How can outcomes be further optimized for patients with inoperable or unresectable
Stage III non-small cell lung cancer (NSCLC)?

Considerations for optimizing CRT in NSCLC: Patient cases.

The views and opinions expressed in this video are those of the individual oncology specialists and do not represent the views or opinions of AstraZeneca. This video contains anecdotal information gathered from a discussion with oncology specialists based on their opinions/experiences. Recommendations are general and may vary with patients. At the time of this filming, the Healthcare Professionals featured were in the roles and at the institutions indicated.

Here, we’ll present a team discussion of three cases of patients diagnosed with NSCLC. One with T3N2, one with T3N3 and one with EGFR mutated T4N3.

Hello, I’m Dr Janakiraman Subramanian. Welcome to our video series on the changing landscape of unresectable Stage III non-small cell lung cancer. In this video, we’ll be discussing 3 cases of patients with unresectable Stage III non-small cell lung cancer.

My name is Bobby Mahajan, and I’m an interventional pulmonologist.

I’m Stephen Chun. I’m a radiation oncologist.

Hi, I’m Dr Boris Sepesi. I’m a thoracic surgeon.

Here is case #1, a patient with Stage IIIA T3N2 NSCLC.

Let’s look at our first patient here.

So, this is Alan, who presented to his primary care with a prolonged and productive cough. He’s 67 years old and a former tobacco smoker with a 40-pack-year smoking history. And this cough has been of prolonged duration and it has not improved despite taking some over-the-counter medication. He does have some additional medication comorbidities like hypertension and asthma, but good performance status ECOG PS at 1. And he had an initial chest X-ray done, which shows a single mass in the lung, and that’s concerning obviously, for malignancy. And so, his primary care refers him to a pulmonologist for further evaluation.

So, Bobby, when you see a patient like this, how does the referral pattern work? How do these patients get referred to you?

The referral patterns are multiple. Sometimes we see nodules that are incidentally found, for example, in a patient who might just have a cough or comes to the ER and they get a chest CT, then shows a lung nodule. Other ways we see our patients who have symptoms associated with possibly larger masses or through lung cancer screening. They are sent to multiple different physicians before they get typically to the right physician or to the multidisciplinary meeting.

That is a challenge for our patients.

So, this patient, when he is seen by his pulmonologist, gets a PET/CT and also has PFTs, and a bronchoscopy done as well. The CT scan identified right lower lobe lung mass measuring four centimeters and invading the chest wall. And on the PET/CT, not just the primary tumor, which was FDG-avid, also the hilar and mediastinal lymph nodes had increased FDG uptake concerning for cancer. So, PFTs are reasonably good—DLCO at 70%, FEV1 at 70%. Bronchoscopy was done with EBUS, and he has both the tumor as well as the lymph nodes are positive for malignancy. And at this point, this patient was referred to see a medical oncologist.

Number four. With a perioperative IO-based regimen, as with all cancer treatments, you, as the patient, are the most important member of your care team. You should feel free to ask all the questions you have of the other members of the care team so that you’re confident in the treatment you’re receiving.

Are there any tests you would get at this point, Bobby, for this patient?

Even though the easiest way to approach this might be just do a needle biopsy of the nodule, it provides us with a diagnosis, but it does not provide us with all the data we need. We really need to be able to stage these patients, see if there’s N2 disease or N1 disease, if it’s single station or multistation. We would want to be able to send this over to our medical oncologist and a radiation oncologist. At that point, then talk to our navigators about getting a PET/CT, a brain MRI so that again, when they hit the medical oncologist’s office, all that data is already obtained.

I definitely think that the biomarker testing should be done essentially immediately at the time of diagnosis. The biological behavior over here is aggressive. I would certainly not recommend an upfront operation in this situation. I think this patient should definitely be treated up front with either systemic therapy or potentially just go the pathway of concomitant chemoradiation. But this is where the biomarkers, they must be done in order to make this decision in terms of is this EGFR or ALK positive and what is the PD-L1 status?

So, Bobby, what are you looking for when you have a really tiny sample in the initial biopsy, or you think it may not be adequate for molecular testing. What do you do to mitigate that?

