BRAIN TUMORSBRAIN TUMORS

Elshami Elamin, MDElshami Elamin, MD

IntroductionIntroduction

• Intracranial neoplasms arise from:• Brain cells• Meninges• Pituitary gland• Skull• Residual embyronic tissue

• Mets from lung, breast etc…

• Most common solid tumors in children

• 2nd cause of cancer death in chlidren

Symptoms, SignsSymptoms, Signs

• Headache• N/V• Papilledema• Lateralizing signs;

• Hemiparesis• Aphasia• Visual-field deficits

• Seizures• Altered Mental Status

DiagnosisDiagnosis

• MRI; (gold standard)• To define number of met nodules• Leptomeningeal dz• High G or malignant tumors are enhancing masses in

the white matter surrounded by edema• Low G gliomas are nonenhancing

• Magnetic Resonance Spectroscopy:• Differentiate between low and high G gliomas

• CT scan• PET scan (75% sensitivity, 83% specificity)

PATHOLOGYPATHOLOGY• Gliomas arise from:

• Astrocytes• Oligodendrocytes

• Ependymomas:• Low G histologically• High recurrence rate

• Medulloblastomas:• High G

• Primitive Neuroectodermal Tumors (PNETs):• High G• Pineoblastomas, neuroblastomas

• Extra-axial• Meningiomas

GRADING of GRADING of GLIOMASGLIOMAS

• Based on endothelial proliferation, cellular pleomorphism, mitosis, necrosis.– High Grade:

– GBM– Anaplastic astrocytoma– Anaplastic oligodendroglioma– Gliosarcoma

– Low Grade:– Astrocytoma– Oligodendrogioma– Mixed oligoastrocytoma

STAGINGSTAGING

• Not applicable in primary Brain tumors:• Locally invasive• Do not spread to LN or distant organs

• Enhanced complete spinal MRI and CSF eval:

• Medulloblastoma• Ependymoma• PENT

PROGNOSISPROGNOSIS

• With conventional treatment:– Anaplastic astrocytoma: MS is 3 Yrs– GBM: MS is 1 Yr – Low G gliomas: MS is 5-10 Yrs

– Pts >40Yrs: MS is < 5 Yrs

– Brain mets: MS 4-6 m– Single met treated with surgery/G-K: MS > 40Wks

TREATMENT TREATMENT

• Supportive:• Anticonvulsant

– Seizure at presentation– Prophylaxis only during peri-operative period

• Steroids;– Most pts stop steroids when complete RT– If steroids >6 wks:

• PCP prophylaxis

• Definitive:

SurgerySurgery•Goals of surgery:

– histologic diagnosis– reducing tumor burden and

associated mass effect– maintaining or reestablishing

pathways for CSF flow– achieving potential “cure” by gross

total removal

RTRT

• Brachytherapy

• Radiosurgery• Gamma Knife

• iodine-131–labeled antitenascin monoclonal antibody

Adult Low-Grade Infiltrative Supratentorial

Astrocytoma/Oligodendroglioma

ManagementManagement

• MRI compatible with primary brain tumor:• Maximal safe resection

– Feasible: • post-op MRI• >45Y; Observe or Post-op RT• <45Y; observe

– Not feasible:• Stereotactic or open biopsy• Post-op observe, RT, or Chem

• F/U: MRI q3-6m x 5Yrs• Recurrence:

• Surgery, RT, Chemo

low-grade gliomaslow-grade gliomas

• complete surgical resection of hemispheric astrocytomas

• Incomplete resection:• Astrocytoma: Post-op RT• oligodendrogliomas or mixed gliomas: may

benefit from chemotherapy

• Recurrent unresectable dz• RT

Adult Intracranial Ependymoma or Anaplastic Ependymoma

• MRI/CT compatible with primary brain tumor:– Maximal resection: (Stereotactic or open biopsy if not feasible)

• Postop staging and Adj therapy:– Negative post-op MRI brain,spine +/- CSF

• Limited-field RT

– Positive post-op MRI brain, spine +/- CSF

• Craniospinal RT

• F/U: • MRI/CT q3-6mx2Y, then q6-12m

• Recurrence:• Resection, RT or Chemotherapy or supportive care

Anaplastic Astrocytoma/Anaplastic

Oligodendroglioma/ Glioblastoma Multiforme

• MRI suggestive of high-G glioma:– Multidisciplinary planning

• Maximal Resection

– Feasible• Max excision +/- BCNU wafer

– Not feasible (Stereotactic or open biopsy)

