The epidemiological study of the brain tumors
world wide is limited, more so in India, due to various factors. It has
been reported that the incidence range is about is 1-10/100,000
depending on the population studied. It is reported to be lowest in
Mexico, and highest in Israel. The incidence of Gliomas (primary brain
parenchymal tumors), the commonest brain tumor is about 5/100,000. The
incidence of Meningioma, the commonest benign brain tumor, is about
1.23/100,000. Metastases constitute 30% to 50% of them.The
tumors form 20-30% of childhood malignancy.
etiology of brain tumors remain largely unknown, except for the
hereditary form of retinoblastomas, genetically determined
syndromes and rare examples of tumors resulting from radiation or
following factors appear to have a role:
factors: Though brain tumors are found throughout the world,
certain varieties appear to be less frequently seen in certain races.
Germinomas are more common in Japan than elsewhere in the world.
Acoustic schwannomas have been reported to be rare in African Blacks.
genetic factors: An inborn, hereditary or inherited factor
plays a role in the origin of gliomas. Oncogenes, a class of structural
genes, play a decisive role in the development of neoplasms. Studies on
malignant and low grade gliomas and on glioma cell lines have led to
some speculative hypotheses about genetic pathways that may determine
the transformation of normal glial cells to glioblastoma cells. < 5% of
glioma patients have a family history of brain tumor. Several inherited
diseases, such as tuberous sclerosis, neurofibromatosis type I, Turcotís
syndrome, and Li-Fraumeni syndrome, predispose to the development of
gliomas. However, these tumors tend to occur in children or young adults
and do not account for the majority of gliomas, which appear in later
are discussed elsewhere.
of ectopic tissue and vestigeal rests: Neoplasms, most often
benign in nature, are seen to arise from vestigeal tissues. These
include the teratomas and teratoid neoplasms, dermoid and epidermoid
cysts, craniopharyngiomas and chordomas. These are clearly of
Age and Sex:
While medulloblastomas and cerebellar astrocytomas are tumors almost
entirely restricted to childhood, glioblastomas are generally seen in
the adult. Primary parenchymal tumors are twice as common in males as in
females, thus implicating obvious hormonal factors in the
etiopathogenesis. Meningiomas are commoner in females, though some
Indian and African neurosurgeons found a slight male preponderance.
While head injury has been invoked in the pathogenesis of meningiomas,
there is no evidence that such an injury plays any significant role in
the development of a subsequent glioma. There are rare case reports of a
glioblastoma occurring in the tract of a leucotomy or at the site of a
Environmental factors: Prior cranial irradiation clearly increases the
risk of subsequent intracranial neoplasms. Certain environmental factors
have been tentatively linked to the development of gliomas, but they
apply to few patients. Severe head trauma, chronic exposure to
petrochemicals, or employment in the aerospace industry may be
predisposing factors. Some reports suggest that with long term use of
cell phones, there appears to be an increased risk for cases with tumors
in the temporal, temporoparietal, or occipital lobe. No increased risk
for brain tumors was found for medical diagnostic x-ray investigations.
Brain tumors are not associated with lifestyle characteristics, such as
cigarette smoking or alcohol use.
While gliomas do not appear to have resulted from previous therapeutic
radiation to the head, this procedure might be an inciting factor in the
production of an intracranial sarcoma. The hazard appears particularly
associated with radiotherapy for pituitary adenomas and the resultant
tumor is more frequently a fibrosarcoma of the dura, developing anywhere
from 20 years later.
factors: Carcinogenic chemicals have long been employed to
induce intracranial tumors in experimental animals. The most important
of those are the nitrosamines-both methyl and ethyl nitrosourea. The
exact mechanism of action is not clear, but may involve the binding of
polycyclic hydrocarbon metabolites to guanine in DNA. It must be noted
that to date no chemical carcinogen has been implicated in the
production of a human cerebral neoplasm. There is no specific evidence
linking human CNS tumors to chemical carcinogens.
agents: Experimentally a large number of viruses have been
used for this purpose in animals. In man the only known virologic
disorder of the brain associated with the production of bizarre
astrocytes consistent with cytologic features of malignant cells, is the
rare condition of progressive multifocal leucoencephalopathy. Here
virions belonging to the papova group of viruses have been detected.
