you are not going to like this--first evidence based guidelines 4 brain met treatment

[Lani]

probably will be used by insurance companies to deny claims

http://www.medscape.com/viewarticle/711826

[hutchibk]

Can't read the article as I don't have access to Medscape... but just FYI, if it is used to justify treatment denials, Medicare will use it first to deny, and then private insurers will follow their lead. That is typically how it works.

I just learned that Medicare has been denying payment to my doctor for about 1/3 of the fractions he deems necessary to treat my brain mets with targeted IMRT SRS. They tell him that they only pay for 10 fractions when his treatment decision called for 15. He has appealed 3 times of the 4 appeals they allow, with all of the necessary documentation. After that, he is not allowed to bill the patient, the cost of the treatments they won't pay for are on his dime. His business office tells me this happens all the time and they often end up writing off about 1/4 to 1/3 of the costs of treating Medicare patients based on Medicare guidelines that don't sync with what is necessary to treat his patients. This is a perfect example of the Govt telling doctors how to practice medicine.

[Joan M]

Brenda,

For some reason I was able to access this news story about the guidelines that were released last week at the Congress of Neurological Surgeons in New Orleans.

The author of the guidelines report, Dr. Steven Kalkanis, codirector of the Hermelin Brain Tumor Center at Henry Ford Hospital in Detroit, said that since no evidence supports the use of chemotherapy for brain mets, "we are specifically recommending that it not be used" for that purpose.

He also commented that radiosurgery has really progressed in the last 10 years and that it offers a "very viable and important option."

Apparently, the full report goes into further details.

And, to Lani's point, the insurance companies will probably use such guidelines to deny claims.

Joan

[Jackie07]

First-Ever Evidence-Based Guidelines on Treatment of Brain Metastases
Zosia Chustecka

November 4, 2009 — The first-ever set of evidence-based guidelines for the treatment of brain metastases is about to be published.
"There have been other documents in the past, but they have not been as multidisciplinary as these are, and they tended to be reviews and consensus statements," said Steven Kalkanis, MD, codirector of the Hermelin Brain Tumor Center at Henry Ford Hospital in Detroit, Michigan. "This is the first time that we have treatment guidelines that are based very rigidly on evidence-based medicine."
Dr. Kalkanis headed a panel of 20 experts in various fields, spanning radiation oncology, medical oncology, neuro-oncology, and neurosurgery, who worked together on the document. The panel collaborated closely with the McMaster University Evidence-Based Practice Center to ensure that a strict evidence-based methodology was followed when the guidelines were being developed, he noted.
The guidelines were released last week at the Congress of Neurological Surgeons in New Orleans, Louisiana, and are scheduled to be published in a special issue of the Journal of Neuro-Oncology in December.
Brain Metastases More Common Than Brain Cancer
Brain metastases develop in about 30% to 40% of patients with cancer, and occur commonly with breast and lung cancer. In the United States, there are an estimated 500,000 new cases of brain metastases every year, in contrast to the estimated 17,000 news cases of primary brain cancer seen each year.
There are also differences in biology between the 2, which means that the treatment of brain cancer can differ from that of brain metastases. Primary brain cancers, such as glioma, tend to be "very aggressive and very invasive, and they are part of the brain tissue," Dr. Kalkanis explained, "whereas brain metastases tend to be walled off and rather separate from the brain tissue," but, he added, "they are no less deadly."
The differences between the 2 means that new targeted agents such as bevacizumab (Avastin), which has shown promise in the treatment of glioblastoma multiforme, might not be as useful in the treatment of brain metastases, "but the evidence is not yet definitive."
We are specifically recommending that chemotherapy not be used for brain metastases.
One point that did arise during the literature search is that there is no evidence to support the use of chemotherapy for the treatment of brain metastases. This is not the situation for primary brain cancer, where agents such as temozolomide (Temodar) are a mainstay of treatment, Dr. Kalkanis noted. "As a result, we are specifically recommending that chemotherapy not be used for brain metastases," he added. Of course, there should be chemotherapy as appropriate for the primary tumor, but once that is under control, there is no need for further chemotherapy aimed at secondaries in the brain, he said.
Another difference is in the approach to the prophylactic use of anticonvulsants to prevent seizures. This tends to be standard practice for patients with primary brain cancer, but for patients with brain metastases, current practice is probably split 50/50 for using or not using these drugs, Dr. Kalkanis explained. In this instance, once again the literature search found no evidence to show a benefit, so the guidelines do not recommend it, he said.
One of the reasons for drawing up the guidelines was to place new developments in the field into context. For example, the use of radiosurgery has really taken off over the past decade, and is no longer being carried out by only a few academic institutions, Dr. Kalkanis noted. This approach uses high-intensity radiation that is targeted very specifically (using magnetic resonance imaging) at the brain metastasis, preventing the trauma of open surgery followed by whole brain irradiation, which is the traditional approach. The panel decided that the new approach of radiosurgery offers a "very viable and important option," he said.
Another new development has been the use of radiosensitizers, such as motexafin, which enhance the effects of radiotherapy and appear "to show promise" for brain metastases, he added.
"Because of the growth of these new technologies, there has been wide variation among physicians on how to treat patients. Some centers use X and Y followed by Z, whereas other centers use Z followed by Y and then X," Dr. Kalkanis explained.
"Our primary goal was to identify best treatment practices leading to the best outcomes for patients," he said. "At the same time, we don't want to unduly restrict the physician's practice," he added.
In cases where there was not enough data to suggest a guideline or recommendation for a particular treatment, the report lists all relevant ongoing clinical trials to encourage physicians to enroll patients. In addition, the document highlights areas in which more research is needed.
Dr. Kalkanis has disclosed no relevant financial relationships

