Keynote: Global Perspectives on State of Lung Cancer
Broadcast LIVE from the Intercontinental Hotel, San Diego, CA, on August 6th, 2021, David Fielding, MD, Thoracic Physician, Royal Brisbane and Women's Hospital, discusses global perspectives on the state of lung cancer.
Presented by:
David Fielding, MD Thoracic Physician Royal Brisbane and Women's Hospital
Yeah, good evening and welcome to the very first annual top Executive summit hosted by intuitive, we're thrilled to have you all here, especially during these times. I'm certainly thrilled to see a room full of smiling faces that are healthy and happy and it's really nice to get together in person and get beyond the, to the environment. So thank you all for coming. We know you traveled far and wide to get here and we hope that it will be extremely impactful to your program. So tonight I would just like to introduce our VP and medical director, Dr Oliver Wagner, who is going to be moderating our keynote speaker tonight. Good evening everybody. Very exciting to see everybody in person. Finally, I already heard a couple of times tonight. Um people are so glad that we didn't cancel this. Um, so you can meet, we can meet in person for the first time in a long, long, long time. I'm very excited to see so many people here. Um and I have the great pleasure to introduce dr David Fielding tonight. Yes, yes. Dr David Fielding is the director of thoracic medicine. Good evening. Good morning. David, uh Director of thoracic medicine and former director of oncology at the Royal Brisbane and Women's Hospital in Australia. He's also that's very exciting, a research fellow again since three years at the Center for Clinical Research, University of Queensland and the Queensland Institute of Medical Research Burke or for that is one of Australia's most successful medical research institutes here. He is conducting research on molecular processing of Abbas T. B. And S. T. D. N. A. Samples for innovative molecular analysis, as well as streamlining lung cancer diagnosis through novel genomic testing methods. David trained in Brisbane as well at the Middlesex Hospital in London. Together with steven spiro jeremy George and martin Hetzel. three renowned interventional lists and pulmonologist in the field, He learned advanced and the bronchial ultrasound with dr Kurimoto in Hiroshima. In addition to the already mentioned research in genomics of lung cancer specimens. His current research interests includes advanced peripheral nausea, biopsy, noninvasive lung cancer biomarkers and optimization of triage and patient journey. For patients with pulmonary modules. Dr feeling was the first physician that has used the iron system clinically in a total of 30 patients. Now, our first in human studies in Brisbane in Australia in 2016 and the beginning of 2017 um we had a lot of exciting experiences some of that he will share tonight. The data later was presented at the chest conference and published in respirable aje again, it's my great honor to introduce dr David Fielding the first iron user ever, the first robotic bronchoscopy pissed that ever used iron in the field. And patients, Thank you very much David. So my child, it's just so nice to be able to speak tonight and I greatly appreciate the opportunity. Um I also want to thank you Oliver. Your drive and enthusiasm and skill has just been so critical to the success of Ion and our experience together in Brisbane was just a really great collaboration. So thank you. So that's just a brief disclosure slide. Our study was funded by intuitive but there were no other relevant disclosures. Uh just to say that I I live in Brisbane and I'm from the state of Queensland and you guys love football and we love football, this is our Queensland Meron state of Origin team and a Queenslander loves rugby league football. Uh this is my hospital in Brisbane. Um we have uh interventional procedure room and we do around 1200 procedures a year with all the different range of diagnostic and interventional procedures. And um it was that sort of stand alone facility that that allowed us to really focus on what was needed to do this first in human study with the robot in the talk tonight. I just wanted to talk about some cases then and now. So To say how how things have changed even in the last sort of 1520 years. To look at the demographics of lung cancer across the world and the resourcing issues that face us across the world in managing this terrible problem. Just to describe the advances in the management that we're all familiar with the importance of ct screening and were guided in robotic bronchoscopy fits in and just go over our first in human study. This is a typical case um of advanced lung cancer. So those not familiar can see uh the C. T. And that's the heart and lungs in the middle and the um sort of oval shape to the left of that black hole in the middle is a lung cancer and it's invaded the media steinem. And this is um you know at least stage three if not stage four lung cancer. And um This is a very common scenario. So back in 1997 what what we would have done this is soon after I started my work as a interventional procedural ist. We would have placed a stent, we would have probably ended up getting a media sign Oscar P. If we couldn't get an endo bronchial biopsy to make the tissue diagnosis. The patient may have had palliative radiotherapy after that. And in general would have been a palliative care referral. Today we do all of those things. But in addition we would definitely be doing a busty DNA. And that would give us the tissue diagnosis without a surgical intervention and importantly get molecular characterization. The patient would receive high dose chemo radiation almost certainly and