Pediatric cental nervous system tumors

Pediatric Central Nervous System Tumors

Pediatric central nervous system tumor 2

• Brain tumors are the second most common group of malignant tumors in childhood,

• accounting for 20% of all childhood malignancies.• Most childhood brain tumors (60–70%) arise from

glial cells and tend not to metastasize outside the CNS unless there is operative intervention.

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Pediatric central nervous system tumor 36/3/2016


Tumors are further classified by grading the degree of malignancy within a particular tumor type. Criteria that are useful microscopically in grading the degree of malignancy include:• Cellular pleomorphism• Mitotic index• Anaplasia and necrosis• MIB-1 index.

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CLINICAL MANIFESTATIONSGeneral Signs and Symptoms of Intracranial Tumors1. Headache. In young children headache can

present as irritability. 2. Vomiting.3. Disturbances of gait and balance.4. Hemiparesis.5. Cranial nerve abnormalities

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CLINICAL MANIFESTATIONS6. Impaired vision

a. Diplopia (6th nerve palsy): In young children diplopia may

present as frequent blinking or intermittent strabismus

b.Papilledema from increased ICP may present as

intermittent blurred vision

c. Parinaud syndrome (failure of upward gaze and setting-sun

sign, large pupils and decreased constriction to light).

7. Mental disturbances – somnolence, irritability, personality or behavioral change, or change in school performance.

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CLINICAL MANIFESTATIONS

8. Seizures – usually focal.9. Endocrine abnormalities10. Cranial enlargement in infants (characteristic of increased ICP).11. Diencephalic syndrome

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CLINICAL MANIFESTATIONSGeneral Signs and Symptoms of spinal cord tumors• Spinal tumors of children may be found anywhere

along the vertebral column• Most spinal tumors have associated muscle

weakness and the muscle group affected corresponds to the spinal level of the lesions.

• Tumors of the vertebra may also encroach upon the spinal cord, leading to epidural compression of the cord and paraplegia

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CLINICAL MANIFESTATIONS

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Spinal tumors can be divided into three distinct groups:

• Intramedullary - glial in origin and are usually gliomas or ependymomas

• Extramedullary–Intradural - neurofibromas often associated with neurofibromatosis. If they arise in adolescent females, meningiomas are more likely

• Extramedullary–Extradural. often of mesenchymal origin and may be due to direct extension of a neuroblastoma through the intervertebral foramina or due to a lymphoma

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DIAGNOSTIC EVALUATIONComputed TomographyThe computed tomography (CT) scan is an important procedure in the detection of CNS malignanciesCT is more useful than MRI in:• Evaluating bony lesions• Detection of calcification in tumor• Investigating unstable patients because of the

shorter imaging time

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DIAGNOSTIC EVALUATIONMagnetic Resonance Imaging

Magnetic resonance imaging (MRI) provides the following additional advantages:

• No ionizing radiation exposure

• Greater sensitivity in detection of brain tumors especially in the temporal lobe and posterior fossa (these lesions are obscured by bony artifact on CT)

• Ability to directly image in multiple planes (multiplanar), which is of value to neurosurgical planning

• Ability to apply different pulse sequences which is useful in depicting anatomy

• Ability to map motor areas with functional MRI

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DIAGNOSTIC EVALUATIONMagnetic Resonance Angiography

Magnetic Resonance Spectroscopy

Positron Emission Tomography

PET is useful to determine:

• Degree of malignancy of a tumor

• Prognosis of brain tumor patients

• Appropriate biopsy site in patients with multiple lesions, large homogeneous and heterogeneous lesions

• Recurrent tumor from necrosis, scar and edema in patients who have undergone radiation therapy and chemotherapy

• Recurrent tumor from post-surgical change.6/3/2016


DIAGNOSTIC EVALUATIONCerebrospinal Fluid ExaminationThe cerebrospinal fluid (CSF) should have the following studies performed:• Cell count with cytocentrifuge slide examination for

cytology of tumor cells• Glucose and protein content• CSF α-fetoprotein (AFP)• CSF human chorionic gonadotropin (hCG).

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DIAGNOSTIC EVALUATIONBone Marrow Aspiration and Bone Scan• These studies are indicated in medulloblastoma and

high-grade ependymomas with evidence of cytopenias on the blood count

• because a small percentage of these patients have systemic metastases at the time of diagnosis.

