RADIATION THERAPY

Background

The term “radiation therapy” actually connotes a variety of treatments that utilize subatomic particles or the radiation that these particles release to treat cancer. The concept of using radiation to treat cancers goes back to the discovery of X-rays in the 19th century. However, its development rapidly advanced after World War II, when the interest in nuclear energy in general, stimulated by the Manhattan Project and the development of the atomic bomb, led to intensive research on the effects of radiation on cells.

Radiation therapy comes in a variety of forms, and it can kill cancer cells by a variety of mechanisms. A detailed discussion of these various types of radiation therapy is beyond the scope of this chapter. However, for patients with primary brain tumors, there are a few forms of radiotherapy that are commonly used, and in this chapter, we will focus on these.

External beam, fractionated radiotherapy

This form of therapy uses high-energy radiation, which is administered from a source that is located outside of the body (“external beam”) to damage the DNA of tumor cells. Tumor cells in general are not as efficient as normal cells in repairing the damage that this form of radiation inflicts. Thus, giving this form of radiation in small doses spaced out over time (“fractionation”) allows the normal cells to recover from whatever damage is produced, while tumor cells are not able to recover. Furthermore, the fact that most of the normal cells in the brain are not actively dividing protects them further from the damaging effects of radiation. Typically, primary brain tumors are treated with a course of external beam radiation that is given in approximately 30 treatments (“fractions”), with one fraction given per day, 5 days per week, for approximately 6 weeks of treatment. A significant amount of work is required to determine exactly how this radiation is to be administered in each patient’s case, and this radiation planning can take up to one week before treatment can begin. Once treatment does begin, it is important to continue with it until it is concluded, without major interruptions, since this would give the tumor cells a chance to recover from the damage produced by the radiation.

Given that primary brain tumors invade normal brain, it is important to be sure that regions of brain that contain microscopic amounts of invasive tumor cells are treated with radiation.This means that some normal brain surrounding the tumor needs to be treated. Minimizing this treatment of normal brain has been a goal of investigators in the field for some time. Over the last decade, there have been significant technical advances that have involved combining state-of-the-art imaging technology (mostly with CT scans) with external beam radiation therapy. These advances now allow more sparing of normal tissue, which should reduce radiation therapy-related side effects (see below).These techniques are referred to as “conformal therapy” since they allow the radiation to better “conform” to the region of brain that has the tumor. They include “intensity modulated radiotherapy” (IMRT) and CT tomotherapy. You should ask your radiation therapist if these methodologies are available and can be used in your treatment.

Other forms of radiation therapy

Brachytherapy: This involves the placement of a source of radioactivity directly into the tumor to deliver a high local dose of treatment. Brachytherapy was extensively used in the past for treatment of high grade gliomas, but generally has fallen out of favor. This is because it also significantly damages normal brain, and can produce a significant amount of neurologic disability from this side effect. More recently, brachytherapy has been re-explored with new technologies that might be safer for normal brain tissue. One of these is an inflatable balloon which is filled with radioactive material (“Gliasite”) and which is inserted into the cavity that the neurosurgeon creates after removing tumor.

Gamma knife, stereotactic radiosurgery: Both gamma knife and stereotactic radiosurgery use the same principle—multiple beams of radiation are administered that converge on a defined volume within the brain. The dose of each individual beam is very small, so any normal brain outside of this volume that gets radiated receives a trivial dose of radiation. However, any tissue within the defined volume receives a very high dose—high enough to effectively kill any tissue within this volume. This type of therapy is highly effective for treating metastatic brain tumors, since these tumors do not invade brain, but rather tend to push normal brain aside. Hence, if the defined volume is limited to the metastatic tumor, this type of treatment will effectively destroy the cancer while leaving the surrounding brain unaffected. However, primary brain tumors invade normal brain, and it is therefore impossible to treat such tumors with gamma knife or stereotactic radiosurgery effectively without also killing a significant amount of normal brain. This means that gamma knife or stereotactic radiosurgery is generally not appropriate for high-grade gliomas and similar primary brain tumors.

Proton beam: This form of therapy involves radiating the affected tissue with a beam of protons, which are subatomic particles. The technology for generating proton beams is complex, expensive, and not widely available. However, proton beam has several advantages over other more conventional forms of radiation therapy. First, proton beams can kill tumor cells by multiple mechanisms that do not apply to external beam fractionated radiotherapy, which may enhance the effictiveness of this therapy. In particular, proton beams can kill tumor cells which are relatively deprived of oxygen (“hypoxic”). Hypoxic tumor is typically resistant to external beam radiation therapy. In addition, it is possible to control how much volume of tissue receives the proton beam in a way that is not possible with external beam radiation, and this may reduce the toxicity to normal surrounding brain. As noted above, proton beams are not widely available. However, if you are interested in finding out more about this possibility, you should ask your radiation therapist. It should be noted that some of the recent technical advances in external beam radiation, including CT tomotherapy, are approaching proton beams in terms of their ability to spare normal brain, and you should expect these technical advances to continue to become available.

