Join Mayo Clinic Comprehensive Cancer Center experts for an insightful webinar on the latest advancements in lung cancer treatment, featuring cutting-edge research and innovative approaches. Discover how a multidisciplinary team successfully treats patients with the help of groundbreaking AI-driven approaches.
Research and innovation
Case Study 1- Stage 3 lung cancer highlighting the multidisciplinary approach?
Case Study 2- Early-stage lung cancer showcasing AI with Canary and the single-stage approach
Hello and uh good morning and welcome to today's session. I'm Eric Dell. I'm a practicing pulmonary physician at Mayo Clinic, Rochester. And we're honored to be here today to discuss our multidisciplinary approach to lung cancer management. So I would like to welcome Doctor Don Owen, who is one of our radiation oncology staff here at Mayo Clinic, Rochester. Doctor Jenny Reisenauer is a member of our thoracic surgery department and also a co appointment to the Division of Pulmonary doing interventional pulmonary work. And Doctor Mohammed uh Shanshal from our medical oncology department. Uh all of us uh have the privilege of carrying for lung cancer patients at Mayo Clinic, Rochester. And we approach as many of our patients as possible with a multidisciplinary uh methodology. We're very fortunate here to actually have one of the most active multidisciplinary tumor board programs probably in the country. By that. I mean, we meet every day at one o'clock for 30 minutes and we will discuss anywhere from 2 to 10 patients. In addition to that once uh every two weeks, we meet with re with our pathologist and our physicians outside the Mayo Clinic and our Mayo Clinic Health system uh to present cases as well today, what we'd like to do is first have each one of our panelists share with you their research at a high level and the management of lung cancer patients. And then we'll, we'll discuss a couple of cases that illustrate the uh complexity but the benefit of the multidisciplinary tumor board in managing those patients. So I'd like to start with Doctor Shasha. Could you please Doctor Shasha? Give the audience a brief overview of some of the exciting research that your team is involved in. Thank you, Doctor Adel. I'm Mohammed shall medical oncologist that specializes with lung cancer and uh cancer drug development. And my primary focus uh is uh developing uh new drugs and also uh sharing the multidisciplinary management of lung cancer. A lot of exciting development in the field of uh lung cancer management. Uh We have seen a lot of uh of the approval over last year. We also have uh um uh a robust clinical trial and uh uh research uh Port Fo in in the thoracic uh in the lung cancer field. From the phase one to the all the way to the phase three, including the innovation and inclusion also uh of biosci and uh C key therapy um for those patients um with the uh different stages of diseases. And uh one of the exciting field also as well is the incorporation of the uh targeted uh therapy and incorporation of the cellular therapy uh team uh as part of the Mayo clinic uh platform. So we, here we have a cellular therapy. We have a dedicated unit um to uh manage and give all of these uh new treatments, including the car T therapy and bici therapy. Doctor Shanel. Just a quick question. How would an uh a um physician get information regarding the uh clinical trials or ongoing a male clinic that they may have a patient to enroll in? Sure. Um So we had created uh uh multiple resources for that either uh by checking the website which uh it has a list of all clinical trials from the early phase, all the way to the uh three stage three phases as well. And there are also uh if that's uh you know, if they want needed some guidance there, we do have also a navigator that can help uh with the contact information and then online format that they can submit to refer the patient to us. Excellent. Excellent Doctor Owen. Could you share with our attendees the exciting work that you and your colleagues are doing. So, my research focuses exclusively on a lot of thoracic malignant, especially non small cell lung cancer. Um We certainly have a lot of programs looking at how to mitigate the risk of pneumonitis from radiation. We have an active proton uh practice as well as um we're looking at potentially uh opening a trial, looking at different doses of steroids for pneumonitis. We have a unique program featuring spatially fractionated radiation, both stage three and four, unreceptable lung cancer, which may boost the immune system and its interaction with immunotherapy, which is a standard of care therapy across uh several stages of lung cancer. And we have a uh very uh active practice uh looking at outcomes of different approaches. And we've recently looked at um uh in collaboration with Doctor Shaw Shaw uh induction systemic therapy followed by chemo radiation, which is has no uh prospective data right now. And potentially there could be a prospective trial in this uh space. So certainly a lot of technologically driven, as well as outcomes driven uh radiation oncology trials. Uh very, very multidisciplinary across several um disciplines. Doctor Owen. Uh I it's, it's, that's very nice that you're sharing what the collaboration within the organization is. Are you also collaborating with other institutions outside of Mayo Clinic? And some of these trials, we do, we have collaborations with MD Anderson. Uh We have also do uh done some other analyses with uh the Moffett uh looking at rare types of uh thoracic malignancies. Uh We also participate in large uh rare disease sites such as it make for Thymomas and also mesothelioma. So we have a very, very active cross collaborative within um the specialties at Mayo but also with multiple other institutions that have subspecialties in thoracic uh radiation oncology. Well, the uh the, the, the weak link of the four of us is my research work, but I've had the privilege of over the last 25 years being the principal investigator of a Thoracic Specimen registry. And what we started is collecting the uh surgical tissue from lung cancers and match blood. And we've been collecting this for, as I said, 2525 years, we have over 25,000 specimens now, a couple of 1000 patients. And it's really exciting to see how this idea and this tissue registry has led to a lot of the collaborative work uh that you hear about. And I'd like to just kind of now pivot to Doctor Eisenhower Eisenhower on how she has utilized some of the tissue registry resource in in uh the work that she's doing here at Mayo Clinic. Thanks