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Central Nervous System Tumors in
Children
Dr Sasikumar Sambasivam
DNB Resident
Radiation Oncology
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20% to 25% of all malignancies that occur in childhood
etiology remains largely unknown
Only 2% to 5% can be ascribed to a genetic predisposition with
neurofibromatosis types 1 and 2,
tuberous sclerosis,
nevoid basal cell (Gorlin's) syndrome, the adenomatous polyposis syndromes, and Li-Fraumeni
syndrome.
ionizing radiation used for diagnostic or therapeutic
purposes
Introduction
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CNS tumors in children
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Astrocytic Tumors
Diffusely infiltrating astrocytomas,
Diffuse astrocytomas (WHO grade II),(or fibrillary)
Anaplastic astrocytoma (WHO grade III),
Glioblastoma multiforme (WHO grade IV) and
variants, Pilocytic astrocytoma (WHO grade I),(MC)
Pleomorphic xanthoastrocytoma,
Desmoplastic cerebral astrocytoma of infancy, Subependymal giant cell astrocytoma.
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Cerebellar astrocytomas (15% to 20% of all CNS
tumors), Hemispheric astrocytomas (10% to 15%),
Midline supratentorial tumors, including the corpus
callosum, lateral and third ventricles, and thehypothalamus and thalamus (10% to 15%),
Optic pathway tumors (app 5% )
Brainstem LGA (10% to 15% of all; 20% to 30% of these
are LGA),
LGA of the spinal cord (3% to 6% of all; approximately
60% of these are LGA).
Low-Grade Astrocytomas (WHO Grades I and II) AstrocyticTumors
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Pilocytic astrocytomas :
MC of all primary CNS tumors
the anterior optic pathway, thecerebellum
well circumscribed and frequently
have an associated cystic component histologically --a biphasic pattern :
compacted bipolar cells with
Rosenthal fibers and loose-texturedmultipolar cells with microcysts and
granular bodies.
Astrocytic
Tumors
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Management of LGA Surgery is the mainstay of treatment.
Complete resectionlikely-- in smaller,well-
circumscribed and those in noneloquent parts.
Role of postop RT following lesser degrees of tumor
resection remains unclear
IF adj RT
avoided in infants and 2-3 yrs of age, bystarting on CT.
CT for Children with NF-1
Astrocytic
Tumors
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Regarding Radiotherapy in LGA:
Not indicated after complete resection.
Indicated in incomplete resection in situations when tumor
progression would compromise neurologic function .
The clearest indication for radiotherapy is in patients with
progressive and/or symptomatic disease that is unresectable
GTV : Preop volumes
CTV :
for a well circumscribed tumor margin of 1 cm or even GTV=CTV , around the GTV as seen on T1 W CEMRI.
If infiltrative, margins of 1 to 1.5 cm as seen on T2 W FLAIR
Astrocytic
Tumors
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Dose: 50 to 54 Gy as std of care
Technique:
EBRTconventional fractionation
Radiosurgery
Brachytherapy
Follow up: Imaging studies
OAS at 10 and 15 years : 80 to 100 %
Astrocytic
Tumors
LGA
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5% of all CNS tumors in children
Adolescents
GBMMC
Site: Cerebrum
Surgery --std of care
Post op RT always indicated dose ranging from
50- 54 Gy if feasible upto 60 Gy
Role of chemo as for adults
yet to be
established
Poor Prognosis
Astrocytic
TumorsHigh-Grade Astrocytomas (WHO Grades III and IV)
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Brainstem Gliomas
Low grade, favorable, tumors:
Focal (solid/cystic) intrinsic tumors
Dorsal exophytic tumors
Cervicomedullary tumors
Unfavorable tumors:
Diffuse intrinsic (pontine)tumors(DIPG)(70-80% )
Primitive neuroectodermal tumorsAtypical teratoid/rhabdoid tumors
Astrocytic
Tumors
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DIPG Brain stem enlargement
Extn to Mid brain and medulla in 2/3 rds
Mostly fibrillary astrocytomas with a propensity
for malignant change
Multiple cranial N palsies,ataxia
MRI if shows ring enhancement
high grade
Biopsy not preferred
Poor prognosis
Surgery no role.
