David Carbone, MD, PhD: Dr Jabbour, how are you measuring pathologic complete response? Now, that’s often a question asked of a surgeon, but I find…after chemoradiation, there’s a lot of evolving changes in the lung. Is this recurrence? Is this a just evolving fibrotic change? Is this derma pneumonitis? How do you solve those questions?

Salma Jabbour, MD, FASTRO: From a radiation oncology standpoint, thinking about response and imaging and how to interpret that, it’s a very difficult scenario. I try to get repeated imaging because I think that tells a lot of the picture of what may be happening at different time points with the patient. For example, after completing a course of radiation, getting imaging at [approximately] 6 to 8 weeks—an early time point before you would expect a significant radiation change in the lung…. Then potentially at the next scan a few months later, expecting to see some radiation changes at that point again at 6 months, and potentially even up till the 12-month mark, seeing that evolution that matches the radiation field. After that, I would start to get worried if things seem out of the ordinary—they’re not matching the radiation field, things seem a little bit more significant in terms of consolidation in odd places. We especially have to worry about other reactions, particularly related to immunotherapy in the era of the PACIFIC trial, where we’re giving durvalumab in the adjuvant setting after chemoradiation. So, it’s complex. These cases we often bring to multidisciplinary board or we have discussions with the medical oncologist specifically about what our concerns are. We may get more immediate imaging if we have concerns, or more closer monitoring. We rely on the imaging a lot. We don’t have the benefit of pathology in those cases.

David Carbone, MD, PhD: Sometimes you do…biopsy, but one thing I’ve learned from my radiation colleagues is when you do these axial cuts, you see it’s a lot of uncertainty about what’s going on. But if you do a coronial or a sagittal reconstruction, sometimes you can see it matched precisely with the radiation field and then you have more confidence that it’s [because of] the radiation.

Patrick Forde, MBBCh: The other thing to keep in mind for patients who’ve had chemoradiation, I often tell them if [they’re] feeling well and we’re not sure what’s on the scan, it’ll tell us what’s happening [in 3 or 6 months’ time].

David Carbone, MD, PhD: You’ll find out eventually.

Patrick Forde, MBBCh: Cancer will either be there or not there. And if it’s not bothering you right now and it’s not bothering us, I would keep watching it.

David Carbone, MD, PhD: We’re going to talk more about it in the surgical setting, but, Dr Dietrich, what do you do [after neoadjuvant] based on the pathologic response? What do you recommend?

Martin Dietrich, MD, PhD: That’s probably the most important question in the neoadjuvant setting right now…. [For] some patients [who] did not have a pathological complete response, is there in an escalation strategy that may be that may be helpful? I think this goes back to the point about evaluating some imaging abnormalities, often circulating tumor DNA, persistence, or recurrence can be helpful in discerning parts. I don’t know that we really have a good answer. If I look at the now 5 regimens of [preoperative] and perioperative regimens that have been compared, I was very surprised that 3 cycles of neoadjuvant immunotherapy seemed to be as effective as basically a full year of immunotherapy. I think there’s still going to be an individualized response assessment that we need to incorporate into clinical practice, but the question is very difficult. What we do in practice is not evidence based. I think we have sometimes switched mechanisms, so if a patient had neoadjuvant pemetrexed-based approaches, we would switch to a taxane or a different mechanism of action to see [whether] we can enhance a depth of response and the cure rate. But those are extrapolations that we can’t really base on good data at this point.

There’s still a lot to be learned [about] what to do with the patients [who] have not fully responded to neoadjuvant chemoimmunotherapy. That’s a big question that is not answered. I’m not sure we have anywhere near a definitive answer for that problem. The hope is—and I think this is very clear as a standalone data piece—that neoadjuvant immunotherapy has a different impact than adjuvant immunotherapy. When I don’t have head-to-head data but if I compare the data pieces in itself, I think the data in the neoadjuvant space is very convincing [and] the adjuvant setting was kind of lukewarm for me. I think those are 2 approved regimens—one within a study that I don’t understand, I know I haven’t really been able to interpret those—but I do think we’ve moved into the neoadjuvant setting of immunotherapy, or what to do with patients [who] don’t have a complete response. This is very difficult to evaluate because we need pathology; patients often have discordance between pathological and radiographic responses, they may have [computed tomography] persistence of disease, but may have full pathological responses. [These are] very challenging and escalatory strategies, [and] different immune angles [are] probably needed. I’m not sure that more of the same is really going to do any better.

David Carbone, MD, PhD: Well, it’s really true that in oncology especially, you can’t tell your patient [to] just wait 5 years [for] phase 3 trial results. You have a patient who comes to you and you have to decide—maybe not today, but within a week or 2—what the treatment regimen will be. Sometimes you will never have that phase 3 trial to answer the questions you’re talking about. Then you have to make these decisions based on the best cross-trial comparisons. Dr Forde, you are famous in this space. Do you have an initial comment? We’re going to talk about it more.

Patrick Forde, MBBCh: Specifically on the pathological complete response, the important thing is that it is assessed and that we work with our pathologists and they’re aware of why we’re doing this and why it’s important to do it. Because apart from our [multidisciplinary team], we’re somewhat siloed. We’re in different departments. We’re not necessarily talking all the time, and they may or may not be aware of the data on neoadjuvant therapy and what the difference is now compared [with], say, 5 years ago. I think that’s key. There [are] some emerging data, perhaps that percent pathological response might be important as well. I think it’s exploratory at the moment, but that could be something in 3 or 4 years where we want to know, was this a 20% response? Was it an 80% response?

David Carbone, MD, PhD: Know what the percentage of tumor was before treatment.

Patrick Forde, MBBCh: Exactly. Pathological complete response should be straightforward, because it’s either tumor or no tumor.

David Carbone, MD, PhD: There’s often a resected lung cancer with no neoadjuvant that will be 30% to 40% viable tumor. It’s a difficult question, for sure.

Transcript is AI-generated and edited for clarity and readability.