Brain Tumors in Dogs

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Years ago, I lost my own personal pit bull to a fast growing brain tumor. Unfortunately, in both human and veterinary medicine, brain tumors can result for no known reason. While genetics and environment may potentially have a role, the underlying cause for brain tumors is typically unknown. Breeds with “smooshed” faces such as Boxers, Boston terriers, and pit bull terriers are overrepresented with brain tumors.

While rare, the diagnosis of a brain tumor in a dog can be devastating to a pet guardian, as the onset of clinical signs is typically very rapid. Clinical signs of a brain tumor include:

  • Aggression
  • Altered behavior
  • Decreased cognitive function
  • Hearing loss
  • Blindness
  • Abnormal pupil size
  • Acute seizures
  • Constant or abnormal panting
  • Inability to walk
  • Walking drunk
  • Circling in one direction

Diagnosis of a brain tumor
The diagnosis of a brain tumor in dogs typically starts with a thorough physical examination by your veterinarian (including a careful neurologic examination to look at the pupils, the response to light, the reflexes in the limbs, etc.). Additional tests to diagnose a brain tumor include:

  • Baseline blood work to make sure the kidneys, liver, and other organs are working appropriately and to evaluate the white and red blood cells
  • Chest x-rays to make sure there is no obvious cancer spread to the lungs
  • A CT or MRI under general anesthesia to look specifically at the central nervous system

Treatment of a brain tumor
Emergency treatment for a brain tumor is often necessary – that’s because dogs often present with acute seizures secondary to a brain tumor. Unfortunately, slow growing brain tumors may encroach on the normal space of the brain. As the tumor gets bigger, it can cause pressure changes within the brain (e.g., cerebral edema), resulting in neurologic signs.

Specific treatment to stop the seizures include:

  • Placing an intravenous (IV) catheter immediately
  • Checking a blood sugar
  • Using IV diazepam (Valium™) to stop the seizures
  • Starting potent anti-seizure medications such as phenobarbital, Keppra™, or other drugs to stop the seizures
  • Using medication to decrease the swelling within the brain (e.g., mannitol)
  • Nursing care to help decrease swelling in the brain (e.g., elevating the head at a 15-30 degree angle, oxygen therapy, etc.)

So what are the options when it comes to treating brain tumors?

  • Euthanasia— Some guardians would elect to euthanize immediately based on the severity of the clinical signs (e.g., seizures).
  • Medical management — This includes using steroids (e.g., prednisone) to help reduce the swelling in the brain along with anti-seizure medications (e.g., phenobarbital, Keppra™). Unfortunately, this treatment only typically extends the lifespan of your dog by 1-2 months. While the steroids are very inexpensive and the anti-seizure medications only moderately expensive, both drugs have significant side effects such as increased thirst, urination, and appetite.
  • Traditional radiation therapy + chemotherapy — Certain specialty veterinary hospitals and veterinary schools offer radiation therapy (RT). This requires daily anesthesia (only briefly for about a few minutes) to help irradiate the general location of the brain. Typically, this occurs once a day, 5 days a week, for 3 weeks in a row. Unfortunately, the RT can zap healthy brain tissue also, potentially causing some rare side effects from RT.
  • Stereotactic radiation therapy (SRT) — This requires a specialized type of RT that is only available in a few veterinary locations throughout the world. This requires brief anesthesia for 1-4 days in a row, and only zaps the tumor – not all the healthy brain tissue. Unfortunately, this is extremely expensive and typically costs $8-10,000.
  • Brain surgery — This is not quite as advanced as human medicine (which is often done while the person is awake and talking during the surgery). Brain surgery requires putting your dog under anesthesia, surgically removing the skullcap, having the tumor surgically "debulked" (which is a nice way of saying "scooped" out). This can also be costly, is cutting edge, and is typically only done by board-certified specialists in neurology or surgery (so not available everywhere). Unfortunately, rare side effects include altered mentation, worsening seizures, and surgical complications.