Some patients with JC virus induced demyelination have developed
There is a
wide histopathological variability (click
for WHO classification) in brain tumors. Most brain tumors are named
after the cells from which they develop. They may be intrinsic and arise
from both the glial
cells (mature and immature neuroepithelial cells), or extrinisic from
of the nerve sheaths, and the
extension from tumors of the skull or paranasal sinuses, metastasis from
a distant organ, and occasionally, primary CNS
lymphoma, form most of
the rest. Hematological disorders, such as, leukemia, and rarely,
myeloma are the other possibilities.
from the vestigeal remnants, and
are also traditionally included in brain tumor category. Other
rare tumors have also been reported.
In fetal life and the
first two years, supratentorial tumors are more common. Between 3 and 15
years infratentorial growth is much more frequent. In adults,
supratentorial compartment is more commonly involved.
Intrinsic tumors produce
regional parenchymal effects include, compression, invasion and
destruction of surrounding brain leading to hypoxia, competition for
nutrients and spread of necrosis. Diffuse Intracranial effects include
elevated intracranial pressure due to tumor induced increases in
the volumes of brain, blood and CSF, vasogenic edema, infarction
due to venous or arterial occlusion, and alteration in the balance of
CSF production and absorption.
Extrinsic lesions, such as meningiomas, displace the
brain, thereby compromising the brain function. In late stages, there
may be degeneration,
hemorrhage or necrosis. Peritumoral cysts arise from adhesions and
accumulation of protein containing CSF, reactive gliosis, fibroblastic
proliferation in the final stage of peritumoral edema or rarely as an
exudate from the tumor surface, and behave like an intrinisic tumor.
There may be associated
hydrocephalus which may be
due to obstruction to CSF pathways, or change in CSF dynamics. It is
more frequent in infratentorial lesions.
While the brain is a
favorite site for metastases from tumors from the rest of the body, it
is well known that central nervous system tumors do not metastasize
outside the nervous system, except on rare occasions, when surgery has
resulted in contact of the tumor with extracranial tissues.
Malignant cells have
been found in the veins in the neighborhood of a malignant glioma. Similarly
such cells are also released into the CSF. There may be an immunological
defence of the body tissue to the circulating malignant glial cells. On
the contrary, the brain itself seems to be incapable of any significant
degree of defence response. Though there are no lymphatic channels in
the brain, mononuclear cells expressing T lymphocytes and macrophage
cell surface markers have been identified in the perivascular spaces of
the brain. It has also been observed that a third of all human gliomas
show lymphocytic and mononuclear infiltration mostly around the blood
vessels. Gliomas containing such infiltrates had a longer survival.
There are a few reports
of the presence of sensitized lymphocytes as well as humoral antibodies
in patients with gliomas. Considerable evidence indicates that
tumors in man and animals can provoke an immune response in the host,
thus providing the basis for employing immunotherapy in the treatment of
human tumors. In the perivascular lymphocytic collections,
cytotoxic and suppressor T lymphocytes are predominant. Monocytes,
macrophages with cell surface expression of major histocompatability
antigens, are also present. Abnormalities in cell mediated and humoral
immunity occur in patients with gliomas. Abnormalities in cell
mediated immunity are more severe in patients with higher grade gliomas.
The evolution of illness is usually insidious
and progressive. Occasionally, as in intratumoral bleed, the symptoms
may be acute. Shorter duration usually suggests malignancy.
In most cases, the general clinical manifestations are due to elevated
intracranial pressure, whereas focal signs and symptoms reflect tumor
action on adjacent structures.
