I've been asked to speak about spine radiosurgery and quality of life in our patients, and I just want to take a step back just to kind of place it in the appropriate context. The problem is big. Cancers are among the leading cause of death worldwide, 8.2 million deaths in 2012. Everybody talks about stroke and stroke intervention and stroke involvement, and the public kind of beats the drum about stroke-related issues, but if you look at the numbers, certainly cancer is one of the leading causes of mortality in patients. And then, again, the lobby groups, AIDS-related deaths, 1.8 million, 2 million, 1.8 million from TB, so infections also take their place. So there's a whole spectrum of things, but again, we have to not lose sight of one of the important things that our profession touches upon. 60% to 84% of patients with solid tumors develop bony metastases, with the skeleton being the third most common site, with half of the skeletal metastases involving the spine. So it's a big, big issue. Survival and disease control rates also are steadily improving, where nowadays we can tell patients that 60% of patients survive five years and more after their initial cancer diagnosis. So it's a problem that is growing, that we'll be seeing more of, and we need to deal with the manifestations of the disease. Used to be median survival for patients with metastatic disease is 10 months. I think with our new biological targeted therapies, that is certainly longer. Death typically results from systemic malignancy, and the spinal vertebrae commonly signals, certainly in certain pathologies, especially lung, et cetera, disseminated disease. In the past, there was a questionable role for treatment. That is not so, because it is important that we consider treating these patients. It's warranted in terms of quality of life rather than cure. These are patients that are going to live a long time. Their quality of life in that interval is exceedingly important. Why? Because we can preserve or restore ambulation. A patient's performance score is obviously dictated by how independently functioning they are. If they have ambulation, then their KPS is graded as higher, and they are candidates for chemotherapy and further treatment for their systemic disease. So that's essential. Bladder control gives dignity and quality of life to patients, as well as pain relief allows life to be bearable. It requires effective therapy, requires multidisciplinary treatments and therapies. We've all got to come to the table with our own specialties. We have to respect and understand each other's specialties. If we are a multidisciplinary invested team, we can more effectively treat the patient. We have to understand the clinical condition, life expectancy assessment, and pay specific attention not to our thoughts about quality of life, but a patient's individualized quality of life. Two big game changers, both of them have been touched upon this morning. The first one is decompressive surgery with the Patchell randomized study published in Lancet in 2005. And the second game changer, and truly a game changer, is spine radiosurgery in the management of spinal metastatic disease. Surgery, surgical treatment was actually widely abandoned for conventional radiation because they looked at initially doing laminectomy. So here's the pathology ventrally, spinal cord in the middle. And what we were doing as surgeons, because it was easier, more accessible because of limitation of instrumentation and approach, is we were doing a laminectomy dorsally. So now we have a compromised ventral column, and now we blow apart the posterior part, and there is instability in the patients, there is kyphosis in the patients, there is injury to the spinal cord over that area, and obviously conventional radiation over surgery plus conventional radiation made sense when we were doing this kind of stuff. In the 80s, we began to do new surgical approaches and improved our instrumentation for stabilization and fusion. We went where the pathology is, and that's how you have to approach these things. And when we started operating ventrally and then stabilizing, then it kind of set the field to do the randomized prospective study. And so I won't go into this in any detail, but essentially it was stopped early because the surgical group fared incredibly better than the conventional radiation alone. This was surgery followed by conventional radiation, and more patients regained ambulation rate, retained ambulation for those that were walking, neurological examinations improved, patient survival improved, I think this is often sepsis related in patients that are non-ambulatory, analgesic use declined, and corticosteroids declined. So the game changed. We started being compelled to do surgery plus conventional radiation for these patients. Spinal oncology focused on new instrumentation and spinal reconstruction. We were able to do front-back procedures, rotisserie procedures as the residents call them, and avoid complications. And we started doing more minimally invasive techniques with vertebral augmentation, et cetera, to stabilize the spine and allow for mechanical reconstruction. So that's what spinal surgical oncology focused on. But what about the oncological aspects of spine metastases? This gave us mechanical stabilization, but what about durable local tumor control? Surgery improves the chance of neurological recovery in patients with high-grade cord compression, restores spine stability. But metastatic tumors are not resectable for cure. The recurrence rate at six months is nearly 60%. And at four years, nearly all the patients who are treated with surgery and conventional radiation all recur. I told you 60% of cancer patients are living five years and more. This is the time that the intermediate consequences are showing up, and we need to address them. So, we need two things for effective metastatic spine tumor treatment. Pain palliation, or in those