doctor El, good morning and thank you for the opportunity this morning to discuss multidisciplinary lung cancer care. As you mentioned, the Thoracic Specimen Registry has really allowed us to leverage um exciting and innovative research in the field of early risk detection, interception and minimally invasive approaches to treatment. So my specific area of interest in research is in robotic bronchoscopy, which we'll discuss a little bit later on in the program but obtaining very small lung cancer specimens in patients and utilizing that to not only identify cancer early but identify potential new opportunities to treat those patients as well. Thanks again. Excellent. Well, I hope you all can see how exciting. It is for someone like myself to work here. And how we keep these people working at Mayo Clinic is because of the the resources, the patients that we get to see. Uh but the camaraderie and the multidisciplinary approach that, that we have, I think everybody that's here, why attending this webinar realized that lung cancer continues to be the leading cause of cancer death in both men and women worldwide and how we've made great advances. But we need to do more. What we'd like to do now is pivot to a multidisciplinary discussion of two very frequent clinical scenarios that come to our tumor board and share with you how we work through these issues and then encourage you uh to ask for any questions or as uh uh after or during our presentation. So the first case that we wanna present is a 64 year old gentleman that was a previous smoker that presents with cough, very, a very active. You can see he's got fairly uh good pulmonary function test and AC T scan was done and a pet scan was done that shows a clinical stage three, a lung cancer. The reason it's clinical stage three A is there is uptake in the N one higher node and there's a little uptake in that four RN two lymph node. What I'd like to do now is ask our panel a few questions for management and therapeutic options. So I'd like to first ask Doctor Eisenhower, what's the standard approach and the tools available to us to adequately diagnose stage and ensure that we get the material needed to optimize the the therapeutic options for this patient. Thanks, Doctor El. Um As you stated, this patient based on imaging does fit into what we would consider probably a stage three, a adenocarcinoma. We would obviously need to prove that patho pathologically and stage three is a bit of a mixed bag in terms of treatment options as you'll see. So step one is understanding as much as we can about the biology of the tumor, the diagnosis component as well as the staging component as well. If you're diagnosing just the nodule in and of itself, there are multiple options. There's a conventional transthoracic ct guided biopsy or there's robotic bronchoscopy, which I mentioned earlier. The robotic bronchoscopy is done in a Bronchoscopy suite. The patient is brought to the Bronchoscopy Suite and put under anesthesia under utilizing a special bronchoscope. We're then able to drive out to the nodule and collect samples from the nodule. If uh there's suspicion of, of uh nodal disease, we may start by staging the mediastinum first. Um or we might do a combination of biopsying the primary lesion and sampling the lymph nodes depending upon the clinical indication regardless with robotic bronchoscopy. We now have shown through the literature in our retrospective reviews that we can obtain enough material sufficient enough to search for uh specific molecular markers that might be amenable to various therapeutics. And not only are we now able to look for those specific markers, we're also exploring research where we're getting the full RN A and DNA profile of all of these tumors, which might lead to more therapies down the road in the future. So the approach of endoscopic sampling of either the primary tumor or the nodes and, and in this case, we would want to assess all nodes that were greater than five millimeters. We're able to get an adequate specimen for molecular testing. What do you do at the time of sampling to ensure that you have enough specimen to fulfill the uh adequacy question for next gen sequencing. Yeah, that's a fantastic question. So we have a mechanism on site uh called rapid on site cytology where we have our pathology team in the room staining and fixing and preliminarily interpreting the slides for us as we're performing the procedure. So they can look at the slides and based on the cellularity of the slide, tell us you're gonna have enough material here for PDL one and and the other molecular marker analysis. We oftentimes take two or three additional samples just to make sure we do have sufficient amounts. But having that um rapid on site cytology has really helped us uh direct sufficiency of material at the time of biopsy, hopefully preventing unnecessary multiple procedures for the patient. Perfect. I'd like to now ask doctor scandal. Um, we've talked about this molecular testing, the next gen sequencing PDL one, that's new in my career. Uh, uh, in fact, we didn't care if it was squamous cell or adenocarcinoma in the, in the past. Why is it so important now for us to have this kind of information as we're looking to treat these patients? Thank you. Excellent question there. Um, uh, one thing is, uh to assess the resectable future resect of disease. That thing is also this molecular marker can help to define what would be the optimal upfront neoadjuvant but uh an aju event therapy. And uh uh the reason behind that is that it's very important to know. For example, that if there is an EGFR mutation uh to define if this patient will benefit from an adjuvant therapy, utilizing a drug like osimertinib. On the other hand, if there is no target mutation, um uh then um one of the options and one of the good option is to consider uh a neoadjuvant approach utilizing chemo immunotherapy. There have been multiple trials that have been launched. Uh For example, the Checkmate 816, which we have a, a four year survival update uh for your uh uh data update there, the pathologic complete response by incorporating immunotherapy increase uh um to uh around 24%. Uh I think what is also important in this case is that the four year update showed a median event free survival really had increased tremendously from many 18 months to 43 months awaiting a final overall survival uh benefit there. So there have been uh an FDA approval for immunotherapy in the Ron setting. There is also an FDA approval for a targeted therapy. I mentioned the EGFR in this case and the uh adjuvant