very likely receive a checkpoint inhibitor with that. And um depending on the results of the molecular analysis, including whole Exxon sequencing might be considered for a trial of targeted therapy And have a very good chance of five year survival. This is another common scenario, a small lesion in the left up alone in a patient who has bullets change of emphysema. So back when I was starting out we might have considered doing a ct needle biopsy. The patient would have a very significant chance of getting a pneumothorax and need a chest drain. There would be a consideration for standard radiotherapy, but we were always concerned about the risk of radiation and a person with borderline radiation pneumonitis in a patient with borderline lung function. And it was not uncommon for these patients to just be observed instead. Um Whereas now we we we know that tissue is the issue and we've got to um we have ways of getting to this, be it with small bronchoscopes and guided bronchoscopy with navigational assistance, including robotic bronchoscopy. Strong consideration for that slow back to me or or um um Saber radiotherapy and molecular and biomarker analysis would almost certainly happen and a variety of novel adjuvant therapies could be considered. So that's just the sort of even in my lifetime and within my career, things have completely changed, but the global problem remains. Um We we know that this lung cancer is a hugely important factor in overall cancer mortality. So if we look at all causes of cancer death in the world from 185 countries last year, There were 19.3 million new cases in the top panels, And lung cancer accounted for 11.4% of that 19 million, which is 2.2 million And a very high. And the commonest cause of cancer death overall at 18 At 1.78 million. And the reason for this very high death rate amongst cases is the fact that we still have patients presenting in late stage. So 75% present in stage three or four, And only around 15% of all cases are alive at five years. If we look at um, the the communist, uh, the cancer deaths across the world, and there's 185 countries that the Communist cancer is color coded here and lung cancer is colored in blue. And if you look at the top panel, that's the countries where lung cancer is the commonest cause of cancer death in males. And it is the commonest cause of cancer death in 93 countries. So it's quite a staggering um global phenomenon. If we look at where that sort of some of the hotspots of lung cancer within populations within countries, there are some countries that stand out in terms of the incidence rate per 100,000 cases. And if you see the top uh for their, there's micronesia and Polynesia at 51 0.6 cases per 100,000 Eastern europe, Eastern Asia and Southern europe, the highest um per population rates of lung cancer. And it just shows that there are some geographic effects going on. This lie just looks at the impact of low and middle income countries in terms of the overall global Sort of weight of lung cancer. So we know that 65% of all lung cancer in the world is in low and middle-income countries. And this graph looks at the change over time. So it goes from 2012 to 2018 to 20,040 projected. And um if you look at the middle panels, the blue, um the blue columns are high income countries and the orange and red panels are low and middle income countries. And you can see that the both the incidence and mortality rates are far higher in those low and middle income countries. And further, if you look at the lines at the top of the graph, you can see the case fatality ratio. So in the middle column in 2018 the case fatality ratio and low and middle-income countries was 90% versus 75% in the high-income countries. So there's a big disparity in terms of how patients can be treated and managed between um the the low and middle income versus the high income countries. And in the far right column, you see the projected Numbers if you like of cases and and basically it's showing that in global terms there will be double the number of cases, but in this coming 20 years and this presumably relates to the ongoing delayed impact of cigarette smoking. So, and just to continue that point where the epidemic is at an earlier stage, including china Indonesia and several african countries smoking has peaked or continues to increase. And this is where this projected rise in cases is going to come from. The good news is that rates of tobacco have declined in 116 countries with strong implement implementation of reduction measures. Um and in 2018 for the first time, the number of men using tobacco locally globally began to decline, But the progress is uneven and there's 59 countries that have yet to adopt a single empower measure of smoking reduction. What what are the some of the barriers and potential solutions for lung cancer access and screening and patient identification and adherence? So so that lung cancer screening is something that can be used to try to counteract this terrible problem. And it's something that is becoming second nature in first world countries. And if we're going to impact these low and middle income countries, then this is certainly uh one of the tools that we could use, but that there is there are barriers to that to rolling out screening. So transportation, road conditions, physician unawareness of screening guidelines, cultural barriers, poverty and gender discrimination and mortality rates being higher in women from rural populations are some of the problems but there's potential solutions so mobile CT scanners And one stopped lung health checks. Increasing use of electronic health records to identify high risk subjects using community health workers. Very importantly developing