treatment options

Brain tumors can be treated in a number of ways also referred to as “protocol.” Talking with your medical team and learning all you can about your options, will help you make an informed decision.

Protocols

greybarThe ultimate goal is to find an effective and safe treatment that will best help the patient.

Any given brain tumor can be treated in a number of different ways. The best protocol depends upon the advice of the individual physician and what his/her associated institution is doing for that tumor at that time. Protocols vary. Patients placed on one mode of therapy are compared with the progress of patients treated with another mode of therapy.

What exactly is being compared? There are three things doctors look for:

TOXICITY

Toxicity from the treatment
(side effects and damage)

RECURRENCE

Time to recurrence
(how long it takes the tumor to come back)

LONGEVITY

Survival
(how long the patient lives on this treatment)

Many will also record quality of life measures such as the Karnofsky Performance Scale, a scale that allows patients to be classified according to their functional impairment.

This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses. The ultimate goal is to find an effective and safe treatment that will best help the patient.

There are four general therapeutic tools:

CHEMOTHERAPY
RADIOSURGERY
SURGERY
TARGETED THERAPY

Chemotherapy

Most chemotherapeutic agents are incorporated into and alkylate the DNA of rapidly dividing tumor cells. Alkylation is the process by which an alkyl group is added, which in turn disrupts the cell cycle – and so the growth of the tumor cells.

Chemotherapy drugs may be cell-cycle specific, acting only during certain cycles of the cell, or they may be non-cell-cycle specific, and so are effective at any point of the cell cycle. A combination of cell-cycle specific and non-cell-cycle specific may also be used to treat larger numbers of tumor cells.

Chemotherapy can be administered via pill, intravenous (IV) injection or a catheter or port, used to make injections easier.

Wafers soaked in a chemotherapeutic agent that are then placed in the surgical cavity produced after removing a tumor are also used in certain cases.

CELL-CYCLE SPECIFIC DRUGS

Hormones
Steroids
Etoposide (VP-16)
Hydroxyurea
Methotrexate (MTX)
Procarbozine
Temozolomide (Temodar)

NON CELL-CYCLE SPECIFIC DRUGS

Nitrosureas
Carmustine (BCNU)
Lomustine (CCNU)
Becacizumab (Avastin)
Cilengitide (EMD121974)
Cisplatin (CDDP)
Irinotecan (CPT-11)
Rapamycin
Vincristine

The Nitrosureas are unique chemotherapeutic agents in that they can cross the blood-brain barrier. Some chemotherapeutic agents also enhance the effect of radiation therapy.

A chemotherapy regimen usually consists of a specific number of cycles given over a set period of time. The patient may receive one drug – or combinations of different drugs – at the same time.

Brain MRIs are given every two or three months to monitor the patient while receiving chemotherapy. Gradually, the length of time between MRI scans increases depending on the tumor’s grade. If the tumor grows during treatment, other treatment options are considered.

Surgery

It is easier and safer to remove a small tumor than a large one.

greybarThe Foundation’s expertise, compassion and resources ensure that brain tumor patients have a powerful ally in their fight against this disease.

MRI scans are suggested every 3-6 months for the first year following surgery and every 1-2 years thereafter to be sure that there is no recurrence.

Important note: Checking for possible recurrence is excellent insurance toward your future health. If your tumor is destined to recur, it would be best to find out as soon as possible.

Surgery in the treatment of brain tumors has three goals:

  • To establish the tumor cell type and grade by providing a sample of the tumor to a pathologist.
  • To relieve internal compression: Removal of some of or all the tumor restores the contents of the skull to normal and lets the elevated intracranial pressure return to normal.
  • To reduce tumor burden: In other words, to reduce the number of tumor cells. In some tumors, such as Meningiomas located on the surface of the brain, some pineal region tumors and some benign tumors within the substance of the brain (usually in children and young adults) – surgery can totally remove all of the tumor, reduce the tumor burden to zero and most effectively treat the patient.

In other tumors, such as Gliomas, surgery can reduce the number of tumor cells, leaving fewer tumor cells to be treated by radiation and chemotherapy.

Surgical Methods

CRANIOTOMY

A procedure in which a “trapdoor” in the skull is opened. This allows the surgeon to find and remove a brain tumor. Typically, these operations are done under general anesthesia. In some cases craniotomies are done under local anesthesia when it is necessary to map important functional regions of the brain (such as speech) by stimulating its surface with an electric current in order to gauge the effects in a conscious patient.

In general the scalp incisions, bone openings and exposures of the brain in traditional craniotomy tend to be larger than necessary to ensure that the surgeon can actually find the brain tumor within the craniotomy opening. The incorporation of stereotactic methods into brain tumor surgery has significantly reduced the invasiveness of surgical procedures to biopsy and removal of brain tumors.

