Bladder, Brain, Head & Neck, Hemangiosarcoma, Lymphoma, Mammary, Mast Cell Tumor, Osteosarcoma, Skin, Testicular Cancers
Antiangiogenesis, Chemotherapy, Clinical Trials, Radiation, Surgery, Complementary & Alternative Treatments
Afterlife
A brain tumor is any intracranial tumor created by abnormal and uncontrolled cell
division, normally either found in the brain itself, in the cranial nerves, in the brain
envelopes (meninges), skull, or pituitary and pineal gland.  Primary brain tumors
(those arising form the cells of the brain and it’s lining) in dogs include meningioma,
glioma, choroid plexus papilloma, pituitary adenoma or adenocarcinoma, and others.
Secondary or metastatic brain tumors originate from malignant tumors (cancers)
located primarily in other organs and metastasize (spread) to the brain.  These
include hemangiosarcoma, mammary carcinoma and melanoma. These tumors carry
a very poor prognosis because they have already spread through the body.

Brain tumors are not uncommon in older dogs, however there is an increasing
incidence of brain tumors occurring in younger dogs. Brain tumors vary widely in their
level of malignancy and some can be treated quite effectively.

The most common forms of brain tumors are outlined below.
Definition
Brain Tumors
Risk Factors
Diagnosis
While there are no definitively identified causes of brain tumors in dogs, we can probably learn from the
suspected causes of brain tumors in humans.  These include:
  • Genetic syndromes

  • Radiation exposure

  • Immunological Factors  - several large studies have reported that gliomas are less likely to occur in
    people with allergies and in people who have had infections with common viruses such as that which
    causes chicken pox.
  • Serious head injuries

  • Pesticides

  • Solvents

  • Electromagnetic fields

  • Nitrosamines that may be created in the digestion of processed meats such as hot dogs, bacon, ham,
    and sausages.
Astrocytomas are probably the most common neuroectodermal brain tumor in dogs. They are usually
found in adult dogs, but they have been reported in dogs less than 6 months old as well. They are common
in brachycephalic (short nose) breeds but can be seen in any breed. The cells tend to be arranged around
blood vessels.
Choroid plexus papilloma are common tumors in dogs, with reported frequency similar to that of
glioblastomas (~12% of neuroglial tumors). Due to their cell of origin, they tend to arise within the
ventricular system and can block drainage of CSF, thus a small tumor can cause very severe neurologic
signs. These tumors are reddish, papillary growths that may bleed. Histologically, they are well defined,
grow by expansion, and have a granular papillary appearance. In both benign and malignant variants of
choroid plexus papillomas, dissemination to other areas of the brain or spinal cord via the CSF pathways
may occur following exfoliation. Obstructive hydrocephalus may occur. Meningeal carcinomatosis may
follow spread of the tumor in the subarachnoid space. Choroid plexus tumors are seen as well-defined,
hyperdense masses with marked, uniform contrast enhancement on CT scans. Marked enhancement,
potentially including hemorrhage and mineralization, is also seen with MRI. Choroid plexus papillomas have
no apparent predilection for brachycephalic.

Ependymomas originate from the epithelium lining the ventricles and central canal of the spinal cord. They
are rare, but have been reported most frequently in brachycephalic breeds. The gray to reddish, soft,
lobular masses tend to invade the ventricular system and meninges, which may result in obstructive
hydrocephalus. Mestastases within the CSF system may be observed. Ependymomas of the fourth
ventricle may encircle the brain stem. Both epithelial and fibrillary varieties have been described.

Gangliocytomas are rare intracranial tumors reported in adult dogs of several breeds. Histologic findings
include mature, neuronal-like cells with multiple processes, a central nucleus, and a nucleolus. Neuroblast-
like immature cells may also be seen, and occasionally, newly formed myelin sheaths. They seem to be
seen most often in the cerebellum.

Suprasellar germ cell tumors are located dorsal to the sella turcica at the base of the brain. They are
often intimately associated with the pituitary gland, which may be trapped within or replaced by the germ
cell tumor. They are thought to result from extensive migration of germ cells during embryogenesis.
Neurologic signs may be acute in onset and may include lethargy; depression; bradycardia; dilated,
nonresponsive pupils; ptosis; visual deficits; and blindness. Affected animals are usually 3-5 yr old;
Doberman Pinschers may be at higher risk than other breeds. Some germ cell tumors have been
misdiagnosed as pituitary tumors or craniopharyngiomas.

