[Oncology Rotation] Done by: Maha Al-Molaiki,Pharm D, Candidate,KSU

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1 [Oncology Rotation] Done by: Maha Al-Molaiki,Pharm D, Candidate,KSU

2 Introduction Epidemiology Etiology Pathogenesis Diagnosis Clinical Features Classifications 5-Years Survival Rate Treatment Modalities Case Presentation

3 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

4 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

5 Asif Mehmood et al. KFSH&RC Annual Report 2011

6 Asif Mehmood et al. KFSH&RC Annual Report 2011

7 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)

8 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

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

10 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 Symptoms are mainly due to secondary increased intracranial pressure due to blockage of the fourth ventricle Children with medulloblastoma commonly present with the following: Abrupt onset of headaches Vomiting Lethargy Unsteadiness, including truncal unsteadiness Some degree of nystagmus Papilledema

11 Tumour Classification T1 T2 T3a T3b T4 Description Greatest tumour dimension <3cm Greatest tumour dimension >3cm Greatest tumour dimension >3cm with spread into the aqueduct of Sylvius and/or foramen of Luschka, cerebral subarachnoid space, third or lateral ventricles Greatest tumour dimension >3cm with unequivocal spread into the brainstem; for T3b, surgical staging may be used in the absence of involvement at imaging Greatest tumour dimension >3cm with spread beyond the aqueduct of Sylvius and/or the foramen magnum Chang CH et alan operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 1969 Dec

12 Metastasis Classification M0 M1 M2 M3 M4 Description No evidence of gross subarachnoid or hematogenous metastasis Microscopic tumour cells in cerebrospinal fluid Gross nodular seeding in cerebellum Gross nodular seeding in spinal subarachnoid space Metastasis beyond cerebrospinal axis Chang CH et alan operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 1969 Dec

13 Giles W. Robinson et al., American Brain Tumor Association., % 80% children with average-risk medulloblastoma can be expected to be alive and free of disease five years from diagnosis 60% 65% children with highrisk disease, effective therapy is possible and results in longterm disease control 30% 50% Outcome for infants is poorer, but for those infants with localized disease at the time of diagnosis

14 Jakacki RI et aloutcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: COG Phase I/II study. J Clin Oncol 2012.

15 Jakacki RI et aloutcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: COG Phase I/II study. J Clin Oncol 2012.

16 Cisplatin Side Effects Etoposide Cyclophosphami de Vincristine Bone Marrow Hypotension Cardiotoxicity Neurotoxicity Suppression Extravasation GI toxicity Hyperuricemia Infusion Site reaction Bone Marrow Suppression Bone Marrow Suppression Hemorrhagic Cystitis Pulmonary Toxicities Respiratory Effect Uric Acid Nephropathy Neurotoxicity Wound Healing Ototoxicity Impairment Nephrotoxicity Lexi-Comp,2014

17 Monitoring Parameters Cisplatin Etoposide Cyclophosphami de Vincristine Renal function test (Scr,BUN,Clcr) Electrolytes(Mg,C a,k) CBC(weekly) Liver function test CBC Liver function Test Albumin Vital Signs(BP) Renal Function Test Signs/Symptoms of Hemorrhagic Cystitis CBC BUN Serum Electrolyte Electrolytes(Na) CBC Constipation Signs/Symptoms of Neuropathy Lexi-Comp,2014

18 Case Presentation

19 F.D. is an 8 years old girl K/C of: omedulloblastoma stage IV Maintained on: ochemotherapy Protocol oradiation

20 Fever Cough SOB

21 Ataxia with unsteady gait Brain tumor was resected, patient needs further chemotherapy management

22 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 29 th -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

23 Then the patient initially presented to the Neurosurgery team with unsteady gait On the 15 th 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 16 th September-2013 histopathology reported as medulloblastoma anaplastic

24 The child was diagnosed as medulloblastoma Stage IV On the 10 th November-2013 They received the patient in a good condition, active, walking with no neurological deficits, Vitally and hemodynamically stable

25 On the 20 th -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 7 th - January 2014 She is due for cycle 2 to receive cyclophosphamide and Vincristine

26 Bronchial asthma Maintained on: osalbutamol Inhaler 100mcg/dos 1 PUFB PRN Neurofibromatosis type I

27 The patient underwent craniotomy and resection and after the surgery the patient transferred to PICU and stayed for two days there

28 Giles W. Robinson et al., American Brain Tumor Association.,2012. Medulloblastoma is not an inherited disease because the genetic changes tend to only occur inside the tumor cells

29 Medications Salbutamol 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

30 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

31 HEMATOLOGY WBC 15.9 RBC 3.69 HGB 11 Hct Plt 260 Neut A 13.6 BIOCHEMISTRY 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 High Low

32 s o A P Daily Cough more at night and early morning BP 110/52 Temp 36.7 RR30 PO2 98% WBC 5.1 RBC 3.16 HGB 9.7 Hct Plt 214 Neut A 4.2 Na 140 K3.5 Urea 1 Scr 35 C.Ca2.43 Ph1.14 Mg0.68 An 8 yrs old girl k/c of M.B. and B.A. Medications: Add Flixotide (Fluticasone)125mcg 1Puff 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

33 s o A P Daily Cough more at night and early morning BP 108/60 Temp 36.7 RR30 PO2 98% WBC 2.5 RBC 3.43 HGB 10.4 Hct Plt 307 Neut A 1.1 Na 135 K3.8 Urea 2.6 Scr 41 C.Ca2.36 Ph1.46 Mg0.83 An 8 yrs old girl k/c of M.B. and B.A. Medications: D/C Bactrim 240mg PO BID(Sun,Mond) Tazocin 1.7g IV Q6hr day6 Add Etoposide 27mg(start date 7 th -May) Add Cisplatin 35mg IV(start date 7 th -May) Add Granisetron 0.4mg(start date 7 th May) Add Septrin 5ml(start date 7 th -May)

34 s o A P Increase vomiting cough improved BP 101/52 Temp 36.7 RR30 PO2 98% WBC 17.5 RBC 3.43 HGB 10.4 Hct Plt 307 Neut A Na 133 K 3.5 Urea 3.4 Scr 43 C.Ca2.30 Ph1.40 Mg0.99 An 8 yrs old girl k/c of M.B. and B.A. Medications: Tazocin 1.7g IV Q6hr day8 D/C Etoposide 27mg OD (On 9 th May) D/C Cisplatin 35mg IV(On 7 th May) Granisetron 0.4mg Septrin 5ml Add Dexamethasone 2mg (start date 9 th -May) one dose only(stat) Add GCSF 95mcg SQ OD (start date 8 th May)

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36 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

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