Transcript
Well, good morning, everybody and welcome to beautiful Munich. It's a real treat to be part of the Novalis Circle program again. This is a third year, third meeting that I've been able to attend and it's always been excellent. Learned a lot. And like the last few meetings, we're gonna start with the topic of brain metastasis, the commonest radiosurgery indication. And I was asked to delve into what's new in research and how research is driving rapidly changing management in this topic, or what I call breaking the rules of brain metastasis patient care.
So what were the old rules? Not that Dr. Yamamoto was old, he's gonna speak in a few minutes. But the old rules, you resect the large tumors, you give postop whole brain. Systemic cancer therapy is of little value. We almost ignore it. The goal is palliation so a few people live, so cognition's really not an issue. And if you have left leptomeningeal disease, you give whole brain or intrathecal chemo. Then we have the still sort of old rules with someone who's sort of old. My friend, Tony Asher will speak next. We go resect the larger tumors, then whole brain. Systemic cancer therapy is of little value for most indications, still palliative radiosurgery for smaller numbers of tumors, still leptomeningeal disease.
What are the new rules? You resect a radio surgery for the large tumors, or you do both. Systemic cancer therapy may have brain benefit for many indications now. The goal is extended survival, not palliation. Never whole brain radiation therapy, unless there's miliary disease. Radiosurgery for any number, perhaps up to 25. We'll talk a little bit about that. Plus drug. The drug is the new whole brain and leptomeningeal disease is changing as well. Now, radiosurgery, if it's focal, whole brain or systemic drug therapy.
So little snapshot from our registry from last year, just to show you that in 2017, only 6.5% of our patients got whole brain radiation at a total of 261 patients with brain Mets that I cared for last year. If you go back four years, it was double 12%. So the number of patients getting whole brain radiation therapy is just going down year after year. Four years ago, we wrote this paper looking at reevaluating what was going on in brain metastasis. This is already out of date again. And really, the rules are changing so quickly. And of course, we can do radiosurgery with different technologies, with different methods of head fixation, framer mask, depending on how you wanna do it, single session, multi session.
So let's talk a little about the rules that are changing. In lung cancer of course, the commonest cause of brain metastasis. It's all about the mutations as we know. Certain patients have EGFR mutation, a mutation for which they're driving therapies. Some of the other mutations do not have specific therapies yet, but this is all about knowing that either there's a mutation or there's a PDL1 level that drives immunotherapy. And of course, if someone has EGFR, we expect them to live. We don't expect them to die now within the shorter timeframe. And this paper, which we wrote in 2016, is already out of date. And the reason it's out of date is because of the new EGFR therapies that did not exist when this paper was written just a couple of years ago.
So we know that survival is changing rapidly based upon the targeted therapies with an EGFR mutation pushing three years here, as opposed to the old median survival for lung cancer, which was always 11 months. All through the 90s and 2000s, no matter what study was done, median survival was 11 months. Now, that's not the case anymore.
So here's a 63-year-old woman with a non-small cell cerebellar vermis. You can see the response to a dose of 18 gy. I'm not a high dose guy. I never go above 20 for example, that's a separate topic. But look what's in the auditory canal. This was a never a radiosurgery case. The radiology report will say leptomeningeal disease. Of course, it is. Patients got a facial weakness. That's a radiosurgery case to us. If it's focal 16 gy, you can see the response with return of facial function.
So focal leptomeningeal disease, I think is an expanding new thing for radiosurgery applications. And in this series, half the patients who had it were able to avoid whole brain radiation, utilizing radiosurgery plus drug. Even in non-mutated non-small cell lung cancer, the drugs Alimta and Carbo are keeping people alive longer. And the radiosurgery response, even in tumors with necrosis can be impressive.
So if they're non-mutated, we're looking at PDL1 levels and what's a positive PDL1? Is it 80%, 20, 10 virtually anything above 10 is driving immunotherapy as a first care. So here's nivolumab. Unfortunately, the patient got side effects of that drug, pneumonitis. So it was stopped. Here's radiosurgery at 19 gy. Two months looks great, four months, it's bigger. Thinking, oh, maybe this is immunotherapy. It's not. Six, five and a half months, it's getting bigger. It's radiosurgery failure. We removed it, but very little tumor except for little islands of cancer cell at the edge still growing. So that dose was not enough in this setting, even with immunotherapy.