Glioblastoma multiforme, considered to be equated with the more malignant forms of astrocytomas, has
been reported with varying frequency in dogs. In one study, the incidence was 12% of 215 neuroglial
tumors. Most are large and found in the cerebrum. They are locally invasive and destructive, well
vascularized, and often contain necrotic zones. Glioblastomas and are most common in brachycephalic
breeds.

Glioma - These tumors arise from the supporting cells of the brain and include astrocytomas,
oligodendrogliomas, glioblastoma multiforme and ependymomas. They are common in certain breeds of
dog, in particular breeds with short noses (brachycephalic breeds) such as the Boxer, the Boston terrier,
and the French and English bulldog. Gliomas can range in malignancy from low grade and slow growing, to
high grade, poorly differentiated malignant tumors (known as glioblastoma multiforme).

Hamartomas are formed by disorderly overgrowth of tissues normally present at a site. They are focal
malformations resembling neoplasms and have been reported only rarely in dogs, usually as a subclinical
finding.

Hematogenous metastatic brain tumors commonly originate from extracranial sites. In dogs, they often
develop from carcinomas of the mammary glands, thyroid, bronchopulmonary epithelium, kidneys,
chemoreceptor cells, nasal mucosa, squamous epithelium of the skin, prostate, pancreas, adrenal cortex,
and salivary glands. Common sarcoma metastases in dogs include fibrosarcomas, hemangiosarcomas,
lymphosarcomas, and melanoblastomas. Brain metastases may accompany intramedullary spinal cord
metastasis in dogs with lymphosarcomas or hemangiosarcomas. Most CNS lymphomas, especially in dogs,
are one part of a multicentric disease, with extensive infiltration of the choroid plexus and leptomeninges a
common finding. Neoplastic angioendotheliomatosis in dogs is thought to be an angiotropic lymphoma,
possibly of the B-cell line. Extraneural tumor cells sometimes localize in the meninges (eg, meningeal
carcinomatosis), often in association with intestinal carcinoma or mammary adenocarcinoma.

Intracranial intra-arachnoid cysts have been reported in dogs. These rare malformation tumors seem to
develop most often in the quadrigeminal cistern. Of the 6 dogs in one report, 3 were <1 yr old, 4 were
males, and 5 of the 6 dogs weighed <11 kg. One dog had additional developmental anomalies (abnormal
corpus callosum and block vertebrae). On CT scans and MRI the cysts were extra-axial, had sharply
defined margins, contained fluid isodense to CSF, and did not show contrast enhancement.

Malformation tumors, including epidermoid and dermoid cysts and teratomas, originate from heterotopic
tissue and are rare tumors in dogs. They typically lie close to embryonal lines of closure. Epidermoid and
dermoid cysts result from inclusion of epithelial components of embryonal tissue at the time of closure of
the neural tube. They reportedly have a predilection for young dogs (e.g, 3-24 mo old), although cysts
have been found in older dogs.

Malignant histiocytosis, which has focal and diffuse forms, is rarely reported in dogs.

Medulloblastomas are highly malignant, uncommon neuroectodermal canine tumors that almost always
develop in the cerebellum. The tumors tend to bulge into the fourth ventricle, often replacing part of the
cerebellar vermis and compressing the midbrain rostrally and the brain stem ventrally. They may infiltrate
the meninges, metastasize within the CSF pathways, and cause obstructive hydrocephalus. While most
cases are seen in young dogs, a cerebellar medulloblastoma with multiple differentiation was recently
noted in a 4-yr-old Border Collie.  

Meningioangiomatosis is a rare, benign malformation of CNS blood vessels, characterized by proliferation
of the vessels and spindle-shaped, perivascular meningothelial cells in the cerebral cortex and brain stem
of juvenile and adult dogs.

Meningioma is the most common primary brain tumor in dogs (and in humans) probably the cause of most
seizures in dogs over 6 years old.  These tumors can also occur in dogs under 6 months old.  It arises from
the arachnoid mater of the meninges (the membranes that line the skull and vertebral column, effectively
surrounding the central nervous system which consists of the brain and spinal cord) rather than the cells of
the brain itself. As such, meningiomas are not strictly brain tumors, but tend to be grouped with them
because they arise within the cranial cavity and compress or invade the brain. These tumors occur more
commonly in long nosed (doliochocephalic) breeds of dog, such as the Golden retriever and collie.