A patient with a 'brain tumor' may present
with one or more of the following:
Symptoms and signs of raised intracranial
pressure: Early morning throbbing headache which gets worse
progressively suggest increased intracranial pressure, especially when
associated with projectile vomiting. There may no nausea. Vomiting is
more common in children. Site of headache has some importance
occasionally. Pain at the back of head may indicate tonsilar herniation.
Papilledema and visual failure suggest long standing increased
Disturbed concentration, judgment, and
memory, may result from increased intracranial pressure. On the
contrary, most children with raised ICP, are well behaved and mature in
Focal or generalized epilepsy:
Seizures occur in about 30% of all brain tumors, and about 50% of all
supratentorial tumors. 1% of all with epilepsy have brain tumors. A
tumor must be ruled out in any late on set epilepsy. It is the first
symptom in 50% of temporal tumors, 78% of frontal tumors, and 93% of
central tumors. Generally, seizure as the only symptom suggest a benign
or low grade lesion. It may be focal or generalized. Focal seizure may
suggest the site of lesion. In late stages of increased intracranial
pressure seizures may occur irrespective of tumor location.
Symptoms related to location: Patients
with left sided dominant hemispheric lesions may have language deficits,
difficulty with verbal learning and memory, problems with verbal
reasoning and impaired right sided motor dexterity. A higher incidence
of depressive disorders along with dementia and psychotic symptoms is
also seen. On the other hand, right hemispheric tumors may produce
visual perceptual difficulties, difficulty in facial recognition and
defects of left sided motor dexterity.
Frontal lobe lesions often results
in profound changes in personality and behavior. Convexity involvement
tumors may manifest with depression and motor programming deficits
and impaired speech initiative. Orbitofrontal involvement is associated
with some degree of impulsivity, lack of inhibition, tendency to make
puerile jokes with silly laughter, and a lack of concern. Medial frontal
involvement is more likely to manifest as an inflexible attitude,
apathy, and impaired motivation.
Temporal lobe lesions, most
commonly, produce seizures, with olfactory and gustatory hallucinations.
Impaired visual and auditory functions can occur. Inferior temporal or
temporo limbic involvement leads to psychiatric symptoms, more commonly
with dominant sided lesions. Involvement of insula, claustrum, and para
hippocampal gyrus may produce panic attacks and anxiety.
Parietal lobe involvement is
suggested by cortical sensory disturbances, such as tactile
localization, joint position sense; sensory inattention, loss of
awareness of the affected half of the body, may be an early feature.
Progressive weakness may be seen in motor strip involvement.
In occipital lobe tumors, visual
field defect is common. Cortical blindness can occur.
Features of associated hydrocephalus may be
predominant in midline lesions. Sella and parasellar lesions
present with visual, hypothalamic-pituitary dysfunction and neighborhood
cranial nerve dysfunction may be there. Lesions near the falx may
cause bilateral signs. Irritation of the supplementary motor area may
result in focal seizures.
Basal ganglia lesions result in
abnormal movements, rigidity or tremors.
Tumors involving the hypothalaums
usually present with hypothalamic-pituitary dysfunction.
Intraventricular tumors usually
present with features of hydrocephalus.
Brainstem lesions are associated
with lower cranial neuropathies with hiccups and swallowing
difficulties. Pupillary abnormalities can occur.Bilateral limb weakness
with hypertonia and sensory disturbances may occur. Features of
associated hydrocephalus may be present.
Cerebellar lesions present with
incoordination and ataxia. Cognitive dysfunction may manifest in
children. Cerebellopontine angle tumors , in addition to cerebellar
signs, may exhibit lower cranial dysfunction.
False signs: A disturbance of blood
supply to distant areas or by shifts and changes in the position of
various structures may lead distant effects which may present as the
primary symptoms. Abducent nerve paresis is the most common, due to its
long intracranial route. However, such false signs occur only in late
stages, which should be rare these days.
Deformity of head: Macrocrania is
common in infants. Localized skull swelling due to long standing lesions
may occur in adolescents. Malignant tumors may erode the skull and
present as skull deformity.