Chemo no role
RT as a direct intervention
Hypo/hyperfractionation vs Conventional: No diff
Astrocytic Tumors
A t ti T
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Management of Brainstem TumorsAstrocytic Tumors
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Ependymal Tumors
5% to 10% of all Paediatric CNS Tumors
Infants and children younger than age 5 years
Supra and infratentorial
Signs of raised intracranial pressure
Well circumscribed, with displacement rather thaninvasion
Completeness of the surgical resection is a matter of
outcome If residual second look Sx
Post op Local RT- Std of Care
The role of chemotherapy--?
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Choroid Plexus Tumors
Choroid plexus papilloma (WHO grade I) and choroid
plexus carcinoma (WHO grade III).
2% to 4% in paediatric CNS Tumors(
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Embryonal Tumors 2nd MCtype of CNS tumor in the pediatric age
Most are PNETs ---undifferentiated round cell tumors with
divergent patterns of differentiation as follows:
Ependymoblastoma,
Medulloblastoma,
Desmoplastic medulloblastoma
Large cell medulloblastoma
Supratentorial PNET.
Two tumor types with distinctly different histologies that appearto evolve by different genetic pathways also are included in the
category of embryonal tumors:
Medulloepithelioma,
Atypical teratoid/rhabdoid tumor.
b l
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Medulloblastoma 15% to 20% of all paediatric CNST
Median age 6 years
MC site-cerebellar vermis and projects into the fourth ventricle
Types: Desmoplastic/nodular
With Extensive nodularity
Anaplastic
Large cell
Frequency of spinal seeding at diagnosis -30-40%
CEMRI of the Craniospinal axis (Solid masses with uniform
enhancement)
CSF cytology IOC primarily (to be obtained preoperatively or 2-3 wkspostop)
Rarely spread outside the CNS -to lymph nodes and bone
Embryonal Tumors
d ll bl
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CT and MRI
appear as solid masses
that enhance usually fairly homogeneously withcontrast material
Medulloblastoma
Medulloblastoma
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Chang Staging System for Metastases in Patients with Medulloblastoma
M0 No metastases
M1 Tumor cells found in cerebrospinal fluid
M2 Gross nodular seeding in the cerebellar,
cerebral subarachnoid space, or in the third or
lateral ventricles
M3 Gross nodular seeding in the spinal
subarachnoid space
M4 Metastases outside the central nervous
system
Medulloblastoma
M d ll bl
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Outcome:
Age,
Presence of leptomeningeal spread at presentationand
completeness of surgical resection
Risk categories: standard and high risk.
Std Risk: complete or subtotal resection with 1.5 cm2) residual tumor
and those with evidence of CSF dissemination at
diagnosis.
Medulloblastoma
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Management ofStandard-RiskMedulloblastoma
>3 years- post op RT-craniospinal axis to a dose of 35 to 36 Gy
followed by a boost to the whole posterior fossa to a total dose of54 to 55.8 Gy, traditionally. (others: reduced post fossa boost)
An alternative strategy consists of reduced-dose CSI followed by a
boost to the posterior fossa to a total dose of 55.8 Gy incombination with systemic chemotherapy(Vincristine and
Cisplatin)
CCG Pilot study: 23.4 GyCSI f/b adj V,CCNU,P ;PFS: 79% at 5 Y
CCG /POG Phase III RCT
Vincristine /Cyclo/Cisplatin
EFS 85%at 4 yrs
Current CCG study -18Gy in children 3-8 yrs--- Pending results
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Management of High-Risk Medulloblastoma
M0-- it would be logical to consider using a
radiotherapy dose to residual disease in theposterior fossa higher than the standard 55.8
Gy
M1 disease controversial and may be
treated like M2/3
Chemotherapy
COG pilot study with Carboplatin (M2/3)
New studies -HART with Pre and Post RT -CT
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Management ofMedulloblastoma in Infants
20% to 40% of all CNS tumors in infants
Desmoplastic /nodular/extensive nodularity
Common
But worser than the older children
The rate of complete resection is lower in this age group
The frequency of leptomeningeal seeding at diagnosis is
higher (as much as 50%)
Chemotherapy has been used in an attempt to either
delay or avoid radiotherapy altogether due to effects on
cognition by RT
Medulloblastoma
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POG study in Infants: Chemotherapy alone: 5
Y OAS :69%
RT still an important component
