Done by: Maha Al-Molaiki,Pharm D, Candidate,KSU

[Oncology Rotation]

• Introduction

• Epidemiology

• Etiology

• Pathogenesis

• Diagnosis

• Clinical Features

• Classifications

• 5-Years Survival Rate

• Treatment Modalities

• Case Presentation

• It is a tumor located mainly in the cerebellum and sometimes

found in the brainstem

• The most common malignant CNS tumor in children

(age 3 - 8)

• Rarely seen in adults

Christina Wong et al. Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol. Feb 21 2012

• It occurs in 15-20% of all pediatric brain tumors

• In children up to 15 years of age the incidence is 0.5 per

100,000 cases

• It is Known as a PNET

(Primative Neuro-Ectodermal Tumor)

Christina Wong et al. Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol. Feb 21 2012

Asif Mehmood et al. KFSH&RC Annual Report 2011

Asif Mehmood et al. KFSH&RC Annual Report 2011

• Genetic abnormalities have been found in medulloblastomas, By:

–The loss of 17p frequently occurring in association with duplication of the

characteristic isochromosome 17q abnormality

–The p53 tumor suppressor gene is located in the short arm

of the 17 chromosome, this has led to the

abnormality in the p53 gene may underlie the

development of medulloblastoma

(Parsons et al 2011), (Takei et al 2009)

Christina Wong et al. Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol. Feb 21 2012

• As the tumor grows, obstruction of cerebrospinal fluid (CSF)

passage through the fourth ventricle resulting in hydrocephaly

• The tumor may spread contiguously to the floor of the fourth

ventricle:

–Anteriorly to the brainstem

–Inferiorly to the cervical spine

–Superiorly above the tentorium

Christina Wong et al. Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol. Feb 21 2012

• Magnetic Resonance Imaging(MRI) of the neuroaxis

• Lumbar puncture:

–Medulloblastoma can metastasize throughout the central

nervous system

–Cytological tests done on the sample to determine if

neoplastic cells are present

• Symptoms are mainly due to secondary increased intracranial pressure due to blockage of the fourth ventricle Children with medulloblastomacommonly present with the following:

Abrupt onset of headaches

Vomiting

Lethargy

Unsteadiness, including truncal unsteadiness

Some degree of nystagmus

Papilledema

Packer RJet al., Embryonal and pineal region tumors. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams and Wilkins, 2011

DescriptionTumour Classification

Greatest tumour dimension <3cmT1

Greatest tumour dimension >3cmT2

Greatest tumour dimension >3cm with spread into the aqueduct of Sylvius and/or foramen of Luschka, cerebral subarachnoid space, third or lateral ventricles

T3a

Greatest tumour dimension >3cm with unequivocal spread into the brainstem; for T3b, surgical staging may be used in the absence of involvement at imaging

T3b

Greatest tumour dimension >3cm with spread beyond the aqueduct of Sylvius and/or the foramen magnum

T4

Chang CH et alAn operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 1969 Dec

DescriptionMetastasis Classification

No evidence of gross subarachnoid or hematogenous metastasis

M0

Microscopic tumour cells in cerebrospinal fluidM1

Gross nodular seeding in cerebellumM2

Gross nodular seeding in spinal subarachnoid space

M3

Metastasis beyond cerebrospinal axisM4

Chang CH et alAn operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 1969 Dec

70%–80% • children with

average-risk medulloblastoma can be expected to be alive and free of disease five years from diagnosis

60%–65% • children with high-

risk disease, effective therapy is possible and results in long-term disease control

30%–50% • Outcome for infants

is poorer, but for those infants with localized disease at the time of diagnosis

Giles W. Robinson et al., American Brain Tumor Association.,2012.

Jakacki RI et alOutcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: COG Phase I/II study. J ClinOncol 2012.

Jakacki RI et alOutcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: COG Phase I/II study. J ClinOncol 2012.

Cisplatin

• Bone Marrow

Suppression

• Extravasation

• GI toxicity

• Hyperuricemia

• Infusion Site

reaction

• Neurotoxicity

• Ototoxicity

• Nephrotoxicity

Etoposide

• Hypotension

• Bone Marrow

Suppression

Cyclophosphamide

• Cardiotoxicity

• Bone Marrow

Suppression

• Hemorrhagic

Cystitis

• Pulmonary

Toxicities

• Wound Healing

Impairment

Vincristine

• Neurotoxicity

• Respiratory

Effect

• Uric Acid

Nephropathy

Lexi-Comp,2014

Side Effects

Monitoring Parameters

Cisplatin

• Renal function

test

(Scr,BUN,Clcr)

• Electrolytes(Mg,C

a,K)

• CBC(weekly)

• Liver function

test

Etoposide

• CBC

• Liver function

Test

• Albumin

• Vital Signs(BP)

• Renal Function

Test

Cyclophosphamide

•Signs/Symptoms

of Hemorrhagic

Cystitis

•CBC

•BUN

•Serum Electrolyte

Vincristine

• Electrolytes(Na)