culture sensitive, sensitive screening approaches. In terms of equipment there's just fewer C. T. Scanners and building infrastructure to get these things in place is costly. Managing the screen detected modules needs experienced radiologists and multidisciplinary teams and furthermore the processing of the samples with complex immune, artistic chemistry and molecular diagnosis is essential but difficult in these countries and only a privileged minority have access to some of the expensive medications. So training is really critical and local management guidelines are essential in different parts of the world. For example Asia brazil and South Africa. Looking at different management guidelines in particular to reduce false positives in TB. endemic areas. So I'm involved in the World Association of bronc ology and for a long time, our society has been working to provide bronchoscopy education through the bronchoscopy education project. And this these pictures show my friend Enrique cult has been a tireless advocate of this and many of you will have, well, no one re and have worked with him in these programs and some of the places that this program has been taken to include Singapore, Malaysia, Indonesia, Argentina, Peru el Salvador et cetera. And it's this kind of education that will improve diagnostic safety and and and skill and give patients the best access to the all important diagnostic approaches that pulmonologist can offer. And and the society also offers travel grants for students from these lower and middle income economies to come to sort of high volume, highly skilled centers to learn uh these all important techniques. So, some of the things that have happened in very rapid succession, really, if you consider On the far left of that Diagram that 1950 was when Dole and Hill wrote their papers linking smoking to lung cancer and in the green, you've got diagnostic and screening techniques and in blue you've got therapeutic techniques on this, on this timeline. You can see E bus there in about 1995 along with pet scanning, so that those are things that are and now, absolutely. First line and um it's amazing how they have just become so part of the furniture now, but back then, not so long ago, they were really quite new. Um and you see there the all important discovery of EGFR mutations there in 2004. Um and by 2011 we had the approval of genotype specific therapies And then all importantly immunotherapy in 2015. The first approval of medications furthermore, you see, the N. L. S. T. Was published in around 2011. So it's 10 in this last 10 years. All of these things have really injected a lot of interest and a lot of enthusiasm into this space. This is the you will you will all be very familiar with these pie charts of a demo carcinomas and this is all so critical to our understanding of how we can impact lung cancer. And it's a change in the way we think about cancer. Back When I started out in 1997, it was kind of a you just had one treatment for the For pretty much 75%, which was to some sort of platinum based chemotherapy. So there was a sort of a a blanket sort of one size fits all and and see how that goes type of approach because we just didn't have these opportunities. And what is developing now is this kind of patchwork understanding of what is going on at a molecular level to the point now that this this this pie chart is getting filled in more and more each year. And very importantly, not just the mutations, but the therapies that go with it. And we now have only that 28% unknown on cryogenic driver identified, 28%. And It's very likely that within the next five years that will be down to, I don't know, 5%. There will be more drivers identified And you know, it depending on where you live in the world. Even now, 60-90% of patients have some driver mutation. And so therefore the other important messages that patients, particularly in those areas continue to get genomic information to ensure that they have the best possible opportunities for therapy. The in terms of checkpoint inhibitors, um this is a really amazing story. Um and that case I showed you at the beginning will now have a a very different experience in a very different life expectancy because of this and this this is incredibly rapidly developing. Um And this this sort of timeline goes only up to 2019. But in the last two years, including at Asco there this year, there's just so much more information even since then. But you see in the green panels, the studies that have looked at lone checkpoint inhibitor therapy and the yellow. It's the studies that have been combining checkpoints with chemotherapy and in the orange panels in the bottom right there, studies looking at duel Checkpoint inhibitors and you see they're going from 2015 where loan therapy was given after platinum chemotherapy to 2016. Where you had first line pembroke in patients with high PDF one expression To 2019. Where you have um therapy for with checkpoint inhibitors even for subjects with more than 1% of PDL- one expression. So so the extension and the applicability of these therapies and the way that they impact survival is increasing all the time. And so you see there the keynote 21 there in 2016 demonstrated that by adding pembroke to chemotherapy, The progression free survival went from 9 to 13 months and there was overall survival hazard ratio of .56 compared to conventional chemotherapy. Uh huh. The CT screening um It's very familiar to all of you um you know the story of the improvement in survival between 20 and 25% lung cancer-related mortality and screened individuals. And this is part of the landscape now for for all of us going forward uh in our clinical practice. But I guess the thing that occupies