Historically, brain tumors have been treated with neurosurgical resection and radiation therapy. Demonstration of the efficacy of chemotherapy has lagged behind that for most other types of tumors, but currently chemotherapy is being employed more frequently. Recognition of the chemo-sensitivity of many types of brain tumors, in conjunction with the still relatively guarded prognoses of many of these patients, has also logically led to exploration of the use of hematopoietic cell support as a means of increasing dose intensity.

1. Pediatric Brain tumorPediatric Brain tumor
&&
Stem Cell TransplantationStem Cell Transplantation
A. Hedayati-AslA. Hedayati-Asl
Mahak Cancer Children’s Hospital
Stem Cell Transplantation Department

2. Most common childhoodMost common childhood
malignanciesmalignancies
0
5
10
15
20
25
30
Leukem
ia
brain
tum
or
lym
phom
a
neuroblastom
a
soft tissue
sarcom
a
W
ilm
s
tum
our
bone
tum
ors
others

3. Brain tumorsBrain tumors

4. • Second malignancy in childhoodSecond malignancy in childhood
• Mortality among this group approachesMortality among this group approaches
45%45%

5. EpidemiologyEpidemiology
• 2,200 primary brain tumor /year2,200 primary brain tumor /year
• 28cases/ million of children28cases/ million of children
• High incidence in infants and youngHigh incidence in infants and young
children up to 7 year of age.children up to 7 year of age.

6. EtiologyEtiology
• Ionizing radiation (tina capitis , ALL )Ionizing radiation (tina capitis , ALL )
• Other cancer (retioblastoma , rabdoidOther cancer (retioblastoma , rabdoid
tumor ,endocrin tumor)tumor ,endocrin tumor)
• Immunosuppression (wiscott-AldrichImmunosuppression (wiscott-Aldrich
syndrome , ataxia-telangectasia ,organsyndrome , ataxia-telangectasia ,organ
transplantation)transplantation)
• Familial (Li-fraumeni)Familial (Li-fraumeni)
• Enviromental exposure (effect ofEnviromental exposure (effect of
cellular plone&mobile, SV40 virus (Mcellular plone&mobile, SV40 virus (M
B,epandymoma)B,epandymoma)

7. CytogeneticCytogenetic
• Delation of 17Delation of 17
• Tisomy 7Tisomy 7
• Monosomy 22Monosomy 22
• Delation 22q11mutation p53Delation 22q11mutation p53

10. Normal Anatomy
of Brain (MRI)
• Supratentorial compartment:Supratentorial compartment:
– Cerebral hemispheresCerebral hemispheres
– Basal gangliaBasal ganglia
– Thalamic nucleiThalamic nuclei
– Lateral ventriclesLateral ventricles
– HypothalamusHypothalamus
– Corpus callosumCorpus callosum
• Infratentorial compartment:Infratentorial compartment:
– CerebellumCerebellum
– Brain stem (MB/P/MO)Brain stem (MB/P/MO)
– 44thth
ventricleventricle
Sagittal
Axial

11. Location of tumorLocation of tumor
• Inferatentorial 43.2% (1-10 years )Inferatentorial 43.2% (1-10 years )
• Meduloblastoma ,astrocytoma ,epandymoma, brain stem gliomaMeduloblastoma ,astrocytoma ,epandymoma, brain stem glioma
• Supratentoril 40.9% (1Supratentoril 40.9% (1stst
year of lifeyear of life
&>10 years )&>10 years )
• Glioma (high ,low grade )epandymoma ,craniopharangioma chiasmatic ,germcellGlioma (high ,low grade )epandymoma ,craniopharangioma chiasmatic ,germcell
tumortumor
• Spinal cord 4.9%Spinal cord 4.9%
• Multiple sites 11%Multiple sites 11%

12. Pediatric brain tumorsPediatric brain tumors
• AstrocytomaAstrocytoma
• MedulloblastomaMedulloblastoma
• EpendymomaEpendymoma
• GliomaGlioma

13. SymptomSymptom
• Headache.Headache.
• SeizureSeizure
• Memory Loss.Memory Loss.
• Motor weakness.Motor weakness.
• Visual symptomsVisual symptoms
• Language deficitLanguage deficit
• Cognitive changesCognitive changes
• Personality changesPersonality changes
• Change inChange in
consciousnessconsciousness
• Nausea and vomitingNausea and vomiting
• Sensory deficitSensory deficit
• PapilledemaPapilledema

14. Pediatric Brain Tumors
Posterior fossa neoplasm – MedulloblastomaPosterior fossa neoplasm – Medulloblastoma

15. Medulloblastoma

16. MedulloblastomaMedulloblastoma
Most common “malignant” brain tumor inMost common “malignant” brain tumor in
childrenchildren
StagingStaging
M0 – no metsM0 – no mets
M1 – positive cytologyM1 – positive cytology
M2 – intracranial metsM2 – intracranial mets
M3 – spinal cord metsM3 – spinal cord mets
M4 – extraneural diseaseM4 – extraneural disease

