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Medulloblastomas
Medulloblastomas
Medulloblastomas
Moderator:
?
Department of Radiotherapy
PGIMER, Chandigarh
Introduction
Percival Bailey
Incidence
6 yrs.
Relevant Neuroanatomy
2. Foramen of Magendie
3. Foramen of Luschka
CSF pathways
Raised ICT Symptoms and signs
Spread around
the 4th ventricle
Invasion of
ventricular floor
CSF Spread
Invasion of brain
(33%)
stem (33%)
Invasion of
brachium pontis
Extra neural spread (7%) : Younger age, males and diffuse subarachnoid disease
Extra neural spread
Calcification uncommon.
Desmoplastic variant: Firmer
appearance and darker color. Also
more common in the lateral
cerebellar hemispheres.
Microscopic Appearance
PNET
Esthesioneurblast
oma Pineloblastoma
Cerebral
Neuroblastoma
Neuroimaging
CT appearance
Hyperattenuated, well-
defined vermian cerebellar
mass
Surrounding vasogenic
edema
Evidence of hydrocephalus
Homogeneous contrast
enhancement
Cyst formation (59% of
cases)
Calcification - uncommon
Neuroimaging
MRI features:
Iso- to- hypointense relative to white
matter (T1 images)
Hyperintense in T2 weighted images
Enhance following contrast
Heterogeneous enhancement.
Vasogenic edema +
Adult Medulloblastomas:
Poorly defined masses located in
the cerebellar hemisphere
Cyst like regions are more
commonly seen
Abnormal leptomeningeal
enhancement (cf. Meningioma) –
desmoplatic variant
Metastatic disease
Leptomeningeal disease:
Spinal cord is the most common site
Most metastases are found along the
posterior margin of the spinal cord –
CSF flow from cisterna magna to
posterior margin of spinal cord
Supratentorial involvement frequently
involves the frontal and subfrontal
regions
Sulcal and cisternal effacement
Ependymal-subependymal
enhancement
Widened tentorial enhancement
Communicating hydrocephalus
Staging Systems
M= Metastasis
A= Age
S: Surgery
P= Pathology
Risk Grouping
Tait and Evan showed that the risk grouping approach could be utilized to
stratify patients into two risk categories:
Poor risk
Average risk
Several studies had shown that the T stage of the Chang's system did
not correlate with survival (possible exception of brain stem invasion) –
so replaced by the definition of the post operative residual tumor
volume concept.
Medulloblastoma
Patient stable
Patient extremely
somnolent
High dose steroids + MRI
Large reduction in SF
tumor.
SF2 Gy = 28% (Fertil et al)
Implications:
Radiosensitive and hence high
degree of local control with post
op RT Small reduction in
Errors in treatment delivery will be dose
magnified as dose just at the
threshold is being delivered.
Craniospinal Irradiation: History
The concept of CSI was advanced by Dr Edith
Paterson (wife of Ralston Paterson).
Before this the patients of Medulloblastomas were
treated with posterior fossa or whole brain radiation
She advocated the treatment of the entire neuraxis –
bringing the concept of CSI
Paterson and Farr reported that with the use of
cranio-spinal irradiation in 27 patient resulted in a 3 yr
survival of 65% (Acta Radiologica – 1953) – This was
despite surgery in form of a partial resection / biopsy
in all but 1 patient.
Rationale for CSI
Miss will
occur here
Inferior extent:
Classical : S2 (ending of the thecal
sac in 66% patients)
High: S1 ( termination in 17%)
Modified: S3 ( termination in 96%)
To cover filum terminale: S5 ->
unacceptable dose to pelvic organs.
Coverage:
Co60: 37 x 37 cm
LINAC: 40 x 40 cm
Solutions to cover the entire neuraxis:
Treat with multiple fields: Problem of field junction matching
Treat at extended SSD:
Allows single field technique
However simultaneous increase in the PDD occurs –
increased organ dose under spinal field ( PDD ∞ SSD)
Posterior fossa boost : Definition of the upper border
Positioning
Prone:
Better immobilization
Better extension of the chin ( reduced dose inhomogeneity in
the mandible)
Visualization of field
Supine: More patient comfort ? Anesthesia access.
