So what I've been asked to do is to give an introduction, and I think rather than starting with a bunch of slides about why we use radiosurgery, when, et cetera, how do we contour, I was asked to give an overview. So I thought it would be important for the residents to just get a little bit of context of where we came from and why we started exploring spine radiosurgery. So to begin with, a picture of Pittsburgh, University of Pittsburgh has a very long history of radiosurgery with the first gamma knife in North America in 1985. For those of you who don't know where it is, I included a map in the bottom right-hand corner. So issues of spine metastases, most of what we're talking about when we talk about radiosurgery for the spine, it is metastatic disease. And there'll be a talk later today about benign tumors, but the vast majority we're still talking about malignant tumors in the spine for radiosurgery. We all know whether you're a neurosurgeon or a radiation oncologist, you're going to, when you're out and done with your residency, you're going to be treating a lot of these metastases, and it's only going to increase approximately over 200,000 new cases each year in the United States. The rule of thumb is that for every brain metastasis in the United States, there's a spine metastasis. And the impact of these metastases are very, very important, especially as these patients are living longer, there's pain, there's loss of mobility, they become, they fracture, leading to instability, leading to requirements for surgery, and even neurologic deficit. So especially for the radiation oncologists in the audience, and where we came from with surgery, well, it wasn't so long ago where we started operating as surgeons in the 1970s and 1980s doing these laminectomies, where you remove the bone from the back or from the front shown on the right, and it was temporarily abandoned. And the reason is that we found that radiation, and I'll show you some slides to support this, was actually just as good, if not better, than doing laminectomy alone. And then in the 1990s, 20 years ago, we started having the ability for new surgical approaches for this instrumentation stabilization that you're more familiar with today, but it wasn't that long ago. So we started doing big surgeries, and so now we can go from the front, back, and side, and we found we were better than the radiotherapy at the time. So the concepts behind our surgical techniques are rather straightforward. We need to decompress the neural elements, and then fixate the spine, so decompression and fixation. These next couple of slides just show the literature at the time, so you can see there from the 1960s, 70s, 80s, into the 90s, where what we found is that radiotherapy alone, conventional fractionated radiotherapy, was really not very good for these patients. And laminectomy alone, also not very good for these patients. You can see that with or without radiotherapy, it really didn't make a difference. So what are the indications for treating spine tumors with surgery, with radiosurgery, with radiotherapy? First and foremost, it's pain. Very different than all the lectures yesterday where we were talking about brain metastases, where none of those patients have pain. The primary reason that we, as clinicians, are seeing these patients is for pain. There are neurological symptoms, rather much less frequent, and instability, gross instability causing mechanical pain. Probably Mark will talk a little bit more about that later. So we have to minimize the effects of the tumor and maximize patient function and quality of life. We have to palliate their pain and control the tumor. We have to do both of those. So then, in the 1980s and 1990s, as I spoke about earlier, we started having the ability to stabilize the spine, and that was those rods and screw constructs. And then, all of a sudden, you see that the improvements in pain, the improvements in function increased tremendously. And then here, we could go from the front, where we could take out the entire vertebral body, not just decompress from the back, not just do a laminectomy, we stabilize, and our results were even better. So these patients are getting better and better, and we're really excited, as surgeons, in the 1990s, we can fix this problem. We're talking about unblocked resections of the metastases, taking out every tumor cell with surgery, and we were patting ourselves on the back. And then there was another trial, and you've all heard of the PATCHEL trial, that was published in 2005, the Spine PATCHEL trial. And it really changed everything, because it was the first evidence, class one evidence, where we randomized patients with spinal cord compression, with neurologic deficit, to surgery and radiotherapy, fractionated radiotherapy, and we found the patients who underwent surgery did better. There was no doubt about it. The trial was even stopped early, because the interim analysis showed that the patients getting surgery were doing so much better. The primary endpoint was ambulation. They had to think of, that was a major endpoint, but there were other endpoints that also improved. So surgery versus radiotherapy, that not only did they improve, but they had a longer duration of ambulation post-op. They were regaining ambulation. They were maintaining continence, regaining continence, even greater survival, and also lower requirements of opioids and corticosteroids after surgery. So in 2005, the medical oncologists were finally convinced, and the radiation oncologists, to send