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Chapter 31
Central Nervous System
Overview
 Central nervous system tumors include brain and spinal cord tumors.
 The tumors can be primary or secondary (metastatic) and benign or malignant.
 Some are regarded as benign because of slow growth rates and their response to therapy.
 Tumors of the CNS, even if benign histologically, are considered malignant in part
because of their inaccessible location.
 Cerebral metastases occur in approximately 30% of patients with cancer and are the most
common brain lesions.
 The most common primary adult brain tumor, glioblastoma multiforme (GBM), is a high
grade astrocytoma, and is one of the most lethal
 Although CNS tumors rarely metastasize, they are often locally invasive and create
significant problems due to inaccessible locations.
 Structures that become involved with these neoplasms are not capable of regeneration (repair
or regrowth).
Extra: from A Cancer Source Book for Nurses
 Glioma is a general term for tumors that arise from glial cells, which provides supporting
structure for the neurons. The types of glial cells are:
 Astrocytes (astrocytomas) are the most common in adults
 Oligodendrocytes (oligodendrogliomas)
 Ependymocyte (ependymomas)
 Meningioma: a slow growing tumor that arises from the dural covering of the brain, benign
by histology
 Medulloblastoma: arises in the cerebellum ad frequently disseminates through the
cerebrospinal fluid.
Epidemiology
 Brain tumors account for 1.5% of all malignancies, 20% of all cancer deaths.
 About 80% of CNS tumors involve the brain, whereas 20% involve the spinal cord.
 Brain tumors are the second leading cause of death in children (behind leukemia).
 Most brain tumors occur in two age peaks: childhood (3 to 12) and later in life (50-80).
 The incidence is higher in men
 Me nare more commonly diagnosed with astrocytoma
 Women with meningioma- benign
 Cerebral metastases are the most common brain lesions.
 The most common primary site of disease responsible for producing brain metastases is
the lung.
 Primary brain tumors are relatively uncommon
 In adults, gliomas comprise 50% of all primary brain tumors
 The most common location of these tumors is the cerebrum, which is the largest part of
the brain and consists of two hemispheres.
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The functions of the cerebrum include interpretation of sensory impulses and
voluntary muscular activities; it is the center for memory, learning, reasoning,
judgment, intelligence, and emotions.
In children, approximately 45% of tumors are gliomas (astrocytomas being most common)
with most involving the cerebellum and to a lesser degree the brainstem
 The cerebellum is the part of the brain that plays a role in the coordination of voluntary
muscular movements
Factors such as the patient’s age, Karnofsky Performance Status, and neurologic signs and
symptoms at the time of diagnosis are important.
Etiology
 Little is known concerning the cause, development and growth mechanisms of CNS tumors
 Fewer than 1% of patients are known to have inherited disorders
 Several growth factors have been associated with tumor growth and progression: protein
kinase C and the p53 gene on chromosome-17
 Environmental factors also play a role in the cause of CNS tumors
 Chemical exposure: such as pesticides, herbicides, and fertilizers and workers in the
petrochemical industries and health care professions
 The only documented link associates gliomas with vinyl chloride and rubber
manufacturing industries
 Studies revealing potential links to N-nitroso compounds, power magnetic fields, dental
amalgams, x-rays, and passive smoking have generated considerable interest.
 Viral infections have recently been associated with the development of CNS neoplasia
 Immunocompromised patients who have CNS lymphomas also have a high incidence of
the Epstein-Barr virus
 Trauma seems to influence the incidence of CNS neoplasia.
Prognostic indicators:
 The three most important factors are age, the performance status and tumor type.
 Unfortunately, one of the most common adult brain tumors, glioblastoma multiforme (GBM),
is one the most lethal and despite years of clinical research, progress has been slow and
disappointing
 The prognosis tends to be better in younger patients, with one exception
 Children younger than 4 present a particular problem with respect to a treatment regimen.