So what's going on? In 2018, high PDL1 pembrolizumab, ALK, crizotinib, now alectinib, now brigatinib. Virtually a drug every 18 months or so, EGFR positive. We've gone from afatinib to alectinib to osimertinib, and now brigatinib and what's coming next in 2019. So what about upfront medical therapy? That's a hot topic right now. Should that be the management and we defer radiosurgery for these small tumors. Well, this very important study from Yale looking at drug alone, showing that upfront drug alone did not do as well as radiosurgery plus drug. So we're very aggressive continuing to use radiosurgery with a 90% control rate for small metastasis. And it's all about the tumor types of course. So we don't have enough literature on subtypes and responses.
So here's a paper on volumetric response. And as a journal editor, I always argue write your articles on specific cancer types, no longer on brain metastases. Don't lump breast cancer with lung cancer. They're different diseases, and they have nothing to do with each other. So even breast cancer subtypes are now very specific, triple negative versus luminal one, luminal two, these are different kinds of tumor and different biology.
And of course, when we see a tumor like this in the motor cortex, if it's breast cancer, we expect a volumetric regression that will be impressive. We would not expect this in melanoma. So the decision to do radiosurgery here is gonna be very different than other cancer types based upon the response. So in a patient like this who's had prior whole brain radiation, has a massive cerebellar tumor as you can see on the left, has a partial resection. There's tumor left over as you can see here, 12 tumors, undergoes radiosurgery to relatively low dose because it's breast cancer, has an impressive volumetric response, and later has over four procedures for 53 tumors over the next three years before she eventually succumbs. And you can see in this young woman, the white matter changes from the original whole brain radiation therapy.
So let's go to the worst situation, which is melanoma, a big problem that we all face. So it's all to be or not to be and be is the BRAF. So melanoma's either a BRAF mutation or not. And if they have it, they're gonna get a BRAF targeted agent. If not, they're typically gonna get combined immunotherapy now. And the impressive thing was median survival for melanoma before this driver was always seven months, six months. Now half of our BRAF series are over three year survivors now.
So single met 20 gy, three years, no tumor, that's a common expectation in patients with a BRAF mutation. And the response to radiosurgery doesn't matter. Whether they're mutated or not, the volume response will be the same. Local control rates are high in the 90% range. And for the first time we've got median survivals for melanoma that are passed one year. So the patients are living long, and this is impressive.
So if you look at this patient with a BRAF tumor, she's 42 year old, she's got multiple metastasis. You can see here, there's a tumor that's small. She has a, I do a couple of craniotomies. Eventually, this tumor enlarges. She has radiosurgery and it shrinks over here, but eventually for a year later, that thing gets bigger. And we watched it and we thought, God, this gotta has to be a radiation effect, but it was not, it was tumor progression. And I sent this to Veronica Chang, who'll be speaking later. She did a biopsy of this conforming cancer and then did laser interstitial therapy of this tumor. I really didn't wanna resect this tumor in this location.
This was the largest tumor that she had done a LITT case on. And you can see the heat-based necrosis from the laser and at four months. And now at 26 months, the impressive regression of this tumor, patients had no active brain disease now for 18 months. 43-year-old patient of cousin of one of my nurses with BRAF melanoma 16 Mets presents during pregnancy is recommended to have whole brain radiation. We treat all 16, goes on drug, and here's the 30 month scan below. These are cases you would never see before.
Melanoma BRAF positive five years with brain metastasis, two craniotomies. I show you this drug response because this is recent. Now, there's on the left, you'll see nodular tumor over here, as well as above the corpus callosum. And there's other tumors, patients failing both dabrafenib and mechanists, traditional BRAF therapy failed immunotherapy. And so what's the next BRAF generation drug? It's binimetinib. This has only been available. It's experimentally for about a month. Patient goes on the drug and you can see within two weeks, the response over here.
Now, look what happens. The patient stops taking the drug. The medical oncologist took them off because of some platelet count issues. And the tumor grows back on the middle slide within five weeks. We said, "Listen, you gotta take your drug." Two weeks later, the tumors are smaller. So what is happening? The targeted agent is doing an amazing thing here. We don't know if this is durable though. So what's the hot topic? It's combined immunotherapy for melanoma. You're probably seeing this report in the "New England Journal." Everybody says, well, this is impressive. To me, this is not that impressive I have to say.
