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Chemoradiation as a Standard of Care for Unresectable NSCLC

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GCVL_LU-E09_Chemoradiation_Standard_Care_Unresectable_NSCLC

 

Dr. Nasser Hanna, Indiana University Health, discusses the development of chemoradiation as a standard of care for unresectable stage III NSCLC.

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So what is the standard of care treatment for those who are not going to have surgery for stage III disease that are either medically inoperable or they are surgically unresectable? Well for decades radiation therapy has formed the backbone of treatment. If you can’t surgically remove a tumor, you can certainly apply radiation to that tumor; you radiate the tumor, the lymph nodes, and some surrounding tissue where microscopic disease may be. That form of therapy can be effective but by itself oftentimes is not curative. It will shrink tumors and oftentimes patients will have a reduction in symptoms, maybe a tumor was compressing an airway or maybe it was causing them to cough up blood or something like that where the radiation therapy can be effective at relieving some of those symptoms.

Historically radiation therapy alone for stage III disease has resulted in about a 5% cure rate — the vast majority of patients will develop growth shortly thereafter, either outside the radiated field, occasionally in the radiated field, but most commonly distant metastatic disease. That’s because even though the disease appears to be confined to the chest, we know that the majority of patients already have microscopic spread of their cancer to other parts of their body. That’s not something that you can see on a CT scan, it’s not something that you can see on a PET scan, it’s certainly not something you can feel on a physical exam, but we know that’s the case because historically when you’ve done surgery alone for this group of patients and successfully removed all the disease you can see, the vast majority of people will still develop distant, recurrent disease usually within about a year’s time. Radiation therapy alone can have some effectiveness for patients, but by and large it’s a short term effect and it oftentimes doesn’t cure patients.

Starting really about three or four decades ago, chemotherapy was beginning to be incorporated in the treatment of patients with stage III disease. In the 1970s it was demonstrated that chemotherapy could shrink cancers that had already metastasized, and perhaps if it could shrink cancers that were large enough to see on x-rays, maybe it would be effective enough to treat that microscopic disease that patients have with stage III lung cancer.

So beginning in the 1970s and really going in full force in the 1980s, chemotherapy was incorporated with radiation strategies and a whole host of different strategies were tried. The most common strategy was to give a couple of courses of chemotherapy first, try to shrink the cancer, try to treat that microscopic metastatic disease early on, and then follow that with radiation therapy. Early efforts into that approach were not terribly successful, and that’s for several reasons. Number one, our staging tools weren’t very good, so oftentimes even though we thought patients have stage III disease, they oftentimes already had stage IV disease and they weren’t going to be cured with that type of strategy. Secondly, many patients who participated in those clinical trials were already not doing well. They had what we call a low performance status, in other words, they had already become very debilitated by their disease and their ability to tolerate therapy wasn’t very good. Thirdly, our radiation techniques were fairly crude at the time, radiation planning was very crude at the time as well. Fourth, our chemotherapy actually was not terribly active; although it was modestly active, it probably wasn’t the most effective therapy that patients could receive. Lastly, it really wasn’t recognized, the clinical significance of having weight loss. So oftentimes patients will have suffered a lot of weight loss which is really a signal that they truly have systemic disease, and when you include all those types of patients on clinical trials, you’re really setting yourself up for failure.

The initial attempts at trying to treat patients with both chemotherapy and radiation therapy really would be considered failures. Outcomes were not very good, we really didn’t seem to improve cure rates over radiation therapy alone, and this was in an era in which chemotherapy was not very well tolerated. That really started to change in the mid-1980s, and really a landmark trial was conducted by a United States cooperative group. In this trial, patients were excluded if they had a really poor functional status, if they had significant weight loss, and so it really narrowed the group of patients who could potentially benefit from this therapy. In this study, patients received two courses of chemotherapy, and then that was followed by six weeks of radiation therapy. For the first time, we were able to demonstrate an improvement in cure rates. It was fairly modest, we went from about a 5% cure rate to about a 15% cure rate.

Because that was the first time that was really ever demonstrated, a second trial was required to really make sure that this was a real finding. So a second trial was done in the United States by other cooperative groups; this was a much larger trial and they essentially replicated that data.

Well in the 1980s and in the 1990s, this strategy of giving chemotherapy and radiation therapy at the same time was becoming a standard approach in many different cancers. This included cancers of the pancreas, of the esophagus, of the head and neck, of the rectum, and so that sort of idea was attempted in lung cancer. Now we weren’t sure if we could actually give chemotherapy and radiation at the same time to somebody who had lung cancer. It’s a bit different radiating the mid-chest area where the heart is going to get radiation, the lungs are exposed to a lot of toxicity from radiation, the esophagus would oftentimes be in the field of radiation. So the first thing we had to do was prove that it was safe and feasible to do, and indeed investigators did demonstrate that. The next step was to determine whether that strategy of giving chemotherapy and radiation at the same time would truly be more effective than giving them separately – there were a lot of theoretical advantages to doing that. First, you would not delay the radiation therapy. Secondly, you might be able to give both therapies at the same time which would work to kill cancer cells in different ways simultaneously, but we knew that it would come at a risk.