Meningiomas are usually relatively slow growing and amenable to treatment, although more malignant
forms do occur.  Because the meningioma is a tumor of the meninges (the outer membranes) these tumors
grow from the skull inward.  This makes them much more surgically accessible (depending on their size).

Meningiomas rarely metastasize outside the brain, but may extend into paranasal regions and lungs or be
seen as primary extracranial masses as a result of embryonic displacement of arachnoid cells or
meningocytes. The reason they are a problem is that there is a limited amount of space within the skull.
The brain and its bath of cerebrospinal fluid takes up almost all the room and when a tumor begins to grow,
the brain tissue is compressed. Inflammation can result leading to more swelling and soon nerves of the
brain are damaged.

Meningeal sarcomatosis are sarcomas which cause diffuse thickening of the meninges; extensive
hemorrhages are common. These rare tumors tend to infiltrate nervous tissue and run along blood
vessels. Cell types include lymphoid, plasmacytoid, mature plasma cells, immunoblastic cells, and
multinucleate giant cells.

Oligodendrogliomas are common tumors in dogs, particularly in brachycephalic breeds. Most grow by
infiltration and destroy invaded tissue.

Pituitary adenoma or adenocarcinoma - The pituitary gland lies beneath the forebrain and is connected
by a stalk to an area of the brain called the hypothalamus. Pituitary tumors (adenomas) are common in
dogs, with an apparent predilection for brachycephalic breeds.  They cause hyperadrenocorticism
(Cushing's disease). Usually they do not cause any other neurologic signs and remain outside the actual
cranial cavity. However, in some cases they expand rapidly and compress the overlying brain. These
tumors are known as pituitary macroadenomas, or adenocarcinomas (if more malignant). There are
several other more unusual tumor types that may be seen in this area such as the suprasellar germ cell
tumor.  

Primary skeletal tumors do not typically cause neurologic signs. Multilobular osteochondroma originates
in the flat bones of the skull, usually in older medium- or large-breed dogs and appears as a firm, fixed
mass. It may erode the cranium and compress, rather than infiltrate, underlying brain tissues.
Radiographically, the tumor contains nodular or stippled areas of mineralization, resulting in a
characteristic “popcorn ball” appearance. Local recurrence and metastasis are common. Vertebral
osteochondroma is the spinal cord counterpart.

Vascular malformations are considered developmental lesions rather than true neoplasms and are
uncommon in dogs. They may be located in the cingulate gyrus, pyriform-hippocampal area of the
temporal lobe, basal ganglia, cerebellum, occipital lobe, or septum pellucidum and fornix and comprise
variable combinations of arteries, veins, and capillaries. The vessels tend to be dilated, sinusoidal in
shape, and accompanied by hemorrhages.
Causes
Adult dogs of several related brachycephalic (short-nose) breeds such as Boxers, English Bulldogs, and
Boston Terriers, are often cited as having the highest incidence of brain tumors among domestic animals.  
These breeds are especially prone to glial tumors, including unclassified gliomas.   A more recent study of
97 dogs indicated that Golden Retrievers also have a high incidence of brain tumors, especially
meningiomas.

Age also appears to be a risk factor, with 95% of canine mengiomas occurring in dogs over 7 years old.
Symptoms
or staggering, forgetting The symptoms associate with brain tumors vary widely but are generally caused by
compressing of or invasion into the brain. The onset of symptoms may occur very suddenly or may
progress slowly over time. Typical signs include:  unsteadiness or staggering, forgetting commands or
failure to recognize familiar people, unexplained aggressiveness or puppy-like behavior, development of
obsessive behaviors, loss of bladder control, change in appetite, loss of hearing or sight, seizures, labored
breathing, or whimpering or head shaking.
breathing, or whimpering or head shaking.

loss of bladder control, change in appetite, loss of hearing or sight, seizures, labored breathing, or
whimpering or head shaking.


