Transcript
I would like to thank BrainLab for setting up this symposium, and thank you for attending. It's actually great to be here, inside, because I just checked and it's like 90 degrees outside. It feels like 97 degrees, though. So the title of my talk is Paradigm Shift in Management of Intracranial Metastasis: A Review of the First 1,200 Tumors Treated.
This is my disclosure. As physicist, we like to have a theory about things and about theory of cancer is actually simple definition of cancer is cells start to proliferate uncontrollably in an organ and spread out to other organs, we call it metastasis. Cancer is a condition that we have to mitigate its effects and its conditions has to be managed. I mean, as you know, we have a term of curing cancer, is about go five years without that disease. Cancer is not only in humans, but also in all biologies, and 90% of cancer deaths are from metastatic disease.
Dave Andrews performed an RTOG study that published and basically brain metastasis is up to 40% of all patients with systemic cancer. Due to improved cancer therapy for systemic disease, it's imperative that improved intracranial therapy be developed as well. Traditional LINAC-based SRS treatment of multiple CNS lesions is performed using multiple isocenters. The treatment time is proportional to the number of lesions treated, at about typically 20 to 30 minutes per isocenter, using the frameless image-guided radiosurgery.
Frameless image-guided radiosurgery is an effective and routine technique for treating multiple cranial lesions, utilizing robotic couch and image guidance, performing the 3D translational and 3D rotational corrections. This is a very improving STX with BrainLab ExacTrac system and IGRS system on that. LINAC-based radiosurgery is basically you are using geometric superposition that you basically divide those in different arcs and converging at the isocenter. Since the inception of radiosurgery back in the late '90s, we have been doing mostly frame-based, and in 2008, we basically almost 100% went to frameless radiosurgery using masks.
Advantage of that is no sedation required, frees up neurosurgeon and nurses, no bleeding and no pain, flexible scheduling, which is very important for physicists. Otherwise we have to stay until everything is treated. Patients can be treated on different days and no sterilization is required.
This is a comparative study of precision of the various types of delivery systems. Gamma Knife, these are end-to-end, including imaging, resolutions, and fusion. So resolutions are similar in terms of...sorry, the precisions are similar, 0.48 mm Cyber Knife, with Chang, published from Stanford, it's 1.1. This is a frame-based radiosurgery system with frameless radiosurgery precision.
This is a 16-year-old male with ALK positive, which developed on presentation brain metastases, which was resected. But his lung cancer is basically controlled, but he kept getting brain metastases. We treated 50 tumors. We started when he was 16. Now he's 23, out of college, and he's totally cancer free. The patients with this kind of genetically positive, like ALK, they can live a long time. This is the dosimetry done on 47 lesions, and the blue color is actually the overall whole-brain dose from all these 47 lesions, which is about 9.5 Gy. But that patient with 47 or 50 lesions, so, even ultimately treated, it takes like 25 hours if you do 50 isocenters.
Kaiser Permanente Radiation Oncology is a regional cancer center, which we cover over four million members. We have three locations in LA, and Ontario, and Anaheim. We have a TrueBeam STx that we basically treated 934 lesions since we commissioned multimed package of elements, back in April of 2017. And then, we are installing, currently as we are speaking, another TrueBeam STx with ExacTrac. Our Anaheim office commissioned it back in 2018 and have treated 60 patients with 290 lesions. And we are also installing another system in our Ontario office doing radiosurgery.
There are various types of MLCs. This is obviously our classical Novalis that we actually replaced with the TrueBeam STx and this is the Millenium MLC in Anaheim, using a wider beam.
Our workflow is the way we set up, the patient comes with an MR either a couple of days before radiosurgery or on the day of radio surgery. Then we do the CT on the same day, and then image fusion. We have a dose volume grade that we are using. As the volume goes higher, obviously dose goes down, and then we do a planning system. And after approval, we do the QA using Map phan, Map phantom. I'm not going to go into detail, because Dr. Arguzelio [SP] is going to cover some of those.
Then, we treat the patient with ExacTrac. Every couch angle we image and then we correct for the robotic inaccuracies and we deliver.
