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Role of Radiation in PediatricRole of Radiation in Pediatric
Brain TumorsBrain Tumors
Dr. Ram Madhavan
CNS tumors account for 20-25% of all
malignancies
Radiation therapy is an important
component in therapy of brain tumors.
Indeed the recent developments in
radiation technology improved targeting
and significantly reduced long term
sequelae.
WHO classification of CNS tumorsWHO classification of CNS tumors
 Tumors of neuro epithelial tissue
Astrocytic tumors
Oligodendroglial
Mixed gliomas
Ependymal tumors
Choroid plexus tumors.
Neuronal and mixed neuronal glial tumors.
Pineal tumors
Embryonal tumors
 Tumors of meninges
 Germ cell tumors
 Tumors of sellar region
 Metastatic tumors.
Distribution of primary brain andDistribution of primary brain and
CNS tumors by histology (0-14CNS tumors by histology (0-14
years)years)
Distribution of primary brain and CNSDistribution of primary brain and CNS
tumors by histology (15-19 years)tumors by histology (15-19 years)
Common pediatric brain tumorsCommon pediatric brain tumors
Astrocytoma
Ependymoma
Medulloblastoma
Germ cell tumors
Craniopharyngioma
AstrocytomasAstrocytomas
Grade 1
Pilocytic Astrocytoma
Pleomorphic Xantho astrocytoma
Desmoplastic cerebral astrocytoma of infancy
Sub ependymal gaint cell astrocytoma
Grade II
Diffuse Astrocytomas
Grade III
Anaplastic Astrocytoma
 Grade IV
Glioblastoma multiforme
Low grade AstrocytomasLow grade Astrocytomas
Indolent clinical course
OS at 10 and 15 years – 80-100%
Most common type is Pilocytic astrocytoma
(grade 1)
Accounting for almost all of LGA at certain
sites [ anterior optic pathway & cerebellum]
Well circumscribed and frequently
associated with cystic component.
Hall mark microscopic feature is Rosenthal
fibres.
Pilocytic AstrocytomasPilocytic Astrocytomas
Well circumscribed.
Often have cystic
component which is
larger than solid
component.
Usually little edema
or mass effect.
Diffuse Fibrillary astrocytomasDiffuse Fibrillary astrocytomas
Little enhancement
with contrast.
T2 weighted or
FLAIR MRI best
demonstrate the
extent of disease.
Management of Low gradeManagement of Low grade
AstrocytomasAstrocytomas
Some children may not require any
tumor specific treatment.
Small asymptomatic tumors like optic
pathway gliomas detected on routine
imaging.
Active intervention is required when
there is progression or symptoms.
Management of Low gradeManagement of Low grade
AstrocytomasAstrocytomas
Surgery is the mainstay of treatment.
Complete resection is more likely in
smaller tumors and those arising from
non-eloquent parts of brain.
Long term OS and DFS is 80 – 100%.
Post OP adjuvant therapy not indicated.
Algorithm for incompletelyAlgorithm for incompletely
resected gliomasresected gliomas
Maximal surgical resection compactable with
good neurological outcome.
Follow up with routine imaging.
Second surgical resection if feasible at the time
of progressive disease.
Radiotherapy or chemotherapy at the time of
progressive disease that is not resectable.
Indications for Radiation therapyIndications for Radiation therapy
Radiotherapy is not indicated after
complete resection.
RT may be indicated following
incomplete resection when tumor
progression compromise neurologic
function.
50 – 54Gy depending upon the age of the
child , location of the tumor and its
relation to critical normal structures.
Brain stem gliomasBrain stem gliomas
Constitutes 20% of childhood tumors.
Most common in children between 3-10
years.
Tissue confirmation is frequently not
feasible in infiltrating lesions.
Associated with poor prognosis.
Clinical presentationClinical presentation
Insidious/sudden onset
Cranial nerve palsies.
Long tract signs [hemiparesis].
Cerebellar signs [ataxia]
Focal - 5-10%
Dorsal exophytic - 10-20%
Cervicomedullary - 5 -10%
Diffuse intrinsic - 75-85%
TypesTypes
Focal tumorsFocal tumors
Surgery should be
attempted.
