The objective of this talk is to provide some basic information on the definitive treatment of stage 1 non-small cell lung cancer with external beam radiation therapy. The pre-lecture questions is, the optimal treatment for a patient with Stage 1 non-small cell lung cancer and poor pulmonary function is? A.Wedge resection, B.Lobectomy, C.stereotactic body radiation therapy, commonly known as SBRT. D, unclear if wedge or SBRT. Or E, none of the above. So in talking about stage one, non-small cell lung cancer, what that means is that there is just the primary tumor in the lung. There's no lymph node involvement, and that Is what is indicated in this picture. Terms of the management of Stage I, non-small cell lung cancer: surgery is generally considered the standard approach. And the surgery can be done in one of two ways. It can be done as a lobectomy which means they remove the lobe of the lung or a wedge resection, sometimes referred to as a segmental resection. Where they're just removing a portion of the lobe of the lung. But not all patients are candidates for or desire surgery and in that case, consideration could be given to treating them with either conventionally fractionated therapy or stereotactic body radiation therapy. Which is, again, referred to by the acronym SBRT or sometimes also the acronym SABR, but these both mean the same thing. So, when you look at Lobectomy versus Wedge Resection these are some data that were published back in the mid 90s. It was a study that was done by the Lung Cancer Study Group and they compared Lobectomy to a more limited resection, generally referred to, again, as a Wedge Resection. And what they found was that for patients who had a Lobectomy there was a decrease in likelihood of recurrence as compared to a more limited resection. But that the overall survival was the same. And most people feel that if a lobectomy could be done safely that would be the prefered approach to again reduce this likelihood of a local reoccurrence. So what about SBRT for a non small cell lung cancer? The idea behind this treatment is that it's intended to deliver an ablative dose of radiation to the tumor. And as I mentioned in a prior lecture, we're going to give a much higher biological dose than we would be giving with conventionally fractionated radiation therapy. So for SBRT, we might use a dose for 54 gray in three 18 gray fractions. Which has a biologically equivalent dose of 151 gray and if you compare that to conventionally fractionated radiation therapy. Which again is 60 gray so its going to be 30 treatments of 2 gray for a total of 60 gray. The idea too with SBRT is that because we are treating a much smaller volume and really only focusing on the primary tumor. The tumor in the lung, and not any lymph nodes, for instance. We can get a much higher dose to the tumor, and limit the dose to most normal tissues to doses that are considered safe. This is just a picture, a diagram, from a treatment planning system showing how we go about delivering a SBRT for an early stage lung cancer. So at the bottom of the slide you'll see a green line. That's actually a contour on a CT scan that's been fused of the spinal cord. The tumor is just in this view, just above that in pink. And then, you can see there's a linear pink structure above that, which is the esophagus, and then the red structure is the heart. And what you can see is that there are, I think in this plan, 11 beams. Coming in from different directions, all of which are centered on the target, the tumor that we're treating. And so what that means is that if we look at the next slide, this is a dose distribution of what the radiotherapy looks like for stereotactic body radiation therapy. There's a very high concentration of dose around the tumor which you can see in this case is around the right lower lobe. And I should mention that when we create targets for this type of treatment, it's not just the tumor that we are targeting but we also need to put some margin around the target. That takes into account any slight variation in patient position, also gives us room to get a sufficient dose to the tumor itself. But as you can see as we get what is sort of equivalent to a topographical map of the dose, where around the tumor there's a very high concentration of dose. And then as we move away, just even a few millimeters from the edge of the area that we're targeting, the dose falls off very quickly. And that helps us to minimize the dose of radiation to the surrounding normal tissues. So when it comes to delivering stereotactic body radiation therapy for non small cell lung cancer. When we do the treatment planning, as I mentioned earlier in the previous lecture. We do a motion assessment, with a four dimensional CT, where the fourth dimension is time. And that's going to allow us to assess whether or not the tumor moves a lot when the patient is breathing. As you might imagine, tumors in the upper lobes tend to move less. Whereas tumors that are in the lower lobes, closer to the diaphragm tend to move more. So we can assess that motion and then we can decide whether or not we need to manage that motion, if it's above a certain threshold say a centimeter. And