Basically, since May of 2017, to a couple of weeks ago, we treated 182 patients, 223 courses of Element SRS. We had cases that they came multiple times, up to four or five courses. Overall, number of lesions was 1,200 or 1,200. Sixty patients with Millenium MLC, and 132 patients treated with HC. The average volume of all the lesions, the minimum volume was 0.66 cc, which is the PTV maximum is 3.48. Overall volume, the tumor burden is 6.86 ccs. The dose varied from 1500 to 2400 cGy. Average MU is 6000. Mean number of lesions per course of radiosurgery is 6, +/- 4. Mean number of lesions per patient is 7 +/- 4. So, the overall Q/A that we have done using 1 to 2 mm DTA and 3 to 5% dose criteria is about 98% passing.
We looked at the subset of our patients, 40 of them, that we treated back in 2017, and these patients had 287 lesions. We planned it with five or six couch rotations, which basically, we have up to 12 dynamic conformal arcs. And we run both 6X and 6X flattening filter free and we compare which one is better. We use that for delivery. IGRS was delivered using 6D robotic couch. Our criteria is to make sure we meet better than 0.5 mm and 0.5 degree corrections.
Out of these 40 patients, we had 47 treatment sessions, 283 lesions. The mean age is 57 years old. Lesions treated is, on the average is five. Out of these, total volume is 3 ccs. Whole brain dose was 123 and median and hippocampal dose is 153 cGy.
The pathology, the distribution is typical for us. It is the majority, non-small cell carcinoma of the lung, and then breast cancer, and basically melanoma in Southern California, especially young patients, and then renal cell carcinoma and other malignancies.
This dose Gy that we are using, basically, this part is less than 0.5 cc, gets 22.5 Gy to 95% volume, and then steadily goes down as volume goes higher. And for over 10 cc, we fractionate in three fractions, and if it's over 20 cc we do five fractions.
This is a beam's eye view of the delivery of multi-mapped, and you can see all the lesions. If it's seen by that particular arc is being treated simultaneously. This is an example of a patient we treated a couple of weeks ago, 17 lesions in two isocenters, and you can see the distribution of the lesions versus anatomy, and the dose distribution looks like this. The other dose is 50% iso line, and then the blue is the whole-brain dose, which, in this patient, was about 5 Gy.
The results after two months imaging, based on image analysis was 85% local control. And six patients showed radiographic enlargement of treated lesions. At the time of analysis 70% were alive, 12% death due to neurological causes. And the death was significantly associated with the number of lesions. Few cases of radiation necrosis. Overall, out of these 1,200, we have about 15 or 16 confirmed necrosis, which is very low.
Three patients developed seizures. Three patients also developed transient fatigue and confusion. Two patients developed weakness, that improved with steroids. On univariate analysis, toxicity was significantly associated with the total treatment volume, which is significant, but not the number of lesions. We have patients that you could have 15 or 20 lesions, but they could be, overall, like 4 ccs. And those are totally respond, and also they can survive much longer.
And we have cases, young patients, like 24, with melanoma with 100 ccs with tumor with three lesions or four lesions, and they basically last one month. So, the numbers is not an issue. The total volume is actually in our series. Toxicities are associated actually with total volume of more than 5 ccs.
So there's a few cases of before and after. This is a patient with renal cell carcinoma, 40-year-old, and he's responded after a few months, and then you have a new lesion. Case two, the volume is like 0.01 cc to 0.26 cc GTV with 1 mm margin, we have 0.05 to 0.5 ccs, and after four and a half months, you can see, basically, the tumors are gone. This one here.
This patient with lung carcinoma with 14 lesions. After four and a half months, you can see the tumor here. This one here. So I just wanted to also show you how small the lesions are. These are really tiny lesions and you can actually treat them very effectively using the IGRS system, because the precision is there. The advantage of a single iso versus multi-iso is shorter overall treatment time, similar conformity and gradient indices, and significantly lower overall monitor units.
I did a case a few weeks ago, that basically, this patient had eight lesions and I did eight isocenters with eight lesions, and this is the conformity index and this is the gradient index. Overall, monitor unit to treat eight lesions with eight isocenters is 35,000 MU. Each lesion takes about 30 minutes, and overall, is like four hours treating this.
And I compared it with single iso, eight lesions, and using the same energy, 6XFFF with Millennium MLC, you get like one fourth of, a quarter of the MUs. If you do 6X Millennium, you get 1/7th, and if you do 6XFFF with HD, you get 7,500. But you can also look at the conformity index on this one, which is 1.23 versus 1.28. So you save a lot of MUs, which actually translates to head of the LINAC leakage, which is 0.1% of the output.
