The objective of this talk is to provide some basic information on the palliative treatment of metastatic non-small cell lung cancer with radiation therapy. The pre-lecture question is: a patient has both a painful humoral metastasis and five symptomatic brain metastases. The optimal courses of radiation are? A.3 gray times ten to both sites. B.8 gray times one and 3 gray times 10, respectively. C.3 gray times 10 and 8 gray times 1, respectively. D.8 gray times 1 to both sites. Or E.4 gray times 5 and 3 gray times 10 respectively. So this is a schematic diagram just showing some of the common sites that lung cancer can metastasize too. And we use the terminology, Stage IV and metastatic lung cancer, interchangeably. So as you can see, lung cancer can metastasize to the brain, it can metastasize elsewhere in the lung. The small lesions here are meant to indicate lung metastases with the larger primary here. It can metastasize not only to the involved lung but to the contralateral lung. It can metastasis to a bony structure, so that's what this is indicating, and also to the upper abdomen, commonly to the liver and to the adrenal glands. So what are the goals of palliative radiation therapy? Well, primarily it's given to relieve any distressing symptoms associated by the metastatic lesions. It can also be given to prevent future symptoms, something that I tend to refer to as Prophylactic palliation. And while it can improve survival, generally speaking, that improvement in survival is modest, and really, secondary to the relief of symptoms. When we're using palliative radio therapy, we also want to as much as we can, minimize the toxicity of that treatment. Since we are trying to relieve symptoms, we don't want to cause any additional symptoms. And also want to give the treatment in such a way that we minimize the cost. And I'm not really speaking so much to the financial cost although that is true but more to the cost to the patients and their families in terms of the time spent travelling to and receiving treatment. So what are some of the common indications for palliative radio therapy? For metastatic non-small cell lung cancer. One of the most common indications is for the relief of pain. Commonly, that's pain related to bone metastasis. Although we sometimes see, for instance, pain related to nerve impingement. Say of a nerve root from a bony lesion in the proximal rib. We can also sometimes see pain associated with invasion of the chest wall. Often times, from a very large and aggressive primary tumor. Another indication for palliative radiotherapy is to relieve compression. We might have compression, say in the spinal cord from a bone metastases. Brain metastases can also cause compression on a normal brain and cause symptoms. We can get compression of an airway which can cause a shortness of breath or a blood vessel which could cause, for instance, superior vena cava syndrome. Palliative radiotherapy can also be used to control bleeding, such as hemoptysis. And I should point out that the use of radiotherapy for palliation is equally effective for non small cell and for small cell lung cancer. So what I want to do now is just run through a few common examples in which we might be using palliative radiotherapy. Just to talk about some of the data that's associated with its use and how we might go about treating patients. So for the example of an uncomplicated painful bone metastasis, say where there's no evidence of an impending fracture or fracture. There've been a number of studies that have been done. Randomized studies, over nine actually, looking at what the best dose schedule at the best fractionation might be. All of the studies show that in terms of a response rate we see improvement in pain of about 60-70% and in about 20-25% is actually complete responsive pain. It often takes some time for patients to achieve improvement in their ain and we can see responses up to four weeks. in terms of looking at different dose schedules. A single 8 gray fraction appears to be equivalent to multiple fractions in terms of efficacy, durability, probably has less toxicity. But when we use a single treatment, we're more inclined to retreat a patient and so, that happens in about a quarter of patients. And based on these data, guidelines and even a quality measure have supported the use of a single fraction of radiation therapy. So this is an example of a patient with a bone metastasis and how he might go about treating them. So this is a 55 year old woman who was noted to have stage four metastatic disease at diagnosis. She went on to receive multiple courses of chemotherapy, but she developed pain in her shoulder, and on imaging, was found to have a metastasis involving her right humerus. Pain was significant, it was 5 out of 10 on a 10 point scale and she was requiring oxycontin, a long acting narcotic pain medication. And oxycodone, a short acting preparation of the same narcotic, to manage that pain. And we gave her a single eight gray fraction, and this is just a digitally reconstructed radiograph from her planning CT scan. Here's the humerus, here in the center of the field. These lines here indicate the field borders. Each of these dashes here Is just a centimeter so that we could measure the field size. And so, this area was the area that was treated with a single 8 gray fraction and she had significant improvement in her pain. So another common use of radiotherapy for palliation of metastatic disease is for the treatment of brain metastases. And sometimes this can be an emergent indication for radiation treatment. Oftentimes, steroids are given first to help to reduce any swelling associated with the metastases. And oftentimes that results in a signficant improvement in the patient's symptoms. Radiotherapy can be used either as a primary treatment, sometimes it's used as an adjunct to surgery in patients that have a solitary brain metastasis or a particularly large symptomatic brain metastasis. And when it comes to the management of brain metastases, options include surgery, stereotactic radiosurgery. Which is a way of delivering very focused radiation which I am going to give you an example of in a minute. We can use hypofractionated stereotactic radiation so giving say five treatments or I can give whole brain radiation therapy alone and we can do combinations of any of these. The data show that radiotherapy improves neurologic symptoms in about two-thirds of patients but that there is really only a modest improvement in survival maybe of two to three months, on average. Especially, in patients that have multiple brain metastases. In terms of the best treatment strategy, there have been multiple randomized studies that have been done. And none of them show a clear benefit in terms of survival. And so, generally speaking, rather than there being one way to manage patients, we try to tailor the management to the patient situation. And oftentimes the radiotherapy approach is determined by the number of lesions, the number of