I'm aware that WBR has been the Gold Standard for treating brain metastases for half a centrury. But although there is anecdotal evidence and personal experiences that support its use I've not been able to find any studies that conclusively demonstrate any benefits. (In order not to start out from a negative position I've made a point of not delving into the area of possible cognitive problems that may follow from the treatment as that is a completely different issue, but have only looked for definite improvements or benefits resulting from WBRT.)
When I mentioned this to my wife's oncologist she agreed but said there are clincal trials underway that will attempt to address that very question. But surely WBR isn't being given without some expectation of success, based on a proven history? I find this particularly perplexing since even chemotherapy (e.g. pemetrexed and cisplatin et al) has had documented success in treating mets, despite something of a reluctance in some circles to acknowledge the ability of certain chemo agents (or erlotinib) to cross the BBB.
It does appear to the uninitiated (me, and others I'm sure) that WBR is held as a long-established article of faith, left over from the days when there was nothing else that could be done in the way treating brain mets. Or, it could be that I'm not looking in the right places?
I would be very grateful for any help in directing me to studies that look more promising.
Tue, 11/20/2012 - 07:46
Let me point you to a couple of posts by our faculty that describe WBR. Please let us know what you think from reading them.
and a newer post describing ongoing research.
Tue, 11/20/2012 - 09:28
Many thanks, Janine, for your prompt reply.
Actually I have read both of those posts, the second one you mention only this morning and the ongoing research does reveal some very interesting developments.
The first post, Doctor West's analysis, gives a really encouraging overview from the professional's standpoint (although we're not privy to the source of the data).
It would be churlish to deny that individuals have benefitted from WBRT, or that there are no cases where brain lesions have shrunk, but although I've read countless times how doctor's advocate WBRT, to date I've yet to find a single study that conclusively demonstrates positive results in general terms. In some of the studies I've seen there appeared to be no material difference between WBRT and best supportive care. And on occasions there seems to be a question mark concerning whether the steroids are controlling the symptoms rather than the radiation therapy.
I hope I'm wrong on all counts and that my search methods will be proved wanting.
Tue, 11/20/2012 - 11:51
My husband, who 2 1/2 years ago, diagnosed with adneocarcinomia of the right upper lobe with mets to the brain. He had been otherwise perfectly healthy up until the initial symptoms of nausea/vomiting and vertigo started, he stayed home from work to go to the doctor, something he never did. Doc did routine exam, labs, found nothing, and my husband insisted to him, "I am sick". These were the first symptoms and it was only about a week that he had them. Thankfully, our primary acted quickly and sent him for an MRI immediately. We had the results that very same afternoon. I figured he had an inner ear infection. Our primary called us and told us that Michael had at least 8 visible mets in his brain. After talking with the Dr. he told us to stay close to the phone as he would have my husband sent in for more scans the very next day. As soon as he was assigned an oncologist, it was a Friday afternoon, we knew we would have to wait through the weekend, but the oncologist's nurse called immediately with an order for steroids to get him through the weekend. With that, his symptoms went away by the next morning.
WBRT was the first thing recommended, so I started to research, I wore Google out! Everything I read scared me so bad, yet knowing that my husband would not last very long as things were, this was the course of treatment that we choose. Bear in mind, it was eight tumors that they could see....who knows what was unseen. Through the entire process, all I could think was, this is as barbaric as sticking your head in a microwave.
After having the treatment, another scan was ordered and you could visibly see the difference. It appeared as though someone had taken a pencil eraser to each of the ones that we could see. With the tumors stabilized, the next task at hand was to slow the disease process, which we were able to do. My husband was able to live two years, four months and two days. He did not suffer, he had minimal side effects, the only cont.
Tue, 11/20/2012 - 12:11
difference that I noticed is that his multitasking skills were slowed. But if someone didn't know him, I don't think they would have noticed. My husband could still talk about history, science, math, current events, and politics, his favorite by the way. It was just too much for him to be in larger groups of people and keep up with conversations. Other than having balance issues in the last months, it was well worth doing, and my husband told me that if he would have made the same choice. A few weeks vs a few years....Hope was always there, and maybe someday for someone there will be other answers.