The resulting symptoms of a brain tumor relate directly to the area of the brain affected by the tumor and
are not specific to the tumor itself: any disease affecting that area of the brain could produce similar signs.  
Clinical signs typically associated with each area of the brain are listed below:

The Forebrain - The forebrain is responsible for "thinking," behavior, and final integration of sensory
information. Tumors in the forebrain are associated with the following symptoms:

  • Behavioral abnormalities such as loss of learned behavior or depression
  • Increased or decreased appetite and thirst
  • Constant pacing or circling,
  • Decreased awareness and vision on one side of the body causing misjudgement of openings to
    doorways and bumping of one side of the body.
  • Sometimes affected animals behave as if they are in pain.
  • Seizures are a classic sign of forebrain disease and in fact, new onset of seizures is the most
    common presenting sign of animals with tumors of the forebrain. These seizures can occur alongside
    any of the other signs listed above, or may occur as the only abnormality. Whenever a dog or cat
    that is greater than five or six years of age has a new onset of seizures, a brain tumor is a possible
    differential and ruled out by a full diagnostic workup.

The Brainstem - The brainstem plays various vital roles including regulation of motor function (the
ability to walk), the level of wakefulness, and the respiratory and cardiovascular systems. The sense of
balance originates in the brain stem. The brain stem is also the source of the nerves that control movement
of and sensation to the face, the eyes, the throat, larynx and tongue, and the muscles of mastication.
Tumors in the brainstem can be rapidly fatal if, for example, they affect the control of breathing, but typically
the first signs of brainstem disease are a loss of balance (vestibular signs), and weakness on one side of
the body. There can be a wide variety of additional signs such as difficulty swallowing, change in voice and
inability to move the eyes. Further progression of the signs can result in paralysis, coma and death.

Vestibular disease symptom include:

  • Head tilt
  • Leaning and falling to the side of the head tilt
  • Drunken gait with loss of balance (ataxia)
  • Circling to the side of the head tilt.
  • Involuntary flicking of the eyes (nystagmus)
  • Loss of appetite, vomiting.
  • Abnormal eye position (strabismus)

The Cerebellum - The cerebellum controls coordination of movements and interacts closely with the
vestibular system to control balance and posture. Signs of cerebellar disease include:

  • Uncoordinated gait characterized by dramatic goosestepping (hypermetria)
  • Head tremors that are worst when the animal is intent on something (for example, food) but disappear
    when the animal is relaxed (intention tremors).
  • Swaying of the trunk
  • Wide based stance
  • Sometimes there can be vestibular signs such as a head tilt
  • The animal's strength remains normal.
Diagnosis
Whenever there are neurological changes in a dog, especially in those older than 5 years, a veterinarian should be consulted to rule
out a brain tumor.  To accurately assess your dog’s condition, the following diagnostic methods will likely be performed by your
veterinarian:

Complete physical and neurological examination to identify any other health problems and to localize the neurological signs to a
particular area of the brain.

Routine blood work to rule out a systemic problem and assess the anesthetic risk.




better able to identify fluid build up, swelling, cysts, bleeding ad other subtle soft tissue changes inside the brain and therefore an MRI
is a better able to identify fluid build up, swelling, cysts, bleeding ad other subtle soft tissue changes inside the brain and therefore an
MRI is a better tool, expecially if the dog has signs of brainstem or cerebellar disease, or if it is a breed of dog that is predisposed to
gliomas, such as the Boston terrier.
the Boston terrier.


A specific tumor type can be suspected from its appearance on a CT or MRI, but can only be definitively identified by taking a sample of
the tumor, either at surgery or by biopsy. Indeed, masses caused by infections (for example abscesses or fungal granulomas) can look
like brain tumors on brain images . It is therefore vital that a sample of the tumor is taken and examined with a microscope to identify
the cell types involved. Not only will this identify the tumor type, but it will also grade the malignancy of the tumor. Many neurologists,
particularly those working in university teaching hospitals, routinely perform CT guided biopsies of tumors.
compresses the surrounding brain. Secondly, brain tissue cannot regenerate, and therefore removal of normal brain tissue
compresses the surrounding brain. Secondly, brain tissue cannot regenerate, and therefore removal of normal brain tissue
surrounding a tumor can have unacceptable repercussions for the patient.
surrounding a tumor can have unacceptable repercussions for the patient.


