Central Nervous System Tumors in Children

7/27/2019 Central Nervous System Tumors in Children

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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.

Central Nervous System Tumors in Children

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