One thing is that, since multi-met your jaws are open, because you are treating multiple lesions. Obviously, if you look at the whole-brain dose, which is in solid, this is slightly worse. Sorry, the dotted is the single iso, the solid line is the multi iso. And slightly less because your jaws are open, you get 1.8% leakage, interleaf leakage from Millennium, and 1.2% leakage from HD, but other structures are very similar.
I just want to emphasize that using single isocenter multi-lesions, you have to make sure that your rotation is corrected adequately. Because you have multi-lesions all over the brain and you have an isocenter, which is a normal brain, and in an experimental where they are matching creating multiple lesions, if you have everything is lined up at the isocenter, you have 96% absolute dose passage. But when you have 1 mm deviation in pitch, roll, and yaw, and if it goes uncorrected, the pass rate goes down to 83%. And like, if you have uncorrected like yaw, then you get up to even 58% passage rate. So you don't deliver correctly. And you can see this is at 0, 0, 0, and then when you go to a yaw, roll, and pitch of 1 degree, you can see the dose distribution changes, and the pass rate is like 80 some percentage. You can see the measurement points, which is off. These are the actually measured, and the graph is actually the plan. And you can see these are actually going linearly as your yaw and pitch and roll are not corrected, your delivery is not that accurate.
Now, I'm going to a different topic that is actually challenging to us. This is a patient that is on Tagrisso with lung cancer, and these patients are EGFR positive, and they get Tagrisso. And this patient had nine lesions, and we treated, and all responded. And sorry my angle is where I can't see very well. So this is a lesion that responded very well, and the same here.
But since he was on Tagrisso, this is October, he came with 12 new lesions. But since he was on EGFR therapy after radiosurgery, all these lesions actually responded to EGFR. So, here, responded to without radiosurgery. And then we had an 80-year-old male, that, well, he was on Tagrisso, and we treated him back in May and the tumor started growing. The patient was going down and we were confused what's going on. And then, when the medical oncologist stopped the Tagrisso, he totally responded. So you have both ways, you can respond, Tagrisso can actually treat some tumors and you can have an adverse effect post-radiosurgery and the same as here.
This is like a couple weeks ago, this patient with three lesions, with EGFR positive under Tagrisso, and we did radiosurgery here, but as you can see like a pseudo-progression here. The same as this tumor, and here, too.
And then, this patient was on Alectinib and was ALK-positive targeted therapy. You can see the tumor is actually, without radiosurgery, is in control. But this patient had a huge lung tumor and we wanted to treat with SBRT. And basically, the medical oncologist stopped the Alectinib, and then all of a sudden, he went down and had a lot of symptoms, cranial symptoms, and then the tumor significantly grew because of stopped the Alectinib. And then, at this point, we gave radiosurgery and a couple weeks later, he totally responded. And you can see the dose distribution.
So, in conclusions, cancer will be soon a number one cause of death in U.S. Current noninvasive radiosurgical techniques in combination with either chemotherapy, targeted therapies, or immunotherapies improve patient survival, quality of life, and local controls. Technology will change how cancer is prevented, detected, and treated in amazing new ways. For patients with multiple brain mets, utilizing IGRS with a single isocentric technique using BrainLab's forward planned dynamic arcs reduced the planning and table treatment times.
This radiosurgical treatment approach helps our patients with multiple brain mets to have access to this new technology that we would have otherwise given whole-brain radiation, which has implications, neurocognition implications, as well as we had to send them to hospice. Our preliminary analysis of the subset of all this data show that 85% local control in two months. Lower monitor units allow for lower whole-brain dose, especially if you compare with VMAT delivery.
Observed toxicities were transient, and possibly unrelated to IGRS treatment in all cases. The patient cases presented illustrates how technology and innovations are providing new hope for cancer patients and their loved ones.
The challenges we see, we have treated patients up to 45 lesions in single iso in several courses. Having the inventory of the lesions being treated is a challenge for us, because we don't want to overtreat patients or retreat those tumors by error. So we have to have a system of, hopefully, a software using AI or other methodology to prevent retreatment by error.
The interaction of the new immuno and targeted therapies with radiosurgery for the management of intracranial metastasis is not well understood and need to be researched to our advantage for better cancer management and improved outcomes.
So we came a long way from Medieval times in terms of having surgery and this kind of, basically, faith-based surgery as well as frame-based radiosurgery, frame-based and frameless and then image-guided multi-isocenter, and then now the single iso and multiple metastases.