these patients for upfront surgery before radiotherapy. And this is just showing the survival time was actually greater in the surgery group than in the radiotherapy group. Just as an aside, and I'm not sure if any of the other speakers are going to speak about the SIN score that was developed, but for the neurosurgeons and the radiation oncologists, where what we have tried to do as a group, and many of the authors of this article are here this morning, where we tried to make it easy to determine who was unstable, or I should say which spine was unstable and which was stable. We have different scoring systems for trauma, but we didn't have one for oncology. So we worked together so that there could be a unified ability to communicate between different types of physicians, medical oncologists and surgeons and radiation oncologists and even radiologists, as to which patients needed to be stabilized and which could just go on for radiotherapy. So we have the ability to perform these major surgeries, as you can see here, with the rods and the screws, etc. But the problem is that we learned, unfortunately, there's a big price to pay. And that is that the morbidity of these operations are very, very high. These are some of our sickest patients. They have wound problems. They get infected. They break down because of prior radiation. And so we found that the complication rate of these surgeries is enormously high. And many of you have experienced those patients, especially the surgery residents, you do a big case and you're very proud of yourself. And then six weeks later, they come back and their wound is open and you're getting plastic surgery involved. You're not really doing a favor to those patients with a limited quality of life. So how did we get here? So this is a T10 renal cell oligometastasis that 20 years ago, before radiosurgery, we would be talking about, and probably Mark would be doing in your training, would be doing an on-block resection of trying to remove this entire tumor, thinking that that was the best treatment. But today we know we can do this with outpatient radiosurgery much safer and, I would say, better, more effective than with open surgery. So spine radiosurgery, several other people are going to be speaking more in depth about this, but the idea of single fraction or hypo-fractionated treatment, one to five treatments, high doses, very conformal, what are the principal applications to the spine as a primary treatment for radio-resistant tumors, re-irradiation after failed prior radiotherapy, and that's where most of the cases that we're doing fall into that category, as a post-operative adjuvant, and as a neo-adjuvant therapy. One of the residents from UCSF was saying how they're seeing a lot of chordomas that they're treating with radiosurgery before the surgeons operate. So where did we come from? Well, back in the days when we were excited about frame-based intracranial radiosurgery, we started performing frame-based spine radiosurgery. This is one of the techniques back in 1995 by Alan Hamilton and others, where you could see they put a clamp on the spinous process, took the patient to the Department of Radiation Oncology, got a CT simulation, and then treated with radiosurgery. It was feasible, but as you can imagine, not very practical. So what we're doing today, we're moving from frame-based to frameless image-guided radiosurgery. Just for those of you who, we threw around the term IMRT frequently yesterday, well, it was actually a neurosurgeon that invented the term IMRT, and that's for another day, about where it came from or how they came up with that word, or the term. But it was back in 1992, Dr. Mark Carroll was a neurosurgeon who was working in a private company north of Pittsburgh and developed a peacock system that was commercialized by Nomos, seen here, where he actually conceived the idea of radiosurgery for extracranial use. So why was spine radiosurgery the first really major area that we focused on extracranial radiosurgery? Well, there are technical reasons, as we all know. There's little motion with respiration of the spine when the patient is lying supine. It allowed for frame-based radiosurgery and then bony image guidance, but there are more practical reasons. First and foremost, we as neurosurgeons, we were already comfortable with radiosurgery, and Drs. Lexell, a neurosurgeon, pioneered or invented the concept of radiosurgery. We knew that radiosurgery would fill a vacuum that we needed to fill, and we were already working side-by-side with radiation oncologists, so we had the terminology, we had the concept, and so we borrowed heavily from that initial experience. What did we start doing? Well, as junior researchers, we started looking at our own series. We were doing it independently, using different doses, different contouring techniques, but what we found is that at our own institutions, we were getting a very long-term pain improvement, very good radiographic control, so we looked, once again, inward. We looked at our own series. We looked at our lung series and our melanomas and our breast cancers and our renal cells, and we wanted to make sure that it was safe with what we were doing, and then we started communicating amongst ourselves. We started looking and comparing institutions—this is one slide of different experiences with how many patients, et cetera—seeing what people were doing, what doses they were delivering to the tumor, what doses they were preventing from the spinal cord from receiving, and we found that we were