X-rays, angiograms, ventriculograms, pneumoencephalograms have become
history and been replaced with CT and MRI these days.
Magnetic resonance imaging (MRI) , introduced by Moorey
Hinshaw in 1979, has made enormous strides and is the imaging
of choice these days. MRI imaging, particularly, contrast enhanced is
much more sensitive than CT due to inherent high contrast and spatial
resolution, multiplanner capability. Soft tissue changes, mass effect,
and the distorted anatomy are better demonstrated by T1 images. T2
images demonstrate the extent of tumor edema complex. Contrast enhanced
MRI is important to assess the vascularity and the blood brain barrier(BBB)
Computerized tomography (CT) scan, introduced by Hounfield in
1967 has equally improved in leaps and bounds. It may be an alternative
when MRI is not available, and is particularly useful to study the
associated bone involvement. 3D images are as informative as a MRI.
Contrast enhancement, as in MRI, indicates the vascularity and BBB
CT anigiogram and MR angiogram
have replaced the conventional 4 vessel angiography. The tumor vascularity,
incasement,and displacement of major vessels, and involvement of venous
sinuses may be studied adequately, before surgery.
Limitations of structural
indicator of true extent of tumor, especially in high grade lesions,
changes (surgical, radiation)
capability to detect tumor recurrence,
in imaging appearance among tumor types and between tumors and
non-neoplastic lesions, with potential implications for treatment
resonance spectroscopy (MRS)
is a non-invasive analytical technique that has been
used to study metabolic changes in brain tumors, strokes, seizure
disorders, Alzheimer's disease, depression and other diseases affecting
MRS can be done as part of a routine MRI on
commercially available MRI instruments. MRS and MRI use different
software to acquire and mathematically manipulate the signal; the
difference is the use of a state of the art technology that analyze the
chemical composition of proton (hydrogen)-based molecules, some of which
are very specific to nerve cells. This technology evaluates the chemical
composition and integrity of functioning upper motor neurons in the
brain, particularly motor neurons.
It has also been used to study the metabolism
of other organs.
Unlike magnetic resonance imaging (MRI),
which gives us a picture of anatomical and physiological conditions, MRS
generates a frequency domain spectrum that provides information about
biochemical and metabolic processes occurring within tissues. It is
useful in distinguishing destructive lesions from neoplastic processes.
In addition, it
provides a definition of tumor grade, aggressiveness, and relevant
biochemistry. It also helps in monitoring of a successful tumor response
before its regression during non-surgical treatments, and conversely the
early definition of tumor recurrence. Increased
choline, decreased NAA, increased lactate, increased Lipid, and
decreased total creatinine, are the biochemical defects in varying
degrees , common to the majority of brain tumors as measured by MRS.
However, it is not reliable in
Recently, multi Voxel chemical shift imaging has shown promising
emission tomography (PET)
scan uses a small dosage of a chemical called radionuclide combined with a
sugar. This combination is injected into patient. The radionuclide emits
positrons. A PET scanner will rotate around a patient's head to detect
the positron emissions given off by the radionuclide. Because malignant
tumors are growing at such a fast rate compared to healthy tissue, the
tumor cells will use up more of the sugar which has the radionuclide
attached to it. The computer then uses the measurements of glucose used
to produce a picture which is color coded. It is ideal for measurement
flow, glucose metabolism, receptor binding, DNA and protein synthetic
helps in distinguishing
recurrent high grade tumors from radiation necrosis,
lymphoma from infectious lesions in AIDS.
It is of limited value in small lesions(<
photon emission tomography (SPECT)
is more widely available and
It utilizes isotopes to study
cerebral blood flow and tissue metabolism of glucose and amino acids,
and helps in
distinguishing recurrent high grade tumors from radiation necrosis,
from infectious lesions in AIDS,
similar to PET scan.
