Accurate statistics for the frequency and outcome of brain tumors are not available. It is estimated that in the

United States in 1990, there were 20,500 new cases of primary brain tumor . New cases of metastatic brain tumor diagnosed in 1990 were estimated to be at least 20,700. The combined estimate of 41,200 new cases of brain tumor included both benign and malignant brain tumors.

 

These statistics are based on the 1989

United States population of 249,000,000 people, and an incidence rate of 8.2 per 100,000 for primary brain tumors, and an incidence rate of 8.3 per 100,000 for metastatic brain tumors.

 

The various types of brain tumors occur with different frequency in children and in adults.

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Brain tumors can be benign or malignant:

•       Benign brain tumors do not contain cancer cells:

•        Usually, benign tumors can be removed, and they seldom grow back.

•        The border or edge of a benign brain tumor can be clearly seen. Cells from benign tumors do not invade tissues around them or spread to other parts of the body. However, benign tumors can press on sensitive areas of the brain and cause serious health problems.

•        Unlike benign tumors in most other parts of the body, benign brain tumors are sometimes life threatening.

•        Very rarely, a benign brain tumor may become malignant.

•       Malignant brain tumors contain cancer cells:

•        Malignant brain tumors are generally more serious and often are life threatening.

•        They are likely to grow rapidly and crowd or invade the surrounding healthy brain tissue.

•        Very rarely, cancer cells may break away from a malignant brain tumor and spread to other parts of the brain, to the spinal cord, or even to other parts of the body. The spread of cancer is called metastasis.

Sometimes, a malignant tumor does not extend into healthy tissue. The tumor may be contained within a layer of tissue. Or the bones of the skull or another structure in the head may confine it. This kind of tumor is called encapsulated.

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Treatment of primary brain tumors and brain metastases consists of both symptomatic and palliative therapies.

Symptomatic therapy

Supportive treatment focuses on relieving symptoms and improving the patient’s neurologic function. The primary supportive agents are anticonvulsants and corticosteroids.

• Anticonvulsants are administered to the ~25% of patients who have a seizure. Prospective studies have failed to show the efficacy for prophylactic anticonvulsants. Those receiving phenytoin concurrent with radiation may have serious skin reactions such as erythema multiforme and Stevens-Johnson syndrome.

• Corticosteroids, usually dexamethasone given 4 to 10 mg every 4 to 6 h, can reduce peritumoral edema (through rearrangement of the blood-brain barrier), diminishing mass effect and lowering intracranial pressure, with a decrease in headache or drowsiness.

Palliative therapy

Palliative treatment usually is done to achieve a longer survival time, albeit only a slight increase [see below]. It includes surgery, radiation therapy, and chemotherapy.

A maximally feasible resection with maximal tumor-free margins (”debulking”) is usually performed along with external beam radiation and chemotherapy. Total cranial irradiation (4500 cGy) with a boosted dose (1500 to 2000 cGy) at the site of the tumor, can increase survival by 5 months [see below]. The addition of the chemotherapeutic agent carmustine alone increases survival slightly. Most oncologists prefer a combination chemotherapy consisting of procarbazine, lomustine, and vincristine (PCV regimen). Another combination includes carboplatin and cisplatin. Their efficacy is limited, and toxicity, particularly with the PCV regimen, can be considerable. Despite initial studies suggesting the superiority of PCV over BiCNU, there are now clear data demonstrating no benefit of PCV over BiCNU in either glioblastoma or anaplastic astrocytoma patients. Brachytherapy (implantation of radioactive beads or needles) and high-dose focus radiotherapy (stereotactic radiosurgery) have not shown to increase survival times.

In a large phase III trial, implantation of BiCNU-impregnated wafers - trade name Gliadel Wafers- at the time of primary resection, improved median survival to 13.9 months, compared with only 11.6 months for placebo wafers (P = .03), in newly diagnosed patients with malignant glioma. Despite initial treatment, virtually all malignant gliomas recur. At relapse, patients may benefit from re-resection, focal radiotherapy techniques (such as radiosurgery), and different chemotherapeutic agents. Depending upon which chemotherapeutic agent was used at initial treatment, temozolomide, procarbazine, or a nitrosourea would be a reasonable conventional choice at recurrence. Clinical trials employing signal transduction inhibitors, epidermal growth factor receptor inhibitors, or antiangiogenic agents may also be available at tumor relapse.

In a recent article, the antimalarial drug chloroquine has been shown to increase mid-term survival when given in combination with conventional therapy (in this case, surgical ablation and carmustine therapy). Further research in this area needs to be done.

Another possible therapy technique is to use viruses to attack the cancer.A recent paper titled “Photodynamic therapy of high grade glioma – long term survival” by Stylli et al. reported on the treatment of glioblastoma multiforme with photodynamic therapy at Melbourne Royal Infirmary, Australia since 1986. Five year survival rates were over 30% with some patients surviving over 10 years.Yet another recent - but still experimental - therapy approach is the treatment using nanoparticles. These consist of an iron oxide core as well as a cover facilitating the infiltration of the particles into the cancer cells. The particles are injected directly into the tumour. The tumour enriched with the iron oxide particles is then repeatedly warmed via alternating magnetic fields to above 46 degree Celsius. In animal models, considerably improved survival terms arose however, at present there aren’t any results from sufficiency studies with men yet, but results are expected to be published later this year.