Stable disease over six months, two out of 94 cases, the response rate was around 55% compared to a radiosurgery response in the 85% to 90% range with an important adverse event profile. It's good, but it's not great. There's a lot of failures. I take care a lot of these failures and there's significant toxicity. No doubt it's gonna help their systemic therapy. Is it a replacement for the treatment of brain disease? In my opinion, it is not. So what to do for large brain metastasis. Tony's gonna speak about this in the next presentation. Everybody's doing something different.
I think if we pulled the room, everybody's doing something on this list. Resect and irradiate, whole brain, large field RT, lower dose radiosurgery and see what happens. Hypofractionated, multiple radio surgeries over a few weeks like in Japan, or, as Tony will talk about, neoadjuvant radiosurgery and then resection. There's no right answer. This is what I do. Here's a 62-year-old physician. I wonder what Tony would do in a case like this, sizable tumor, swelling, having balance problems.
I said, "Listen, I would resect this, radiate, do the bed standard type of thing." She said, "I don't wanna a resection." Fine. So we do radiosurgery alone. She's got another tumor in the other cerebellum, 17 gy and 18 gy colon cancer, kind of a variable response expectation, steroids for four weeks, repeat the scan. You can see the volumetric response. So she needs nothing else. And here's the 18-month scan there. Were we lucky, or is this the expectation? To me, it's about radiosurgery and assessing the biology over a month. And if it's going in the right direction, I observe. If it's not going in the right direction, I resect.
How many is too many? A big question that research has addressed over the years. Well, when I started doing this over one was heresy. If you had two tumors, when I started doing this, we would turn you down. It was amazing. We thought this is inappropriate to do radiosurgery for two tumors. Then it was four. Then it was 10. You know, what is heresy now? We're all kind of heretics in some way.
Dr. Yamamoto is really the person responsible for pushing the limits of numerical-based radiosurgery. Of course, his seminal paper showing that five to 10 tumors was no worse than two to four tumors, but how many is too many? This is a 45-year-old attorney with breast cancer, has had whole brain radiation, 26 tumors, seven months later. This, she needed whole brain radiation. It's a little dark, but you can see that she had miliary disease and the whole brain radiation cleared this only for tumors to develop. So it was needed. So we took care of this 13 tumors one week, another 13 the next week. They all, for the most part resolved. And five years later have treated more than 100 tumors at 11 radiosurgery still works as an attorney.
Again, one of the interesting things was she lived long enough to go on a clinical trial geared to preventing new brain metastasis and breast cancer. And that cleared her for about 18 months before new tumors came up. So [inaudible 00:13:44] will be speaking later. [inaudible 00:13:45] is here. The concept of younger people avoiding whole brain radiation, having improved outcomes with radiosurgery alone is provocative. And of course, the seminal study from Dr. Asher and Paul Brown, looking at cognition with limited numbers of tumors, showing that the avoidance of whole brain radiation was a good thing.
Again, we all know it's going away. Tumor bed, we're gonna talk about the concept of how to manage the tumor either before or after resection. 10 years ago, this science starts, but now it's been evaluated in randomized trials at several centers. The research shows observation after resection six months, radiosurgery, 14 months, and then this other important study, postoperative radiosurgery, more cognitive decline with whole brain is just not needed, but no survival benefit.
We'd love to show you what's going on in adverse radiation effects. We're always challenged with this. My personal goal in life is to get rid of decadron and replace it with something better. And hopefully it'll be bevacizumab. There's a lot of good work going on, including the Alliance Trial that we participating randomizing patients to with steroids or bevacizumab. And I think routine avastin is the future.
But to show you here's a case of ovarian cancer in an older woman I took care of, 17.5 gy. Two months, looking a little expanded, three months, not looking gr...she's asymptomatic, amazingly enough, thinking, oh my God, maybe this was a glioblastoma and we missed it. And so we sent her over for the trial. They didn't put her on the trial, just gave her a little dexamethasone and observed. You can see the complete resolution about 95% of the volume over the next year and a half. So no avastin needed.