Most are JPA
If surgery is morbid
then RT
Usually good
prognosis.
Dorsal exophytic lesionsDorsal exophytic lesions
Insidious onset
Surgery should be
attempted.
Mostly low grade JPA.
Favorable prognosis.
RT for residual/
progressive disease.
Cervicomedullary tumorsCervicomedullary tumors
Typically present with
cranial nerve palsies
and long tract signs.
Surgery is the
treatment of choice.
Usually low grade JPA
RT for residual/
progressive disease.
Diffuse pontine gliomasDiffuse pontine gliomas
Typically present
with short history.
Surgery including
biopsy not feasible.
Mostly fibrillary
Direct RT in view of
clinical radiological
picture.
EpendymomaEpendymoma
Third most common CNS tumor in
children.
Can occur at any site in ventricular
system or spinal canal.
5-10% has leptomeningeal seeding at time
of diagnosis.
Gadolinium enhanced MRI of whole CNS
and CSF cytology are essential
components of work up.
Management principlesManagement principles
Maximum surgical resection.
Post OP radiation therapy is the standard is
the standard of care for all children with
ependymoma. RT dose – 54 Gy
Post OP RT can be avoided in
1. completely resected Ependymoma of spinal
cord
2. Supraventricular ependymomas resected
with wider margin.
MedulloblastomaMedulloblastoma
Most common malignant brain tumor in
Children.
Belongs to the family of small blue round
cell tumor.
Median age at presentation is 5- 8 years.
High propensity for CSF dissemination
[20-30%]
Hence contrast MRI of spinal axis and
CSF cytology is essential.
RadiologyRadiology
Vermian location.
Occasionally cerebellar
hemispheric
 Well circumsribed,
spherical
Hemorrhage, cysts
Calcification occasionally
Risk stratificationRisk stratification
Initial surgical resection is the standard.
Standard risk
<1.5 cm2 of residual tumor after resection.
No CSF dissemination.
High risk
>1.5 cm2 of residual tumor after resection.
CSF dissemination present.
Craniospinal Irradiation [CSI]Craniospinal Irradiation [CSI]
Target volume
Whole brain with its meninges.
Spinal cord down to the caudal end of
the thecal sac(usually S2 but should be
verified by saggital MRI)
 Primary tumour
RT doseRT dose
Standard risk
CSI 23.4 Gy followed by tumor bed
boost of 54 Gy.
High risk
CSI 36 Gy followed by posterior fossa
boost of 54 Gy
ImmobilizationImmobilization
RT fields used in CSIRT fields used in CSI
Dose distribution in CSIDose distribution in CSI
ChemotherapyChemotherapy
Vincristine weekly during Radiation.
Followed by adjuvant PCV regimen for 6
cycles
POG protocol
Vincristine 1.4mg/m2
CCNU 75 mg/m2
Cisplatin 75mg/m2
In some protocols CCNU was replaced by
Cisplatin.
Germ cell tumorsGerm cell tumors
More common in Asia
Accounts for 15 – 18% of all CNS tumors
in children.
Peak incidence is 10 -12 years.
Boys affected more frequently than girls.
Arise from primordial germ cells around
third ventricle.
Germ cell tumorsGerm cell tumors
Non germinomatous germ cell tumors
more common in pineal gland region.
Germinomas more common in supra
sellar region.
Leptomeningeal spread is <10% with
germinomas and 10-15% with NGGCT.
CSF tumor markers [B HCG in
germinomas and choriocarcinomas AFP in
yolk sac tumors] is essential.
Management of GerminomasManagement of Germinomas
Very radiosensitive tumor
CSI 21 Gy followed by boost to primary
site 40-45 Gy.
Dose per fraction 1.5 Gy can be used to
decrease injury to normal cells.
Instead of CSI whole ventricular
Radiation can be used for used for
unifocal germinomas.
Cisplatin based chemotherapy is used.
