So, I'm just going to focus on diagnostic bronchoscopic platforms. I just want to thank a couple of my colleagues who we have collaborated over the years together. We often use different platforms among our institutions, and I think there's a lot to be learned by the published literature that's evolving, as well as our own experiences along the way as these technologies evolve. I'm going to really focus on the aspects of the peripheral pulmonary nodule and how do we get there, and when we make the decision to get there, how do we best do that, and show you some of the data based on meta-analysis and other published literature. I think we all can appreciate that once a decision is made to try to make a diagnosis in the least invasive way, potentially, the ability to not only diagnose the nodule, but when appropriate, to do mediastinal staging in one setting, one procedure, in the safest manner possible, there's certainly strong consideration as we work toward that goal in increasing our diagnostic yield. And I think it's important that so many variables play into this. Technical performance, the technology, does it serve us well? The operator, there's an operator learning curve for all these different technologies, not to mention all the things that we've talked about before, nodule characteristics, the type of tools we use to biopsy, cytologic interpretation, definitions, cancer prevalence. All these things build up to what ultimately becomes a procedural outcome in terms of complications and diagnostic yield. And I'm also going to highlight in the literature, there's high variability of what defines diagnostic yield, and that's why when we read the literature about the technologies, we have to appreciate that the diagnostic yields may vary from publication to publication, and why does that matter? So the ideal navigational tool, well, seems obvious, but it's accurate, able to overcome the CT to body divergence in real time when you have a patient who's maybe mechanically ventilated under anesthesia. There's different dynamics of the lung that can shift the target in terms of location after you've done your mapping pre-procedure. We're looking for a low complication rate. Is it easy enough to learn that could bring all providers up to the same level so that all patients have equal access to high-level care for diagnosis? Is it versatile, and is it inexpensive? I think we have work to do in terms of inexpensive, but I will show you some things that have evolved over the last few decades. So I think we can appreciate more and more the early-stage lung cancers, as opposed to the Nelson trial, rather, noted that there was more and more peripheral location, if you will, of the peripheral nodule in the outer third of the lung, also in areas that have been historically very difficult to reach with a standard bronchoscope, white light and fluoroscopy, for example. I think more than ever now, we're closer to the nodule than we've ever been. I'm going to highlight three of the commercially-available robotic platforms and show you their strengths and their limitations, and this is just an example showing more of a shape-sensing tool in the sense of the navigation, rather, robotic bronchoscopy called the ION. I'm really platform agnostic in my presentation, but try to give you equal representation of them. I think this highlights – I'm going to show you a few snapshots in my own clinical practice. If you'll notice here, this is a patient who had a PET-AVID lesion periordic. Historically, that would be difficult to do with an IR biopsy through CT guidance, and also, it would not be the procedure of choice to do a surgical resection without a known diagnosis of clarity of what this is, and so we were able, in my clinical practice, you can see the dexterity of the catheter with the robot shape-sensing technology to get to the lesion and diagnose an adenocarcinoma with no complication. This is just a few snapshots in my own clinical practice just to give you a sense of what nodules can be accessed with the navigational robotic bronchoscope platform, and you can see here a small nodule, ultimately diagnosed as adenocarcinoma. Keep in mind, historically, if a lesion was two centimeters or smaller, with standard fluoroscopy and a white light bronchoscope, the yield for that was only about 30 percent, so we've come a long way, but we're not 100 percent, to be clear. If you can look carefully here, you'll see a patient who had a history of breast cancer, had an incidental lung nodule, and basically needed a tissue diagnosis because it had shown a slight interval growth. We were able to reach that with the robot. If you notice here, this is a classic cystic lesion with a lesion inside it, certainly could have been an aspergilloma, something benign or something malignant, but the navigation with the robot allowed us to get to that nodule safely without complication. So I think the picture is worth a thousand words. Not that every diagnostic yield is 100 percent, as I mentioned, but just to give you a sense of how challenging some of these biopsies along the yellow area here, the periaortic, the dexterity of the catheters often allowed us to create a safe boundary to take a sample. So I'm going to go through kind of a whirlwind of different biopsy or platforms that exist that have evolved. There's some technologies that have kind of come and now waned, and others that are kind of in their peak, if you will, or starting to evolve nationwide or globally. There's augmented fluoroscopy. There's three different platforms for robotic bronchoscopy. One of the platforms combines digitized tomosynthesis technology and augmented fluoroscopy, and then the shape-sensing that I mentioned, but I think you'll hear a common theme. These are often coupled with other imaging in real time to autocorrect during the procedure is crucial, and radial probe EBIS has a certain platform in which to integrate into any and all of these other platforms that I've mentioned. So how do you decide which platform? It's kind of a whirlwind. I did this slide to make it a little busy on purpose, but there's so many different platforms. And again, I'm going to remain platform agnostic here, but one system uses electromagnetic technology. It was cleared by the FDA in 2018. It can get to 6th, 7th, 8th, and now 9th generation airways. As the catheters become smaller, their reach to the periphery becomes better and greater. Better technology cleared in 2019, commercially available. A smaller catheter size. It has almost a caterpillar-like dexterity to allow to make sharp angles and turns, especially in the upper lobe and the superior segments. The latest technology was just approved and FDA cleared in March of 2023, and it actually incorporates with a C-arm integration of tomosynthesis as well as augmented fluoroscopy that can help you autocorrect if your mapping is not felt successful with your prior mapping that you've used to navigate to the lesion. I think there's a lot of earlier experiences. Now there's more multicenter experiences that have enhanced the diagnostic yield using the robotic bronchoscope, even as high as 81% if you have concentric view with the EBUS. I'll show you a few examples of those in a moment. I think this is just an example of different things that you can utilize. Think of tomosynthesis where you're actually getting multiple slices that reconfigure a volumetric 3D imagery to allow you to be more enhanced in terms of beyond far, far beyond a 2D image itself. And then augmented fluoroscopy allows you to see tool in lesion. That can be done with a CO spin CT scan. I'll talk a little bit about cone beam. It's quite expensive, sometimes not feasible at most institutions to have all these platforms. But I'm also going to take us back a little bit. I'm just highlighting these for pictorial examples of augmented fluoroscopy in real time with a C-arm fluoro to get to a smaller nodule. This is the, there's actually portable COCT cone beam that can actually be ported to your bronchoscopy suite and that can allow you to in real time see tool in lesion, which I think is a common theme for success, but not foolproof. I think this is a nice example of different nodules and how augmentation with a peripheral ultrasound is helpful. This is actually using an ultrathin bronchoscope. So an ultrathin bronchoscope coupled with a peripheral nodule using an ultrasound