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Whole Brain Radiation


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http://www.eurekalert.org/pub_releases/ ... 092208.php


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Whole brain radiation increases risk of learning and memory problems in cancer patients

Nearly half of patients experience impaired neurocognitive function, prompts possible change to standard practice

BOSTON - 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.

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(Eureka Alert, Source: University of Texas, MD Anderson Cancer Center in Houston, September 22, 2008)


The information contained in these articles may or may not be in agreement with my own opinions. They are not posted as medical advice of any kind.

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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.

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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.

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


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  • 3 weeks later...

I often thought about the problem of unintended self-interest bias which may be a factor in this problem.

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!

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