I want to acknowledge my colleagues, physicists, as well as radiation oncologists and residents. And thank you for your attention.
This is my disclosure. As physicist, we like to have a theory about things and about theory of cancer is actually simple definition of cancer is cells start to proliferate uncontrollably in an organ and spread out to other organs, we call it metastasis. Cancer is a condition that we have to mitigate its effects and its conditions has to be managed. I mean, as you know, we have a term of curing cancer, is about go five years without that disease. Cancer is not only in humans, but also in all biologies, and 90% of cancer deaths are from metastatic disease.
Dave Andrews performed an RTOG study that published and basically brain metastasis is up to 40% of all patients with systemic cancer. Due to improved cancer therapy for systemic disease, it's imperative that improved intracranial therapy be developed as well. Traditional LINAC-based SRS treatment of multiple CNS lesions is performed using multiple isocenters. The treatment time is proportional to the number of lesions treated, at about typically 20 to 30 minutes per isocenter, using the frameless image-guided radiosurgery.
Frameless image-guided radiosurgery is an effective and routine technique for treating multiple cranial lesions, utilizing robotic couch and image guidance, performing the 3D translational and 3D rotational corrections. This is a very improving STX with BrainLab ExacTrac system and IGRS system on that. LINAC-based radiosurgery is basically you are using geometric superposition that you basically divide those in different arcs and converging at the isocenter. Since the inception of radiosurgery back in the late '90s, we have been doing mostly frame-based, and in 2008, we basically almost 100% went to frameless radiosurgery using masks.
Advantage of that is no sedation required, frees up neurosurgeon and nurses, no bleeding and no pain, flexible scheduling, which is very important for physicists. Otherwise we have to stay until everything is treated. Patients can be treated on different days and no sterilization is required.
This is a comparative study of precision of the various types of delivery systems. Gamma Knife, these are end-to-end, including imaging, resolutions, and fusion. So resolutions are similar in terms of...sorry, the precisions are similar, 0.48 mm Cyber Knife, with Chang, published from Stanford, it's 1.1. This is a frame-based radiosurgery system with frameless radiosurgery precision.
This is a 16-year-old male with ALK positive, which developed on presentation brain metastases, which was resected. But his lung cancer is basically controlled, but he kept getting brain metastases. We treated 50 tumors. We started when he was 16. Now he's 23, out of college, and he's totally cancer free. The patients with this kind of genetically positive, like ALK, they can live a long time. This is the dosimetry done on 47 lesions, and the blue color is actually the overall whole-brain dose from all these 47 lesions, which is about 9.5 Gy. But that patient with 47 or 50 lesions, so, even ultimately treated, it takes like 25 hours if you do 50 isocenters.
Kaiser Permanente Radiation Oncology is a regional cancer center, which we cover over four million members. We have three locations in LA, and Ontario, and Anaheim. We have a TrueBeam STx that we basically treated 934 lesions since we commissioned multimed package of elements, back in April of 2017. And then, we are installing, currently as we are speaking, another TrueBeam STx with ExacTrac. Our Anaheim office commissioned it back in 2018 and have treated 60 patients with 290 lesions. And we are also installing another system in our Ontario office doing radiosurgery.
There are various types of MLCs. This is obviously our classical Novalis that we actually replaced with the TrueBeam STx and this is the Millenium MLC in Anaheim, using a wider beam.
Our workflow is the way we set up, the patient comes with an MR either a couple of days before radiosurgery or on the day of radio surgery. Then we do the CT on the same day, and then image fusion. We have a dose volume grade that we are using. As the volume goes higher, obviously dose goes down, and then we do a planning system. And after approval, we do the QA using Map phan, Map phantom. I'm not going to go into detail, because Dr. Arguzelio [SP] is going to cover some of those.
Then, we treat the patient with ExacTrac. Every couch angle we image and then we correct for the robotic inaccuracies and we deliver.
Basically, since May of 2017, to a couple of weeks ago, we treated 182 patients, 223 courses of Element SRS. We had cases that they came multiple times, up to four or five courses. Overall, number of lesions was 1,200 or 1,200. Sixty patients with Millenium MLC, and 132 patients treated with HC. The average volume of all the lesions, the minimum volume was 0.66 cc, which is the PTV maximum is 3.48. Overall volume, the tumor burden is 6.86 ccs. The dose varied from 1500 to 2400 cGy. Average MU is 6000. Mean number of lesions per course of radiosurgery is 6, +/- 4. Mean number of lesions per patient is 7 +/- 4. So, the overall Q/A that we have done using 1 to 2 mm DTA and 3 to 5% dose criteria is about 98% passing.