[Joe]

For all those who wish to access Medscape:

Username: her2support
Password: member

[hutchibk]

To reiterate my point about coverage denials... Medicare sets the guidelines for the industry to justify treatment denials. Medicare will use it first to deny, and then private insurers will follow their lead. That is typically how it works.

[Diane H]

As I understand this and as Lani says in her header this is the first evidence based guidelines for brain met treatment -

"First-Ever Evidence-Based Guidelines on Treatment of Brain Metastases
Zosia Chustecka

November 4, 2009 — The first-ever set of evidence-based guidelines for the treatment of brain metastases is about to be published.
"There have been other documents in the past, but they have not been as multidisciplinary as these are, and they tended to be reviews and consensus statements," said Steven Kalkanis, MD, codirector of the Hermelin Brain Tumor Center at Henry Ford Hospital in Detroit, Michigan. "This is the first time that we have treatment guidelines that are based very rigidly on evidence-based medicine."
Dr. Kalkanis headed a panel of 20 experts in various fields, spanning radiation oncology, medical oncology, neuro-oncology, and neurosurgery, who worked together on the document."

While I find the results very disappointing it does seem based on some solid factual evidence. Wish the results did point to chemo being a good option for brain mets.

[Lani]

My problem is that if they don't keep trying they won't find out what DOES help

Sometimes it might be the combo of chemo plus something else(but if no chemo is paid for we won't find out)

Sometimes it might turn out that it only helps a subset (like with Iressa against lung cancer) and if it is small percentage (like with Iressa) they won't find out because they will have thrown out the baby with the bathwater

It might also turn out that it the sequence/timing/chronicity that makes the difference--again we won't find out unless they are allowed/paid to try.

A few years ago it was dogma that anthracyclines worked particularly well for her2 positive breast cancer and should always be used.

How can we find out "evidence based" results if we stop gathering ALL the possible evidence?

[Diane H]

Hmm, that's a really good point Lani. Here's a question, I don't have a clue about whether the different treatment decisions by doctors as a whole throughout the country/world are gathered and analyzed as to efficacy. Seems like that would be great information to have in addition to trials and studies. Does such a database exist?

[StephN]

Thanks, Lani. And Jackie for posting the article.

My rad onc has been talking about the improvements in radiosensitizers. He is an ardent fan of Gamma Knife for brain mets.

This report did not specifically mention TYKERB and any of the other new targeted drugs that are supposed to work inside the brain. Would they still come under "clinical trials."

Also, Temodor seems NOT recommended for mets?

I was not quite sure what to make of the following:

Of course, there should be chemotherapy as appropriate for the primary tumor, but once that is under control, there is no need for further chemotherapy aimed at secondaries in the brain, he said.