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TREATMENTSurgeryThe purpose of neurosurgical intervention1. To provide a tissue biopsy for purposes of histopathology and cytogenetics.2. To attain maximum tumor removal with fewest neurologic sequelae.3. To relieve associated increased ICP due to CSF obstruction.

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TREATMENTThe ideal goal • is a gross-total resection of tumor (likely leaving

microscopic residual) as removal of a margin of normal tissue would cause devastating neurologic sequelae.

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TREATMENTRadiotherapy

• Most patients with high-grade brain tumors require radiotherapy to achieve local control of microscopic or macroscopic residual.

• Radiation therapy for intracranial tumors consists of external beam irradiation using conventional fields or three-dimensional conformal radiotherapy.

• The latter decreases radiation to normal brain tissue by up to 30%.

• Intensity-modulation radiation therapy (IMRT) decreases radiation to normal tissue

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TREATMENT• The wider use of ionizing radiation in pediatric brain

tumors has resulted in improved long term survival. • However, the significant long-term effects on cognition

and growth,• especially in patients requiring craniospinal irradiation

(e.g. PNET) can be devastating.• The total dose of radiotherapy depends on: Tumor type (which also influences volume of treatment) Age of the child Volume of the brain or spinal cord to be treated.

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TREATMENT• Brachytherapy, stereotactic radiosurgery and

fractionated stereotactic radiosurgery are alternatives to conventional radiation therapy presently under continuing study and may prove useful in relapsed patients

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TREATMENTChemotherapy • plays an expanding role in the management of

recurrent disease in many newly diagnosed patients.

• The rationale of instillation of chemotherapy into the CSF compartment is most applicable in cases of meningeal spread or in those tumors in which the risk of spread through the CSF is high.

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ASTROCYTOMAS• approximately 50% of the CNS tumors • with peaks between ages 5–6 and 12–13 years.• The following are the histologic subtypes: Pilocytic astrocytoma (WHO grade I) Diffuse or fibrillary (WHO grade II) Anaplastic astrocytoma is (WHO grade III) Glioblastoma multiforme (WHO grade IV).

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ASTROCYTOMAS

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Pilocystic astrocytoma Diffuse fibrillary astrocytoma


ASTROCYTOMAS

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Anaplastic astrocytoma Glioblastoma multiforme


ASTROCYTOMAS

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Pilocystic astrocytoma Glioblastoma multiforme


ASTROCYTOMASWHO grade II subtype• Pleiomorphic xanthoastrocytomas • Pilomyxoid astrocytomas The majority of cerebellar astrocytomas remain confined to the cerebellum

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Management of AstrocytomasLow-Grade Astrocytomas (WHO Grades I and II) Surgery• Surgical excision is the initial treatment.• Gross total resection is desirable.• Pilocytic astrocytomas are slow-growing and well-

circumscribed with a distinct margin.• These features permit complete resection in 90% of

patients• If removal is complete, no further treatment is

recommended

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Management of AstrocytomasRadiotherapy

• Radiotherapy is used when chemotherapy has failed in unresectable symptomatic tumors, especially in older patients.

• Dosing is 5,000–5,500 cGy, depending on age, to the original tumor bed with a 2 cm margin.

• In deep midline locations, chemotherapy tends to be used to avoid long-term effects of radiation to vital areas, including the pituitary.

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Management of AstrocytomasChemotherapy

• in patients younger than 5 years of age Carboplatin and vincristine

• In patients older than 5 years of age a regimen consisting of eight 6-week cycles of 6- thioguanine, procarbazine, CCNU and vincristine

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Management of Astrocytomas

High-Grade Astrocytomas (WHO Grades III and IV)

Surgery

• Complete surgical removal of these tumors is rarely accomplished because of their infiltrative nature

Radiotherapy

• Postoperative irradiation increases survival in high-grade astrocytomas.

• The treatment field should include the tumor bed and a 2-cm margin of normal surrounding tissue. The dose is 5,000– 6,000 cGy in children over 5 years of age.

• The use of stereotactic increases local tumor doses.

