases the risk of postoperative
speech and language deficits. The degree and type of impairment also depends on
other patient and tumour variables.
Neuroradiology
To replicate and further extend the association between certain
neuroradiographic features and development of the CMS established by previous
studies (prospective observational study). Hypothesis: Different
neuroradiographic features carry different risks for the development and
progress of CMS.
Background summary
Central nervous system (CNS) tumours constitute 25% of all childhood cancers,
and more than half of these are located in
the cerebellum. One of the most troublesome late effects after operation for
such a tumour is the cerebellar mutism syndrome
(CMS) which is seen in up to 25% of children after surgery. It is characterized
by mutism, hypotonia, ataxia and irritability, and
the exact causes have yet to be identified.
Although a cure may have been achieved with respect to their brain tumour, the
CMS and its consequences can still
represent a lifelong challenge for these children. Since roughly half of all
paediatric brain tumours reside in the posterior
fossa and require operative removal, the CMS constitutes both a common and
severe problem in paediatric neurooncology.
Study objective
The purposes of this study are to uncover
1. Which surgical methods are least likely to cause the CMS and if there is a
difference in risk between primary surgery and
reoperation
2. Which patients may be genetically predisposed to developing the CMS 3. The
effect that corticosteroids may
have on the development and clinical course of the syndrome 4. Differences in
incidence and clinical course of the CMS
according to tumour type, comorbidities, handedness, the effect of attempted
symptomatic medication and chemoand
radiotherapy
We hope that the results will contribute to an overall reduction in incidence
and severity of the CMS as well as increasing
understanding and awareness of the syndrome. Furthermore, this study can lead
to harmonization of the treatment of these
patients.
Study design
Multicenter prospective observational cohort study
Study burden and risks
Patients participating in the study will be treated according to the local
standards. Additionally, we will take preand postoperative speech samples that
take about 10 minutes each. We will also ask for one extra blood sample of 2 cc
for genetic analysis, that can be taken at any time point during the study (for
example, along with other routine blood samples). Participating in the study
will not impact or interfere with the child*s treatment plan and the child will
not be exposed to any additional risks or disadvantages by participating in
this study except for the blood sample which carries minimal risks and
discomfort.
CMS is almost exclusively seen in children. Very few cases of CMS in adults can
be found in the literature, and thus it would not be possible to perform this
study in an adult population.
Besides contributing to an increased understanding and awareness of the CMS
this study has the direct prospect of reducing both the incidence and the
severity of the syndrome, which would be a great advantage for other children
with CMS.
Blegdamsvej 9
Copenhagen 2100
DK
Blegdamsvej 9
Copenhagen 2100
DK
Listed location countries
Age
Inclusion criteria
- Age <18 years at the date of first imaging showing this tumour
- Tumour in the cerebellum/4th ventricle/brainstem with intention to treat with
surgical resection or open biopsy. Second and further surgeries are also
included.
- Signed Informed consent from custodial parent(s) and/or patient
Exclusion criteria
No informed consent
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02300766 |
| CCMO | NL81967.041.22 |