patients that haven't yet developed pain, pain prevention by stopping the disease from growing and compressing the cord or the nerve roots, as well as tumor control and prevention of neurological compromise. This can be achieved either with monotherapy, such as radiosurgery alone, or combination multimodality therapy, and I'm not going to get into this in any extent for the interest of time, but radiosurgery is not only a standalone treatment, but it's sort of like a double barrel treatment, and I heard Mark referring to separation surgery, and that's exactly what we mean by combination treatment in order to achieve durable control. Stereotactic radiosurgery. You've heard a little bit about this, but I just want to reemphasize, who do we treat with spine radiosurgery? Patients with pain or tumor progression. Spinal to moderate spinal cord compromise, and we saw Sam talked about some of the effects on moderate spinal cord compromise and the outcomes in these patients. The big, big new thing is previously irradiated lesions. Nearly half of our patients are previously irradiated with conventional radiation and have failed. When we originally started up the program, we said to the radiation oncologists, send us all your failures. These are patients that you can't re-irradiate with conventional treatment. Send them to us, and let's see what we can do in terms of their pain relief or slowing down their tumor progression. Residual or recurrent disease after surgical treatment. So again, in the separation surgery, we do minimal debulking and let the radiosurgery do the yeoman's work in order to control the disease. Difficult surgical approaches. If a patient is too sick for a surgical intervention, if they only have a three-month survival, you don't want them two-and-a-half months in the ICU, and significant medical comorbidities that prevent them from surgery. What are our local tumor controls? Well, they're the same, essentially, independent of institutions. We're talking 85 to 90 to 90-plus control rate in terms of tumor. There's not a lot of cancer therapies that you can say, man, we've got an 85% chance that we can control your disease at this spot. Unfortunately, it's only spot welding, but that counts in certain settings. And pain relief, again, 85 to 100%. Boy, that's a nice modality to do in a 20-minute treatment session. How do spine metastases present? Well, over 90% of them present with persistent, progressive nighttime pain. Neurological symptoms, fortunately, are less common, with about 10% being the upfront manifestation of weakness, spasticity, bowel, and bladder symptoms. This was the part that surprised me when I initially started in the field. It was about 50% of patients that come don't have a prior diagnosis of cancer when they come with spine metastases. So this is the guy who's like, I was in the backyard pulling out weeds, and I strained my back, and my back's not getting better, et cetera. And these are the patients that you find can present with diffuse or focal spine metastases. Just a comment that in a patient with a known cancer history, if they develop nighttime pain, refractory back pain, et cetera, no matter what kind of strenuous activity they have or have not been doing, it's a red flag. They need to have their spine imaged. Because it's the most common syndrome encountered in cancer patients is metastatic bone pain, and you can see why. What causes the pain? Well, multifactorial infiltration and bony destruction, altered biomechanics and spinal instability, neurological compression, tumor inflammatory mediators, unknown mechanisms. On an individual basis, though, all these things isn't what's in the patient's mind. This is what they're thinking. My disease is back or worse. My treatment's not working. I'm going to die. It's an important thing to address their quality of life. The concern, the clinical course of metastatic disease can be relatively long. Nearly 80% of patients with bone mets experience severe pain before they get to the right therapy to palliative medicine or to treatment modalities that control their pain. And bone pain is not adequately treated by many physicians. We worry about patients getting addicted more than we worry about addressing their pain needs. Patients at time experience sequential complications over several years. So in addition to pain, they get loss of mobility, skeletal fractures, hypercalcemia, spinal cord and nerve root compression, all of which results in impaired quality of life. We need to study it. We need to address it in order to appropriately evaluate and offer modalities for it. I use this frog as a bit of a tip off to Peter, who was one of the original people who I learned spine radiosurgery from. And his frogs leapfrog and mine just sit on thorns hoping we don't get zinged. But pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It's difficult to assess, difficult to manage. There's John Sue pulling at his collar when I come at him to ask for, you know, can we do something new in this program? And he's going, oh man, it's Angelov again. So we need a method to understand the nature and extent of the pain in cancer and better pain management and impact therapy. Pain and cancer. We've got to understand how frequent it is, how severe it is, how disruptive it is and what kind of interference it is. We actually prospectively evaluate our patients. Steve just talked to you about under-reporting. It's not like the patients that are coming to us with degenerative spine where they're looking to vamp up how much pain they're experiencing because often there is, not always, but there can be a disability case, there can be an injury case related to it. These are patients who want to underplay what their pain is. When we do it prospectively and we follow, we can determine serially what real impact we're having in these patients, but it's important to address because these patients don't want to be in pain because it signals lots