Prognosis of a brain tumor
Unfortunately, the prognosis varies depending on whether medical management, surgical management, or RT is chosen. The prognosis also varies with what “type” of brain tumor it is; however, it is often difficult to determine the exact “type” until surgery occurs (and a piece of tissue can be biopsied or analyzed). Some brain tumors such as meningiomas have a much better prognosis with brain surgery (to remove or debulk the tumor). Fast, invasive types of brain tumors such as glioma or glioblastoma have a poor prognosis, even in human medicine.

When in doubt, talk to your veterinarian and an oncologist or neurologist. Remember that making an appointment with an oncologist or neurologist doesn't commit you to a several thousand-dollar RT or surgical plan – it lets you weigh your options with those who have the cutting edge knowledge in that area.

Questions to ask your veterinarian

  • Does my dog need a referral to a neurologist?
  • How much is a CT or MRI?
  • What are the side effects of the medications?

If you have any questions or concerns, you should always visit or call your veterinarian -- they are your best resource to ensure the health and well-being of your pets.

Reviewed on:

Tuesday, January 13, 2015

Neurology: Brain Tumors in Dogs and Cats

Cancer affecting the brain is not uncommon in older dogs and cats, although the need for advanced imaging of the brain (such as magnetic resonance imaging, or MRI) in order to detect a brain tumor means that they frequently go undiagnosed. There is also a concerning trend for brain tumors to arise in young dogs of certain breeds, such as the Boxer or the Boston terrier. Developing a brain tumor has serious implications and many owners feel helpless when such a diagnosis is made for their pet.

However, these tumors vary widely in their level of malignancy and some can be treated effectively. Unfortunately, there is still a lot that we do not yet know about how different types of brain tumor behave in dogs and cats, and this can make it difficult to advise owners as to the best form of treatment for their pet. This web page provides information on what we do know about the diagnosis, treatment and prognosis of different types of brain tumor and describes ongoing research efforts at North Carolina State University College of Veterinary Medicine.

What is a brain tumor?

Strictly speaking, the term brain tumor simply means a mass in the brain. However, it is commonly used to describe a cancerous (or neoplastic) mass inside the cranial cavity (figure 1). Brain tumors may be primary, arising from the cells of the brain and its lining (figure 2), or secondary, arising elsewhere and spreading to the brain.

Primary brain tumors seen in dogs and cats include meningioma, glioma, choroid plexus papilloma, pituitary adenoma or adenocarcinoma, and others.

Meningioma – This is the most common primary brain tumor in dogs and cats (and in humans). It arises from the arachnoid mater of the meninges (the membranes that line the brain) 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. Figure 3 is a MRI of a meningioma. These tumors occur more commonly in long nosed (doliochocephalic) breeds of dog, such as the Golden retriever. Meningiomas are usually relatively slow growing and amenable to treatment, although more malignant forms do occur.

Secondary brain tumors

Secondary tumors represent spread (metastasis) of another tumor to the brain from elsewhere in the body. Examples of tumors that may spread to the brain include hemangiosarcoma, mammary carcinoma and melanoma. These tumors carry a very poor prognosis because they have already spread through the body. It is routine practice to take radiographs of the thorax and even to ultrasound the abdomen to check there is no evidence of cancer elsewhere in the body whenever a diagnosis of a brain tumor has been made or is suspected.

What signs do brain tumors cause?

Brain tumors cause signs by compressing or invading the brain. The resulting signs relate directly to the area of the brain affected and are not specific to a tumor: any disease affecting that area of the brain could produce similar signs. As a general rule, brain tumors cause progressive signs in older animals. Signs may start very suddenly or quite insidiously, and they can wax and wane in severity.

The Forebrain: The forebrain is responsible for “thinking,” behavior, and final integration of sensory information. Tumors in the forebrain may therefore cause:

  • Behavioral abnormalities such as loss of learned behavior and 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 (figure 7). 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 signs 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 and 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 (i.e., 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

How is a brain tumor diagnosed?

