Medulloblastoma management..

1. management
Medulloblastoma
: Dr Puneet Kumar Bagri

2. SURGER
Y
NCCN Guidelines Version
2.2013
Maximal safe resection possible Maximal safe resection not possible
Maximal safe resection
Stereotactic biopsy
or
Open biopsy
or
Partial resection
Contrast enhanced MRI compatible with primary brain tumor
Contd

3. POSTOP STAGING
Contrast enhanced brain & spine MRI, CSF analysis
Standard risk of
recurrence
•No e/o mets or
(brain, spine, CSF, extraneural)
• Small vol residual ds or
(contrast vol <1.5 cm2)
• Classic or desmoplastic histology
High risk of
recurrence
• Unresectable tumor or
residual >1.5 cm2 or
• Disseminated ds within or
outside neuroaxis or
• Large cell/anaplastic or
Supratentorial PNET
CSI
or
CCRT f/b postRT chemo
CSI and postRT chemo
(consider collecting
stem cells before CSI)
Brain MRI : Within 24-
72 hrsSpine MRI : Atleast 2-3 wks postop to avoid post
surgical artifactsLumbar puncture : After spine MRI ; Atleast 2 wks after surgery to avoid
false +ve cytologyBone scan, CT scan chest, abd & pelvis and Bone marrow Bx only if
clinically indicated Contd

4. FOLLOW UP
- Brain MRI every 3 mo for 2 yrs; then every 6 mo for 3 yrs; then yearly
- For pts with previous spine ds, concurrent spine imaging as clinically indicated
Localized brain
recurrence Disseminated disease*
• Chemotherapy
and/or
• Additional Radiation, such as stereotactic
radiosurgery, after resection
or
• High dose chemotherapy with autologous
stem cell reinfusion**
• Chemotherapy
or
• Palliative/Best supportive
care, including focal
radiation, if indicated
RECURRENT DISEASE
•MRI brain & spine
•CSF analysis
•Bone scan, CT chest, abd & pelvis; Bone marrow Bx (if clinically
indicated)
Maximum safe resection
* Consider resection for palliation of symptoms, where
indicated** Only if patient is without e/o disease after surgery or conventional dose re-induction

5. Radiotherapy
Medulloblastom
a

6. Adult Medulloblastoma
CSI
Posterior fossa
boost
 Full dose CSI (36 Gy) in high risk ds
 Reduced dose CSI (23.4 Gy) in healthy
young adults with avg risk ds as long as
appropriate chemotherapy is
administered*
 Total dose 54-55.8 Gy
Postop RT should begin within 28-30 days following surgical resection whenever possible
* Older pts & Pts with comorbidities may not
tolerate postRT chemo;
Longterm outcome is not known
• Spinal mets boost upto 45-50 Gy
• Intracranial mets boost upto 50-54 Gy
Role of adjuvant chemotherapy remains unclear in adults
Brandes et al.
Avg risk : RT alone; 5yr OS 80%, 5yr PFS 80%
High risk : 2 cy upfront CT f/b RT & adjuvant CT; 5yr OS 73%, 5yr PFS 69%
1.8 Gy/fr

7. Adult Medulloblastoma
Evidence-Based Treatment Summary
 There are no prospective, randomized trials evaluating
major therapeutic issues in this disease in adults
 Maximal surgical resection should be performed,
where feasible
 Standard treatment consists of postop radiotherapy to
the craniospinal axis followed by a boost to the
posterior cranial fossa
 The use of chemotherapy generally follows the
pediatric indications and guidelines