Here's one of mine. Again, it's looking a little expanded, seven months, eight months. There's a couple of Mets looking bigger, more inflammatory. We put this patient on the study. We don't know if they get bevacizumab or steroid, but what do you think the patient got? Because look at the 10-month and 20 month scans, it looks like a bevacizumab response with less enhancement. I don't know if that's the case though.
What about peri-radiosurgery bevacizumab? So here's a patient who got whole brain radiation for 12 tumors, a young man with a positive lung cancer. One of the 12 tumors grew and it grew over a year. Patient refused to have radiosurgery for whatever reason, came to us. Tumor was pretty big. Eventually look at size on the third slide when we took care of this. So we put them on avastin first, a few cycles. We did five gy times five in the midst of avastin, then another three or four cycles. And you can see the four-month scan. We got away with this. Perhaps the avastin helps. And now we're starting to use this drug around complex tumors.
So a lot's changing. And we always thought we knew something about radiation sensitivity. Melanoma's more resistant. Breast is more sensitive. Maybe lung is in the middle. We've been taught this in medical school for 50 years. Is it really true? Well, there's some really interesting work going on, looking at individual patient radio sensitivity based upon the genetic array of their tumors. So not every breast cancer is sensitive and not every melanoma is resistant necessarily, which probably explains why it works better than we think it should work, and it doesn't work when we think it shouldn't work. And so we're doing next generation sequencing of primary lung cancers correlating with the brain tumor response to radiosurgery, to study this concept.
When we talk more about registries and Brainlab's been a tremendous supporter of the National American Registry and Radiosurgery, I call this databased discovery. So all of our patients are entered into prospective data collection systems so we have a better sense of the dynamic. What will be next? Well, in the world of neurosurgery and radiation oncology for the last 25 years, we've got an 80% to 90% response rate treating brain metastasis that's mostly durable with no systemic toxicity. The new kid on the block is the medical oncologist taking care of brain metastasis with a drug response maybe at 40% to 55%, less durable, often toxic.
So my goal is keeping brain metastases small, and if you treat them medically and they grow, there can be edema. There can be a seizure. Now there's a neurologic problem that they didn't have before. And these are not trivial. And so it's not, we have to be very careful with how we take care of these fragile patients. Keeping the tumors small and in control is what we do and what we do very well. So I'm gonna stop there and happy to make, take any questions or move on to the next talk. Thank you very much.
So what were the old rules? Not that Dr. Yamamoto was old, he's gonna speak in a few minutes. But the old rules, you resect the large tumors, you give postop whole brain. Systemic cancer therapy is of little value. We almost ignore it. The goal is palliation so a few people live, so cognition's really not an issue. And if you have left leptomeningeal disease, you give whole brain or intrathecal chemo. Then we have the still sort of old rules with someone who's sort of old. My friend, Tony Asher will speak next. We go resect the larger tumors, then whole brain. Systemic cancer therapy is of little value for most indications, still palliative radiosurgery for smaller numbers of tumors, still leptomeningeal disease.
What are the new rules? You resect a radio surgery for the large tumors, or you do both. Systemic cancer therapy may have brain benefit for many indications now. The goal is extended survival, not palliation. Never whole brain radiation therapy, unless there's miliary disease. Radiosurgery for any number, perhaps up to 25. We'll talk a little bit about that. Plus drug. The drug is the new whole brain and leptomeningeal disease is changing as well. Now, radiosurgery, if it's focal, whole brain or systemic drug therapy.
So little snapshot from our registry from last year, just to show you that in 2017, only 6.5% of our patients got whole brain radiation at a total of 261 patients with brain Mets that I cared for last year. If you go back four years, it was double 12%. So the number of patients getting whole brain radiation therapy is just going down year after year. Four years ago, we wrote this paper looking at reevaluating what was going on in brain metastasis. This is already out of date again. And really, the rules are changing so quickly. And of course, we can do radiosurgery with different technologies, with different methods of head fixation, framer mask, depending on how you wanna do it, single session, multi session.
