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Multimodality Approaches to Locally Advanced NSCLC

Insights From: Suresh Senan, MD, VU University Medical Center; Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois
Published: Friday, Mar 09, 2018



Transcript: 

Marina Chiara Garassino, MD: The treatment goals can be palliative and curative, according to the conditions of the patients. And we have to think that stage 3 non–small cell lung cancer is a very heterogeneous stage of non–small cell lung cancer because in the same stage 3, you may have a totally different picture of the patients. So, you may have, for example, a large T volume or a large N volume, and this is really important to take when making the decisions, the surgery or the radiotherapy, for each patient.

The second point is that the majority of patients have several comorbidities. And so, for example, in some cases, you are not able to go to surgery maybe because they have COPD and they have some lung functional test not allowing some treatment. And the second point is that you have different toxicities with the different treatments. And it is also important to have the decision patient-by-patient, according to the goals that are important for a single patient. For example, if you are 80, your goal is to have a good quality of life. Maybe if you are 60, your goal is to have a curative intent treatment.

So, it is a very heterogeneous field and we have to think about which is the better solution for each patient, with a multidisciplinary team. Try every time to go with a curative intent, but sometimes also palliative intent can be important for a category of patients with several comorbidities or several problems in their life.

Solange Peters, MD, PhD: In locally advanced non–small cell lung cancer, the major advance we have been doing in the past years is not to refine chemotherapy, radiotherapy, or change the paradigm there, but it’s more about how to integrate these various modalities. We’ve been improving the integration of the same chemotherapy and the same radiotherapy, but we’ve been improving how to deliver it to the patients. This can be due, in my opinion, to the fact that we collaborate better with the colleagues from other disciplines. So, this disease, this stage imposes the existence of multimodality meetings—what we call tumor boards—in order to be sure that every single patient has a personalized treatment, including surgery or not, including chemotherapy or not, and really time frame in terms of being as fast as possible. But what, for example, has been shown in the disease is, as far as you can tell, you should really deliver radiotherapy and chemotherapy at the same time. So, this needs some organization and it needs also to be really well trained in terms of a multimodality team around the patient to be sure that the treatment is optimally delivered without delay and so on.

So, we’ve been improving the fact that it’s not just to give lots of chemotherapy before and after. You have to give chemoradiotherapy at the same time, and it can be a short treatment, but this has to be like that. In this locally advanced disease setting, you have to first give chemotherapy and then surgery. But everything is important; the time between one modality and the other one counts and all these kinds of things. So it’s really about sharing together for the best way to treat the patient, and this is where we have been making advances. Not in the chemotherapy, not in the radiotherapy, and not in the surgery, but how to make people meet around the patient.

Suresh Senan, MD: In locally advanced non–small cell lung cancer, the disease extent has an important place in determining the treatment strategy, just as the patient fitness has. So, patients with single station ipsilateral N2 disease have an option of undergoing chemoradiotherapy or surgery. And the tumor board can make the decision based on the extent of likely surgery and the fitness of the patient. If the patient is not a candidate for limited surgery, then we proceed to definitive chemoradiotherapy. In some patients with limited disease, we give induction chemoradiotherapy until about 50 gray, to be followed by surgery, if the surgeon feels that the preceding treatment, induction treatment, is necessary in order to ensure a complete resection.

In all other patients—patients with multiple N2 disease or large bulky N2 disease or contralateral N3 disease—the standard of care is concurrent chemoradiotherapy to a dose of at least 60 gray, given in once-daily fractions of 2 gray. The European guidelines do allow us to go up to 66 gray, so 3 fractions more, in smaller-volume disease where the likelihood of tissue damage is limited. So, basically 60 gray is considered the standard dose with 2 cycles of platinum-containing chemotherapy.

It’s often said that 3A’s potentially operable whereas 3B non–small cell lung cancer is not. But for a radiation oncologist, that distinction is less important than the extent of the radiation field. So, a smaller volume, stage 3B, is potentially just as curable as the stage 3A, whereas the very extensive stage 3A with extensive nodal disease can actually result in considerable radiation toxicity, for example, to the esophagus.

So, one of the factors that influences our strategy is the fitness of the patient to undergo full-dose chemotherapy. If a patient can undergo chemotherapy, then we look at the radiation fields and judge if the risk of acute toxicity, especially radiation esophagitis, is likely to be limited or can be well tolerated by the patient. And then we would prefer to go to concurrent radiotherapy at the start. So, at least 2 cycles together with the radiation, which takes 6 weeks.