• CBC

• Constipation

• Signs/Symptoms

of Neuropathy

Lexi-Comp,2014

Case Presentation

• F.D. is an 8 years old girl K/C of:

oMedulloblastoma stage IV Maintained on:

oChemotherapy Protocol

oRadiation

• Fever

•Cough

• SOB

• Ataxia with unsteady gait

• Brain tumor was resected, patient needs further

chemotherapy management

• The patient went to Al Kharj Hospital and they did CT

brain that showed left cerebellar lesion.So, she referred

to PSMMC for further management and surgical

resection

• On the 29th -Aug-2013 The Patient presented to the

hospital with history of headache, vomiting and

neutropenia for the last four days. Her parents Brought

her to PSMMC hospital due to the low oral intake

• Then the patient initially presented to the Neurosurgery

team with unsteady gait

• On the 15th –September-2013 MRI done for her and

showed a mass brain tumor, for which she was taken for

surgical resection by the Neurosurgery team

• On the 16th –September-2013 histopathology reported

as medulloblastoma anaplastic

• The child was diagnosed as medulloblastoma Stage IV

• On the 10th –November-2013 They received the patient in

a good condition, active, walking with no neurological deficits,

Vitally and hemodynamically stable

• On the 20th -Mar-2014 The patient was started on IV fluids only and finished

the first cycle of chemotherapy in which she received cisplatin and of

VP16(Etoposide) for 21 days. Also, finished her radiotherapy on 7th - January

2014

• She is due for cycle”2” to receive cyclophosphamide and Vincristine

• Bronchial asthma Maintained on:

oSalbutamol Inhaler 100mcg/dos 1 PUFB PRN

• Neurofibromatosis type I

• The patient underwent craniotomy and resection and after the

surgery the patient transferred to PICU and stayed for two days

there

•Medulloblastoma is not an “inherited” disease

because the genetic changes tend to only occur

inside the tumor cells

Giles W. Robinson et al., American Brain Tumor Association.,2012.

MedicationsSalbutamol Inhaler 100mcg/dos 2 puffs PO Q6hr PRN

Co-Trimoxazole 240mg/5ml Susp,5ml Q12hr 2 days aweek(Sun,Mon)

Specific Mouth Wash 5ml

Fusidic Acid 2% Cream Apply to affected area FOUR times daily X2 WKS

Fluticasone 250mcg Inha 1 puff PO BID

Filgrastim inj (GC-SF) 300MCG,Inj SQ 0.1 ml(30mcg),OD,X10 DAYS

The patient not pale , jaundiced or cyanosed

• Vital signs:

• BP: 117/82mmHg

• Weight: 19kg

• Height: 129cm

• BMI: 11.4 kg/m2

• Temperature: 37.8C

• Oxygen saturation: 97% on room air

• Chest: Bilateral Cripitations

• Abdomen: Hepatomegaly

BIOCHEMISTRYHEMATOLOGY

• Na 137• K 3.9• Urea 3.2• Scr 38• C.Ca 2.27• Ph 1.38• Mg 0.75• Glucose 4.8• Albumin 45• ALP 113• AST 22• ALT 15• Gamma GT 12• Alkaline Phosphatase 144

• WBC 15.9• RBC 3.69• HGB 11• Hct 0.310• Plt 260• Neut A 13.6

HighLow

PAos•Medications: Add Flixotide

(Fluticasone)125mcg1Puff BID

Paracetamol 300mg PO q4-6 hr PRN(for fever)

Ventolin (Sulbutamol)2 Puffs by mouth TID

Bactrim 240mg PO BID(Sun,Mond)

Tazocin 1.7g IV Q6hr

day 3

An 8 yrs old girl k/c of M.B. andB.A.

• BP 110/52• Temp 36.7• RR30• PO2 98%• WBC 5.1• RBC 3.16• HGB 9.7• Hct 0.271• Plt 214• Neut A 4.2• Na 140• K3.5• Urea 1• Scr 35• C.Ca2.43• Ph1.14• Mg0.68

Daily Cough more at night andearly morning

PAos•Medications:

D/C Bactrim 240mg PO

BID(Sun,Mond)

Tazocin 1.7g IV Q6hr day6

Add Etoposide 27mg(start

date 7th -May)

Add Cisplatin 35mg IV(start

date 7th -May)

Add Granisetron 0.4mg(start

date 7th –May)

Add Septrin 5ml(start date 7th

-May)

An 8 yrs old girl k/c of M.B. andB.A.

• BP 108/60• Temp 36.7• RR30• PO2 98%• WBC 2.5• RBC 3.43• HGB 10.4• Hct 0.298• Plt 307• Neut A 1.1• Na 135• K3.8• Urea 2.6• Scr 41• C.Ca2.36• Ph1.46• Mg0.83

Daily Cough more at night andearly morning

PAos•Medications:

Tazocin 1.7g IV Q6hr day8

D/C Etoposide 27mg OD

(On 9th –May)

D/C Cisplatin 35mg IV(On

7th –May)

Granisetron 0.4mg

Septrin 5ml

Add Dexamethasone 2mg

(start date 9th -May) one

dose only(STAT)

Add GCSF 95mcg SQ OD

(start date 8th–May)

An 8 yrs old girl k/c of M.B. andB.A.

• BP 101/52• Temp 36.7• RR30• PO2 98%• WBC 17.5• RBC 3.43• HGB 10.4• Hct 0.298• Plt 307• Neut A 16.61• Na 133• K 3.5• Urea 3.4• Scr 43• C.Ca2.30• Ph1.40• Mg0.99

•Increase vomiting

•cough improved

Discharge Medications

Filgrastim (GC-SF) 300mcg,Inject 0.1 ml(30mcg)SQ OD for 10 days

Granisetron 0.2MG/ML SUSP 2 ml PO BID for 4 days

Co-Trimoxazole 240mg/5ml Suspens 5ml BID Two days aweek Friday and Saturday for 1 month

Salbutamol Resp Soln 5mg/ml 20ml 2 puffs PO Q6hr PRN

Fluticasone 125mcg Inhaler 1 puff PO BID