guidance to confirm that you are seeing the lesion that you're targeting can be very telling in terms of making a diagnosis. This is actually one of the newer tools, again, cleared by FDA, becoming commercially available this year. This is called the iNod. It basically is a tool that has an ultrasound probe connected to it. So your needle and your ultrasound in real time, you're visualizing your needle going in through the nodule with this, at the time you have driven to the lesion, you're actually sampling and can see all of it and making sure that your depth is appropriate. And that can be also helpful. More studies need to be done to see how it compares to other platforms. This highlights a number of different platforms. I've mentioned electronavigation, some of it's coupled with robots, some without. Virtual bronchoscopy, ultrasound, radial probe, a combination of all the above. And looking at the different tools, oftentimes the look, the decision to make, you know, what type of biopsies do I make once I get there and see that visual image that I'm there? Well, a couple of things. So far, the tBNA transbronchial needle aspirate seems to have the highest yield in all comers. Now there's also the concept of tracheal transbronchial biopsy forcep, cryobiopsy with a stamp cytology to look at quality of sample in real time with on-site. Different approaches to biopsy, I think more and more data is being published looking at the center target, the periphery, obviously not missing the lesion, but by getting there and having a view in real time confirms that you are in the lesion and that you increased your likelihood of diagnostic yield. So tool and lesion, this is just an example of a number of studies published looking at if you could get your tool in the lesion, does it equate to the same yield? The answer is no, but it's certainly far better than the less than two centimeter nodule with plain white light bronchoscopy and fluoroscopy, which was quoted at 20 percent or 30 percent or less. But this is now getting diagnostic yields across the platforms of 70 to 90 percent. And remember, CT-guided transthoracic needle aspirate is not 100 percent yield either. This is just a quick look at cryobiopsy. One thing that's evolved and more literature will be coming out more in case series but hopefully in multi-centers is using the 1.1 millimeter, the newer cryoprobe. It can actually traverse through the catheters of the robotic or even a standard ultra-thin bronchoscope and allow for a larger tissue sample and maintain the integrity of the tissue without getting crushed artifact. I want to kind of in the next few minutes just define what diagnostic yield is defined by in the literature. There's a high variability. The strictest sense of diagnostic yield is either you diagnose malignancy or you have a specific benign diagnosis. An intermediate characterization of diagnostic yield is either malignancy specific or nonspecific diagnosis with negative follow-up after one to two year minimum. And a more liberal diagnosis or diagnostic yield qualifier is either malignancy or no malignancy and no evidence of malignancy and follow-up. So it's important to say buyer beware when we look at the diagnostic yields in the published literature except that on average across all platforms in meta-analysis it's about 70 percent. This is actually looking at when we define alternative approaches to diagnostic yield calculations and studies on bronchoscopic technologies. The stricter the definition as I mentioned, the lower the yield, 66 percent. The more liberal the definition, up to 88 percent. So there can be high variability when you look at that, which is important. This is just where we've come from. In 2012, Wang and others did a meta-analysis on all the different platforms that existed looking at less than two centimeter and greater than two centimeter lesions, and you can see the difference here. Now take us up 10 years later, and across the platforms, all of which I've mentioned, the diagnostic yield on average can be anywhere from 50 to 77 percent, but it strikes more of an average in the 70 percent range. So I think that other studies are coming out, multi-center perspective looking at diagnostic yield, but again, cautiously look at the literature in terms of what diagnostic yield is defined as. This highlights some of the practical points of the variety of the platforms, where ultimately based on the different, whether it be a thin scope with a radial probe E-Bus, whether it be a virtual bronchoscopic platform, the other three, robotics, there's variations, and all of them probably benefit from some type of augmented real-time imaging, whether it be augmented fluoroscopy, tomosynthesis in real-time, or cone beam, or portable CT scan. I think this is an interesting study, it says, comparing shape-sensing robotic versus digital tomosynthesis and electromagnetic bronchoscopy in a single center, looking at their first six months of using those two tools, and ultimately, they perform very similarly, and here, it actually highlighted that the electromagnetic navigation performed slightly better, but not statistically different, they were comparable. Cone beam enhances, kind of in the interest of time, I'll highlight this, the thing that cone beam, when compared to primary electromagnetic navigation, they both augmented each other, but cone beam enhanced the electromagnetic visualization confirmation more so, but they both kind of needed each other, if you will. To wrap up here, I'll just wrap up with these comments, that there's numerous platforms, we've come a long way over the last two decades, and more recently, acceleration of the robotic platforms over the last five years, and I think there's more to follow in terms of, can we reproduce this across many centers across the globe, and how does that lead us down to a pathway where we can be ablative, minimally invasive ablation, after making a diagnosis, potentially staging, and confirming the accuracy is kind of key. I think the take-home here also is that augmented imaging is necessary to really maximize any of the technological tools, and having some real-time auto-correction, when you are not quite where you thought you were, in terms of the pre-planned procedure. And with that, I'll stop. Okay, so, straight to the chase. Indications for CT-guided lung biopsies, any masses with suspicious features, for example, speculated margins, FDG avid lesions on PET CT, patients of high risk of malignancy, multiple nodules of unknown etiology, persistent focal infiltrates of unknown etiology, sub-solid lesions which are persistent, these would be pure GGOs which are persistent or increase in size on follow-up six to 12 months later. In general, we biopsy anything larger than 1 to 1.5 centimeters. Semi-solid GGOs, which has a higher index of suspicion on follow-up, three to six months, size threshold that we use in my center would be five to eight millimeters in diameter. Note that for the smaller lesions, especially the semi-solid GGOs, surgical resection biopsies may be considered, usually with the help of what we term radiological tattooing. And I'll go into a little bit of that towards the end of the lecture. Contraindications, obviously, if the patient doesn't give consent, there's no, we're not going anywhere. This is the main contraindication to any percutaneous lung biopsy, lack of a safe path to the lesion. And of course, we'll determine this by examining in great detail the pre-procedure CT scan. Relative contraindications, which can be corrected, coagulopathy, poor pulmonary reserve, patients who are hemodynamically unstable. Of course, if patients are pregnant, we try to do it after pregnancy, or we'll have to do adequate shielding during the procedure, and lack of cooperation from patients. We may find some patients demented or restless, and we may require the help of one of our anesthetic colleagues to sedate the patient. The speaker before me spoke extensively on endoscopic biopsies, and especially with robotic and AI assistance, I think we'll see more endoscopic biopsies taking over from the percutaneous lung biopsies. And of course, the surgical biopsy, plus or minus with pre-surgical radiological tattooing. Okay, preparation before biopsy, we need a good coagulation profile, PT, PTT, and to ensure that there's no thrombocytopenia, anything above 50,000 platelets