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Glioblastoma Multiforme (GBM), also known as grade 4 astrocytoma, is the most common and aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBM’s occur at only 2-3 cases per 100,000 people in Europe and

North America.

Treatment can involve chemotherapy, radiotherapy and surgery; all of which are acknowledged as palliative measures, meaning that they do not provide a cure. The five year survival rate of the disease has remained unchanged over the past 30 years, and stands at less than three percent. Even with complete surgical resection of the tumor, combined with the best available treatment, the survival rate for GBM remains very low.

CausesAlmost all cases of GBM are sporadic, without a familial predilection, although chromosomal aberrations such as PTEN mutation, MDM2 mutation, and p53 mutation are commonly seen in these tumors. Growth factor aberrant signaling associated with EGFR, and PDGF are also seen.

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Gamma Knife

Gamma Knife surgery represents one of the most advanced means available to manage brain tumors; arteriovenous malformations and pain or movement disorders. The procedure is unique because, with the Gamma Knife, no surgical incision is performed to expose the target.

The Gamma Knife can destroy deep-seated blood vessel malformations in the head and brain tumors once considered inoperable. It can also eliminate pain conditions and certain movement disorders, as well as silence malfunctioning areas of the brain precisely, to stop seizures or ease disabling pain problems that have not responded to other management strategies.

 

 

Cyber Knife

 

The role of radiation therapy for the treatment of tumors of the brain and spine has been well established.

The Cyber Knife, manufactured by Accuray, Inc. of

Sunnyvale, CA, is operational at UPMC Shadyside. This device is an image-guided stereotactic radiosurgery delivery system that does not require the application of a head frame for cranial radiosurgery. It also has the ability to deliver fractionated radiosurgical treatment plans for larger lesions and also provide radiosurgery for spinal lesions. UPMC has one of the largest experiences in the world in treating spine tumors with radiosurgery.

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Sometimes physicians describe their operations in terms that are very foreign to the patient. The following is a primer for patients and their families in neurosurgical procedures which will help them better understand the surgical options for brain tumors.

Craniotomy

This means to make a trap-door in their skull to expose its contents. An incision must be made in the scalp and the scalp is peeled back to expose the bone of the skull. One or several holes (about 1/2 inch in diameter) are made in the skull using a special saw. Then the plate of bone is removed, exposing the outer membrane covering the brain — or dura mater. The dura is cut and the surface of the brain is thus exposed. The operation to remove a brain tumor or perform some other task then proceeds. When this is completed, the dura is usually closed with sutures and the bone plate is replaced. This is held in place with wire or nylon sutures. The scalp is then closed.

Craniotomies are usually named for the part of the skull in which they take place: e.g. Frontal craniotomy, temporal craniotomy, etc.

Stereotactic Biopsy

Stereotactic (from Greek: Stereo-three dimensions; tactic-to probe) is a term to describe procedures done in precise and defined three dimensional space. These are ordinarily done with the patient’s head held in a rigid frame (called a stereotactic frame). The frame is used to direct a probe into the brain through a small hole in the skull. The figure at left shows an axial CT of a patient’s head in a stereotactic frame. The white dots outside the patient’s head are part of the internal calibration of the stereotactic frame.

Volumetric Stereotactic Procedures

Volumetric stereotaxis is a method for gathering, storing and reformatting imaging derived three dimensional volumetric information defining an intracranial lesion with respect to the surgical field. Most importantly, this information is displayed to the surgeon intraoperatively and scaled to the actual size and location of the surgical field. With this technique a surgeon can plan and simulate the surgical procedure beforehand, reach deep-seated or centrally located brain tumors employing the safest and lest invasive route possible.

Why is volumetric stereotaxis necessary?

Intracranial mass lesions are volumes in space. This is easily apparent on review of contiguous CT and MRI slice images of the lesion. However, translation of this three dimensional information from the imaging studies ( CT and MRI) to three dimensional surgical operating space within the patient’s head is difficult and imprecise during an open operation. A surgeon may have difficulty in knowing where tumor ends and normal brain begins; in spite of the fact that this information is usually clear on the imaging studies. Indeed, there may even be difficulty in finding some subcortical tumors.

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For patients undergoing brain tumor surgery, it is important to perform certain medical tests beforehand to provide the safest possible surgery. All patients should be in generally stable medical condition.  

Patients over the age of 40 should have an EKG and chest x-ray, as well as several other tests to evaluate factors such as blood pressure and diabetes. If the patient has uncontrolled hypertension or diabetes, their blood exhibits anticoagulation, or they have active coronary ischemia, surgery usually is not done. Surgery is used to diagnose and treat brain tumors. Complications occur in less than 5% of cases, and depend on the type of tumor andof cerebrospinal fluid.

Most types of surgery involve temporarily removing a section of the skull, opening the dura (outer membrane that covers the brain), and then removing the tumor and replacing the bone.