Takes me back to the Tykerb question.

[Lani]

Steph--what annoyed me is that by aiming one's treatment against the primary, you may be treating the brain met completely wrong. 40% of mets have a different ER,PR or her2 status than the primary. Without biopsying the brain or having a spect MRI, special PET(both still works in progress and theoretical) or other study which might identify
the brain met as being her2 positive or not how will we improve things.

It is easy to say that chemo is not effective --but if it is because it is the wrong chemo/targetted agent because it is aimed against the wrong culprit
than this "evidence" based medicine is only keeping us from learning how to improve treatment.

[hutchibk]

This trend towards strict evidence based medicine seems to fly squarely in the face of the trend of "individualized" novel treatment regimens that we hear about every year at SABCS, that seem to be the trend the researchers feel is the future of mets treatment.

Also, Lani's points are exactly my worries about the unintended consequences of the newly mandated CER (Comparative Effectiveness Research Council) and what the potential might be for it to stifle treatment advancements, innovation and novel approaches.

[StephN]

The brick wall I was banging against is the HER2 one for brain mets spread.

The primary could "seem" under control, but there are many HER2 patients who get the brain as the first site of mets.

Is the adjuvent Herceptin having an affect on the incidence of that??

[Joan M]

Perhaps some of this report is being influenced by the trend toward cutting the cost of healthcare currently happening in the United States.

I've read a lot of news stories lately in the monthly AARP Bulletin and elsewhere that keep bringing up delivering better healthcare more efficiently, but they don't say how to do that specifically. One guru mentioned doing fewer "frivolous scans," and likewise in other stories. There's also words used to imply "rewarding" doctors who are "more efficient." Now, what does that mean?

And this ties to Lani's original point about insurance companies denying claims and Brenda's point about Medicare setting precedent.

Joan

[Rich66]

I too wonder about blanket terms like "chemotherapy". There are things like Tykerb, antibody approaches and small molecule approaches which may have efficacy. Are those "chemotherapy"?
Best conflicted quote:

"new targeted agents such as bevacizumab (Avastin), which has shown promise in the treatment of glioblastoma multiforme, might not be as useful in the treatment of brain metastases, "but the evidence is not yet definitive."
We are specifically recommending that chemotherapy not be used for brain metastases. "

Evidence isn't in..but the recommendation is. I get it.


But wait...3.5 seconds on pubmed shows:

Ann Oncol. 2009 Oct 19. [Epub ahead of print]
Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT).

CONCLUSIONS: HER2-positive and triple-negative breast cancers have special predilection for metastases to the brain. Survival from brain metastases depended on performance status and the use of systemic treatment.

More on variable efficacy


Herceptin prolongs survival

"extended survival"


PMID: 19840953 [PubMed - as supplied by publisher]

Womens Health (Lond Engl). 2009 Nov;5(6):603-12.
Lapatinib in metastatic breast cancer.

Frenel JS, Bourbouloux E, Berton-Rigaud D, Sadot-Lebouvier S, Zanetti A, Campone M.
Oncologie Médicale, Institut Regional du Cancer Nantes Atlantique CRLCC René Gauducheau, Bd Jacques Monod 44805 Nantes Cedex/Saint-Herblain, France. jsfrenel44@aol.com
Lapatinib is an oral, small-molecule, dual kinase inhibitor that targets both HER2 and the EGF receptor. Lapatinib was approved in June 2008 in Europe for the treatment of advanced HER2-positive breast cancer. Promising results in trastuzumab-refractory metastatic breast cancer were obtained from Phase I, II and III studies in combination with chemotherapy. Diarrhea and rash are the most common side-effects and are mostly moderate and treatable. Cardiac toxicity occurs rarely and mostly as an asymptomatic and reversible decrease of left ventricular ejection fraction. Unlike trastuzumab, some data show that lapatinib could cross the blood-brain barrier, with some evidence of activity in treating or preventing brain metastases. Its evaluation is actively ongoing, in combination with trastuzumab and in the adjuvant setting.

PMID: 19863462 [PubMed - in process]

Lapatinib with Capecitabine partial responses

Sagopilone in phase II, including BC

ANG1005 Taxol+Peptide crosses BBB

Another overlooked aspect of Tamoxifen?

