A Patient Guide to Brain Tumors

A Patient Guide to Brain Tumors


Every year, approximately 17,000 patients are diagnosed with cancer of the brain. For
children and adolescents these tumors are among the most common cancer-related causes
of death. However, most commonly affected are adults in their 5th decade of life. In this
population as many as 2 in 10,000 individuals are afflicted each year - a figure which has
risen over the last decades. Brain tumors are now the second fastest growing cause of
cancer death among those over the age of 65. Unlike lung cancer and melanoma, which
are the first and third on that list, there are no known lifestyle or behavioral changes that
will reduce the risk of developing a brain tumor.
High-grade gliomas account for over three-quarters of these tumors. As these tumors are
rare and therapies complicated to perform, patient care has shifted to tertiary care
facilities such as the Yale Brain Tumor Center able to provide multidisciplinary care
including surgery, radiation and chemotherapy.
In addition to patients with primary cancer of the brain there are 80,000 more diagnosed
with metastatic (or secondary) tumors that have spread to the brain from elsewhere in the
body. The Yale Brain Tumor Center provides not only the latest therapeutic approaches
to brain metastases but also gives patient access to a large number of subspecialists at the
Yale Comprehensive Cancer Center covering the whole spectrum of systemic cancer.
Office visits are coordinated in a way that minimizes the number of visits to New Haven
and the length of the overall stay.

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Primary brain tumors are still classified based on their resemblance to normal cells and
structures of the nervous system. The nervous system consists of nerve cells – the cells
that form the neural network that enables us to move, feel, see, hear, smell, taste and
think – and supporting cells – the so called ‘glial’ cells which are comprised of
astrocytes, oligodendrocytes, ependymal cells and cells of the choroid plexus. Astrocytic
tumors (‘astrocytoma’) predominate, followed by ‘oligodendroglioma’, and mixed
tumors. Least common are growths in proximity to the ventricles and choroid plexus
(‘choroid plexus papilloma’ and ‘ependymoma’).
Brain tumors are also classified into four grades according to their anticipated
aggressiveness. Grade I and II are considered ‘low grade’, grade III and IV ‘high grade’.
‘Low-grade glioma’ is a descriptive term and does not always imply a benign clinical
course. A ‘benign’ infiltrating astrocytoma of the brainstem can lead to disability and
death; a similar lesion in the visual pathway causes blindness and ‘low-grade glioma’
within the spinal cord can produce irreversible paralysis. ‘High grade’ tumors have a
tendency to grow more rapidly and require multi-modality therapy (surgery, radiation
and/or chemotherapy). ‘Low grade’ tumors can evolve into a high grade tumor and thus
follow-up with your doctor in regular intervals is warranted.

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Specific Brain Tumors

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A. Astrocytic
Tumours

Low grade Astrocytomas

Astrocytomas are derived from brain or spinal cord astrocytes. The best therapeutic
approach is still controversial. We provide biopsy or tumor removal, if possible, to
establish a diagnosis as early as possible. Radiation or chemotherapy is reserved for
patients with astrocytomas that can not be removed due to their location in critical areas
of the brain, cause symptoms such as seizures or weakness or those that show early signs
of transformation into a ‘high grade’ tumor.

Pilocytic Astrocytoma

Most pilocytic astrocytomas are located in the cerebellum, the coordination center of the
brain. For these, complete surgical removal is often feasible and potentially curative. The
remainder grows in areas of the brain called the hypothalamus, the optic chiasm or the
brainstem. These structures are crucial for normal vision and endocrine function (water
and electrolyte household, sexual functions, or temperature control). Tumors growing
within these areas can not be completely removed. However, pilocytic astrocytomas
usually grow very slowly if at all and thus radiation therapy is only provided if severe
symptoms are present.


Pleomorphic Xanthoastrocytoma

Pleomorphic xanthoastrocytoma (PXA) is a rare, usually benign superficial glioma.
Complete resection is feasible in most patients and potentially curative.