setting and uh the for the elk mutation, we have, the lectin have been uh um uh approved there. One additional advantage here we have at Mayo is that we have uh created a good clinical um trial that um uh capture all of these rare mutation uh target mutation. Uh For example, we have a trial that uh include the use of targeted therapy for different type of mutation in the Aron setting for those patients, including for example, the ros one red mutation B A mutation, we know from the previous experiences, the metastatic setting that they tend to respond better to target therapy rather than the chemo immunotherapy here. So I think having a, an idea about the biology of disease is very important in this case. The other thing that we consider when we uh do the multi d um evaluate multidisciplinary evaluation there, uh we still look into the tumor of histology. So the regular adenocarcinoma squamous cell carcinoma, we have a very good data from all the uh keynote study check may, but we also see often see rare cancers like sarcomatoid or mucinous. And um we put that into our decision making. If that patient, that specific patient would be a candidate for upfront therapy um system of therapy versus we would rather treat with a definitive approach in this case. Excellent. So as I said earlier, this patient has very good performance status. Pulmonary function tests are good. Uh Doctor Eisenhower based upon that, do you see any reason why we wouldn't think even though it's stage three A? And I know a lot of our clinicians are thinking that's a later stage cancer than what we're used to for surgery. But is there anything here that would say this patient would not be a potential surgical patient? Yeah, that's a, that's a good question. Definitely. We would assess candidacy based on comorbidities, which it sounds like this patient has relatively none and pulmonary function testing which sounds like a relatively sufficient uh to be tolerant of a lobectomy. Many of the clinical trials that Doctor Chanchal have alluded to does appear to show a benefit for patients that undergo surgery as part of a multidisciplinary approach for patients with stage three disease. If we feel we can confine surgery to more or less a lobectomy and not a a an extensive operation. And we feel like we can get good control of the disease with either neo neoadjuvant or adjuvant therapy. So this is a perfect example of a case that we would bring to multidisciplinary tumor board, make sure everybody is aligned on the team and on the plan and um, and offer surgery if the patient is open and willing to do it. Um, and eyeballs to be a sufficient candidate and surgically would be tolerant of a lobectomy, both from a patient factor standpoint and a tumor factor standpoint. So doctor on, uh, I've heard what doctor Shasha talks about with, with some of the checkmate 816 and the aura trial. And we get these, the nextgen sequencing and, and there's lots of drugs out there that I thank goodness you guys keep track of if this, this patient comes right now. He, he we're talking about him here at the tumor board. The material is out there waiting. Uh Ho what can you tell us about the difference in your mind when the evidence based upon the studies that are out there, the advantage of either chemo ads and then surgery versus neoadjuvant chemo immuno and then surgery and would protons ever be put right into the discussion of that situation? This is a great question. There are no randomized trials comparing these new period operative approaches to chemo radiation. However, about 10% of patients on the trials and actually, when you look at some of the new retrospective data, looking at implementation of this approach, can't, don't make it to surgery, either there's some progression or the patients are debilitated after some new adjuvant therapy and they come our way for a potentially receptible candidate and certainly more radiation is the Saturn unreceptable lung cancer. And so it's very difficult to compare the uh directly compared to outcomes. But if you look at the overall survival in the Perative trials, as well as those compared to Pacific, they're fairly comparable. And I think that uh either approach is good. I think the way that I view it is surgery and radiation are our chemo radiation are both local control uh treatments. We are going, uh the surgeon is going in and, and resecting um the cancer and there still needs to be some systemic therapy on board to prevent this metastasis. And the same is true with chemo radiation. Certainly, the standard of care is to have a consolidated immunotherapy. So our treatments for the local control portion also need to make sure that the patient will be well enough to receive any sort of adjuvant therapy or neoadjuvant therapy. Uh because both though it's a combination of multidisciplinary uh uh approach that really results in that survival benefit or good long term survival for these stage, three lung cancer patients in terms of proton therapy, you know, I I think that the way I view when to use protons and certainly not all cases require it. Uh it would be patients with, it's usually more an unreceptable setting where patients have much larger tumors where we have difficulty meeting our standard lung and heart constraints. But also in patients who have a lot of ability where we're concerned that excess doses of the heart or the lungs could be very, very morbid and we can certainly minimize the risk of that with proton radiation. And it, and then the other thing is pneumonitis. Um, that's something that can happen in up to a quarter or a third of patients of chemo radiation. We know that the adjuvant therapies, whether they have an EGFR mutation, using osimertinib or whether they, they received their Valium A as their consultative therapy increases the risk of this pneumonitis and using protons uh in select settings where we can minimize that risk. We en enhance the success of these patients going on to those systemic therapies which have the survival benefit. Excellent review. Excellent. And I really like the, the nuance. I think it's important in the art of medicine and the, and the power of the multidisciplinary tumor board. The knowledge that Doctor Owen brought to remind us that there are no clinical trials comparing chemo rats to neoadjuvant chemo immuno that we're starting to do that. It just shows uh it just shows the breadth of information we still have to, to uh to obtain in the future. Now, so here we are, we've got this uh patient uh the test that the sample has been collected. It is an adenocarcinoma. Yeah. PDL