Oh..and in an e-mail from a researcher/drug developer on BBB:
"Sometimes this barrier is compromised in brain metastases, sometimes not. "
Not sure if he was talking about BC but..

[StephN]

I guess all these questions point back to another reason my oncologist favors going after brain mets with targeted radiosurgery as it will kill the tumors no matter WHAT their biology. (He sees people who have had all sorts of treatment, and has experience as to what is efficacious in various circumstances.)

My rad onc naturally believes in systemic therapy as part of the process to control the mets, along with the radiotherapy and close surveillance.

[Joan M]

Gee, that sounds very familiar. ... It's what the interventional radiologist who did my lung radiofrequency ablation says about RFAs and cryoblations -- they burn and freeze tumors no matter WHAT their biology.

Joan

[Carolyns]

Lani - You are right!

"Re: you are not going to like this--first evidence based guidelines 4 brain met treat
My problem is that if they don't keep trying they won't find out what DOES help" So true Lani.

I asked this question at a conference on evidence based guidelines. Most of the women in the room were "survivors" and I am a mets patient. I raised my hand and said that I was "dying of cancer" (***not that I feel that way but I needed the greatest impact and to make a point... I looked just like them). I told them that most folks don't even know I am sick. I told the speaker that the vast majority of treatments that I have received have not been approved for breast cancer treatment... no evidence (but they have all worked). Hmmmmm... so what about folks like me??? Not much of an answer other than to say that compassionate use and expanded access would help. Not so much, I found out later when I tried.

I didn't say this but I often wonder why am I different from the person standing out on a cliff waiting to be rescued? There isn't any evidence that they could actually save them and yet they send in the teams to try.

The other thought that I have is I am wondering if many types cancer have a lower response rate once there is mets and BC is being lumped in with other forms of cancer. If so, this is a distinction that needs to be made. Breast Cancer specialist need to be calling the shots when it comes to treating Breast Cancer... mets too. I have had more than 11 lines of therapy in 4 years and I still work full time and raise my son. Still kicking...

Those are my thoughts...

Carolyn

[Joan M]

Carolyn,

I've also opted for unconventional treatments. There's a standard of care, and to some oncologists it's blasphemy to step outside the guidelines.

For example, last week I checked in with the onc at the major NYC cancer center who I've been consulting for about four years, and he wasn't "warm and fuzzy" because I've never taken his advice.

He kept saying that when my cancer recurred the first time I belonged on systemic therapy (which he has said before), but that instead I kept doing "radical treatments" like the lung wedge resection and then the RFA (also, he's done three things under the table to try to interfere with my treatments, which I learned about from other docs).

He also reminded me that he has 20 years of experience, and then he asked me why I even bother making appointments to see him. He also said I was "undermining" my local oncologist by consulting him (even though she knew I was there and they had spoken on the phone just minutes prior to my appointment). He said that he was trying to give me confidence in my local onc, that they were on the same page. (Ironically, although she's not a bc specialist, she also has a doctorate in molecular biology of bc, and a paper she wrote was chosen by a major cancer group for presentation at its annual meeting several years ago. The problem is that I'm not crazy about my local hospital, except I like the cancer institute and my onc).

He said, yet again, that I continue to pick weeds and that it doesn't solve the problem because the problem is systemtic. When I told him that my "weed picking" has to do with my quality of life, he completely ignored that. It's as if my quality of life and ability to work (until recently because I've "retired" now) was besides the point.

I consider myself "fortunate" (if advanced cancer can be considered that way), that I have been able to avoid chemo for almost three years since the nodule in my left lung first showed up in a CT scan in late Dec. 2006, just over 3 years after my mastectomy and stage IIb cancer diagnosis in Sept. 2003. That means that except for the inconvenience of surgery and the RFA procedure, I've felt good every day. Even this last surgery, the thoracotomy, which was a bull, was worth it.

He didn't seem to comprehend or grasp the quality issue. And until future scans show otherwise I'm NED again.

I felt like a "little" cancer patient being bullied by the big guy on the block because I hadn't taken any of his advice. It's very difficult to navigate.

Joan