Well, I think that in a lot of ways, we have to use all the resources available to our disposal. Really, it is important to take your time, biopsy at least 2 malignant nodes if present so that oncologists and the pathologist especially can choose between different cell blocks on which sample should be sent for NGS to get the best chance of actually getting a full panel back.

Boris, in your opinion, do you think this patient is resectable or borderline resectable? And overall, how do you manage patients with Stage III N2 disease?

I think that I would classify this patient as a borderline resectable because he has a primary tumor that’s abutting, at least the parietal pleura. And certainly, it seems that the nodal disease is already spreading from N1 station to multistation N2 disease. From anatomical standpoint, I think that this operative field sort of encompasses the entire visible disease on the CT scan. And therefore, I would believe that in my hands, this is still potentially a resectable disease; however, with the caveat of the way this disease is acting biologically, and this is why I would to know the biomarkers prior to this as well, as I would discuss this patient in a multidisciplinary setting for different neoadjuvant or other treatment options or options for nonsurgical options as well for concomitant chemoradiation.

I want to also echo Dr Sepesi’s comments and emphasize the importance of reflexly getting biomarkers. I also want to discuss a potential situation of a patient like this receiving neoadjuvant therapy. I would argue for involving the radiation oncologist up front before making that determination, because it’s possible, like in this case, that a radiation treatment volume could be developed safely that did not require neoadjuvant therapy. I want to emphasize that even in tumors that, let’s say, do not respond to neoadjuvant therapy or even, let’s say, suddenly progress on neoadjuvant therapy, that does not necessarily mean that it would not respond to concurrent chemoradiation. That’s a great pearl of wisdom I learned from the great Wally Curran, actually—just because someone doesn’t respond to chemotherapy doesn’t mean that they won’t respond to chemoradiation. But my preference is that radiation be involved very early on and before decisions are made regarding neoadjuvant therapy.

In summary, this Stage IIIA patient was deemed borderline resectable. MDT communication was crucial in formulating the treatment plan. Understanding this patient’s biomarkers was an important part of appropriate treatment planning.

This is case #2, a patient with unresectable Stage IIIC T3N3 NSCLC.

So, here we have our second patient who’s a former tobacco smoker presenting with cough and diagnosed with a lung mass or a lung opacity on the right side on her chest X-ray. Good performance status. So, she has a CT scan, which shows 5.2-centimeter, right middle lobe mass. And the lesion or the tumor is FDG-avid on the PET scan. And then she has a CT-guided biopsy that shows that this is a non-small cell lung carcinoma, and they also get an MRI of the brain done, and she has a tumor board discussion on this case as well.

So, looking at this particular case, Stephen, what do you see as some of the challenging issues when you look at the PET scans?

So, looking at this particular case, I think what jumps out at probably all of us here is the extent of disease and whatever local therapy, I don’t want to speak for surgery, but whatever local therapy is going to be used, this is a very large area that needs to be locally controlled. From a radiation standpoint, it is very important to have the best imaging possible so that we can make the radiation treatment fields as conformal and specific to the patient anatomy as possible. It’s also very important for the patient to be optimized in terms of nutrition, in terms of side effect management, because there’s going to be a very large amount of esophagus exposed to radiation. And also, I think very close coordination with medical oncology where concurrent chemotherapy would be administered. I also want to emphasize, this case, when I look at the PET scan, we see supraclavicular nodes or N3 nodal disease. I just want to emphasize because I see this sometimes confused in some of my examinees, but this is Stage III disease. It’s not Stage IV. And a patient like this, while treatment may be very challenging, these patients are very much candidates for curative intent chemoradiation followed by appropriate consolidative therapy based upon their molecular profile. In this situation, surgery made a determination this was not appropriate for a resection with what we see here, bilateral mediastinal metastasis, right supraclavicular nodal metastasis, and a fairly locally advanced right middle lobe tumor.

So, Boris, what are the clinical characteristics that you look for in determining whether a patient is either technically resectable as well as whether they are medically operable?