Surgery
The goal of surgical removal of a brain tumor is either to cure the disease by complete removal (which only occurs rarely) or to alleviate
the clinical signs by decompressing the brain. This can be life saving if the mass is very large. Brain tumors can be removed surgically
if they are located in a site that can be reached safely. There are two considerations for this, firstly, how close is the tumor to the
surface of the brain and secondly, how close is the tumor to critical areas of the brain. Tumors of the brainstem pose problems on both
of these fronts. They are difficult to access, because of the thick bone surrounding them, and their location close to the floor of the
cranial cavity, and the brainstem does not have much redundancy of function so damaging it could be fatal. In contrast, there is much
more functional redundancy in the forebrain: you can resect certain parts of the forebrain with out long-term effects. Meningiomas tend
to be located on the surface of the brain and are therefore the best candidates for surgical removal. Gliomas are more difficult to
remove because they lie deep within the substance of the brain.

Radiation Therapy
Radiation will slow the rate of growth of most types of brain tumor.  There are many different schedules used for radiation treatments:
some weekly, some daily, some on alternate days.  Radiation can be done instead of surgery or in combination with surgery and what
protocols yield the longest survival times is not clear. Currently, the philosophy on treatment is that a combination of surgery plus
radiation yields the best results for dogs.

The full dose of radiation is administered in fractions, the number and timing of which vary between veterinary institutions. Because the
brain cannot tolerate large doses of radiation, the total dose is limited and side effects are usually minimal. It is common to see a
change in hair color in the area irradiated, and other side effects depend on the area that is being irradiated. For example, if the ear is
included in the radiation field, there may be some irritation of the ear canal (rather like an ear infection) that will resolve once the
course of radiation is completed. In order to complete a course of radiation safely, the animal must be healthy enough to have a
general anesthetic for each dose of radiation. Therefore, if the animal has a very large mass, it is preferable to surgically remove as
much of it as possible first, thus decompressing the brain and enabling the animal to survive the course of radiation. The cost of
radiation varies geographically, but you can expect to pay several thousands of dollars for this treatment.  Radiation is currently the
treatment of choice for gliomas.

Chemotherapy
The brain is protected from circulating substances in the blood by a barrier called the blood brain barrier (BBB) and this barrier limits
the effectiveness of chemotherapeutic agents. As a result, chemotherapy has not been advocated all that often for treatment of canine
and feline brain tumors and we have very little if any data on the efficacy of such drugs in our patients. However, some drugs, such as
the alkylating agents lomustine (CCNU), carmustine (BCNU) and a more recently developed drug, temozolomide, can cross the BBB
and may be effective when treating gliomas. Recently, temozolomide has shown to be effective for this purpose in people although
there are no data in dogs as yet. Chemotherapy is a reasonable alternative when treating a glioma if radiation is not an option. Drugs
like CCNU can be administered once every three weeks in tablet form at home, by the owner. There are dose limiting side effects on
the liver and bone marrow and so these must be monitored closely by the attending veterinarian while receiving treatment. Recently,
drugs such as 5-hydroxyurea have been used to treat meningiomas, but as yet there are no data on the efficacy of this approach.

Pallative Treatment
If none of the above therapies are an option, it is possible to treat the symptoms caused by a brain tumor.  For seizures caused by
brain tumors, dogs can be place on an anti-seizure drug such as Phenobarbital or potassium bromide. Tumors tend to cause the
accumulation of fluid (edema) around them and this can be treated with a corticosteroid such as prednisone. As many of the clinical
signs can be due to the edema, some animals show a dramatic improvement within 24 hours of starting treatment with prednisone.  In
one study of dogs with meningioma, the tumor’s blood volume decreased by 21% within 24 hours of beginning prednisone.  This
response is often short lived as the tumor itself is not being treated by this drug, but can certainly give dogs some good quality time.
Prognosis
Unfortunately, most brain tumors can not be cured, but many can be treated. The primary goal of treatment is to extend a good quality of life for as long as possible.

