This is a paper that I prepared for my Cancer Biology course at Ball State University. It covers a general overview of the disease and possible treatments for the cancers of the CNS.

1. Ben Alcini
Cancer Biology: 2015
Cancer of the Central Nervous System
04/14/15

2. In today’s world, cancer is one of the most deadly diseases and is one of the
highest causes of death. Cancer in general, is the abnormal growth of cells into a tumor.
A tumor can either be benign or malignant, both dealing with the severity of the tumor
and the survival rate of the cancer. Cancers can arise from anywhere in the body and at
any age, but usually it is seen mostly in older patients. The reasoning behind the trend
seen with older people being diagnosed with cancer is that for the cancer to form,
events need to occur and mutations also need to take place. The timing for the
mutations to occur and the time between the mutations can be weeks to years, and
more often than not, the timing between the mutational events is years. In the most
recent years, cancer has become a more “household” name, and the more major
cancers or the more common cancers have become very well known to the general
public. These cancers include: lung cancer, colon cancer, breast cancer, and more. But
there are more than just the more frequent types of cancers, one being cancer of the
central nervous system (CNS).
In this type of cancer, tumors can form anywhere in the CNS with the majority of
them forming in the brain. Cancers of the CNS are rare and unlike other cancers, have
been known to affect a large number of children as well as adults. Cancer of the CNS is
a very serious type of cancer and not much is known about this cancer. Studies have
been done to determine more about this cancer in hopes to find a treatment, prevention,
and cause of the disease. A great amount of research is being done on cancer today, in
hopes to prevent or cure all the types of cancer. CNS cancer consists of different
cancers, all originating within the CNS of the body. The most common CNS cancer is

3. named Glioma, which can be broken down into 5 different types of cancer based on
what tissue they arise. The types of glioma are as follows: astrocytoma, ependymoma,
and oligodendroglioma. All of these types of glioma are slightly different from glioma in
the tissue they arise from and the events needed for their respected cancers to come
about. Astrocytoma is a cancer that arises from the astrocytes, the star-shaped cells
found in the brain; and ependymoma arises from ependymal cells that line the spinal
cord and ventricles of the brain. Like all cancers, CNS cancer has its share of known
causes, stages, and treatments. In most cancers, one can predict if whether or not the
cancer the patient has was inherited or sporadic based on the age and occupation of
the patient. Patients who are diagnosed with cancer at a young age and do not come in
contact with known causes, other than the unavoidable causes, the chances of that
person inheriting a mutation that started the cascade of events that lead to the cancer
are much higher. A cancer that is termed sporadic would be one found in older people
and takes years to develop due to the person needing the first mutation to start the
cascade. CNS cancer is no different, especially that of Glioma and ependymoma.
Glioma is the most common type of CNS cancer. Glioma affects both the brain
and the spinal cord, affecting 9 per 100,000 person- year with malignant tumors,
averaging adults 20 years and older (1). While this may seem like a small number over
the short time span of 1998 to 2002, the amount of malignant CNS tumors seen then
was increasingly high. Glioma is a cancer of the glial cells of the central nervous
system, which includes astrocytoma, ependymoma, and oligodendrogliomas. Glioma
accounts for approximately 80% of all malignant brain tumors and is one of the most
dangerous (1). Glioma can affect anyone at any time, but is mostly seen in either

4. children or adults and not between. There is a significant amount of children diagnosed
with CNS cancer each year, but not in the quantity that adults are diagnosed. Children
are able to develop the cancer because of the brains are in a state of developing rapidly
or that their parents passed on a mutation. The fact that children are being diagnosed
with this cancer is giving an emerging need for research on this cancer and possible
treatments.
In other studies performed by Ohgaki and Kleihues, they found that Caucasians
have a higher incidence rate of Glioma than both African American and Asian
populations (2). This can be due to the sample size of the different populations causing
the data to be skewed or it can be due to genetic differences in different geological
locations. Glioma, like other cancers, can be caused by mutations in the cell. Glioma
itself may or may not be inheritable but it is uncertain due to the fact that we still do not
know what exactly can cause the Glioma to occur in the first place. Due to the amount
of incidence in children, one can conclude that the cancer is inheritable and can occur
much faster through inheritance than through sporadic events. For the cancer to occur
sporadically, carcinogens must alter the cell in some way to allow for the cancer to form
and spread. As of today, there is only one known direct cause for Glioma, and that is
exposure to therapeutic dose or a high dose of radiation (1). The radiation causes an
alteration in the glial cells of the CNS and then the cascade takes place leading the
formation of the Glioma. Not much is known on how this causation occurs or why, or if
there is even any other exogenous causes to the cancer. In studies done on children
being treated for acute lymphoblastic leukemia via radiation have shown an increase
risk for Glioma, usually within a ten year span after the initial start of the treatment (2).