Tue, 11/20/2012 - 14:26
Because I'm not a radiation oncologist, I don't have those data at my fingertips. I must confess that, having treated many patients with brain metastases for the past 15 years, I consider the value of WBRT for multiple brain metastases to be pretty close to a truism, that I would not consider the responsiveness of brain metastases to chemo to be in the same ballpark as that of WBRT, and that I would have an ethical dilemma about randomizing patients to receive WBRT or some alternative for multiple brain metastases. We don't have randomized trials proving the value of parachutes either...just anecdotal reports of their value.
I'll try to see if a radiation oncologist has those historical data. In the meantime, I would say that, despite the fact that I have more incentive to favor chemotherapy than radiation, I have never remotely considered chemotherapy to be a good alternative to WBRT for patients with multiple brain metastases.
Tue, 11/20/2012 - 15:24
Indeed - one needs to look back a few years. See Khuntia et al, Journal of Clinical oncology, 2006: 24;1295-1304. Nonrandomized studies suggest that whole brain radiation therapy increased median survivan by 3-4 months in comparison to 1-2 months with best supportive care and/or steroid medication.
I hope that helps.
Wed, 11/21/2012 - 03:47
Thank you all very much for your replies, they’ve gone some way to reassure me.
I’m very aware of the current trend where people scan the Internet for medical information and assume to have gained an understanding that in fact is incomplete being merely surface knowledge. Nevertheless I cannot rid my mind of the view that chemotherapy should be the first line treatment for brain metastases.
The point that I’m trying to make here is that, and let’s be realistic, we must expect all treatments to ultimately fail, or answer to the principle of diminishing returns. Now my understanding is that WBR can only be done once. This, to me, suggest that life, and perhaps the quality of life, can be extended by giving chemotherapy first-line and holding off on WBRT until or unless events make it necessary? Of course I’m not proposing that other chemotherapy regimes should continue to be sought where an existing one clearly is not working, in which case WBRT may then be the best course of action.
Now I believe I’m right in thinking that chemotherapy and WBRT cannot be given together, but patients with brain mets given chemotherapy as a first line response benefit from the systemic action helping to prevent the disease metastasising to other parts of the body as well as treating the primary site.
This whole body approach makes sense to my admittedly non-medically trained mind.
Wed, 11/21/2012 - 03:52
I thought it might help if gave a brief summary of my wife's situation.
In May 2011, after having motor problems, instability when walking, and a feeling of pressure at the back of her head, my wife was diagnosed with lung cancer metastatic to the brain.
After three cycles of platinum based chemotherapy the oncologist reported a ‘remarkable response’, for three out of the four brain mets had ‘gone’ and the tumour on the lung was stable. My wife has since been experienced vomiting and nausea. A scan showed two large mets. My wife was offered WBRT, which she declined at that point and was instead offered Docetaxel monotherapy (my wife doesn’t have the EGFR mutation, and so Tarceva was not an option). Last week, and with two more cycles to go, a scan revealed that the lung tumour has shrunk and the brain mets were now stable. (I’m told that Docetaxel has a small capability to penetrate the BBB). The option of WBRT still remains on the table.
Wed, 11/21/2012 - 04:32
undredseesee, I wanted to comment on your post last night but didn't, on the basis that personal experiences were not what you were interested in hearing. I also wanted to upload the article Dr Loiselle cited, which is from a subscription-only journal, and am trying to find out whether the site will allow me to do that.
I am very glad to hear that your wife's brain mets resolved with chemotherapy. I think it is a fair point that some aspects of cancer treatment may not have a rigorous evidence base; on the other hand, as Dr West suggests, the treatment of brain mets is such a sensitive area that it could be ethically problematic to run clinical trials. There have been trials for agents such as Temodar, and our own Dr Pinder is among those investigating the potential of a new drug called GRN 1005:
We've had discussions about Alimta crossing the blood-brain barrier, and if you try a site search you will find you are not alone in believing that chemotherapy can work on brain mets. For example:
But these are personal stories, and I understand your wariness of anecdotal evidence. However I take seriously the testimony of experienced clinicians like Dr West. They will have seen many patients with brain mets and are therefore well qualified to form a judgement - over the years and across a large group of people. My best to you and your wife.
