Brain tumors & Stem Cell Transplantation
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Historically, brain tumors have been treated with neurosurgical resection and radiation therapy. Demonstration of the efficacy of chemotherapy has lagged behind that for most other types of tumors, but currently chemotherapy is being employed more frequently. Recognition of the chemo-sensitivity of many types of brain tumors, in conjunction with the still relatively guarded prognoses of many of these patients, has also logically led to exploration of the use of hematopoietic cell support as a means of increasing dose intensity.
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Brain tumors & Stem Cell Transplantation
- 1. Pediatric Brain tumorPediatric Brain tumor && Stem Cell TransplantationStem Cell Transplantation A. Hedayati-AslA. Hedayati-Asl Mahak Cancer Children’s Hospital Stem Cell Transplantation Department
- 2. Most common childhoodMost common childhood malignanciesmalignancies 0 5 10 15 20 25 30 Leukem ia brain tum or lym phom a neuroblastom a soft tissue sarcom a W ilm s tum our bone tum ors others
- 4. • Second malignancy in childhoodSecond malignancy in childhood • Mortality among this group approachesMortality among this group approaches 45%45%
- 5. EpidemiologyEpidemiology • 2,200 primary brain tumor /year2,200 primary brain tumor /year • 28cases/ million of children28cases/ million of children • High incidence in infants and youngHigh incidence in infants and young children up to 7 year of age.children up to 7 year of age.
- 6. EtiologyEtiology • Ionizing radiation (tina capitis , ALL )Ionizing radiation (tina capitis , ALL ) • Other cancer (retioblastoma , rabdoidOther cancer (retioblastoma , rabdoid tumor ,endocrin tumor)tumor ,endocrin tumor) • Immunosuppression (wiscott-AldrichImmunosuppression (wiscott-Aldrich syndrome , ataxia-telangectasia ,organsyndrome , ataxia-telangectasia ,organ transplantation)transplantation) • Familial (Li-fraumeni)Familial (Li-fraumeni) • Enviromental exposure (effect ofEnviromental exposure (effect of cellular plone&mobile, SV40 virus (Mcellular plone&mobile, SV40 virus (M B,epandymoma)B,epandymoma)
- 7. CytogeneticCytogenetic • Delation of 17Delation of 17 • Tisomy 7Tisomy 7 • Monosomy 22Monosomy 22 • Delation 22q11mutation p53Delation 22q11mutation p53
- 10. Normal Anatomy of Brain (MRI) • Supratentorial compartment:Supratentorial compartment: – Cerebral hemispheresCerebral hemispheres – Basal gangliaBasal ganglia – Thalamic nucleiThalamic nuclei – Lateral ventriclesLateral ventricles – HypothalamusHypothalamus – Corpus callosumCorpus callosum • Infratentorial compartment:Infratentorial compartment: – CerebellumCerebellum – Brain stem (MB/P/MO)Brain stem (MB/P/MO) – 44thth ventricleventricle Sagittal Axial
- 11. Location of tumorLocation of tumor • Inferatentorial 43.2% (1-10 years )Inferatentorial 43.2% (1-10 years ) • Meduloblastoma ,astrocytoma ,epandymoma, brain stem gliomaMeduloblastoma ,astrocytoma ,epandymoma, brain stem glioma • Supratentoril 40.9% (1Supratentoril 40.9% (1stst year of lifeyear of life &>10 years )&>10 years ) • Glioma (high ,low grade )epandymoma ,craniopharangioma chiasmatic ,germcellGlioma (high ,low grade )epandymoma ,craniopharangioma chiasmatic ,germcell tumortumor • Spinal cord 4.9%Spinal cord 4.9% • Multiple sites 11%Multiple sites 11%
- 12. Pediatric brain tumorsPediatric brain tumors • AstrocytomaAstrocytoma • MedulloblastomaMedulloblastoma • EpendymomaEpendymoma • GliomaGlioma
- 13. SymptomSymptom • Headache.Headache. • SeizureSeizure • Memory Loss.Memory Loss. • Motor weakness.Motor weakness. • Visual symptomsVisual symptoms • Language deficitLanguage deficit • Cognitive changesCognitive changes • Personality changesPersonality changes • Change inChange in consciousnessconsciousness • Nausea and vomitingNausea and vomiting • Sensory deficitSensory deficit • PapilledemaPapilledema
- 14. Pediatric Brain Tumors Posterior fossa neoplasm – MedulloblastomaPosterior fossa neoplasm – Medulloblastoma
- 15. Medulloblastoma