is fine with me. Blood thinness, aspirin should be discontinued three days before, Plavix five days before. The new order anticoagulants, two to three days before. Okay, and what does the radiologist look for in a pre-biopsy review of the CT? Of course, the location of the lesion, and how we're going to position the patient. Supine, decubitus, prone, oblique, choose a safe needle path in. Obviously, avoid crossing major vessels. For example, you can see blood vessels here and here, and that's the tumor. So try to avoid crossing the blood vessels and get the needle nicely into the tumor without crossing them. Avoid crossing fissures, if possible, because the principle is we try to cross as few layers of pleura to get to the nodule. And as you know, in the pleura, they overlap, in the fissure, they're overlapping pleural layers, so that increases the risk of a pneumothorax. Pet CT review, if possible, if the patient has a pet CT, have a look at it, because just because you've got a great big lesion doesn't mean that you're going to get a good yield from the entire lesion. Take for example this huge lesion here, portion in the center which is photopenic. If your needle happens to go towards there, you're not going to get a good yield. This other patient here, there's a big elephant in the room here with this mass here, but it's completely non-FDG-AVID, and sure enough, there's no diagnostic yield from this, and we got the diagnostic yield from the FDG-AVID lesions. Technique for CT biopsies. We do a pre-procedure planning CT with the patient in the appropriate position, and based on the correlation with the prior CT, we decide on the path again. We may or may not require intravenous contrast to delineate the vessels, and I'll show you an example of why we may need to delineate vessels. All our procedures are done under CT fluoroscopy, and this is the greatest invention for an interventional radiologist since sliced bread. I started doing biopsies when we did everything under AP and lateral fluoroscopy screening. So from that to graduate onto real time CT fluoroscopy is amazing. We can get to never thought of before lesions. Everything is done under local anesthesia. Very, very rarely do we require the help of an anesthetist to come in and sedate the patient. Everything is done under quiet respiration. I prefer to let the patient breathe quietly while I advance the needle to the nodule and time my needle movement with the patient's breathing because the worst thing is to tell the patient to hold your breath and he goes, and the nodule moves by about five centimeters away from you, and after that, he becomes very conscious of the way he breathes and it's impossible to get the nodule. Okay, so quiet respiration, advance the needle. You can usually time your movement quite nicely with his quiet respiration. Now this one, this one plucked the track prior to removing the needle to reduce the risk of pneumothorax. I personally do this routinely because I use a coaxial needle system to do biopsies. So there's usually some blood inside the coaxial system. You can push through that little blood clot as you withdraw the needle and that helps to reduce the risk of pneumothorax. Some will actually go so far as to inject some saline into the system, into the needle before removing it. So this is my usual setup, CT fluoroscopy with the reference images here, PET CT, planning CT, and the real-time images will appear here. So this is a typical lung biopsy. This nodule here, note the big vessel. Needle, coaxial needle inserted. Through that, a smaller needle is inserted and you can do multiple course through a single needle puncture. Of course, always make sure that before you fire off the biopsy needle that the vessel hasn't crossed, hasn't been crossed. You can see this here. Again, we've avoided the large vessel, avoided this other vessel here. Small hematoma, which is not unexpected. We can do multiple passes and with minimal pulmonary hemorrhage. This is an example of a tumor in the hilum, very hot on PET. I had to give IV contrast for this very reason so that I could see where the hilar vessels were so that the needle does not go into any of the major hilar vessels. And biopsy needle inserted, can do multiple course safely. Another hilar lesion, patient's place prone. You can see the lesion here, bronchus here. Huge blood vessel here, so I think an endoscopic biopsy may have been a little bit dangerous because I have to cross this big blood vessel to get into the tumor. This was a very safe path in, relatively avascular parenchyma as the needle track, for the needle track into the tumor. And you can see that the needle is placed parallel to the vessel so that the risk of pranging the vessel is minimal. Of course, the patient got a small pneumothorax but this was inconsequential. What do I use? I think this is the gold standard nowadays for most radiologists. It's a coaxial needle, 19-gauge hollow needle with a sharp trocha, puncture into the tumor. Remove the trocha, put in a coaxial 20-gauge semi-automatic core biopsy needle to do multiple passes. So with one needle puncture, you can take multiple course, especially for histology and molecular typing. Now my personal preference is after I remove the core needle, I put in a skinny 22-gauge Chiba needle through the trocha and I aspirate for cytology and washings if you need it for cultures. If you have this in your center, this is very, very important. It's a rapid screen of the slides. What I do with the cores is I do a roll or imprint slide of the core onto the slide, send it off to the lab for a stat reporting of the air-dried slides. I'm very privileged that I have the pathologist just next door to radiology. So I get a pathologist reading the air-dried slides immediately and we get a stat provisional report. If you can't have a pathologist on site, next best scenario is to have a cytotec on site to tell you whether you're lesional or not because for us, the worst thing is to send the patient back, the biopsy results come back two to three weeks later and they say it's negative, please try again and you have to explain to the patient and the relatives that you have to go through the whole process once again. Adequacy, now this is the million dollar question, isn't it? How much is enough? This paper actually says that 20-gauge cores are large enough and that's essentially what I've been doing for the last actually 20 years. I've been using 20-gauge cores. How many specimens? Now I know with molecular typing and all the biochemical markers and gene mutations, people, especially the oncologists, have been asking us to do more and more cores but we know actually that more than six cores does not increase the yield. The reason being is that you find that a lot of times you're going to end up just biopsying the hematoma around the needle track. So the sweet spot's between two to four cores. I personally do four and I think most of my oncologists and pulmonologists are quite happy with the yield that we get. Complications, procedure is considered a low risk. Mortality rate is less than 0.05%. Now the pneumothorax rate is up to 30% so we do have to counsel them for that but of which only about five to 10% will require a chest tube. Of course, hemoptysis usually is self-limiting but sometimes it can be grade three or higher. Embolism is extremely rare, something like 0.06% and of course, track seeding. In a Japanese paper in 2006 of 10,000 lung biopsies, the track seeding rate was quoted as 0.06%. What I do with the biopsies which have a significant pneumothorax, simple eight French pigtail catheter inserted under CT floral guidance. The pneumothorax is aspirated and is connected to this wonderful device which the next speaker introduced to me. It's a SINAPI device which is a Heimlich valve with a little 50 mil reservoir. This is wonderful because the patients don't have to be connected to the great big underwater seal. They can actually move around the ward very easily with this little device and we're quite comfortable actually sending the patients home at the end of the day and they can come back to the clinic for removal one or two days later. What's radiological tattooing? I don't know whether this is a recognized term but this is what we use in my department. These are for small lesions which I think I can't get a good yield. Usually referred to by the thoracic surgeons