High grade Astrocytomas

Anaplastic Astrocytoma, Glioblastoma multiforme

High-grade gliomas are the most common primary brain tumors in adults. Following
diagnosis, treatment should not be delayed due to their rapid growth. Treatment usually
consists of surgical removal of the tumor, radiation and chemotherapy.
Radiation therapy is the single most effective treatment for malignant glioma. Standard
treatment consists of so called ‘fractionated external beam irradiation’ provided five days
a week for six weeks.
Chemotherapy represents an additional treatment option for high-grade astrocytic tumors.
Since the early 1970s a group of drugs called ‘nitrosoureas’ (BCNU or carmustine,
CCNU or lomustine) have been the standard chemotherapeutic agents. Temozolomide is
an alternative to these classical agents. It is typically given for five days every four weeks
but various modifications to this protocol exist. High-grade astrocytomas can grow
resistant to this type of chemotherapy. Alternative drugs include, among others, cisplatin,

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carboplatin, etoposide, and irinotecan. In addition, new treatments are being tested in
clinical trials.


Gliomatosis cerebri

Diffuse infiltration of large areas of the brain with glioma cells is denoted as gliomatosis
cerebri. As the tumor can not be resected, only a biopsy is obtained. Radiation therapy is
given if the tumor causes symptoms. Chemotherapy is provided if symptoms deteriorate
after radiation.


B. Oligodendroglial
Tumours

Oligodendroglioma. Oligoastrocytoma.

Surgical tumor removal is the treatment of choice for ‘low grade’ and ‘high grade’
oligodendrogliomas whenever feasible. These tumors also respond to irradiation and
chemotherapy, such as a combination of drugs called ‘PCV’ which stands for
procarbazine, lomustine and vincristine. We provide PCV therapy to benign
oligodendrogliomas that cannot be resected, are symptomatic, or show features of a more
aggressive tumor. It is not clear whether this therapy should be given before radiation is
provided; but this has been our approach in many patients.
Oligoastrocytomas are mixed glial tumors that contain cells resembling astrocytes and
oligodendrocytes. Treatment is identical to the ‘pure’ oligodendrogliomas.

Anaplastic Oligodendroglioma. Anaplastic Oligoastrocytomas.

Patients whose oligodendroglial tumor shows ‘high grade’ features are usually treated
with surgery, chemo- and radiation therapy.


C. Ependymal
Tumours

Ependymoma, Anaplastic Ependymoma

Ependymomas can occur anywhere within the central nervous system. In adults,
ependymomas are usually located within the spinal cord but they can also be found in the
brainstem and the balance center (the cerebellum) or even within the hemispheres of the
brain.
Complete surgical removal should be attempted whenever feasible and may cure the
patient with a low-grade ependymoma. Patients with residual tumors that cause
symptoms, those with relapsing tumor, or those with ‘high-grade’ tumors benefit from
radiation therapy. Chemotherapy is reserved for patients whose ‘high-grade’ tumors are
resistant to other types of treatment.

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D.
Choroid Plexus Papilloma

Choroid plexus papillomas are tumors of childhood. In adults, they are extremely rare.
Choroid plexus papilloma is derived from the structure that produces cerebrospinal fluid,
the fluid that surrounds the brain and fills the ventricles, large spaces within the brain.
Surgical resection is the treatment of choice and potentially cures the patient.


E.
Neuronal and mixed Neuronal-glial Tumours

Ganglioglioma and Gangliocytoma

Gangliogliomas contain two cell populations: nerve cells (‘gangliocytes’) and glial cells.
Prognosis after total removal is excellent. A small portion of tumors that can not be
removed completely can transform into a ‘high-grade’ tumor which requires radiation
therapy and chemotherapy.

Central Neurocytoma

Central neurocytoma is a nerve cell tumor occuring in young adults located in the
ventricles of the brain. The mainstay of treatment is surgical removal. The tumor adheres
to adjacent structures and thus some tissue is usually left behind. Prognosis is excellent
even in patients in whom total removal could not be achieved. Few tumors are more
aggressive and require radiation therapy.


F.
Tumors of the pineal gland

The pineal gland is a structure at the base of the brain that is involved in maintaining our
circadian rhythm. Tumors of this gland are rare in adults and a large number of them are
of ‘low grade’. Complete tumor resection is attempted. Patients with ‘high grade’ tumors
require radiation therapy. The use of chemotherapy is restricted to patients with high-
grade tumors that disseminate along spinal fluid pathways or recurrent tumors.