Most recurrences as early as 6 to 12 months North American studyRT limited to a volume of
tumor bed plus CTV of 1 cm margin for children
without Lepto meningeal seeding
Medulloblastoma
Medulloblastoma
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Cranio Spinal Irradiation
CSIStd of Care
Coverage of entire target volume that includes the
meninges overlying the brain and spine including the
extensions along the nerve roots is critical
Medulloblastoma
hMedulloblastoma
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Treatment Techniques-CSI
The CTV for CSI has an irregular shape that consists
of the whole of the brain and spinal cord andoverlying meninges
Some use the lower borders of lateral whole-brain
fields are matched to the cephalad border of a
posterior spine field
Some use a moving junctionbetween the brain andspine fields to minimize the risk of underdose or
overdose in the cervical spinal cord
Medulloblastoma
Medulloblastoma
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Patient Positioning and Immobilization
Prone/ Supine* full-body immobilization
using neck extension together with careful
selection of the level for the junction of thebrain and spine fields
it is possible to avoid including the dentition in the
exit from the superior aspect of the spinal field, and
thus any damage to developing teeth that may
result in stunted tooth growth, impaction,
incomplete calcification, delayed development, and
caries.
Medulloblastoma
Technical Considerations for Craniospinal Irradiation Medulloblastoma
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p
Problem Possible Solutions
Target volume definition may be difficult using
conventional simulation
Use CT simulation with CT-MRI co registration
Prone position uncomfortable, difficult to
monitor airway
Supine position preferred
Field matching over cervical spine, risk of over-
or underdosage
Angle brain fields
Use half beam block for brain fields
Use couch rotation or match line wedge
Choice of extended SSD or second field for
treatment of spinal axis
Two fields preferred
Inhomogeneity along spinal axis Use compensator, MLC
Irradiation of normal tissues:
Mandible/teeth Neck extension
Care with level of junction
Thyroid Use lower junction
Heart Care with width of spine field
Use electrons, IMRT, protons
GI tract Use electrons, IMRT, protons
Gonads Care with lower limit and width of spine field
GI, gastrointestinal; IMRT, intensity-modulated radiation therapy; MLC, multileaf collimator; SSD,source-skin distance.
Medulloblastoma
T t V l D fi itiMedulloblastoma
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Target Volume Definition
CT simulation is necessary to ensure adequate coverage of CTV in subfrontal
region:Cribriform plate
invaluablein identifying the lateral aspect of CTV for the
spine field that includes the extensions of the meningesalong the nerve roots to the lateral aspects of the spinal
ganglia.
The field, which must be wide enough to encompass
the intervertebral foramina in the lumbar region, can
be blocked laterally in the dorsal region to avoid
unnecessary irradiation of the heart and lungs
Medulloblastoma
Medulloblastoma
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In the lumbar region, it is important to avoid an
excessively wide field that will result in unnecessary
irradiation of the bone marrow and gonads.
MRI is required to determine the lower limit of CTV for
the spine field.
Traditionally the lower border of the spine field was
placed at the lower border of the second sacral vertebra,
but it is well documented that the lower border of the
thecal sac can be as high as L5 or as low as S3.
It is below S2 in 7% of children ; MRI is helpful.
Medulloblastoma
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CT simulation with CT-MRI co registration ---required
for accurate determination of the target volume for the
posterior fossa boost, both for definition of the targetvolume and for contouring of critical normal structures
such as the cochlea, pituitary/hypothalamus, and brain
that will allow accurate estimation of the dose to these
structures.
CSI is followed by a boost to posterior fossa
Traditionally entire post fossa received 54 to 55.8 Gy
Sparing of at risk organs a consideration
Medulloblastoma
Medulloblastoma
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Another option in Std Risk: reduced target volume
for the boost
FukunagaJohnson et.al found a low risk of isolated
failure outside tumor bed in posterior fossa and SFOP
studies support this approach.