and the next speaker is one of the thoracic surgeons whom I work very closely with. The patients come into my department half an hour before surgery. Under CT floroscopic guidance, a 22 gauge Chiba needle is inserted right onto the surface of the tumor and methylene blue is injected. Now we explored different means of localizing and tattooing these tiny nodules including putting in a hook wire or injecting fluorescent dye but we found that good old methylene blue is still the best. Now don't inject too much if not everything is gonna turn blue and you'll be amazed how much 0.2 cc can turn blue. Okay but essentially 0.2 cc of methylene blue onto the tumor, 0.1 to 0.2 cc as you withdraw the needle to the pleural surface. Very important before you start anything, local anesthesia right down onto the pleural surface because methylene blue hurts like hell when it irritates the pleural and the patients do not appreciate that. Okay so this is a typical example of a small nodule. Needle right down onto the pleural surface, inject local anesthetic right down. You can see a little bump raised by the LA there and then the needle is inserted and methylene blue is injected. Okay what about biopsy and local ablation? There are a few cases that we do where we biopsy and immediately ablate the lesions. We can do that as long as the patients understand that there is a possibility that it may be a benign yield or an inconclusive yield but usually for high risk tumors because of family history or because of the appearance of the tumor, sometimes we will biopsy and ablate immediately. Having a pathologist on site works wonders to making sure that we do indeed ablate malignant tumors. Okay and what do we do? My ablation method of choice is cryoablation. So during the procedure, a biopsy needle is inserted into the tumor. A cryoprobe is inserted immediately next to it and you activate the stick function so that the tumor sticks to the cryoprobe because once you start doing the biopsy, you may develop a pneumothorax and the tumor may fall away and it will be very difficult for you to get your cryoprobe in. So biopsy needle, cryoprobe inserted, stick function and you can see actually it was a good thing we did it like that because the patient had a pneumothorax and for anyone who's tried to chase a small tumor in the setting of a pneumothorax, you know that it just keeps moving further and further away from your needle. This is another example of a very suspicious semisolid GGO. Biopsy needle is inserted, cryo needle is inserted above and below to stick and you can do the biopsy and ablate immediately after. And that's my last slide. Thank you very much. In conclusion, CT lung biopsies are safe. We can get a good yield. I think what's most important is an extremely close relationship with your pulmonologist, your oncologist and your thoracic surgeon and I think all working together will get very good outcome for our patients. Thank you. Thank you Chairman and I'd like to thank all of you. Thank the organizing committee and Professor Lee Peng for giving me the privilege of giving this talk. I'm a thoracic surgeon so I was asked to talk on multiple pulmonary nodules. So one of the main downsides to lung cancer screening is that up to 50% of lung nodules detected are multiple and though there are many causes for multiple lung nodules, multiple primary lung cancers or GGOs will be the focus of my talk today. So as I said, one of the main downsides to lung cancer screening is that up to 50% of lung nodules detected are multiple. Though there are many causes for multiple lung nodules, GGOs are multiple primary lung cancers. So the incidence of GGOs detected on routine lung screening is about eight to 30% of which up to 30% are multiple and 30% of surgically resected GGOs have other associated GGOs. So as we all know that lung cancer undergoes adenoma to cancer to invasive adenocarcinoma in a linear progression sequence and this is reflected radiologically as pure GGO to semi-solid GGO and then solid nodule. So if you look at benign GGOs, benign GGOs radiologically tend to be transient and disappear within six months. They tend to be polygonal with ill-defined margins and with no solid component. Malignant GGOs tend to be well-defined, have round margins with radial growth and may have solid components and can persist for more than six months. So but are all multiple GGOs early, multiple GGOs early primary cancers? No. So this is a patient with left upper lobectomy which I did for stage 3 CA lung in 2019 and in 2023, she presented multiple semi-solid GGOs and when we biopsied, it's actually a metastatic GGO from metastatic nodules from the previous lung cancer and this was proven on biopsy and NGS mutation study. So what is the natural history of multiple malignant GGOs? Majority of the GGOs have no change in size and remain stable for more than 10 years. 5% can disappear or regress spontaneously. Only 10% of all GGOs below one centimeter progress and up to a quarter of semi-solid GGOs can increase in size over 36 months. So this is a 60-year-old Chinese female with more than 16 multiple bilateral GGOs since 2019. All the GGOs have remained stable in size to date except the left upper lobe dominant GGO which has increased in size and also solid components since October 2022. So the question is why do some GGOs progress and some don't? And to understand this, we have to go back to the biology of lung cancers. So if we look at the biology of lung cancer, the commoner cell or the adenocarcinoma which undergo adenoma to invasive cancer cells usually arise from the type two alveolar cells and the stem cells from the terminal respiratory unit. The terminal respiratory unit is the unit which is most distal to the airway. And how does, so terminal respiratory unit undergoes mutation in two ways. One is by the EGFR mutation. So if you have developed EGFR mutation, it goes to AH, EIS, MIA and become invasive adenocarcinoma. The second pathway is the KRAS mutation. So when they develop KRAS mutation, patient goes to AH, but they must develop EGFR mutation before they can proceed to EIS, MIA and invasive adenocarcinoma. If they do not develop EGFR mutation, the nodule remains stable or they can regress. So KRAS not only does it cause mutation, but it can also cause cell senescence or cell death. And non-TRU cells can undergo, especially the papillary and the mucinous adenocarcinoma, they can actually go become invasive adenocarcinoma by the de novo pathway. Therefore, why do many GGOs remain stable for long periods without progression? This is because most are adenomas and maintain their size for long periods due to KRAS induced cellular death. Only 10% of KRAS mutated adenoma cells progresses to invasive tumors. In the early stages, tumor progression is the balance between KRAS induced cell division and cell death. Once the tumor acquires the driver mutation, it overcomes the barrier of cell death and becomes invasive. So what's the prognosis of multiple GGOs? As most GGOs are adenomas and remain stable with some undergoing regression, the overall risk of progression to invasive cancer is low. The main prognostic factors are size of the domino lesion and the degree of solid component in the GGOs. 30% of multiple GGOs progress and do so in the first three years, especially the semisolid ones and those which are more than one centimeter. And this is the group which you should be closely monitored. So if you look at the natural history and the biology of most lung cancer, especially most resectable early stage one lung cancers, they are radiologically early by biologically late cancers in their natural history and half-life. Most of them harbor adverse prognostic factors like visceral plural invasion, lymphovascular invasion, spread through aspergers, micro papillary features, and mucinous features. All these features are high risk for systemic metastasis, which is the reason why there's a current drive to have adjuvant and new adjuvant treatment for this group of patients so that you can increase survival. However, these GGOs which we are talking about, they are biologically a different set of cancers because their survival is totally different from what I've addressed to you before. And the reason why they have such a good prognosis is most of them are in C2 regions and are biologically early and localized. They do not have spread through