Whole ventricular RTWhole ventricular RT
NSGCT - classificationNSGCT - classification
Good prognosis
Mature teratoma
Intermediate prognosis
Immature teratoma
Mixed germ cell tumors.
Poor prognosis
Teratoma with malignant transformation
Embryonal carcinoma
Yolk sac tumor
choriocarcinoma
NSGCTNSGCT
Initial maximum safe surgical resection
for tissue diagnosis.
The current standard of care consists of
platinum based chemotherapy followed
by radiotherapy.
RT consists of CSI 36 Gy followed by
boost 54 Gy to primary site.
CraniopharyngiomasCraniopharyngiomas
Benign cystic epithelial tumors.
Arise in sellar region from remnants of
Rathke’s pouch
Accounts for 5% of CNS tumors in
children.
Mostly ademantinomatous type
Peak incidence 5-14 years.
Clinical presentationClinical presentation
Neuro endocrine deficits
Visual field deficits.
Cognitive and behavioral changes
Compression of third ventricle
Hydrocephalus.
RadiologyRadiology
Solid and cystic
areas in varying
proportions.
Calcification in
majority of cases.
Solid portion and
cyst capsule enhance
with contrast.
Role of RadiationRole of Radiation
Complete surgical resection is the standard of
care.
Indications of RT
Incomplete resection
Progression
Recurrence.
Dose is 54 Gy in 30 fractions over a period of 6
weeks.
DFS 80-100% in most series.
Classical 3 field techniqueClassical 3 field technique
General principles of RT in PediatricGeneral principles of RT in Pediatric
brain tumorsbrain tumors
Avoidance of RT altogether if possible.
Delay RT in young children [3-8 years] by
the use of chemotherapy.
Use focal than Extended field RT
Daily anesthesia and better immobilization
helps to reduce planning target volume.
General principles of RT in PediatricGeneral principles of RT in Pediatric
brain tumorsbrain tumors
Use Image based treatment planning
[3DCRT/IMRT]
Reduce the total dose of RT
Use smaller fraction size where
appropriate
General principles of RT in PediatricGeneral principles of RT in Pediatric
brain tumorsbrain tumors
Field size a little generous as kids may be
un cooperative
Conventional 3D conformal Radiation
therapy.
No great benefit with hi-fi techniques.
IMRT/SRT may be beneficial in the setting
of reirradiation.
Long term effects of pediatric brainLong term effects of pediatric brain
irradiationirradiation
Neurocognitive and neurophysiological
dysfunction.
Endocrine abnormalities and hormonal
imbalance
Growth retardation – spinal component.
Ototoxicity – especially with platinum based
chemotherapy.
Gonadal toxicity and reduced fertility
Cerebrovascular accidents
Second malignancies.
Does reduction in dose andDoes reduction in dose and
volume impact upon long-termvolume impact upon long-term
outcomesoutcomes
 Neuro-cognitive dysfunction: YES (Reduced )
 Neuro-physiologic dysfunction: YES (Reduced)
 Endocrine dysfunction: YES (Lesser )
 Oto-toxicity: EQUIVOCAL (Reduced cochlear dose offset
by addition of platinum
 Hematologic: YES (Significantly incresed with CT)
 GI toxicity: YES (Significantly increased with CT)
 Second malignant neoplasms: EQUIVOCAL (conflicting
data)
Follow up during and after RTFollow up during and after RT
Acute side effects like nausea and
vomiting can be prevented by 5HT 3
antagonists.
Head ache is not common and should be
investigated for raised ICT if present.
Steroids can be tapered by third or
fourth week of treatment.
Get back to their routine 6 weeks to 2
months following RT
Long term follow upLong term follow up
Hormonal deficits especially GH deficit
secondary to Hypothalamo-pituitary axis
irradiation [CSI] and hypothyroidism
should be closely monitored.
Access neuropsychologist for evaluation
of any special needs.
May require vocational assessment and
counseling.
ConclusionConclusion
Management of pediatric brain tumors has
improved a lot in past three decades.
Improved imaging, newer techniques in
pathology, better neurosurgical techniques and
evolution of high precision radiotherapy
revolutionized the treatment
Currently 5 year survival rate is estimated at
75% for all CNS tumors in 0-19 years age
group.