This is actually that interesting case that as I look at it as a surgeon. So, on one hand, middle lobe is the smallest of all lobes; it’s only two segments, contributes 10% to lung function. This tumor is already pretty much including the entire middle lobe. So, from the pulmonary standpoint, removing the lobe probably would not be that morbid for the patient. But the deal-breakers over here for me is certainly the contralateral disease and supraclavicular disease, because that’s a disease distribution that is outside of the field, it’s outside of the incision that I would make. I can certainly take out the node, but I cannot control the disease and therefore I would not want to do a disservice to this patient even though this patient was technically operable. I am unable to achieve complete resection of all visible disease and therefore, I think this patient would be best served with my colleagues from radiation and medical oncology.

We have to look at all the collateral issues that could come not only before and after treatment. So I think that when we have everyone on the same page on a regular basis, looking at not only what are we going to do today, but what are we going to do two, three months from now, in this case, no appreciable disease as opposed to surgical care.

In summary, this patient has unresectable Stage IIIC NSCLC. Patients with unresectable Stage III NSCLC can be candidates for curative intent CRT followed by consolidation therapy. Radiation oncology should be involved early in determining the appropriate treatment plan.

Here is case #3, a patient with unresectable EGFR-mutated Stage IIIC T4N3 NSCLC.

So, we are here with our final case for this program. So, we have Henry, who’s a 68-year-old retired police officer and who presents with cough and shortness of breath. And he is a former tobacco smoker, but quit long back, and he basically presents to his primary care.

So, we do know that he has lung cancer because he has a PET/ CT—there you can see a hypermetabolic mass with mediastinal adenopathy—has an EBUS and the biopsy was positive for lung adenocarcinoma. No intracranial metastases is what we have. And he is highly motivated in getting a curative intent treatment.

So, knowing this particular case, Stephen, what would you recommend as his frontline treatment?

So, again, I think in alignment with what we were discussing earlier, the importance of doing reflex biomarker testing. I would want to have that information before proceeding with treatment. So I’d want a surgical opinion. I’d want invasive staging to determine the lymph nodes that were positive. And I would also want just baseline information, MRI of the brain, full staging workup before proceeding.

So, to you, Bobby, at what point would you consider biomarker testing for Henry?

So, looking at this case, I would recommend biomarker testing immediately upon diagnosis and getting tissue.

As a medical oncologist, the first thing I’m looking is whether they have the biomarker testing done. So Stephen, when you are seeing a patient like this, when do you typically see the biomarker results becoming available to you?

If there’s some kind of a delay, something that is unresectable, determined to be unresectable, whether or not there is a biomarker like EGFR or PD-L1 or ALK, the initial standard is still concurrent chemoradiation.

In your institution, who orders the testing?

So, medical oncologists have been kind of in charge of that, but we are really right now trying to educate everyone, so surgical teams as well as pulmonologists. And again, we really try to involve navigators to help to make sure that this is done. I honestly think that it should be done reflexively by pathologists. I think that is the most efficient way of doing this.

In summary, this patient has unresectable Stage III EGFRm NSCLC. All eligible patients should receive biomarker testing around the time of diagnosis. CRT is part of standard-of-care treatment in unresectable NSCLC.

So, this brings us to the end of our discussion on patient cases with unresectable Stage III non-small cell lung cancer. I believe they’ve helped highlight the importance of MDT communication and collaboration, as well as the increasing importance of biomarker testing for ensuring optimal clinical and treatment decisions in this setting.

Managing CRT-induced Adverse Events in Unresectable Stage III NSCLC.

The views and opinions expressed in this video are those of the individual oncology specialists and do not represent the views or opinions of AstraZeneca. This video contains anecdotal information gathered from a discussion with oncology specialists based on their opinions/experiences. Recommendations are general and may vary with patients. At the time of this filming, the Healthcare Professionals featured were in the roles and at the institutions indicated.

Today, we will discuss how to manage toxicities as a multidisciplinary team, with a focus on the importance of early and frequent communication across the team, as well as the roles and responsibilities of everyone involved. We will also cover how proactive management of adverse events could help avoid treatment breaks.