 Therapy must be modified because of the developing brain, which is more sensitive to
radiation; therefore, radiation treatment in children younger than 4 years must be
avoided if possible
 Doses may be modified to prevent later learning difficulties
 Mean IQ scores after treatment indicated slightly decreased scores as whole brain
dose radiation increased
 The location of the tumor is of great importance, serving as a natural prognostic indicator for
survival time and neurologic defects
 The Karnofsky Performance Scale (KPS) measures the neurologic and functional status,
allowing for measurements of the quantity and quality of nuerologic defects (lower score =
worse prognosis)
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Tumor grade rather than size is the primary factor involved with prognosis
 The tumors are normally grouped into benign or low-grade and malignant or high-grade
categories
 Typically the higher the grade, the shorter the survival time
The presents or absence of necrosis in a tumor has a prognostic significance
 Necrosis is the death of a cell of cell group resulting from disease of injury
Almost all patients experience a recurrence (with high grade tumors) postoperatively, and
80% of all recurrences within a 2 cm margin
Friable: easily broken, pulverized, high grade, worse.
Anatomy and Lymphatics
 The brain is composed of two cerebral hemispheres and two cerebellar hemispheres, the
cranial bones, meninges, and cerebrospinal fluid (CSF) provide an outer covering of
protection for the brain
 The ventricles are cavities that form a communication network with each other, the center
canal of the spinal cord, and the subarachnoid space
 The cerebral hemispheres and the sella, pineal, and upper brainstem regions are located in the
supratentorial region
 The infratentorial region which leads to the upper spinal cord houses the brainstem, pons,
medulla and cerebellum
 The CNS is composed of 40% grey matter and 60% white mater
 The grey matter contains the supportive nerve cells and related processes
 It forms the cortex, or outer part of the cerebrum and surrounds the white matter
 The white matter (corpus callosum) is composed of bundles of nerve fibers, axons
carrying impulses away from the cell body, and dendrites carrying impulses toward the
cell body
 The spinal cord is also composed of grey (inner) and white (outer) matter
 The blood supply for the brain comes from the internal carotid arteries and vertebral arteries
via the circle of Willis
 Vertebral arteries are protected by the transverse foramina of the cervical vertebrae
 The blood that enters the brain contains oxygen, nutrients, and energy rich glucose, which
is the primary source of energy for the brain cells
 If the blood supply to the brain is interrupted, dizziness, convulsions, or mental confusion
may result.
 The cord continues down to the level of the first and second lumbar vertebrae where it
becomes a bundle of nerves (cuada equine)
 From the spinal cord come 31 pairs of nerves; come out of the intervertebral foramina
formed by the superior and inferior vertebral notches.
 No lymphatic channels exist in the brain substance
 The blood brain barrier (BBB) which hinders the penetration of some substances into the
brain and CSF, exists between the vascular system and brain
 Substances that can pass through the BBB must be lipid soluble
 Lipid soluble substances include alcohol, nicotine, and heroin
 Water-soluble substances require a carrier molecule to cross the barrier by active
transport
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 Water-soluble substances are glucose, some amino acids, and sodium
The CSF is a clear, colorless fluid resembling water produced in the choroid plexus.
 The entire CNS contains 3 to 5 oz, which is composed of proteins, glucose, salts and urea
(a compound formed in the liver and excreted by the kidney)
 The CSF performs several functional roles
 Buoyancy to protect the brain
 Link in the control of the chemical environment of the CNS
 A mean of exchanging nutrients and waste products with the CNS
 A channel for intracerebral transport
 If the flow of CSF is interrupted, it may contribute to increased intracranial pressure
(ICP)
Natural History of Disease and Patterns of Spread
 Most gliomas tend to spread invasively because they do not form a natural capsule that
inhibits growth
 They do not metastasize through a lymphatic drainage system and rarely metastasize outside
the CNS
 Local invasion and CSF seeding provide the major patterns of spread for CNS tumors
Clinical Presentation
 The location of the tumor correlates with the presenting symptoms
 The initial symptom may be a headache, which is usually worse in the morning. This is due
to the differences in the CSF drainage from the recumbent to upright positions.
 Seizures and difficulties with balance, gait, and ambulation are also common presenting signs
 Focal signs are usually unilateral
 Other neurologic symptoms can include disphasia (difficulty speaking), hemiplegia (paralysis
of one side), and paresis (partial loss of movement).
