management of medulloblastoma

1. Diagnostic Workup & Management Of
Medulloblastoma
Presenter :- Dr. Vijay.P.Raturi
J.R 2 Radiotherapy Deptt
K.G.M.U
Moderator :- Dr. Rajender Kumar

2. Introduction
• The origin of Medulloblastoma is from medulla (Latin for marrow), blastos
(Greek word for germ) and oma (Greek for tumor);
means “tumor of primitive undeveloped cells located inside the cerebellum”.
• Most common malignant primary brain tumor of child age group.
• First described by Harvey Cushing and Percival Bailey in 1930.
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3. Anatomy

4. Medial surface of brain

5. C.T images of brain

6. C.T images of brain

7. Lateral Ventricle
Foramen of Munro
Third Ventricle
Foramen of Luschka
Foramen of Magendie
Central canal of Spinal Cord
Subarachnoid Space
CSF Pathway

8. Epidemiology
• Overall account ~ 7% all brain tumors
• 10-20% of brain tumors in pediatric age group
• 40% of tumors of the posterior fossa
• Peak incidence at the age of 5 –6 yrs In children and 25 yrs in
adults
• Approximately 20% of Medulloblastoma present in infants younger
than 2 years old;.
• Male : female (3:2)
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9. Natural History
Arising in the midline
cerebellar vermis (roof of
the 4th ventricle
Grow & fills into the
4th ventricle
CSF spread
Invasion of
brainstem , pons &
ventricular floor

10. Clinical Presentation
Mass effect
CSF Obstruction
Raised ICT
Head ache,
nausea,
vomiting
Cortex Irritation Seizure
Compression & Invasion
Neurological
symptoms

11. Diagnostic Work up
Detailed Clinical history
Complete Physical examination:
 General examination
 CNS examination
 Ophthalmoscopy examination for papilloedema
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12. Diagnosis
• For most pediatric brain tumors, magnetic resonance
imaging (MRI) with gadolinium is the modality of choice in
brain imaging at diagnosis, assessment of postoperative
residual, and follow-up.
• Postoperative MRI of the brain is done within 48 h of
surgery, as surgically induced changes can mimic residual
tumor and may not resolve until ~ 2 weeks after resection.
• In tumors with known propensity to spread throughout
the neuraxis , MRI of the spine and CSF cytology from a
lumbar tap may indicate tumor dissemination, and are
used for staging

14. Fig: (B,) non-contrast axial T1-weighted (C,) T2-weighted MR images; the
solid portion of the tumor appears mildly hypointense on T1-weighting and
mildly hyperintense on T2-weighting (arrow). Following intravenous
gadolinium, an axial T1-weighted image
(D,) demonstrates irregular patchy contrast enhancement of the solid areas
of the tumor (arrow).
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15. Sagittal , T1 weighted Gadolinium contrast enhancement – Medulloblastoma with
metastatic spread to the meninges within the posterior fossa and with a large
intramedullary deposit.

16. Staging & Classification
Chang system (Chang et al. 1969)
T1: <3 cm
T2: >3 cm
T3a: > 3cm with extension into the aqueduct of Sylvius and/or the foramen of Luschka
T3b: > 3cm with unequivocal extension into the brainstem
T4: > 3cm with extension up past the aqueduct of Sylvius and/or down past the
foramen magnum
M0 No metastases
M1 Microscopic cells in CSF
M2 Gross Nodular seeding in cerebellar, cerebral subarachnoid space, third or lateral
ventricles
M3 Gross Nodular seeding in spinal subarachnoid space
M4 Extraneuraxial metastasis
Risk categories Standard risk: age >3 years and GTR/STR with <1.5 cm2 residual and M0
High risk: age <3 years or >1.5 cm2 residual, or M+
Survival Standard-risk DFS 60–90% High-risk DFS 20–40%, increased to 50–85% with
adjuvant chemo

17. Prognostic factors for Medulloblastoma

18. Treatment of Medulloblastoma
Surgery Radiotherapy Chemotherapy

19. Surgery
Objective:
 Relieve ICP & local pressure effect ,i.e. Shunting.
 Remove or Reduce as much of the tumor's bulk as possible.
 Tissue Diagnosis and staging – Biopsy.
Surgery is classified as:
 No evidence of residual tumor at surgery and negative postoperative
imaging : Gross total resection
 > 90% : Total or near total
 51 - 90% : Subtotal resection
 11 - 50% : Partial resection
 < 10% : Biopsy
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20. Radiotherapy in Medulloblastoma

