management

Medulloblastoma

: Dr Puneet Kumar Bagri

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

…

POSTOP STAGINGContrast 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 PNETCSI

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

…

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

chemotherapy

Radiotherapy

Medulloblastom

a

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

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

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

Pediatric

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

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 neurocognitivefunctions

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…

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%

RADIOTHERAPY

Objective: To treat microscopic cancer cells / residual

tumor with the goal of reducing its size orstopping 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).

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

Target Volume:Entire brain and its meningeal coverings with the CSF

Spinal cord and the leptomeninges with CSF

Posterior fossa – boost

Energy4-6 MV linac or Co60

PortalsWhole 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

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

PLANNING STEPS

Positioning

Immobilization

Simulation

Field arrangement

Matching of CSI

Aligning of spinal field

Implementation of plan

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

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

FIELD ARRANGEMENTS

Whole brain

In the simulator, opposing lateralfields are applied to the whole brainwith a collimator rotation of 7-11o tomatch the divergence of the directposterior spinal field.

SFOP guidelines- Therecommended

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 ofthe 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.

Spinal field

Laterally- 1 cm margin beyond thepedicles, to cover the spinal cord andmeninges along the nerve roots uptothe spinal ganglia

Caudal- 1 cm below the termination ofthe thecal sac i.e. L5 –S3.

2 spinal fields are used if the length is >36 cm.

In Dorsal Region, block lat. Field tocover heart and lungs.

In Lumbar Region, reduce field tospare BM and Gonads.

SSD techniqueGantry 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 .

Posterior fossa boost

Volume includes entire Infratentorialcompartment.

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

TECHNIQUES OF MATCHING CS

FIELDS

Collimator/Couch

rotation

Half beam block

Asymmetric jaws

Moving Junction

technique

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).

Collimator rotation allowscranial field to matchspinal field divergence

Coll θ = arc tan (L1 /2 x SSD)

For Co60 SSD = 80 cm

Zone of overlap of spinal field if collimator rotation isnot applied in cranial field

SSD

L1

Collimator rotation :While treating cranial field rotate Collimator of lateral field so thatits inferior border is parallel to divergence of superior aspect of spinal field.

θ

COLLIMATOR

ROTATION

In order to avoid theoverlap resulting from infdivergence of cranialfield, rotate the couchtowards the collimator sothat fields margins of twofields become parallel.

Degree of couch rotationdepends upon the lengthof lateral cranial fieldsand 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 tomatch the caudal margin of the lateral cranial fields with thecephalad margin of the posterior spinal field.

COUCH ROTATION

Couch θ = arc tan (L2/2 x SAD)

For Co60 SAD = 80

L2 ( Length of

cranial field)

Cranial field

SAD

Zone ofoverlap

Spinal field

Couch rotation

during

treatment of

cranial field

θ

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)

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 ofthe craniospinal setup. A couch angle on the lateral cranialfields can cause the contralateral temporal lobe to beunderdosed

Half Beam Blocking

Actual Cranial Field LengthSpinal field

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

Moving junction in CSI

Feathering after every 5-7fraction smoothes out any overor underdose over a longersegment 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.

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

Fixed or calculated gap spinal

fields

Gap calculation formulaS= ½ x L1(d/SSD1)+½ x L2(d/SSD2)

Cold Spot Hot Spot

SSD 2 SSD 1

L2 S L1

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 spinalfield is shortened

Upper Spine Lower Spine

Day 2: The lower spinal field isshortened

Junction on D 1 Junction on D 2

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

Monitoring during CSI

CSI results in predictable, if quantitatively variable, acutechanges in the peripheral blood counts.

Neutropenia or thrombocytopenia are most often notedduring 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 withbleeding manifestations

If blood counts necessitate interrupting CSI for more than2 consecutive days, initiation of posterior fossa irradiationcan be done

A biweekly hemogram should be done – one on Mondayand the next on Thursday.

Pediatric

Medulloblastoma

Prognosis :5yr survival rate

Standard risk ds – 78%

High risk ds – 30-55%

Infants – 30%

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

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