8. Pediatric Medulloblastoma
Standard risk medulloblastoma
POG#8631, CCG-923
Thomas PR et al.
M-SFOP 92
Carrie C et al.
Full dose CSI :
5 yr EFS –
67%
8 yr EFS –
67%
Reduced dose
CSI :
5yr EFS – 52%
8yr EFS – 52%
HFRT :
36 Gy/36fr CSI
68 Gy/68fr Post fossa
boost
3yr OS – 89%
3yr PFS – 81%
In reduced dose CSI :
Increased risk of early
relapse,
Early isolated
neuraxis relapse,
Lower 5yr EFS
Not assosiated with
early relapses in
children
CCG/POG ph III study
(A9961)
Packer RJ et al.
Reduced dose CSI,
Posterior fossa
boost and 1-2 cy
adjuvant CT
5yr OS – 86%
5yr EFS – 81%
Encouraging EFS rate,
Infections were more common in
Cyclo + CDDP + VCR,
Electrolyte abnormalities were
more in CCNU + CDDP + VCR
POG : Pediatric Oncology Group
CCG : Children’s Cancer Group
M-SFOP : French Cooperative Group

9. Medulloblastoma
High risk medulloblastoma
 CSI : 36 Gy
 Posterior fossa boost upto 55.8 Gy
 Additionally :
19.8 Gy to focal metastatic site
 Spinal disease :
Additional boost upto total of 45 Gy if tumor is
located above the termination of spinal cord
Upto 50.4 Gy if tumor is located below the
termination of cord

10. Pediatric Medulloblastoma
Medulloblastoma in infants
 Age <3yrs : The poorest risk group
Rate of complete resection is lower
Leptomeningeal seeding at diagnosis higher (
50%)
 Role of Radiotherapy is controversial
 RT causes significant risks to neurocognitive
functions
 COG study : Chemotherapy alone
Without mets – 3yr PFS 29%
With mets – 3yr PFS 11%
 POG study : Chemotherapy f/b delayed Radiation
2yr PFS 34%
Contd…

11. Pediatric
Medulloblastoma
Medulloblastoma in infants
 North American study :
» Tumor without leptomeningeal seeding RT
GTV : tumor bed
CTV : 1 cm margin to GTV
» With mets – Intensive Chemotherapy
Trials
High dose chemotherapy f/b autologous stem cell
rescue
showed good initial response; OS 30-40%

12. RADIOTHERAPY
Objective:
 To treat microscopic cancer cells / residual
tumor with the goal of reducing its size or
stopping its progression.
 Prevent or treat spread through CSF.
Covering the entire subarachnoid space is an
essential component in the management of
medulloblastoma. So We do Craniospinal
irradiation (CSI).

13.  CSI is a very complex technique
 Goal is to achieve uniform dosage throughout
the subarachnoid space, encompassing the
entire intracranial vault and spinal canal
 Fundamental is
 the use of opposed lateral fields including the
cranium and upper cervical spinal canal,
 matching a posterior spinal field including the full
spinal subarachnoid space with cranial field
 in larger children, the upper posterior spinal field
matching with a separate lower posterior spinal field

14. Target Volume:
Entire brain and its meningeal coverings with the CSF
Spinal cord and the leptomeninges with CSF
Posterior fossa – boost
Energy
4-6 MV linac or Co60
Portals
Whole Brain: Two parallel opposed lateral field.
Spine: Direct Posterior field
Scheduling of radiotherapy:
Starting time : within 28 days following surgery
Duration of treatment : 45 to 47 days

15. Dose
CSI (Phase I)
30 - 36 Gy in 18 - 21 fr over 4 weeks to the cranium @ 1.5
- 1.8 Gy/fr
30 - 36 Gy in 18 - 21 fr over 4 weeks to the spine @ 1.5 -
1.8 Gy/fr
Posterior fossa boost (Phase II)
18-20 Gy in 10-11 fr over 2 weeks to the posterior fossa

16. PLANNING STEPS
 Positioning
 Immobilization
 Simulation
 Field arrangement
 Matching of CSI
 Aligning of spinal field
 Implementation of plan

17. Patient position
 Prone (preferred):
 Supine:
 More patient comfort
 In-anaesthetic patient
 Head position
 Slightly extended and the shoulders
pulled down
 to avoid beam divergence into the
mandibule & dentition
 Facilitates the use of a moving junction
between the cephalad border of post.
Spine field and the lower borders of
cranial fields
 Lumbar and Thoracic spine ll to
couch