one is 12% and Doctor Chanal, we're sending it off for next gen sequencing. Uh Now, I don't care what panel people are doing. A lot of people have panels within their organization, some send them out to other places in the country. But frankly, it's gonna take maybe 2 to 3 weeks for this patient to know um whether they're going to have a target uh mutation or not. What do we do as clinicians when we're working together in the multidisciplinary tumor board or counseling the patients? What do we do is it, is it better to wait and get that uh the results of that next gen sequencing? Should we start chemotherapy? Now, how do we manage that in that, in that setting? And I know that's a you, I I may have thrown you a curveball. I don't know if I told you I was gonna ask you this, you muted. Uh Well, uh thank you very much. Uh That's a common scenario and uh o oftentimes create a lot of anxiety for the patients. Uh I think uh depending on the case here. So patients, for example, this uh uh gentleman um um if I see a patient non-smoker, young and healthy, um I, I, you know, there is up to 50% chance uh a non-smoking patient that we might find a target of mutation that could potentially change the course uh of treatment uh through either an upfront uh uh uh standard of care versus uh targeting it through a clinical trial approach. There. One advantage about seeing a patient here also that we do have a very rapid turnover of these testing uh through the male panel that we have available um including testing for those uh uh rapid egfr testing and LKM MU testing. And uh if I feel like uh that usually we, we should get, we get an answer within a week. Um Sometimes we also incorporate the uh CT DNA uh that has a, a good correlate uh with the treatment, I think in this case. And this is specific case in a pa if a patient is, if never a smoker, um it will be important to know at least what's the EGFR here. Uh Before we make our final decision, since we have uh uh good trials there that we think the patient might uh benefit from. Excellent that I'm glad you brought up the, the point of the rapid uh testing because that is something potentially that referring physicians could take advantage of here at Mayo Clinic. Secondly, and thank you for mentioning the um uh uh the serum testing for next gen sequencing the liquid biopsy. We sometimes refer it to because I think we're seeing advances in that and we're doing a lot of work here at Mayo Clinic uh in, in evaluating that as well. Well, uh I do believe in shared decision making and true informed consent. So this patient was uh uh dis was counseled after the Multidisciplinary Tumor Board discussion that he has a low likelihood of a target mutation that it will take anywhere from a week to two weeks. Uh Even with sometimes the rapid, he was very comfortable waiting for the next gen sequencing uh and he had no target mutation. So he went on, he had chemo immunotherapy as uh ad neoadjuvant treatment. He went on and had resection and had a complete pathologic response. And he's now being monitored in our uh post procedure uh lung cancer group uh for uh recurrence. I'd like to ask the final question to Doctor Eisenhower. Uh We now have a patient who's uh ned at least at the complete pathologic response at, at surgery. Uh What is the monitoring for this patient as we go forward? That's a great question. So typically, we see those patients back at about a month after surgery, usually just with a conventional chest X ray to make sure that healing has gone appropriately. Um And they, they don't have any side effects from the surgery. I will just add that in 2024 committing a patient. There's some myth myths out there about rendering a patient for chemotherapy upfront doesn't allow them to be a candidate for a minimally invasive surgery thereafter. That's not true. We oftentimes offer a minimally invasive surgery upfront for these patients regardless of what their neoadjuvant or adjuvant status might be. Um And, and, and most of us attempt at least a minimally invasive operation re regardless of what sort of neo Ament treatment the patient has had upfront. So, um in that setting, we anticipate a fairly quick recovery after surgery. We typically see them back at about a month, 4 to 6 weeks afterwards. Um to ensure that healing is gone appropriately and there's no post-operative concerns, we typically then see them back in conjunction with medical oncology because at that time, the pathology report is finalized and we can get a sense of, did we really see sterilization of the medias dynam? Meaning was there residual disease in the lymph nodes or not? What was the control of the primary tumor? Did we see any shrinkage? And that's the other benefit if sometimes neoadjuvant treatment upfront is that you can compare what you have pathologically from the diagnosis and staging upfront to what you're seeing on the surgical specimen after treatment. And it gives you some sense of how this tumor behaves biologically in response to systemic therapy. So we typically see these patients back in conjunction with medical oncology and then based upon review of the final pathology or make a decision in terms of whether adjuvant treatment is then potentially warranted in the uh by means of immunotherapy versus just ongoing observation. And typically for a patient like this, you're you're looking at a surveillance imaging probably on the order of every 3 to 4 months. Excellent. Now, so you led into the next question for both Doctor Shasha and Doctor Owen, is there uh a uh standard of care that would place the uh tell this pa tell us what this patient needs uh going into the future. In other words, do we keep going with the his immunotherapy? Is there, is there a need for any radiation adjuvant in this setting? Doctor Shasha? Could you go first? Yeah, very, very good question. Again. Uh This is uh uh always a debate and I think the data comes from the uh um uh 77 T trial where they looked actually and the patients specifically who achieved the uh complete pathologic response and the checkmate 77 T. And uh the, the benefit that we see so far now is that there is an event free survival benefit even for patients with complete pathologic response. This is an area of a very active investigation. Do we really need to continue based on that uh on the adjuvant therapy versus, you know, there is a, a research going on now about utilizing CT DNA and uh beside the treatment of those patients um would require uh um uh further aju therapy or not. Uh what I would say so far. II I make a um AAA discussion of the