- 16. MedulloblastomaMedulloblastoma Most common “malignant” brain tumor inMost common “malignant” brain tumor in childrenchildren StagingStaging M0 – no metsM0 – no mets M1 – positive cytologyM1 – positive cytology M2 – intracranial metsM2 – intracranial mets M3 – spinal cord metsM3 – spinal cord mets M4 – extraneural diseaseM4 – extraneural disease
- 17. MedulloblastomaMedulloblastoma RadiographsRadiographs •• well delineated masswell delineated mass •• arises from vermis 75%arises from vermis 75% •• fills 4th ventriclefills 4th ventricle •• calcification 15%calcification 15% •• hydrocephalus 95%hydrocephalus 95% •• enhancesenhances •• subarrachnoid seedingsubarrachnoid seeding
- 18. IntrinsicIntrinsic pontine gliomapontine glioma Pediatric Brain Tumors
- 19. Brain Stem GliomaBrain Stem Glioma
- 21. Pediatric Brain TumorsPediatric Brain Tumors Supratentorial tumors – Astrocytoma & ependymoma Pinealoblastoma & craniopharyngiomaPinealoblastoma & craniopharyngioma
- 25. Common Brain TumorsCommon Brain Tumors Location Percentage Infratentorial 45-60 Supratentorial Hemispheric Midline – Suprasellular / Pineal region 25-40 15-20
- 26. Distribution of common brain tumors in children –Distribution of common brain tumors in children – location and histologic appearancelocation and histologic appearance Infra-tentorial % of all brain tumors PNET (Medulloblastoma) 20-25 Low grade astrocytoma cerebellar 12-18 Ependynoma 4-8 Malignant glioma, brain stem 3-6 Other 2-5 Total 45-60 INTP - PPO, PHO, IAP. P2 – 17/27
- 27. Supratentorial % of all brain tumors Low grade astrocytoma 8-20 Malignant glioma 6-12 Ependymoma 2-5 Mixed glioma 1-5 Ganglioglioma 1-5 Oligodendroglioma 1-2 Chorioid plexus tumor 1-2 PNET 1-2 Meningioma 0.5-2 Other 1-3 Total 25-40 Distribution of common brain tumors in children –Distribution of common brain tumors in children – location and histologic appearancelocation and histologic appearance INTP - PPO, PHO, IAP. P2 – 18/27
- 28. Staging Work upStaging Work up • Dissemination extraneurally rare – stagingDissemination extraneurally rare – staging work up seldom indicatedwork up seldom indicated • Spinal MRI/CSF cytology – mandatorySpinal MRI/CSF cytology – mandatory Medulloblastoma,Medulloblastoma, • PF ependymoma, Germ cell tumorPF ependymoma, Germ cell tumor • Blood / CSF -Blood / CSF - ααFP,FP, ββHCG – Germ cellHCG – Germ cell tumorstumors
- 30. TreatmentTreatment • SurgerySurgery • RadiothrapyRadiothrapy • ChemotherapyChemotherapy • HSCTHSCT
- 34. Pediatric brain tumors-prognosisPediatric brain tumors-prognosis • Low: 5-20% survival in brain stem tumorsLow: 5-20% survival in brain stem tumors • High: 60-80% survival in medulloblastomaHigh: 60-80% survival in medulloblastoma
- 35. Problem Associated tumors Peri / intraoperative Management Postop management Odema Large tumors small tumors in critical areas Corticosteroids Dexona 0.1mg/kg Q6h Corticosteroids tapered Obstructive hydrocephalus Intra and periventricular tumors External ventricular drain placement or VP shunt Closure or permanent Seizures Tumors of cerebral hemispheres Anticonvulsant phenytoin Stopped in follow-up Hypothalamic Pituitary hormonal insufficiency Tumors close to hypothalamus Endocrine Evaluation, Steroids fluid and electrolyte balance Hormone replacement Perioperative ManagementPerioperative Management
- 36. RadiotherapyRadiotherapy • High energy machinesHigh energy machines • Volume – Craniospinal irradiation, localisedVolume – Craniospinal irradiation, localised irradiationirradiation • Dose – 50-60 Gy / 24-36 Gy, 180-200 Gy / #Dose – 50-60 Gy / 24-36 Gy, 180-200 Gy / # • STRS/STRT – Interstitial brachytherapy /STRS/STRT – Interstitial brachytherapy / conformal and intensity modulated treatmentconformal and intensity modulated treatment • Delay/defer irradiation for children younger thanDelay/defer irradiation for children younger than 3 years3 years TreatmentTreatment General principlesGeneral principles
- 37. Useful and standard Medulloblastoma, malignant astrocytomas, optic pathway / hypothalamic gliomas, malignant tumors in children less than 3 years of age. Upfront CT / neo-adjuvant CT, HD CT - BMT Useful drugs: CCNU/VCR/Prednisalone, Procarbazine, Carboplatinum, Vincristine, Temozolamide TreatmentTreatment General principlesGeneral principles ChemotherapyChemotherapy