Wed, 11/21/2012 - 07:48
Certain Spring, thank you for your kind remarks and for the links. I agree with you of course that we should take seriously the testimony of Doctor West, Dr Loiselle, and the other professionals. In fact I’m very grateful and hugely impressed with the informed contributions they make to this excellent site.
But it is also true to say there are views held by other oncologists equally worthy of consideration, which is certainly not to say one is right and the other wrong. About a year ago I came across an article by a US oncologist who made a compelling and eloquent case for chemotherapy to be given as the first line treatment for NSCLC with mets to the brain, which influenced my wife and I in our treatment decisions, and which thankfully resulted in a good measure of success. This personal experience doesn’t count as some kind of universal proof but simply confirms Dr West’s own wise words: “There’s really no meaningful work to suggest that one lung cancer treatment is significantly more effective against brain metastases compared”.
Wed, 11/21/2012 - 08:21
undredseesee, I am sorry to hear what you and your wife are going through. Again, I am not a professional and all I can offer is personal experience. My Dad, prior to WBRT, was experiencing gait, speech and cognitive function issues. All of these resolved rapidly following WBRT. I have heard that WBRT cannot be administered repeatedly, but I wonder if there is a hard cap of 'one'. I would imagine that if a sufficient long time has elapsed for a patient since his first WBRT, this may qualify him for a second treatment. And if this is correct, it would be logical to administer WBRT as early as possible. Also, I wonder how other forms of RT feature in your concern - for instance gamma knife (which is focused on troubled spots and not the entire brain) following a prior WBRT.
In terms of the sequential use of treatment with a view to prolonging survival, I can follow your reasoning but I suppose your assumption is that chemotherapy and RT are equally capable of treating cancer regardless of where the sites are. If treatments A and B are designed to do exactly the same thing, it would make sense to use them sequentially and not blow both options concurrently. With that being said, I wonder if RT and chemotherapy are truly characterised as analogous treatments and alternatives of one another, each designed to do exactly the same thing.
Wed, 11/21/2012 - 09:33
undredseesee, I wonder if you have a reference for the article you mention? It would be interesting to see the argument the oncologist is making. On your original question about studies, there is an excellent summary of the available evidence in a presentation by Dr Minesh Mehta, who's a professor of radiation oncology in Chicago (p. 8 onwards in the transcript):
One observation I should like to make is that there are different scenarios to consider: for example, when a patient's cancer does not respond to first-line chemotherapy, and there are mets in the brain. If you haven't given WBR, on the assumption that chemo might do the job instead, you have wasted valuable time and given the mets time to grow in the brain. This is addressed in a Q&A by Dr Mehta. For him, the dilemma is: how does a doctor single out the patients (and he acknowledges that there are some) for whom chemotherapy will work on the brain mets? (p. 4)
As to Dr West's view, I confess I read Dr West's position as being rather more definite, certainly as expressed on this thread:
"I have never remotely considered chemotherapy to be a good alternative to WBRT for patients with multiple brain metastases."
Wed, 11/21/2012 - 11:21
I'll need to admit that my clinical experience is an impression -- no more and no less. There is the saying that "the plural of anecdote is not data", so as someone trying to avoid overemphasizing the alarmist view created by anecdotes about serious cognitive problems from WBRT, it's fair for me to acknowledge that my experience managing many cases is not a true refutation of a data-based point.
I do think it's fair to consider chemo prior to WBRT in asymptomatic or minimally symptomatic people, with the thought that it would be helpful to initiate WBRT in a very timely way if a person's brain metastases aren't responding to chemo. However, I don't think that's leading with the most effective treatment for brain metastases. It's not that you can't get away with it, but some patients may experience the new development of seizures, headaches, vision changes, and a decline in performance status from progressing brain metastases while receiving chemotherapy when WBRT would have neutralized that threat if given initially.
Thu, 11/22/2012 - 04:52
Certain Spring, I would so dearly love to find that web page that comprised a video and text, but without knowing the oncologist’s name the quest is like searching for the proverbial needle in a haystack.