17. MedulloblastomaMedulloblastoma
RadiographsRadiographs
•• well delineated masswell delineated mass
•• arises from vermis 75%arises from vermis 75%
•• fills 4th ventriclefills 4th ventricle
•• calcification 15%calcification 15%
•• hydrocephalus 95%hydrocephalus 95%
•• enhancesenhances
•• subarrachnoid seedingsubarrachnoid seeding

18. IntrinsicIntrinsic
pontine gliomapontine glioma
Pediatric Brain Tumors

19. Brain Stem GliomaBrain Stem Glioma

20. EpandymumaEpandymuma

21. Pediatric Brain TumorsPediatric Brain Tumors
Supratentorial tumors – Astrocytoma & ependymoma
Pinealoblastoma & craniopharyngiomaPinealoblastoma & craniopharyngioma

22. Cerebellar AstrocytomaCerebellar Astrocytoma

23. Cerebellar AstrocytomaCerebellar Astrocytoma

24. AstrocytomasAstrocytomas

25. Common Brain TumorsCommon Brain Tumors
Location Percentage
Infratentorial 45-60
Supratentorial
Hemispheric
Midline – Suprasellular /
Pineal region
25-40
15-20

26. Distribution of common brain tumors in children –Distribution of common brain tumors in children –
location and histologic appearancelocation and histologic appearance
Infra-tentorial % of all brain tumors
PNET (Medulloblastoma) 20-25
Low grade astrocytoma
cerebellar
12-18
Ependynoma 4-8
Malignant glioma, brain stem 3-6
Other 2-5
Total 45-60
INTP - PPO, PHO, IAP.
P2 – 17/27

27. Supratentorial % of all brain tumors
Low grade astrocytoma 8-20
Malignant glioma 6-12
Ependymoma 2-5
Mixed glioma 1-5
Ganglioglioma 1-5
Oligodendroglioma 1-2
Chorioid plexus tumor 1-2
PNET 1-2
Meningioma 0.5-2
Other 1-3
Total 25-40
Distribution of common brain tumors in children –Distribution of common brain tumors in children –
location and histologic appearancelocation and histologic appearance
INTP - PPO, PHO, IAP.
P2 – 18/27

28. Staging Work upStaging Work up
• Dissemination extraneurally rare – stagingDissemination extraneurally rare – staging
work up seldom indicatedwork up seldom indicated
• Spinal MRI/CSF cytology – mandatorySpinal MRI/CSF cytology – mandatory
Medulloblastoma,Medulloblastoma,
• PF ependymoma, Germ cell tumorPF ependymoma, Germ cell tumor
• Blood / CSF -Blood / CSF - ααFP,FP, ββHCG – Germ cellHCG – Germ cell
tumorstumors

29. ImagingImaging
• MRIMRI
• CTscanCTscan

30. TreatmentTreatment
• SurgerySurgery
• RadiothrapyRadiothrapy
• ChemotherapyChemotherapy
• HSCTHSCT

34. Pediatric brain tumors-prognosisPediatric brain tumors-prognosis
• Low: 5-20% survival in brain stem tumorsLow: 5-20% survival in brain stem tumors
• High: 60-80% survival in medulloblastomaHigh: 60-80% survival in medulloblastoma

35. Problem Associated tumors Peri / intraoperative
Management
Postop
management
Odema Large tumors small
tumors in critical
areas
Corticosteroids
Dexona
0.1mg/kg Q6h
Corticosteroids
tapered
Obstructive
hydrocephalus
Intra and
periventricular
tumors
External ventricular
drain placement or
VP shunt
Closure or
permanent
Seizures Tumors of cerebral
hemispheres
Anticonvulsant
phenytoin
Stopped in
follow-up
Hypothalamic
Pituitary
hormonal
insufficiency
Tumors close to
hypothalamus
Endocrine
Evaluation,
Steroids fluid and
electrolyte balance
Hormone
replacement
Perioperative ManagementPerioperative Management

36. RadiotherapyRadiotherapy
• High energy machinesHigh energy machines
• Volume – Craniospinal irradiation, localisedVolume – Craniospinal irradiation, localised
irradiationirradiation
• Dose – 50-60 Gy / 24-36 Gy, 180-200 Gy / #Dose – 50-60 Gy / 24-36 Gy, 180-200 Gy / #
• STRS/STRT – Interstitial brachytherapy /STRS/STRT – Interstitial brachytherapy /
conformal and intensity modulated treatmentconformal and intensity modulated treatment
• Delay/defer irradiation for children younger thanDelay/defer irradiation for children younger than
3 years3 years
TreatmentTreatment
General principlesGeneral principles

