Radiation therapy is a common treatment for brain tumors where surgery or radiosurgery can not be utilized. Radiation therapy affects both normal and tumor cells, but normal cells are thought to be more capable of repairing themselves. As the therapy continues, the tumor cells should die and eventually shrink. Radiation therapy does not remove the tumor.
Radiation therapy can be utilized after surgery for highly malignant tumors, instead of surgery for inoperable tumors, or to take care of a residual tumor after surgery. Radiation therapy is not recommended for use in young children as it may cause a deficit in intellectual development that will be permanent.
Radiation therapy or fractionated radiotherapy is not recommended for acoustic neuromas. With the newer specialized radiation techniques, such as IMRT, the usage of radiation therapy is decreasing.
Side effects of radiation therapy will depend on the type of radiation received, the amount of the surface of the brain targeted, the site targeted, and the total dose of radiation. In general, there will be hair loss, skin irritation, possible hearing problems, nausea, vomiting, loss of appetite, and neurologic effects. The most prevalent side effect is fatigue which is may last through treatment and for many months afterwards. The neurologic effects most affecting quality of life are eventual permanent memory and speech problems. These are just a few of the problems that can develop.
Some specific indications for radiation therapy are discussed below.
Cancers arising outside the brain in such diverse organs as the lung or breast can travel through the blood vessels to grow in the brain. Tumors that have spread in this fashion are known as metastases. Metastases may be discovered before or after they cause symptoms; a CT scan or an MRI are the tests most frequently used to diagnose brain metastases. Brain metastases may develop at different times (early or late) in the course of the disease in different patients.
Whole brain irradiation is frequently prescribed for patients with brain metastases. This treatment uses radiation to treat the visible lumps of tumor and the presumed invisible tumor deposits that are so small they may not be seen on even a sensitive MRI scan. Therefore, large areas of the brain may be treated to stop the spread of the tumors.
Symptoms caused by tumors metastatic to the brain usually respond to whole brain radiation therapy; different studies have reported response rates of 50 to 70 percent.
The Radiation Therapy Oncology Group (RTOG) performed randomized studies that showed a course of 10 treatments over two weeks to give a total dose of 30 Gray (the same as 3000 centiGray or 3000 rads, to use older terms) was as good as more extended courses of radiation therapy that give higher doses. In some situations, a shorter or longer course of treatment than two weeks may be preferable. For patients who have a single brain metastasis that is removed surgically, whole brain radiation therapy was found in a randomized study to give great improvements in preventing cancer from regrowing in the brain and in prolonging survival.
Stereotactic radiosurgery can be combined with whole brain radiation therapy for brain metastases. The whole brain radiation therapy will treat the visible metastases and any presumed microscopic tumor deposits as well. This is possible because whole brain radiation therapy is given as a low dose to a larger volume and targeted to the tumor and the area of possible tumor spread, while stereotactic radiosurgery is a high dose given to a very small volume and targeted only within the tumor itself. The two treatment techniques can be thought of as complementary in achieving control of metastases to the brain.
Whole brain radiation therapy can cause shrinkage of visible brain metastases, sometimes making them more amenable to stereotactic radiosurgery or microsurgery. The addition of whole brain radiation therapy to stereotactic radiosurgery can decrease the possibility of additional metastatic lesions and decrease the chance that visible lesions treated with radiosurgery may have recurrences after radiosurgical treatment. Omission of whole brain radiation therapy for brain metastases is slightly controversial, but this is an area of ongoing intensive research.
Recently, some investigators have tried stereotactic radiosurgery alone without whole brain radiation therapy for selected patients with brain metastases to avoid causing the side effects of whole brain radiotherapy. Because whole brain radiation therapy can be given at a later date to these patients if their metastases are not controlled by the radiosurgery, this strategy may relieve symptoms effectively while not adversely affecting survival.
There is a widely accepted belief that for melanoma, kidney cancer and sarcomas that spread to the brain, stereotactic radiosurgery may be more effective at controlling the lesions than whole brain radiation therapy. The Eastern Cooperative Oncology Group (ECOG) is evaluating radiosurgery as a solitary treatment for patients with one to three brain metastases of these types of tumors.
Meningiomas are tumors arising from the meninges, one of the protective layers surrounding the brain and its cushioning cerebrospinal fluid. They are usually slow-growing tumors that do not spread to other places in the brain or elsewhere in the body.
It is generally acknowledged that an operation that completely removes a meningioma does not require radiation therapy afterwards to prevent regrowth. An operation in an area where it is difficult for the surgeon to completely remove the meningioma from the surface of the brain can leave tumor cells behind that can lead to tumor regrowth.
For meningiomas that are completely removed, approximately 20 percent will regrow in 10 years and 33 percent by 15 years's time. Up to one third of patients with meningiomas who undergo an operation will be left with obvious residual tumor. More than half of patients with residual tumor after an operation will have regrowth of the tumor by 10 years's time and about 10 percent will not have had regrowth by 15 years's time.