There is little solid data on the outcome of different tumor types because many dog owners do not have the necessary diagnostic testing performed to determine the exact
type of tumor that afflicts their dog. However, there are several studies looking at the effectiveness of radiation for treating brain tumors. As a general rule, median survivals
of around a year are obtained when a brain tumor is irradiated. Better survivals may be obtained when treating meningiomas with surgery followed by radiation.  There are
some general guidelines that can be applied to individual animals when considering prognosis:

  • The more severe the signs, the worse the outcome
  • The larger the tumor the worse the outcome
  • Supratentorial tumors (tumors of the forebrain) have a better prognosis than infratentorial tumors (tumors of the brainstem and cerebellum).
  • Radiation therapy does prolong lifespan in most cases
  • Meningiomas have a better outcome than tumors that lie within the brain (e.g. gliomas)
Treatment

Clinical trials open to
dogs with brain tumors
By Fran Howard






Batman, the first patient to undergo a breakthrough
experimental treatment for brain cancer in dogs, has
become a poster dog for the revolutionary protocol. The
pointy, black ears of the 10-year-old German shepherd mix
gave the cancer-surviving superhero his name, but his
doctors gave him back his life. Without treatment, Batman
was not expected to survive past Halloween 2008. Given
the circumstances, one wonders whether Batman’s doctors,
John Ohlfest, Ph.D., and G. Elizabeth Pluhar, D.V.M., Ph.
D., aren’t the true superheroes.

The University’s dynamic duo developed a combination
treatment plan for dogs with glioma, a very aggressive and
relatively common form of brain cancer. The treatment,
which is now available to other dogs with brain cancer,
dramatically extended Batman’s life. The three-pronged
treatment approach consists of first surgically removing the
tumor, then treating the surgical site with a form of gene
therapy to attract immune cells that will recognize and
destroy remaining tumor cells, and finally administering an
anti-cancer vaccine made from the dog’s own cancer cells
to prevent tumor recurrence.

Now nearly a year after Pluhar, a veterinary surgeon at the
Veterinary Medical Center, and Ohlfest, head of the
neurosurgery gene therapy program at the Masonic
Cancer Center, gave Batman his initial treatment, the
celebrated dog is still enjoying life. The neurological deficits
that led to his diagnosis have been almost eliminated. “We
documented an anti-tumor immune response that has
correlated to control of the tumor,” says Ohlfest. In other
words, the treatment appears to have worked, and the
implications could be far-reaching.

“There is the potential for this type of therapy to be used
on nearly any type of systemic cancer in dogs, not just
brain cancer, because the immune response covers the
entire body,” says Pluhar. “I’m hopeful this therapy may in
time be used for other types of systemic cancer in dogs.”

Through the help of grants from government agencies and
private foundations, Ohlfest and Pluhar have since treated
four other dogs for similar tumors. The second dog to
receive treatment exhibited an impressive tumor regression
following six vaccinations, and Ohlfest and Pluhar are
optimistic that the other dogs will show similar responses.

Canine brain cancer therapy has been organized within the
canine brain tumor clinical trials program. The treatment
team already has funding to treat up to 50 dogs. That
number could soon exceed 100, though, if additional grants
and charitable donations come through.

The area of medicine in which Ohlfest and Pluhar work is
called comparative oncology. They use what they learn in
veterinary medicine to help humans, and they extrapolate
what they can from human medicine to help pet animals.
Batman is an excellent case in point.

Ohlfest’s work in gene and immune therapy led to a first
generation anti-cancer vaccine to be used in a human
clinical trial. However, the early vaccine was expensive and
difficult to produce. He subsequently used that vaccine to
develop a more potent and less expensive vaccine for dogs.

Now it’s Batman’s turn to return the favor. “I would be very
disappointed if we couldn’t write a protocol for humans
within a year from what we have learned from our work with
dogs,” says Ohlfest. “This is first and foremost a new
therapy for dogs, but at the same time, it will be more
predictive of what might happen in people than any other
form of research.”

The cost of therapy for one dog can range between
$10,000 and $20,000. However, dogs with tumors that
originate in the brain may be eligible for the canine brain
tumor clinical trials program. The program will cover the
vast majority of the cost of treatment including surgery and
supportive care while the dog remains enrolled in the trial.

Learn more about the trials online at www.cvm.umn.edu. To
enroll a dog in a trial, call Kelly Noyes, Small Animal
Surgery case manager at 612-624-7441 to schedule an
appointment with Dr. Pluhar or visit our Web site at www.
cvm.umn.edu. To donate to the research effort, click here
and select “new gift” then designate the gift is for the “CVM
canine brain tumor clinical trials” effort. Or you can contact
Sharon Staton, director of advancement, at 612-624-1247,
or e-mail her at stato001@umn.edu.