Radiation Therapy Side Effects

Local and short-term side effects:

Skin irritation: Radiation therapy to the head can produce side effects to the skin that resemble those from excessive sun exposure. Scalp redness, drying, and itching are common, and can respond to local ointments. Be sure to ask your radiation therapist which treatments are recommended and which ones should be avoided.

Hair loss: The hair follicles are particularly sensitive to radiation therapy, and loss of hair over the treated area is nearly universal. Hair regrowth will frequently occur, but can take a year or longer to do so, and regrown hair may be gray or white. Some things you can consider include the following:

• Do not over shampoo your hair.
  
  
• Use a mild shampoo, such as a baby shampoo.
  
  
• Do not use hot rollers, curling irons, hair sprays or dyes.
  
  
• Consider purchasing a wig, scarves, or caps. Hair-pieces and wigs might be tax-deductible or covered by insurance.
  
  
• If your wig is covered by insurance, get a prescription for a wig from the physician.

Dry mouth, altered taste: Some radiation is invariably administered to the salivary glands and to the tongue and palate. The former can produce mouth dryness, while the latter will alter your ability to taste food. Many patients complain that food has a “metallic” taste. Both of these effects are temporary and will improve over the 3-6 months following the radiation. Things to keep in mind include the following:

• Drink plenty of water.
  
  
• Suck on sugar-free hard candy or ice pops, or chew sugar-free gum.
  
  
• Rinse with a mouthwash recommended by the doctor.
  
  
• Serve foods with sauces, gravies, and salad dressings to make them moist and easier to swallow.
  
  
• Drink liquids with meals
  
  
• Thrush – superficial yeast infection of the mouth and throat. If you notice a white coating or have problems swallowing call your doctor. Treatment is easy and effective. Using Biotene or similar mouthwash and good oral hygiene may help prevent this in the first place.

Fatigue: This typically becomes apparent after 3-4 weeks of treatment. Many patients find that they need to take a nap during the middle of the day. This side effect is the major reason we recommend that patients take a leave of absence from work at least during the course of radiation treatment. Fatigue typically improves by about three months after the end of radiation therapy. However, for those who choose to work through their treatment or who do not completely recover from this symptom, there are medications that can be prescribed that are very effective in helping with this symptom.

Long-term side effects:

These problems tend not to become apparent until at least one year after treatment. They include the following:

Hormonal problems, including early menopause, loss of libido, and hypothyroidism: When the tissue radiated includes the base of the brain, some radiation will be unavoidably administered to the hypothalamus. This region of the brain controls the release of a variety of hormones that are important for normal functioning. Some of these hormones are needed for normal reproductive and sexual functioning, and their loss can lead to premature menopause in women and loss of sex drive in men and women. Some of these problems can be addressed with hormone replacement or other medication, and you should check with your neuro-oncologist or primary care physician if you are concerned. Loss of thyroid function can lead to fatigue, weight gain, as well as other problems. We routinely check thyroid function in our patients periodically to check for this, since low thyroid can be easily and effectively treated.

Intellectual problems, including memory loss: When portions of the brain that control memory receive radiation therapy, the result can be a slow decline in memory and intellectual function. This has provided the major impetus to find newer forms of radiation administration, such as conformal therapies, that spare as much normal brain tissue as possible (see above). This problem has become less severe as these methodologies have become generally available. How much of a problem this will be for any individual patient will depend on the location of the tumor and on how much radiation will be given. You should discuss this concern with your radiation therapist at the onset of your treatment. Neuropsychological testing can be useful in identifying specific problematic areas (language, reasoning, memory, spatial skills, etc.) and can be used in conjunction with cognitive, speech, or vocational therapy to develop a plan to address these problems. Medications have also been used with varying degrees of success in the treatment of radiation-related memory problems, and you should ask your neuro-oncologist or radiation therapist about these. You should also remember that a number of medical and emotional problems, including low thyroid, uncontrolled diabetes, and depression can produce difficulty with memory and intellectual function, and these need to be evaluated and treated if they are present.

Secondary tumors: It has been known for some time that radiation to the head can lead to the formation of several types of tumors.The most common of these are acoustic neuromas and meningiomas, and both are generally treatable with surgery and/or gamma knife radiotherapy. The risk of this is still relatively low, and should not be used as a reason to avoid radiation therapy for treatment if you have a high-grade glioma.