However, it has
resolution and decreased sensitivity
as compared to
Functional MRI (fMRI)
is a convenient technique for providing
complimentary information to other imaging studies. fMRI offers
possibility of performing these cortical localization routinely and in
existing rather than new instrumentation. It is an indirect way of
assessing the neuronal integrity. Neuronal activity results in a
disproportionately increased cerebral blood flow in the region causing
an overcompensation of the fall in oxyhemoglobin. Reduced
deoxyhemoglobin and increased oxyhemoglobin levels contribute to the
fMRI signal which is subsequently processed and activation maps created.
fMRI has been used to map the sensorimotor cortex, visual cortex,
primary auditory cortex, association areas and language regions. This
preoperative mapping allows evaluation of surgical feasibility and
approach. It can also provide information post surgical recovery. It can
also be used to visualize epileptic focus.
It is likely to replace wada test.
whenever possible, may give a
clue to the nature of the tumor, especially in high grade lesions. In
addition to neoplastic cells,
tumor markers, such
as alpha fetoprotein (AFP) and
human chorionic gonadotropin (HCG) are useful for diagnosis and
monitoring therapeutic responses.
gives the final diagnosis
so that optimal
treatment and prognosis can now be determined.
Tumor pathology may be
studied at operation (by frozen section or by cytological preparation),
or in the postoperative period.
A comprehensive range of
histochemical, and molecular biological tests can be performed on
sections of frozen or formalin-fixed, paraffin embedded tumor tissue
using light and electron microscope techniques. When a tumor is
morphologically undifferentiated or anaplastic, its nature may be
which demonstrates the expression of proteins that characterize particular
cells. One example would be the presence of glial fibrillary acidic
protein (GFAP) in astrocytic tumors and other gliomas. An alternative
approach is to examine the tumor at the ultrastructral level for
diagnostic cytological features, such as core vesicles in tumors of
therapy is discussed
Surgery in some tumor types, such as
meningiomas, and schwannomas, surgery may be curative.
Surgery has a
central role in interdisciplinary glioma management, currently
representing its basic therapy
Total excision is the goal, with resultant
improvement in neurology and quality of life.
proximity of vital brain structures may limit
the ideal goal of complete tumor removal with preservation of function.
Surgery may not be offered to patients who
might benefit from it on the assumption that their tumor is too close to
so-called 'eloquent' brain, such as the areas responsible for
controlling movement or speech.
Nowadays, a variety of tools are available to
help the neurosurgeon counter this problem.
have made removal of a strategically located tumor possible.
(with or without a
frame) involves preoperative localization the lesion stereotactically.
A small superficial cortical or subcortical
lesions or deep lesions that can be easily missed by conventional means;
and also when accurate localization
is crucial to excise tumors in highly eloquent areas.
also termed cortical mapping, with awake craniotomy, uses electrical
stimulation of the cortical surface to define areas of functional
cortex, such as primary motor, sensory, or speech cortex. By pinpointing
the exact location of these areas prior to tumor resection, the surgeon
can perform a more aggressive resection and still safely avoid these
structures, thereby preserving neurologic function. Recent advances in
imaging techniques allow for nonivasive brain "mapping", by which the
precise relationship of areas controlling brain function to a nearby
tumor can be determined. One such method is functional MRI, or fMRI.
sophisticated computer, which is capable of taking information from
the CT and MRI scans is used intraoperatively in advanced centers. It
creates a display on a computer screen in the operating room which the
surgeon can use during surgery. It is able to use a special pointer in
the area where surgery is being performed, and that location will be
displayed on the screen in reference to the abnormalities on the imaging
studies. During the procedure continuous exhibition of the distance as
well as the orientation towards the target point minimizes unnecessary
destruction of brain tissue.