data with the patient present the risk and the benefit here that we do have a event free survival benefit. But really the main thing is here. Uh Also we wanna see a long term survival benefits for those patients. Uh One thing we could uh we put also in our consideration is the financial toxicity and the risk of toxicity from the A therapy. So that that part will be more of a shared decision making with the patients. Uh When it comes to the uh uh patient, obviously, you know, not all patient achieve a pathology, complete response. This was reported in around 24% of the patients. Uh So it's a good, a good uh a good discussion, you know. Um or, or a good question here is is to answer is uh uh do we continue or not? What about the role of adjuvant radiation in this setting? Um The short answer is no, there have been two recent randomized trials, Lung Art and Port C and these were pre immunotherapy error trials. Um And so pre perioperative approach and there was detriment in the lung heart trial. And I think that trial did terrible radiation. But that's an aside and then the Port C trial uh where there was no survival benefit uh but also no detriment. And I think that uh that's for R zero resection. Um for anyone who has microscopically positive margins or R two or gross residual disease, there is definitely a role for adjuvant radiation and possible even adjuvant chemo radiation for R two resection, there's a lot of surgical literature that shows significant increased risk of local regional relapse as well as distant relapse, there's residual disease. So I do think that if there's any concern about that, then uh they should see a radiation oncologist, the great controversy is in multis station N two disease. We just don't know, we certainly know patients with a lot of N two nodes kind of surprise or there is certainly trying to define the um the parameters of re respectability that multi station and two knows even by as o certainly, in a multidisciplinary discussion was hotly debated that these patients might still be considered surgical candidates after new adjuvant uh chemo immunotherapy, those patients remain at risk of regional relapse. And uh there are some subgroup analysis of potentially some benefit, but again, they're in a preoperative uh period. So I think that if there's any question, call up your uh you know, we're happy to see them or to talk about it. I do think there's, there's definitely a role for protons and adjuvant radiation. The toxicity that came from adjuvant radiation was from ra conformal. So very old school radiation or IM RT uh in some cases also could cause toxicity and protons, we can treat a very, very small strip where there's minimal dose of contralateral lung, the remaining lung and to the heart. And so that's a very important consideration if there's thought to offer poor or post operative radiation. Again, these types of cases require a lot of multidisciplinary discussion about the appropriateness of consideration of radiation. The other thing is we may be moving into an area using circulating tumor DNA after pert of therapy to define, do we need local therapy at this point, if they look like they've had a complete metabolic response, do we need radiation? Do we need surgery? Do we watch these patients? And so that may be coming in in the future that uh lung cancer will start to use circulating tumor DNA to decide on local therapies or additional adjuvant therapies after before or after any local therapy? Excellent summary. Excellent. I'm just looking at the chat box. I don't see any questions from our participants or audience. Uh I think we've used this case is a very good example of what I would say is one of the more frequent stages of lung cancer that the Multidisciplinary Tumor board struggles with and that's the stage three lung cancer. Uh So I hope that the audience is resonating with the challenges and the benefit of having this multidisciplinary uh discussion surrounding a patient such as this. So now let's let's flip to another what I am, what I would describe as a frequent occurrence at the Multidisciplinary Tumor Board and is probably occurring because of the biology change of lung cancer, but also because of our screening strategies nationally. And this is a case of a 65 year old, again, previous smoker that underwent AC T scan for screening because of the age and the tobacco history. And I'm showing you a s a couple of scans that illustrate the multicentric adenocarcinoma spectrum suspicious uh patient. So as we look at this, I'd like to, I'd like to start with Doctor Eisenhower. Uh Can you review for the audience, some of the tools that are available to help determine not only the pret test probability of malignancy, but even some of the newer tests that are saying the likelihood of this thing, we think it's a cancer that it could be a cancer at resection. Could you comment on those tools that we are using? Sure. Absolutely. Thanks for the question. So there's a couple of different ways to look at how we look at what we call an indeterminate pulmonary nodule or something that got incidentally diagnosed on AC T scan? And do we pursue it? Because just so the audience is aware, there are many times that things show up on AC T scan that look like a cancer that are not cancer. So how can you based on just imaging alone, make that distinction and make that differentiation at Mayo clinic? We have developed a Mayo clinic scoring calculator. It's the solitary pulmonary nodule malignancy risk score, which takes into fact, mul takes into account multiple factors such as the patient's age size of the nodule, smoking, history, prior history of cancer. Um and, and location of the tumor and morphology, meaning is it speculated solid and that gives you some sense of the probability of malignancy. We also then clinically look back if the patients had any prior CT scans to look and see if there's been evidence of growth or change. Now, at Mayo, we have developed a more sophisticated way of doing the ladder uh which we affectionately call Rami. We've been able to take a patient's historical imaging that's been conducted and actually scientifically measure patterns of growth or change based on various radio make variables that has actually been developed internally um labeled canary analysis. It's been published and validated through multiple internal and external populations um and give some sense of an aggressivity of a nodule. So particularly in a patient that has multiple nodules and the multidisciplinary team here is coming together just because there's a nodule on