 Ocular symptoms may result in decreased vision, oculomotor defects, proptosis (drooping of
the eye), and ophthalmic defects
 Other presenting signs may be expressive aphasia, sensory aphasia, mental and personality
changes, short-term memory less, hallucinations and changes in intellectual functions
 Increased ICP can result from the obstruction of CSF flow
 The symptoms can result from direct invasion of the tissue by the tumor, destruction of brain
tissue and bone, and increased pressure.
 Patients with spinal cord tumors have pain, weakness, loss of sensation and bowel and
bladder control problems
 Weakness usually occurs in the distal part of the extremity
Detection and Diagnosis
 Because some CNS tumors are genetic, associated with exposure to chemicals, or related to
infection, previous medical, family, and social histories are extremely important
 Information gathered from people other than the patient may also be beneficial in making a
diagnosis
 Mental changes, personality changes, and changes in behavior are not often noticed by
the patient but are noticed by other individuals
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Symptoms of long duration may indicate a slow growing tumor
A test for intellectual function includes orientation to person, place, and time and the
quickness of the response to these questions
Coordination skills (including walking, balance, and gait) sensations, reflexes, and motor
skills are also examined
Ophthalmoscopy is a test designed to check for papilledema (edema of the optic disc) which
results from increased ICP
Benign tumors generally cause symptoms produced by pressure, whereas malignant tumors
can cause pressure and destruction of CNS tissue
The involvement of specific regions of the brain generally produces symptoms specific to the
areas controlled by those regions
Location
Frontal
Parietal
Temporal
Occipital
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Symptoms
Personality changes, impetuous behavior, excessive
jocularity, defective memory, gait disorders, speech
disorders, increased ICP
Symptoms of increased ICP, loss of vision, spatial
disorientation, seizures, weakness, loss of memory
Loss of smell, disturbance in hearing, tinnitus, etc; speech
disturbance, increased ICP
Loss of vision, increased ICP
The CT scan can distinguish the CSF, blood, edema, and tumor form normal brain tissue, use
iodine based contrast to enhance the study
 Provides information regarding tumor extension, grade, and growth patterns
MRI is useful for showing the normal anatomic structure and changes in the parenchyma
 MRI provides a method of evaluating tumor response or recurrence after RT or surgery
 Tumors smaller than 1 cm can be detected
 Gadolinium, which is a non-iodine based intravenous contrast agent helps differentiate
between edema and tumor and can detect surface seeding
PET is useful in determining differences between necrosis and malignancy, which are
associated with areas of high metabolism
 Uses radionuclides and CT to help detect lesions
 Differentiate between various types of CNS lesions, infections, and degenerative
processes
A stereotactic biopsy (a procedure commonly performed during neurosurgery to guide the
insertion of a needle into a specific area of the brain) allows all areas of the tumor and its
borders to be studied
Debulking procedures are performed if the tumor location is accessible and the tumor volume
is large
 Accomplishes a reduction is tumor size and the opportunity to obtain a pathologic
diagnosis
Pathology
 The most important prognostic factor for CNS tumors is the histopathologic diagnosis
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Benign lesions are indicative of a better prognosis
Tumor growth is not hindered in most gliomas because CNS tumors do not form a natural
capsule to contain them
Necrosis is an important feature in high-grade tumors
Staging
 GTM: based on grade, tumor, metastasis
 Grade (G) has prognostic significance, ranging from well differentiated to poorly
differentiated (G1 to G3)
 G4: anaplastic
Treatment techniques:
 No treatment: survival of 17 wks
 Resection: survival of 70 wks
 Biopsy is extremely important for diagnostic purposes and essential for therapeutic decision
making
 Surgery (best treatment for brain tumors)
 Surgery should be performed on tumors that are symptomatic and offer a chance of
complete resection
 The primary goal for surgery is to remove the tumor and to obtain a histologic diagnosis
 Debulking is indicated with a large tumor volume and if a complete resection is not
possible
 Surgery can be limited by the tumor location and extent, patient status, and risk of
causing debilitating neurologic deficits
 Early and radical excision provide the best chance for a good outcome because of an
accurate histologic diagnosis, control of a mass effect, and cytoreduction, which allow or
enhance adjuvant therapy
 Radiation Therapy
 Radiation therapy is indicated for malignant tumors that are incompletely excised,
inaccessible from a surgical approach, and associated with metastatic lesions
 Radiation therapy usually follows surgery in an attempt to prevent tumor regrowth or
recurrence
 Determining doses for treatment: tumor type, tumor grade, and patterns of recurrence are
important
 The total dose must be limited by normal tissue tolerance because radiation necrosis
(tissue destruction) develops if tissue tolerance is exceeded (6000 cGy)
 These side effects include acute reactions (or those encountered during the course of
treatment), early delayed reactions occurring from a few weeks until up to 3 months after
treatment, and late delayed reactions occurring months to years later
 If brain metastases are present from another primary site of involvement; whole brain
irradiation is the preferred treatment
 Immobilization is extremely important and can be achieved through the use of head
holding devices
 Lateral ports are used for treating the whole brain. The inferior margin of the field
intersects the superior orbital ridge and external auditory meatus (EAM).
