Whole Brain Radiation Therapy

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 most leading cancer centers, use a more focused radiation field that includes only 2-3cm beyond the periphery of the tumor site. This may involve therapy once a day for about six weeks and allows radiation up to 60gy. This begins as soon as the surgical incision has healed.

My wife received postoperative whole brain radiation in addition to focal radiation to the local tumor bed for a large (3.5cm) solitary brain metastasis in the summer of 1998. Reactions to radiation may include fatigue, hair loss, scalp irritation and nausea. Long term side effects may include long term fatigue, memory loss, mental deterioration and hormonal deficiencies. The worst kind of side effect is radiation necrosis. This means that part (if radiation is focused) or most (if radiation is diffused) of the brain can die from the effects of radiation.

My wife began developing brain radiation necrosis within 6-10 months after whole brain radiation, confirmed by an "enhanced" MRI in June of 1999. Her twenty fractions of whole brain radiation resulted in diffuse necrotic effects. Because of previous platin-type drug treatment (carboplatin), it lowered her central nervous system's resistance to future radiation treatments and made side effects more pronounced.

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. The whole brain radiation treatment my wife received was not the proper treatment for her. In her case, tumors greater than 2cm in size should be excised and depending on the surgeon's success (his was 99%), focal radiation to the local tumor bed is indicated (a more focused radiation field that includes only 2-3 cm beyond the periphery of the tumor site). Her radiation oncologist's ideas were different from those of the neurosurgeon and gave her twenty fractions of whole brain radiation to a perfectly good brain. The radiation oncologist had not told us of any of the late-delayed reactions that could happen from whole brain radiation.

Professional liability in the field of radiation oncology may result from inadequate explanation to the patient of the intent, risks, side effects and expected results of radiation treatment. A patient must always be fully informed whenever risky protocols are followed. It is "vital" that the radiation oncologist coordinate the radiation treatments with surgeons so as to ensure that any treatments follow accepted protocol. This hadn't occurred! Inappropriate technique or dosage may subject a patient to increased risk of side effects and complications.

The radiation oncologist at our local home town hospital took it upon himself to give my wife 5 fractions (at 2.0gy per) of focal radiation to the local tumor bed, plus 20 fractions (at 2.0gy per) of whole brain radiation over a 35 day period. 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 (my wife was 66 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.

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 os 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.

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 (all symtoms my wife developed). 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 (my wife suffered a stroke to the left basal ganlia area of the brain, confirmed by an "enhanced" MRI). Other long-term effects can include loss of vision, development of secondary maligancies (the risk is 16 times greater) and endocrine disturbances. Late delayed radiation necrosis is often progressive and irreversible, leading to severe disability or death (a reaction that happened to my wife).

Even the study performed by Dr. Roy Patchell, et al, in the early 90's has been recognized incorrectly, sometimes, in the radiation oncology profession. The study was 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 (she had 16 times greater risk of developing secondary maligancies).

Patchell's study, conducted over an eight year period at numerous institutions was given to only 146 eligible patients. It convincingly showed there was no survival benefit or prolonged independence in patients who received postoperative whole brain radiation therapy. 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.

The diagnosis of radiation necrosis may be difficult to confirm. An MRI may show a contrast-enhancing mass with extensive white matter alterations and hyperintensity of the periventricular white matter. Cerebral cortical atrophy is manifest as enlarged cerebral sulci and ventricular dilatation. Many patients have a mixture of tumor and radiation necrosis and a biopsy may be necessary to distinguish it. Neither symptoms nor radiographic findings clearly distinguish radiation necrosis from tumor. The FDG-PET scan and T1-SPECT studies have been useful in differentiating radionecrosis from recurrent tumor.

An EEG, three enhanced MRI's (over a period of ten months) and a Pet Scan, all showed increased diffuse white-matter injury (radiation necrosis). Her additional twenty fractions of whole brain radiation resulted in diffuse necrotic effects.

The EEG showed generalized diffuse slowing that was significant with global encephalopathy. It is most commonly seen in toxic metabolic and degenerative conditions. There appeared to be a real amount of focal right sided slowing which would indicate cortical dysfunction on that side. The MRI's showed the ventricles overall were prominent and there was widening of the sulci consistent with cerebral atrophy (wasting away of brain cells and tissues). There was diffuse, abnormal signal intensity within the periventricular white matter, consistent with post radiation changes. The signal abnormality within the white matter appeared slightly increased compared to her prior studies. The Pet Scan showed globally decreased radiotracer uptake within the brain, bilaterally, consistent with involutional change and prior radiation therapy.