There are many brain tumors that comprise a solid tumor tissue mass (which can be removed surgically) surrounded by regions of brain tissue infiltrated by isolated tumor cells (which usually cannot be removed). In addition, sometimes potentially removable tumors involve structures that cannot be removed, such as vital arteries or veins. In many of these cases post-operative adjuvant therapy, radiation and/or chemotherapy are advised.

STEREOTACTIC PROCEDURES

Stereotactic surgery is a method for precisely localizing areas inside the head. Three-dimensional coordinates, calculated with respect to external reference points (points marked on the scalp and/or face and neck), are utilized to allow the surgeon to select a precise approach to tumors or lesions. This technique is used to biopsy and remove brain tumors.

STEREOTACTIC BIOPSY

In this procedure a probe is directed by means of an instrument called a stereotactic frame – frame to hold the head which uses x, y, z coordinates – to precisely locate an intracranial tumor. The position of the tumor within the patient’s head will have been determined by CT scanning and/or MRIs. Samples of the tumor are obtained by the probe. Several sites within the tumor can be sampled by this method.

COMPUTER ASSISTED VOLUMETRIC STEREOTAXIS

With this technique a surgeon can plan and simulate the surgical procedure beforehand, in order to reach deep-seated or centrally located brain tumors employing the safest and least invasive route possible.

This method is ideal for gathering, storing and re-formatting imaging from three-dimensional volumetric information. This defines the tumor or intracranial lesion with respect to the surgical field.

Volumetric Stereotaxis has major advantages for brain tumor patients, which include the smallest possible skin incision, craniotomy and brain incision – minimizing injury to normal brain tissue.

Secondly, since the surgeon knows exactly where the tumor ends and normal brain begins, a more complete tumor removal can be accomplished with much less risk to surrounding brain tissue.

Finally, the postoperative neurologic results are better than those associated with conventional (non-stereotactic, non-volumetric) surgical techniques.

There are multiple tumors that can be excised completely by surgical removal. These include Meningiomas, Acoustic Neurinomas, Craniopharyngiomas, Pilocytic Astrocytomas, some Oligodendrogliomas and Gangliogliomas, Colloid Cysts, Choroid Plexus Papillomas, Hemangioblastomas and some pineal region tumors such as Teratomas, Pinealocytomas.

The consistent feature with all of these tumors is the fact that they are all histologically circumscribed – meaning there is a clear microscopic interface where tumor cells stop and normal tissue begins.

There are many brain tumors that comprise a solid tumor tissue mass (which can be removed surgically) surrounded by regions of brain tissue infiltrated by isolated tumor cells (which usually cannot be removed). In addition, sometimes potentially removable tumors involve structures that cannot be removed, such as vital arteries or veins. In many of these cases postoperative adjuvant therapy, radiation and/or chemotherapy are advised.

Radiosurgery

Radiation Therapy damages the DNA in all cells. Normal cells can repair the damage quickly; tumor cells cannot. In order to minimize the dose of radiation given to the scalp and overlying brain tissue, the radiation beam is usually directed from several angles toward the brain tumor by a device called a linear accelerator (LINAC) .

Stereotactic Irradiation

Stereotactic techniques (a system of three-dimensional coordinates for locating the tumor) can be combined with standard radiation therapy by placing radiation sources directly into the tumor (Stereotactic Interstitial Irradiation) or by coupling a linear accelerator (LINAC) to a stereotactic frame.

In both these procedures the tumor volume is defined in three-dimensional space by stereotactic CT and MRI.

In stereotactic interstitial irradiation, multiple radioactive sources are placed within the tumor tissue. These sources generate a radiation dose field that has been pre-calculated to match atop the shape and size of the tumor volume.

This therapy is invasive and about 40% of patients may require an open operation to remove dead tissue (radiation necrosis).

In stereotactic external beam irradiation, the tumor volume is placed into the center of the radiation beam from the LINAC. This therapy can also be fractionated, meaning it is given in a series of daily treatments, usually over a six-week period. The only drawback with fractionated treatments is that a stereotactic frame would have to be fitted for each treatment. However, there are now some techniques for holding the patient’s head in place in a non-invasive manner.

OTHER STEREOTACTIC IRRADIATION THERAPIES

BNCT
(Boron Neutron Capture Therapy) is one of several experimental radiation methods presently being investigated. The patient is given a Boron compound which is taken up by tumor cells. The patient’s head is then positioned so neutrons can be absorbed into the Boron. This forms gamma irradiation and an alpha particle that kills the tumor cell.

The reason that boron neutron capture therapy (BNCT) is being used to treat brain tumors is that it provides a way to selectively destroy malignant cells and spare normal cells. It is based on the nuclear capture and fission reactions that occur when boron-10, a nonradioactive constituent of natural elemental boron, is irradiated.