Optimal CTV for a reduced volume post fossa boost
remains to be defined
But anatomically confined expansion of 1.5cm around
GTV reasonable (Current COG study)
Medulloblastoma
Medulloblastoma
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Whole post fossa Vs Reduced Volume Boost
Medulloblastoma
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Medulloblastoma
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Treatment Planning and Delivery In general, photons in the 6 to 10 MV range provide
satisfactory coverage of the PTV.
A variation of dose along the spinal axis of >10% will require
the use of dose compensation that can be achieved using
dynamic MLCs
To cover the clinical target volume for craniospinal irradiation,
lateral opposed fields are used to treat the brain and a direct
posterior field is used to cover the spinal axis.
Electrons are also used to treat spinal axis.
Medulloblastoma
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The field junction, which is over the cervical cord at a level
that avoids the inclusion of the teeth in the exit of the spinal
field, usually is moved weekly to avoid over- or underdosage
Supratentorial PNET Embryonal Tumors
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Supratentorial PNET
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The standard of care --- >3 years with S-PNETs without leptomeningeal
spread consists of ---maximal surgical resection
followed by postoperative radiotherapy (CSI plus a boost to doses similar to those used for high-risk
medulloblastoma) followed by chemotherapy
Supratentorial PNET
Atypical Teratoid/Rhabdoid Tumor
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Atypical Teratoid/Rhabdoid Tumor
Uncommon, highly malignant embryonal tumor
unique to childhood
Peak
birth to 2 yrs
Composed ofrhabdoid cells with or without fields
resembling a classical PNET
Diagnosed on the basis of the characteristic
molecular findings, namely deletion and/or
mutation of INI1 locus on Chromosome 22
Most commonly arises in the posterior fossa
Leptomeningeal seeding in 1/3 at presentation
ATRT
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Diagnosis
MRI Magnetic resonance imaging of the brain and spine
Lumbar puncture to look for M1 disease
CT of chest and abdomen to check for a tumor
Bone Marrow Aspiration and Bone marrow biopsy
Bone scan.
It is difficult to diagnosis AT/RT only from radiographicstudy; HPR is essential with IHC and Cytogenetic study
ATRT
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Sx-induction chemotherapyearly RT(CSI)-
Consolidation Chemo
DOSE-
< 3 yr, up to 24 Gy to whole brain and spinal cord, and
boost local site up to 54 to 56 Gy.
> 3 yr up to 36 Gy to whole brain and spinal cord, and
boost local site up to 56 Gy.
Germ Cell Tumors
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Germ Cell Tumors GCT of CNS-morphologic homologues of
germinal neoplasms arising in the gonads and at
other extragonadal sites.
Germinoma,
Embryonal carcinoma,
Yolk sac tumor (endodermal sinus tumor),
Choriocarcinoma,
Mature teratoma,
Immature teratoma,
Teratoma with malignant transformation,
Mixed germ cell tumors
GCTs
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Asia---account for as many as 15% to 18% of all CNS
tumors occurring in childhood
10 to 12 years. Boys more frequently than girls, with a
ratio of approximately 3:1
CNS germ cell tumors arise from primordial germ cells
in structures about the third ventricle, with the region
of the pineal gland being the most common site of
origin, followed by the suprasellar region.
Nongerminomatous germ cell tumors are the most common
tumor type in the former area, and germinomas in the latter
GCTs
Bi or multifocal disease around the third ventricle is seen in
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Bi- or multifocal disease around the third ventricle is seen in
approximately 10%
CE MRI of the spinal axis is an essential part of the work-
up to exclude leptomeningeal dissemination, which is
found at diagnosis in
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Germinoma Unifocal disease and without leptomeningeal spread --
radiotherapy (CSI and boost)
A combined approach using platinum-based
chemotherapy followed by reduced-volume, reduced-
dose radiotherapy is a very attractive option that is
being investigated by many groups, with disease-freesurvival rates in the 90% to 96% range.
Hence options:
craniospinal radiotherapy,
limited volume (whole-ventricle)
radiotherapy alone, and
chemotherapy followed
by whole ventricle or local radiotherapy
N i GCT
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Non germinomatous GCT
A multimodality approach that includes both
chemotherapy and radiotherapy appears to be
associated with the best outcome
Favourable--- Whole Ventricle RT
Unfavourable --- CSI and Boost
A dose of 36 Gy is used, followed by a boost to
the primary site to a total dose of 54 Gy.