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Role of radiation in pediatric brain tumors16 5-2014

  • 1. Role of Radiation in PediatricRole of Radiation in Pediatric Brain TumorsBrain Tumors Dr. Ram Madhavan
  • 2. CNS tumors account for 20-25% of all malignancies Radiation therapy is an important component in therapy of brain tumors. Indeed the recent developments in radiation technology improved targeting and significantly reduced long term sequelae.
  • 3. WHO classification of CNS tumorsWHO classification of CNS tumors  Tumors of neuro epithelial tissue Astrocytic tumors Oligodendroglial Mixed gliomas Ependymal tumors Choroid plexus tumors. Neuronal and mixed neuronal glial tumors. Pineal tumors Embryonal tumors  Tumors of meninges  Germ cell tumors  Tumors of sellar region  Metastatic tumors.
  • 4. Distribution of primary brain andDistribution of primary brain and CNS tumors by histology (0-14CNS tumors by histology (0-14 years)years)
  • 5. Distribution of primary brain and CNSDistribution of primary brain and CNS tumors by histology (15-19 years)tumors by histology (15-19 years)
  • 6. Common pediatric brain tumorsCommon pediatric brain tumors Astrocytoma Ependymoma Medulloblastoma Germ cell tumors Craniopharyngioma
  • 7. AstrocytomasAstrocytomas Grade 1 Pilocytic Astrocytoma Pleomorphic Xantho astrocytoma Desmoplastic cerebral astrocytoma of infancy Sub ependymal gaint cell astrocytoma Grade II Diffuse Astrocytomas Grade III Anaplastic Astrocytoma  Grade IV Glioblastoma multiforme
  • 8. Low grade AstrocytomasLow grade Astrocytomas Indolent clinical course OS at 10 and 15 years – 80-100% Most common type is Pilocytic astrocytoma (grade 1) Accounting for almost all of LGA at certain sites [ anterior optic pathway & cerebellum] Well circumscribed and frequently associated with cystic component. Hall mark microscopic feature is Rosenthal fibres.
  • 9. Pilocytic AstrocytomasPilocytic Astrocytomas Well circumscribed. Often have cystic component which is larger than solid component. Usually little edema or mass effect.
  • 10. Diffuse Fibrillary astrocytomasDiffuse Fibrillary astrocytomas Little enhancement with contrast. T2 weighted or FLAIR MRI best demonstrate the extent of disease.
  • 11. Management of Low gradeManagement of Low grade AstrocytomasAstrocytomas Some children may not require any tumor specific treatment. Small asymptomatic tumors like optic pathway gliomas detected on routine imaging. Active intervention is required when there is progression or symptoms.
  • 12. Management of Low gradeManagement of Low grade AstrocytomasAstrocytomas Surgery is the mainstay of treatment. Complete resection is more likely in smaller tumors and those arising from non-eloquent parts of brain. Long term OS and DFS is 80 – 100%. Post OP adjuvant therapy not indicated.
  • 13. Algorithm for incompletelyAlgorithm for incompletely resected gliomasresected gliomas Maximal surgical resection compactable with good neurological outcome. Follow up with routine imaging. Second surgical resection if feasible at the time of progressive disease. Radiotherapy or chemotherapy at the time of progressive disease that is not resectable.
  • 14. Indications for Radiation therapyIndications for Radiation therapy Radiotherapy is not indicated after complete resection. RT may be indicated following incomplete resection when tumor progression compromise neurologic function. 50 – 54Gy depending upon the age of the child , location of the tumor and its relation to critical normal structures.
  • 15. Brain stem gliomasBrain stem gliomas Constitutes 20% of childhood tumors. Most common in children between 3-10 years. Tissue confirmation is frequently not feasible in infiltrating lesions. Associated with poor prognosis.