So let's talk a little about the rules that are changing. In lung cancer of course, the commonest cause of brain metastasis. It's all about the mutations as we know. Certain patients have EGFR mutation, a mutation for which they're driving therapies. Some of the other mutations do not have specific therapies yet, but this is all about knowing that either there's a mutation or there's a PDL1 level that drives immunotherapy. And of course, if someone has EGFR, we expect them to live. We don't expect them to die now within the shorter timeframe. And this paper, which we wrote in 2016, is already out of date. And the reason it's out of date is because of the new EGFR therapies that did not exist when this paper was written just a couple of years ago.
So we know that survival is changing rapidly based upon the targeted therapies with an EGFR mutation pushing three years here, as opposed to the old median survival for lung cancer, which was always 11 months. All through the 90s and 2000s, no matter what study was done, median survival was 11 months. Now, that's not the case anymore.
So here's a 63-year-old woman with a non-small cell cerebellar vermis. You can see the response to a dose of 18 gy. I'm not a high dose guy. I never go above 20 for example, that's a separate topic. But look what's in the auditory canal. This was a never a radiosurgery case. The radiology report will say leptomeningeal disease. Of course, it is. Patients got a facial weakness. That's a radiosurgery case to us. If it's focal 16 gy, you can see the response with return of facial function.
So focal leptomeningeal disease, I think is an expanding new thing for radiosurgery applications. And in this series, half the patients who had it were able to avoid whole brain radiation, utilizing radiosurgery plus drug. Even in non-mutated non-small cell lung cancer, the drugs Alimta and Carbo are keeping people alive longer. And the radiosurgery response, even in tumors with necrosis can be impressive.
So if they're non-mutated, we're looking at PDL1 levels and what's a positive PDL1? Is it 80%, 20, 10 virtually anything above 10 is driving immunotherapy as a first care. So here's nivolumab. Unfortunately, the patient got side effects of that drug, pneumonitis. So it was stopped. Here's radiosurgery at 19 gy. Two months looks great, four months, it's bigger. Thinking, oh, maybe this is immunotherapy. It's not. Six, five and a half months, it's getting bigger. It's radiosurgery failure. We removed it, but very little tumor except for little islands of cancer cell at the edge still growing. So that dose was not enough in this setting, even with immunotherapy.
So what's going on? In 2018, high PDL1 pembrolizumab, ALK, crizotinib, now alectinib, now brigatinib. Virtually a drug every 18 months or so, EGFR positive. We've gone from afatinib to alectinib to osimertinib, and now brigatinib and what's coming next in 2019. So what about upfront medical therapy? That's a hot topic right now. Should that be the management and we defer radiosurgery for these small tumors. Well, this very important study from Yale looking at drug alone, showing that upfront drug alone did not do as well as radiosurgery plus drug. So we're very aggressive continuing to use radiosurgery with a 90% control rate for small metastasis. And it's all about the tumor types of course. So we don't have enough literature on subtypes and responses.
So here's a paper on volumetric response. And as a journal editor, I always argue write your articles on specific cancer types, no longer on brain metastases. Don't lump breast cancer with lung cancer. They're different diseases, and they have nothing to do with each other. So even breast cancer subtypes are now very specific, triple negative versus luminal one, luminal two, these are different kinds of tumor and different biology.
And of course, when we see a tumor like this in the motor cortex, if it's breast cancer, we expect a volumetric regression that will be impressive. We would not expect this in melanoma. So the decision to do radiosurgery here is gonna be very different than other cancer types based upon the response. So in a patient like this who's had prior whole brain radiation, has a massive cerebellar tumor as you can see on the left, has a partial resection. There's tumor left over as you can see here, 12 tumors, undergoes radiosurgery to relatively low dose because it's breast cancer, has an impressive volumetric response, and later has over four procedures for 53 tumors over the next three years before she eventually succumbs. And you can see in this young woman, the white matter changes from the original whole brain radiation therapy.
So let's go to the worst situation, which is melanoma, a big problem that we all face. So it's all to be or not to be and be is the BRAF. So melanoma's either a BRAF mutation or not. And if they have it, they're gonna get a BRAF targeted agent. If not, they're typically gonna get combined immunotherapy now. And the impressive thing was median survival for melanoma before this driver was always seven months, six months. Now half of our BRAF series are over three year survivors now.
So single met 20 gy, three years, no tumor, that's a common expectation in patients with a BRAF mutation. And the response to radiosurgery doesn't matter. Whether they're mutated or not, the volume response will be the same. Local control rates are high in the 90% range. And for the first time we've got median survivals for melanoma that are passed one year. So the patients are living long, and this is impressive.