A brain tumor should be suspected whenever there is new onset of neurological signs in an animal older than 5 years. It is important to understand, that with rare exceptions, brain tumors are tumors of the soft tissues of the brain and they cannot be seen on radiographs of the skull. The brain can be imaged using magnetic resonance imaging (MRI) or computed tomographic (CT) scans. The following diagnostic steps are recommended:

  1. Complete physical and neurological examination to identify any other health problems and to localize the neurological signs to a particular area of the brain
  2. Routine blood work to rule out a systemic problem and assess the anesthetic risk
  3. Thoracic radiographs to check there is no evidence of spread (metastasis) of cancer to the lungs (a common site of metastasis)
  4. CT or MRI of the brain. This has to be done under general anesthesia. As a general rule, MRI shows the brain in more detail than CT and is the test of choice when assessing for brain tumors. However, it is a more expensive test and less widely available. CT images will identify most meningiomas and choroid plexus papillomas but can fail to identify gliomas. CT images also have a lot of artifact when trying to assess the brainstem and cerebellum. We therefore strongly recommend an MRI if the animal 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.
  5. Tumor type can be suspected from the appearance of the mass on 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 (figure 8). 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.

How are brain tumors treated and what is their prognosis?

The options for treating brain tumors include surgical removal, radiation therapy, chemotherapy, and palliative treatment of the symptoms. Unfortunately, we have relatively little data to present on the outcome of tumors because it is common for owners to decide not to treat their pet, or because pets are treated with radiation therapy or chemotherapy without ever determining the tumor type. This mentality is changing as CT guided biopsies become more routinely offered, and one of our research aims is to generate a large data base of how different tumors respond to different types of treatment, and what happens if they are not treated at all (see research).

Brain tumors present unique problems related to their location and the tissue that they affect. Firstly they arise in the restricted space of the cranial cavity (Figure 1). The cranial cavity is formed by the bones of the skull and encloses and protects the brain. While a delicate structure like the brain must be protected in this way, it means there is no room for anything else within the cavity and when a tumor grows, it 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.

Surgical Removal

The aim 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, their location close to the floor of the cranial cavity, and because 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 without 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

We do know that radiation will slow the rate of growth of most types of brain tumor. The full dose of radiation is administered in fractions, the number and timing of which vary between veterinary institutions. At NCSU, we administer 16 small doses of radiation on consecutive days (with breaks for the weekend). 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 (Figure 9), 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 is usually in the region of $3000-4000. Radiation is currently the treatment of choice for gliomas. To learn more about Radiation Therapy for brain tumors at NC State, click here.


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 is 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 therefore, 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 signs caused by a brain tumor. For example, any dog with a brain tumor that has seizures will be placed on an anti-epileptic drug such as Phenobarbital. 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. This response is often short lived as the tumor itself is not being treated by this drug, but can certainly give owners and pets some good quality time.


It is important to understand that most brain tumors can be treated but not cured. Thus the major aim of treatment is to extend a good quality of life for as long as possible. Another critical point is to understand exactly what is meant when data on efficacy of treatment is presented. Useful terms include:

  • Median. Used in the context of survival, a median survival of three months means that 50% of the animals are alive at three months, but 50% have died. It does not give any information of the range of survival of individuals from within the group. For example, individual animals may have survived for only a day to several years. A median survival is very useful to allow comparison between different types of treatment.
  • Survivalmeans just that: how long an animal stayed alive, usually from time of diagnosis, but it could also mean from time of treatment, or from time the owner first noticed signs of a problem. It does not give any information on what the animal’s quality of life was during that time.
  • Progression free survivalis the time the animal survived without progression of the clinical signs. This gives a better idea of the quality of life.

It is fair to say that we have little solid data on the outcome of different tumor types. There are several studies looking at the effectiveness of radiation for treating brain tumors, but in most instances, the actual tumor type was not known. As a general rule, however, 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, particularly meningiomas in cats. 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)

With your help, we hope that we will be able to generate much more specific and useful data on how different types of brain tumor respond to different therapies.