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Classification of Nongerminomatous Germ Cell Tumors
Good prognosis
Mature teratoma
Intermediate prognosis
Immature teratoma
Mixed germ cell tumors consisting of
germinoma with either mature or immatureteratoma
Poor prognosis
Teratoma with malignant transformationEmbryonal carcinoma
Yolk sac tumor
Choriocarcinoma
Mixed germ cell tumors including a
component of embryonal carcinoma, yolk
sac tumor, choriocarcinoma, or teratoma
with malignant transformation
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Tumors of the Sellar Region
Craniopharyngioma,
Adamantinomatous craniopharyngioma
Papillary craniopharyngioma
Xanthogranuloma,
Pituitary adenomas.
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Craniopharyngioma
Benign partly cystic epithelial tumors that arisein the sellar region from remnants of Rathke's
pouch
MC in Children- adamantinomatous
5% of intracranial tumors in children
5 and 14 years.
have both suprasellar and intrasellarcomponents
Craniopharyngioma
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Children typically present with neuroendocrine deficits,
especially diabetes insipidus and growth failure.
Visual-field deficits bitemporal hemianopia often go unnoticed
initially.
Compression of the third ventricle may lead to hydrocephalus andsymptoms and signs of raised intracranial pressure.
Craniopharyngioma
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On neuroimaging:
with solid and cystic
areas in varying
proportions;
calcification is seen
in the majority of
cases.
The solid portionsand the cyst capsule
usually enhance with
the use of contrast
material.
l l ( h d lCraniopharyngioma
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Complete surgical resection(Transsphenoidal
approach), as confirmed on postoperative imaging, is
associated with long-term tumor control in 85% to
100% of patients
Patients with
tumors that are smaller and/or subdiaphragmatic in locationand without hypothalamic symptoms would be managed
surgically,
while other patients at higher risk for complicationssecondary to surgery would be managed with biopsy, cyst
decompression, if necessary, and radiotherapy
Craniopharyngioma
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Role of RT as sole therapy:
After biopsy
After incomplete surgery
At progression
Recurrence
Other options
Injection of radioactive colloid P32 and Y90--- if the
lesion has a small solid comp. and a simple cyst
May be combined with Stereotactic RT to solid comp.
Craniopharyngioma
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EBRT
Target Volume: entire lesion with preop MRI
0.5 cm margin or even 0 cm can be justified for a
CTV (Studies show excellent results)
Dose: 54-55 Gy over 30 fractions
During even after RT--Cyst may enlarge
Emergency cyst decompression may avoid further
neuro complications
Radiation Dose Fractionation in Children
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Conventionally 1.8 Gy / Fr
Avg dose: 54.5- 55.8 Gy
If it is a primary tumor of spinal cord: 50.4 Gy
In case of Germinomas: even doses of 1.5 Gy /fr and
lower doses of 30 to 45 Gy
HFRT may be a useful strategy in situations where dose
escalation cannot be obtained by conventional
fractionation
di i hild
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Issues regarding RT in children
Neurocognitive sequelae
Myelinization and functional maturation of the CNS
continue until well into adolescence and even into
young adulthood.
Failure to acquire new knowledge and skills at an age-
appropriate rate and show a progressive decline in IQ
over time
Endocrine deficits
T Mi i i th l t ff t
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To Minimize the long-term effects
Avoidance of radiotherapy altogether
Delay to radiotherapy for young children
Use of focal rather than extended-field
Use of daily anesthesia and improved immobilization
techniques Use of image-based treatment planning
New radiation modalities
Reduction of the dose of radiotherapy Use of smaller fraction sizes where appropriate
Use of hyperfractionated radiotherapy (HFRT)
Follow up
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Follow up
During treatment:
For vomitting ,headache ICT
Fatigue
Usually recover quickly after treatment
After treatment: (apart from imaging)
For hormonal deficits (esp. Primary hypothyroidism in CSI
by photons and GH deficit secondary to incln. Of
hypothalamo pituitary axis) Ophthalmology and audiology f/u
Access to neuropsychologist in case of special needs
,vocational assessment sos.
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Thank you.