GENERAL BACKGROUND
There are many types of tumors which can arise within the skull. These can arise from the brain, the cranial nerves (those nerves which work the eyes, the ears, the facial muscles, and the feelings of the face area), the coverings of the brain, the pituitary gland, and the blood vessels of the brain. The most common tumors arise from the glial cells within the brain, which are the fibrous tissues of the brain giving the brain its support. Forty percent of the malignant tumors of the brain arise from these structures. They can occur anywhere within the brain, but usually occur in the upper portions of the brain. These are the areas that control memory, motion, and speech.

Each year, there are about 15,000 to 17,000 new cases of primary brain tumor diagnosed in the United States. These tumors occur twice as often in Caucasians than in African-Americans. They occur about 50 percent more often in men than they do in women. Most of these tumors occur in patients over the age of 70. There is a small incidence of such tumors occurring in children between the ages of five and ten years.

There is no clear cause for brain tumors, but animal research has shown that certain factors may give rise to tumors of the central nervous system. These can include genetic factors, with such diseases as von Recklinghausen disease or von Hippel-Lindau disease; environmental factors, such as various chemical exposures; viruses; and actually radiation received as a fetus.

Primary brain tumors spread invasively within the skull because there are no natural fibrous capsules to stop their growth. They can present in many ways depending on the part of the brain in which they arise. The most common tumors -- the gliomas -- tend to arise in one side of the brain. Some will extend across the midline into the other side of the brain.

Local spread usually occurs along blood vessels and nerve pathways. These tumors tend to grow quite rapidly, especially the more malignant types of gliomas. Since the skull is a closed space, any swelling around the tumor makes the symptoms from the tumor worse than they would be otherwise.

The most common types of findings from tumors in the brain include seizure activity, headaches, confusion, a decrease in the ability to move an extremity (arm or leg), or difficulty speaking. Sometimes there is memory loss.

DIAGNOSIS | Back to Top
When there is a suspicion of a brain tumor, the patients are given an intense neurological examination by their physician. This assesses their mental condition, their coordination, their sensation throughout the body, their reflexes, their strength, and the nerves that work the face. Generally, a CT (computed tomography) scan or an MRI (magnetic resonance imaging) scan of the brain is performed. This gives specific information regarding the intracranial condition of the patient. Depending on the types of tumor found, the patient may also have a PET (positron emission tomography) scan, an electroencephalogram (a test measuring the electrical potentials throughout the brain), or a lumbar puncture (a spinal tap) to see if there are any unusual cells within the spinal fluid.

For the malignant gliomas, the strongest factors which determine how patients may do are age, the type of tumor, the status of the patient's performance, and the extent of any surgery which may need to be done. The older the patient, the worse the prognosis with regard to these tumors. Patients who have seizures many times have an earlier diagnosis, and, therefore, they might fare a little better with these diseases. The performance status of the patient is very important since it may indicate a smaller amount of tumor. A long duration of the patient's symptoms before the discovery of the tumor may indicate a slower-growing tumor and therefore a better chance of survival.

Gliomas are divided into relatively benign and malignant types. These are described as grades of tumor extending from Grade I to Grade IV. Grade I tumors are considered benign. Grade II tumors are considered to be low-grade tumors and make up about 15 to 20 percent of all the intracranial gliomas. The more malignant tumors are Grade III (anaplastic astrocytoma) and Grade IV (glioblastoma multiforme). The malignant tumors tend to be very aggressive and have a poor prognosis compared to the Grade II low-grade astrocytomas.

The amount of surgery which can be performed has a direct effect on the prognosis of the patients. Patients who can have a total resection or near total resection do much better in the long run than patients who have a partial resection or a biopsy only. In general, brain tumors are treated with surgical resection followed by radiation therapy, and in some cases chemotherapy is given. Even when it appears that a tumor cannot be totally removed, some type of surgical procedure, whether it be a biopsy or subtotal resection, tends to be done.

Detailed three-dimensional analysis of a CT scan or an MRI scan by the diagnostic neuroradiologist enables the neurosurgeon to perform a stereotactic biopsy through a small hole drilled in the skull. Debulking surgery is generally indicated when the tumor is in an accessible portion of the brain and is rather large. Postoperative radiation is frequently indicated after partial tumor resections. If there is a significant amount of swelling or edema causing pressure in the brain, then steroids are used to reduce that edema or pressure.