  • 16. Clinical presentationClinical presentation Insidious/sudden onset Cranial nerve palsies. Long tract signs [hemiparesis]. Cerebellar signs [ataxia] Focal - 5-10% Dorsal exophytic - 10-20% Cervicomedullary - 5 -10% Diffuse intrinsic - 75-85% TypesTypes
  • 17. Focal tumorsFocal tumors Surgery should be attempted. Most are JPA If surgery is morbid then RT Usually good prognosis.
  • 18. Dorsal exophytic lesionsDorsal exophytic lesions Insidious onset Surgery should be attempted. Mostly low grade JPA. Favorable prognosis. RT for residual/ progressive disease.
  • 19. Cervicomedullary tumorsCervicomedullary tumors Typically present with cranial nerve palsies and long tract signs. Surgery is the treatment of choice. Usually low grade JPA RT for residual/ progressive disease.
  • 20. Diffuse pontine gliomasDiffuse pontine gliomas Typically present with short history. Surgery including biopsy not feasible. Mostly fibrillary Direct RT in view of clinical radiological picture.
  • 21. EpendymomaEpendymoma Third most common CNS tumor in children. Can occur at any site in ventricular system or spinal canal. 5-10% has leptomeningeal seeding at time of diagnosis. Gadolinium enhanced MRI of whole CNS and CSF cytology are essential components of work up.
  • 22. Management principlesManagement principles Maximum surgical resection. Post OP radiation therapy is the standard is the standard of care for all children with ependymoma. RT dose – 54 Gy Post OP RT can be avoided in 1. completely resected Ependymoma of spinal cord 2. Supraventricular ependymomas resected with wider margin.
  • 23. MedulloblastomaMedulloblastoma Most common malignant brain tumor in Children. Belongs to the family of small blue round cell tumor. Median age at presentation is 5- 8 years. High propensity for CSF dissemination [20-30%] Hence contrast MRI of spinal axis and CSF cytology is essential.
  • 24. RadiologyRadiology Vermian location. Occasionally cerebellar hemispheric  Well circumsribed, spherical Hemorrhage, cysts Calcification occasionally
  • 25. Risk stratificationRisk stratification Initial surgical resection is the standard. Standard risk <1.5 cm2 of residual tumor after resection. No CSF dissemination. High risk >1.5 cm2 of residual tumor after resection. CSF dissemination present.
  • 26. Craniospinal Irradiation [CSI]Craniospinal Irradiation [CSI] Target volume Whole brain with its meninges. Spinal cord down to the caudal end of the thecal sac(usually S2 but should be verified by saggital MRI)  Primary tumour
  • 27. RT doseRT dose Standard risk CSI 23.4 Gy followed by tumor bed boost of 54 Gy. High risk CSI 36 Gy followed by posterior fossa boost of 54 Gy
  • 29. RT fields used in CSIRT fields used in CSI
  • 30. Dose distribution in CSIDose distribution in CSI
  • 31. ChemotherapyChemotherapy Vincristine weekly during Radiation. Followed by adjuvant PCV regimen for 6 cycles POG protocol Vincristine 1.4mg/m2 CCNU 75 mg/m2 Cisplatin 75mg/m2 In some protocols CCNU was replaced by Cisplatin.
  • 32. Germ cell tumorsGerm cell tumors More common in Asia Accounts for 15 – 18% of all CNS tumors in children. Peak incidence is 10 -12 years. Boys affected more frequently than girls. Arise from primordial germ cells around third ventricle.
  • 33. Germ cell tumorsGerm cell tumors Non germinomatous germ cell tumors more common in pineal gland region. Germinomas more common in supra sellar region. Leptomeningeal spread is <10% with germinomas and 10-15% with NGGCT. CSF tumor markers [B HCG in germinomas and choriocarcinomas AFP in yolk sac tumors] is essential.
  • 34. Management of GerminomasManagement of Germinomas Very radiosensitive tumor CSI 21 Gy followed by boost to primary site 40-45 Gy. Dose per fraction 1.5 Gy can be used to decrease injury to normal cells. Instead of CSI whole ventricular Radiation can be used for used for unifocal germinomas. Cisplatin based chemotherapy is used.
