Case 1: Frontline Treatment of ALK+ NSCLC With Brain Metastases


Shared insight on a patient case of ALK+ non–small cell lung cancer with CNS metastasis and the role of brain MRIs in clinical practice.


Stephen Liu, MD: With that in mind and these unique characteristics of ALK fusion-positive non–small cell lung cancer, let’s talk about our case for our Virtual Tumor Board® today. Our patient is a 47-year-old African American woman who presents to her local urgent care clinic with a cough. A chronic cough for the past 4 months. She did have COVID-19 5 months ago, so she [attributed] it to that. Small amounts of blood were noted in the sputum. There’s no relevant past medical history. A former light social smoker, she drinks white wine on a regular basis, but has a good performance status. Really, it’s the cough.

She was referred for a chest x-ray. No infiltrate was noted, but there was a small mass in the right upper lobe. This prompted a CT scan, and the next day we saw multiple nodules, unfortunately, in both lungs. That right upper lobe lesion measured 2 cm, but we have nodules in both lungs. We have pathologically enlarged lymph nodes in the right hilum and upper mediastinum. A staging brain MRI showed 2 sub-centimeter intracranial lesions, so we do have, unfortunately, asymptomatic brain metastases, one in the frontal lobe, the other in the cerebellum. [There were] no speech, vision, cognitive, memory, or functional symptoms or impairment with these brain metastases. My first question going to our panel is, is this patient presentation typical for those you encounter with ALK-rearranged non–small cell lung cancer? Jillian, I’ll start with you.

Jillian E. Thompson, NP: I would say yes, this is a typical presentation that we see. You mentioned that brain metastasis is very common, and in this case, this patient has it at diagnosis.

Stephen Liu, MD: Ross, anything unique about this case, or is this pretty typical of what you might see in your clinic?

Ross Camidge, MD, PhD: I think it’s fairly typical. I think patients often have little or no smoking history, and so the specter of lung cancer isn’t at the forefront of their mind. This lady thought she had COVID-19. But unfortunately ALK is enriched in those who have never smoked, and in fact, for people under the age of 40, it’s the most common oncogene found.

Stephen Liu, MD: Jyoti, presenting with metastatic disease, is that common in this setting?

Jyoti Patel, MD: I think, unfortunately, it’s far too common. As Ross alluded to, many of these patients may have some generalized or low-grade symptoms, but because lung cancer is the last thing on their radars, often diagnosis is deferred. These aren’t patients who are appropriate for screening, for example. So generally, they come to attention when something else is happening, whether it’s bone pain, whether it’s more shortness of breath, but symptoms that correlate with more advanced disease.

Stephen Liu, MD: Hopefully, over the past few years, we’ve sent the message out that lung cancer can occur in anyone, regardless of smoking history, and needs to be on our differential diagnosis for any pulmonary complaints. We need to consider lung cancer as a possible explanation. When I think back to the cases we’ve had here at Georgetown [University], I find that ALK+ lung cancer often presents with a pretty high burden of disease in our own practice. I’m not sure if that’s something you’ve noted in your practices. Ross, what proportion do you think of your patients have brain metastases at the time of diagnosis?

Ross Camidge, MD, PhD: I think it’s about 30%. It’s slightly higher than average. These patients stay alive longer and the initial drugs we had didn’t get into the brain, and as you said, there may be an overall tropism to the brain, so then the lifetime incidence is about 50%.

Stephen Liu, MD: Jyoti, how important is it to do that MRI at screening even if patients don’t have symptoms?

Jyoti Patel, MD: I think it’s important for a number of reasons. One is selection of therapy, there are certainly many schools of thought about that, but I would say that we know, unfortunately, that brain metastasis is an adverse prognostic factor. Unfortunately, patients with brain metastasis are more likely to experience earlier progression than those who have lung-only confined disease, for example.

Stephen Liu, MD: Jillian, are you pursuing MRIs over the course of therapy? Is this an area you continue to watch?