Steroids are also continued during the course of radiation to reduce any edema or irritation which may be caused by the radiation itself. It is important to never stop steroids abruptly. They should be gradually reduced a little bit at a time because they have the effect of shutting down the adrenal glands, and the adrenal glands do need time to recover from the effect of steroid medication.

Low-grade astrocytomas make up 15 to 20 percent of all intracranial gliomas. Seventy-five percent of these occur in the upper portions of the brain. These tumors can be cystic or solid in nature. Usually, the cystic lesions can be cured with surgery alone, while the more solid, less cystic lesions may in fact spread more through the brain and be more difficult to resect totally at the time of surgery. In the cystic tumors, the survival is directly related to the completeness of the resection. For the more diffuse tumors, the prognosis appears to be independent of exactly how much tumor can be resected.

There is quite a bit of controversy regarding the use of radiation therapy for the treatment of the low-grade astrocytomas; however, it is important to remember that only about one-third of astrocytomas can be totally resected surgically. In a study performed at the University of California in San Francisco regarding patients with low-grade gliomas, those patients who had postoperative radiation had a longer five-year recurrence-free survival (46 percent) than those patients who had the incomplete resection only (19 percent).

The ten-year survival rates were 35 percent for those with radiation and 11 percent for those who were not irradiated. In that study, also, by the time 20 years had passed all the patients who had not received radiation and had an incomplete resection of their tumor had died. Twenty-three percent of the patients who had received radiation were still alive and free of recurrent disease. In general, patients who have neurologic problems, evidence of a tumor progressing, or tumors which become more malignant undergo radiation therapy. There is a trend, however, among some practitioners to defer treatment in asymptomatic patients or those with seizures only.

The proponents of that approach argue that it is not certain whether early radiation has an advantage over delayed radiation or that radiation therapy has an impact at all on the natural history of low-grade glioma. However, one thing is clear: Postoperative radiation is not indicated when a complete or near-complete surgical excision has been performed in a pilocystic (cystic) astrocytoma. After a subtotal surgical removal, either immediate radiation therapy or close follow-up of treatment reserved for disease progression should be recommended.

The high-grade malignant astrocytomas represent 40 percent of all intracranial primary tumors. The overall five-year survival rate for these patients is less than 10 percent. These are divided into two grades, Grade III and IV, with Grade III tumors being described as anaplastic astrocytomas, and Grade IV tumors being described as glioblastoma multiforme. These tumors have the same neoplastic (malignant) features, except the glioblastomas also contain necrosis (dead areas) within the tumor. Unfortunately, these tumors are very aggressive, and it has been found that most of these patients cannot be cured with surgery and radiation. The median survival for anaplastic astrocytoma is 36 months, while that for glioblastoma multiforme is about 9 months.

There are three important prognostic factors in the patients with malignant gliomas. These are age, the extent of surgery, and the performance status of the patients. Younger patients (those less than 60 years of age) tend to have a better prognosis than older patients. Patients who have a good performance status (out of the hospital, taking care of themselves, and getting around reasonably normally) are also in a more favorable group.

There is some indication that a large tumor decompression will allow longer survival than patients who have a biopsy only. Approximately 30 years ago, the primary treatment for patients of malignant gliomas included treatment of the whole brain. With the introduction of the CAT (computerized tomography) scan in the mid 1970s and then the evolution of the MRI (magnetic resonance imaging) scan in the 1980s, localization of tumors within the brain became much more accurate. With this data more concise (smaller) radiation treatment fields were designed.

Despite the fact that autopsy studies have found tumors more than two centimeters away from the contrast enhancing regions of CT scans (supposed edges of the tumors), tumors tend to recur within the primary site as demonstrated on CT scans and MRIs. For that reason, localized treatment with high doses of radiation has become the primary mode of delivery for radiation after surgery in patients with malignant gliomas. Various dose-seeking studies have been performed, and six weeks of radiation was found to be the optimal treatment. This will increase the median survival of these malignant gliomas from approximately 27 weeks to 49 weeks and increases the one-year survival from 20 percent when radiation is not used to 45 percent when radiation is given.

Chemotherapy in Grade III astrocytomas (anaplastic astrocytomas) has been found to increase survival. A combination of CCNU, Procarbazine, and Vinblastine has been found to increase survival in these patients with approximately 25 percent having long-term survival. Unfortunately, the survival in patients who have Grade IV astrocytomas (glioblastoma multiforme) has not been enhanced by the use of BCNU chemotherapy.

