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Is There a Role for PCI in Locally Advanced NSCLC?

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GCVL_LU-E10d_Role_PCI_Locally_Advanced_NSCLC

 

Dr. Nasser Hanna, Indiana University Health, addresses the issue of prophylactic cranial irradiation (PCI) in locally advanced NSCLC.

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Unfortunately many people with stage III disease are not cured of their cancer. We’re doing better, but we’re not doing good enough for most people and for those people who are not being cured, oftentimes the cancer will recur in what we call “distant sites.” That may be bones, it may be the liver, it may be the adrenal glands, these two small glands that sit above the kidneys, and sometimes it can be the brain.

When cancer progresses and shows up in the liver or shows up in the adrenal gland, it can certainly be disconcerting, sometimes it can cause symptoms and people don’t feel well, but oftentimes it’s something we just see radiographically. That’s oftentimes not true when cancer recurs in the brain. When it recurs in the brain, oftentimes it’s very unpleasant for somebody. They may have headaches, they may have double vision, they may have unsteadiness or nausea, they may pass out, they may even have seizure activity. So the idea of trying to prevent cancer from spreading to the brain is of paramount importance.

Now in another type of lung cancer, small cell lung cancer, we have utilized a strategy of prophylactically radiating the brain because we know that so many patients with small cell lung cancer eventually develop cancer in the brain. Prophylactically radiating the brain before any signs of cancer have appeared there may do one of two things. Number one is there actually may be microscopic disease in the brain that we really can’t detect on imaging studies for which you’re radiating when you’re doing the so-called prophylactic brain radiation. Secondly, some people believe that when you radiate the brain, it forms sort of an inhospitable environment for cancer to subsequently implant and seed. Either way, we’ve demonstrated that in patients with small cell lung cancer, you can reduce the incidence of brain metastases and in some cases actually help people live longer if you prophylactically radiate the brain.

Now the incidence of brain metastases in those with stage III non-small cell lung cancer is not as high as those with small cell lung cancer. Having said that, about 30-35% of those with stage III disease do eventually develop brain metastases. So the question has come up: should we or could we prophylactically radiate the brain and achieve fewer brain recurrences and perhaps maybe even help people live longer or cure more disease? Well the answer to this question is really unknown — there was one attempt at a carefully conducted clinical trial to test this idea, and unfortunately it was very difficult to accrue to this clinical trial, and it ended up only accruing about a third of the patients that it was meant to accrue.

We got some limited information from this clinical trial and what we learned is yes, we can reduce the incidence of cancer appearing in the brain by prophylactically radiating it. We really weren’t able to demonstrate in this small group of patients an ability to cure more people or help more people live longer, and certainly prophylactically radiating the brain does come with some side effects such as hair loss, fatigue, sometimes headaches, and sometimes nausea.

As of today, it is not standard to prophylactically radiate the brain in patients with non-small cell lung cancer and I’m not sure we’re ever going to get the completion of a clinical trial that will adequately address that, so I suspect for now and probably forever that will not be a standard approach for patients with stage III disease.


GRACE Video

Managing Three Compartments in Stage III Disease (Local, Distant, CNS)

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GCVL_LU-E02_Mark_Socinski_WCLC_2

 

Dr. Mark Socinski, University of Pittsburgh Medical Center, defines the three compartments in stage III (locally advanced) NSCLC, each of which must be treated.

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When I see a patient with stage III disease, I am thinking about how I’m going to potentially cure these patients, because I believe, in a good performance status patient, the long term goal should be a cure of the disease. Now, having said that, there are three major compartments that I am concerned about in this patient population.

As I say to my patients, we have to first devise a strategy that’s going to control and eradicate the disease in the chest — obviously, in stage III disease you typically have a lung primary with mediastinal involvement — and what’s the best strategy to eradicate the disease that you can see in the chest?

The second issue is, almost all patients with stage III disease have what we refer to as micrometastatic disease. You have to think about controlling the systemic micrometastatic disease, and that really falls under the responsibility of systemic chemotherapy, in this particular setting.

So, local/regional control and distant systemic control are the first two issues. A third issue in this patient population is the central nervous system. We know that if we control the first two compartments effectively and seemingly, potentially cure a patient, that up to a third of patients may relapse in the brain itself. Some of those patients with limited relapse and aggressive brain treatment can be salvaged at this point, but it is a huge challenge.

There is some evidence that whole brain radiotherapy, prophylactically, can reduce that risk. However, it’s not clear that it leads to an overall survival advantage, so it’s not considered part of the standard of care, and there are many issues about how to adequately follow patients: how often should you go looking for recurrence in the brain with MRI screening and that sort of thing. So, there are no agreed upon guidelines for this, however, I think each individual physician kind of has their own guidelines in terms of how often they would check an MRI to see if they can diagnose CNS disease early, and perhaps eradicate it with the usual treatments we have for that condition. Of course, that would render the patient stage IV at that time, which really is a whole other set of circumstances that we deal with.


GRACE Video

Have Your Practices Changed Regarding Prophylactic Cranial Irradiation for Extensive Stage SCLC Patients?

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WCLC_2015_23_Practices_Changed_Prophylactic_Cranial_Irradiation_Extensive_Stage_SCLC

 

Drs. Ben Solomon, Leora Horn, & Jack West discuss whether the data highlighting cognitive deficits from whole brain radiation therapy (WBRT) for patients with brain metastases should change our recommendations for prophylactic cranial irradiation (PCI).

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Dr. West:  What about patients with extensive stage small cell lung cancer who don’t have brain metastases, and complete four or six cycles of chemotherapy, and still have a good performance status? We’ve seen conflicting results on the potential value of prophylactic cranial irradiation — some suggesting a significant survival benefit, some even suggesting harm, and a greater concern, I would say, throughout cancer, and certainly lung cancer, about cognitive side effects of brain radiation. So, where does that leave you in terms of what you say to a patient who’s finishing first line therapy and still has a good performance status; Leora?