  • 35. Whole ventricular RTWhole ventricular RT
  • 36. NSGCT - classificationNSGCT - classification Good prognosis Mature teratoma Intermediate prognosis Immature teratoma Mixed germ cell tumors. Poor prognosis Teratoma with malignant transformation Embryonal carcinoma Yolk sac tumor choriocarcinoma
  • 37. NSGCTNSGCT Initial maximum safe surgical resection for tissue diagnosis. The current standard of care consists of platinum based chemotherapy followed by radiotherapy. RT consists of CSI 36 Gy followed by boost 54 Gy to primary site.
  • 38. CraniopharyngiomasCraniopharyngiomas Benign cystic epithelial tumors. Arise in sellar region from remnants of Rathke’s pouch Accounts for 5% of CNS tumors in children. Mostly ademantinomatous type Peak incidence 5-14 years.
  • 39. Clinical presentationClinical presentation Neuro endocrine deficits Visual field deficits. Cognitive and behavioral changes Compression of third ventricle Hydrocephalus.
  • 40. RadiologyRadiology Solid and cystic areas in varying proportions. Calcification in majority of cases. Solid portion and cyst capsule enhance with contrast.
  • 41. Role of RadiationRole of Radiation Complete surgical resection is the standard of care. Indications of RT Incomplete resection Progression Recurrence. Dose is 54 Gy in 30 fractions over a period of 6 weeks. DFS 80-100% in most series.
  • 42. Classical 3 field techniqueClassical 3 field technique
  • 43. General principles of RT in PediatricGeneral principles of RT in Pediatric brain tumorsbrain tumors Avoidance of RT altogether if possible. Delay RT in young children [3-8 years] by the use of chemotherapy. Use focal than Extended field RT Daily anesthesia and better immobilization helps to reduce planning target volume.
  • 44. General principles of RT in PediatricGeneral principles of RT in Pediatric brain tumorsbrain tumors Use Image based treatment planning [3DCRT/IMRT] Reduce the total dose of RT Use smaller fraction size where appropriate
  • 45. General principles of RT in PediatricGeneral principles of RT in Pediatric brain tumorsbrain tumors Field size a little generous as kids may be un cooperative Conventional 3D conformal Radiation therapy. No great benefit with hi-fi techniques. IMRT/SRT may be beneficial in the setting of reirradiation.
  • 46. Long term effects of pediatric brainLong term effects of pediatric brain irradiationirradiation Neurocognitive and neurophysiological dysfunction. Endocrine abnormalities and hormonal imbalance Growth retardation – spinal component. Ototoxicity – especially with platinum based chemotherapy. Gonadal toxicity and reduced fertility Cerebrovascular accidents Second malignancies.
  • 47. Does reduction in dose andDoes reduction in dose and volume impact upon long-termvolume impact upon long-term outcomesoutcomes  Neuro-cognitive dysfunction: YES (Reduced )  Neuro-physiologic dysfunction: YES (Reduced)  Endocrine dysfunction: YES (Lesser )  Oto-toxicity: EQUIVOCAL (Reduced cochlear dose offset by addition of platinum  Hematologic: YES (Significantly incresed with CT)  GI toxicity: YES (Significantly increased with CT)  Second malignant neoplasms: EQUIVOCAL (conflicting data)
  • 48. Follow up during and after RTFollow up during and after RT Acute side effects like nausea and vomiting can be prevented by 5HT 3 antagonists. Head ache is not common and should be investigated for raised ICT if present. Steroids can be tapered by third or fourth week of treatment. Get back to their routine 6 weeks to 2 months following RT
  • 49. Long term follow upLong term follow up Hormonal deficits especially GH deficit secondary to Hypothalamo-pituitary axis irradiation [CSI] and hypothyroidism should be closely monitored. Access neuropsychologist for evaluation of any special needs. May require vocational assessment and counseling.
  • 50. ConclusionConclusion Management of pediatric brain tumors has improved a lot in past three decades. Improved imaging, newer techniques in pathology, better neurosurgical techniques and evolution of high precision radiotherapy revolutionized the treatment Currently 5 year survival rate is estimated at 75% for all CNS tumors in 0-19 years age group.