our minds is um the way ct screening inevitably finds nah jewels that um don't turn out to be a malignant. And this this is the problem that is going to be part of our working lives. Is working out this problem. We know that it helps but we've got to ensure that we're using um as much clinical and biological information as we can to limit the the experience of patients having to go through unnecessary testing for for na jewels which don't turn out to be cancer. So so all of you will be familiar with, you know many of these um nah jal classification systems which look at size and radiologic components and other clinical factors. And lung rods for example um is very well known. Um in this space and with this type of assessment it's been demonstrated that the false positives in the LST trial, had they had lung rads applied to them could have had us very significantly reduced false positive radiologic classification of cancer. So for example, with lung rads um the false positive classification would have been only 13% versus 26% in the actual study. And very important to note that 2% of all the patients screen had an invasive biopsy for false positive results from that first publication. And so this is something that will continue to occupy our minds. Radio mix is one of the tools that will be become critical not only in terms of volumetric analysis which was used in the nelson study but to actually characteristics the the modules by way of pixel distribution and shape and and edge analysis and so on. This is going to be absolutely fundamental to how we how we manage this problem. These clinical predictive models are also extremely important and you know we used the brock risk calculator every day. Um and if that looks at you know the lesion size and numbers of lesions and position. And you can also put in the pet divinity which hurt her. And the treat study have shown and you can see this the range of different rock analysis e or rock success rates if you like for prediction of um Prediction of Malignancy including the study by Maldonado there in 2020 you know a rock of more than .9. So so again this is these clinical parameters. There are things we all have on our phones and we use them pretty much every time we see a patient. But the thing that we need is actual biologic tools to kind of help us understand what we're dealing with. We've got a nodule we need certainly we can have a box score and another pet scan but we can have something that looks for all the world like a cancer which isn't. And um likewise we've all seen things that we thought were particularly likely to be benign that were malignant. So we need sort of biologic tools be they from blood, be they from um breath be though from saliva and in blood testing all of you will be probably experienced. And even using liquid biopsy in your clinical practice today and I won't talk about liquid biopsy today but it's obviously something that is going to form a very important part of our approach to this, this huge clinical problem that we're trying to address. Um the circulating T. U. R. D. N. A. Or circulating tumor cells. Um The sensitivity is getting better all the time when they're positive. They're fantastic. But it's the problem of the sensitivity at this stage being a little low. We know that these tools are incredibly important in monitoring um and uh in particular looking for transformation of mutations. But this space is filled with research effort at the moment and I fully expect that in the next 5 to 10 years we'll have a much better biologic approach to this problem. But we're still this is where we're stuck here. We're stuck with the fact that, you know, stage three and four cancer is where this is happening. And we need to shift patients to the left. We need to be picking them up earlier and you know, so we need tools that can get us to diagnose things earlier at points where we wouldn't even previously have considered sampling nah jewels. For example, There's just one last thing that's further complicated the picture all of us in this space. And like I go back to 1997, the squamous cell cancer was the commonest thing that we did. And taking a biopsy inside the bronchus, you see that panel in the middle. That's if you can see something that you can buy up, see it very easily. Whereas you see the bottom right panel that's adenocarcinoma and you see the little um sort of a bunch of bunches of grapes there in the periphery of the lung, which don't actually sit in an endo bronchial compartment. And they represent the most common forms of tissue. Now, the tissue diagnosis and and it's this it's a common cancer but it also is radio it's radiological, peripheral and difficult to access. So this is this is where we're at. We've got too many Nagy als in the wrong place in the wrong patients with the wrong histology to facilitate and a bronchial biopsy. So we know that if you if you use smaller bronchoscopes um your success rate is better. And we all started out with the little scopes on the right and we continued to move to the left. And this is the work of DR Okey and colleagues who've done absolutely phenomenal work just bringing these ideas to the world that and that we just need smaller scopes to access these peripheral um nah Jal's this is also the something that that we've known about for a long time. The benefits of virtual bronchus copy that. It's one thing to see a nodule on a CT scan but it's another to match up the pathway to get there. And Dr Asano is um has always sort of provided this incredibly elegant data using software that his team and others have developed to facilitate the way we can get out there and so with or without radio lee bus. And he's demonstrated that you know, you