In the younger patients, there’s often less doubt, but in the older patient population the clinicians are sometimes hesitant to do combined chemoradiotherapy. And I think the data from recent large trials internationally and North America suggest that the esophagitis rate is actually quite modest, closer to 6% to 15%. So, many patients are willing to accept that risk if they are informed that there’s a good chance of long-term survival from the lung cancer.

So simply considering other treatment options because a patient is elderly is not appropriate. And elderly patients may have single station N2 disease, which is a very low risk of esophagitis, and it’s quite acceptable to commence with that strategy. And if the patient doesn’t tolerate it, change the plan rather than presuming that a patient would be unfit to undergo that.

Some of the newer insights coming from trials are that perhaps carboplatin-containing chemotherapy, which is sometimes better tolerated in elderly patients, seem to be just as effective in the combined modality setting. Especially in Europe in the past, there has been a tendency to consider fitness to undergo cisplatinum-based chemotherapy as the criteria for combined modality. Perhaps if these ideas are critically evaluated again, we might put more patients into concurrent chemoradiotherapy if they’re only fit for carboplatin.

So, I think we have to have a rethink. In North America, it’s much more popular to use carboplatin regimens, whereas in Europe, it’s less. And use of carboplatin for concurrent chemoradiotherapy may allow more elderly patients to undergo concurrent chemoradiotherapy for locally advanced non–small cell lung cancer.

In expert multidisciplinary teams, often the trimodality approach is considered. So, that’s to say, chemoradiotherapy plus surgery. In such a patient population, it often means that limited surgery may be possible—for example, a sleep lobectomy—or a more radical surgery may be possible if the patient undergoes induction therapy. But it’s important to realize that this position should be taken to a multidisciplinary team before the patient undergoes any planned treatment, so that the surgeon is prepared, gives a commitment, the patient is aware what the options are, and this treatment strategy is best limited to patients who are treated in expert centers with radiation and surgical expertise available.

It should not be an ad hoc decision in a patient who’s undergoing planned full-dose chemoradiotherapy to stop suddenly and then say, “Well, perhaps we should have thought about surgery.” It’s confusing for the patient, it’s bad for the planning, it might result in unnecessary interruptions and delays, and the surgical team may not be happy to suddenly be asked to consider this late in the treatment path.

Transcript Edited for Clarity 
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Transcript: 

Marina Chiara Garassino, MD: The treatment goals can be palliative and curative, according to the conditions of the patients. And we have to think that stage 3 non–small cell lung cancer is a very heterogeneous stage of non–small cell lung cancer because in the same stage 3, you may have a totally different picture of the patients. So, you may have, for example, a large T volume or a large N volume, and this is really important to take when making the decisions, the surgery or the radiotherapy, for each patient.

The second point is that the majority of patients have several comorbidities. And so, for example, in some cases, you are not able to go to surgery maybe because they have COPD and they have some lung functional test not allowing some treatment. And the second point is that you have different toxicities with the different treatments. And it is also important to have the decision patient-by-patient, according to the goals that are important for a single patient. For example, if you are 80, your goal is to have a good quality of life. Maybe if you are 60, your goal is to have a curative intent treatment.

So, it is a very heterogeneous field and we have to think about which is the better solution for each patient, with a multidisciplinary team. Try every time to go with a curative intent, but sometimes also palliative intent can be important for a category of patients with several comorbidities or several problems in their life.

Solange Peters, MD, PhD: In locally advanced non–small cell lung cancer, the major advance we have been doing in the past years is not to refine chemotherapy, radiotherapy, or change the paradigm there, but it’s more about how to integrate these various modalities. We’ve been improving the integration of the same chemotherapy and the same radiotherapy, but we’ve been improving how to deliver it to the patients. This can be due, in my opinion, to the fact that we collaborate better with the colleagues from other disciplines. So, this disease, this stage imposes the existence of multimodality meetings—what we call tumor boards—in order to be sure that every single patient has a personalized treatment, including surgery or not, including chemotherapy or not, and really time frame in terms of being as fast as possible. But what, for example, has been shown in the disease is, as far as you can tell, you should really deliver radiotherapy and chemotherapy at the same time. So, this needs some organization and it needs also to be really well trained in terms of a multimodality team around the patient to be sure that the treatment is optimally delivered without delay and so on.

