Medulloblastoma

Question 1

What percetage of pts have CSF dissemination at Dx

Answer 1

33%

Question 2

Peak ages for group C

Answer 2

4-6 yrs

Question 3

Peak ages for SHH

Answer 3

25 ys

Question 4

What % are familial and what are the disorders

Answer 4

Turcot and Gorlin
2-5%

Question 5

What is the workup for medulloblastoma

Answer 5

-H&P including neurological exam, fundoscopic exam
-Imaging: MRI of brain and spine
-If very symptomatic, best to go straight to surgery with placement of posteror fossa drain (not shunt)
-Do not obtain CSF cytology before surgery due to risk of herniation
-MRI of brain 24-72 hrs post surgery
-Obtain CSF cytology 10-14 days after surgery to avoid false positives
Other imaging: CT CAP
Labs: CBC, CMP
Bone marrow biopsy as indicated for adults
Baseline audiometry, neurocognitive/IQ testing, growth measurements, neuroendocrine, and ophthalmology

Question 6

What are infatentorial/posterior fossa tumors

Answer 6

medulloblastoma, ATRT, mets, ependymoma, JCA

Question 7

Differential dx for small round blue cell tumors

Answer 7

LEARN NMR
lymphoma
ependymoma
ALL
rhabdomyosarcoma
Neuroblastoma
Neuroepilioma
medulloblastoma
retinoblastoma

Question 8

What is a characteristic histopatholoigc factor seen in 40% medulloblastoma

Answer 8

Home Wright Rosettes
( These are also seen in pineoblastoma, neuroblastoma, PNET)

Question 9

What is a characteristic genetic factor seen in 50% medulloblastoma

Answer 9

17q deletion in 50%

Question 10

What are the genetic subgroups of medulloblastoma

Answer 10

WNT
SHH
Group 3
Group 4

Question 11

Describe the WNT subgroup

Answer 11

18% of patients
CTNNB1 mutation
Best prognosis
Not seen in infants
18Gy CSI on new protocol

Question 12

Describe SHH subgroup

Answer 12

19% of patients
PTCH1 (Gorlin), MYCN mutation
Usually desmoplastic
Occur laterally
Most common in children and adults

Question 13

Describe Group 3

Answer 13

Myc amplified
Worse prognosis
Typically occurs before puberty
Distant mets at diagnosis are common

Question 14

Describe group 4

Answer 14

CDK6 , MYCN amplification
adolesence

Question 15

Describe the M staging for medulloblastoma

Answer 15

M0- no mets
M1- + CSF
M2- intracranial nodules
M3- spinal nodules (M3a spine only, M3b spine and brain nodules)
M4- mets outside CSF

Question 16

What is standard risk medulloblastoma?

Answer 16

> 3yrs
GTR or <1.5 cm residual disease
Classic or desmoplastic histology

Question 17

What is intermediate risk medulloblastoma

Answer 17

> 3 yrs
GTR or <1.5 cm residual disease
but with large cell or anaplastic histology

Question 18

What is high risk medulloblastoma

Answer 18

< 3 yrs
> 1.5 cm residual disease
Diffuse anaplasia
M+
PNET

Question 19

What is the treatment paradigm for <3 yrs vs. > 3 years medulloblastoma

Answer 19

> 3yo: Maximal safe surgical resection followed by concurrent chemoRT within 31 days post-op then Adjuvant chemo

<3yo: Maximal safe surgical resection followed by chemotherapy alone. RT for salvage.

Question 20

What is the most important predictor of survival in medulloblastoma patients

Answer 20

extent of surgery

Question 21

What chemotherapy is used in kids <3 yrs who cannot receive chemotherapy

Answer 21

cyclophosphamide/vincristine
carboplatin/etoposide

Question 22

Should standard risk adults get chemo

Answer 22

No

Question 23

What chemo is used for concurrent chemoRT

Answer 23

Vincristine

Question 24

What labs are needed for starting CSI in medulloblastoma and what should be done if these heme values are not met?

Answer 24

ANC>1000
platlets>100K

If these lab values are not met, then do boost fields first, and do spine fields after

Question 25

Describe sim set up

Answer 25

-can be prone or supine aquaplast mask for immobilization -chin extended to avoid divergence through the oral cavity -shoulders pulled down as much as possible -scan vertex through mid femur for patients 0-4 years- opposed laterals for brain and matched electron fields for spine

Question 26

What is the benefit of using protons

Answer 26

proton CSI can improve conformality to high dose regions and reduce risk of secondary malignancy and dose to heart, esophagus, stomach, bowel etc.