We knew that it would come at a risk of increased side effects when you give the treatments together versus giving them separately. Several randomized trials were conducted in the United States, in Japan, in Europe, that looked at comparing the concurrent administration of chemotherapy and radiation to the sequential administration of those two. Those trials by and large demonstrated that while it was more difficult on patients and there were certainly more side effects, you could improve cure rates by giving the treatment concurrently.

So really through the 1990s and into the early 2000s, the standard of care treatment for those who were well enough and fit enough for this type of therapy was to give concurrent chemotherapy and radiation therapy.


GRACE Video

The Basics of a Lung Cancer Workup

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GCVL_LU-B00_Lung_Cancer_Workup_Basics

 

Dr. Gerard Silvestri, Medical University of South Carolina, describes the steps necessary to work up a lung cancer diagnosis, from initial scan to choice of treatment.

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What are the basics of working up a lung cancer? When I see a patient in my clinic, usually they haven’t had anything done yet. They’ve been referred to me with a “spot” or lesion, or a mass on their lungs, and again, the first thing I need to do is take a good history and physical. How long have you had your symptoms, have you had weight loss, do you have bone pain, have you had headaches, what are some of the things going on — what diagnostic workup have you had? Sometimes they’ll already have had a biopsy. My job though is to do these three steps, absolutely simultaneously and sometimes in order — what is it, where is it, what I can do about it — diagnosis, stage and treatment.

The first visit is almost always trying to review the imaging and decide whether you need more imaging, do a good physical exam, do a good smoking history, find out what other health issues the person may have like heart disease, that can give us a challenge in terms of how we’re going to treat the cancer. So that’s the first part.

Sometimes I have to say that some patients are — it’s thought they may have a lung cancer, and in fact it’s something else. It could be a fungal infection or something else going on in the lungs. So usually what happens over sort of the course of the next ten working days is, either some more imaging, or a biopsy, and then perhaps a PET scan to help us with the staging portion of this. So sometimes we get a PET scan that will help us both direct the biopsy, but also help us with the stage. Over the next ten days or so we’ll try to get those tests done.

In addition, we always present our new cases at a multidisciplinary tumor board. What’s that? A multidisciplinary tumor board is where all the different specialties get together to look over the imaging, the biopsy results, the pathologic results, and come up with a better treatment plan. So who’s in the room during the tumor board? A pulmonologist usually, a chest surgeon or a thoracic surgeon, a medical oncologist, a radiation therapist, a pathologist, sometimes you’ll have a dedicated chest radiologist who will help review the films, and then also people from other ancillary services that are extremely helpful like clinical trials staff, like palliative care nursing. So we have all those people in the room at the same time, and they’re either reviewing brand new cases, or difficult and challenging cases that are coming back to the tumor board for consideration.

So that kind of happens in that first ten days and for us, we know how anxious patients can get during that time period that they just want to get something started, but I would urge anyone listening to this to consider is, if you don’t get it right, if you don’t give the person the correct stage and the correct treatment options, you won’t get the best care. Yes, speed is important, but you’ve got to get it right — what is it, the diagnosis, where is it, the appropriate stage, and then what are your treatment options, which really differ depending on stage. For stage I it’s usually surgery, for stage II, surgery followed by chemotherapy, for stage III, chemotherapy and radiation, and for stage IV, chemotherapy alone or some of the targeted agents. So if you don’t get that right, you’re going to get the wrong treatment, so be patient with that and if your doctors need to biopsy in a different area, as long as they’re explaining it appropriately to you, you should try to stay with that program.

So that’s the general workup of a patient. I will say, every patient gives a little bit of a nuance and so sometimes a patient seemingly needs something that’s a bit unusual in terms of a biopsy or the location of a biopsy or how to best go about getting that biopsy, and I can also say that sometimes the tumor board is split. Sometimes there’s no right answer about whether we should do it via a needle biopsy through the chest wall, or a bronchoscopy, and sometimes talking that through with a patient, they can help us – you can help us as patients make a decision about which way we would go next. That’s the general workup of a lung cancer.


GRACE Video

PET Scan Imaging: What Does It Tell Us?

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GCVL_LU-B02_PET_Scan_Imaging_Lung_Cancer_Workup

 

Dr. Gerard Silvestri, Medical University of South Carolina, discusses the use of PET scans in lung cancer workup.