5. Here, Ohgaki and Kleihues conclude that the therapeutic radiation does play a major
role in the development and initiation of Glioma and possibly other CNS cancers.
A Glioma tumor can be classified into two different subclasses, a primary low
grade glioma and a secondary low grade glioma. With the primary glioma tumor, the
tumor is not known to have a precursor, whereas the secondary tumor does. (1). With
this separation, it is easier to help diagnose the patient and more definitive for the
treatment of the tumor. Secondary Glioma tumors can rise from a TP53 mutation in a
low-grade glioma, and is relatively consistent with all Gliomas. The role of the TP53
mutation in the formation or proliferation of the Glioma is still not clear, but it is clearly
seen along with EGFR amplifications (1, 2). These mutations, while the roles are not
clear, can be interpreted as significant based on the fact that in the majority of Glioma
patients these mutations have occurred in the secondary tumors.
Patients who have developed Glioma experience symptoms of cranial pressure
such as headaches, possible seizures, vision problems, changes in behaviors or habits,
or even nausea. All of these symptoms can be signs of a larger problem that could lead
to death if not treated right away. Since Glioma is a cancer of the CNS, it is extremely
hard to diagnose in the early stages because the symptoms do not appear till later in
the progression of the cancer. The methods of which are used to diagnose a patient
with Glioma is through the use of an MRI machine, CT scans, and a lumbar puncture
(3). The MRI and CT scans allow the doctors to be able to see the possible tumor and
its location and size. From there, they are more able to determine the classification of
the grade and potentially the type of glioma tumor. If the tumor is present on either
scan, a biopsy is performed in order to determine what exactly the tumor is and how to

6. proceed. Lumbar punctures are performed in order to determine whether or not the
cancer has metastasized, or spread to other parts of the CNS (3). CNS cancers will not
metastasize to outside of the CNS, and will be found in either the brain or the spinal
cord. If only one tumor is present on the MRI scan, then the tumor may have spread to
the spinal cord. A common problem with diagnosing a patient with Glioma is that just
based on the MRI alone, once cannot determine whether or not the tumor is Glioma
or just a brain abscess. In order to discern which the tumor is without having to do a
biopsy, tests called diffusion weight imaging can be performed to determine which the
tumor is (10). Based on this testing, brain abscesses can be differentiated from Glioma
based on the characteristic of brain abscesses having a reduced diffusion coefficient
while Glioma does not exhibit this characteristic (10). Being able to discern whether or
not the abnormal growth seen in the MRI is actually Glioma or not without having to take
a piece of the growth for examination is greatly needed and is quite helpful in the
diagnosis of Glioma. Had a patient just have a brain abscess and be treated for Glioma,
major consequences could follow and the patient would suffer to no reason.
Once the patient has been diagnosed and the examination of the tumor is
complete, the cancer will then be classified. Unlike other cancers that are classified into
stages, Glioma is classified based on many different aspects of the tumors. The Glioma
is first classified based on its cell type and location. As mentioned before, the type of
Glioma the cancer is, it is based on which type of cells they arise from such astrocytoma
is from the astrocytes of the brain (4). Instead of staging the tumor, Glioma is graded.
There are different levels of grading and are termed “WHO”, which is a grading system
based on the World Health Organization (11). There are four levels of which a Glioma

7. can be graded under the WHO system, WHO I, WHO II, and WHO III and WHO IV.
WHO I graded tumors are commonly found in the lower portion of the spinal cord and
not the brain, while WHO II tumors are commonly found in the upper spinal cord and no
the brain (5). This difference between the two grading levels shows the increase in the
intensity of the cancer from a cancer growing in the lower spine to a cancer that has
moved through the spine. WHO III is an anaplastic Glioma, and has metastasized
through the CNS either from the brain to the spine or throughout the brain (5) In general
WHO I tumors have a low potential for proliferation; WHO II is a tumor of low mitotic
activity. WHO III and IV are tumors that are more malignant, with WHO IV being
mitotically active and WHO III is not (11). The use of the WHO grading system is a way
for everyone internationally to understand what the tumor is and how far it has
progressed. This new system has cleared up the past confusion of how staging of a
Glioma should be completed, with it taking place in two different but key points in the
CNS.
Another method of which is used to classify the Glioma of a patient is classifying
the cancer as either low grade or high grade tumors and this deal with the size of the
tumors. Molecularly, Glioma tumors are broken down into two different pathways, a
primary and a secondary pathway (1). Primary pathways do not need a precursor for
the tumor to proliferate and the secondary tumor does. All of these classification tools
allow for the treatment of the cancer to be more effective and ideally shorter. By being
able to more accurately narrow down the type of Glioma a patient has, the more
chances there are for the patient to make a full recovery.