Use of a small wedge to support chest – better patient
comfort.
Head position:
Extended: Most common – allows the mandible to move out of
the spinal field
Flexed: Probably straightens the cervical spine – more
homogeneous dosage.
Overcoming matching problems
L1
SAD
L2 ( Length of cranial
field)
Cranial field
Zone of
overlap
Couch rotation
Spinal field during
treatment of
cranial field
Field gap technique: Will result in a cold spot above and a hot
spot in the deeper tissues.
“Feathering” of the gap can smoothen out the dose gradients
N.B.: Half beam block technique can't be used (as used in cranial field)
Double Junction technique
Day of Planning
Junction on D 1 Junction on D 2
Double Junction Technique
Method to ensure dose
homogeneity without the need for
gaps.
Described: Johnson and Kepka
(Radiology, 1982)
Principle : An overlapping
segment is treated with two
different fields on alternate days
The junction is therefore
automatically feathered on
alternate days
Receives homogeneous dose 50%
of the time
Receives junctional dose in the
remaining 50% time.
No cold spots are generated
Field Gap Technique
SSD 2 SSD 1
L2 S L1
SSD 1 SSD 2
L1 L2
D
Gap Feathering
“Feathering” refers to
movement of the junction of
the two fields across the
treatment length.
Purpose:
Reduce overdose (due to
overlap)
Reduce underdose (due to
gap)
Allows a longer segment of
the cord to be exposed to
more homogeneous dose
As the treatment progresses the under- Feathering also reduces
/over -dose gets spread over a greater the impact of setup errors.
area of the spinal cord allowing more
homogeneous dose distribution
Gap Feathering..
2 mm overlap
No gap
2 mm gap
No Feathering Feathering
Clinical Marking
Cranial field
Position :
Supine
Ask patient to stare up straight to the ceiling
Draw a line along the pupillary line on the forehead : Line 1
Draw a line joining the lobule of the ear and the lateral canthus of the
eye and extend it to the former line: Line 2
With patient prone draw on the neck a line 6 cm transversely along
the C2 / C3 vertebrae: Line 3
Extend line 2 to the back to join line 3
Give gap of 1 – 0.5 cm with the spinal field and draw the spinal fields.
Posterior fossa
Anterior border: 2 cm Anterior to the tragus
Superior border 2.5 – 3 above the superior border of the zygoma
Inferior border below ear lobule
Posterior border: Keep open
Half Beam Blocking
Instruction for
biweekly hemogram
Instruction for
posterior fossa boost
Disadvantage of the half beam technique
Requires asymmetrical jaws.
10% - 25% dose inhomogenity at the match line
Width of inhomogeneous strip is 2 -4 mm.
In event of misaligned jaws or improper movement unintended dose
inhomogeneities
Increase divergence to opposite eye under the block.
Spinal field size reduced – two fields needed in most children.
0.6 cm wide
Hockey Stick Technique
D1 D2
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 per cumm
The neutrophil count falls below 1,000 cells per milliliter
Platelet count falls below 80,000 per 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
In PGI a biweekly hemogram is done – one on Monday and the
next on Thursday.
Posterior fossa Irradiation
Craniospinal irradiation:
36 Gy in 20 # over 4 weeks to the cranium
Dose per fraction: 1.8 Gy
30 Gy in 20 # over 4 weeks to the spine
Dose per fraction: 1.5 Gy
ANSWER: NO!!
CSI Controversies..
Can Lower CSI dose be given?
MED84 trial – SIOP (Neidhart et al 1987)
25 Gy / 20# vs 35 Gy / 25# in good risk patients
In low dose group more frequent relapses after 1st year
1st CCSG study: Evans et al (J Neurosurgery 1990)
Significant association between low dose and poor EFS
CCSG & POG study (Deutch et al 1991)
36 Gy / 23# vs 23.4 Gy / 13# in good risk patients
Lower dose increased risk of recurrence
Hughes et al (Cancer 1998)
Small reduction in survival with spinal cord doses < 27 Gy (60%
vs 69%)
However local spinal control not different
CSI Controversies..
Goldwein et al (Cancer 1991)
Used 18 Gy in 10# with 50 – 55 Gy PF boost + Vincristine during
RT + Vincristine & CCNU after RT – good risk patients
All patients younger than 5 yrs.