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1 cm of flash or shine over should be seen at the anterior, posterior and superior
borders of the field
 The fields may be treated isocentrically or with a fixed SSD,
 Isocentric setups are quicker to set up and carry out and reduces error rates
For complex treatment to the craniospinal axis (the brain and spinal cord) the patient is
simulated and treated most frequently in the prone position
 Care must be taken to match the beam divergence, allowing no overlap
 Hot or cold spots can be avoided by feathering the gap
 This can be accomplished be shifting the gap by 1 cm every 1000 cGy
The treatment volume for gliomas is determined by the tumors extent, which includes the
gross tumor volume (GTV) and related edema
 Because tumor cells have been found in edema, this area should be included in the
treatment field with a 2.5 cm margin for malignant tumors and a 1-2 cm margin for
benign tumors
Doses:
 For palliation of mets: whole brain field 3000-4500 cGy, 250-300 cGy daily
 For curative of primary 5000-6000 cGy in 5-6 weeks, 180 – 200 cGy/day
Side effects:
 Most commonly, patients complain of fatigue.
 Temporary hair loss (alopecia) occurs with doses ranging from 2000 to 4000 cGy,
 With doses of greater than 4000 cGy, hair loss may be permanent.
 Erythema, tanning, dry and moist desquamation (especially behind ears), and edema
are side effects of the treatments
 Cataracts can be reduced using blocks
 Early delayed reactions include drowsiness, lethargy, a decreased mental status, and a
worsening of symptoms
 These reactions can occur up to 3 months after treatment, are usually temporary,
and disappear without therapy
 Radiation necrosis (tissue death resulting from the effects of radiation) is a
complication that rarely occurs from 6 months to many years after irradiation
 Late reactions are usually irreversible and progressive
Chemicals that enhance the lethal effects of radiation are known as radiosensitizers
 Hypoxic cell sensitizers
 Hypoxic cells are more radioresistant than well-oxygenated cells
 The use of sensitizers makes the cells more susceptible to the radiation without
increasing the radiation effects to the normal tissue, which is well oxygenated
 Halogenated pyrimidines
 Halogenated pyrimidines are used with DNA to increase the sensitivity of the cells
to radiation and ultraviolet light
Interstitial implants (brachytherapy) are done with the use of radioactive seeds that are
temporarily placed in tumors
 Adjacent normal tissue is spared from excessively high doses
Stereotactic radiosurgery uses a halo device
 The target volume should be spherical and only up to 3 cm at its maximum dimension
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A local dose to the tumor can be increased while sparing surrounding tissue
 Radiosurgery: 1 treatment
 Radiotherapy: course of treatment fractionated; given with cones
 Accelerated fractionation: faster treatment time, regular dose
 Hyperfractionation: more dose, sublethal damage to tumor, less to normal tissue
 Hyperthermia: concept that heat kills cells used in combination with radiation
 Cells in S phase are sensitive to heat, heat inhibits repair of sublethal damage,
 Enhances effects of chemo drugs,
 Radiation must be given within half hour after hyperthermia
Chemotherapy
 Gliodel wafers: a temporary chemo patch placed directly on the tumor during surgery.
 Effective chemotherapy for CNS tumors is hindered by the BBB, which impedes the
penetration of the drugs into the brain.