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Whole Brain Radiation Therapy

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

Traditional external beam radiation therapy for cancer is very imprecise in its targeting, resulting in sometimes severe side effects due to the volume of healthy tissue radiated. Metastatic disease has historically not been treated very well with radiation, due to lack of efficacy and side effects. Observation, with radiation delayed until evidence of progression, or focal radiation (SRS) is a better choice in solitary metastasis patients.

Studies performed by Patchell, et al in the early and late 90's measured tumor recurrence and not long-term survival. His studies 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 his studies 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 or SRS of a solitary brain metastasis.

Editiorials to the studies describe the morbidity associated with whole brain radiation and emphasized the importance of individualized treatment decisions and quality-of-life outcomes. Patients do not remain functionally independent longer, nor do they live longer than those that have surgery or SRS alone.

Even MD Anderson notes in their OncoLog 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.

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.

http://www2.mdanderson.org/depts/oncolog/articles/05/1-jan/1-05-1.html
http://www2.mdanderson.org/depts/oncolog/pdfs-issues/05/oncolog1-05.pdf
http://www.cancer.gov/clinicaltrials/results/stereotactic-radiosurgery0806

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

"Study Suggests Underlying Cause of Dementia after Cancer Treatment"

Researchers at Wake Forest University School of Medicine have identified changes in brain chemistry that may be associated with the dementia that many cancer patients develop after whole-brain radiation treatment.

"By identifying exactly how radiation causes these side effects, our hope is that we can find a way to prevent or reverse them," said Lei Shi, MD, PhD, lead author and a research fellow. Whole-brain radiation is widely used to treat recurrent brain tumors as well as to prevent breast cancer, lung cancer and malignant melanoma from spreading to the brain.

About 200,000 people receive the treatments annually. Starting at about a year post-treatment, up to one-half develop progressive memory problems. Researchers don't know precisely how radiation injures the brain, but suspect it causes changes in the brain's communication system. To test this theory, Shi and colleagues evaluated rats that had been treated with radiation and developed learning and memory impairments.

Today, at the annual meeting of the Radiation Research Society in Philadelphia, the researchers said they found changes in brain receptors for glutamate – a neurotransmitter, or molecule that carries signals between nerve cells. They said the receptors change in composition as a result of whole-brain irradiation and that the changes seem to be associated with cognitive deficits.

These findings are significant because they may lay the groundwork for developing new therapies to prevent or reverse these potentially devastating impairments induced by whole-brain irradiation. "There is a growing concern about the cognitive consequences of whole-brain radiation," said Judy Brunso-Bechtold, PhD, a professor of neurobiology and anatomy and senior researcher.

"Our findings suggest that very subtle changes may be critical and that glutamate receptors may be one of those changes." The researchers focused on middle-age rats because middle-age adults are most prone to the cancers that require whole-brain irradiation treatment.

Half of the rats received doses of whole-brain radiation similar to what humans receive. The other half received "sham" treatments that involved no radiation. One year later, researchers tested the rats' learning and memory using a water maze. The rats that had received radiation performed significantly worse than the untreated animals.

Additional experiments were conducted to determine if these deficits were associated with cell-to-cell communication in the hippocampus, a region of the brain associated with learning and memory. The scientists specifically looked at glutamate receptors that lie on cell membranes. There are several different subtypes of the receptors that differ in the types of brain chemicals that most readily bind to them.

They found that the composition of these subtypes was different in the animals receiving whole-brain irradiation. "This shift in composition could impair synaptic communication and lead to the spatial learning and memory deficits measured in the treated rats," said Shi. Next, the researchers will see if the chemical changes also extend to the synapses themselves.

They also want to focus on why some animals – and people – experience cognitive deficits while others don't. Eventually, they hope to test drug therapies that may prevent the effects. Shi received the 2006 Marie Curie Award from the Radiation Research Society for the research. The research is supported by a recently funded grant from the National Institutes of Health and is part of a broad collaboration among researchers led by Michael Robbins, PhD, in the Department of Radiation Oncology.

Other co-researchers were Michelle Adams, PhD, Michelle Nicolle, PhD, William Sonntag, PhD, and Kenneth Wheeler, PhD, all from Wake Forest.