21. Positioning & Immobilization for CSI
Prone vs Supine :- Prone preferred due to direct
verification , good alignment of spine
Disadvantages
• Relatively poor reproducibility
• Larger scope for patient movement
• Discomfort to the patient
• Difficult anesthesia if needed

22. Customized Immobilization
Customized
prone head rest
Vacuum bag

23. Phase I :- a> Two lateral cranial fields
b> 1 or 2 spinal fields
Phase II: - Posterior fossa boost
a> Two lateral cranial fields
b> Conformal technique in low risk cases.
Radiotherapy Planning

24. CSI for average-risk disease
(age >3 yrs, M0 status, and residual <1.5 cm2)
• Standard dose CSI: 35-36 Gy/21-20#/4 weeks @ 1.67-1.8 Gy/#
• Reduced dose CSI: 23.4 Gy/13#/2.5 weeks @1.8 Gy/# (+ adj CT)
• Very reduced dose CSI: 18 Gy/10#/2 weeks @ 1.8 Gy/# (+ adj CT)
Boost for average-risk disease
• If Standard dose CSI : PF or TB boost: 19.8 Gy/11#/2 weeks
• If reduced dose CSI: Tumour bed boost: 32.4 Gy/18#/3.5 weeks
• If very reduced dose CSI: Tumour bed boost: 39.6 Gy/22#/4.5 weeks
Total tumour bed dose: 54-56 Gy/ 30-33#/ 6.6.5 weeks (conventional #)
Doses & volumes as per risk Stratification

25. CSI for high-risk disease (age <3 yrs, M+ status, and
residual >1.5 cm2)
• Standard dose CSI: 35-36 Gy/21-20#/4 weeks @ 1.67-1.8
Gy/#
• Higher dose spinal RT: 39.6 Gy/22#/4.5 weeks @1.8 Gy/#
Boost for high-risk disease
• Whole posterior fossa boost: 19.8 Gy/11#/2 weeks
• Boost for gross focal spinal deposit: 7.2-9 Gy/4-5#/1 week
High risk Medulloblastoma

26. Borders
• Anterior: Posterior clinoid process.
• Posterior: Internal occipital protuberance.
• Inferior: C2-C3 interspace.
• Superior: Midpoint of foramen magnum & vertex or 1
cm above the tentorium (as seen on MRI).
Field arrangement
• Two lateral opposing fields.
• 3DCRT boost to the preop tumor bed with
appropriate margins is being studied
Posterior fossa boost

27. Posterior Fossa boost (Conventional Simulation)

28. Spinal Field
• Spinal field simulated first (get to know the divergence
of the spinal field)
• SSD technique
• 2 spinal fields if the length is > 36 cm
• Upper border at low neck
• Lower border at termination of thecal sac or S2
whichever is lower
• In case of 2 spinal fields , junction at L2/L3

29. Gap Correction Formula

30. SPINAL FIELD (UPPER BORDER )

31. Techniques for matching craniospinal
fields:-
• Collimator/couch rotation
• Half beam block
• Asymmetric jaws

32. Divergence Of Cranial Field
CRANIAL FIELD

33. Solution to prevent overlapping
divergence of Cranial field

34. Rotation of couch

35. Asymmteric block

36. Divergence of Spinal Field
SPINAL FIELD

37. Solution to prevent overlapping
divergence of Spinal field

38. Rotate the Cranial Field Collimator
Collimate cranial field

39. Use Asymmetric Spinal Block

40. • Ability to virtually simulate, thereby minimizing the time
a patient must remain immobilized.
• Better definition of critical organs (spinal cord) and
target volume (cribriform plate)
• Graphical overlays of anatomic CT data onto digitally
reconstructed radiographs (DRRs) - improves field
placement, shielding accuracy & direct calculation of gap
between the fields.
C.T Simulation