18. Immobilization method
1.Orfit cast for
immobilization of the
head, cervical spine
& shoulder
2.Small children –
inverted full body
plaster cast with
facial area open for
access for
anesthesia
3.Alpha cradle
4.Vacuum devices

19. FIELD ARRANGEMENTS
Whole brain
In the simulator, opposing lateral
fields are applied to the whole brain
with a collimator rotation of 7-11o to
match the divergence of the direct
posterior spinal field.
SFOP guidelines- The
recommended
placement of block is:
o 0.5 cm below the orbital roof .
o 1 cm below and 1 cm in front of the
lower most portion of the temporal fossa
.
o 1 cm away from the extreme edges of
the calvaria.
In Medulloblastoma nearly 15-20% of recurrences occur at cribriform plate site
which is attributed to overzealous shielding ,because of its proximity to ocular
structure it often get shielded.

20. Spinal field
 Laterally- 1 cm margin beyond the
pedicles, to cover the spinal cord and
meninges along the nerve roots upto
the spinal ganglia
 Caudal- 1 cm below the termination of
the thecal sac i.e. L5 –S3.
 2 spinal fields are used if the length is >
36 cm.
 In Dorsal Region, block lat. Field to
cover heart and lungs.
 In Lumbar Region, reduce field to
spare BM and Gonads.
SSD technique
Gantry Angle = 0 degree
Important point is length and
depth of spinal fields.
Field of approx.4–6 cm wide
box over the spinal
cord/vertebral bodies extends
from C2 –S2 .

21. Posterior fossa boost
 Volume includes entire Infratentorial
compartment.
 Field arrangement :
 Two lateral opposing fields
SFOP Guidelines :
 Ant- 0.5 cm in front of clivus
 Upper- 1 cm above midpoint b/w line
joining foramen magnum and the
skull.
 Post- ll to ant margin in air
 Lower- 1 cm below occipital foramen
or lower border of C2

22. TECHNIQUES OF MATCHING CS
FIELDS
 Collimator/Couch
rotation
 Half beam block
 Asymmetric jaws
 Moving Junction
technique

23. Collimator Couch rotation
 Classically described technique.
 Divergence of the spinal field
into the cranial field is overcome
with collimator rotation
 Divergence of the cranial fields
into the spinal fields is
overcome with couch rotation
(rotated so that the foot end
moves towards the gantry).

24. Collimator rotation allows
cranial field to match
spinal field divergence
Coll θ = arc tan (L1 /2 x SSD)
For Co60 SSD = 80 cm
Zone of overlap of spinal field if collimator rotation is
not applied in cranial field
SSD
L1
Collimator rotation : While treating cranial field rotate Collimator of lateral field so that
its inferior border is parallel to divergence of superior aspect of spinal field.
θ
COLLIMATOR
ROTATION

25.  In order to avoid the
overlap resulting from inf
divergence of cranial
field, rotate the couch
towards the collimator so
that fields margins of two
fields become parallel.
 Degree of couch rotation
depends upon the length
of lateral cranial fields
and SAD
 Θ couch = arc tan
(1/2 x L2 /SAD)
L2 = Cranial field length
COUCH ROTATION
Fig: Rotation of the couch toward the gantry is necessary to
match the caudal margin of the lateral cranial fields with the
cephalad margin of the posterior spinal field.

26. COUCH
ROTATION
Couch θ = arc tan (L2/2 x SAD)
For Co60 SAD = 80
L2 ( Length of
cranial field)
Cranial field
SAD
Zone of
overlap
Spinal field
Couch rotation
during
treatment of
cranial field
θ

27. Disadvantage of Couch Collimator rotation
 The lesser separation at
the neck can increase
the dose to the spinal
cord.
 Due to the couch
rotation the cranial
portions of the skull can
move away and get
treated a greater SSD
(resulting in under
dosage)

28.  Conversely in case
of the spinal cord the
lower SSD will result
in an increased
dose.
 Areas of the
opposite lower
temporal lobe can
get lower dose if
customized blocks
are used - lower
border of the cranial
fields need to be
more generous.
Figure: This figure illustrates a potential complication of
the craniospinal setup. A couch angle on the lateral cranial
fields can cause the contralateral temporal lobe to be
underdosed

