Whole Brain Radiation and Solitary Brain Metastasis

The initial approach to using radiation postoperatively to treat brain metastases, used to be whole brain radiation, but this was abandoned because of the substantial neurological deficits that resulted, sometimes appearing a considerable time after treatment. Whole brain radiation was routinely administered to patients after craniotomy for excision of a cerebral metastasis in an attempt to destroy any residual cancer cells at the surgical site. However, the deleterious effects of whole brain radiation, such as dementia and other irreversible neurotoxicities, became evident.


This raised the question as to whether elective postoperative whole brain radiation should be administered to patients after excision of a solitary brain metastasis. Current clinical practice, at a number of leading cancer centers, use a more focused radiation field (Radiotherapy) that includes only 2-3cm beyond the periphery of the tumor site. This begins as soon as the surgical incision has healed.



Many metastatic brain lesions are now being treated with stereotactic radiosurgery. In fact, some feel radiosurgery is the treatment of choice for most brain metastases. There are a number of radiation treatments for therapy (Stereotatic, Gamma-Knife, Brachyradiation and IMRT to name a few). These treatments are focal and not diffuse. Unlike surgery, few lesions are inaccessible to radiosurgical treatment because of their location in the brain. Also, their generally small size and relative lack of invasion into adjacent brain tissue make brain metastases ideal candidates for radiosurgery. Multiple lesions may be treated as long as they are small.



The risk of neurotoxicity from whole brain radiation is not insignificant and this approach is not indicated in patients with a solitary brain metastasis. Observation or focal radiation is a better choice in solitary metastasis patients. Whole brain radiation can induce neurological deterioration, dementia or both. Those at increased risk for long-term radiation effects are adults over 50 years of age. However, whole brain radiation therapy has been recognized to cause considerable permanent side effects mainly in patients over 60 years of age. The side effects from whole brain radiation therapy affect up to 90% of patients in this age group. Focal radiation to the local tumor bed has been applied to patients to avoid these complications.



Aggressive treatment like surgical resection and focal radiation to the local tumor bed in patients with limited or no systemic disease can yield long-term survival. In such patients, delayed deleterious side effects of whole brain radiation therapy are particularly tragic. Within 6 months to 2 years patients can develop progressive dementia, ataxia and urinary incontinence, causing severe disability and in some, death. Delayed radiation injuries result in increased tissue pressure from edema, vascular injury leading to infarction, damage to endothelial cells and fibrinoid necrosis of small arteries and arterioles.



Even the studies performed by Dr. Roy Patchell, et al, in the early and late 90's have been recognized incorrectly, sometimes, in the radiation oncology profession. The studies were thought to have been the difference between surgical excision of brain tumor alone vs. surgical excision & whole brain radiation. It was a study of whole brain radiation of a brain tumor alone vs. whole brain radiation & surgical excision. The increased success had been the surgery. And they measured "tumor recurrence", not "long-term survival". Patients experiencing any survival could have been dying from radiation necrosis, starting within two years of whole brain radiation treatment and documented as "complications of cancer" not "complications of treatment". There was less "tumor recurrence" but not more "long-term survival". In my wife's case, tumors recurred.



Patchell's studies convincingly showed there was no survival benefit or prolonged independence in patients who received postoperative whole brain radiation therapy. The efficacy of postoperative radiotherapy after complete surgical resection had not been established. It never mentioned the incidence of dementia, alopecia, nausea, fatigue or any other numerous side effects associated with whole brain radiation. The most interesting part of this study were the patients who lived the longest. Patients in the observation group who avoided neurologic deaths had an improvement in survival, justifying the recommendation that whole brain radiation therapy is not indicated following surgical resection of a solitary brain metastasis.



An editorial by Drs. Arlan Pinzer Mintz and J. Gregory Cairncross (JAMA 1998;280:1527-1529) described the morbidity associated with whole brain radiation and emphasized the importance of individualized treatment decisions and quality-of-life outcomes. The morbidity associated with whole brain radiation does not indicate whole brain radiation therapy following surgical resection of a solitary brain metastasis. Patients who avoided the neurologic side effects of whole brain radiation had an improvement in survival. There is no survival benefit or prolonged independence in patients who received postoperative whole brain radiation therapy. There may have been some less tumor recurrence but not more long-term survival.



Had fatigue, memory loss and other adverse effects of whole brain radiation been considered, and had quality of life been measured, it might be less clear that whole brain radiation is the right choice for all patients. These patients do not remain functionally independent longer, nor do they live longer than those that have surgery alone, said researchers in a report in an issue of The Journal of the American Medical Association.



Sometimes, symptoms of brain damage appear many months or years after radiation therapy, a condition called late-delayed radiation damage (radiation necrosis or radiation encephalopathy). Radiation necrosis may result from the death of tumor cells and associated reaction in surrounding normal brain or may result from the necrosis of normal brain tissue surrounding the previously treated metastatic brain tumor. Such reactions tend to occur more frequently in larger lesions (either primary brain tumors or metastatic tumors). Radiation necrosis has been estimated to occur in 20% to 25% of patients treated for these tumors. Some studies say it can develop in at least 40% of patients irradiated for neoplasms following large volume or whole brain radiation and possibly 3% to 9% of patients irradiated focally for brain tumors that developed clinically detectable focal radiation necrosis. In the production of radiation necrosis, the dose and time over which it is given is important, however, the exact amounts that produce such damage cannot be stated.



Late effects of whole brain radiation can include abnormalities of cognition (thinking ability) as well as abnormalities of hormone production. The hypothalamus is the part of the brain that controls pituitary function. The pituitary makes hormones that control production of sex hormones, thyroid hormone, cortisol. Both the pituitary and the hypothalamus will be irradiated if whole brain radiation occurs. Damage to these structures can cause disturbances of personality, libido, thirst, appetite, sleep and other symptoms as well. Psychiatric symptoms can be a prominent part of the clinical picture presented when radiation necrosis occurs.



Again, whole brain radiation is the most damaging of all types of radiation treatments and causes the most severe side effects in the long run to patients. In the past, patients who were candidates for whole brain radiation were selected because they were thought to have limited survival times of less than 1-2 years and other technology did not exist. Today, many physicians question the use of whole brain radiation in most cases as one-session radiosurgery treatment can be repeated for original tumors or used for additional tumors with little or no side effects from radiation to healthy tissues. Increasingly, major studies and research have shown that the benefits of radiosurgery can be as effective as whole brain radiation without the side effects.



Even the Department of Neurosurgery at The University of Texas M.D. Anderson Cancer Center, from their OncoLog, admits that whole brain radiation may still be the standard for "four or more" brain tumors, however, there are a variety of effective treatment modalities for people who have fewer than four tumors, and in particular for a solitary brain metastasis. The metastasis that I write about is a "solitary" brain metastasis. In treating metastatic disease, the prime principle is to not make the treatment worse than the disease, thus good treatment becomes "finesse."