CT. We don't decide that we want to treat all of them all at the same time, some of them might make sense to wait because they're not as aggressive. Some may never progress to the point of of being something that we need to worry about. And that's where this ramic analysis, this ramic tool can give us a sense of what is the most serious or the most aggressive lesion here and based upon that severity score, so to speak, we can then decide does it make sense to treat it um with, with one therapeutic modality versus another? Excellent. So I I put on the screen and the first slide that we showed were, was illustrating a couple of nodules that I think there were 32 in the left upper lobe, one in the right upper lobe. And then the next slide that I'm showing. The audience show is the Canary analysis, which stands for computer aided nodule assessment and risk yield. And as Doctor Eisenhower stated over uh more thousands of the CT scans, they've uh evaluated nodule density and then looked at pa pathologic specimens to correlate whether or not the density of this has anywhere from good to worrisome for malignancy. And you'll see on this slide, the characterization of that predominant nodule in the left upper lobe. And the next slide shows that there were actually six nodules on this patient uh that were evaluated with the canary analysis. Now, i it's a, it's a bad presentation when you apologize for your slides, but I'll walk you through it. Those top three with all the colors l little illustrate by more dense complex and likely malignant at the time of reception. The bottom three show a much more benign profile for the density of the nodule and the radio mix that Doctor Eisenhower uh was talking about. So we have a patient multicentric adenocarcinoma, very concerned uh that the nodules and particularly in those top three have been labeled as likely malignant and they're interested now in what the multidisciplinary tumor board would say about management. So it comes to us and the first thing that I would ask is Doctor uh Owen and Doctor Shasha, what's the, what's the, how ma how badly do you need to know that this is cancer or not? Um Yes. Uh Thank you. I think one of the important thing that we uh uh is is this part of uh a unique multi center like solitary cancer arising there versus that part of uh uh metastatic disease that we're dealing with. Uh And I think one of the major thing is uh is to try to attempt uh to resect the, the one that was the highest yield. Um And this is an area where a pathologist, the expert of the pathologist and the next generation sequencing also help us to decide if this is a spectrum of disease where the separate primary uh uh cancers arising there versus uh a metastatic lesions there to help us to decide what will be the subsequent uh therapy there. Uh Multicentric uh lung adenocarcinoma is, is a spectrum of disease and um it can present with a different ways there, meaning either ool primary cancers in one side versus a metastatic lesions there. So those factors that as a medical oncologist, this is what I'm looking for uh to help make a decision about c the excellent doctor Owen. So I I think multi focal primary lung cancer, multicentric lung cancer is very challenging. First of all, I think you need to individualize care. What's the patient's performance status? What are the patient's expectations and what is the rate of growth or solidification of some of these ground glass nodules? Many times it is not an emergency. But anytime you bring up the concern that this is an adenocarcinoma spectrum or cancer patients are get it out. I need to deal with it right now. Meanwhile, they may have multiple comorbidities that are more likely to be their terminal event than this. So it's this is where our multidisciplinary uh tumor board and collaboration shines because the question is, let's say the patients really, really fit the patient is a great candidate for any treatment. And we talk about local treatment often first and reserve systemic therapy for if there's multifocal synchronous rapid progression. And as doctor Sean shall mentioned, looking for certain mutations and there are some patients who have EGFR mutations, for example, uh sometimes observation is the best thing to do if the lesion is growing very slowly, vision has a lot of other things going on. So the question that Doctor Dell always asks me is, do you need a biopsy? I do think a biopsy is important if possible. So the patient is very fit. I certainly hope and we'll throw the question to doctor rise an hour at some point that we can get a good surgical specimen for both NGS and then also just for pathologic confirmation. I think that's important for any future systemic therapy. And I think it's reassuring to say, well, I'm treating a cancer, but we do run into scenarios where patients are very frail. Um They maybe uh smokers for many years, they're on oxygen and we're asked to see them and we're concerned that if they have any sort of biopsy, they're very high risk with anesthesia. We do a navigational bronchoscopy or robot. They're very high risk of a pneumothorax where that could be uh nearly fatal or required IC U admission if they have a transthoracic biopsy. And in that case, this is where canary is very helpful because we have this validated rad path correlation showing that this might be a poor outcome or very aggressive looking lesion where we would be comfortable treating empirically with serial growth and potential FDG avidity when we're very, very concerned about a cancer. And sometimes I'll say, well, we're afraid to biopsy this patient. What, what does the radiologist think of you? If our whole panel is very concerned, this is a malignancy. I would be, I can treat it empirically with stereo tactic radiation. And we also have a discussion with the patient about the stereotactic radiation that we would offer because certainly there's a very risk of pneumonitis. But for a patient, for example, as an F PV 100 leader, we have to be very concerned if that happens. So again, it's, it's a very individual to the patient, to the pace of the disease through comorbidities as to when we treat. And if we treat, and I think it's very important for us to be comfortable managing uh expectations and uncertainty. And that's doctor Aahs favorite term, we have to manage uncertainty and be comfortable with sometimes watching things that are not going to evolve very quickly, excellent review. So um you can see how much fun it is when we have these discussions at our Multidisciplinary Tumor Board uh regularly and why we keep coming