aspergers, they don't have intralobal lymphatic metastasis, and they don't have lymphovascular or visceral plural invasion which makes them very amenable to lesser resections, lung-preserving resections like wedge resection and segmentectomy without a compromise in their survival. But is surgery the ideal treatment for many of these early small lung cancers? So to understand this, to answer this question, you have to look at what is the precedence or standard treatment for other pre-invasive or in-situ cancers in other organs like the stomach, the esophagus, and the cervix. If you look at this group, their early lesions are all treated with local endoscopic ablation or excision therapy with excellent cure rates and organ functional preservation with low morbidity and mortality and reserving salvage surgery for recurrences. And surgery many times can be overkill for these biologically small early lung cancers because segmentectomy can be technically a very difficult surgery compared to lobectomy due to the complex anatomy and the variation of the segmental anatomy, giving rise to loss of lung function and also higher morbidity and mortality. And the cost of doing a segmentectomy is much more expensive than doing a lobectomy because of the use of newer technologies to localize the nodule and the intersegmental plane. And the other thing is there's always this belief that segmentectomy preserves lung function, but more and more studies are showing that the benefit which you get from segmentectomy, the touted lung preservation, is not as what it has been touted to be if you look at the real-world experience. This is because the post-operative lung volume after segmentectomy and lobectomy is almost the same because the lung expansion after lung lobectomy is much, much higher, so there's no functional advantage of segmentectomy was observed during long-term follow-up, possibly due to the compensatory lung growth after lobectomy. So is there also a role for local ablation therapy for pre-invasive early small lung cancers? So if you look at the types of lung ablation therapy, there's radiofrequency, there's cryoablation, there's microwave, and you also have the non-invasive stereotactic ablational radiotherapy, which is also a form of ablation therapy. So invasive ablation therapy can be done by CT-guided or by bronchoscopy. And the main attraction of invasive lung ablation therapy for lung GGOs is because it's minimally invasive. You can do a tissue diagnosis, you can use an eBas to stage the mediastinum, and you can ablate at the same time, and you can ablate up to four GGOs at any one time, and you can always repeat the ablation at frequent intervals with low morbidity and mortality, and all this can be done in one session. But how good is ablational therapy for pure and semi-solid GGOs? And all studies to date, these are all the major studies which has been done, and they all show that there's similar efficacy with all techniques with overall survival and cancer-specific survival rates with almost 95 to 100 percent at five-year survival. Is SBRT suitable for GGOs? They're not ideal for pure GGOs, and they're better for semi-solid GGOs because if you have pure GGOs, there's difficulty in real-time image guidance during treatment because there's lack of solid component, so there's a risk of underdosing the target volume by more than 20 percent. So it's more suitable for semi-solid GGOs. But unfortunately, because it's not an invasive procedure, there's no tissue diagnosis, and it's a one-time use because it cannot be repeated again. So what are the factors determining treatment choice in multiple GGOs? One is the age and function of the patient, lung function of the patient. Two is the number and size of GGOs. Three is the biology of the GGOs, which indicates the growth rate and the solid component of GGOs. And of course, one of the more important things is the site, whether it's peripheral or deep location. So based on these factors, treatment is often a combination hybrid therapy of surgery and or ablational therapy. For solitary GGO, it should be ablational or vaginal resection if peripheral, and segmentectomy if it's deep or solid. Ablational therapy should be done for new solitary GGOs appearing after the first surgery. For multiple GGOs, ablation should always be tried, so as far as possible, to preserve lung function. And segmentectomy should be reserved for GGOs which are central, centrally located, solid, and near critical mediastinal structures. SBRT is an option when surgery or ablational therapy is not feasible. So this is a 79-year-old lady who is now 79, but in 2015, she had right upper lobe adenocarcinoma and multiple GGOs. I did an upper lobectomy for her. Then in 2017, she developed the right lower lobe GGO was increasing in size, so I did a right switch resection. And unfortunately, in 2019, she had multiple GGOs were increasing in size bilaterally, which was ablated by cryoablation. I think with that, I'll end my talk. Thank you for your attention. Now, thank you for presenting the slides. It all worked. It's now synchronic. Thank you for the introduction. Yeah, the Fernalurin trial is designed as an implementation trial, so we regard more or less the mortality reduction proven after the Nelson results. And we think we can do a lot better by optimizing certain parameters that we now control better than we did in the Nelson study. The Nelson study, as you probably know, was completely volumetric based, and now we really want to implement the volumetry and more standardize it and also implement AI on this. Furthermore, we want to answer a very important question if we can stretch the intervals for certain categories on baseline results. And last but not least, we also want to introduce the co-morbidities. Now, normally, incidental findings like calcium and also like emphysema are regarded as incidental findings, but we go to an other definition and, in the meantime, I try to... Yeah, it works. In the meantime, we try to also implement those two new parameters, so that is the calcium score and the emphysema score as also introduced as a result of the smoking of this population that we are screening. Now, we have to mention that the study is funded, the Fernalurin study is funded by the EU Horizon 2020 grant, and, of course, we have in between the corona period in which, anyway, in the Netherlands, the research funding, the research, clinical research was really hampered, but we could start immediately after the corona stopped. So we started last year, and, in the meantime, we could build up the whole infrastructure needed to implement 26,000 participants in five European countries, the Netherlands, Germany, France, Italy, Spain, and the U.K. And we, as I said before, we want to develop and implement the most optimal and personalized CT lung cancer screening methodology schedule and program for high-risk individuals. And furthermore, so we do not call it incidental findings anymore, we also want to detect cardiovascular disease, so the calcium score, and the emphysema score is still under development and it's real research while we are building on the Robinska outcome studies, and now we, as I will show you, we will also communicate the calcium score with after referral. So we started the recruitment, and that was a very successful recruitment. So the countries all have a different way of recruiting, so we use the population registry with standard paper, yeah, that is something that our health council demands, also standard line, and standard tailored. So the inclusion criteria were a little bit different than the Nelson, so we had the higher age group, 60 to 78, and the PAC years more than 35 PAC years. We included current smokers or smokers that stopped less than 10 years. Now here you can see the different things we published on the website, so information per topic, decision and supporting informed decision making, infographic animation videos and contact from a call center is all in place at the moment, so that really needs a lot of preparation. Now the successful recruitment, we had 43 former smokers could we select from this inquiry that we sent to 420,000 people, so that is quite a lot response, and we could also reach the lower social economic status, so that is hard to reach is a very important topic, and we really reached the hard to reach population with low social economic status. About 