The following paragraph in Dr Mehta’s discussion, and the dilemma he identifies, highlights exactly the thinking that my postings respectfully question:
“One observation I should like to make is that there are different scenarios to consider: for example, when a patient’s cancer does not respond to first-line chemotherapy, and there are mets in the brain. If you haven’t given WBR, on the assumption that chemo might do the job instead, you have wasted valuable time and given the mets time to grow in the brain.”
One can’t help but notice that while there is the assumption that first line chemotherapy may fail in achieving a response, no such possibility is admitted in the case of WBRT, whereas in fact it is not difficult for even a layperson such as myself to find instances where WBRT achieved no meaningful response. And in those situations it seems to me that the scenario that Dr Mehta describes, where valuable time is wasted, may very well apply in the case of favouring WBRT over chemotherapy!
Dr Mehta has this view on the initial treatment of metastases with chemotherapy:
“… we don’t have a good handle on who are the best patients in which
this approach can be used when we delay the whole brain radiotherapy, so that the
systemic therapy gets a chance to come in quickly. I think it’s a great idea; we just
need to find out who are the patients that really benefit from it.”
Despite the very real difficulties that Dr Mehta identifies, it is encouraging to see the chemotherapeutic approach is not being ruled out. Dr West also had something extremely interesting to say on the matter as long ago as 2007. "Chemotherapy for Brain Metastases More Helpful than it’s Given Credit for" (Not sure how to post the link.)
Thu, 11/22/2012 - 05:17
Thu, 11/22/2012 - 05:29
Just for the record, the first quote ("One observation ...") is actually from me, the second ("we don't have a good handle") is Dr Mehta. I thought his point was very relevant - how do you identify the patients whose brain disease will respond to chemo? But as I understand it you are querying the presumption that WBR will work on every patient. Dr Mehta is saying that on the balance of probabilities he'd rather take the chance of the WBR working than hope that such-and-such a patient will belong to the smaller group for whom chemo will be effective in the brain. The answer to the obvious riposte - "How do we know the chemo-responsive group is smaller than the WBR-responsive group?" - would be simply to defer to his clinical observation. (Hence my point about putting a degree trust in doctors and their experiences of treating patients.)
As for Dr West, he can speak for himself but I suspect he was just reporting (5 years ago) on an interesting new development - he often reports on new drugs or practices that he would not necessarily endorse or use himself.
It does strike me that clinical practice cannot be as dogmatic as you imply, or your wife's oncologist would not have been content to rely on her excellent response to chemotherapy, but would have pushed for WBR as well.
I'll sign off now as - although I think it is good to question received wisdom - I am only a patient, and others are more competent to debate this topic than I am. I hope your wife continues to do well for a long time to come.
Thu, 11/22/2012 - 05:55
It's great that your wife had this response with the brain mets using chemo only. How many mets did she have in the brain? As you know, with brain mets a patient is considered stage IV therefore advanced. There is no telling as Dr. Mehta has mentioned, who would benefift from chemo alone to treat brain mets. And with a patient being advanced, there is no way to get a clinical trial to find out if chemo and what chemo passes the BBB vs WBR of gamma/cyber knife treatments. This to me would be like playing Russian Roulette with the possibility of only a few months to live. If it were my decision, I would opt for WBR whether it only extended my life a few months, it's better than the alternative of the mets continuing to grow and cause more damage in the brain very quickly. I know you're not in the US just from your response and it's fine that your wife and you opted out of WBR and things worked out well. We have all that choices on how we want to be treated. Wishing her the best.
Take care, Judy
Thu, 11/22/2012 - 09:06
Yes, I’m sure it’s true to say that a degree of trust is necessary with any medical opinion, but the subject matter may of course be open to interpretation and differences in the application. But I cant say that dogmatism is something I’ve recognised in clinical practice, although I suspect that on occasions there may be a natural reticence to pioneer procedures that are not in line with mainstream thinking. And it is to our oncologist’s credit that she has never pushed for any particular treatment; the decisions have been ours alone based on the range of information we’ve been given.
There are numerous references where, due to the likelihood of serious cognitive impairment, WBRT is being given to recipients who only have a short survival expectation. Happily our trust in the medical oncologist was not misplaced and we’re now coming up to the 18-month point since diagnosis. My wife has what I believe is called a good ‘performance status’ – and there are none of the cognitive complications resulting from WBRT.