41. • Patient positioned using all ancillary devices and the spinal columns aligned
with the sagittal external laser.
• Three-point reference marks drawn on the mask in a transverse plane at the
center of the head with the aid of the external lasers.
• Two or three reference marks were placed on the posterior skin surface along
the spinal column
• Spiral CT images of 3-5 mm thickness are acquired.
• Following image acquisition, all spinal reference marks are tattooed and the
patient permitted to leave.
• A total of 130 - 170 images are reconstructed depending on the patients
height.
Step in C.T Simulation

43. Studies/Trials in Medulloblastoma
a Source: Tait DM, Thornton-Jones H, Bloom HGJ et al (1990) Adjuvant chemotherapy for medulloblastoma: the fi rst multi-centre control
trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer 26:464–469
b Source: Evans AE, Jenkin RDT, Sposto R et al (1990) The treatment of medulloblas- toma. Results of a prospective randomized trial of RT
with and without CCNU, vincris- tine and prednisone. J Neurosurg 72:572–582
c Source: Krischer JP, Ragab AH, Kun LE et al (1991) Nitrogen mustard, vincristine, procarbazine and prednisone as adjuvant chemotherapy
in the treatment of medullo- blastoma. J Neurosurg 74:905–909
d Source: Taylor R, Lucraft H, Robinson K et al (2003) Results of a randomized study of preradiation chemotherapy versus radiotherapy
alone for nonmetastatic medullo- blastoma: the ISPG/UK Children’s Cancer Study Group PNET-3 Study. J Clin Oncol 21;1581–1591

44. Based on the results of a phase II Children’s Cancer
Group (CCG) study, it is felt that low-dose craniospinal
irradiation (CSI) to 23.4 Gy CSI with chemotherapy is
equivalent to, if not better, than 36-Gy CSI
a A phase II CCG study showed that reducing the CSI dose to 23.4 Gy with chemotherapy
resulted in a 5-year PFS of 79%
b Tumor bed irradiation only may not compromise local control
Source: Packer RJ, Goldwein J, Nicholson HS et al (1999) Treatment of children with
medulloblastoma with reduced-dose CSI and adjuvant chemotherapy: a CCG study. J Clin
Oncol 17:2127–2136

45. • Neurocognitive & neurophysiological dysfunction
• Endocrine abnormalities & hormonal imbalance
• Growth retardation - spinal component
• Ototoxicity- particularly with platinum based adj CT
• Cerebrovascular accidents
• Gonadal toxicity & reduced feritility
• Second malignant neoplasms
Long-term sequelae of RT in Medulloblastoma

46. Chemotherapy
• Indication for CT :
1. As Adjuvant with Surgery in child <3 yrs to delay/avoid RT.
2. In Recurrent /Progressive disease .
3. In patients with Extra cranial mets .
4. High risk Pt. to improve cure rates.
5. In avg. risk group to allow reduced RT dose.
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47. Delay in starting RT results in inferior outcome: Halperin
Prolongation of RT duration negatively impacts upon
survival: Del Charco & SIOP PNET 3
Pre RT CT inferior to post RT CT: CCG 921 and HIT 91
Pre RT CT does not improve survival compared to RT
alone: SIOP II & SIOP PNET 3
Pre RT CT followed by reduced dose CSI inferior: SIOP II
Integration of R.T with C.T

48. Average-risk disease
• Definitely NOT
• CCG 942 & SIOP I
High-risk disease
• Definitely YES
• Evans, Tait et al
• HIT 91, CCG 942 & SIOP I
• POG 9031 & SIOP PNET 3
Adjuvant C.T relationship with Survival

49. Recurrence
Relapses occur in nearly 75% of paediatric cases within 2 years.
Sites
• Post. Fossa
• supratentorial region including cribriform plate
• spinal cord
• ventricular walls
Diagnosed by neuroimaging;
• occasionally, clinical progression precedes neuroimaging findings.
Treatment at relapse:
• Localized brain recurrence: Surgery“radiation therapy combined with
various chemotherapy schedules.”
• Disseminated disease: Chemotherapy or best supportive care including
radiation.
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50. Follow up
• In standard risk :
Brain MRI - every 3 months, for the first 2 years.
Spinal MRI - every 6 months, for the first 2 years;
then Brain MRI every 6 months up to 3 years and
spinal MRI every year for 3 yrs.
• In high-risk :
Brain and spinal MRI - every 3 months for
the first 2 years then every 6 months.
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51. Thank You....