Patients with meningiomas that are unresectable because of the extent or location of the tumor may be offered radiation therapy to try to prevent its further growth. There have been no randomized controlled (phase III) trials evaluating the effectiveness of a course of irradiation in preventing meningiomas from recurring after an operation, but radiation therapy is recognized as helpful in this role. Various researchers have found the control rates for incompletely resected meningiomas treated with radiation therapy as being in the range of 75 to 90 percent at 10 years. A significant decrease in post-radiation recurrences occurred when radiation oncologists started using MRI and CT scans to plan the radiation therapy. It was then possible to avoid accidentally missing the meningiomas when administering treatment! The University of California San Francisco has reported that the five-year recurrence rate for incompletely resected meningiomas after radiotherapy in the modern era is only 2 percent.
There has been less of a role for radiation therapy in the management of pituitary tumors in recent years because of progress in multidisciplinary medical management of the benign tumors arising in this important endocrine organ.
Improved neurosurgical technology and microsurgical techniques have also led to less of a need for postoperative radiation therapy to prevent regrowth of incompletely removed tumors. High resolution MRI imaging and sensitive hormone analyses can help assess the completeness of resection of tumors. Medications can help suppress hormone hypersecretion from some pituitary adenomas.
Many patients who have pituitary tumors that cannot be completely removed with surgery are offered stereotactive radiosurgery to try to prevent recurrence or further growth of the tumor. This is sometimes not possible because of proximity of the optic nerves to the pituitary tumor and because treating the tumor with an effective dose of irradiation may cause damage to the optic nerves, resulting in a loss of vision. A five- to six-week course of external beam radiation therapy has been shown to be effective in preventing further growth of these tumors with a low risk of damage to vision and has even been shown to improve vision when unresectable tumor is pressing on the optic nerves.
There have been no randomized controlled (phase III) trials evaluating the effectiveness of radiation therapy to prevent regrowth of pituitary tumors and there have been no similar trials to comparatively evaluate stereotactic radiosurgery and external beam radiation therapy. Stereotactic radiosurgery with its precise targeting may offer a good alternative after surgery for these types of tumors. As with meningiomas, it is most common to use either radiosurgery or radiation therapy for a pituitary adenoma, reserving the other treatment technique for any failures to control the pituitary tumor.
Radiation therapy for pituitary tumors has been associated with delayed side effects. The normal pituitary gland can produce decreased hormone levels following a course of radiation therapy, resulting in the need for hormone supplementation. It has been argued that this results from the radiation being given to the hypothalamic region of the brain (just above the pituitary). Follow-up of patients currently being treated with stereotactic fractionated radiotherapy may help determine whether this technological advance decreases these late side effects by more precise irradiation of the pituitary gland. Long-term follow-up has shown that patients treated with radiation therapy for residual pituitary tumors have a slightly increased risk of developing second tumors a decade or more after their irradiation. More precise, modern irradiation techniques may decrease the incidence of second tumors.
Gliomas and Malignant Tumors
This group of tumors arises from the cells supporting the neurons in the brain. Some of these tumors initially present as low-grade, slowly -growing masses and can eventually progress to more aggressive, high-grade tumors. There are also tumors that are more aggressive and malignant at their outset.
This group includes astrocytoma and oligodendroglioma as well as tumors in which these cell types are combined oligoastrocytomas or mixed gliomas. More aggressive tumors have the word anaplastic in their descriptive name. The most aggressive type of glioma is called glioblastoma multiforme. Anaplastic gliomas and glioblastoma multiforme are termed malignant gliomas and represent approximately 40 percent of all brain tumors.
Malignant gliomas will spread from the site of origin to other areas in the brain but will almost never spread outside the brain. There is typically a gradient of infiltrating tumor cells that decreases as the distance from the margin increases. Most commonly, the tumor will recur at the same location that it started or immediately adjacent thereto. Radiation therapy treatment recommendations for malignant gliomas currently advise that several centimeters of apparently normal brain tissue around the tumor be treated to try to prevent these tumors from recurring at the edge of the area where the radiation is given.
A current study being run by the RTOG is using 3D conformal treatment and dose escalation to evaluate whether this promising technology can safely deliver higher doses of radiation to the tumor in patients who have had an operation for glioblastoma multiforme. Prior studies have not shown any benefit from higher doses of radiation than is conventionally given over six weeks's time, but it is hoped that modern technology may help limit the dose of radiation to normal brain tissue to a greater extent than was previously possible. If this can be safely done, one outcome may be improved survival from lower failure rates, but this remains to be proven.
Current trials are underway evaluating the role of chemotherapy in the treatment of malignant gliomas and low-grade gliomas. Oligodendrogliomas seem to be more responsive to chemotherapy than other gliomas. There have been promising initial results. New drugs active against gliomas will be found through these trials and physicians will learn how best to integrate them with surgery and radiation therapy.