There have been multiple studies which have demonstrated that BCNU has only a slight influence on survival, except in patients between the ages of 40 and 60 where the two-year survival rate in a Radiation Therapy Oncology Group study increased from eight percent without BCNU chemotherapy to 23 percent with BCNU chemotherapy.

Once the patient has surgery for his tumor and a diagnosis is made, a referral to the radiation oncologist is made. Generally, radiation therapy is not begun until two or three weeks after the completion of the surgical procedure so that adequate healing can take place and the patient can adequately recover from the surgery performed.

At that time, a complete history and physical examination will be performed by the radiation oncologist, and there will be a comprehensive discussion of the type of tumor, the findings, the results of the surgery, the type of radiation, the dose of radiation, the time involved, and the results to expect from therapy. It is a good idea for the family to come in with the patient at this time so all may discuss the various options and what to expect since this can be extremely different in each and every patient. Once the initial consultation and discussion have been performed, and the patient and family have decided therapy is to be pursued, a treatment simulation is scheduled. At the time of simulation, an immobilization mask will be manufactured.

The beams to be designed will be quite precise, and it is necessary for the patient to have the cranium in the same position every day so that the entire tumor is treated adequately and portions of the brain which do not need therapy are spared radiation. X-ray films will be made; then a CT scan will be performed with the immobilization device in place. The CT scan will be transferred to the treatment planning system and three-dimensional treatment planning, as well as possibly intensity modulated radiation therapy (IMRT) plans will be designed to offer the most precise dosage to the tumor with the maximum sparing of surrounding normal brain tissue. Initially, the tumor margins will be quite wide to cover the entire contrast-enhancing tumor as seen on the MRI, as well as the edema with the margin around that.

After approximately two-thirds of the length of the treatment, the radiation fields will be reduced to cover only the area of tumor plus a 2 cm margin. Generally, a dosage of 60 gray delivered in six weeks (30 fractions five days a week) will be utilized in the treatment of these tumors. Once the treatment has begun, it is given daily, Monday through Friday, until completion.

SIDE EFFECTS | Back to Top
During the course of treatment, the patient will not have any pain from the therapy. The patient will probably be on steroids due to swelling in the brain caused by these tumors, and the patient should continue on steroids during the course of the radiation due to the fact the radiation itself may cause swelling in the brain.

Most patients will not have any specific effects from the radiation on a daily basis. The only sensation from treatment is to hear the machine turn on and off. On about the twelfth or thirteenth treatment, the patient may notice there is beginning to be some mild hair loss and some redness on portions of the skull. By the fifteenth treatment, the patient will have lost a significant amount of hair.

At times this hair loss may be permanent. Some patients become quite nauseated and have vomiting, but they are in the vast minority; most patients do not experience nausea and vomiting. Some patients do become quite tired and sleep excessively. Families are advised not to be too concerned with this. Unfortunately, with glioblastomas about one-third of the tumors will grow despite the radiation, and at times it is necessary to stop the treatment because the tumors are progressing. Progression of tumor is made evident by worsening of the patient's symptoms.

In the patients who have long-term survival from radiation, a small percentage will have some death of brain tissue in the area of the surgical procedure and the targeted radiation volume. This is called "brain necrosis." These patients many times will have a return of the symptoms which were present at the time of the primary tumor resection. In the past, it has been difficult to determine whether such findings were secondary to an actual recurrence of the tumor or from death of brain tissue since both look the same on MRI and CT scan.

Today, PET (positron emission tomography) scan often times can tell us whether the patient has necrosis or tumor recurrence. Tumor necrosis is curable by a surgical drainage. Unfortunately, recurrent malignant gliomas are not cured.

During the course of the radiation treatment, the patient will be seen at least once a week by the attending radiation oncologist. The patient will be seen daily by the radiation therapist who delivers the treatment, and the therapist will be asking the patient or the family various questions regarding the patient's health. The patients can be seen by the doctor any time they are having problems. They or their family only need to let the radiation therapist know.

In summary, gliomas of the brain are serious diseases which have been shown to have better survival chances when surgery is followed by postoperative radiation. The most modern treatment methods are used at the Carolina Regional Cancer Center, including IMRT when it is indicated. The patient will be monitored at least weekly by the physician, and we are always open to questions regarding the treatment or the patient's situation.