brain metastases their location, their size, the age of the patient. The patient's performance status, the extent of a disease outside of the brain, what their options might be in terms of systemic treatment and also patient preference. So this is a case of a treatment with a brain metastasis where we used whole brain radiation therapy. So this was a 63-year-old patient, who was first initially diagnosed with stage III disease, but developed a bone metastasis about a year later. Went on to receive multiple courses of chemotherapy and then presented with headache and nausea, and on imaging including a CT scan and an MRI of the brain was found to have eight brain metastases. And because of the diffused nature of his disease and the fact that in addition to these lesions we could see that there was probably metastatic disease. That we couldn't see, we recommended whole-brain radiation in this case and use the standard dose of 30 gray and 10 fractions. And what we're indication here again, this is another digitally reconstructed radiograph that was generated from the planning CT scan. This is a lateral projection and what we did here, these lines here sort of cut off unfortunately. But Indicate the borders of the field and then we use that multileaf collimator that I had mentioned in the previous lecture to shape the field. Basically, to exclude the patients face, so in this case, we're treating the whole brain with lateral fields. And so, we would have one lateral field coming from the right and the other from the left. Now what about stereotactic radiosurgery? So this actually came before the SBRT that I mentioned previously. But conceptually, they're very similar. So this was a patient who had just a solitary brain metastasis, that was in a location, in this case, very close or partly within the brain stem. Where the patient was not a candidate for surgical resection but we wanted to deliver a very focused radiation to this lesion. And so what we did, and this is often done with a stereotactic head frame or it can be done frameless, but in this case, it was down with the head frame and this here indicates the metastasis that we were targeting. These are the patient's eyes here. This green structure is the optic chiasm which wasn't too far away. And we used multiple beams of radiation that were arranged along three arcs, and each of these fields intersected in the center of the tumor. So we get a very high concentration of dose of radiation to the lesion, which is indicated over here. And then, as you move away from the lesion, the dose of radiation actually falls off pretty quickly. So this is an example of stereotactic radiosurgery. One disadvantage of this treatment is that patients are at risk for developing brain metastases elsewhere in the brain and so, they need to be monitored after receiving such treatment. So what about palliative radiotherapy for pulmonary symptoms? We can use it for a variety of indications. When we look at how successful it is, usually we do get good palliation, good relief of symptoms in the majority of patients. Unfortunately, these data come from multiple retrospective studies and so, the effectiveness of the therapy has wide ranges. But for patients that had dyspnea, shortness of breath, we'd expect to see improvement in about 40-90% of patients. For patients that have hemoptysis, coughing up blood, 70-90% cough, we see improvement in cough in about 60-90% of patients. Pain, say due to chest wall involvement in about three-quarters of patients. And in patients who have a compression of the superior vena cava, improvement in about half to almost all patients. So what about radiotherapy? In this setting well, the dosing is dependant on the clinical situation. The extent of the disease, the patients performance status whether they've had a lot of of weight loss. The volume of the target in the lung that we're treating and also patient preference, that's always a consideration. For patience that have a poor performance status or a limited life expectancy we might consider using shorter regimens, such as 20 gray in five, four gray fractions. For patients that have better performance status their actually data showing improved outcomes with higher doses of radiation, so we might commonly use 30 gray in ten treatments. Sometimes we'll give 15 treatments but generally speaking in the palliative setting I wouldn't go any higher. And there's really no rule for concurrent chemotherapy when we're getting regular therapy in the palliative setting. And sometimes, we consider using brachytherapy if patients progress after prior external beam radiation. I didn't talk about brachytherapy much in these lectures because it isn't used commonly for the treatment of non-small cell lung cancer. But this is a treatment where we use a radioactive source on a wire that has a very high activity. And it can be sent down a tube that was placed bronchoscopically in the airway that can be used to treat an obstructing lesion, say that has developed after prior external beam radiotherapy. So this is an example of the use of radiotherapy for palliation, of shortness of breath. So this was a 72 year old Asian female, who never smoked. And, as you may know, that is a common scenario for patients having genetic mutation, EGFR mutation. And in this case, the patient had several months of shortness of breath, and a cough. CT scan demonstrated a very large hilar mass, with an impeding collapse of her right lower lobe, plus she had a bony metastasis. She had a biopsy, and again was found to have this EGFR mutation, which made her a candidate for erlotinib, which is a tyrosine kinase inhibitor. As far as the radiotherapy went, we delivered 30 gray in 10 tx. She would be expected to have a better prognosis than the average patient with metastatic disease. And again, this digitally reconstructed radiograph has superimposed on it the shape of the radiation treatment field. We were treating some mediospinal and hilar nodes as well as the primary tumor because they were so close to the primary tumor that was causing the impending collapse. And again, blocked out some of the surrounding normal lung that we didn't need to treat. So in terms of a take home point, I think it's important to realize that radiation therapy can be an effective form of treatment for many different types of symptoms caused by metastatic non-small cell lung cancer. And the post lecture question is a patient has both a painful humeral metastasis in five symptomatic brain metastases. The optimal courses of radiation are? A.3 gray times 10 to both sites. B.8 gray times 1 and 3 gray times 10, respectively. C.3 gray times 10 to the bony metastases and 8 gray times 1 to the brain metastases. D.8 gray times one to both sites. And E.4 gray times 5 and 3 gray times 10 respectively. And thee answer is B.8 gray times 1 to the bone metastasis and 3 gray times 10 to the brain metastasis. Thanks a lot for listening to this lecture and I'm hoping that you got a lot of this series of lectures.