This is still being studied in treatment of Glioblastomas and other brain tumors. BNCT is highly specific to destroying tumor cells and cell growth.

This is a proton therapy. The dose deposited by a proton beam increases gradually with increasing depth until close to the maximum proton range and then rises to a peak – the Bragg Peak.  A proton beam can be used so that the Bragg Peak occurs precisely within a volume of a 3-5 mm radius, a precision that can almost never be achieved with x-ray (photon) beams. The dose of radiation immediately beyond the Bragg Peak is essentially zero, which saves all normal tissue at the backend of the tumor volume.

Proton Therapy
Photon Therapy, such as Bragg Peak irradiation and Helium Ion irradiation are now being studied in the treatment of some brain tumors.

Because photon beams (regular radiation) carry a lower radiation charge and a much lower mass than proton beams, the energy of the photon beam is deposited in healthy tissue surrounding a tumor. This causes more side effects and unnecessary tissue damage – sometimes not even reaching the tumor with adequate doses of radiation.

However, protons carry a greater charge and have a greater mass than photons. The dose deposited by a proton beam increases gradually with increasing depth until close to the maximum proton range and then rises to a peak – the Bragg Peak.  A proton beam can be used so that the Bragg Peak occurs precisely within a volume of a 3-5 mm radius, a precision that can almost never be achieved with x-ray (photon) beams. The dose of radiation immediately beyond the Bragg Peak is essentially zero, which saves all normal tissue at the backend of the tumor volume.

Proton radiation contributes to quicker recovery times and minimal side effects, though some potential side effects include nausea, vomiting or diarrhea.

THE LEKSELL GAMMA UNIT (LGU)

The LGU – often referred to as Gamma Knife – was first used only for treatment of small benign tumors at the base of the skull, but its use has expanded to treat other types of tumors, such as metastatic tumors and small, high-grade Gliomas.

A modern Gamma Knife contains radioactive sources, known as 201 Cobalt-60. These are arranged in a spherical housing. The housing provides lead-lined receptacles for each radioactive source and a narrow opening where each beam of gamma irradiation escapes. These openings (collimators), direct the beam to the center where the beam will go through the spherical housing. Then a spherically shaped, inner-collimator helmet narrows the beams even further. The Leksell Gamma Unit (LGU) typically has four collimator helmets that differ only in the size of the opening in the collimator (4mm, 8mm, 12mm and 18mm).

LEKSELL GAMMA UNIT (LGU)

Leksell Gamma Unit

Treatment Planning
The preparation involved for Leksell Gamma Unit treatment is not as overwhelming as it may sound. Essentially, it is similar to being set up for an MRI – just more specific about the beam angles.

The patient’s head is fitted into a stereotactic frame that is used during CT and/or MRI database acquisition and during the actual radiosurgical procedure. The stereotactic CT or MRI database defines the tumor as a three-dimensional object in space.

Database Acquisition
The imaging data from the stereotactic CT and/or MRI is then transferred to a treatment planning computer system. Here the surgeon, the radiation oncologist and the radiation physicist simulate various dose plans using different collimator sizes and added “shots”.

A “shot” is one radiosurgical treatment – this produces an essentially spherical volume of radiation. However, few tumors are exactly spherical, and other “shots” may be necessary to treat different parts of the tumor. A computer adds up the radiation from all of these “shots”, and the result is a radiation dose field that should have the same shape as the tumor.

The computer then prints out the stereotactic coordinates for each “shot” (X, Y and Z) and the amount of time that the patient will be in the gamma knife to receive the prescribed radiation during each “shot”.

Radiosurgical Procedure
The rest is fairly straightforward. The patient, whose head is still in the stereotactic frame, is moved to the couch of the Gamma Knife. The X, Y and Z adjustments are made on the stereotactic frame. The appropriate collimator helmet is chosen in advance and fastened to the head of the couch. The patient’s head is then fixed to the inside of the collimator helmet. The radiation dose time is entered into the control unit of the Gamma Knife. Everyone (except the patient) leaves the Gamma Knife room, and a lead-lined door is closed. All the surgeon has to do now is push a button.

After the button is pushed, a series of events take place. The doors on the Gamma Knife unit open. The couch with collimator and patient are then moved automatically into the Gamma Knife. The collimator helmet locks into place, and a timer starts counting the seconds. When the prescribed amount of time for the radiation dose delivery has passed, the couch with collimator helmet and patient is automatically withdrawn and the doors to the Gamma Knife close.

Adjustments are then made for further “shots”. The patient is removed from the collimator helmet and new X, Y and Z adjustments are made on the stereotactic frame. Sometimes the collimator helmet is changed for another collimator helmet having apertures of different sizes. Once these tasks have been completed, the process described above begins again.