Hello, I’m Janakiraman Subramanian. I’m a medical oncologist. Welcome to our video series on the changing landscape of unresectable Stage III non-small cell lung cancer. In this video, we’ll be talking about optimizing the use of concurrent chemo RT in unresectable Stage III non-small cell lung cancer. To help with that discussion, I’m joined by 2 thoracic oncology experts.

I’m Stephen Chun, I’m a radiation oncologist.

Hi, I’m Megan Roy. I’m an oncology nurse navigator.

Managing toxicities as a multidisciplinary team: The importance of early and frequent communication

Stephen, in your opinion, how important is the collaboration within the multidisciplinary team so that we are managing these patients effectively, so that they complete the course of chemotherapy and radiation?

Collaboration with the full multidisciplinary team is of, in my opinion, utmost importance. The multidisciplinary team can be involved at times with input from the interventional pulmonologists, the nurse navigator with day-to-day management of patients as they undergo treatment. For me, it’s mostly a partnership with the medical oncologists and myself, to coordinate care during chemoradiation about what they’re going through regarding adverse events.

With chemoradiation, we want to make sure they get through the full treatment course without treatment breaks, and that requires frequent communication about how the patient’s doing. Because the patient comes in more frequently for radiation than for, let’s say, weekly chemotherapy, we oftentimes can observe changes that might be happening more quickly than the medical oncologists. If there’s an adverse event like esophagitis, or fatigue, or whatever adverse effect there is, we’re the first line of defense, but we immediately let medical oncology know. So they’re also on the lookout as to whether they need to do more workup in relation to side effects of chemotherapy.

So, Megan, how do you see yourself in making sure that the collaborative environment continues to work so that the patient is managed appropriately throughout their course of chemotherapy and radiation treatment?

My role is to bridge those communication gaps between medical oncology, and radiation oncology, and the rest of the team that’s involved. I have reinforced the education of what adverse events they should look out for. So this way, they can report it as soon as they start feeling it. Because again, you know, if they say to me like, “Gosh, all of a sudden, I was short of breath walking out to my car,” it’s a red flag to let somebody know, to maybe they need some imaging, to make sure they don’t have pneumonitis or something.

And during tumor boards, again, these multidisciplinary tumor boards are so important, so we got to make sure we have all the relevant information, so the specialists can make their decisions. I’ll report any issues the patient’s having to get them through treatment. For example, if the plan’s for them to come to the city every day, but they live right near one of our satellites, I might mention like, “Hey, they don’t have to drive. Is there any reason why they can’t go out to facility?” and help with those logistics. And also, keeping that patient voice up and present. A patient does have the final say of what treatment they want, so making sure that they are part of that treatment-decision process.

How do you keep them motivated, so that they can continue through with their treatment?

I really do think that morale is such an important part of what we do, whether it’s morale on a boat or morale during chemoradiation. But I always like to frame this in the broader perspective, that today, with chemoradiation and consolidative therapy, this truly is curative treatment.

Our next topic is roles and responsibilities across the team.

So what do you think is the role for the multidisciplinary team in helping you manage these adverse events for these patients?

I had a recent case of a patient, it was in the middle of chemoradiation, people didn’t know what was going on, because worsening respiratory status. I was pretty clear that this is probably not from radiation, because pneumonitis doesn’t happen during radiation. This patient also, because I talked with the pulmonologists, they thought that their COPD wasn’t bad enough to be causing their hypoxia, that they would be really surprised, looking at the pulmonary function tests, if the COPD was doing this. And sure enough, viral panel, it was influenza. So, the multidisciplinary team should always be looked to, especially when things might not be going as planned.

Agreed. You know, I’ve personally found it helpful, just like you said, to talk to my partners in the multidisciplinary team. Sometimes, it may be looking at an imaging study with my thoracic radiologist to help me understand what’s going on. Like you said, is it pneumonitis, or is it something else that’s happening for these patients? Could be an infection. And as you said, the timing of pneumonitis, knowing that is key, because radiation pneumonitis takes at least several weeks after radiation to develop.

The final topic is helping patients avoid treatment breaks through proactive management of AEs.