MRI and CT images are
superimposed on volume in the stereotactic space which allows a
volumetrical tumor resection as well as staying oriented within the
lesion during resection.
has been developed in various surgical specialties including brain and
The evolution of
robotic neurosurgery has been very rapid since the first robot assisted
surgery by James M Drake in 1991. It can perform brain
surgery that was not possible till now. It is supposed to perform so
accurately in areas where human hand till now was not considered
The robot is guided by
extremely high resolution brain scans, allowing it to work to an
accuracy of a millimeter, marking it possible to operate close to vital
parts of the brain. In contrast, neurosurgeons operating by hand have an
accuracy of only a couple of millimeters and have to avoid various
operations in case they cause permanent and possibly fatal damage. There
are large areas in the brain that the surgeons are unable to operate
computer controlled robotic system that positions and inserts an
'Endoscopic Surgical Laser' through a hole in the skull 3 mm across. The
robot head needs a path through the brain only 1 mm wide. Tests suggest
that the robot will be able to remove a tumor in about half an hour but
more complex operations may take several hours, but unlike
human surgeon the robot doesn't get tired. With little damage to the skull
and the brain the patients should be able to leave the hospital in 24
hours.It may be just a beginning. The uses of such a robot may be
procedures have contributed in successful excision of highly vascular
anesthesia have greatly
helped the surgeons towards his goal.
involving the ENT and plastic surgeons have been refined and complex skull
base tumors can now be excised with satisfying outcome.
Yasergil introduced Intraoperative microscope in Neurosurgery. A
quality microscope in mandatory.
CUSA (cavitron ultrasonic
aspirator) by Epstwein, and laser by Tew in 1983,
facilitates tumor resection.
endoscopy was introduced by Oppel in 1987.Neuroendoscopic
techniques, even though in its infancy, have greatly reduced the
morbidity in selected procedures.
Use of endoscopy,
during microsurgery greatly facilitates in visualization of vital
neighborhood structures, such as brainstem in acoustic surgery, with
minimal brain retraction.
'A fool with a tool is
still a fool'. All the recent advances are not a substitute for
meticulous microsurgical techniques.
Various approaches and modifications are discussed in individual tumor
a central role in the treatment of most brain tumors, whether benign or
It is discussed elsewhere.
In selected, strategically located
benign tumors, such as, acoustic schwannoma,
increasingly being used with success, especially in residual lesions.
Very occasionally, pre operative radiotherapy is employed to
reduce the tumor vascularity.
Chemotherapy forms an
essential adjuvant therapy in gliomas. It is
are occasional reports on use of Tamoxifen, and Bromocriptine in
Use of bromocreptine is well
established in pituitary prolactinomas.
the most appealing means of curing brain tumors is to correct the
underlying defects in the genes that lead to tumor control. Genes that
promote growth could be turned off, those that suppress growth could be
turned on, defective monitoring mechanisms could be turned on, genes
that produce a beacon for the immune system could be delivered, and so
therapy has been used successfully in mice to rid them of primary and
secondary tumors. The principal problem with gene therapy as the primary
treatment of brain tumors is that, in theory, every tumor cell must be
treated with gene therapy. If even one cell escapes, it could regrow
into a large tumor.
It is in the experimental stage, with
encouraging reports as an adjuvant treatment for gliomas. However, there
appears to be a role in meningiomas and other benign tumors as well.
For patients with brain
tumors, gene therapy offers the hope of replacing the defective genes,
amplifying the immune response to cancer. The malignant phenotype of a
brain tumor results from a series of mutations, including genetic
deletions. Therefore, the simple paradigm of replacing a defective
protein does not typically apply to children with brain tumors.
is possible to inject enough reparative genes into a tumor in a mouse to
eradicate the tumor, it is quite a different thing to inject enough gene
therapy into a human brain tumor, which is likely to be much larger. To
date gene therapy has been shown to kill human tumor cells,
unfortunately, current delivery mechanisms are inefficient and unable to
deliver enough to cure the whole tumor. Nonetheless, gene therapy may
well become an important future treatment of human brain tumors, alone
or in combination with the above therapies.