We looked at the subset of our patients, 40 of them, that we treated back in 2017, and these patients had 287 lesions. We planned it with five or six couch rotations, which basically, we have up to 12 dynamic conformal arcs. And we run both 6X and 6X flattening filter free and we compare which one is better. We use that for delivery. IGRS was delivered using 6D robotic couch. Our criteria is to make sure we meet better than 0.5 mm and 0.5 degree corrections.
Out of these 40 patients, we had 47 treatment sessions, 283 lesions. The mean age is 57 years old. Lesions treated is, on the average is five. Out of these, total volume is 3 ccs. Whole brain dose was 123 and median and hippocampal dose is 153 cGy.
The pathology, the distribution is typical for us. It is the majority, non-small cell carcinoma of the lung, and then breast cancer, and basically melanoma in Southern California, especially young patients, and then renal cell carcinoma and other malignancies.
This dose Gy that we are using, basically, this part is less than 0.5 cc, gets 22.5 Gy to 95% volume, and then steadily goes down as volume goes higher. And for over 10 cc, we fractionate in three fractions, and if it's over 20 cc we do five fractions.
This is a beam's eye view of the delivery of multi-mapped, and you can see all the lesions. If it's seen by that particular arc is being treated simultaneously. This is an example of a patient we treated a couple of weeks ago, 17 lesions in two isocenters, and you can see the distribution of the lesions versus anatomy, and the dose distribution looks like this. The other dose is 50% iso line, and then the blue is the whole-brain dose, which, in this patient, was about 5 Gy.
The results after two months imaging, based on image analysis was 85% local control. And six patients showed radiographic enlargement of treated lesions. At the time of analysis 70% were alive, 12% death due to neurological causes. And the death was significantly associated with the number of lesions. Few cases of radiation necrosis. Overall, out of these 1,200, we have about 15 or 16 confirmed necrosis, which is very low.
Three patients developed seizures. Three patients also developed transient fatigue and confusion. Two patients developed weakness, that improved with steroids. On univariate analysis, toxicity was significantly associated with the total treatment volume, which is significant, but not the number of lesions. We have patients that you could have 15 or 20 lesions, but they could be, overall, like 4 ccs. And those are totally respond, and also they can survive much longer.
And we have cases, young patients, like 24, with melanoma with 100 ccs with tumor with three lesions or four lesions, and they basically last one month. So, the numbers is not an issue. The total volume is actually in our series. Toxicities are associated actually with total volume of more than 5 ccs.
So there's a few cases of before and after. This is a patient with renal cell carcinoma, 40-year-old, and he's responded after a few months, and then you have a new lesion. Case two, the volume is like 0.01 cc to 0.26 cc GTV with 1 mm margin, we have 0.05 to 0.5 ccs, and after four and a half months, you can see, basically, the tumors are gone. This one here.
This patient with lung carcinoma with 14 lesions. After four and a half months, you can see the tumor here. This one here. So I just wanted to also show you how small the lesions are. These are really tiny lesions and you can actually treat them very effectively using the IGRS system, because the precision is there. The advantage of a single iso versus multi-iso is shorter overall treatment time, similar conformity and gradient indices, and significantly lower overall monitor units.
I did a case a few weeks ago, that basically, this patient had eight lesions and I did eight isocenters with eight lesions, and this is the conformity index and this is the gradient index. Overall, monitor unit to treat eight lesions with eight isocenters is 35,000 MU. Each lesion takes about 30 minutes, and overall, is like four hours treating this.
And I compared it with single iso, eight lesions, and using the same energy, 6XFFF with Millennium MLC, you get like one fourth of, a quarter of the MUs. If you do 6X Millennium, you get 1/7th, and if you do 6XFFF with HD, you get 7,500. But you can also look at the conformity index on this one, which is 1.23 versus 1.28. So you save a lot of MUs, which actually translates to head of the LINAC leakage, which is 0.1% of the output.