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NC State CVM researchers found that stereotactic radiation therapy, or SRT, is a feasible, less time-intensive option for treating intracranial meningiomas and results in survival rates similar to other approaches.

June 25, 2018

At the NC State Veterinary Hospital, personalized care means more than just offering a wide range of treatment options — it means constantly developing the best therapeutic approaches for each and every animal we see.

The hospital’s radiation oncology service traditionally — and effectively — treats meningiomas, a common type of brain tumor in dogs, with surgery and radiation therapy. While surgery quickly removes the tumor, a schedule of up to 20 daily treatments makes radiation therapy inaccessible for some dogs and their families, said Mike Nolan, assistant professor of radiation oncology and biology.

So Nolan and fellow CVM researchers Krista Kelsey and Tracy Gieger tested a different way. The team found that stereotactic radiation therapy, or SRT, is a feasible, less time-intensive option for treating intracranial meningiomas and results in survival rates similar to other approaches. The pilot study was recently published in the journal Veterinary Radiology & Ultrasound.

We spoke with Nolan about the promising research and the potential for future advances in treating canine brain cancer.

What does this study suggest about the therapeutic value of stereotactic radiation therapy?

We were able to conclude that stereotactic radiation therapy, given in a single treatment session, is a reasonable alternative to full-course radiation therapy for many dogs.

Our results suggest that there may be a somewhat higher risk of serious side effects with SRT, but for most dogs treatment is well tolerated. For many families, the increased risk is balanced by a significant improvement in convenience and a significant reduction in anesthesia.

The good news is that for dogs who tolerate SRT well, the long-term prognosis is just the same as what we expect with full-course RT. The bottom line is that SRT can be a highly efficient treatment for meningiomas.

If we take a big picture view, it’s sort of like using a spotlight to find your way around a dark room rather than using a floodlight. With the spotlight, you can shine a super bright light on the door, but the rest of the room remains pitch black.

SRT does the same thing. It dumps huge amounts of radiation into cancerous tumors while physically shielding the surrounding normal tissues from potentially damaging doses. SRT utilizes specialized training and technology to ensure rapid, accurate and precise delivery of large doses of radiation to a well-defined target.

Mike Nolan, assistant professor of radiation oncology and biology.

Why should SRT be considered in treatment plans for canine brain tumors? When is it considered more desirable than a different type of treatment?

SRT is great. It’s convenient and often associated with outcomes that rival or exceed that which is expected from more conventional irradiation techniques, but there are circumstances when SRT can be more dangerous or can yield inferior prognoses. That’s why when deciding if SRT is the right choice for your pet, it’s incredibly important to have an in-depth discussion with an experienced radiation oncologist who can help navigate all of the options.

How far have we come in the past decade or so in treatment of canine brain tumors?

We’ve come pretty far. Not only can we now safely and non-invasively treat a range of canine brain tumors with SRT, but there have also been improvements to the more conventional radiation therapy techniques.

Beyond radiation, there is also a range of novel surgical techniques that benefit certain patients. There’s promising new immunotherapies, too. Together, these emerging therapies hold a lot of promise and should help us make even more impressive gains in the decade to come.

Do the results of the study make you feel optimistic about canine brain tumor treatment advancements?

I don’t expect miracles, but my hope is simply that we can inch closer to a cure. This study was our first step, but there is still plenty to learn. I think the biggest success is the fact that we’ve been able to use the results of this study to modify our SRT approach for management of canine intracranial meningioma.

From each dog, we learn something that can hopefully benefit the next dog who is diagnosed with a similar problem. As long as we stick with that approach, I remain incredibly optimistic.

For more information on the NC State Veterinary Hospital’s radiation oncology service — and stereotactic radiation therapy — go here.