40 to 50% were eligible, and we had also internet users, and okay. Now furthermore we implemented an end to end solution in which all the data come together, and I think this extremely important to monitor your screening, and also have the information to change the policy if needed, and also have those reports every month, quality reports, knowing if your systems are working well. Now here you can see the complete list of data that are going into the system, and are used to manage program, automatically plan the next screening rounds, and also yeah, invitation letters, everything that is needed in such a program comes together in this system. So that's I think key for further research, and also for further analysis of the data. Furthermore we developed with, we are using dual source systems, because we want to also have the optimal performance for the other comorbidity parameters, like the calcium score and emphysema score, and we do this in one single scan, and with a very low dose protocol, so 0.7 to 1.5 millisievert, when you are yeah, very corpulent, then you come to 1.5 millisievert. We have a high temporal resolution, pitch of 3.0, and we use of course a fixed field of view, and a quantitative recons. The logistics end up to 8 to 9 participants per hour, and by using we proved that in other studies that we published, we do not need an ECG triggering. So if you want to do it without, with monosphere systems, to get a reliable calcium score, you need ECG triggering. Then of course we have the dose reports, and also all the other data that are in the DICOM header are available. Now this is important for the workup. You see here the nodule management protocol at the left. I will not go into this in detail. It's a little bit different, but not that different from, for example, LungRats, for the volumetric part of LungRats. Both use this 6 millimeter or 5.8 millimeter and 100 cube millimeter as the lower volume of the, the lowest volume of an assiness, and yeah I think this new threshold that has been developed in the Nelson study is I think a very good way to go, and that's what we also implement in this foreign lung study. Now the clinical management is, so we have three categories, a negative outcome of course, an indeterminate outcome, and then we do a three months follow-up, and a positive outcome then referred to the specialist. Then we work up, so we have also an AI implementation. We do a first read that is done by an experienced radiologist, and that is an independent read. Then we do a second read by the AI, also completely independent. So the first read is done without AI, and then if there are discrepancies between both, we do a third read with an expert panel. Now you see a very simple example here. So this has been the first read, negative 1A. The second read by the AI was 3A. There was a nodule of 134 cubic millimeters, and the expert panel saw too much part of vessel of, yeah, that was also segmented by the AI, by which the nodule was lower than 102 millimeter. So then it rendered, it came out as a negative one. So that is how the whole process works. Then in this process, we have an agreement for nodule categorization up to almost 80 percent, so that's very high. That gives also an indication that AI and Marjolein Heuvelmans will address this, can really come to a workload reduction for the radiologist. We had arbitration cases, of course. Forty-five were classified in the same category as determined by the first radiologist. Thirty-four was determined as the AI read, so that is almost the same, and 21 were classified to another category, then proposed by both. Then the final categorization was 72 percent were negative, and determined at 23 percent, and I think a very good positive threshold is now overall, we know, lower than 4 percent. So that's, we have, of course, the Nelson results, and that is really near to what we also got in the Nelson study. Now this is the implementation of the calcium score. So you see we can analyze it by vessel. Here you get a very nice example of the LED. Very high calcium score in this case. We can define it also as a circumflex or a right coronary artery vessel, which probably that will come out of the study, of course, also have a lower mortality risk. Now the combination with the calcium score in this foreign deliverance study is very interesting because we can come to final result in terms of mortality, and we can also address easily now the comments of the health council that probably, as has been mentioned before this morning, that a lot of people will die earlier and get oral cell morbidity early from the cardiovascular complications of smoking than from the lung cancer itself. So we find here, and I think this is a distribution that you will find also in later results, a low risk, so that is more, it could be the heavy smoker, and it could also be that it is related to a very low chance of developing lung cancer, and at the end, that with zero score you can also exclude them for the rare group of lung cancer. So this is a very, very nice data. More than 20 percent. Then moderate risk up to 30 percent, then high risk between 100 and 400, about 20 percent, and then more than 400, so that's very high risk, and it's a large group, 31 percent. And they really are, yeah, treatment is needed in those cases with statins. Now at the moment we passed the 5,000, so we do at the moment 1,000 per month that will go up probably to 1,500 per month, and then by the end of next year we will have full inclusion of the 26,000 people. Now here you see on the dashboard, very nice, the 4A classification that is lower than 4 percent, and here the intermediates, and those are in between, so the discrepancy rate is about 25 percent, and the intermediates is a little bit lower classification. Now altogether, we think that a multi-angle strategy, so recruitment you do, you use all the means that you have more or less to say it in my words as a non-epidemiologist, and then, yeah, you probably get such nice results that we got in the Netherlands. If possible, you should use, in our view, population registries to get a real, yeah, equal distribution of invitation, which is, of course, a problem in Asian countries like China, where they as you saw also this morning, it's a lot of the lung cancer screening is related to the health checks that are done, and are paid by the companies that provide this health check, and that is, of course, a kind of selection of the population that is not really relevant for the targeted population that we are looking for. Then I think it is feasible to have an online monitoring of all key lung cancer screening parameters. The first prospective results show now that AI can be used as a second reader, and we will later address how it can be reached as a real workload reduction, yeah, reader. The arbitration rate is only needed in one out of five, so that is also a very nice aspect. We have less than 4 percent of participants following a single baseline CT scan that have to be referred. And thanks to the whole group, which is, of course, larger and getting larger and larger, so this is the core group. Those are the members of Foreign Deliverance, but we are getting more and more partners, too. Thank you. Okay. So it is very exciting for me to be here today. Thanks to the organizers. Thanks to all the other speakers. This has been a great session, and I am very excited to be able to share with you some very preliminary results from our Watch the Spot trial. And we'll see if we can get the slides to advance. Okay. So as some of you may know, Watch the Spot is a large, pragmatic, comparative effectiveness trial. We use cluster randomization by hospital or health system to enroll patients with small pulmonary nodules measuring up to 15 millimeters in diameter in typical clinical practice settings and diverse healthcare settings throughout the United States. Ultimately, we enrolled 34,701 individuals with small lung nodules, and the intervention in the study was to compare more versus less intensive recommendations for lung nodule management. The study was powered using a noninferiority design to test the hypothesis that less intensive management would not result in more small cancerous nodules that progressed beyond stage T1B disease, which is to say a small tumor that progresses beyond 20 millimeters in diameter. We looked at TNM stage distribution as