37. Useful and
standard
Medulloblastoma, malignant astrocytomas,
optic pathway / hypothalamic gliomas,
malignant tumors in children less than 3
years of age.
Upfront CT / neo-adjuvant CT, HD CT - BMT
Useful drugs: CCNU/VCR/Prednisalone, Procarbazine,
Carboplatinum, Vincristine, Temozolamide
TreatmentTreatment
General principlesGeneral principles
ChemotherapyChemotherapy

38. Infratentorial TumorsInfratentorial Tumors
• High riskHigh risk
• MM11
• >1.5 cms residual tumor>1.5 cms residual tumor
• <3 years<3 years
• RT + CTRT + CT
• Standard riskStandard risk
• RTRT
• ?CT?CT
Medulloblastoma Sx  Adjuvant Treatment
Cerebellar Astrocytoma
Ependymomas
Brain stem glioma
Sx alone ?RT (adjuvant)
Sx  Adjuvant RT
RT alone

39. MedulloblastomaMedulloblastoma
• ‘• ‘Standard risk’ stageStandard risk’ stage
<1.5<1.522
cm residual,cm residual,
>3 yrs of age,>3 yrs of age,
no spreadno spread
•• TreatmentTreatment
surgical resectionsurgical resection
craniospinal radiationcraniospinal radiation
((2340 cGy to CSA with boost to 53402340 cGy to CSA with boost to 5340))
chemotherapychemotherapy

42. EpendymomaEpendymoma
•• Peak incidence between birth and 4 yrsPeak incidence between birth and 4 yrs
•• male:female :: 1.4:1male:female :: 1.4:1
•• Majority are histologically benignMajority are histologically benign
•• Locally invasive and difficult to resectLocally invasive and difficult to resect
entirelyentirely
•• Controversies exist regarding role ofControversies exist regarding role of
adjunctive radiotherapy and/oradjunctive radiotherapy and/or
chemotherapychemotherapy

43. Supratentorial TumorsSupratentorial Tumors
Hemispheric tumors:
Gliomas: Low grade: Sx alone
High grade: Sx  RT + CT (adjuvant)
Ependymomas: Sx  RT (adjuvant)
Optic pathway/ Sx  ↑ CT  ↓ RT
Hypothalamic
Gliomas
Craniopharyngioma Sx  RT
Pineal region tumors Individualized treatment
Midline Supratentorial Tumors

44. Hemispheric AstrocytomaHemispheric Astrocytoma
•• Outcome determined by:Outcome determined by:
tumor histology, extent of resection, locationtumor histology, extent of resection, location
•• 5 yr survival with subtotally resected low5 yr survival with subtotally resected low
grade gliomas is 90%grade gliomas is 90%
low grade tumors may remain quiescentlow grade tumors may remain quiescent
•• ControversiesControversies
adjuvant therapy (chemotherapy beforeadjuvant therapy (chemotherapy before
radiotherapy)radiotherapy)
treatment of epilepsytreatment of epilepsy
radiotherapy modalityradiotherapy modality

45. PNETPNET
•• < 5% of supratentorial< 5% of supratentorial
tumors in childrentumors in children
•• Radical surgical resectionRadical surgical resection
–– gross total improvedgross total improved
survivalsurvival
•• CSF disseminationCSF dissemination
commoncommon
•• Adjuvant treatmentAdjuvant treatment
–– craniospinal irradiationcraniospinal irradiation
–– chemotherapychemotherapy
•• survivalsurvival
–– <30% at 5 yrs<30% at 5 yrs

46. Treatment…ChemotherapyTreatment…Chemotherapy
Most commonly used agentsMost commonly used agents
• CyclophosphamideCyclophosphamide
• VCRVCR
• CarboplatinCarboplatin
• CisplatinCisplatin
• EtoposideEtoposide
Newer agentsNewer agents
• TemozolomideTemozolomide
• Molecularly targeted therapy (erlotinib, RAD001,etc.)Molecularly targeted therapy (erlotinib, RAD001,etc.)
• Anti-angiogenic therapy (bevacizumab,Anti-angiogenic therapy (bevacizumab,
• ImmunotherapyImmunotherapy

47. BT & HSCTBT & HSCT
• Historically, brain tumors have beenHistorically, brain tumors have been
treated with neurosurgical resection andtreated with neurosurgical resection and
radiation therapy. Demonstration of theradiation therapy. Demonstration of the
efficacy of chemotherapy has laggedefficacy of chemotherapy has lagged
behind that for most other types of tumors,behind that for most other types of tumors,
but currently chemotherapy is beingbut currently chemotherapy is being
employed more frequently.employed more frequently.

48. BT & HSCTBT & HSCT
Recognition of the chemo-sensitivity ofRecognition of the chemo-sensitivity of
many types of brain tumors, in conjunctionmany types of brain tumors, in conjunction
with the still relatively guarded prognoseswith the still relatively guarded prognoses
of many of these patients, has alsoof many of these patients, has also
logically led to exploration of the use oflogically led to exploration of the use of
hematopoietic cell support as a means ofhematopoietic cell support as a means of
increasing dose intensity.increasing dose intensity.