The trials that Doctor West reports on in that link self-evidently show great promise, and Dr West’s last paragraph in the piece is far-sighted, especially when at that time there was still a significant degree of scepticism concerning the permeability of the BBB.
Thank you again for your kind words and good wishes.
Thu, 11/22/2012 - 09:26
Judy, my wife had ‘multiple mets’, certainly four sizeable ones, and with what appeared to be others developing. Some people have faith in WBRT, which seems to have a variable short-term effect. We’ve viewed it as a rather barbaric, scattergun treatment to be called upon only as a last resort. No denying there is a place for it, but hopefully one day we’ll all look back and shudder at the very idea. But the important thing is exactly as you say, we all have choices as to how we want to be treated. Thank you for your post.
Thu, 11/22/2012 - 11:48
I still believe what I said in that post, which hasn't led me to recommend chemo over WBRT in patients with multiple metastases, though I don't think it would be wrong to try chemotherapy in someone with smaller, asymptomatic brain metastases (as long as the patient is informed about the treatment options). As certain spring summarized above, my view is that WBRT is meaningfully more likely to lead to disease control in the brain than chemotherapy, and I also feel that the possibility of cognitive side effects from WBRT, while not to be discounted, is likely far less than the risk of tragic neurologic complications from poorly controlled brain metastases.
Fri, 11/23/2012 - 10:11
Doctor West, I understand that you espouse the prevailing orthodoxy concerning the treatment of brain metastases especially for multiple mets, in order to prevent neurological decline, but as metastatic brain disease has a very poor prognosis the expectation must be that neurological complications will sadly follow in any case; and even discounting for the moment the very real likelihood of debilitating side effects, WBR doesn’t appear to have a good track record for extending life - or even in fully controlling the symptoms in a majority of situations.
I have enormous sympathy for physicians who are expected to treat this appalling disease and I can understand why WBRT is recommended in the case of multiple mets, and I can also understand why patients opt for it, since the very term itself implies direct action at the target site.
Another poster questioned whether giving chemotherapy for brain mets amounted to playing Russian Roulette? Perhaps! But the same might also be said where WBRT is given instead of chemotherapy? There is now no question that some people with brain mets respond exceptionally well to chemotherapy (with the clear advantage of treating the primary site as well). However I fully accept the difficulty, which you and other doctors have pointed out, of identifying the patients who will do well with this treatment (other than those who have tested mutation-positive, making them suitable for erlotinib etc). My hope is that we will see a movement away from WBRT in the coming years due to further development of successful systemic treatments.
I’m grateful for the opportunity to air my views. My thanks to everyone, the doctors and all contributors, for your interesting and considered replies.
Fri, 11/23/2012 - 10:42
The Best of luck you and your wife. This is truly a horrible disease to share with a love.
Fri, 11/23/2012 - 19:30
undredseesee, all the best to you and your spouse. I hope you will never have to use WBRT given your disinclination, and if you ever do, it will provide you will a good and sustained response.
Fri, 11/23/2012 - 20:56
There's some room here for personalization of care to the priorities and anatomy of the individual patient. I do sometimes use chemotherapy first for patients with very small, asymptomatic brain mets and have seen it control them. But, I don't feel that I can count on chemotherapy for brain mets in the same way that I can count of radiation. When my patient is truly suffering, or at risk for suffering from brain mets, I trust radiation more. The great weakness of radiation is that it only works where you shine the beam. In the case of brain mets, this means that it does nothing for the rest of the body, and, because we don't give chemo simultaneously with WBXRT, it can delay the administration of needed chemo. On the other hand, it's great strength is that it tends to work very well where the beam is shined. This is important, because the brain is a very tight space--small amounts of tumor growth can lead to disproportionate suffering (including death) as compared to more forgiving spaces, such as adrenal mets (which can be painless even with pretty big growth). Can we still try to spare side effects from WBXRT? Absolutely. For a small number of mets, we can consider cyberknife. When WBXRT is needed, there are new ideas (currently being studied) such as hippocampal sparing radiation that hope to deliver the benefits of WBXRT, with less of the memory/cognitive side effects.