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You may be asked when you’re diagnosed with lung cancer to have something called a PET scan. Unlike a CT scan, a PET scan tells us not where it is, but is it active — so a PET scan works on this idea that if it “lights up,” it’s an active lesion. Now things that are active tend to be rapidly dividing cells, and so PET is actually not useful in the brain where we are thinking all the time, we have very rapid metabolism. If a lesion lights up in the lung it’s rapidly dividing cells and it may be cancer, although sometimes infections in the lung can cause the PET scan to light up and even changes after radiation treatments can cause a PET scan to “light up.”

The PET scan can tell us if and where lesions are active, and they sometimes pick up disease we didn’t suspect outside the chest, for example in the bone, or the adrenal gland, or the liver, so the PET scan is useful if it’s positive and it tells us that a lesion is active. It’s also incredibly useful if it’s negative — so sometimes we have benign spots in our lung and if the PET scan is negative in that area it means, by and large, it’s not cancer.

One strong recommendation in this area though is if you have a positive PET scan it doesn’t always mean cancer; 20% of the time it’s falsely positive, especially in patients that have infections around a certain area. We often recommend doing a biopsy to confirm that the PET scan is in fact really cancer, or could it be something else. Sometimes we’re really surprised at the results of the biopsy in patients who have a positive PET scan and it turned out not to be cancer, which is good news for our patients.


GRACE Video

Radiation Management of Limited Stage SCLC

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GCVL_LU-GA04_Radiation_Management_Limited_Stage_SCLC

 

Dr. Vivek Mehta, radiation oncologist, reviews the basic principles and treatment approach for limited stage small cell lung cancer, which combines chest radiation with concurrent chemotherapy.

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Small cell cancer of the lung is a type of lung cancer. Small cell cancer of the lung come in two shapes and sizes, if you will. Limited stage disease is cancer that’s affecting only the chest, or what we think about in radiation oncology as sort of “the box,” if you will, and extensive stage disease is small cell cancer that started in the chest, that spread to other parts of the body — for example, the liver, the bone, or other tissues.

The treatment for limited stage disease is often to use a combination of chemotherapy and radiation treatment. The chemotherapy goes throughout your body, killing not only the cancer that you can see, but the cancer that you also could be hiding somewhere that’s too small to detect. The radiation is directed at the bulky cancer that’s within the chest. The radiation treatment is delivered Monday through Friday, generally over a period of five or six weeks. The treatment is used in combination because, when you do radiation alone, you don’t kill most of the cancer that’s hiding elsewhere in the body — when you do chemotherapy alone, there’s a high risk of the cancer coming back in the region that it started. When you combine the radiation and chemotherapy together, you have a much greater chance of eradicating every last cell. Eradicating the last cell is the hope in this whole cancer, because you’re trying to cure these patients.

We’ve done studies in terms of the timing of when it’s best to give the radiation, relative to the chemotherapy, and what we’ve learned is that, if you can get the radiation and the chemotherapy started at the same time early on, that’s actually more effective than doing chemotherapy first and having the radiation at the tail end of treatment. So, our preference here at this center is to treat everybody with upfront chemoradiation, when it’s possible, in patients that can tolerate it, with limited stage disease. We’re hoping, again, to try to cure as many of these patients as we possibly can.


GRACE Video

Reirradiation of Tumor in a Previously Radiated Field

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GCVL_LU-E12_Lung_Cancer_Tumor_Reirradiation

 

Radiation oncologist Dr. Chris Loiselle reviews the possibility of re-treating with radiation for lung cancer, typically using stereotactic technique, in a previously irradiated field.

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Reirradiation of lung cancer is an area where we discuss a lot with patients, the risks and benefits, and think a lot about the unique situation that each patient is finding themselves in. I think it’s often an area too where many people are told by their physicians that once they’ve had radiation, they can’t have it again, and that is not true, generally. We often will consider doing reirradiation, or a second course of radiation; we’ll often do reirradiation with stereotactic techniques, like the CyberKnife, to really minimize any collateral damage, but it is a careful discussion of risks and benefits.

We think about doing reirradiation when we see patients who, typically, are in one of two circumstances. The first one being a patient who has an early stage disease treated with surgery or radiation, and they have a recurrence which, typically, is not operable. In this situation, we are treating with curative intent, and in the setting of curative intent, we may be willing to accept some increased risk depending on the certain circumstances in an effort to potentially cure a life-threatening lung cancer.

On the other side of reirradiation, the circumstance that we see most is a patient who has radiation, either to a primary site or perhaps to a metastatic site in the body, and they recur there, and it’s causing problems — it’s causing spinal cord compression, it is compressing an airway, and we think about this as a multidisciplinary team. We think about all options: we think about chemotherapy, targeted therapy, surgery, but sometimes when surgery or chemotherapy or systemic therapy are not a good option, and reirradiation, though it carries some risks, is an option, we move forward with a mutual understanding between ourselves and our patients about what we’re getting into, and we are looking toward doing the best that we can — again, sometimes thinking about understanding increased risks.


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