back. So this patient uh we did the canary high likelihood of at least three that if at resection they're going to be malignant, this performance status is excellent. The patient wants to proceed. Doctor Eisenhower. Could you describe the program that we're we have here, what we call single stage and how this patient might be a candidate for that? Because theoretically, this would be in order to get both of these cancers, a lobectomy and the importance of tissue confirmation before a patient were to undergo a lobectomy. Yeah, it's a great question. So the NCCN guidelines would suggest obtaining some sort of tissue confirmation of malignancy in a patient prior to going to lobectomy when and if at all possible as Doctor Owen. So eloquently mentioned in some situations, doing a biopsy beforehand is not really uh necessary in other circumstances. The NCC A guidelines do allow for biopsy at the same time as resection, whether that's a diagnostic wedge resection as a part of the initial surgery or what we have started to introduce in a situation where a wedge may not be feasible. Um Is a bronchoscopy biopsy at the time of the resection. So the way that we do that is to bring a patient into the operating room. We consent the patient ahead of time that will start with a biopsy. And then based upon the results of the biopsy, if they're confirmatory or not for malignancy, then we have a plan set up to go ahead straight to surgery. We bring the patient to the or we put them to sleep under anesthesia. We then introduce the robotic bronchoscope, which is uh uh uh a very slim, ultra slim 2 to 3 millimeter uh remote controlled catheter that can be steered to within 99% of any and all pulmonary nodules um through the airway. Uh we use uh a hybrid operating room. So we have advanced imaging applicable and available to us if we need to better direct exactly how to get into the nodule and the proximity of our robotic bronchoscope to the nodule. We then obtain a biopsy with the pathologist in the room that can give us a quick overread to confirm. Yes, this is in fact, cancer. Um And in that setting, if they're able to do that, we're then conveniently positioned in an operating room with the patient already intubated, we then turn the patient on their side and then perform a minimally invasive resection. A lobectomy. In this case, with um mediastinal sampling, we also have the capability to do EBUS and mediastinal staging if and un clinically appropriate as it would potentially be in this scenario with bilateral lesions. Um We have shown that that um program has reduced delays in getting a patient to potentially surgery or at least through the diagnostic and work up phase of a patient's journey care journey. Um and have in some circumstances also avoided such surgery when we have definitive confirmation of benign disease on the biopsy. Excellent. Excellent. Ok. Well, uh the patient was very interested and he underwent uh the single stage uh management strategy. The lobe was reset with proven for aoc carcinoma. Prior to resection, the lobe was resected and these were both adenocarcinoma i invasive adenocarcinoma in the left upper lobe, both lesions. Ok. Now, doctor Shasha, does this patient, does this patient need systemic therapy? So, uh uh uh uh going back to the same is, is really, is uh to define is uh is this part of uh uh same biology that uh does all those, don't you have the same biology? Is it to help us to do to know if this is a metastatic lesion versus a separate primary lesion that is more of att one a each one of them. So those multicentric they can evolve at a different time point and sometimes they can evolve at the same time point. So not necessarily, those always represent a metastatic disease, meaning set spread of those nodules to different sites. It represents a different biologic disease. And how do we determine that? Yeah. Excellent question. And, and that's when it comes to, you know, I mentioned you know, the pathologist uh role in this case, I oftentimes call the pathologist and discuss with them. What do you think is this is uh a separate uh primary tumor there or do you think this is all part of the same quest, uh part of the same disease? Um And uh oftentime our pathologists are very good at telling us that most of the time this is a separate uh evolving uh primary cancer sometimes where we face where it's not clear to them. And this is where the role of the NGS comes to help us uh is is uh to see what's a mutational panel. There are those similar or not. So these factors that I put into consideration before I decide to give an therapy versus an observation. And it's important to tell the patient that uh uh multifocal um uh disease, uh Multicentric disease can evolve in the future, meaning you can develop a future cancer and those usually present as a ground glass opacity that continue to evolve over time. So, surveillance is very important for those group of patients here at Mayo. We have done a uh a very good retrospective uh analysis of all of those tissue. One of our colleagues and um doctor Ro Rod and also had looked into those. And as uh a minority of them actually uh can express test mutation like the EGFR which can drive the growth of those cancer. Uh uh it's not implemented if the size is less than four centimeters. So there's no role for a TGFR therapy there. But it's good to know that some of certain subsets can evolve because of underlying on oncogenic mutation. Excellent, excellent. I'm glad you have uh mentioned the pathology colleagues too because here's a perfect example to me that a multi ca comprehensive cancer center that deals with cancer on a regular basis like mayo clinic and other places in the country. The specialist of lung pathologists are so critical. A general pathologist does a lot of great work, but it's very hard for their, from them to know the nuances of these different uh uh histologic features, morphological features that they might see to be able to say these are separate primaries. So you're correct. We went back to our pathologist. They were very confident that these are unique, separate primaries within the right upper lobe based upon their histologic and morphological features. And they were, they were uh very comfortable calling this multisensory adenocarcinoma spectrum. I think the reason I'm bringing this up is that when colleagues outside of mayo are uh confronted with something like this, we also have a consultative pathology uh service that reviews pathology from outside regularly. So now we have the patients very happy, they have taken care of two