G. Peripheral Neuroblastic Tumours

Aesthesioneuroblastoma

Aesthesioneuroblastoma is a malignant tumor arising from the neuroepithelium of the
upper nasal cavity – the receptors for smell. It frequently invades the skull and sometimes
even the brain or its coveruings through the cribriform plate, a thin bony plate that
separates the nasal cavity from the brain. Frequently surgical removal is followed by
radiation therapy. Radiation may not be necessary in low-grade tumors that can be taken
out completely. Patients with tumors that can not be controlled with surgery and
radiation, recurrent or disseminated tumors, or high-grade tumors should be treated with

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chemotherapy. Usually a combination of drugs is given almost always containing a drug
called cisplatin. Some centers offer patients radiation or chemotherapy before surgery in
order to facilitate complete removal of the tumor in the operating room. Some patients
may be eligible for radiosurgery.


H. Embryonal
Tumors

Medulloblastoma

Medulloblastomas are rare tumors in adults. The majority of patients present before 40
years of age. The tumor is restricted to the posterior fossa – the back and lower portion of
the skull in more than half of adult patients. Dissemination into the spinal fluid is seen in
one third of cases. As opposed to most other primary brain tumors, medulloblastoma can
spread to places outside of the nervous system, especially bone.
The neurosurgeon tries to remove the tumor completely but this can frequently not be
accomplished as the tumor infiltrates adjacent vital structures. After surgery,

craniospinal irradiation is given (radiation to brain and spine). Chemotherapy benefits
high risk patients, i.e. those with residual tumor after resection or spread into the spinal
fluid. Combination of several chemotherapy drugs such as cisplatin, cyclophosphamide,
nitrosoureas or etoposide have been most successful. Chemotherapy is usually given
before radiation since the blood stem cell reserve after craniospinal irradiation may be
exhausted. Chemotherapy may have a role in patients with low-grade medulloblastomas
as well.


Supratentorial Primitive Neuroektodermal Tumors

Supratentorial primitive neuroektodermal tumours are much less common than
medulloblastomas. The therapeutic approach to these tumors is similar to
medulloblastoma. Surgical removal provides the diagnosis and reduces the tumor burden.
This is followed by a combination of radiation and chemotherapy.


I.
Tumors of cranial and peripheral Nerves

Schwannoma, Neurofibroma

Schwannomas and neurofibromas are benign tumors of the peripheral nerve sheath – the
insulation of nerves. Schwannomas arising from cranial nerves are much less common.
Schwannomas most commonly affect the vestibular division of the eighth cranial nerve
(acoustic Schwannoma) – the nerve that transmits information from the receptors for
movement to the brain. The majority of acoustic Schwannomas remain undetected.
Incidentally found tumors with typical MRI appearance and location as well as clinically
stable tumors with minimal symptoms can be followed with serial MRI scans.
Symptomatic tumors are amenable to microsurgical resection or stereotactic radiosurgery.

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Malignant Peripheral Nerve Sheath Tumour

Malignant peripheral nerve sheath tumor (MPNST) is a rare neoplasm of peripheral
nerves including cranial nerves. Wide surgical excision of the tumor and the tissue
surrounding it is the primary treatment of choice. Radiation therapy before or after
surgery is clearly of benefit. ‘Brachytherapy’ – the temporary placement of a source of
radiation close to the tumor - intraoperative irradiation in addition to external beam
radition may improve outcome in selected patients and avoid amputation of a limb. 20 to
40 % of patients are given chemotherapy as part of their initial treatment. Chemotherapy
does not seem to have a role in the initial treatment of MPNST for patients without
metastases in whom gross total tumor resection is accomplished.


J. Meningeal
Tumours

Meningioma

Meningiomas are usually benign tumors of the covering of the brain or spinal cord – the
meninges. Treatment is dependent upon location, appearence on imaging studies, the
patient’s symptoms and age. Incidentally found asymptomatic small meningiomas can be
safely watched with serial MRI scans. In symptomatic meningiomas overlying the
hemispheres of the brain, surgical resection is the primary treatment and can be curative.
Challenging are tumors invading blood vessels and tumors arising from the base of the
skull. Less aggressive conventional surgery in association with radiosurgery reduces
treatment-related complications.
Atypical (6 % of all meningiomas) and malignant meningiomas (2 %) require a
combination of surgery, radiation and sometimes chemotherapy.