So, we’ve been improving the fact that it’s not just to give lots of chemotherapy before and after. You have to give chemoradiotherapy at the same time, and it can be a short treatment, but this has to be like that. In this locally advanced disease setting, you have to first give chemotherapy and then surgery. But everything is important; the time between one modality and the other one counts and all these kinds of things. So it’s really about sharing together for the best way to treat the patient, and this is where we have been making advances. Not in the chemotherapy, not in the radiotherapy, and not in the surgery, but how to make people meet around the patient.

Suresh Senan, MD: In locally advanced non–small cell lung cancer, the disease extent has an important place in determining the treatment strategy, just as the patient fitness has. So, patients with single station ipsilateral N2 disease have an option of undergoing chemoradiotherapy or surgery. And the tumor board can make the decision based on the extent of likely surgery and the fitness of the patient. If the patient is not a candidate for limited surgery, then we proceed to definitive chemoradiotherapy. In some patients with limited disease, we give induction chemoradiotherapy until about 50 gray, to be followed by surgery, if the surgeon feels that the preceding treatment, induction treatment, is necessary in order to ensure a complete resection.

In all other patients—patients with multiple N2 disease or large bulky N2 disease or contralateral N3 disease—the standard of care is concurrent chemoradiotherapy to a dose of at least 60 gray, given in once-daily fractions of 2 gray. The European guidelines do allow us to go up to 66 gray, so 3 fractions more, in smaller-volume disease where the likelihood of tissue damage is limited. So, basically 60 gray is considered the standard dose with 2 cycles of platinum-containing chemotherapy.

It’s often said that 3A’s potentially operable whereas 3B non–small cell lung cancer is not. But for a radiation oncologist, that distinction is less important than the extent of the radiation field. So, a smaller volume, stage 3B, is potentially just as curable as the stage 3A, whereas the very extensive stage 3A with extensive nodal disease can actually result in considerable radiation toxicity, for example, to the esophagus.

So, one of the factors that influences our strategy is the fitness of the patient to undergo full-dose chemotherapy. If a patient can undergo chemotherapy, then we look at the radiation fields and judge if the risk of acute toxicity, especially radiation esophagitis, is likely to be limited or can be well tolerated by the patient. And then we would prefer to go to concurrent radiotherapy at the start. So, at least 2 cycles together with the radiation, which takes 6 weeks.

In the younger patients, there’s often less doubt, but in the older patient population the clinicians are sometimes hesitant to do combined chemoradiotherapy. And I think the data from recent large trials internationally and North America suggest that the esophagitis rate is actually quite modest, closer to 6% to 15%. So, many patients are willing to accept that risk if they are informed that there’s a good chance of long-term survival from the lung cancer.

So simply considering other treatment options because a patient is elderly is not appropriate. And elderly patients may have single station N2 disease, which is a very low risk of esophagitis, and it’s quite acceptable to commence with that strategy. And if the patient doesn’t tolerate it, change the plan rather than presuming that a patient would be unfit to undergo that.

Some of the newer insights coming from trials are that perhaps carboplatin-containing chemotherapy, which is sometimes better tolerated in elderly patients, seem to be just as effective in the combined modality setting. Especially in Europe in the past, there has been a tendency to consider fitness to undergo cisplatinum-based chemotherapy as the criteria for combined modality. Perhaps if these ideas are critically evaluated again, we might put more patients into concurrent chemoradiotherapy if they’re only fit for carboplatin.

So, I think we have to have a rethink. In North America, it’s much more popular to use carboplatin regimens, whereas in Europe, it’s less. And use of carboplatin for concurrent chemoradiotherapy may allow more elderly patients to undergo concurrent chemoradiotherapy for locally advanced non–small cell lung cancer.

In expert multidisciplinary teams, often the trimodality approach is considered. So, that’s to say, chemoradiotherapy plus surgery. In such a patient population, it often means that limited surgery may be possible—for example, a sleep lobectomy—or a more radical surgery may be possible if the patient undergoes induction therapy. But it’s important to realize that this position should be taken to a multidisciplinary team before the patient undergoes any planned treatment, so that the surgeon is prepared, gives a commitment, the patient is aware what the options are, and this treatment strategy is best limited to patients who are treated in expert centers with radiation and surgical expertise available.

It should not be an ad hoc decision in a patient who’s undergoing planned full-dose chemoradiotherapy to stop suddenly and then say, “Well, perhaps we should have thought about surgery.” It’s confusing for the patient, it’s bad for the planning, it might result in unnecessary interruptions and delays, and the surgical team may not be happy to suddenly be asked to consider this late in the treatment path.

Transcript Edited for Clarity 
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