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Whole Brain Radiation and Solitary Brain Metastasis

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

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 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, 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 was less "tumor recurrence" but not more "long-term survival". In my wife's case, tumors recurred.

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 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. There is 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.

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.

Even the Department of Neurosurgery at The University of Texas M.D. Anderson Cancer Center, from their OncoLog, admits 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. The metastasis that I write about is a "solitary" brain metastasis. In treating metastatic disease, the prime principle is to not make the treatment worse than the disease, thus good treatment becomes "finesse."

lilgigi
Posts: 5
Joined: Jul 2005

My best friend was recently diagnosed with multiple lesions in her brain, 19 lesions one 3 cm in size. She was diagnosed with large cell lung cancer in Aug of 2004 and had 1 lobe removed where the tumor was located and chemo.
You seem to have alot of experience in the area and due to her prognosis (3 weeks untreated and 5 months with whole brain radiation) I hope you might have some feedback. My concerns are all of the mixed diagnosis from the doctors and very limited resources out there on this many lesions. It seems with every treatment (she has had 3 of the 15 prescribed) she loses more short term memory and her behavior changes more. After watching her go through the chemo (which put her in the hospital 3 times due to complications, I have began to question the treatment and quality of life.
I would appreciate any advice or comments.

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001
Localized Therapy for Limited Metastatic Disease to the Brain: A Phase II Study of Surgery (S), Stereotactic Radiosurgery (SRS) and Stereotactic Radiotherapy (STR) in Favorable Patients

Dr. Lucien Nedzi, of UT Southwestern's Simmons Cancer Center presented the lastest report on Whole Brain Radiation vs Gamma Knife at the International Stereotactic Radiosurgical Society's annual meeting in Paris. A summary of the report appears in UTSW's The Target newsletter, Vol 2, Fall 2011.

The purpose of the study was to determine the feasibility and efficacy of Surgery (S), Stereotactic Radiosurgery (SRS) and Stereotactic Radiotherapy (STR) without Whole Brain Radiotherapy (WBRT) in favorable patients with four or fewer brain metastases.

Surgery, Stereotactic Radiosurgery and Stereotactic Radiotherapy are prospectively feasible in patients with KPS >= 70% and four or fewer metastases. The majority of such patients can be managed without ever receiving whole brain radiotherapy. There is no evidence survival is inferior to historical controls.

Source: UT Texas Southwestern Simmons Cancer Center

Treatment of Five or More Brain Metastases With Stereotactic Radiosurgery

Grant K. Hunter, M.D., John H. Suh, M.D., Alwyn M. Reuther, M.P.H., Michael A. Vogelbaum, M.D., Ph.D., Gene H. Barnett, M.D., Lilyana Angelov, M.D., Robert J. Weil, M.D., Gennady Neyman, Ph.D.

Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH

Abstract

Purpose:

To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS).

Methods and Materials:

Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS).

Results:

The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60–100). A KPS of ≥80 significantly influenced OS (median OS, 4.8 months for KPS ≤70 vs. 8.8 months for KPS ≥80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191–0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of ≤70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157–4.049, p = 0.0157).

Conclusions:

Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with metastatic cancer, especially for patients previously treated with WBRT. A KPS of ≥80 predicts for an improved outcome.

International Journal of Radiation Oncology * Biology * Physics Volume 83, Issue 5 , Pages 1394-1398, 1 August 2012

http://www.redjournal.org/article/S0360-3016(11)03388-8/

 
No difference in overall survival with whole brain radiation therapy
 
http://cancerfocus.org/forum/showthread.php?t=526
roro5306
Posts: 1
Joined: Jul 2005

Hi Great info you gave in your discussion, But when I tried to tell my doc he wanted to know where all this info came from JAMA, AMA, MAYO, CLEVELAND ? I am sure your got your info at a great sourse . could you let me know so I can again back up my info, my husband is due to have whole brain radiation, I would like to have him receive focal radiation, his tumor was removed a single tumor that they suspect came from the lung. It was still small with no apprent symtoms, it was found by accident in checking something else out.
Thank you so very much and good luck to you Ro

lilgigi
Posts: 5
Joined: Jul 2005

roro,
I noticed that gdpowel didi not respond to you so I thought I might let you know how it was going with my friend. While it sounds like they caught it early with your husband and my friend has multiple (over 11 lesions) I will let you know that she has 3 more treatmeants left - out of 15 and as far as I can tell she is doing very well. It is so hard to tell the effects of the treatment from the desease and the medication (the Decadron is horrible with behavioral side effects that the Doc's rarely mention - I will be more than happy to lead you to an article that helped all of us on the effects of this drug). She has lost some of her short term memory but is still able to perform many executive functions. Unfortunately we will not know the status of the treatments sucess for 3-6 weeks (they wait until the swelling goes down on the brain-an effect of the radiation) to give her a follow up cat scan. I will let you know of any status as soon as I get one. I guess, my advice is to listen to your Doctor, every case is so unique and I do believe they will treat the desease to the best of their knowledge.
Let me know what happens or feel free to send me an e-mail through this web site with my user name.
My prayers are with you and your husband.
-lilgigi

AuthorUnknown
Posts: 1564
Joined: May 2006

Hello,

You can always contact a member throught the internal CSN email system in case they are no longer checking the discussion boards regularly. You can do this by clicking on the envelope icon below their message.

Take care and be well,

Dana
CSN Dana

btlaw
Posts: 1
Joined: Aug 2011

It's more than 7 years since the EORTC and Dr Patchell ..et al has published some of their studies on risk and benefits of WBRT as followup treatment for solitary brain mets of cancer from some where else in the body. Are there any other more up to dates data around for the best approach for such?

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