3/10 patients relapsed – study closed
All had relapsed at the spine
CCG-923/POG #8631 (JCO 2000)
Comparison of 23.4 Gy CSI vs 36 Gy
EFS at 8 yrs 52% (vs 69%) in the low dose group (p = 0.08)
Significantly increased risk of neuraxis failure
Biological rationale:
Vascular tumors
High growth fraction
Experience extrapolated from other childhood tumors
(including PNETs)
Settings for adjuvant CCT:
Post-operative : In infants and children < 3 yrs to delay / avoid
RT
Post RT:
In high risk patients: To improve cure rates
In average risk patients: To allow reduced RT dose
Chemotherapy schedules
Single agent CCNU: 8-in-1 regimen
Lomustine 100 -130 mg/m2 6 weekly Methyl PDN 300 mg/m2
PCV Vincristine 1.5 mg/m2
CCNU 75 mg/m2
Procarbazine 60 – 75 mg/m2 PO D18
– 21 Procarbazine 75 mg/m2
CCNU 110-130 mg/m2 PO D1 Hydroxyurea 1500 mg/m2
Vincristine 1.4 mg/m2 IV D8 and D29 Cisplatin 60 mg/m2
Cisplatin-Etoposide: Cytarabine 300 mg/m2
Endoxan 300 mg/m2
Cisplatin 30 mg/m2 IV D1 – D3 CVP
Etoposide 100 mg/m2 IV D1 – D3
CCNU 75 mg/m2
CCV
Vincristine 1.5 mg/m2
CCNU 75 mg/m2 Prednisone 40 mg/m2
Cisplatin 75 mg/m2
Vincristine 1.5 mg/m2
Adjuvant CCT in High Risk
Many trials – few randomized comparisons with standard RT alone
arms.
Randomized trials in both CCG and SIOP) between 1978 and
1981 documented the impact of adjuvant chemotherapy
(lomustine and vincristine, with prednisone added in the CCG
study)
Significant improvement in disease control and survival among
patients with locally advanced, incompletely resected, and
metastatic disease.
Particularly the study conducted by Evans et al (CCG) showed a
significant difference in the 5 yr EFS of 46% vs 0% in the patients
who had not received CCT. (Evans , 1990)
Packer et al (1994) administered adjuvant VCR + Cisplatin +
CCNU after CSI (with concomitant VCR) – 85% EFS in 63 patients
with high risk medulloblastomas.
Adjuvant CCT in High risk
In contrast two randomized trials conducted by Tait et al (1990)
and Kirscher (1991) showed no significant benefit of CCT with
VCR+CCNU or MOPP respectively.
Adjuvant CCT may improve the disease control rates but long term
follow up studies will be required to assess the impact on the OS.
May be suitable in patients with disseminated disease at
presentation.
The considerable additive cost and toxicity are deterrents to
routine implementation in 3rd world countries.
Adjuvant CCT in average risk
Packer et al reported on the largest series of patients treated with
adjuvant CCT following low dose CSI
421 patients with non disseminated medulloblastoma
Age > 3yrs
Randomly assigned to treatment with 23.4 Gy of CSRT, 55.8 Gy of
posterior fossa RT, plus
Cisplatin + CCNU + VCR x 8 cycles
Cisplatin + Cyclophosphamide + VCR x 8 cycles
5 year EFS and OS were 81% and 86% respectively
Considerable Rx toxicity: (Grade III/IV)
Hematologic: 98%
Hepatic: 12%
Renal 12%
Nervous System 50%
Hearing 28%
Infections 30%
Also no comparison with standard RT alone arm !!
Adjuvant CCT to delay RT
Pediatric Oncology group: (Duffner et al, NEJM, 1993) n = 198
Preirradiation CCT can thus reduce OS , increase relapse and impair delivery
of radiation in the poor risk patient
Recurrent Medulloblastomas
Importance of RT quality
Moderator:
?
Department of Radiotherapy
PGIMER, Chandigarh
Target Volume Cranium: Method 1
Homogeneous dose
profile at the beam
abutment region
Penumbra field 1
Penumbra field 2
3 cm