Further study is required.
represents a promising new class of treatments that, in theory, could
confer lifelong immunity to a variety of tumors affecting the brain and
is still in experimental stage as a treatment for gliomas.
theory, the body's immune system should recognize tumor cells as
abnormal and then attack and destroy them. This immune surveillance
probably occurs daily and destroys many early tumor cells. A tumor cell
may develop, however, that can fool the immune system by making
substances that block the signals that tell the immune system to seek
and destroy the abnormal cells. Or, the body's immune system may be
weakened by HIV infection, drugs, or alcoholism and allow tumor cells to
escape control. Animal studies have shown that a healthy immune system
that is being fooled by the tumor can be taught to recognize the tumor
and resume its control duties.
This is a form of therapy aimed at activating the patient's own immune
system in order to kill tumor cells. This group of substances includes
the interferons, interleukins, growth factors and others.
Radioimmunotherapy is showing special promise as a treatment approach to
brain tumors. It typically employs monoclonal antibodies (MAbs), which
are genetically engineered antibodies designed to work against a
specific target. MAbs are bound with radioactive substances and
delivered directly into the brain and sometimes into the tumor. The MAbs
are specifically designed to lock with the surface of certain cells in
the tumor. Once they do so, the radioactive substances destroy the cell.
The approach is
essentially mini-radiation therapy without the damage or severe side
effects of standard radiation treatments.
A number of different
radioimmunotherapies are being investigated, and trials of some are
reporting improved survival rates in high-grade gliomas. Some experts
believe this approach could prove to be the most effective therapy
against these cancers.
Interleukins are natural proteins created by the immune system. Certain
tumor cells carry receptors for specific interleukins, which are being
investigated for a possible therapeutic role. For example, some drugs
combine an interleukin with an agent that is toxic to cancer cells. The
interleukin locks onto the receptor on the cancer cell and the toxic
chemical enters the tumor with the intent to kill it. Some interleukins
are also being investigated alone for their own tumor-cell killing
Tumor cells removed from the patient are inactivated to form a vaccine;
when they are transferred back to the patient, they are harmless but can
elicit a powerful immunologic response against the tumor. For example, a
vaccine that combines tumor proteins with the patientís nerve cells is
being tested in astrocytomas.
augment patientsí immune responses to tumors by means of enhancing
agents, passive immunity, and adoptive immunity have been
ineffective. Active immunotherapy by administration of interferon,
interleukin-2 and/or lymphokine-activated killer cells (LAKC) however,
yielded encouraging results in some trials. Since the tumors are
extremely heterogeneous with respect to cell cycle, antigen-expression
and growth-factor/cytokine susceptibility, immunotherapy has to be
improved before it becomes apart of standard therapy protocols.
is a promising new technique. Many tumors produce substances that promote
the growth of new blood vessels to help provide oxygen and nutrients for
their nearly insatiable needs. Eventually these tumor cells become
dependent on these new vessels. Substances (antiangiogenesis factors)
that inhibit these blood vessels, thereby starving the tumor cells.
These factors can obliterate certain malignant tumors in mice, although
they have not been used in humans.
Angiogenesis inhibitors are drugs that interfere with the growth of blood
vessels in the tumor, effectively starving tumors of vital nutrients and
include the following:
Thalidomide was one of the first drugs tested. In one 2001 study of
recurrent glioblastoma the one-year survival rate was 35%. Researchers
are investigating different doses to improve results.
another angiostatic agent, produced a delayed response in some patients
with high-grade gliomas and was well tolerated. Antiseizure medication
did not affect it. It is now being studied in combination with radiation
of similar agents are under investigation. Recent reports have suggested
that these drugs may lead to a cure of cancer within two years. Although
this predication may prove to be true for some tumor types, primary
brain tumors are, unfortunately, composed of cells that are
metabolically voracious and cells that have much more modest
Antiangiogenesis treatment, if it works, may only turn high-grade tumors
into lower-grade ones. Furthermore, there are situations in which
production of new blood vessels is important for health. The role of
antiangiogenesis factors in humans is promising but remains to be