Chemotherapy

• Procarbazine (or prednisone), CCNU and vincristine is the current standard, 6/3/2016


MEDULLOBLASTOMA• Medulloblastoma (posterior fossa PNET) is the most common CNS

tumor in children,

• representing approximately 20% of all childhood brain tumors with

• 80% of the cases presenting before the age of 15 years.

• The tumor presents in the posterior fossa and widespread seeding of the subarachnoid space may occur.

• The frequency of CNS spread outside the primary tumor can be as high as 40% at the time of diagnosis.

• Extraneural spread to bone, bone marrow, lungs, liver, or lymph nodes occurs in approximately 4% of patients.

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MEDULLOBLASTOMA

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Radiological figure of medulloblastoma


MEDULLOBLASTOMA

Staging studies should include • MRI of the spine (preferable preoperatively),• lumbar CSF cytology, • liver function tests and, if clinically symptomatic,• bone scan and/or • bone marrow examination.

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Management of MedulloblastomaSurgery

• Surgical excision is employed as the initial therapy with an objective of gross total resection or near total resection with less than 1.5 cm2 of residual tumor

Radiotherapy

• Radiation therapy plays a critical role in treatment.

• The standard dose of radiotherapy is

• 5,400–5,580 cGy to the area of the primary tumor, with 2,340 cGy given to the neuroaxis.

• Use of intensity modulated radiation therapy (IMRT) to spare the cochlea is important in decreasing therapy-induced hearing loss.

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Management of MedulloblastomaChemotherapy• In patients who have high-risk disease adjuvant

chemotherapy in combination with 36 Gy craniospinal radiation

• improves the disease-free survival for medulloblastoma.

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BRAIN STEM TUMORS• Brain stem gliomas comprise 15–20% of all

childhood CNS tumors. • The median age at presentation is 6–7 years of age. • Fifty percent of the patients present with cranial

nerve and long tract signs.• These are typically WHO grades II–IV gliomas

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BRAIN STEM TUMORS

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Radiological figure of brain stem tumors


Management of Brain Stem tumorsSurgery• Surgical resection is not usually possible because of

the proximity to vital structures, • limited room for expansion and swelling and • possible damage to medullary structures

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Management of Brain Stem tumorsRadiotherapy• Limited field irradiation is standard palliative care in

patients with infiltrative pontine gliomas. • A tumor dose of approximately 5,400 cGy is standard.

The treatment field should include the extent of the defined tumor and a 2-cm margin around the tumor.

Chemotherapy• The use of combination chemotherapy after

radiotherapy has not improved the disease-free survival in brain stem tumors

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EPENDYMOMAS• Fifty percent of all ependymomas occur during

childhood and adolescence • constitute approximately 9% of all primary childhood

CNS tumors. • The tumors occur either infratentorially or

supratentorially. • The fourth ventricle is the most common location. • Ependymomas can also occur in the spinal cord and

account for 25% of spinal cord tumors. • Obstructive hydrocephalus is the most common

presenting condition.6/3/2016


EPENDYMOMAS

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4th ventricle ependymoma


Management of ependymomas

Surgery

• Total removal of these tumors is difficult to accomplish,

Radiotherapy

• The recurrence rate with surgery alone is extremely high

• postoperative radiotherapy results in a significant increase in survival

• Use of 3D-conformalradiation or IMRT is appropriate

• The dose is 5,400–6,000 cGy for intracranial lesions.

Chemotherapy

• No advantage has been demonstrated from the use of adjuvant chemotherapy

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OPTIC GLIOMA• constitute 5% of the primary CNS tumors in childhood

and • the majority is diagnosed by 5 years of age • Involvement of the optic chiasm is usually seen in

older children. • Neurofibromatosis is present in up to 70% of patients• Patients may present with decreased vision, proptosis,

optic atrophy and papilledema.• In young children asymmetric nystagmus may be the

presenting sign of a chiasmatic tumor. Histologically approximately 90% are low-grade astrocytomas.

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OPTIC GLIOMA

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Management of Optic gliomaSurgery

• Biopsy may compromise vision,

• MRI and CT should be used to make a clinical diagnosis

• Surgery should be reserved for tumor extension into the optic canal or increasing visual compromise.

Radiotherapy

• May have a beneficial role in preserving vision.

• Radiation may be indicated in patients with progressive disease instead of surgery, especially for chiasmatic–hypothalamic lesions.