can improve diagnostic yield using virtual bronchoscopy. So we know that these modules are peripheral that a pickle. We know that ct biopsy can can get us an answer but it has more morbidity than bronchoscopy. But bronchoscopy by conventional methods, even using small scopes and navigational assistance is still not getting there in terms of the overall diagnostic yield. So this is where the robot came in and um it, to me that's why I was so excited about it because it actually was coming at a time when the technology had reached its kind of ability to deal with this problem. And this effort was to me it made perfect biologic sense if you like. All of you are familiar with the concept of combining a C. T. Into a pathway that can then be linked to a robotically guided catheter to drive through the airway and allow sampling. And this is the the shape of the system and you see that the catheter at the top which has a 3.5 millimeter outer diameter and a 2.2 millimeter channel. So it's basically the same as that bronchoscopes of, Okay is that I showed you before in terms of diameter but it's got a two millimeter channel versus a 1.7. And if you like it's an inside out bronchoscopes it's the channel is the system and the video probe goes into it and that can be removed and then placed replaced with with the needle or any bus pride or both. And this is the one of the remarkable things about this catheter that it's, it has this ability to be sensed no matter how far or in what shape it is. And it's a matter to use that shape sensing to ensure that as we bend it or move it or advance it, we know exactly where it is. And this assists the computer in giving feedback on where we are with respect to the nodule. It's just so um, This was the study design and we just took 30 jewels that just came through the door in succession. Um, these were the first cases that we did and um, the, the, the idea was to basically just demonstrate feasibility and safety and we excluded nah jewels that were within the first three airway generations patients who weren't fit enough to undergo endotracheal intubation and patients who had prior for asic surgery or had known pulmonary metastases ease. Mhm. So this is, this is us here in our department, that's my friend and colleague, Farzad bash Azadeh. And as mary Ann Todman in the bottom right corner, she was our head nurse. Um and uh as I mentioned, it was a massive team effort and um it was logistically just really fantastic their support we received to do this. So we had the largest uh blake nodule size was 14.8 mm and the largest cardinal diameter was 12 mm. So this was, these are very small nodules, difficult modules and mostly in the upper lobes and every bronchoscopes knows that it's harder to get there. You see, this is a typical nah jal in that we that we had as part of this study and as I mentioned before, the problem with adenocarcinoma as they sit outside the airway. And when you get there and you put an Airbus probe into place the you see that the mini probe there and the nodule is not is outside the bronchus. It doesn't surround the the mini probes. So It this was the case in um basically half or 40% of the patients that there was no airway that went direct to the nodule. And this this is where the robot really comes in overall. We it was very safe procedure and we could get there in all but one case. And the bottom line was that we had an overall diagnostic yield for malignancy of 89% and a system diagnostic yield of 80%,, Taking a mean nodule size of 12.3 mm. It's very small. It's a typical case um of a small nodule. You see there in the left upper lobe which we got to and biopsied and confirmed as being a non specific fibrosis with organization and abundant fibrin. So that's a very suspicious looking nodule and the ability to provide a kind of a positive diagnosis of benign disease was in that particular case. Very important. So these are some of the images that you'll be familiar with. So you see the left um is the real image. The right is the virtual image. And we're following the green path. And you can see on the far right panel the approaching catheter getting close to the red nodule. And as as we got closer the the pathway turned red and at that point we would stop and um sort of fine tune the position of the of the robot into into place. And you see that um That this this is the still images of the different positional uh um uh angular rations if you like. And I think dr Pritchard will explain all of that in detail. Tomorrow this is another case, a very common scenario of a small Lepic looking cancer and the right apex. And we were able to biopsy that with with the system and and it just shows that the very significant degree of angle ation through which we were able to plus pass very large biopsy forces and needle sampling. So the thought to be able to turn such a corner and get into such a difficult position to get really good diagnostic material would really be unthinkable with a lot of other systems or previous work. So this is that's a my preacher there and his work is really looked not only at the diagnostic ability of this system in the clinic, but he's shown the ability or the learning times are actually very rapid, both for himself and his colleagues in his work. And the reason, one of the reasons is you see him using the trackball there. This is something that we're all familiar with. It's not like holding a bronchoscopes and holding a bronchoscopes is actually quite a challenging thing and it's quite physically tiring and difficult. And but but what this what the robot does is not only allow easy turning an easy redirection, but it stays still when you take your hands off. This is also an important part of