we can do that either by restricting the patients breathing through abdominal compression. We can use a gating technique for instance, where we would hold the patients breath. At a certain reproducible point in the breathing cycle, and then turn the machine on during that breath hold. And there are even some very sophisticated systems for tracking the motion so that the machine can sort of move the tumor and track it during the breathing cycle. And then another important aspect of the treatment is, during the treatment we use image guidance, so that we have the capability on the treatment machine to do a CT scan. And we can use that information and compare it to the planning a process to help us to localize the tumor within millimeters. And then also their are systems that allow us to monitor the patient while the treatment is actually is being delivered to make sure that the patient hasn't moved for instance. So these are some data about the use of stereotactic body radiation therapy for inoperable early stage lung cancer. This was a study that was done by the radiation therapy oncology group. It was a phase two multicenter study, where they looked at the use of SBRT for peripheral, early stage lung cancers, and used the fractionation schedule that I mentioned earlier of 18 gray times three. And there were 55 patients that were treated in this study, and as you can see the local control at three years was extremely high, over 97%. There were some patients that had failures in untreated mediastinal nodes, but that was low. Unfortunately, with lung cancer patients can develop metastatic disease, so the disease-free survival at three years was around 50%. But the three year overall survival was 55%. So generally speaking, when it came when one compares the use of SBRT for conventionally fractionated radiation therapy for early stage on lung cancer. The tumor control is much higher than what we would expect and so this is really when these data were published. Quite exciting when thinking about how to use radiotherapy to treat early stage lung cancer. So the next question that might obviously come to mind is well, that might be very good for inoperable patients, what about operable patients? Do we have any data that we can use to compare SBRT to a Wedge resection. And so these are some data that were published about five years ago now, from Beaumont Hospital in Royal Oak Michigan. And what they did in this study was they retrospectively compared about 70 patients treated with surgery to about 60 patients treated with radiation therapy. The follow up was relatively short, only about two and a half years. But what they found, if you look at the local control graph on the left was that the local control appeared to be higher for SBRT than for wedge resection. Which again hearkens back a little bit to that data that I showed you earlier showing increased likelihood of local recurrence in patients that have wedge versus lobectomy. And then when you look at cause specific survival, it didn't appear that the use SBRT was any worse than wedge resection. These are some data that are a little bit more recent, published just last year, that compare a lobectomy to SBRT for operable lung cancer again. Unfortunately, as you might imagine such a trial can be difficult to carry out, randomizing patients between surgery and radiation. And so, this was actually a meta analysis of two studies that were done. One that was in the US and the other in Europe that failed to meet their accrual goals and closed quite early. And unfortunately, only in total randomized about 30 patients to radiation and 30 patients to surgery. But interestingly enough, if we look at the data on the left is a graph looking at local control. And you can see that surgery and radiation were equivalent but looking at the graph on the right and looking at overall survival. There was actually an improvement in overall survival associated with the use of radio therapy as compared to surgery. And so while this meta-analysis just contained over about 60 patients, that's hard to draw any firm conclusions, but at least these data are hypothesis generating. And suggest that at least maybe there's not a decrement to the use of SBRT as compared to lobectomy for patients who are surgical candidates who have stage one non-small cell lung cancer. So to follow up on that, as far as take home points, I think most people would agree that surgery is still considered the standard treatment for operable stage I non-small cell lung cancer. But there are growing data supporting the use of SBRT for sure in inoperable patients and even some suggestive data in operable patients. So the post-lecture question is, the optimal treatment for a patient with stage I non-small cell lung cancer and poor pulmonary function is? A.a wedge resection. B, Lobectomy. C.SBRT. D.Unclear if a wedge would be better than SBRT. And E. None of the above. And the answer is D, I think it's still unclear if a wedge resection or SBRT is going to be the best option for a patient in these circumstances. Thanks for listening, and the next lecture, I'm going to talk about the use of radiotherapy for locally advanced non-small cell lung cancer.