One thing is that, since multi-met your jaws are open, because you are treating multiple lesions. Obviously, if you look at the whole-brain dose, which is in solid, this is slightly worse. Sorry, the dotted is the single iso, the solid line is the multi iso. And slightly less because your jaws are open, you get 1.8% leakage, interleaf leakage from Millennium, and 1.2% leakage from HD, but other structures are very similar.
I just want to emphasize that using single isocenter multi-lesions, you have to make sure that your rotation is corrected adequately. Because you have multi-lesions all over the brain and you have an isocenter, which is a normal brain, and in an experimental where they are matching creating multiple lesions, if you have everything is lined up at the isocenter, you have 96% absolute dose passage. But when you have 1 mm deviation in pitch, roll, and yaw, and if it goes uncorrected, the pass rate goes down to 83%. And like, if you have uncorrected like yaw, then you get up to even 58% passage rate. So you don't deliver correctly. And you can see this is at 0, 0, 0, and then when you go to a yaw, roll, and pitch of 1 degree, you can see the dose distribution changes, and the pass rate is like 80 some percentage. You can see the measurement points, which is off. These are the actually measured, and the graph is actually the plan. And you can see these are actually going linearly as your yaw and pitch and roll are not corrected, your delivery is not that accurate.
Now, I'm going to a different topic that is actually challenging to us. This is a patient that is on Tagrisso with lung cancer, and these patients are EGFR positive, and they get Tagrisso. And this patient had nine lesions, and we treated, and all responded. And sorry my angle is where I can't see very well. So this is a lesion that responded very well, and the same here.
But since he was on Tagrisso, this is October, he came with 12 new lesions. But since he was on EGFR therapy after radiosurgery, all these lesions actually responded to EGFR. So, here, responded to without radiosurgery. And then we had an 80-year-old male, that, well, he was on Tagrisso, and we treated him back in May and the tumor started growing. The patient was going down and we were confused what's going on. And then, when the medical oncologist stopped the Tagrisso, he totally responded. So you have both ways, you can respond, Tagrisso can actually treat some tumors and you can have an adverse effect post-radiosurgery and the same as here.
This is like a couple weeks ago, this patient with three lesions, with EGFR positive under Tagrisso, and we did radiosurgery here, but as you can see like a pseudo-progression here. The same as this tumor, and here, too.
And then, this patient was on Alectinib and was ALK-positive targeted therapy. You can see the tumor is actually, without radiosurgery, is in control. But this patient had a huge lung tumor and we wanted to treat with SBRT. And basically, the medical oncologist stopped the Alectinib, and then all of a sudden, he went down and had a lot of symptoms, cranial symptoms, and then the tumor significantly grew because of stopped the Alectinib. And then, at this point, we gave radiosurgery and a couple weeks later, he totally responded. And you can see the dose distribution.
So, in conclusions, cancer will be soon a number one cause of death in U.S. Current noninvasive radiosurgical techniques in combination with either chemotherapy, targeted therapies, or immunotherapies improve patient survival, quality of life, and local controls. Technology will change how cancer is prevented, detected, and treated in amazing new ways. For patients with multiple brain mets, utilizing IGRS with a single isocentric technique using BrainLab's forward planned dynamic arcs reduced the planning and table treatment times.
This radiosurgical treatment approach helps our patients with multiple brain mets to have access to this new technology that we would have otherwise given whole-brain radiation, which has implications, neurocognition implications, as well as we had to send them to hospice. Our preliminary analysis of the subset of all this data show that 85% local control in two months. Lower monitor units allow for lower whole-brain dose, especially if you compare with VMAT delivery.
Observed toxicities were transient, and possibly unrelated to IGRS treatment in all cases. The patient cases presented illustrates how technology and innovations are providing new hope for cancer patients and their loved ones.
The challenges we see, we have treated patients up to 45 lesions in single iso in several courses. Having the inventory of the lesions being treated is a challenge for us, because we don't want to overtreat patients or retreat those tumors by error. So we have to have a system of, hopefully, a software using AI or other methodology to prevent retreatment by error.
The interaction of the new immuno and targeted therapies with radiosurgery for the management of intracranial metastasis is not well understood and need to be researched to our advantage for better cancer management and improved outcomes.
So we came a long way from Medieval times in terms of having surgery and this kind of, basically, faith-based surgery as well as frame-based radiosurgery, frame-based and frameless and then image-guided multi-isocenter, and then now the single iso and multiple metastases.
I want to acknowledge my colleagues, physicists, as well as radiation oncologists and residents. And thank you for your attention.