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, Cyber-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 may have been less "tumor recurrence" but not more "long-term survival".

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 to Patchell's studies 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. His studies convincingly showed there was 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. Patchell's standard for proving the value (improving overall survival) of whole brain radiation fell short of this criteria.

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.

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.

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.

And, 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/1-05-1.html

http://www2.mdanderson.org/depts/oncolog/pdfs-issues/05/oncolog1-05.pdf

http://www.cancer.gov/clinicaltrials/results/stereotactic-radiosurgery0806

*** Edited 4/7/2007 4:30:54 AM UTC by gdpawel***

Cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone, according to new research from The University of Texas M. D. Anderson Cancer Center.

The findings of the phase III randomized trial were presented at today's 50th annual meeting of the American Society for Therapeutic Radiology and Oncology.

Led by Eric L. Chang, M.D., associate professor in the Department of Radiation Oncology at M. D. Anderson, the study offers greater context to the ongoing debate among oncologists about how best to manage the treatment of cancer patients with one to three brain metastases.

The American Cancer Society estimates approximately 170,000 cancer patients will experience metastases to the brain from common primary cancers such as breast, colorectal, kidney and lung in 2008. More than 80,000 of those patients will have between one and three brain metastases.

Over the last decade, SRS, which uses high-doses of targeted x-rays, has gained acceptance as an initial treatment for tumors that have spread to the brain. SRS is also commonly used in combination with WBRT, radiation of the entire brain, to treat tumors that are visible and those that may not be detected by diagnostic imaging.

"Determining how to optimize outcomes with the smallest cost to the quality of life is a treatment decision every radiation oncologist faces," said Chang. "While both approaches are in practice and both are equally acceptable, data from this trial suggest that oncologists should offer SRS alone as the upfront, initial therapy for patients with up to three brain metastases."

The seven year study observed 58 patients presenting with one to three newly diagnosed brain metastases who were randomized to receive SRS followed by WBRT or SRS alone. Approximately four months after treatment, 49 percent of patients who received WBRT experienced a decline in learning and memory function compared to 23 percent in those patients who received SRS alone.

An independent data monitoring committee halted the trial after interim results showed the high statistical probability (96.4 percent) that patients randomized to SRS alone would continue to perform better.

M. D. Anderson researchers measured participants' neurocognitive function using a short battery of neuropsychological tests, with the primary endpoint being memory function as tested by the Hopkins Verbal Learning Test Revised. Patient performance that decreased more than a predefined criteria relative to their baseline were considered to exhibit a marked decline.

"This is a case where the risks of learning dysfunction outweigh the benefits of freedom from progression and tip the scales in favor of using SRS alone. Patients are spared from the side effects of whole brain radiation and we are able to preserve their memory and learning function to a higher degree" said Chang. "Here the research suggests patients who receive SRS as their initial treatment and then are monitored closely for any recurrence will fare better."

The study builds on previous research by senior author Christina A. Meyers, Ph.D., M. D. Anderson's chief of the Section Neuropsychology in the Department of Neuro-Oncology, examining neurocognitive function in patients with brain metastases treated with whole-brain radiation. "Unlike past studies comparing the two treatment strategies which did not use sensitive cognitive tests or closely follow patients after being treated with SRS, radiation oncologists in this trial were able to identify new lesions early and treat them with either radiosurgery, surgery, whole brain radiation or less commonly, chemotherapy," Meyers said. "We believe doctors and patients alike will favor this method over upfront whole brain radiation."

M. D. Anderson is a leader in the application of SRS to cancers of the spine and head and neck, as well as research determining the effects toxic cancer treatment, like radiation therapy, has on brain function. Based on these results, future research studies are planned to determine if there are expanded indications of using SRS alone for patients with more than three brain metastases.