the learning curve and this is courtesy of mike Sim off. This is the way this fine tuning at the very end of the procedure can direct the catheter towards the target. incredibly important aspect to deal with this problem of the nodule that's outside the airway. Just to say that there's ongoing studies of ion in the clinical space as well as the other robotic system, the monarchs system. Both these are eagerly awaited and um it's a very exciting time to be in the interventional pulmonologist face. So just in conclusion, um just to say, lung cancer does remain a global health challenge. Especially in low and middle income countries, Smoking rates are coming down and there's been incredible improvements in diagnosis and management in the last 10 years. City screening throws up a whole new set of challenges and our diagnostic tools need to be better than ever. And I do think that robotic bronchus copy addresses this need. And just it's customary to thank people at the end of talks like this. And I just always thank our bronchoscopy nurses who have been tireless and excellent and without whom none of our work could be done. So once again, thanks a lot everybody. And I've really appreciated the opportunity to speak today. Thank you, David. Excellent talk. I I always enjoy the 1st 1st cases that you present here. I think most mostly in the room. Haven't seen the user interface that you were working with. And also the old system, which basically was chopped up da Vinci tower and we put it monitor on top that all has changed today. Very exciting. I want to open um, Q. And A. Here. Any questions in the room? Okay. Maybe. I started with the first question, David. You mentioned the learning curve for the robot and then we have seen the procedure of times where anywhere between 26 minutes for the fastest case 140 minutes for the longest case and uh There was quite a learning curve. How how would you describe the learning curve? The most important steps that you went through in these 30 cases? And what would be your recommendation for novice using the robotic technology in the first cases? I think the is to um are you getting feedback with my voice? I'll just keep speaking but the key is to just select things that you would normally consider relatively straightforward for um in any bus guide sheets. So something with an airway, something that's um you know, two or three terms outside, you know the low bar bronchus. Right? So don't don't select the hardest case. First our problem was that we as you remember we had to take things as they came to us, but with, with learning it's there's so much other things to become familiar with that you need. Um You should just um not make it too hard to start with. Um I think the second thing is that all of the same things apply that your pre procedure thinking should remain the same. You should should look at study the C. T. Scan and the way you always would before an ever skied ship. I think one of the things Oliver that you remember is this this problem of um the full shortening of the lower lobes in particular because of the volume changes that happen in a patient who is under anesthetic compared to having when they're taking a deep breath when they're having their cat scan. Right? So the length of the bronchus changed and that was something that we worked at we knew about. But we were sort of really focused on in our study and I know that the technology has improved and your ability to determine just exactly how far you've gone with this instrument really addresses this problem. But I think it's always something for to be really aware of that. You're particularly in the lower lobes, in a patient who's asleep, you're going to get to it faster than you think you would. Right. So in the upper lobes it doesn't change much because there's not so much volume loss in the upper lobes um in a supine patient. But those, those are probably just a couple of points. Oliver, thank you. Thank you. David. Any other questions over there in the back? Yeah. Uh Thank you. Um I'm actually interventional pulmonologist at University of Oklahoma. So we are into like 30 cases and I think we have a pretty decent here. Uh the first two cases where we had difficulty, it's always very easy to get to the target right away. 2 3 minutes. But then, as you mentioned, some of the most of the audios are outside the airway. And you don't really know whether it's 12 o'clock, two o'clock, six o'clock. And so how do we navigate about it? You know which side or just to a cloud biopsy? Mhm. Look, I think that's the, well the first thing to say um is that needles are really important in this space. Right? So it's a trans bronchial needle aspiration of these lesions. And I think that that should be the mindset of the procedural list as opposed to conventional brushing and biopsies. I'm sure that you're using that. But just to reinforce that this to me, the system is about uh about a directing, directing a needle aspiration. I think the look, one of the things um I think, you know, the role of ultrasound is important in this space. And one of the ways that we do use ultrasound even without robotics is to try to get a sense of um the way the ultrasound image changes as we go down or up with the tip of the bronchoscopes and going up, it gives a better image than going down. For example, close to the nodule. Then we know that we have to kind of direct the tip of the catheter upwards. And this is a principle that you can sort of apply with the robot. I think I think the other thing is in practice is to ensure that you start thinking a little bit earlier than you otherwise would. So. So if anything come to come further away from the nodule and ensure that the needle that you're