• A local field to the tumor of 4,500–5,000 cGy over 5–6 weeks is usually recommended

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Management of Optic gliomaChemotherapyChemotherapy has been used to treat progressive disease. Regimens used include:• Actinomycin D and vincristine. • Carboplatin • Carboplatin and vincristine

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CRANIOPHARYNGIOMAS• Craniopharyngiomas may involve the pituitary gland.

• They account for 6–9% of all CNS tumors in children.

• The peak incidence is 5–10 years of age.

• Patients present with symptoms of increased ICP, visual loss and endocrine deficiencies.

• They typically require replacement therapy with cortisone, thyroxine, growth hormone and/or sex hormones.

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CRANIOPHARYNGIOMAS

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Management of Craniopharyngiomas

Surgery• Craniopharyngiomas should be completely

removed if possible without producing untoward neurologic sequelae.• Complete excision is possible in 60–90% of cases• Complete tumor removal is most easily

accomplished in cystic tumors and is most difficult in solid or mixed tumors larger than 3 cm in size.

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Management of Craniopharyngiomas

Radiotherapy• In tumors in which conservative surgery is performed,

the addition of radiotherapy reduces the local recurrence rate and improves long-term survival. For children older than 5 years, 5,000–5,500 cGy are given.

• In children less than 5 years of age the dose may be reduced to 4,000–4,500 cGy.

• For patients with complete resections, radiation may be reserved for those who relapse.

Chemotherapy• At present there is no established role for systemic

chemotherapy in craniopharyngioma.6/3/2016


INTRACRANIAL GERM CELL TUMORS

• Primary intracranial germ cell tumors (GCT) comprise 1–3% of primary pediatric brain tumors.

• The peak age is between 10 and 21 years of age.• Multiple tumor types can be seen: germinomas (55%), teratomas and mixed germ cell tumors (33%) and the remaining 10% are malignant endodermal sinus

tumors, embryonal cell carcinomas, choriocarcinomas and teratocarcinomas.

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INTRACRANIAL GERM CELL TUMORS

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Management of Germ cell tumorsSurgery• Surgical biopsy is indicated in all germ cell tumors to make an

appropriate • For patients with benign tumors such as teratomas or

dermoids, surgery can be curative.Radiotherapy• Conventional radiotherapy for a CNS germinoma includes

doses to the primary tumor of 5,000 cGy with 3,000 cGy craniospinal therapy.

• Nongerminoma germ cell tumors (NGGCT) respond poorly to radiation therapy but the use of chemotherapy with radiation appears to improve survival

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Management of Germ cell tumorsChemotherapy

In both germinomas and nongerminoma germ cell tumors, • cycles of cisplatin 20 mg/m2/day IV days 1–5 with

etoposide 100 mg/m2/day IV days 1–5 alone or alternating with cyclophosphamide 1 g/m2/day for 2 days with vincristine 1.5 mg/m2/day weekly for 3 days

For high-risk disease (nongerminomatous disease, HCG .50 mIu/ml or elevated AFP)• doses of cisplatin and cyclophosphamide have been

doubled or ifosfamide has been added to the cisplatin/etoposide above at 1.5 g/m2/day for days 1–5.

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MALIGNANT BRAIN TUMORS IN INFANTS AND CHILDREN LESS

THAN 3 YEARS OF AGE• Infants and very young children with brain tumors

have a worse prognosis than older children. • They are also at higher risk for neurotoxicity including mental retardation, Growth failure and leukoencephalopathy. • Due to these factors there is a reluctance to treat

infants and young children with radiation therapy.

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MALIGNANT BRAIN TUMORS IN INFANTS AND CHILDREN LESS

THAN 3 YEARS OF AGE• Recent studies have been designed to use

chemotherapy and to either withhold radiation therapy or postpone its use to a time when the patient is older.

• Postoperative chemotherapy with cyclophosphamide, vincristine, chemotherapy is administered for 48–96 weeks, depending on age at diagnosis, to delay radiation until as close to age 3 as possible or beyond.

• The use of second-look surgery is also being evaluated in current trials.

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ReferencePhilip Lanzkowsky. 2011. The manual of pediatric haemotology and oncology. 5th edition.

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THANK YOU

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Health & Medicine

Pediatric cental nervous system tumors