New surgical techniques include stereotactic biopsy or surgery that use computer guidance to exactly locate and either biopsy or remove the tumor, endoscopic surgery, laser surgery, and surgery under local anesthesia.

Stereotactic Surgery
The word stereotactic comes from Greek and Latin words meaning “three dimensions” and “to touch.” This technique utilizes CT scan and MRI scan of the brain to find the exact location of the tumor. A special frame is placed on the patient’s head and only a very small hole is drilled through the skull. Stereotactic surgery reduces the rates of complications normally associated with performing an open resection (cutting or removing a tumor) in the brain, which involves cutting a wide opening in the skull. With computer guidance, the neurosurgeon is able to operate very precisely.

Endoscopic Surgery
Endoscopic surgery is a type of surgery used to remove pituitary adenomas. In the past, pituitary adenomas were removed by making an incision in the mouth, beneath the upper lip, and then using a microscope to look up through the tissue to the base of the skull where the pituitary gland is located. With an endoscope, the tumor can be removed without any incision at all. Instead, the surgeon goes through the nose and is able to reach and remove a tumor in the pituitary gland through existing nasal channels. This procedure is less painful and has a quicker recovery time. Other tumors that are at the base of the skull can also be removed using endoscopic surgery.

Laser Surgery
The use of lasers (light amplification by stimulated emission of radiation) allows a surgeon to remove diseased tissue by aiming a beam of concentrated light on it rather than using a scalpel to cut it away. Laser surgery is often used following traditional surgery to remove any residual tumor tissue.

Surgery under Local Anesthesia
Surgery under local anesthesia involves the use of brain mapping techniques. A brain mapping technique that allow a surgeon to operate in sensitive areas of the brain, such as those that control motor function or speech. Small electrodes can be used to stimulate specific pathways so that the nerve response can be measured and a surgeon can determine the function of the nerve. The patient is awake during surgery.

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A diagnosis of a brain tumor is a big thing to deal with alone. Sometimes, talking to someone who has “been there” can help. These are suggestions from kids who have a brain tumor, and their brothers and sisters. They were sent to us by our friends at the Brain Tumor Foundation for Children. 

•       Live each day to the fullest.

•       Keep fighting. Never, never give up!

•       Bald is beautiful and trendy!

•       Live, love and above all laugh!

•       Keep a sense of humor.

•       Don’t ever give up!

•       Pray.

•       Keep thinking about tomorrow!

•       Be nice to your parents, they only want to help.

•       Tomorrow will be better.

•       Look forward to your last day of chemo, it will come.

•       Don’t think of yourself as a victim.

•       The less you complain the better you will feel.

•       Life is short, don’t miss out!

•       Don’t let cancer slow you down, you can do anything you want to do!

•       Keep a positive attitude. It makes a big difference in the way you will feel.

•       Remember it could always be worse!

When you are afraid, pretend you are floating on a big puffy cloud.

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Symptoms of brain and spinal cord tumors generally develop slowly and worsen over time unless they are treated. The tumor may be classified as benign or malignant and given a numbered score that reflects how malignant it is. This score can help doctors determine how to treat the tumor and predict the likely outcome, or prognosis, for the patient. 

 

What research is being done?

Researchers are studying brachytherapy (small radioactive pellets implanted directly into the tumor) and advanced drugs and techniques for chemotherapy and radiation therapy. In gene therapy for brain and spinal cord tumors, scientists insert a gene to make the tumor cells sensitive to certain drugs, to program the cells to self-destruct, or to instruct the cells to manufacture substances to slow their growth. Scientists are also investigating why some genes become cancer-causing. Since tumors are more sensitive to heat than normal tissue, research scientists are testing hyperthermia as a treatment by placing special heat-producing antennae into the tumor region after surgery. In immunotherapy, scientists are looking for ways to duplicate or enhance the body’s immune response to fight against brain and spinal cord cancer.

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Technology is evolving and helping to make the treatment of brain tumors more precise.

• Stereotactic localization. This technique utilizes a MRI scan to map a tumor’s exact location within the brain. Techniques using lasers and ultrasound also make removal of the tumor more precise, reducing the risk that cancer cells will be left behind and that healthy tissue will be harmed.

• Stereotactic radiosurgery. This treatment precisely focuses radiation beams to a tumor. No scalpels are involved. Gamma knife stereotactic radiosurgery delivers radiation beams in the exact size and shape of the tumor, with the aid of brain-imaging techniques.

• Drug-delivering implants. Researchers are also studying new ways to deliver cancer-fighting drugs to brain tumors. For instance, biodegradable wafers containing cancer-fighting drugs are being implanted in some tumors during surgery.

• Other approaches. Gene therapy, drugs that cut off a tumor’s blood supply and agents that may be able to interrupt tumor growth or to seek out and kill brain cancer cells are all under investigation.

Clinical trials

Many of the newer treatments for brain tumors are being tested in clinical research trials. If you have a brain tumor, particularly a malignant brain tumor, participating in a clinical trial can help you have access to the newest experimental treatments and take part in helping to define the role of these new treatments.

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