Virginia-Maryland College of Veterinary Medicine

Brain tumors are a significant problem in the canine population, but are not often definitively diagnosed because of the need for advanced imaging (magnetic resonance imaging - MRI) studies of the brain and ultimately pathologic examination of representative brain tissue (Figure 1). Primary brain tumors can arise from any of the resident cells within the brain tissue itself, or the protective lining surrounding the brain. Brain tumors cause clinical signs primarily by compressing or invading the brain tissue. Seizures, behavioral changes, visual disturbances, and vestibular signs (vertigo) are common abnormalities observed by owners of dogs with brain tumors. Although these signs may often indicate where in the brain the problem is arising from, they are rarely specific for what disease is causing the problem.

The brain tumor clinical trials being offered at VMRCM are focused on improving the treatment of brain tumors called gliomas. Gliomas are the second most frequent type of primary canine brain tumor encountered in clinical practice, and arise from the supporting cells of the brain, namely the astrocytes (astrocytoma) and oligodendroglia (oligodendroglioma). Gliomas typically affect middle-aged to older dogs (7-10 years), and are common in short-nosed (brachycephalic) breeds of dogs, such as the Boxer, Boston Terrier, and English and French Bulldogs. The biological behavior of canine gliomas is quite diverse and currently poorly understood, but all types of gliomas include slow-growing (low-grade) and aggressive, highly malignant (high-grade) variants.

Conventional treatment for brain tumors in dogs include surgery, radiation therapy, and chemotherapy.

Understandably, not all brain tumors can be removed surgically. Tumors can only be removed if they are located in an area that can be reached safely. There are two considerations for this:

  1. The proximity of the tumor to the surface of the brain.
  2. The proximity of the tumor to critical areas of the brain.

Tumors that are on the brain surface are more likely to be removed successfully by surgery. To reach a tumor deep within the brain, a large area of healthy brain tissue will have to be cut through, the effect of which may be devastating for the recovery of the dog patient.

Many dogs recover after surgery without much complication, although sometimes dog parents have reported some kind of "personality change" in their dogs after surgery.

New technology and medical development may give dogs with brain tumors a new lease on life. See this video on a potentially revolutionary treatment (combining surgery with gene therapy and vaccine) for canine brain tumors:

For a tumor that is deep seated and therefore poses significant surgical risks, radiation therapy can be used to slow down the growth rate of the tumor.

Radiation can result in dramatic and rapid improvement of signs. Unfortunately, radiation alone usually cannot destroy the tumor completely. The dog patient may go into remission, only to suffer from a recurrence of tumor growth 8-14 months later.

Also there may be some side-effects caused by radiation, such as occasional nausea, mouth ulcers, or ear infections.

At University of Florida's Evelyn F. and William L. McKnight Brain Institute, a rather new radiation therapy is now available. (Update: also see

The therapy involves using a 3-dimensional ultrasound guidance system to accurately pinpoint the tumor's location. Because of the accuracy, radiation beams can be targeted precisely at the tumor cells, leaving the surrounding tissues unharmed.

Also, since high-dose, precisely targeted radiation treatment can be given in one session, the dog does not have to be treated repeatedly over a period of several weeks as is required in other radiation treatment protocols. This is especially good news for older dogs since radiation treatment requires anesthetic to keep the dog patients from moving, and the single treatment avoids repeated anesthesia.


As the brain is a very well-protected site, there are not too many drug choices that are effective in treating brain tumors. Recently, there is a drug called temozolomide that may be effective in treating gliomas.

For other types of tumor, drugs are primarily used to lessen some of the symptoms caused by the tumor.

For example, to reduce brain swelling, anti-inflammatory drugs such as prednisone will be prescribed. To control and manage seizures caused by the tumor, anti-seizure drugs such as phenobarbital will be used.

By relieving some of the symptoms, the dog patient can feel better. However, understand that these drugs do not destroy the tumor itself and the therapy may only give the dog patient temporary relief of a few months.

Watch the video: Canine Brain Tumor-Signs and Symptoms

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