A recurrence of a cerebral metastasis was very likely to happen in the future. It was observed via an "enhanced" MRI and Pet Scan. Four, mm-sized tumors were found in and around the previously excised cerebeller tumor and because of my wife's weakened condition, Gamma-Knife would have been the best medical protocol. She received Gamma-Knife treatment. During the whole time of her admission at the hospital, the doctors kept referring to her continued diffuse white-matter injury (radiation necrosis or radiation encephalopathy), as if she may be too far advanced in that injury to survive much longer. She died at the age of 68 from cardio-pulmonary failure. Minutes before she expired, her temperature was normal, her blood pressure was nromal but her pulse was 150 (tachycardia). Her heart was racing to keep up with the lack of brain function and finally quit. The white matter disease she experienced and caused her death was "primarily" a result of whole brain radiation.

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.

The UCLA Metastatic Brain Tumor Program treats metastatic disease focally so as to spare normal brain tissue and function. Focal treatment allows retreatment of local and new recurrences (whole brain radiation is once and done, cannot be used again). UCLA is equipped with X-knife and Novalis to treat tumors of all sizes and shapes. For patients with a large number of small brain metastases (more than 5), they offer whole brain radiotherapy.

http://neurosurgery.ucla.edu/Programs/BrainTumor/Metastatic_

As reported in MD Anderson's OncoLog, in the past the only treatment for multiple metastases was whole brain radiation, which on its own had little effect on survival. There are now a variety of effective treatment modalities for people who have fewer than four tumors. Dr. Jeffrey Weinberg at the Department of Neurosurgery at MD Anderson has said "with a small, finite number of tumors, it may be better to treat the individual brain tumors themselves rather than the whole brain." Anderson is equipped with Linac Linear Accelerator. The critical idea is to focally treat all tumors.

http://www2.mdanderson.org/depts/oncolog/articles/05/1-jan/1

The results of a study at the University of Pittsburgh School of Medicine reported that treating four or more brain tumors in a single radiosurgery session resulted in improved survival compared to whole brain radiation therapy alone. Patients underwent Gamma-Knife radiosurgery and the results indicate that treating four or more brain tumors with radiosurgery is safe and effective and translates into a survival benefit for patients.

http://newsbureau.upmc.com/UPCI/GammaKnifeStudy2005.htm

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.

Of course, surgical excision is the gold standard of treatment for surgically accessible lesions. Many studies in the medical literature clearly demonstrate the efficacy and superiority of surgical resection followed by radiation over radiation therapy as a first-line treatment for metastatic brain tumors. Doctors at UCLA and MD Anderson say that even for patients with up to four metastases, surgical excision of all intracranial disease has been shown to provide the long survival with good quality of life, and has the same prognosis as someone who has only one brain tumor.

 

Dear Gdpawel:In 1986 my wife was diagnosed with a ventricular ependymoma,partially excised and then treated with brain and spine radiation.In 1986 she experienced a recurence and recieved chemo.Slowly she began to develop cognitive problems, and in 2001 hyprenuetermia. Her problems were monitored with MRI, and for years no major chnges were evident.Recently her sodium dropped to 114, but was slowly brought to normal levels in a Phoenix ICU(five Days).I expected her to return to her diminished but functional baseline as she had done in the past,but she immeadiately developed severe cognitive difficulties and vision loss.Doctors were unsure of the cause and prognosis and treated her with steroids before releasing her.At home she slowly stabilized but failed to reach hr previous baseline.A recent PET scan showed Alheimer like damage with much of the blue-green coloring which the Nuerologist tells me is progressive and irreversible damage.My question is why did my wife suffer this sudden fall off?What will happen now?No one can tell me anything other than take your wife home and give her salt pills.She is also taking Aricept,but after3 weeks I see no change.My wife is now a 46 year old woman who easily passes for 35.Her physical apperance belies the severity of her condition.If anyone is aware of a similar situation,and has treatment or prognosis information it would be appreciated.Your loss leaves me with great sorrow.We are judged not by how we are loved,but by how we love others.Comfort.

my mother-in-law has brain cancer and underwent brain radiation. The effects hit her fast and hard.  She can't eat, sleep, has no idea what day or time it is, doesn't recognize her own family, has visions of things.  It's very sad to see her like this and to know she won't get better from this.  If the doctors would have said there was a possibility of 1% chance of any of this, then she would have never gone thru this.  It's a shame that we trust doctors, and they misguide you.   

Hello,

My father underwent whole brain radiation as a precautionary measure that his brain tumor would not reoccur. During his treatment he started talking confused, and had uncontrollable urinatiing, so I attended a visit with his onocologist and asked him could this be side-effects from the radiation. He sat 2 feet away from me and assurred me it was not, he told me that iwas his blood sugar and steriods that were causing this.My father went through 20 treatments onw he lays in a hospital bed in his living room.My husband,kids,and I went to visit yesterday he doesn't talk, he cannot feed himself, he cannot use a bedpan, he just lays their and looks at you like he wants ot say something. My father now is cancer free and in this state.I wish I would have been more informed, my dad is 68 and the kindest man you could ever meet, and I miss him.

Brenda