Jillian E. Thompson, NP: It is. We at least are going to do it at baseline, and I think considering these patients and the likelihood of progression to the brain, it is something you want to consider doing more frequently to keep an eye on those areas of progression.

Stephen Liu, MD: And yet, I think right now, correct me if I’m wrong, Ross, I don’t think it’s in the NCCN [National Comprehensive Cancer Network] guidelines to do an annual MRI in the absence of brain metastases, correct?

Ross Camidge, MD, PhD: It’s not. That’s a great point. It’s there at screening in everybody, but I think the NCCN hasn’t cottoned on to the modern idea of what you have to do for these people who are staying alive for years.

Stephen Liu, MD: I think waiting until symptoms seems like you’re waiting way too late. The whole point is to identify that before then.

Ross Camidge, MD, PhD: I think if you have symptoms, you’ve already lost some neurons, so I totally agree with that.

Stephen Liu, MD: Jyoti, have you ever gotten some pushback on doing MRIs periodically for patients without brain metastases?

Jyoti Patel, MD: Fortunately, I have not. But I certainly could foresee a scenario unless we codify this in many ways. Again, the quality of life burden of symptomatic CNS [central nervous system] disease is significant. Many of our patients are on the younger end of the spectrum. Many of them are working, driving is important, and remaining independent as long as they can, so I think early detection is important in this patient population.

Stephen Liu, MD: I agree. I think it’s got to be an important part for anyone with an ALK fusion non–small cell lung cancer. We have to do these MRIs regularly because treating a subcentimeter asymptomatic brain metastasis is a lot easier, there are a lot more options, than waiting until someone were to develop symptoms.

So this patient, they’ve developed this lung cancer, and they had the MRI right at the time of diagnosis. In this case, she had enlarged lymph nodes and metastatic disease. In someone with localized disease, let’s say we find an incidental stage I lung cancer. Are you still doing an MRI in that setting, Ross?

Ross Camidge, MD, PhD: I am because I’ve been burned so many times. The surgeons [think] you don’t need to do it, but honestly, you can get isolated [metastasis] spread to the brain. So if you walk through the door, even with a stage I lung cancer, I’m going to push for an MRI, cost be darned.

Stephen Liu, MD: Yes, it’s not this typical pattern of, first in the lung, then the lymph nodes, then other organs, then brain. You don’t have that sequence. It can be a small primary [tumor] and then spread to the brain.

Ross Camidge, MD, PhD: There’s that, Steve, but also the fact that you’re assessing the lymph nodes based on radiographic imaging, which is not the same as pathological, where lymph nodes are involved.

Stephen Liu, MD: Exactly right, that’s an excellent point. Jyoti, is your practice the same?

Jyoti Patel, MD: It is, and this is one of the cancers I sort of characterize as a small dog [with a] big bite. Unfortunately, sometimes we’ll see a small tumor, as was detected on the patient you’re presenting, but will end up on evaluation having either bone metastasis or CNS disease. So an appropriate evaluation in my mind includes MRI.

Stephen Liu, MD: Ross, let me go back to something you said. A surgeon who would be resecting a stage I ALK+ [lung cancer], I assume you feel all of these patients should be treated, or at least seen by a medical oncologist, correct?

Ross Camidge, MD, PhD: Well, I’m sure we all have the experience of surgeons who, the patient presents to them, they do some basic body staging, and they [say], “I can fit you in this afternoon.” That happens, and then they get their MRI done a week after their operation showing brain metastases. So, in an ideal world, which it’s not, yes, you would have multidisciplinary input.

Stephen Liu, MD: Jillian, in this case, the patient had no neurologic symptoms. Am I right in assuming you would do the MRI regardless of symptoms?

Jillian E. Thompson, NP: Of course. Again, we talked about how it’s part of the baseline screening for the diagnosis to get that done without presenting with symptoms initially.

Stephen Liu, MD: Yes, we really want to catch these before symptoms occur.

Transcript edited for clarity.

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