Hi, my name is Dawn and welcome to this portion of the thoracic oncology course. Today, we'll be talking about stereotactic body radiotherapy for oligometastatic lung cancer or SBRT. I am an assistant professor in the Department of Radiology at the University of Michigan. And I work at Allegiance Hospital, which is one of their affiliates. The objectives of the current lecture is to provide introduction to SBRT for various body sites, and to review the evidence for SBRT for oligometastatic lung cancer. So we're going to go through a pre lecture question, and we'll go through this after the lecture as well. Which of the following is incorrect about SBRT? A, high doses of radiation per fraction. B, 10 or more treatments of radiation. C, small precise targets. Or d, five or more fewer treatments of radiation. And I hope by the end of the lecture today you'll be able to answer that question. So what is SBRT? Well, it's really the delivery of very high doses per fraction greater than 6 grade per fraction on extracranial sites. So to put this in the context, we normally give two grade per fraction, grade being how we measure does and radiation, and normally, we give it over several weeks but in SBRT we'll give it a one to five fractions so really large doses in a small period of time. The target radiation margin is very, very tight, it's in millimeters. Where specifically we're talking about 1 to 2 centimeters for conventional radiation. And we are very strict daily physics monitoring and imaging to make sure we are very accurate target coverage. And to avoid overradiating critical structures. You might also hear it referred to on Internet and also in the media as SABR, stereotactic ablative body radiotherapy. Basically one group thought that sounded cooler than SBRT, but it's the same thing. So what really is Oligometastatic Disease? Well, it's generally defined as fewer than or equal to five metastases. Any organ in the body. More patients are presenting like this now because we've got better staging. It's often we do PET CTs, we've got more targeted immune therapies in metastatic lung cancer so that patients are living longer. And they may pop up with a few metastases at a time or present with very few metastatic sites. And a rationale for local treatment to metastatic disease is that we achieve good local control then we might be able to defer systemic intervention. So we're thinking we zap these individual sites with SBRT. The cancer is gone in these areas. We washed them for a bit and new things popped up. We didn't talk about morosphere to you or chemotherapy or other systemic therapies. So the oligometastatic state is is not a new concept, but we're thinking about it more and more because of the things we talked about in previous slide. So we would consider local treatment for example for de novo or synchronous metastases at presentation. Metachronous or oligorecurrent metastases arising after some period of disease control. So meaning new things popping up after we've given some chemotherapy or systemic therapies. Or inducing an oligometastases or oligopersistent disease where most of the cancer has responded to the systemic therapy, but one or more sites isn't really responding and so we can consider giving SBRT to kind of help it die. Oligoprogressive disease is similar in that context. So the rationale for SBRT in oligometastatic lung cancer is that when you have a very small burden of disease, there's only a few sites of metastasis. And we know that local control with SBRT is really high. It's going to be more than 90%. If we kill the metastatic disease, we might prevent further seeding SBRT itself is an immune modulator and some cases there are a lot of immune therapies which we sometimes induce of huge immune response and SBRT can help with that. And that's really the last point on this slide where less seeding and activating the patient's immune system, you might actually delay progression and improve overall survival in a subset of metastatic lung cancer patients. So common SBRT fractionations, as I said, very large doses per fraction and very few fractions. So in the spine we given in 27-30 Gy/3 fractions or 16-24 Gy/1 fraction, in the lung we may give 54 Gy/3 fractions of 50 Gy/5 fraction in the liver also 50 Gy/5 fractions. So by all means different institutions will do slowly different things but these are very common dose fractionations. So this this is an example of Spine SBRT as you can see. The colored lines are represent the radiation dose. See how tightly at halves of a tip or body, and how we're able to drive the dose away from the spinal cord so very, very safe for us to deliver very high doses of radiation while avoiding the spinal cord itself. And this is an example of Lung SBRT. You can see there two spots in the lung, we treat both of them. They have very, very tight doses, again the colored lines hug the tumor, and we're avoiding most of that same lung, as well as the contralateral lung. So again, very, very safe. This is the liver, and you can see two spots. And you can see that part of the liver is right next