WBR Increases Risk Of Learning And Memory Problems In Cancer Patients With Brain Mets

[gdpawel]

Whole Brain Radiation Increases Risk Of Learning And Memory Problems In Cancer Patients With Brain Metastases

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

New Perspectives on Brain Metastasis

http://cancerfocus.org/forum/showthread.php?t=526

[gdpawel]

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.

[hutchibk]

This is already pretty well documented and understood here on our site. We have been aware of longterm cognitive effects of WBR for years...

That's precisely why we fight to be monitored more regularly with MRIs, so that we can be dx'ed when smaller and less lesions/tumors can potentially be found as early as possible - giving us more treatment options than WBR. But for some who are members here, WBR is the only option, and we need to support them in that decision when it is necessary. It's definitely a risk vs benefit decision, and it is not always an easy decision to move forward with WBR.

Please tell what are the dates on these two referenced studies?

[pattyz]

Brenda,

Don't think you'll get a reply from this man...

His wife died after WBR, many yrs ago now. He has made it his mission to 'inform' people of what he believes killed her in the end, by dropping long documents in many sites and forums.

It is good you posted as it will give another point of view to the issue for any one who happens by/reads/has concerns.


xoxo
patty

[gdpawel]

This is but another study about whole brain radiation. This was presented again by MD Anderson at the 50th annual meeting of the ASTRO on September 23rd. Anderson had presented information, "New Perspectives on Brain Metastasis" on their OncoLog.

http://www2.mdanderson.org/depts/onc...ncolog1-05.pdf

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.

Editorials to Patchell's studies by Drs. Arlan Pinzer Mintz and J. Gregory Cairncross (JAMA 1998;280:1527-1529).

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. For more information on UC San Diego's Hyperbaric Medicine Center: http://health.ucsd.edu/specialties/hyperbaric

[gdpawel]

Yes pattyz, the only way to make sense of losing the love of your life is to turn the tragedy into anothers hope. I was introduced to this disease unwittingly twelve years ago. I was a spouse/caregiver to a cancer patient and became intensely interested in it by virtue of working through, enduring and surviving my wife's illness. With the discipline of a college education, the experience helped me to gather knowledge by virtue of voluminous reading and hundreds of hours of past and ongoing personal communication with noted authorities and experts in the field.

[pattyz]

Please don't misunderstand Mr. Pawel.

Long ago, when I saw your information on the brain tumor site, it helped bolster my own decision to refuse WBR.

It's been six yrs since the first of five focalized tx's for my brain mets.

And currently (well for three yrs) have been on Xeloda/Temodar to deal with the 6-8 brain mets that live with me.

I've seen your history with your wife, and have been moved. You are a passionate man, who adored his woman.

best wishes to you,
pattyz

[gdpawel]

I sincerely appreciate your clarification pattyz. Your five "focalized" treatments for brain mets is a testament to your strength and perseverance. The reason for what seems like my information is everywhere is a simple one. For four years, I was responding with information to hundreds of emails every year. I decided to put on the information on the internet instead. Peace and Blessings to your continued zest for life.

[Sherryg683]

I know I appreciate any information I can get on the subject, especially when I don't have to search and look it up myself. And I also admire a man who loved and cared about his wife so much that he still is looking for answers that may help or inform others. ...sherryg683

[SoCalGal]

There are many of our her2 family who have no other choice but to undergo WBR or die. I could not even comment at first because I know that Greg means well but this post just made me so upset.

[gdpawel]

The Department of Neurosurgery at the University of Texas M.D. Anderson Cancer Center, from their OncoLog (as well as the UCLA Metastatic Brain Tumor Program and University of Pittsburgh School of Medicine), admits that whole brain radiation may still be a standard for four or more brain mets. However, there are a variety of effective "focal" treatment modalities for people who have fewer than four tumors.

That being said, there maybe some value in having chemotherapy, instead of going the route of whole brain radiation. Temador is one of the targeted drug regimens that has had much success with brain mets, if it is "sensitive" to the cancer cells. Temodar has been shown to benefit those that are benefitting from it.

[pattyz]

Flori,

I can't think of one thing that is NOT upsetting about brain mets nor the treatment options available for them.

However, I do believe it is the right of the individual to be FULLY INFORMED with the most current research on the potential for devastating side effects of any tx's.

Most especially since those of us with Her2+++ are extending our survivals with the addition of Herceptin (and perhaps Tykerb, now.) Quality of Life during that longer survival is also a right of all.