an alternative primary outcome. We're also looking at survival in time to diagnosis as additional cancer related outcomes. We also have now published our baseline results looking at patient reported outcomes of nodule related anxiety and emotional distress, and we have forthcoming papers that look at things like radiation exposure, and importantly, adherence with recommended surveillance. These are the settings of the trial, 14 diverse, large healthcare systems throughout the United States that varied by location, type of setting, including hospitals and community settings, university settings, and tertiary referral settings. I should mention that we enrolled patients with both screening-detected and incidentally-detected lung nodules. More on that in a minute. Our protocols for follow-up for patients with incidentally-detected nodules reflected a comparison between the current Fleishner Society recommendations, published in 2017, and the original Fleishner recommendations, which, as you probably know, were somewhat more intensive or aggressive than the current recommendations. For participants with screening-detected nodules, our less-intensive strategy was modeled on the Lung RADS version 1.0 protocol, and we compared that with something that I'll call a supercharged version of Lung RADS, where essentially we stage-shifted patients, so to speak, such that a participant with a Lung RADS 2 finding would get Lung RADS 3 recommended management. Someone with a Lung RADS 3 finding would get 4A management, and so on. And by doing this, we're able to ask a very targeted, specific research question, which stated in plain English is, are current recommendations from both Fleishner and Lung RADS, are current recommendations for lung nodule evaluation sufficiently aggressive? So this is a very, very busy, complicated consort diagram that reflects the pragmatic design of the trial. And overall, the pragmatic design reflects the fact that we embedded trial procedures into existing clinical practice to the greatest extent possible, and tried to do this study such that it would be generalizable to settings, diverse settings, not only in the U.S., but internationally as well. And so we allowed sites to use methods for identifying, assessing for eligibility, and enrolling participants that were most consistent with workflow in their institutions. And so, again, the consort diagram's a little messy. The essential features are that over the 28 months of enrollment at these 14 different healthcare systems, there were 3 quarters of a million patients who underwent chest CT scanning. And depending on the location, a small nodule measuring up to 15 millimeters was identified in 8 to 15% of those patients. About half of them were ultimately excluded. The most common reasons for exclusion were a prior lung cancer or extra thoracic cancer, or the nodule was old and found on a prior study. Importantly, we used automated technology-enabled methods primarily to identify patients, and then they were enrolled in the trial passively, and at most sites given a chance to opt out from having their data used. And only 4% of patients exercised that opt-out provision. So at the end of the day, we, again, enrolled over 34,000, almost 35,000 participants, about 17,000 in the more intensive arm, and 18,000 in the less intensive arm. Again, with an imbalance there related to the cluster randomization. We were randomizing by site as opposed to by participant. So any given patient who's enrolled at a certain site is gonna get the same management recommendations, but they may differ from recommendations at another site. So here I have several busy tables to share with you, and I'll take you through this quickly. So if you turn your attention to the far right column, you could see that in general, we enrolled an older population, not surprisingly with a mean age of 65 years. About half of the participants were women. We had terrific diversity with 18% of patients being of Hispanic ethnicity, 26% being of non-white race. 35% of our participants were never smokers. And almost a quarter of the patients had multiple comorbidities with three or more Charleston comorbidities. The most common comorbid conditions, not surprisingly, were COPD, diabetes, and peripheral vascular disease. And in general, the comorbidity profiles were balanced between the two groups, although there were some imbalances, some residual imbalances resulting from cluster randomization in terms of ethnicity and particularly race. If we look at the characteristics of the scans, who ordered them, and then the nodules, 75% of all scans were ordered by either a primary care physician or a pulmonologist. 70% of the nodules were detected incidentally. 30% were detected by screening. Not surprisingly, the radiation doses for the incidentally detected nodules were much higher and much more variable than the radiation doses in the screening detected patients. Almost 40% of nodules were in the upper lobe. There was a slight preponderance for nodules in the right lung as opposed to the left. 50% of nodules were solid in attenuation. About 14% were non-solid, either part solid or pure grand glass. And importantly, in over a third of the cases, in these usual typical practice settings, including university settings and other tertiary referral settings, attenuation was not specified by the interpreting radiologist. And it gets even worse if you look at other nodule characteristics like edge or border characteristics where 75% of the time the nodule characteristics were not mentioned by study radiologists. The nodule characteristics were pretty well balanced between study arms. There were some imbalances, some very important imbalances in terms of who was ordering the scans and the percent of scans detected by screening. The reasons for that we can talk about later because it's a long story that I don't have time for now. Here's the distribution of nodule size with a histogram showing that they largely overlap by study arm. You can see that the median nodule size is five millimeters. The mode is four millimeters. And that in general nodule size is a little bit larger in group B, which is the less intensive arm compared to group A. You'll also notice that again, these are all nodules that are reported by practicing radiologists. And 70% of them are six millimeters in diameter or less. 40% are four millimeters in diameter or less. So the overwhelming majority of these small nodules are actually very, very small. And about 30% of them are getting into the range where we consider them to be more interesting. Nodule distribution by study site was pretty consistent overall. So let's look at preliminary cancer outcomes. And this, I'm gonna stratify these data according to the mode of detection. So another busy table, this is for the incidentally detected nodules. There were 27,600 of them. I'll show you the screening detected nodules next. This is not by study arm. We don't have those data yet. And Dr. Arenberg, who's the chair of my DSMB wouldn't let me present them yet anyway. So I'm gonna blame Doug. So interesting findings here. So not surprisingly, I already told you that most of the nodules are smaller nodules. And not surprisingly, the frequency of cancer is much lower in the smaller nodules than it is in the larger nodules. Overall, 1.6% of these patients with incidentally detected nodules including 35% of them or more who were non-smokers had a cancerous nodule. Four per thousand in the under four or up to four millimeter group, 6.3% in the greater than eight to 15 millimeter group. One of the, well, I told you already that the primary outcome of the study is how many of these small cancerous nodules progress to a size that is greater than T1B. A size that's greater than 20 millimeters in diameter at the time of diagnosis. And you can see here that, and surprisingly to us, about a third of them progressed over the time of followup. Importantly, under conditions of less than perfect adherence. I don't have adherence data to share with you today. So you have to keep that caveat in mind. But suffice it to say, during some period of observation, one third of these patients progressed from a T1A or T1B tumor to a T1C tumor or greater. And we think that that's important. I'll also point out that it doesn't matter how big the nodule was at the time of detection. The frequency of progression was the same for the small ones as it was for the larger ones, at least as a percentage. So very similar findings for the screening-detected nodules of which there were almost 7,100. In this case, the frequency of lung cancer was higher. It was 2.7%. You remember for the incidentals, it was 1.6%. And again, we see, as expected, that the risk of cancer increases as you go from a lung RADS-2 to a 3 to a 4A. And then we have to truncate at 15 millimeters according to our study protocol. But the 15-millimeter tumors obviously had the highest frequency of lung cancer. And we see the same thing here, that 29% of these small cancers at the time of initial detection progressed to greater than 20 millimeters at the time of cancer diagnosis. And here, it's even more striking that the frequency of progression is even greater for the smaller nodules, the less than six, than it is for the 8 to 15. So what can we, you know, what inferences or conclusions can we make based on these preliminary data? So first of all, radiologists in usual clinical practice are finding a lot of small nodules of arguable significance. 