Diagnostic Workup & Management Of Medulloblastoma

Presenter :- Dr. Vijay.P.Raturi J.R 2 Radiotherapy Deptt K.G.M.U

Moderator :- Dr. Rajender Kumar

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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Anatomy

Medial surface of brain

C.T images of brain

C.T images of brain

Lateral Ventricle

Foramen of Munro

Third Ventricle

Foramen of Luschka

Foramen of Magendie

Central canal of Spinal Cord

Subarachnoid Space

CSF Pathway

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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Natural History

Arising in the midline cerebellar vermis (roof of

the 4th ventricleGrow & fills into the

4th ventricle

CSF spread Invasion of

brainstem , pons & ventricular floor

Clinical Presentation

Mass effect

CSF Obstruction Raised ICT

Head ache, nausea, vomiting

Cortex Irritation Seizure

Compression & Invasion Neurological symptoms

Diagnostic Work up

Detailed Clinical history

Complete Physical examination:

General examination

CNS examination

Ophthalmoscopy examination for papilloedema

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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

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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Sagittal , T1 weighted Gadolinium contrast enhancement – Medulloblastoma with metastatic spread to the meninges within the posterior fossa and with a large intramedullary deposit.

Staging & Classification

Chang system (Chang et al. 1969) T1: <3 cm T2: >3 cmT3a: > 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

Prognostic factors for Medulloblastoma

Treatment of Medulloblastoma

Surgery Radiotherapy Chemotherapy

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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Radiotherapy in Medulloblastoma

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

Customized Immobilization

Customized prone head rest

Vacuum bag

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

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

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

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

Posterior Fossa boost (Conventional Simulation)

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

Gap Correction Formula

SPINAL FIELD (UPPER BORDER )

Techniques for matching craniospinal fields:-

• Collimator/couch rotation

• Half beam block

• Asymmetric jaws

Divergence Of Cranial Field

CRANIAL FIELD

Solution to prevent overlapping divergence of Cranial field

Rotation of couch

Asymmteric block

Divergence of Spinal Field

SPINAL FIELD

Solution to prevent overlapping divergence of Spinal field

Rotate the Cranial Field Collimator

Collimate cranial field

Use Asymmetric Spinal Block

• 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

• 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

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

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

• 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

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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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

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

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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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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Thank You....