of problems. We have to have appropriate pain instruments. I think the residents are a little bit too young to remember Family Circle, but maybe some of the faculty remember reading this as a kid, but not only do we have to have a reliable instrument, an instrument that measures the same thing all the time, but we have to have a valid instrument just like Billy here is saying, think harder PJ, I can't hear a thing. So we need to have a test which measures what it's supposed to measure. The scale that I started using for these patients prospectively is the brief pain inventory. It's a pain scale developed back in 83 and it was based on McGill pain questionnaire. Ron Malzach developed the gait theory of pain in neurosurgery and is one of the forefathers of this, and so this is sort of launched off the McGill pain questionnaire. It is considered to be valid and reliable in patients with cancer and rheumatoid arthritis. It was used by the RTOG for palliative radiation for osseous mats. It's intended to be used in order to estimate pain prevalence and severity. It's easy, it is indeed brief, and easily understood. It's a 10-item scale that evaluates all these components in terms of sensory pain and relative components of pain, including depressions, suffering, and perceived availability of relief. This is what it looks like. This is, I think, the older version. It actually looks a little bit simpler, cleaner. Patients fill this out extremely quickly. Pain relief also may be affected by mood and insight. So just doing a pain score, you need to also compare it with quality of life data formally to see what the, sort of jointly, what the impact of the treatment is. In order to do that, I looked at a number of quality of life questionnaires and actually settled on the ERTC quality of life C30 as appropriate for this. It's a nine multi-item scale. There's functional scales, a global quality of life symptom scale. It's appropriate in malignancy, validated and palliative radiation, and there is over 2,000 studies that use this. Thought this would be a very useful way to prospectively evaluate our patients. Our patients, actually, we leave it in the room once they come and see me. The BPI, one of us does it, either my nurse practitioner, my fellow, or myself. The ERTC, we leave it with the patients and they can very simply fill it out and it's at every clinic visit that we document this information. We did prospective study evaluating their pain outcomes, quality of life, and local disease. We did the BPI's. We actually call, we did it at time zero pre-radio surgery. We called them one week post-treatment, week two post-treatment, three at one month. We saw them clinically at that same time. We did a quality of life, because nobody's quality of life changes week by week, but their pain does. And then we would do imaging studies to correlate with this. We have 108 unique patients, 140 procedures. These are the patient demographics, 154 lesions treated. Most of them are single level, but you see two, three, or more. In our early days, we were limited because we were using an ovalis classic, which was a 10 by 10 field, so we weren't treating more than three contiguous levels. I still believe that this is a treatment for oligometastatic disease. It is not for pan spine treatment, but it is focal therapy, spot welding, as I tell my patients. And predominantly thoracic treatments, because that has the most vertebral bodies, so that's where you see it most frequently. Primary tumors, we have a renal bias. It's actually very exciting to offer 90% control rate in something that is traditionally perceived to be very radio-resistant. We are well above the normal radiobiological constraints, and we're in radioblative dosages in our doses used. This is our mean follow-up of 30 months. Tumor volumes and maximum linear size. Again, at that time it was restricted. You can see the bowels. Initially we used to contour. We don't do that so much in the kidneys, and we calculate the dose to kidneys and again take into account organs at risk, as well as the spinal cord posterior to the vertebral bodies involved. Indications for treatment. Pain, 81%. Of course, most of the patients are in pain. And see, you can almost see a virtual 50-50 split of de novo treatment in radiosurgery versus salvage treatment after conventional radiation. All of these we did single fraction treatment. Median follow-up, 11.2 months. Someone was asking how quickly you see the improvement. This table shows the improvements statistically significant improvement at one week post-treatment. I remember in the early days there was one patient, and I always tell a story that he couldn't get up from bed, hospital bed, he was hospitalized for pain, from hospital bed to the bathroom without a walker, without severe pain. When I saw, and we were very early on and relatively inexperienced, when I saw him in clinic one month later, he told me that the week before he had been to his nephew's wedding and actually even danced with his wife briefly. It's a big change. There's lots of these patients that sleep upright in a recliner for two years because their spine is involved and it's grumbling along and the conventional radiation helped for a while. And they tell you, Doc, it's just changed everything that I do and it has given me incredible quality of life that I can lie in bed next to my wife of 35 years. It's a big impact for 20 minutes. The follow-up is durable at one month, three months, nine months, etc. So statistically improved over the entire course, all prospectively collected. And not only is their pain better, but it's better on less medication. So the white line you can see here is the cohort of patients that are now not using any pain meds. Now remember, these are patients with stage 4 disease and suddenly just by treating one level, a greater number of patients are able to get off all narcotics or reduce their dosing of narcotics along the