role of radiation in pediatric brain tumors

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

28. ImmobilizationImmobilization

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.