40% of all nodules measured up to four millimeters, 70% measured up to eight millimeters. Important, crucial nodule characteristics like attenuation were not specified by the practicing radiologists in many cases. Lung cancer was diagnosed less frequently in patients with incidental nodules compared with the screening-detected nodules, not particularly surprising. And the frequency of cancer, again, has been reported widely, but primarily in screening settings. So here's an example of a large study of primarily incidental nodules where we see the frequency of cancer varying by nodule size, ranging from four per thousand to 6.3% in the incidentally-detected nodules. And tumor progression occurred in about 30% of all cases with a similar or greater frequency of progression in the smaller or the smallest of nodules. So to wrap up, we believe that the failure to specify nodule characteristics is an important target for quality improvement in chest radiology. The frequency of cancer progression is surprisingly high under current conditions of imperfect adherence. And then, just to be provocative, what does this mean for nodules, incidental nodules that measure up to six millimeters or up to four millimeters or wherever you wanna draw the threshold. So the frequency of cancer is low, but among those with cancerous nodules, the frequency of progression is relatively high. So among all people with small nodules, the frequency of progression is lower. And it raises the question, what's the appropriate threshold for follow-up? Where do you draw the line? And I know many of you have struggled with this question when you're designing protocols and formulating recommendations for Fleishner and LungRads. But I think this is very provocative and I hope these data will help to inform those conversations. I think lastly, if the probability of progression is independent of nodule shot size, does this mean that we should be using the same follow-up schedule for all actionable nodules that meet that threshold? And we can have a conversation about that during the discussion if you like. Thanks very much for your time. Thanks to my co-PIs and funding from PCORI. And that's all I got. Thank you for an excellent session. And I just wanna make a mission up front. I'm a respiratory physician or a pulmonologist or a respirologist, depending on which country you live in, and I don't have a robot. So I would like one, I would like some new tools, but I don't have one. And I'm gonna talk about things today about my thinking about the problem from the other end, nodules first, and then going into the diagnostic strategy. Now, it was really quite surprising, I think, Michael, your results with the incidental program. And we know that incidental nodule programs been published in the US have been nearly achieving very good results for patients and having higher resection rates. So whether we have a screening-detected nodule or an incidental nodule, it's clear that we have to pay attention to them and they do need surveillance. And what we really need to see with these nodules is progression over time. There's different approaches to nodule management, probabilistic, using something like the PanCan, risk score at the baseline scan, and others are more categorical, measuring volume, as in the Nelson study, they've shown that very well, or using axial measurements in lung rats. And there's no wrong approach, there's just different approaches. And what we've heard about today is an update in the four-in-the-lung run trial showing that they're now to fine-tune nodule management programs, which is so important for the future. One of the biggest costs to screening is the number of CT scans that we do. And how many should we do? Do we need to do so many? I think they're really important things that are being teased out. The probabilistic approach currently was the only one that screened people or managed to triage people to having a biannual scan rather than an annual scan. So I think we'll be seeing more of that out of the four-in-the-lung run study in the future with more confidence. But one thing we haven't talked about today is what is the decision to act? Because as a respiratory physician, I run a clinical nodule program as well as our screening program. And we get referred people from all over the place with incidental nodules and screen-detected nodules. And we have to then decide when do we act. Is it the high-risk lesion found in a screening program or in an incidental program? And what do we do at that point? It's generally assessing change over time. And it's a fairly simple thing. If you've got old scans or repeat scans, if something's clearly growing or changing, that's when we act. And that's when we need the new tools or we need to help diagnose these cancers. And they're very challenging. I think we've heard about some of these fantastic new approaches today with navigational and image-guided bronchoscopy. Now, I remember first using radial ultrasound back in 2005 and making my own guide sheet with Stephen in Vancouver and using the thicker probes and then getting some navigational software and the Kurimoto technique to help us navigate out to lesions. It's so much fun. I call it hunting for treasure in the bronchoscopy suite. And I look on with envy with some of my colleagues in the U.S. who've got some of the new systems. But, and I think they have a lot to add, but it was important, I think, Carly mentioned that the diagnosed yield overall currently is still only around 70%, which is kind of what it is for radial ultrasound in expert hands. So I think these new technologies are interesting. I particularly like the augmented imaging that can be used in the bronchoscopy suite to ensure that you've found the lesion, you confirm where you are with ultrasound and then to help you take the samples. I think that's really interesting. And I think, again, kind of basically going back to my comment I made earlier in the session today, we've got to focus on lesions less than 20 millimeters, not bigger lesions. I don't want to see data coming out for 30, 40 millimeter tumors. We need 15, 10s, you know, small lesions. That's what we, and we've got to improve our diagnostic yields, including the right terminology as raised by Michael and the team on the panel, using the right terminology to assess those yields. So I think the future is looking bright, more fun tools in the tool shed to play with. I'm very excited to see what happens. And I think we're at that point in time where we'll be getting a lot of work in many countries with screening programs being implemented. There's a lot of challenges ahead for us. We've got to work as a multidisciplinary team with our radiologist colleagues and as bronchoscopists and our surgeons to work together to work out, look at all the factors for each individual patient, how to diagnose that nodule. And it's very different from person to person. And that's the art that we have to bring into our science. Thank you.

diagnostic bronchoscopic platforms

peripheral pulmonary nodules

less invasive methods

accurate mediastinal staging

robotic bronchoscopy platforms

augmented imaging techniques

biopsy approaches

optimal tool-in-lesion placement

diagnostic yield

nodule management

small lung nodules

cancer progression