GAMMA KNIFE VS. LINAC

There is usually confusion about the “best” method for radiosurgery: Gamma Knife or LINAC. Radiosurgery with the Gamma Knife (LGU) is similar to radiosurgery delivered with a linear accelerator (LINAC).

Here are the nuances:

In LINAC radiosurgery, the linear accelerator head moves around its isocenter in a spherical arc. Here a patient’s head is also fixed in a stereotactic frame that is used to position the head so that the tumor is in the center of the intersecting beam arcs. In LINAC radiosurgery, the beam is constantly moving but there is only one beam that intersects itself from many different directions.

In the Gamma Knife there are many beams from fixed radiation sources that intersect in the center of the unit. In the LINAC, the radiation beam is produced electronically by a linear accelerator.

Patient Selection
Although the idea of non-invasive “surgery” may sound appealing, radiosurgery is appropriate for only a small percentage of brain tumors.

In general, appropriate tumors are relatively small (less than 3cm in diameter) and geometrically regular. This means that the tumor should be relatively spherical, ovoid or cylindrical. Tumors that are irregular in shape (i.e. star-shaped or crescent-shaped tumors) are not good candidates for radiosurgery because it is virtually impossible to fit a radiation dose volume to the tumor without also delivering a lethal dose of radiation to the surrounding brain tissue.

In addition, there is a tumor size limitation. Tumors larger than 1 inch in diameter are probably not appropriate for radiosurgery for two important reasons: First, tumors larger than this must be treated with two or more “shots”. This diffuses the radiation dose so that the surrounding brain gets radiated – not in a fractionated way but in a single session. This can potentially damage the surrounding brain tissue.

Radiation Necrosis
Another reason that large tumors are not good candidates for radiosurgery is that the risk of radiation necrosis increases with the size of the tumor irradiated. Radiosurgery turns a live tumor into a dead tumor (radiation necrosis). The dead tissue must then be carted away from the brain by an inflammatory reaction. The bigger the dead tissue mass, the greater the inflammation. This can make the patient sicker and dependent on high doses of steroids in an attempt to keep the swelling under control. This usually takes place between 6 and 18 months after the radiosurgical procedure. The most common neurologic symptom was dizziness.

It is important to understand that radiation necrosis can actually be asymptomatic, in which case it will only be diagnosed by changes in imaging.

Sometimes patients require open surgery to remove this mass of dead tissue because the mass of the dead tumor plus the mass of the surrounding edema (swelling) is causing an elevation of intracranial pressure and/or neurological deficit.

Radiation necrosis is regarded as the most relevant adverse event after Stereotactic Radiation Surgery.

Targeted Therapy

Targeted therapy, a relatively new form of cancer treatment, is used to identify and attack specific cancer calls that will result in less harm to normal tissue.

greybarThe goal of anti-angiogenesis therapies is to “starve” the tumor.

One type of targeted therapy already used is Anti-angiogenesis Therapy. Anti-angiogenesis Therapy is focused on stopping the process of making new blood vessels (angiogenesis).

Since tumors need the nutrients delivered by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to “starve” the tumor.

Bevacizumab (Avastin) is an anti-angiogenesis therapy used to treat Glioblastoma Multiforme when prior treatment has not worked. Avastin used in combination with Irinotecan (Campastor) has proven to be more effective since both medications can cross the blood-brain barrier. Researchers are still working to find new, better therapies that will bring a greater survival rate for patients with Glioblastomas (see Tumor Types Glioblastoma for more information on Novacure). There are treatments that are still in clinical trial (see Clinical Trials).

Recurrence
For most primary brain tumors, despite imaging tests showing that the tumor growth is controlled or there are no visible signs of a tumor, it is more common than not for a brain tumor to recur. This is why patients continue to be monitored and receive MRI scans.

Such uncertainty causes many people to worry that the tumor will come back. It is important to talk with your doctor about the possibility of the tumor returning. Understanding your risk of recurrence and the treatment options may help you feel more in control, calmer, and prepared if the tumor does return.

A recurrent brain tumor generally comes back near where it originally started. Rarely does it recur in another place.

Tests will be done to learn as much as possible about the recurrence, followed by a discussion with the doctor about further treatment options.

Often, the plan will include one or a number of different treatments which may be used in a different combination or given at a different pace.

People with recurrent cancer often experience emotions such as disbelief or fear. For most patients, a diagnosis of a recurrent brain tumor is very stressful and, at times, difficult to bear.

Patients and their families are encouraged to talk to their doctors, nurses, social workers, or other members of the health care team and to ask about support services to help them cope. It may also be helpful to talk with other patients in a support group.

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