putting through the airway wall is is not shooting past the nodule if you see what I mean. It's all about come to the come to the a point before the nodule and start thinking about your cloud biopsy at that point as opposed to coming a right adjacent to the nodule. But yes I mean that that's a challenge and that's um that's a and I think mike will no doubt tell you a lot more about that than I can because he's he's so much more experience with this now and and I'm sure that his teaching will will help all of us to be honest. Thank you. Mhm. I have a question that great to talk dr fielding on the topic of the worldwide burden of lung cancer. You mentioned a little bit about increasing screening within low and middle income countries. But as you think about then you know diagnosing and then treating the actual cancer in the low to middle income country. You know surgery, minimally invasive surgery. S. P. R. T. These are not really feasible options. Do you see in this context a role for catheter based ablation because it's more scalable. I mean I I thought I should have had a slide in there about that point because um you know I think that this is where we all feel that that robotic bronchoscopy is headed but we just don't have the data yet. We know the potential for this and I just think that this is a discussion that is still in its earliest phases but the potential is obvious and I agree with your thinking. You know it's it's there's a lot of there will be a lot of logistic issues even with that even with the fact of um you know in a blade of therapy that will require a lot of skill that will require a lot of training. And even though it won't require necessarily in intensive care or hospitalist like days in hospital, I think there will be technical challenges that will require a lot of thinking over the long term. But bottom line, you know, I mean if we're finding a lot more things, we've got to have a lot more tools to be able to treat them. So we have surgery and radiotherapy as you mentioned. But there there will be um you know, the need for alternatives. We have microwave ablation now, but we we need even more and there will be scenarios that are particularly suited to each one of these things. And I think so look, I I think the short answer is um there's a potential but we need more experience and a lot more data and but it's uh you know, the the potential is really excellent. Mhm. Thank you, David. We have time maybe for one last question. Mhm mm. Okay. After feeling that was an excellent presentation for those of us. Real privileged to hear you present those early cases. It's nice to hear from someone that's been such a leader. With the recent report. The NIH came out and showed that the United States has seen a decline in the mortality of lung cancer beyond the incidents. And my oncologist were quick to jump on that and say HAC molecular therapeutics here is the answer. How do you think this impacts are position in diagnostics with lung cancer? Yeah. Um do you mean that the improvement in survival is based on the the importance of um molecular guided therapies? Or do you mean that we have to ensure that as bronchoscopes we get the necessary tissue to allow those kind of therapies to happen. I'll let you choose which of those two because I think there's there's interesting direction you can go with either one with either deliveries of therapies locally or positioning ourselves to make sure that we're we remain on that cusp. Because they really believe honestly that that's the reason why the decline has been seen. Yeah. I think the other thing and i is is okay so we have ct screening but you and I will have seen like effectively the impact of far more widespread ct screening full stop or C. T. The performance of C. T. Full stop in our careers. Right. So so by that I mean that there's kind of been a de facto screening going on for a long time And as we sit in our, you know, it's a in the last 5-10 years as clinicians we are being referred more and smaller and smaller modules that have been picked up by more and more vigilant radiologists. Even before CT screening was formalized. And I wonder whether that's been a part of the fact as well, that, you know, it's like the the movement of CT screening has has kind of commenced and therefore, you know, we're seeing these earlier cases. Um look, I I think I'm sure that um, you know, and the other thing that the other part of this equation that we haven't really talked about is how staging itself has made us. We're better at staging lung cancer, I think, and I don't want to upset Oliver, but he'll he'll agree with me. I think that the widespread attention to detail about staging that we have all become part of with the bus, I think that's also helped to ensure that patients are getting the right adjuvant therapies. So I think it's a whole range of things that are happening in the background even before. Um even allowing for these great effects of targeted therapies and the great effects of, you know, checkpoint inhibitors. I think there's these other sort of almost intangible aspects um that we've been part of in our clinical practice, you know, staging lymph nodes much better, working harder with smaller nah jewels that seem to get sent to us all the time by hypervigilant radiologists. And so look, I think we can all claim success. Let's put it that way. All right, David, thank you so much. Excellent keynote speech this evening. Uh we are very grateful that you started the journey with us only regrettable that you cannot be with us here tonight and I hope this will change and we can see in person hopefully soon. Thank you so much. Uh Dr David Fielding, Thank you. Thanks for everyone. Take care. See you. Mhm.