all getting very, very similar results independent of technology. So what is the current evidence support? I do this every couple of months from PubMed. Right now there are over 65 single institution reports dealing specifically with radiosurgery, and it can get very, very complicated because some institutions are including cases from other institutions or they're updating their series. But more or less, that's why you can't give a specific number, but about 65 single institution reports. There's no randomized data available. There's the RTOG trial that I'm sure Sam will speak about in his talk. So what are the current recommendations for spine radiosurgery? The big take-home message from this morning. One is that we are using radiosurgery for oligometastatic disease and for radio-resistant histologies. We know what can be treated with radiosurgery and what cannot. This is a reliability analysis that Mark and others proposed where, so now we can see cases up at the top, the 0, the 1A, the 1B, even the 1C, and say, oh, those cases can easily be treated with the technology that we have in 2014 for radiosurgery. Type 3 in the bottom right-hand corner, still that patient requires, depending upon the histology, still requires open surgery, but followed by radiosurgery. And do we know that that works, that combining surgery and radiosurgery works? Yes. We have experience. So really, we're changing the paradigm as surgeons. Just like we've changed the paradigm for intracranial radiosurgery, the goal is to avoid further surgery. This is a patient who had a recurrent chordoma, had prior surgery, was not a candidate for further surgery. We treat this now with, you can see we did a corpectomy in the front, recurred in the back. We treated this with radiosurgery. We are changing the paradigm of the treatment. We're combining as surgeons with minimally invasive approaches. We can make small incisions as an outpatient. We can remove tumor. We can stabilize the spine and then follow with radiosurgery. These are several publications from different centers, what we call minimal access spine surgery or MAS for decompression and stabilization. All of a sudden, radiosurgery has become part of the surgical approach. So the surgeon isn't thinking, I'm going to do the surgery and see what happens. The surgeon is thinking, I'm going to do the surgery, decompress the tumor, stabilize the spine, and then we are going to do radiosurgery. We are thinking about radiosurgery from the beginning as we approach the patient. We're finding that with radiosurgery, this is a paper from the Cleveland Clinic, where the rates of the fusion and hardware failure were less in the radiosurgery group because you're just treating the tumor. You're not treating the bone or the bone interface with the instrumentation. You're not treating the incision. So it's perhaps better for these patients to have radiosurgery after surgery rather than fractionated radiotherapy. We can get even fancier. We can do percutaneous fracture reduction, kyphoplasty or vertebroplasty, where we go in, get a biopsy, stabilize the spine with cement, and then follow up with radiosurgery. This is a patient who was sent to us where a well-meaning neurosurgeon performed a kyphoplasty or put a little bone cement into the spine but didn't really address the mechanical instability of the patient. He actually put the cement on one side but really didn't do anything on the other side. This patient needs a stabilization procedure as well as an oncological procedure, radiosurgery. We went in, filled up everything with cement, and then performed radiosurgery, 22 gray in a single fraction. We know with renal cell carcinoma in our experience that the likelihood of long-term radiographic control approaches 100%. It's very, very effective. There are just other minimally invasive techniques along the way where we can not only put the cement in but we can actually remove the tumor from the inside in a percutaneous fashion here and then blow up balloons and put that cement all the way up against the bony interface and then perform radiosurgery. Once again, radiosurgery is part of the surgical tool, just like with intracranial radiosurgery. It's not a standalone treatment but part of the whole paradigm shift. What's the paradigm shift? The paradigm shift is in oligometastatic disease. For all of you who are in training but you're going to be leaving and out in practice in a few years, you're going to start seeing these patients that a decade or 20 years ago the medical oncologists weren't talking about oligometastatic spine disease. They thought, oh, that patient has disseminated metastatic disease, that that patient is a palliative case. Well, no longer. These patients are living for decades now with bone-only disease, so we have to start thinking about each of these metastases as an individual tumor that should be treated in the long-term setting. That's why we're using radiosurgery. Just like the whole debate yesterday, we talked about whole brain radiotherapy versus radiosurgery for brain disease, intracranial metastases, we're talking about the same for the spine. Tomorrow, where are we headed? Radiosurgery decompression. Sam, hopefully we'll touch on a little bit of that. He certainly has published more than anyone. This is my own case that I was telling him about the other day. This is a patient with a lung cancer metastasis, had had an outside surgery where they had done a decompression and instrumentation, but they left a tremendous amount of tumor behind. We decided