Batman’s Treatment Now Available to Other Dogs
with Brain Tumors
By Fran Howard

Batman with Dr. John Ohlfest and Dr. Liz Pluhar Batman,
the first dog to undergo a breakthrough experimental
treatment for brain cancer, has become a poster dog for
the revolutionary therapy. The pointy, black ears of the 10-
year-old German shepherd mixed breed dog gave the
cancer-surviving superhero his name, but his doctors and a
novel therapy gave him back his life. Without treatment,
Batman was not expected to survive past Halloween 2008.
Given the circumstances, one wonders whether Batman’s
doctors, G. Elizabeth Pluhar, D.V.M., Ph.D., and John
Ohlfest, Ph.D., aren’t the true superheroes.

The University’s dynamic duo developed a combination
treatment plan for dogs with glioma, a very aggressive and
relatively common form of brain cancer. The treatment,
which has given Batman a new lease on life, is now
available to other dogs with brain cancer. The three-
pronged approach to treatment consists of surgical removal
of the tumor, treatment of the surgical site with a form of
gene therapy to attract immune cells to destroy remaining
tumor cells, and administration of an anti-cancer vaccine
made from the dog’s own cancer cells to prevent tumor
recurrence.

Pluhar, a surgeon at the Veterinary Medical Center, and
Ohlfest, head of the neurosurgery gene therapy program at
the Masonic Cancer Center, gave Batman his initial
treatment in August 2008. Today, the neurological deficits
that led to his diagnosis have been almost eliminated.

“We documented an anti-tumor immune response that has
correlated quite well with tumor regression,” says Ohlfest. In
other words, the treatment appears to have worked, and
the implications could be far-reaching for both animals and
humans.

“There is the potential for this type of therapy to be used
on nearly any type of
systemic cancer in dogs, not just brain cancer, because the
immune response covers the entire body,” says Pluhar. “I’m
hopeful this therapy may in time be used for other types of
systemic cancer in dogs.”

Through funding from government agencies and private
foundations, Ohlfest and Pluhar have treated four other
dogs for similar tumors. The second dog to receive
treatment exhibited an impressive tumor regression
following six vaccinations, and Ohlfest and Pluhar are
optimistic that the other dogs will show similar responses.

soon exceed 100 if additional funding is achieved.
soon exceed 100 if additional funding is achieved.


The cost of therapy for one dog can range from $10,000 to
$20,000. However, dogs with tumors that originate within
the brain may be eligible for the brain tumor clinical trials
program. The program will cover the vast majority of
treatment costs while a dog remains in a trial.



Batman in Memoriam (1998-2010)

We were very saddened to hear that Batman, the dog
whose brain tumor was being successfully treated with an
experimental gene therapy at the University of Minnesota,
has died of pneumonia. His dog mother, Anna Brailovsky
emailed us to say that "We are extremely lucky that Batman
touched so many lives and we can at least share our
sadness with others outside our family who understand our
loss and know how irreplaceable he was. The very good
news is that it was not to brain cancer, so we can still
consider him to be a great success story.”

Anna and her husband Eric Baker found Batman him on
the streets of Berlin as graduate students in 1999. He
returned with the couple to the United States in 2001, and
was happy and healthy until he had a series of seizures in
2008. A tumor was diagnosed and Batman ended up at the
University of Minnesota, where Dr. Elizabeth Pluhar, a
veterinary surgery professor, and John Ohlfest, a pediatrics
professor, had been considering an experimental brain
tumor treatment for about three years. Batman underwent
the procedure — which, though it had been tried on mice,
had never used on a dog before. Surgeons removed most
of Batman’s tumor, much of which was then used to make a
vaccine for the dog.  A year later the tumor was gone. The
experimental treatment could someday help people with the
same disease. “The study now has many more dogs in
various stages of treatment and recovery, and they are
steadily moving toward developing the protocol for human
trials,” Brailovsky said. To keep Batman’s memory, she and
her family created a website that tells his story and features
a university-made video on his treatment:   Click here to
view  
Batman in Memoriam (1998-2010).


Rest in Peace, sweet Batman.  You are an inspiration
to us all and you have given us the gift of hope
through your bravery.  You will always be in our
hearts.
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