lung cancers, but they have a third. That's in that right upper lobe, Doctor Owen, we're gonna refer that third. But after our discussion at the multidisciplinary tumor board, you volunteered to see him the next day. You were very or her. You were very accommodating as you always are. And she's coming to you to discuss the role of radiation here. She did ok with surgery, but she'd like to try and avoid surgery if that's a possibility. What would you, what kind of conversation information would you give her? Well, there are very small trials comparing SP RT and surgery and there's a pooled analysis showing that there's comparable outcomes in operable candidates. And there's also uh a small randomized trial that the RT OG ran showing comparable outcomes between surgery and also SP RT. And there's a larger trial now that has accrued 400 or 500 patients and we report hopefully in the next 3 to 5 years uh on surgery versus radiation. The NCCN does accept SAT tactic radiation for patients who are non operable candidates where, where our concern is we need to do lung sparing treatments and certainly in patients who have multifocal primary lung cancer, that is a concern. Doctor Eisenhower can keep, can you know, resect many lesions, but we have to also try to preserve some lung pama. And I uh I do talk to the patients about serote radiation. Um There's no evidence out there, but I typically like to wait 4 to 6 weeks. I wanna make sure at the very least the patient's lung is reinflate it on the contralateral side that the patient is doing well postoperatively. I will, you know, we we often consider simulating the patient at the time of the postoperatively visit about 3 to 4 weeks in conjunction with them, seeing the thoracic surgeon postoperatively. And then we talk about the number of treatments that can range anywhere from 1 to 5 treatments for the lesion. And certainly that one in the right up is very, very amenable to cro tactic radiation. The local control is excellent. There's uh some long term outcome now based on prospective trials on having a very good 90 plus percent local control. Uh So, uh we, I think that it would be a discussion um about what we would need to do, which would be to do a special ct scan to plan the radiation. Uh We can typically start a stereotactic radiation with x rays, which is a standard uh within two business days. So we can scan them and start in two business days later, insurance permitting. So we're one of the fastest in terms of getting patients started on any radiation therapy. So, uh also I always get uh doctor risen's blessing, you know, is this patient OK, to get radiation right now because certainly there's a small risk that my inflammatory response after they've had an inflammatory response after surgery could be synergistic. And certainly the patients had multiple um post-operative complications are very, very rare, but we do have a small handful of patients. We have to be cognitive that and again, uh that lesion while it is concerning does not need to be treated. Even at the four weeks after the post-operative visit, we could also talk to the patient about a timeline uh of when the patient might want that treated. So, um again, all of this still requires a multidisciplinary consultation. Excellent review. Excellent. Well, this has been uh a very enjoyable conversation uh around a couple of clinical scenarios that are commonly seen. I'm gonna look in the chat box again, I'll ask our mode our uh external moderators if they see any questions. I don't. Uh II I see one. It looks like it's more for Doctor Shan. They uh somebody's asking if there's more information about CT DNA that you can provide. There are ongoing trials looking actually there have been a trial conducted already. For example, I mentioned the checkmate 77 did include CT DNA as a biomarker, you know, for to the side of those patients will require an adjuvant therapy there. Um uh And there are also commercially available CT DNA. Uh The challenges is not FDA approved yet. So the my main challenge I tried myself to order for a couple of patients and insurance uh would not cover that. Um As of now, this remain investigational and but there are ongoing trials, actively looking into that do. And with the main question is, how do we require, what's the intensity of adjuvant therapy? Do do all of those patients require adjuvant therapy, post resection, for example or not. So we're waiting for those results and I I thought I was looking in the wrong box. I see another chat. I think this one might be for you, Doctor Eisenhower. Uh One of our attendees is asking, is there a standard minimum tumor size for the use of biopsy to produce sufficient? I'm assuming molecular analysis, not just diagnostic. It's a great question. I don't know that we've specifically studied that um we have been able to get um uh our median lesion size for robotic bronchoscopy for all comers is somewhere between 13 to 14 millimeters. And we've demonstrated the ability retrospectively to get molecular analysis on up to 80% of those tumors. I would expect that number to be much higher if we were doing it in a prospective study. Um uh Generally tumors less than a centimeter in size unless it's a specific metastatic indication don't clinically need, usually need molecular testing. So there hasn't been any specific data gathered around tumors that are 567 millimeters in size. So it's a difficult question to answer. Um But certainly we do the best we can regardless of the size of the nodule. I might add that this is very operational dependent when we're talking about use of navigation and robotic bronchoscopy. And it also is very operation dependent when we're doing CT guided biopsy. So, uh the, the, the Doctor Eisenhower said it's real hard to say, but the expertise is uh of your procedurals grows with experience. So uh there, there might be more to come on that. I don't see any other. I just wanna on behalf of uh our tumor board and the Mayo Plank wanna thank doctors Owen Reisenauer Shasha for an exciting and very educational uh session and interchange. I always learn something when, when we get together. That's why I long for the one o'clock tumor boards. If you uh have any ques further questions uh regarding how to refer a patient here or any questions regarding cancer care at Mayo Clinic. Please look at the uh the contact information to the referring physician office. Don't hesitate. We're all available by our emails that you see out there. You can't bother us with too many emails if we can help you with your patients. Thank you, everyone.