Question 27

Describe 3D CSI Script

Answer 27

-Prone positioning, extend the neck to avoid divergence of spinal fields into oral cavity -Arms at sides with shoulders relaxed to allow lowest possible edge of spinal fields  Set the spine field first for the collimator angle to match divergence * Superior = C4-7, or as low as possible without going through the shoulders. * Inferior = thecal sac (S2-3) + 1-2cm margin inferiorly * Lateral = 1cm lateral to transverse process, spade at sacrum to include SI joints * Use a single field if length <40cm

Question 28

What should be done if the spine measured over 35 cm

Answer 28

Treat at 120cm SSD – increased divergence to tissue, increased scatter, higher Mus, higher PDD, and greater penumbra results in higher mean doses to all anterior normal structures Use two fields – match distal to the cord with the skin gap equation. Consider moving the gap if this is over gross disease. Gap S = (0.5)(d)(L1/SSD1 + L2/SSD2)

Question 29

What must be done to reduce hot and cold spots if using 2 fields

Answer 29

feathering the junction over 5-7 treatments (once/week)

Question 30

What should be done to reduce the superior divergance of the spine fields

Answer 30

rotate the collimator of the cranial fields to match the superior divergance of the spine fields

Question 31

What should be done to minimize the inferiror divergance of the cranial fields

Answer 31

Kick the couch towards the gantry (usually 7-10 degrees)

Question 32

Describe the radiation regiment for standard risk patients

Answer 32

CSI 23.4Gy --->involved field (IF) boost 54Gy + concurrent weekly vincristine **Adjuvant chemo **(cisplatin, vincristine, cyclophosphamide or CCNU are all options) * CTV5040 = preop tumor + bed + 1.0-1.5cm, anatomically constrained, allowing 2mm into brainstem unless involved

Question 33

Describe the radiation for intermediate risk patients

Answer 33

CSI 23.4Gy * CTV5040 = preop tumor + bed + 1.0-1.5cm, anatomically constrained, allowing 2mm into brainstem unless involved * Involved field (IF) boost 54Gy + concurrent weekly vincristine ( Consider adding carboplatin in these patients)

Question 34

Describe treatment of high risk patients

Answer 34

CSI 36Gy  posterior fossa (PF) boost 54Gy + concurrent weekly vincristine +/- carboplatin followed by adjuvant cisplatin-based chemo

Question 35

What should you boost M2 (intracranial mets to)

Answer 35

intracranial metastases boosted to 55.8Gy

Question 36

What should you boost M3 (intracranial mets to)

Answer 36

spinal metastases above cord boosted to 45Gy, below cord to 50.4Gy

Question 37

M4 diffuse LMD?

Answer 37

CSI to 39.6Gy

Question 38

What are the borders of a posterior fossa boost

Answer 38

Superior = tentorium Inferior = C2-3 junction, through foramen magnum Lateral = bony walls of occiput and temporal bones Anterior = posterior clinoids and anterior C1, block pituitary unless involved Posterior = cerebellar fossa/internal occipital protuberance

Question 39

Describe posterior fossa syndrome

Answer 39

Occurs in 25% of patients within 1-2 days after surgery o SAME-R = swallowing difficulties, truncal ataxia, mutism, emotional lability, respiratory failure, gaze palsy o Do not delay radiation – typically improves over 1-6 months, but dysarthric speech and ataxia may remain

Question 40

Describe side effects after CSI

Answer 40

o Short seated stature o Alopecia o Endocrinopathy, infertility, sterility o Intellectual/IQ decline:  Post-surgical complications are a significant contributor to decline in IQ  Protons have less IQ decline than photons because of conformality of boost volume (boost volume in posterior fossa does not leak into supratentorial brain)  Young age at RT, especially <3yo, associated with severe IQ decline

Question 41

Describe outcomes in pediatricts and adults with medduloblastoma

Answer 41

Pediatrics: o Standard risk 5-yr EFS = 80%; 5-yr OS = 80% o High risk 5-yr EFS = 65% - Adults: o 5-yr PFS: 72% o 5-yr OS: 75%