for a variety of reasons, he developed a DVT, was on Coumadin, we decided to just treat him with radiosurgery, 27 gray in three fractions, shown here, and look what the MRI looks like in three months. The canal is completely empty of tumor. This is, I would say, radiosurgical decompression. It wasn't open surgical decompression, but we can achieve such decompression of the spinal cord with radiosurgery alone. We have class one evidence, or we're developing class one evidence for spine radiosurgery. This is the RTOG trial, 0631, that we completed the phase two trial, and Sam published this just a few months ago. Finally, to end with, how are we adopting spine radiosurgery? Well, similar to intracranial radiosurgery, it parallels the approach. We can avoid surgery altogether. We can alter the actual surgery performed. We can perform more minimally invasive approaches. We can integrate radiosurgery into systemic therapy that always keeps the medical oncologist happy so they can continue their cycles of chemotherapy. We use radiation or radiosurgery as a boost after conventional radiotherapy, but there are issues unique to the spine. The first and foremost one is the issue of the spinal implants. We found very early on that it could be very difficult to contour these tumors when there's spinal instrumentation and methamethacrylate. We found that 30 percent of our patients have spinal implants, including methamethacrylate, and that's probably increasing in size, in percentage. So what we looked at very early, and I won't bore you with the details, is looking at the setup accuracy with the spinal implantation. But here's a gentleman with thyroid carcinoma who has had multiple different surgeries by different surgeons, shown here, and unfortunately developed a metastasis right in the middle of his construct. We didn't want to do any major open surgeries. He had radiotherapy at multiple levels. We just treated this with radiosurgery, 18 gray in a single fraction. That's how this patient should be treated in the future, not with open surgery, but radiosurgery is a much better treatment option for the patient. I just want to end with a little bit about the benign tumors. This is something that I am particularly interested in. These are some of the publications from different institutions, from UCSF and Stanford, and our own experience. What I would argue is that now that many of these intradural tumors that before were only in the realm of surgeons and open surgery, where radiation oncology really had little role to play with fractionated conventional radiotherapy for such tumors, these tumors in the future are going to be treated primarily with radiosurgery as opposed to open surgery. Not every benign intradural extramedullary tumor, but many of them will be. This is a schwannoma, shown here. Very difficult surgical case would be very high morbidity. At L3, you'd have to resect the entire nerve root, and I would argue 16 gray in a single fraction. The pain resolution is within one month, and this patient, I think, would have complete long-term radiographic control. This is another patient who was referred to us, was being treated, had a history of prostate cancer, and the oncologist thought that this was a metastasis, and was just continuing with systemic therapy, then finally sent to radiation oncology, and then we got hold of the patient. This was just a benign nerve sheath tumor, had 10 out of 10 severe radicular pain. We treated with radiosurgery in a single fraction. Six months, patient is absolutely, completely pain-free. The issue of spinal cord tolerance, just to end with, we spoke a little bit about this yesterday in some of the breakout sessions, as long as you keep the spinal cord to 10 to 12 gray in a single session, the likelihood of injuring the spinal cord is exceedingly low. And then finally, to end with, the importance of multi-institutional, multinational collaboration. We as the speakers, we all know one another because we have worked together on all, you'll see over and over again, in all these manuscripts, many people from many different institutions, we have to share our experiences as we move forward. So final take-home message, yesterday we spoke almost solely about intracranial radiosurgery, the importance of today is that spine radiosurgery does not equal intracranial radiosurgery. They are very, very different. The indications are very different, the technologies are completely different, the outcomes as we look at how these patients are doing are completely different, whether it's pain, long-term survival, radiographic control, completely different than for intracranial radiosurgery. The limitations of our technologies are very, very different because we are no longer using frame-based technologies and, of course, the organs at risk. Neurosurgeons don't normally think about toxicity to the esophagus or the kidneys or the stomach, but those are very, very important as we develop these plans and we're working side-by-side with our radiation oncologists. So in summary, in a similar fashion to the way that radiosurgery is today an essential part of the treatment paradigm for intracranial pathologies, radiosurgery today has become an essential tool in the multimodality treatment for spine pathologies, and I think you all realize that. And if you don't, within a few hours after you hear several more of these lectures, you certainly will. We're only at the beginning. Thank you very much.

spine radiosurgery

neurosurgeon

metastases

surgical techniques

radiation

evidence