8. Like any other cancer, once a patient has been diagnosed with the cancer it is
best to start treatment right away. Treatment for cancer of the CNS is tricky and can be
quite risky in some cases, especially that of Glioma. Once diagnosed with Glioma and
the grading and stages have been determined, the usual course of action would be to
perform surgery to remove the cancer from the brain or spine if it had metastasized (6).
Surgery is the most efficient way to rid someone of Glioma, but it does come at a price.
In order to remove any cancer through means of surgery, a small amount of normal
tissue must be removed with it. In the case of Glioma, a small portion of the brain must
be removed in order to completely remove the tumor. This could cause serious damage
depending on the location of the tumor in the brain. Typically to treat the Glioma,
surgery is performed to remove as much of the tumor as possible with only removing
the minimum amount of normal tissue, leaving some of the Glioma tumor behind. Then
after the surgical removal of the tumor, the patient then must undergo radiation
treatments reduce and potentially kill the remaining pieces of the tumor (6). Due to the
nature of Glioma and that therapeutic radiation is a known cause for the formation of
Glioma, using radiation to treat the tumor can be perceived as counter-productive (1).
The known effect of the radiation on the tumor is not clear, and potentially causes the
tumor to increase in severity, in theory, though the surgical and radiation treatments
together work in treating the patient. In the worse scenario, if the surgery and radiation
treatments are not effective in treating the tumor or it the tumor returns, chemotherapy
is used as a last resort treatment (6). It is used as a last resort due to its effects on the
body and the nature of how it treats the patient. Using chemotherapy on Glioma could
potentially cause more damage than treatment.

9. Due to the nature of Glioma and the uneasiness of the current treatment options,
research is currently being done to look for more treatment options for Glioma and other
CNS cancers. As of today, due to the lack of knowledge of Glioma and its causes,
studies are being conducted in order to develop preventative measures or ways to
reduce the risk of developing Glioma. One method of treatment that is being studied
currently is the potential use of monoclonal antibodies (7). This new way of treatment
would allow for more specificity in the treatment of the cancerous cells in the brain. If we
were more able to only target the cancer cells and no the normal tissues, the likelihood
for the patient to survive without any more damage to the brain or spine would increase
significantly (7). Monoclonal antibodies would be able to target the cancer cell more
specifically than radiation or chemotherapy. The problem with the study of the use of the
monoclonal antibody is that without knowing more of the causes of Glioma or what is
mutated, the development of the antibody would take years to develop and in the world
of today the treatment would be inefficient. In the ways of prevention, research is being
conducted in the finding of a biomarker for Glioma (8). A biomarker is a substrate that
allows for the detection of a disease affecting the body in some way. By the use of the
biomarker, the potential of early detection of the Glioma is increased greatly, and
therefore the treatment of the tumor is also greatly increased. The current biomarkers
that are being researched on that could be used in the early detection of Glioma
include: MGMT, EGFR, VEGF, and PTEN (8). The use of these biomarkers would
greatly increase the survival and treatment rate of patients diagnosed with Glioma.
Future studies are being more focused on knowing more of the causes of the cancer,
and ways to be able to treat the cancer based on those causes. Like most others,

10. researchers of Glioma are focusing on better ways to more directly target and rid the
body of the cancer. The use of the monoclonal antibodies is a great step forward into
this new direction of treatment, especially with a cancer such as Glioma where you do
not want to damage or kill off any of the surrounding normal cells.
Other studies are currently being performed in hopes to find a treatment suitable
for Glioma. One method of treatment that is being researched on is based on the effects
of thermotherapy on Glioma tumors (9). In a study performed by Andreas and his team
studied the effects of thermotherapy on male Fisher rats. They used different kinds of
particles and frequency to determine which one, if any, would have an effect on the
tumor growth in the rats. What they found was that the thermotherapy resulted in a
antigrowth and antitumor effect in the rats (9). This new method for treating the tumor
cells would be efficient for Glioma in that it would not damage the surrounding normal
tissue and it would be less invasive that surgery. The use of thermotherapy would allow
for the treatment of Glioma, or any CNS cancer, to be more successful without the
damage to the normal tissue of the brain or spine. With the use of the biomarkers and
thermotherapy, early detection and treatment for Glioma would be more efficient and
allow for a decreased account of Glioma patients currently and in the future.
Overall, Glioma is a very complicated and still unknown cancer that greatly
affects many people throughout the world. Glioma is one the most common types of
CNS cancer, amounting to approximately 80% of the brain tumors seen in patients.
Glioma can be considered to be one of the more deadly cancers that it is not a
“household name such as lung cancer or breast cancer. Glioma and other CNS cancers
of the like are extremely hard to detect treat. With the limited knowledge of Glioma,

11. treating patients is not efficient some of the time. The use of surgery and radiation could
cause more harm than good for the patient that is diagnosed with Glioma, especially
with the only known environmental cause for Glioma is high-dose of radiation. The
process of staging and grading a tumor of Glioma is beneficial in that it create a more
accurate treatment method and routine, allowing for a more a greater chance of survival
for the patient. In the future, studies that look into the possible use of other means of
treatment and learning the causes of Glioma would increase the chance of survival and
for the prevention of Glioma from affecting more patients.

12. References
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http://www.abta.org/secure/ependymoma-brochure.pdf
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