And, if indeed WBR is found to be neccessay, there are very good current researchers who have found that 'less is more' and longer time frames less potentially damaging. That is also a message that needs to get out there, rather than 'same old same old' procedures.

best to you,
pattyz

[Joe]

The HER2 Support Group in cooperation with Leksell (Gamma Knife) and the CINN Foundation produced a paper on CNS tumors that we distributed at the 2006 ASCO meeting in Atlanta.

It was peer reviewed by both Dr. Eric Winer and Dr. Keith Black and meant to inform both patient and practitioner on the treatment of brain mets:

http://www.her2support.org/paper.pdf

More effective treatments are leading to longer survival rates for all breast cancers. Unfortunately most of these treatments do not cross the blood brain barrier. As a result the incidence of CNS tumors is rising and unfortunately women who are HER2 have a greater propensity to develop these tumors. Recent studies have shown that as many as 40% of HER2 positive women will develop brain mets. Also frightening is a study presented at San Antonio several years ago that of all women who are HER2 positive who develop brain tumors, 10% develop cns tumors as their initial metasthesis. NO PRIOR WARNING.

We must therefore press for routine Brain MRI's for women who are HER2 positive.

Another warning, although we are passionate about the usefulness of the Serum HER2 test, this test will not detect cns tumors.

Regards
Joe

[gdpawel]

The studies performed by Patchell, et al that is cited in the paper Joe has presented (thanks Joe), measured tumor recurrence and not 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. 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 by Mintz and Cairncross 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.

Also in the paper above, it mentions lapatinib (Tykerb). Antivascular activity of Tykerb (and Avastin) in primary microcluster clutures of breast cancer and other human neoplasms in a "real-world" study was presented at the recent Breast Cancer Symposium. While the other clinically-available 'nib' drugs have been shown to have anti-vascular activity, anti-vascular activity of Tykerb has not been previously reported.

http://her2support.org/vbulletin/showthread.php?t=35512

http://cancerfocus.net/forum/showthr...1c7cb1e5&t=648

[hutchibk]

Joe is correct that we have limited chemo/trageted agent options that cross the BBB. It is not always a viable choice, and many of us have been on most of those options already. Some are dx'ed when those options are not realistic, sometimes making WBR the only (and probably last resort) choice for many people. I know we have one member currently who is facing WBR as her real only choice. I would hope that we could all be supportive of those who have no choice but to face this difficult option...

I know this thread will scare some folks, but I hope those who have no other option will not recoil from their decision strictly based on this thread. Sometimes it takes what it takes and WBR is still a viable option for many, risk vs benefit. It will be wonderful when ONE DAY IN THE FUTURE we will have less debilitating treatments, but this is still an important one in the tool box for where we are today.

[Emmay]

Regarding chemo agents that cross the BloodBrainBarrier: another option that is currently showing startling success for my sister (since May '08) and three other women with breast cancer brain mets (who are being treated at the same hospital) is a combination of CPT-11 (also known as Irinotecan or Camptosar) plus Avastin.

[Sherryg683]

OMG 40% is such a high statistic, that has me really worried. I had a brain MRI done 9 months ago and a brain CT scan done 3 months ago, and each were clear. Are CT's reliable in detecting brain tumors, I know MRI's are better, maybe I will have to have my oncologist do another MRI..sherryg683

[Gerri]

I'm with you Sherry, I was surprised to see that number. Since I was early stage, my onc doesn't order tests of any kind outside of a yearly mammogram and breast MRI every six months, unless of course I have symptoms. I guess I could always go in with "frequent headaches" and get her to order it. This concerns me.

Joe, do you have access to that study stating those statistics? I would like to talk to my onc about all of this, but without something to back me she will probably not go along with ordering a brain MRI.

[gdpawel]

And for those who think they need WBR there is hyperbaric oxygen therapy (above). 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 WBR.

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.

Emmay points out something important. One of the most popular combinations for brain tumors is CPT-11 (Camptosar) and Avastin. As with most targeted therapy drugs, Avastin does not necessarily benefit every patient and it is expensive. Until now, there were not tests that existed to show reliably who would benefit from anti-angiogenic agents.

http://www.medicalnewstoday.com/articles/89186.php

[hutchibk]

Sherry - MRI is the best for looking at the brain and bones. CT is best for torso/organs.