- 38. Infratentorial TumorsInfratentorial Tumors • High riskHigh risk • MM11 • >1.5 cms residual tumor>1.5 cms residual tumor • <3 years<3 years • RT + CTRT + CT • Standard riskStandard risk • RTRT • ?CT?CT Medulloblastoma Sx Adjuvant Treatment Cerebellar Astrocytoma Ependymomas Brain stem glioma Sx alone ?RT (adjuvant) Sx Adjuvant RT RT alone
- 39. MedulloblastomaMedulloblastoma • ‘• ‘Standard risk’ stageStandard risk’ stage <1.5<1.522 cm residual,cm residual, >3 yrs of age,>3 yrs of age, no spreadno spread •• TreatmentTreatment surgical resectionsurgical resection craniospinal radiationcraniospinal radiation ((2340 cGy to CSA with boost to 53402340 cGy to CSA with boost to 5340)) chemotherapychemotherapy
- 42. EpendymomaEpendymoma •• Peak incidence between birth and 4 yrsPeak incidence between birth and 4 yrs •• male:female :: 1.4:1male:female :: 1.4:1 •• Majority are histologically benignMajority are histologically benign •• Locally invasive and difficult to resectLocally invasive and difficult to resect entirelyentirely •• Controversies exist regarding role ofControversies exist regarding role of adjunctive radiotherapy and/oradjunctive radiotherapy and/or chemotherapychemotherapy
- 43. Supratentorial TumorsSupratentorial Tumors Hemispheric tumors: Gliomas: Low grade: Sx alone High grade: Sx RT + CT (adjuvant) Ependymomas: Sx RT (adjuvant) Optic pathway/ Sx ↑ CT ↓ RT Hypothalamic Gliomas Craniopharyngioma Sx RT Pineal region tumors Individualized treatment Midline Supratentorial Tumors
- 44. Hemispheric AstrocytomaHemispheric Astrocytoma •• Outcome determined by:Outcome determined by: tumor histology, extent of resection, locationtumor histology, extent of resection, location •• 5 yr survival with subtotally resected low5 yr survival with subtotally resected low grade gliomas is 90%grade gliomas is 90% low grade tumors may remain quiescentlow grade tumors may remain quiescent •• ControversiesControversies adjuvant therapy (chemotherapy beforeadjuvant therapy (chemotherapy before radiotherapy)radiotherapy) treatment of epilepsytreatment of epilepsy radiotherapy modalityradiotherapy modality
- 45. PNETPNET •• < 5% of supratentorial< 5% of supratentorial tumors in childrentumors in children •• Radical surgical resectionRadical surgical resection –– gross total improvedgross total improved survivalsurvival •• CSF disseminationCSF dissemination commoncommon •• Adjuvant treatmentAdjuvant treatment –– craniospinal irradiationcraniospinal irradiation –– chemotherapychemotherapy •• survivalsurvival –– <30% at 5 yrs<30% at 5 yrs
- 46. Treatment…ChemotherapyTreatment…Chemotherapy Most commonly used agentsMost commonly used agents • CyclophosphamideCyclophosphamide • VCRVCR • CarboplatinCarboplatin • CisplatinCisplatin • EtoposideEtoposide Newer agentsNewer agents • TemozolomideTemozolomide • Molecularly targeted therapy (erlotinib, RAD001,etc.)Molecularly targeted therapy (erlotinib, RAD001,etc.) • Anti-angiogenic therapy (bevacizumab,Anti-angiogenic therapy (bevacizumab, • ImmunotherapyImmunotherapy
- 47. BT & HSCTBT & HSCT • Historically, brain tumors have beenHistorically, brain tumors have been treated with neurosurgical resection andtreated with neurosurgical resection and radiation therapy. Demonstration of theradiation therapy. Demonstration of the efficacy of chemotherapy has laggedefficacy of chemotherapy has lagged behind that for most other types of tumors,behind that for most other types of tumors, but currently chemotherapy is beingbut currently chemotherapy is being employed more frequently.employed more frequently.
- 48. BT & HSCTBT & HSCT Recognition of the chemo-sensitivity ofRecognition of the chemo-sensitivity of many types of brain tumors, in conjunctionmany types of brain tumors, in conjunction with the still relatively guarded prognoseswith the still relatively guarded prognoses of many of these patients, has alsoof many of these patients, has also logically led to exploration of the use oflogically led to exploration of the use of hematopoietic cell support as a means ofhematopoietic cell support as a means of increasing dose intensity.increasing dose intensity.