to the bowel. And again, we're very careful to avoid the bowel. You can see that most of the radiation dose, the high dose areas, which are not the red and the blue ones, those are low doses. Avoid most of the liver, avoid the bowel, the high doses far away from kidneys, from the vessels even from the bone, so again, very conformal treatment. This is bone SBRT, so you can see again within the liver very high doses of radiation, it's conformal. You can see it's right next to the penile bulb highlighted in light green and also the rectum. And again, very, very safe because we're very precise about how we deliver this radiation. So there's been a limited data but we're moving towards it for aggressive treatment of oligometastatic lung cancer. De Ruysscher et al., looked at a Phase II trial of 40 lung cancer patients. Again, they define oligometastasis as less, and are equal to five metastases, any site in the body. And they actually allow treatment with either surgery or radiation. Because in some cases such as liver or spine or in some cases even lung, you can have a section or a section of the tumor itself. 95% have prior chemotherapy, the Median overall survival was 13.5 months and 3 yr overall survival was 17.5%. That's actually excellent compared to chemotherapy alone where usually the 3 yr overall survival is less than 5%. Collen et al., that another Phase II trial of 26 lung cancer patients again with less or equal to 5 metastases, any site. You are treated with SBRT to the primary tumor. So this was a pure SBRT trial and the patients were allowed to have induction chemotherapy. The medium progression free survival was 11.2 months and there was very little toxicity involved with the treatments again because we're so precise about what we target, the radiation and SBRT. There was also another trial by Iyengar et al., this was, again, very small patient numbers, 24 lung cancer patients. They allowed up to six metastases, any site outside of the brain. And they treated them with concurrent erlotinib which is our targeted therapy towards patients EGFR mutations. The median progression can survive as very good as 14.7 months and the median overall survival was 20.4 months. And only 3 out of the 47 sites treated and you can imagine because there are 24 patients over which for 47 sites showed local progression, excellent local control. They're hoping to launch a Phase III trial in patients EGFR mutation because perhaps a concurrent delivery of a TKI such as erlotinib may also help prevent other distant metastases from occurring as we deliver SBRT and it was safe concurrently with radiation. So there are now other ongoing Phase II trials that we tried to launch them especially for oligometastatic lung cancer. You can see there are two NCT trials. They were closed due to poor accrual but the results are pending. They have not been reported yet. There was one trial that tried for combining consultive local therapy, mostly SBRT to metastatic sites, but they allowed less than you could four sites in patients and they had to be on tyrosine kinase inhibitors so similar to a lot of trials we've discussed in the previous slide. There are also ongoing trials that have expanded inclusion criteria to include any cancer with oligometastatic disease. It was too hard to accrue only lung cancer patient so now they've allowed any and their SABR-COMET and the NRG BR001. And NRG BR001 has actually opened it to University of Michigan right now. So the take home points today would be that all of the metastatic lung cancers are actually more common now due to better systemic therapy and target therapies. SBRTs are very good modality for local treatment of these sites, the first systemic therapy, and they result in longer progression-free survival and overall survival, compared to systemic therapy alone. We're still trying to understand which patients benefit the most and how to select them. So there's a lot of research going on to try to identify the oligometastatic sites. So thanks very much for your attention, and let's go to the post lecture question. And hopefully, you can answer this after you've listened to the lecture. So which of the follow is incorrect about SBRT? A, high doses of radiation per fraction. B, 10 or more treatments of radiation. C, small precise targets. Or d, 5 or fewer treatments of radiation? So let's go through these answers. So a is actually correct so SBRT by definition is using very high doses of radiation towards a very small target. In fact, regular radiation uses two grade per fraction and we typically treat more than five grades for SBRT. B, 10 or more treatments of radiation is incorrect and that's because for SBRT by definition we have to treat with fewer than or equal to 5 treatments of radiation for the total cost of radiation for SBRT. C, small precise targets is correct about SBRT. We really hone in on a very small area, just really the tumor itself. And d, 5 or fewer treatments of radiation, as we discussed this is correct because by definition, that is what SBRT is. Thanks very much. I hope you enjoyed the lecture series.