Stephen, how do you try to avoid interruptions to radiation treatments or dose reductions? The delays or dose reductions could be significantly detrimental for their ultimate outcomes, isn’t it?

Oh, that’s absolutely correct. And we know from many decades of research at this point that interruptions or dose reductions lead to less of an ability to control not just lung cancers, but all sorts of lung cancers. I break it down to patients: “We’re trying to kill this cancer, and we keep kicking it, and you want to keep kicking it while it’s down. If you have a break in radiation and allow that cancer to stand back up, you are risking not being able to kill that cancer.”

That, in a nutshell, that’s how I conceptualize it, you know, “Kick it while it’s down, and don’t let it get back up.” And this is also why I think involving social work is incredibly important. While we certainly have a lot of medical issues, medical logistics to address, there are also incredible social logistic issues. We can address all of the medical logistic issues as much as we want, but if the patient doesn’t have a car or transportation, it almost becomes a moot point.

Managing proactively is critical to maintaining that morale that we spoke about earlier. Having the patients have a good outlook, and that helps avoid breaks in radiation, which we know is detrimental to local control and survival. I actually tend to call in the supportive care team early in treatment, especially for a patient who’s running into trouble.

Megan, how do you kind of help to manage these adverse events for these patients?

I don’t manage these toxicities directly, but I help bridge the gap to the teams that need to be managing them. So, if a radiation nurse notices that this patient’s looking dehydrated and especially fatigued, I might reach out to the medical oncology team and say, “Hey, do you think IV fluids might benefit this patient?” and help connect the dots both ways.

So, what tips do you have for the different adverse effects that the patients are dealing with when they’re going through chemotherapy and radiation treatments?

We encourage the patients to stay hydrated by drinking their 8 glasses of water a day. We’re going to be monitoring their blood pressure and checking their labs, checking their skin turgor, to make sure that they’re not dehydrated and they don’t need IV fluids. For weight loss, the labs are also going to be checking their albumin. We’re going to be weighing them, to make sure that their weight’s staying stable. And again, the nutritionist is a crucial part of the team, and they can recommend some nutritional supplements, liquid if needed, and help them set their calorie goals and protein goals for their intake and decide whether it’s time to start thinking about a PEG tube.

The most common side effect that we see during radiation that gives us the most problems is the esophagitis. It causes pain, and because of that pain, patients don’t eat, it causes weight loss. So I usually start patients on an antacid, because if there is any acid reflux component of their esophagitis, we want to neutralize that stomach acid.

Other medications that I prescribe in addition to pain medicines, I always send in a prescription for a stool softener, because I know invariably that narcotics are going to cause constipation.

The whole idea, like you said, is to be proactive and have a combined multidisciplinary approach, so that we can prevent and control these adverse events as much as possible, so they don’t become too severe as soon as treatment’s either completed or stops treatment in the middle. We don’t want that, either. So we want our patients to be as healthy as possible after treatment, so that they can recover. And also, because treatment’s not over yet, there is consolidation part of the treatment—they should be in a good shape to go ahead and get those treatments.

Yeah, and I’ll typically talk to medical oncology after radiation is over to discuss when we should schedule the post-chemoradiation scan, to check for disease status, particularly checking if there’s progression, because that determines what the next steps of consolidative treatment are going to be. We’ll typically schedule the scan between 2 and 6 weeks after completing chemoradiation, although that can vary, depending on the medical oncologist and the situation of the patient.

And we need to keep in mind sometimes, when we do these scans early on, we may not necessarily see a great response to treatment. We may actually see some tumor changes that might suggest that there is progression. But we need to keep in mind that not every slight change in tumor size is progression of disease. Particularly, if you look at the RECIST criteria that maximal diameters of these tumors should be increased by more than 20%, really to say that it’s true progression, or they should have some new lesion that’s clearly cancer to call it progression.

In summary, manage adverse events along with the multidisciplinary team to help patients complete therapy. It’s important to keep patients motivated, and proactive management of adverse events may help patients avoid treatment breaks.

This concludes the videos in our series on the changing landscape of unresectable Stage III non-small cell lung cancer. Thanks for watching.