Adjuvant TherapyAdjuvant Therapy

• Anaplastic astrocytoma or Anaplastic oligodendroglioma:– Adj RT +/- Chemo

• Glioblastoma Multiforme (GBM):– s/p BCNU wafer:

• Adj RT ± chemotherapy

– No BCNU wafer:• Adj RT ± concurrent and adj temozolomide

High G GliomasHigh G Gliomas

• Post-op RT:• Involved-field 60Gy prolong Survival

– 50% of anaplastic astrocytomas respond– 25% of GBM respond– Complete response is rare

High G GliomasHigh G Gliomas

• Adj chemo + RT prolong survival:• BiCNU• PCV• Temozolomide

– GBM: Adj Temodar + RT standard of care

Chemotherapeutic regimens for Chemotherapeutic regimens for gliomasgliomas

• Single-agent BiCNU• BiCNU 200 mg/m2 IV q8wk

• (maximum cumulative dose,1,500 mg/m2)

• Single-agent temozolomide• Temozolomide 150-200 mg/m2 PO on days 1-5

• Repeat cycle every 28 days.

• Standard PCV• Procarbazine 60 mg/m2/d PO on days 8-21• Lomustine (CeeNu) 110 mg/m2 PO on day 1• Vincristine 1.4 mg/m2 IV on days 8 and 29

• (maximum dose, 2 mg)• Repeat cycle every 6-8 weeks, optimally for 6 cycles.

• Intensified PCVa• Procarbazine 75 mg/m2/d PO on days 8-21• Lomustine (CeeNu) 130 mg/m2 PO on day 1• Vincristine 1.4 mg/m2 IV on days 8 and 29

• (no dose limit)• Repeat cycle every 6 weeks.

High G Gliomas High G Gliomas F/UF/U

– MRI 2-6 wk after RT– Then every 2-3 m x 2-3 y

High G Gliomas High G Gliomas F/UF/U

• MRI 2-6 wk after RT:– Then every 2-3 m x 2-3 y

• Recurrence:– Diffuse, Multiple:

• Best supportive care if poor PS• chemo• Surgery for symptomatic, large lesions

– Local:• Resectable: surgery +/- BCNU polymer, RT, chemo• Unresectable: RT, chemo

Limited (1-3) metsLimited (1-3) mets

• SCLC or Disseminated systemic dz:• WBRT

• Limited systemic disease:• Surgery or Stereotactic radiosurgery

– consider WBRT

• If unresectable; WBRT and/or radiosurgery

>3 Metastatic Lesions

• WBRT ± stereotactic radiosurgeryc

Leptomeningeal disease

• DIAGNOSIS:– Positive CSF cytology OR – Positive MRI with supportive clinical

OR– CSF findings in a pt known to have

cancer OR– Signs and symptoms with

supportive CSF in a pt known to have amalignancy

Leptomeningeal disease TreatmentTreatment

• Poor risk:– Palliative RT, supportive care

• Good risk:– IT chemo– Palliative RT to symptomatic/bulky sites– Systemic chemo

Leptomeningeal disease

• CSF flow scan:– Normal flow:

• Induction IT chemo x 4-6wks– Recheck CSF

– Abnormal flow:• RT to site of obstruction +/- IT chemo

– Repeat CSF flow scan

Leptomeningeal disease Post-induction Therapy

• Negative CSF:• Maintenance IT chemo• Monthly CSF

• Positive CSF:– Clinical leptomeningeal dz;

• Supportive care, RT, chemo

– No Clinical leptomeningeal dz;• Continue IT chemo

– CSF continues to be +ve: • Supportive care

NonimmunosuppressedPrimary CNS Lymphoma

• CT/MRI suggestive of lymphoma:– Hold steroids, if possible– CSF, Biopsy– Slit lamp eye exam– HIV test– Spinal MRI

NonimmunosuppressedPrimary CNS Lymphoma

TREATMENT• Good PS, CrCl > 50:

– High-dose MTX-based +/- RT– LP or spinal MRI +ve,

• consider IT chemo

• Poor PS, CrCl < 50:– Whole-brain RT (45 Gy) or Chemotherapy– Eye exam +ve

• RT to orbits– LP or spinal MRI +ve,

• consider IT chemo + focal spinal RT

Metastatic Spine Tumors• Asymptomatic:

– Surgery or RT or Chemo or Observation

• Symptomatic (Pain, Neuro): – Steroids if abnormal neuro exam– Spinal MRI:

• Spinal Cord Compression:– Surgery if:

• Spinal instability• Radioresistant• Rapid neuro deterioration• Unknown primary• Previous RT

– RT– Chemo

• No Spinal Cord Compression:– RT, Vertebroplasty, Surgery if spinal instability