SOURCE: Wake Forest University Baptist Medical Center

November 2006

bluerose's picture
bluerose
Posts: 1089
Joined: Jul 2009

I had a bone marrow transplant back in 1991 and had total body radiation too with killer chemo. I have had no end of side effects, some serioius and many debillitating including a damaged heart from the chemo drug adriamycin (have a pacemaker now), early osteoarthritis, bronchial chronic infections, blah blah blah blah blah. Recently they found a cyst and node on my right ovary and in Canada where I live the waits are long for OR's and it has been a long wait for a biopsy. I have had memory and cognitive issues for years now and have to make notes or script talks to doctors or others if the thoughts are many, can't put them together, the thoughts I mean. On paper I do better but verbally forget about it if there are too many ideas etc. It's frustrating and frightening really and many look at this in a very negative way thinking you are stupid or something even when you explain. When I talked to a neurosurgeon at a memory clinic I went to the neurosurgeon said other things cause these things in cancer patients too though and they include stress and memory and cognitive issues that come from pain.

I had a bit of a problem following some of your post as it is so medically stated and I am kind of slow anywho, lol, but I was wondering if radiation of the head in a total body radiation situation would produce the same kind of mental issues? I dont know if radiation solely to the head would be more destructive or not? I guess there are different rad protocols for different tumours and stages of cancer that could dictate but just wondered. They are doing a CT of my head as part of a memory clinic testing program I went through recently. Some of the drugs I had did break the blood brain barrier the neurosurgeon said.

would be interested in your ideas. Thanks Bluerose

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

There are a number of theories as to why chemobrain may occur. One is that some types of chemotherapy can cross the blood/brain barrier. Another is that the cognitive problems are created by free radicals, the toxic elements that many types of chemotherapy produce. And yet another is that some people have a genetic (epigenetic) background that makes them more susceptible to the effects of chemotherapy. Most likely it is not just one factor but many factors that combine to set the stage for chemobrain to occur.

According to studies by Dartmouth-Hitchcock Medical Center, even standard-dose chemotherapy can negatively impact the cognitive functioning of cancer survivors up to 10 years after treatment. Reports of depression, anxiety, and fatigue, all of which can affect cognitive functioning, suggests that the differences in performance on cognitive tests were due to the chemotherapy itself, not to greater levels of depression, anxiety, and fatigue in patients who received chemotherapy.

Leukoencephalopathy syndrome is a disorder that results from structural alterations of cerebral white matter, is characterized by cerebral edema, and can occur in patients of any age. It is the destruction of the myelin sheaths which cover nerve fibers. These sheaths, composed of lipoprotein layers, promote the transmission of a neural impulse along an axon.

Certain chemotherapy agents, especially those used in high-dose protocols, are causal agents. Because this syndrome alters neurobehavioral function, patients may present in a confused state, which can progress quickly to irreversible dementia, coma, or death, depending on its severity.

Necrotizing Leukoencephalopathy is a form of diffuse white matter injury that can follow chemotherapy. The chemotherapy drugs that most likely cause it are the vinca alkaloids (vincristine, vindesine and vinblastine), platin drugs (cisplatin, carboplatin), and the taxanes (taxol, taxotere). These drugs have the potential of interfering with nerve function.

Filley & Kleinschmidt-DeMasters, 2001
Journal of Clinical Oncology, January 15, 2002
Cossaart, SantaCruz, Preston, Johnson, & Skikne, 2003

corina.verdon
Posts: 1
Joined: Jul 2011

Hi sir my father had undergone a 10 sessions of radiation therapy that ended March 2, 2011 after a metastatic brain surgery. He is experiencing neurological deficit such as speech (he can no longer talk) memory loss and cant even move. How come doctors did not explain to us the possibility of such radiation side effects? Is the condition of my dad still reversible?

angelatg
Posts: 4
Joined: Aug 2012

My mother took WBRT for eight weeks in 1990 after successful removal of a brain tumor, medullablastoma.  The surgery and radiation has kept my mother alive but the radiation has left her with many deficits.  My mother is now almost 65 years old with advanced dementia.  She requires full time care for her safety.  I also had wondered if there was other people who have experienced dementia and other cognitive impairments from WBRT.  My prayers are with anyone who has to take WBRT.  The side effects have been a heart wrenching process for our family. 

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