way. That's huge. Quality of life. I was actually very pleased when we did this. This is a one month follow-up that the parameters that are relevant are the ones that showed to be statistically improved. Doing spine radiosurgery doesn't improve their fatigue. No kidding. Doing spine radiosurgery doesn't really affect diarrhea, as expected. But the ones that do improve pain, statistically improved, insomnia, they don't hurt, they sleep. Constipation, they're not taking opioids as much, constipation improves. So that the relevant quality of life in a 30 question questionnaire, the ones that pop are exactly the ones that you would expect to pop. And it's durable. Again, at nine months, global quality of life consistently improved after treating a single level or a single block of vertebral bodies. So what are the major potential benefits of radiosurgery? Short treatment time in the outpatient setting, no recovery time. I had a patient who came, he was found to have a chordoma of the spine after he fell off a bicycle in Israel, and he was sent to us from Israel to do radiosurgery. And that day, after his treatment, he said, any restrictions in going anywhere when we first simmed him? I said, no, not really, but I wasn't exactly thinking what he was planning. He got on a plane after his spine radiosurgery treatment and flew to Florida and got on a cruise ship. And came back and saw me a week and a half later to say, I'm going back to Israel, just wanted to make sure you were fine with everything that's going on. No recovery time. Nice tumor treatment. Good symptomatic response, successful tumor control, low morbidity. Who don't you treat? Patients with rapidly progressing neurological deficits. If they are a grade three on five, that's about the limit as far as strength that you should be treating these patients with radiosurgery without surgery. They have to be able to stand and be capable of some minimal ambulation, at least, because he can't reverse them fast enough. When they're going down the drain, spine radiosurgery typically isn't the treatment. I've even treated multiple myeloma patients who we had simmed on the Friday and we were getting them ready, or a Thursday, we were getting ready to treat them on a Monday, and they deteriorated to two on five over the weekend. But nobody kind of reported that, oh, well, they couldn't move their legs off the bed so much. And you just kind of take them on good faith that nothing has changed. You take them, 24 hours later they're in the operating room because they've lost all motor function. It doesn't evaporate the tumor fast enough for you to use it typically as a decompressive modality. Cord compression by bone or disc. Look at your images. This is important. Radiation does nothing for bony fragments. Make sure you look carefully at what you've got, because just because you have a hammer, not everything is a nail. And no known cancer tissue diagnosis. You certainly don't want to be irradiating TB of the spine. And overt spinal instability. Mark referred to this aspect, but it's very important that you understand what's oncological pain, what's mechanical pain, and listen to your patients in clinic. That listening, then examining, then looking at the images gives you so many clues up front. The future. Hey, wouldn't it be nice if one road said this way for success and failure? We don't have that. It's not quite as easy. It kind of looks like this, and most of the time you're looking at the future going, where is that sign pointing to? Not really clear, but we have to at least kind of mine our experience, understand our experience, and spend time evaluating appropriately. Reminder, patients are surviving longer. We should consider the intermediate consequence and outcomes of our interventions. Surgery and SRS combinations have proved effective. Synergy, open surgery and instrumented fusion and instrumented fusion failure may be less with radiosurgery. Separation surgery, vertebral augmentation, and radiosurgery, you've heard all about that to some extent today. Reasons to combine, better local control, separation, fusion rates. So in summary, radiosurgery, I hope I've been able to show you, results in rapid and durable control in terms of pain control, radiographic control. It's an effective standalone treatment modality. It has a role in multi-modality treatment of spine tumors. It truly has been a game changer. The reason that it works effectively in all our centers is because everybody in the team brings complementary tools to the table and they're all important components. None of us work in silos anymore and it's inappropriate to consider these highly complex patients in a vacuum. How do we best treat spine metastases? I'm not sure I have the answers, but I do have some very, very gratifying stories about how to treat spine metastases. And I'll close with this one. This is a patient who initially presented to my clinic. He's a 52-year-old male with papillary carcinoma of the thyroid. He had a T9 hemicorpectomy in 05. He recurred based on PET and you can see there he had a focal recurrence in 2006. We did radiosurgery. This was one of our earliest cases when we first started the program with 14 gray single fraction treatment. His PET SUV was 7.1. Here he is, his five-year follow-up. Actually now we're eight-year follow-up and he's running the Cleveland Triathlon, crossing the finish line in front of the Rock and Roll Hall of Fame. His disease remains stable on MRI. His SUV has never gone below 3.9, but it just lives there. Now I see him. He's actually in Switzerland now. He's running up and down the Alps for training because his job transferred him there. He's fully active and he comes once a year to get new spine imaging and a new PET. So we can get quality of life with one single 20-minute treatment in patients. All right, well thank you for your attention.

cancer

mortality

spine metastases

quality of life

survival rates

treatment options