Dr. Horn:  So, I do talk to patients about the data being fairly controversial. In my clinical experience, the patients who don’t get PCI — many of them do end up with brain metastases at some point.

Dr. West:  It’s very common in small cell.

Dr. Horn:  Yeah, and so I tell them it may delay it, or if it’s not something you want to do, we don’t have to do it at this point. But, I do worry about those patients that we’re not doing PCI [for] anymore, because the Japanese studies suggested, you know, maybe we shouldn’t.

Dr. Solomon:  Yeah, so one of the things that I’ve wondered about that Japanese study, which might make it different from the Slotman study, was the Japanese patients had pretty rigorous imaging of their brain, even prior to entry onto the study, so that study, to my recollection, gave PCI to patients who didn’t have brain metastases, and I wonder whether that might be an explanation for the differences seen. So, again, we have the discussion about PCI with the concerns about neurocognitive effects, but I wonder whether an alternative in someone who doesn’t want to have PCI is to have a policy of CNS imaging — but that’s not yet supported by data, but it might be something to think about.


GRACE Video

Prophylactic Cranial Irradiation for Extensive Stage Small Cell Lung Cancer

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GCVL_LU-GB03_PCI_Extensive_Stage_SCLC

 

Why radiate a perfectly good brain? Dr. Vivek Mehta, radiation oncologist, discusses the possible role for prophylactic cranial irradiation (PCI) for extensive stage small cell lung cancer (SCLC) to decrease risk of brain metastases and improve survival.

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Small cell carcinoma comes in two flavors — one is limited stage disease in the chest, and the other is extensive stage disease. Extensive stage disease means that the cancer has spread to multiple parts of the body, outside of the chest — sometimes that’s the bone, the liver, adrenal glands, or other parts of the body. When you have extensive stage disease, you’re often treated with chemotherapy; sometimes in the setting of extensive stage disease, the cancer completely responds to the treatment and practically goes away. In that setting, we often look to see if the cancer has spread to the brain. If there’s no evidence of spread to the brain, and you had a very nice response to systemic chemotherapy, some people will celebrate — but a lot of people will say that there’s still a risk that the cancer could come back in the brain because, unfortunately, small cell carcinoma has a predilection to get back into the brain, and the chemotherapy, the mainstay of treatment so far, has a tendency to not get to the brain with any sort of meaningful effect.

Now, what to do about that risk that we know exists, is a little bit in controversy. There has been some work suggesting that, in this group of patients that has responded so nicely to chemotherapy, we should be offering them prophylactic cranial irradiation. We offer prophylactic cranial irradiation to patients with limited stage disease — just as a review, prophylactic cranial irradiation really means a low dose of radiation delivered to the whole brain. It’s a lower dose of radiation than you would give somebody that has brain metastasis, and the whole purpose of that lower dose of radiation is simply to reduce any microscopic cells that might be in the brain. Other people think that, because you have extensive stage disease, your risk of the disease coming back elsewhere in the body, even with a dramatic response like that, is going to dwarf any potential benefit of this prophylactic cranial irradiation. It’s certainly an area for discussion — it’s certainly an area for more research. Our personal bias here has been to look at each patient as an individual, and to assess whether or not they would benefit. We tend to take the patients that are younger, more robust, more healthy, and had the best response to treatment, and offer them prophylactic cranial irradiation.


GRACE Video

Prophylactic Cranial Irradiation for Limited Stage Small Cell Lung Cancer

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GCVL_LU-GA02_PCI_Limited_Stage_SCLC

 

Radiation to the brain is a component of our treatment of limited stage small cell lung cancer, even with no evidence of cancer there. Dr. Vivek Mehta, radiation oncologist, reviews why we would do such a thing.

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Small cell cancer is a type of lung cancer that presents in basically two formats. One format is that the disease is actually limited to what classically, in the old days, radiation oncologists called “the box,” meaning that it was limited to the chest. When we talk about limited stage small cell carcinoma, we’re talking, potentially, about a disease that is very responsive to treatment, and sometimes can be cured. When we cure those patients, with a combination of chemotherapy and radiation for limited stage small cell carcinoma, we often look to see if the cancer has spread to the brain. We do this by getting MRI studies of the brain; if there’s no evidence of disease in the brain, and the treatment has effectively worked in the chest at eradicating the disease, we all are very happy.

Unfortunately, if you follow these patients over time, they have a very high chance of having the cancer come back in the brain — the brain is thought to be a sanctuary site, meaning that it doesn’t get the treatment from the chemotherapy that the rest of the body gets, so if any cells have snuck up there, they sometimes can grow without the treatment that’s been delivered so far.

One of the things that we’ve done in the past is deliver a very low dose of radiation to the whole brain, as a prophylactic treatment — that’s often called PCI, or prophylactic cranial irradiation. We offer this routinely to patients with limited stage disease because the studies have demonstrated that if you give prophylactic treatment, you reduce the chances of the cancer coming back in the brain, and if you reduce the chances of the cancer coming back in the brain, you presumably reduce the chances of all those symptoms that cancer in the brain can cause.

We often talk about the brain as being the “high rent district.” If we can keep cancer out of the brain, we can keep people much more functional, not have the risks of strokes, and mental problems, and seizures that cancer in the brain can cause, so we often give prophylactic cranial irradiation.

Prophylactic cranial irradiation is a little bit different than whole brain radiation: the doses that you give each day are lower, the dose that you give overall is lower, because you’re treating disease that you can’t see, you’re not treating the disease that is actually already there — hence the word prophylactic cranial irradiation.


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