In addition to Chang and Meyers, M. D. Anderson researchers contributing to the study include Jeffrey S. Wefel, Ph.D., Department of Neuro-Oncology; Kenneth R. Hess, Ph.D., Division of Quantitative Sciences; Fredrick F. Lang, M.D., Department of Neurosurgery and Pamela K. Allen, Ph.D., David Kornguth, M.D., Anita Mahajan, M.D., Moshe Maor, M.D., Christopher Pelloski, M.D. and Shiao Y. Woo, M.D., all of the Department of Radiation Oncology.

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For four of the past six years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report.

http://www.mdanderson.org

The University of California, San Diego Medical Center's Hyperbaric Medicine Center is part of a nationwide effort to compile and evaluate data in order to validate whether cancer patients being treated for radiation-related wounds heal more quickly and more thoroughly with hyperbaric oxygen therapy.

It's good to see a resurgence of research into this valuable technology. Until the new millenium, the only treatment for patients for radiation-induced necrosis was pentoxifyline or heparin therapy, and it was almost always unsuccessful. Both Duke University for Hyperbaric Oxygen Therapy and the University of Cincinnati previously had successful clinical trials on this science. The most common condition treated at some hyperbaric oxygen therapy centers is tissue injury caused by Whole Brain Radiation.

Wound healing requires oxygen delivery to the injured tissues. Radiation damaged tissue has lost blood supply and is oxygen deprived. Chronic radiation complications result from scarring and narrowing of the blood vessels within the area which has received the treatment. Hyperbaric oxygen therapy provides a better healing environment and leads to the growth of new blood vessels in a process called re-vascularization. It also fights infection by direct bacteriocidal effects. Using hyperbaric treatment protocols, most patients with chronic radiation injuries can be healed.

http://www.medicalnewstoday.com/articles/111502.php

For more information on UC San Diego's Hyperbaric Medicine Center:

http://health.ucsd.edu/specialties/hyperbaric

*** Edited 9/28/2008 1:52:49 PM UTC by gdpawel***

Some years back, the government had asked Joseph P. Newhouse, a health policy professor at Harvard, and his colleagues to look into how the Medicare reimbursement system may affect how doctors prescribe chemotherapy.

His study "Does Reimbursement Influence Chemotherapy Treatment For Cancer Patients?" co-authored with Dr. Craig C. Earle, was finally published in Health Affairs in 2006. This joint Michigan/Harvard study added to the 'smoking gun' survey by Dr. Neil Love, "Patterns of Care."

I wrote to both of them to ask if their study methodology on reimbursements influencing chemotherapy treatments, could be applied to reimbursements influencing radiation treatment?

Before the days and widespread use of Stereotatic, Gamma-Knife, Cyber-Knife, and the like, the most expensive treatment for postoperative brain surgery for a solitary brain metastasis was whole brain radiation. With the newer treatments, whole brain radiation was abandoned because of the substantial neurological deficits that resulted with its use, sometimes appearing a considerable time after treatment. Today, cutting-edge clinical practices use a more "focused" radiation field.

During the last twenty years when the preponderance of cancer care shifted from the institution-based, inpatient setting to community-based, ambulatory sites for treating the majority of the nation's cancer patients, many of these community-based settings did not have the cutting-edge high-tech toys.

Was there an incentive for radiation oncologists at community cancer centers to chose whole brain radiation treatments, as these were the most expensive, for them? Could Newhouse's methodology collect data documenting a clear association between reimbursement to radiation oncologists for whole brain radiation treatment which is based on how much incentive occurs to the radiation oncologist?

They thought that there were similar issues, but their methodology would be different because radiation isn't something that individual doctors buy, sometimes at a discount, and then profit from if they're reimbursed more for it, as in the case with chemotherapy.

They relied upon price variation across regions in Medicare, which was pseudo-random and had been eliminated. To their knowledge, there was no comparable price variation in radiology that they could have used.

However, they did mention a radiation oncologist in Michigan, who had done some work looking at the number of palliative fractions of radiation given to patients with advanced lung cancer as being a situation in which there is a lot of discretion on the part of the physicians: one fraction is as good as 10, but 10 will reimburse more. I'm not sure if he ever published or presented his results? Interesting!

*** Edited 10/18/2008 7:12:26 AM UTC by gdpawel***