29. Half Beam Blocking
Actual Cranial Field Length
Spinal field

30. Disadvantage of the half beam
technique
 Requires asymmetrical jaws
 In event of misaligned jaws or improper
movement unintended dose inhomogenecities
 Spinal field size reduced – two fields needed in
most children

31. Moving junction in CSI
 Feathering after every 5-7
fraction smoothes out any over
or underdose over a longer
segment of cord
 Usually shifted by 1-2cm at
each shift
 Either in cranial or caudal
direction
 Lower border of superior spinal
field & superior border of
inferior spinal field are also
shifted superiorly, maintaining
the calculated gap b/w them“Feathering” refers to movement of the junction of the two fields across the
treatment length.

32. Aligning Spinal field
 Abutting fields will result in heterogenous
dose to the spinal cord
 To overcome this various techniques are
available
o Gap technique
o Double junction technique
o Moving junction technique

33. Fixed or calculated gap spinal
fields
Gap calculation formula
S= ½ x L1(d/SSD1)+½ x L2(d/SSD2)
Cold Spot Hot Spot
SSD 2 SSD 1
L2 S L1

34. Double junction techniques
 The post field
divided into two
halves.
 An overlapping
segment is treated
with two diff. fields
on alternate days.
 The junction is
therefore
automatically
feathered on
alternate days
Upper Spine Lower Spine
Day of Planning
Upper Spine Lower Spine
Day 1: The upper spinal
field is shortened
Upper Spine Lower Spine
Day 2: The lower spinal field is
shortened
Junction on D 1 Junction on D 2

35. RADIATION TOXICITY
ACUTE TOXICITY
 Nausea, vomiting
 Neutropenia,
thrombocytopenia
 Fatigue, headache,
drowsiness
 Alopecia, mild
dermatitis
 Serous otitis media
 Mucositis,
oesophagitis (exit
dose from spinal cord)
Spinal cord Chronic progressive myelitis
Brain Radiation necrosis
Intellectual deficit
Lens of eye Cataract formation
Retina Radiation retinopathy
Optic nerve Optic neuritis
Inner ear Sensorineural hearing loss
Hypothalamic-
pituitary axis
Endocrinopathies ( hypothyroidism
and decreased growth hormone
secretion)
Secondary
Malignancy
LATE TOXICITY

36. Monitoring during CSI
 CSI results in predictable, if quantitatively variable, acute
changes in the peripheral blood counts.
 Neutropenia or thrombocytopenia are most often noted
during or after the third week of CSI.
 Traditionally, CSI is interrupted if:
The TLC falls below 3000/cumm
The neutrophil count falls below 1,000 cells/ml
Platelet count falls below 80,000/cumm
Any neutropenia with fever or thrombocytopenia with
bleeding manifestations
 If blood counts necessitate interrupting CSI for more than
2 consecutive days, initiation of posterior fossa irradiation
can be done
 A biweekly hemogram should be done – one on Monday
and the next on Thursday.

37. Pediatric
Medulloblastoma
 Prognosis :
5yr survival rate
Standard risk ds – 78%
High risk ds – 30-55%
Infants – 30%

38. Summary
 Medulloblastoma is pediatric age group tumor
 Raised ICT is the most common presentation
 CT, MRI have important role in diagnosis and treatment
 Surgery is the primary modality of treatment
 RT has central role in treatment
 Standard risk:
 Surgery  CSI or
CCRT followed by post radiation chemotherapy
 High risk: CSI and post RT chemotherapy
 Infants treated with intent to avoid or delay the RT
 Long term neurological sequalae seen in CSI

39. Medulloblastom
a
Prediction 2019
 Imaging diagnosis of tumor
 Stereotactic biopsy for molecular profiling and
subclassification
 Chemotherapy alone ( conventional and novel
pharmacotherapeutics )
 Aggressive surgical therapy and radiation therapy
will be relegated to past
THANKS