So if you look at this patient with a BRAF tumor, she's 42 year old, she's got multiple metastasis. You can see here, there's a tumor that's small. She has a, I do a couple of craniotomies. Eventually, this tumor enlarges. She has radiosurgery and it shrinks over here, but eventually for a year later, that thing gets bigger. And we watched it and we thought, God, this gotta has to be a radiation effect, but it was not, it was tumor progression. And I sent this to Veronica Chang, who'll be speaking later. She did a biopsy of this conforming cancer and then did laser interstitial therapy of this tumor. I really didn't wanna resect this tumor in this location.
This was the largest tumor that she had done a LITT case on. And you can see the heat-based necrosis from the laser and at four months. And now at 26 months, the impressive regression of this tumor, patients had no active brain disease now for 18 months. 43-year-old patient of cousin of one of my nurses with BRAF melanoma 16 Mets presents during pregnancy is recommended to have whole brain radiation. We treat all 16, goes on drug, and here's the 30 month scan below. These are cases you would never see before.
Melanoma BRAF positive five years with brain metastasis, two craniotomies. I show you this drug response because this is recent. Now, there's on the left, you'll see nodular tumor over here, as well as above the corpus callosum. And there's other tumors, patients failing both dabrafenib and mechanists, traditional BRAF therapy failed immunotherapy. And so what's the next BRAF generation drug? It's binimetinib. This has only been available. It's experimentally for about a month. Patient goes on the drug and you can see within two weeks, the response over here.
Now, look what happens. The patient stops taking the drug. The medical oncologist took them off because of some platelet count issues. And the tumor grows back on the middle slide within five weeks. We said, "Listen, you gotta take your drug." Two weeks later, the tumors are smaller. So what is happening? The targeted agent is doing an amazing thing here. We don't know if this is durable though. So what's the hot topic? It's combined immunotherapy for melanoma. You're probably seeing this report in the "New England Journal." Everybody says, well, this is impressive. To me, this is not that impressive I have to say.
Stable disease over six months, two out of 94 cases, the response rate was around 55% compared to a radiosurgery response in the 85% to 90% range with an important adverse event profile. It's good, but it's not great. There's a lot of failures. I take care a lot of these failures and there's significant toxicity. No doubt it's gonna help their systemic therapy. Is it a replacement for the treatment of brain disease? In my opinion, it is not. So what to do for large brain metastasis. Tony's gonna speak about this in the next presentation. Everybody's doing something different.
I think if we pulled the room, everybody's doing something on this list. Resect and irradiate, whole brain, large field RT, lower dose radiosurgery and see what happens. Hypofractionated, multiple radio surgeries over a few weeks like in Japan, or, as Tony will talk about, neoadjuvant radiosurgery and then resection. There's no right answer. This is what I do. Here's a 62-year-old physician. I wonder what Tony would do in a case like this, sizable tumor, swelling, having balance problems.
I said, "Listen, I would resect this, radiate, do the bed standard type of thing." She said, "I don't wanna a resection." Fine. So we do radiosurgery alone. She's got another tumor in the other cerebellum, 17 gy and 18 gy colon cancer, kind of a variable response expectation, steroids for four weeks, repeat the scan. You can see the volumetric response. So she needs nothing else. And here's the 18-month scan there. Were we lucky, or is this the expectation? To me, it's about radiosurgery and assessing the biology over a month. And if it's going in the right direction, I observe. If it's not going in the right direction, I resect.
How many is too many? A big question that research has addressed over the years. Well, when I started doing this over one was heresy. If you had two tumors, when I started doing this, we would turn you down. It was amazing. We thought this is inappropriate to do radiosurgery for two tumors. Then it was four. Then it was 10. You know, what is heresy now? We're all kind of heretics in some way.
Dr. Yamamoto is really the person responsible for pushing the limits of numerical-based radiosurgery. Of course, his seminal paper showing that five to 10 tumors was no worse than two to four tumors, but how many is too many? This is a 45-year-old attorney with breast cancer, has had whole brain radiation, 26 tumors, seven months later. This, she needed whole brain radiation. It's a little dark, but you can see that she had miliary disease and the whole brain radiation cleared this only for tumors to develop. So it was needed. So we took care of this 13 tumors one week, another 13 the next week. They all, for the most part resolved. And five years later have treated more than 100 tumors at 11 radiosurgery still works as an attorney.