Haemangiopericytoma

Intracranial hemangiopericytoma is a rare neoplasm of the covering of the brain and
spinal cord. In spite of treatment, these tumors frequently grow back in the same place
where they started or spread to other body parts (most commonly bone and liver). Late
recurrences beyond five years of initial treatment are frequent. Surgical removal is the
primary treatment of choice. Radiation therapy appears to reduce the local recurrence
rate. Chemotherapy may benefit the patient with metastases or local therapy-refractory
disease.


K.
Tumours of the hematopoietic System

Primary Central Nervous System Lymphoma (PCNSL)

PCNSL is a very aggressive tumor of B-lymphocytes (the antibody-producing cells of the
immune system). Chemotherapy with a drug called methotrexate alone or in combination

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with other agents such as cytosine arabinoside or thio-TEPA is currently the single most
effective treatment for PCNSL.
In patients whose lymphoma has spread to the spinal fluid, chemotherapy may also be
given into the spinal fluid. This is usually done through a reservoir that is placed
underneath the skin of the scalp (‘Ommaya reservoir’; see the chemotherapy section of
this website).
An increasing number of brain tumor physicians save radiation therapy for recurrent
tumors or those that don’t respond to chemotherapy alone. Radiation is very effective but
used without chemotherapy, tumor relapse occurs within less than a year.
Lymphoma diffusely infiltrates the brain. Thus it can not be removed surgically.
However, tissue needs to be obtained to make the diagnosis. This is accomplished
through stereotactic biopsy (see the surgical section of this website).
Even after combined treatment with radiation and chemotherapy, the relapse rate of
PCNSL is high. Regular follow-up visits and brain scans are necessary in order to
diagnose relapsing disease early. Over the last ten years, the prognosis of patients with
this disease has dramatically improved.
Patients with the Acquired Immune Deficiency Syndrome (AIDS) are predisposed to
developing PCNSL in the advanced stage of their disease. A severely compromised
immune system and concomitant opportunistic infections frequently precludes them from
receiving chemotherapy. Thus whole brain radiation therapy has been the standard
treatment for PCNSL in AIDS patients. The introduction of highly aggressive
antiretroviral therapy (HAART) has led to a marked reduction in the number of AIDS
patients who suffer from PCNSL and an increase in the number of patients eligible for
chemotherapy.


L.
Germ cell Tumours

Germ cell tumors of the central nervous system are extremely rare in adults (less than 0.1
% of primary brain tumors). 90 % of patients are diagnosed before age 20. They are much
more common in East Asia. The most common germ cell tumor occurring within the
CNS is called ‘germinoma’. This tumor is identical to certain tumors of the testis and the
ovary. Much less common are ‘non-germinomatous’ germ cell tumors which are called
teratoma, embryonal carcinoma, yolk sac tumor (endodermal sinus tumor),
choriocarcinoma, and mixed germ cell tumors. Germ cell tumors preferentially affect
‘midline’ structures of the brain such as the region of the pituitary gland – an important
hormone secreting structure at the base of the brain - and the pineal gland, an organ
involved in the regulation of our daily rhythm.
Treatment for germ cell tumors depends on the tumor subtype. Commonly surgical
resection or biopsy is followed by radiation therapy. Chemotherapy given before
irradiation can shrink the tumor and reduce the size of the radiation field.


M.
Tumours of the sellar Region

Craniopharyngioma

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Craniopharyngioma is a benign tumour derived from a developmental remnant called
Rathke’s pouch. Microsurgical resection is the primary treatment in symptomatic cases.
Radiation may benefit patients whose tumor can not be completely removed.

Pituitary Adenoma

The pituitary gland is a structure at the base of the brain where important hormones
regulating growth, thyroid function, sexual function and electrolyte/water balance are
secreted into the blood stream. Adenomas are benign tumors derived from this gland.
Surgical removal is the treatment of choice for pituitary adenomas above a size of 1 cm (a
third of an inch) in diameter, and those causing damage to adjacent structures of the brain
(such as the visual pathway). Radiation therapy is given to patients who can not be
operated upon and or in whom only partial removal was achieved. The majority of
patients treated with surgery and radiation require replacement of pituitary gland
dependent hormones. Treatment with medication – so called ‘dopamine agonists’
(bromocriptine, cabergoline, quinagolide, pergolide) - can lead to a reduction in tumor
size and improvement of symptoms.

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