Case 4: Stage IV Adenocarcinoma Without Genetic Driver

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD:Let’s move on to the final case, case 4. This is a patient with stage IV adenocarcinoma without a genetic driver, which is probably the most common type of case that at least I see and you see. This is a 68-year-old Caucasian male who is presenting to the emergency department with severe chest pain and dyspnea. He has a history of hypertension and osteoarthritis. He’s a former smoker—20 pack-years. He has moderate alcohol use. He is still active and plays golf. His physical exam is noted for generalized weakness and pallor, and his breath sounds are reduced significantly in the left lung base.

He has a chest x-ray that shows a very large pleural effusion on the left and a left-sided mass. A CT [computed tomography scan] of the chest and abdomen reveals a 9-cm, very large spiculated mass in the left lower lobe, a pleural effusion in the left hemithorax, and right adrenal metastases.

The PET [positron emission tomography] scan basically confirmed what’s seen on the CT scan, as well as some disease in the lining of the pleura, and also some additional liver lesions. The MRI [magnetic resonance imaging scan] shows 2 solitary brain metastases—1 cm each with limited edema.

He has a thoracotomy and drains almost 2 L of blood. We can maybe talk about whether that was the optimal approach in this case. A biopsy of the lung mass shows a poorly differentiated adenocarcinoma of the lung. He has next-generation sequencing [NGS] testing done, and he’s negative forEGFR,ALK,BRAF,HER2,MET, andROS1. The PD-L1 [programmed death-ligand 1] expression is less than 5%.

So we’ve got a patient with stage IV symptomatic disease with a pleural effusion. This is a good opportunity to engage the surgeon and the pulmonologist on optimal ways to manage the pleural effusion. And then I’d also like to get the pathologist’s input as well.

Lonny, walk us through your management for pleural effusions. It’s a very common thing in these lung cancer patients. How you optimize that? What do you do?

Lonny Brett Yarmus, DO:Sure. I think the issue here is, as you suggest, diagnosis and palliation. The nice thing about pleural disease is those 2 things often go hand in hand. Achieving a minimally invasive approach is warranted, so I agree. The choice of thoracotomy—I’m not quite sure about that. But I think a thoracentesis, where you can potentially alleviate symptoms and provide ample tissue for a diagnosis, would be a great first step. And then we kind of take each patient step-by-step and see if they respond, from a symptomatic benefit, from having pleural drainage. If they do, what’s our next step? Are indwelling pleural catheters appropriate, or is pleurodesis an option? And so this kind of goes hand in hand with the initial interventions.

Benjamin P. Levy, MD:OK. I’m going to push you a little further. Fast-forward. You drain the fluid twice. What is your threshold to do a PleurX? Or should this patient see the surgeon and do a VATS [video-assisted thoracic surgery] pleurodesis?

Lonny Brett Yarmus, DO:It’s a little complicated, and it really is patient specific. The early factors include: does the patient derive symptomatic benefit from pleural drainage? If they don’t, there’s not really a great indication or reason behind more invasive procedures. Most do, and I think then it’s a question of, how quickly is the recurrence rate? Sometimes recurrent thoracenteses are not unreasonable.

From our standpoint, the care has really migrated toward indwelling pleural catheters or tunneled pleural catheters. They’re done in the outpatient setting. They’re minimally invasive. Patients get to go home on the same day, can control the amount of drainage, and really derive symptomatic benefit. And then well over 50% of patients achieve pleurodesis just from the catheters themselves. If theirs fail, then I think Mickey’s role is certainly an important one.

Benjamin P. Levy, MD:Mickey, your thoughts?

Michael J. Walker, MD:I agree wholeheartedly. There are only a few reasons for which I think I would perform VATS. I don’t know why they did a thoracotomy here, but certainly I think about a minimally invasive approach. If more tissue is needed, I think that’s another reason we’ll go in with the scope. But outside of that, we don’t typically decorticate malignant pleural effusions. With any surgery, I think you’re going to delay the start of what they really need, right? And that’s systemic treatment. So I think the PleurX, you can go and just blow right through. They can get chemotherapy throughout the PleurX insertion, as opposed to a VATS procedure, which may delay it. But certainly, if they need more tissue, I’d do VATS.

If they were a younger, very good performance status person, I probably would lean maybe to a VATS pleurodesis. But you have to remember that 25% to 30% of those patients may have trapped lung syndrome, so the pleurodesis isn’t going to work. You’re going to end up putting in a PleurX anyway. Most of the time, again, this is very patient specific, as Lonny said. But for a younger person with a great performance status who doesn’t want a long-term catheter, because they get infected—and I’m sure we’ve all seen that—that’s really a death sentence for a lot of our patients. Or more tissue.

Benjamin P. Levy, MD:Yeah, it’s like everything else in lung cancer. It’s an individualized treatment approach based on patient preference, performance status, and a lot of other factors. I don’t know if there’s any hard-and-fast rules here, but it’s good to get the input of both of you.

Sam, let’s talk about pleural fluid and how successful we are giving mutational analysis off pleural fluid. You know, I just had a case a couple of weeks ago. A patient who is similar to this case presented with a large pleural fusion. They were able to get off 2 L, or a liter and a half, spin it down, and get something that can be put in paraffin. I call my pathologist. “Do you have enough? Do we need more? The patient doesn’t want another biopsy. We’d like to get the information.” What’s the comfort with getting molecular testing off pleural fluid?

Samuel Caughron, MD:DNA is DNA. If you’ve got malignant cells there, it depends. Has the lab that’s going to do the testing validated against a cytology sample that’s been spun down and put into formalin?

We like cytology samples. Often, DNA is better preserved because of those cells. You do need to look at the ratio of your tumor cells to your nontumor cells. Often, there are some very reactive mesothelial cells, a lot of inflammatory cells in these specimens. So that needs to be looked at to make sure you don’t get a false negative by whatever methodology you’re going to use. But they can work great. We like them.

Benjamin P. Levy, MD:Yeah, I think they can. I think that the message is to try to aim for a biopsy—either a core needle or an FNA [fine needle aspiration]. But there are times—and we try not to use them for molecular testing because sometimes we just come up short with the information we need off them and some highly cellular fluid, as you mentioned, if it’s highly cellular and it’s got a lot of cancer in there. Then we can get the information we need. But I would say that the attempt should be made to get a core needle or an FNA. But as a 1-off, sometimes you can, as you said, get enough to make the diagnosis, do PD-L1, and do NGS.

Samuel Caughron, MD:Yeah. In fact, we had 1 of our firstALKcases that was positive with a pleural effusion, that was just packed with malignant cells. So in some cases, it’s actually the better sample. I think, again, it just requires that multidisciplinary discussion. What do we have? With pathology providing the input on what the options are with what we’ve got.

Transcript edited for clarity.