Again, one of the interesting things was she lived long enough to go on a clinical trial geared to preventing new brain metastasis and breast cancer. And that cleared her for about 18 months before new tumors came up. So [inaudible 00:13:44] will be speaking later. [inaudible 00:13:45] is here. The concept of younger people avoiding whole brain radiation, having improved outcomes with radiosurgery alone is provocative. And of course, the seminal study from Dr. Asher and Paul Brown, looking at cognition with limited numbers of tumors, showing that the avoidance of whole brain radiation was a good thing.
Again, we all know it's going away. Tumor bed, we're gonna talk about the concept of how to manage the tumor either before or after resection. 10 years ago, this science starts, but now it's been evaluated in randomized trials at several centers. The research shows observation after resection six months, radiosurgery, 14 months, and then this other important study, postoperative radiosurgery, more cognitive decline with whole brain is just not needed, but no survival benefit.
We'd love to show you what's going on in adverse radiation effects. We're always challenged with this. My personal goal in life is to get rid of decadron and replace it with something better. And hopefully it'll be bevacizumab. There's a lot of good work going on, including the Alliance Trial that we participating randomizing patients to with steroids or bevacizumab. And I think routine avastin is the future.
But to show you here's a case of ovarian cancer in an older woman I took care of, 17.5 gy. Two months, looking a little expanded, three months, not looking gr...she's asymptomatic, amazingly enough, thinking, oh my God, maybe this was a glioblastoma and we missed it. And so we sent her over for the trial. They didn't put her on the trial, just gave her a little dexamethasone and observed. You can see the complete resolution about 95% of the volume over the next year and a half. So no avastin needed.
Here's one of mine. Again, it's looking a little expanded, seven months, eight months. There's a couple of Mets looking bigger, more inflammatory. We put this patient on the study. We don't know if they get bevacizumab or steroid, but what do you think the patient got? Because look at the 10-month and 20 month scans, it looks like a bevacizumab response with less enhancement. I don't know if that's the case though.
What about peri-radiosurgery bevacizumab? So here's a patient who got whole brain radiation for 12 tumors, a young man with a positive lung cancer. One of the 12 tumors grew and it grew over a year. Patient refused to have radiosurgery for whatever reason, came to us. Tumor was pretty big. Eventually look at size on the third slide when we took care of this. So we put them on avastin first, a few cycles. We did five gy times five in the midst of avastin, then another three or four cycles. And you can see the four-month scan. We got away with this. Perhaps the avastin helps. And now we're starting to use this drug around complex tumors.
So a lot's changing. And we always thought we knew something about radiation sensitivity. Melanoma's more resistant. Breast is more sensitive. Maybe lung is in the middle. We've been taught this in medical school for 50 years. Is it really true? Well, there's some really interesting work going on, looking at individual patient radio sensitivity based upon the genetic array of their tumors. So not every breast cancer is sensitive and not every melanoma is resistant necessarily, which probably explains why it works better than we think it should work, and it doesn't work when we think it shouldn't work. And so we're doing next generation sequencing of primary lung cancers correlating with the brain tumor response to radiosurgery, to study this concept.
When we talk more about registries and Brainlab's been a tremendous supporter of the National American Registry and Radiosurgery, I call this databased discovery. So all of our patients are entered into prospective data collection systems so we have a better sense of the dynamic. What will be next? Well, in the world of neurosurgery and radiation oncology for the last 25 years, we've got an 80% to 90% response rate treating brain metastasis that's mostly durable with no systemic toxicity. The new kid on the block is the medical oncologist taking care of brain metastasis with a drug response maybe at 40% to 55%, less durable, often toxic.
So my goal is keeping brain metastases small, and if you treat them medically and they grow, there can be edema. There can be a seizure. Now there's a neurologic problem that they didn't have before. And these are not trivial. And so it's not, we have to be very careful with how we take care of these fragile patients. Keeping the tumors small and in control is what we do and what we do very well. So I'm gonna stop there and happy to make, take any questions or move on to the next talk. Thank you very much.