therapy for lung malignancies. I'm Calvin Ng and I'm Professor of Thoracic Surgery at the Chinese University of Hong Kong. I'll be your presentation moderator today. We'll start this activity with some brief housekeeping items. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education, ACCME. The International Association for the Study of Lung Cancer, ISLC, is accredited by the ACCME to provide continuing medical education for physicians. The International Association for the Study of Lung Cancer designates the live format for this education activity for maximum of 1.0 AMA, PRA, Category 1 credits. Physicians should only claim credit commensurate with the extent of their participation in the activity. All faculty planners and reviewers for the webinar today have disclosed their conflicts of interest. This information is provided on the following four slides. So I'll be our first presenter today and my topic will be bronchoscopic ablation therapy in Asia. So bronchoscopic ablation is a new form of therapy. It's a local therapy like any other ablation that's often pitched against wedge resection and SBRT. In the past, ablation has been done through a percutaneous route, most commonly, and it's associated with a lot of problase complications, including pneumothorax and fistula formation of up to 50%. Radiofrequency energy has been the energy of choice and often associated with small ablation zones and are often unpredictable. There's a lot less data with ablation, so many people would be discussing SBRT in the MDT meetings for non-surgical candidates, and ablation has not been so popular compared to radiation. But one must bear in mind that actually radiation also carries a risk of radiation pneumonitis and also pneumonia of up to 20%. More recently, there's a potential game changer, which is to do these ablations for the endobronchial route that may reduce probase complications, as previously described, and different energy sources like microwave that may cause a bigger ablation zone and may be more predictable. When you're looking at ablation and radiation therapy, there are lots of reviews and meta-analysis available. This one was from Yale University from four or five years ago, looking at patients with biopsy-proven non-small cell lung carcinoma, very well staged with imaging and invasive imaging as well, invasive staging as well. And they looked at 28,000 patients, comparing 1,000 to 27,000 SBRT patients. And regarding overall survival, thermal ablation was not inferior to SBRT for management of primary treatment of stage one non-small cell lung carcinoma. More recently, myself also involved in this meta-analysis, as well as our latest speaker, Mike, as well, looking at over 40 studies on ablation, thermal ablation versus 215 studies on radiation therapy, comparing 2,700 to 55,000. And again, similar finding that were no significant difference in outcomes between the two, and perhaps microwave is a little bit better than radiofrequency ablation. This is the one form of catheter that we use for our ablation. It's a two millimeter wide flexible catheter. You can see over a 10 minute ablation period of 100 watts, you create about four centimeter ablation zone through thermal energy. To do this kind of ablation, you need imaging through usually availability of cone beam CT, often in the form of a hybrid operating room, and you need a navigational platform, and also you need energy source that can be delivered through that bronchoscopic platform. The first stage is really to navigate to the lesion using the navigational platform to reach it accurately. And then it's about the placement of your energy source, in this case, the microwave catheter into the tumor using imaging guidance. And then you need to optimize the position of your catheter through imaging, especially cone beam CT or some form of CT scan, so that you can have it at the best position for your ablation, and then you would deliver the energy. After your energy has been delivered, you would perform the CT scan to show that you have indeed created the ablation zone that you so require, and it covers the tumor with a good margin. We're offering this form of treatment to primary lung cancer patients who are not suitable for surgery because of advanced age and also comorbidities or very poor lung function, or patients who are not suitable or decline SBRT. There are some patients who decline surgery really for personal reasons in our region. We're also offering this therapy to very highly select patients with ground glass opacities that are persistent or growing, who have often had a previous history of lung cancer that has been resected. So this patient had a left lung resection lobectomy already for lung cancer and has other GGOs that need to be treated. Treatment of metastasis by ablation is a lot of the guidelines and is one of the treatment targets that can be used for this bronchoscopic ablation. And also patients who've had radiation to the area before and who are not suitable for further radiation therapy. So patients who've had breast cancer, have some chest wall radiation, they may not be suitable to have further radiation in that area, in which case we can deliver thermal ablation. And we're seeing more and more complex patients who are at stage three or stage four lung cancer who've had a combination of chemo or targeted therapy, immunotherapy, who have controlled disease bar one or two nodules that are not responding as well or are kind of growing a little bit. But we can control this kind of local ablative therapy and in highly selected patients they may also benefit from this therapy. So our first bronchoscopic microablation was back in March 2019 and you can see that this preablation left upper lobe tumor has the catheter inside it and 10 minutes after the ablation on the right side with the ground glass change over the tumor with margins as well. Our first report really was back in a couple of years ago and back in 2021 of our first 30 cases reporting just safety and one month safety in a retrospective study and we looked at 30 nodules that were ablated with a moderate comorbidity index, mean size of around two centimeters up to three centimeters in size. There was no virtually no blood loss and the median hospital stay was one day. There was one patient who stayed for 16 days because of pneumothorax who needed a drain and also grew some bugs in the peripheral effusion that required two weeks of IV antibiotics. Some patients who have bigger tumors require what's called a double energy delivery or what we call double ablation in the same session with the catheter either pulled back in the same position or re-navigated to a different area. A couple of patients have what we call a hybrid approach to a nodule. We take the biopsy and we confirm it with on-site pathology and then do the ablation in the same session. Cases takes about two hours to do for this ablation and we have a margin of around six points a minimum margin of 6.6 millimeters in this early experience. So for bigger tumors in fact we sometimes need to navigate to two areas of the tumor. This sometimes is called a bracket ablation. You can see two pathways in our navigational platform that reaches the two ends of the tumor in order to deliver two packages of microwave energy that covers a more elongated or larger lesion. You can see on the right side far right the size of the tumor and here on slightly on the left the post ablation with the overlay of the tumor covering it relatively adequately. Our early experience shows that 80 odd percent of patients have no pain after procedure. There were two cases of pneumothorax representing six percent of our experience early experience and some patients have a low grade temperature and post ablation reaction accounting for six percent. One case of hemoptysis that was self-limiting post-operatively just need observation and then one infected diffusion that I described earlier on. We then took part in a prospective study with the London St. Bart's group Kelvin Lau's unit in recruiting 30 patients again in a prospective manner looking at the safety and for nodules less than three centimeters patients not suitable for surgery or SBRT. They should not be too close to the fissure or the pleura. They should be more than five millimeters from that. So these nodules all had biopsies two-thirds were primary lung one-third were metastases two-thirds were in the most peripheral aspect of the lung and one-third was in the mid zone of the lung. The median nodule size was a little bit smaller than our initial experience. It's around 12 millimeters in size the median size and range up to 27 millimeters. Technical success was 100 percent in ablating all of them with a mean ablative margin of 9.9 millimeters and that one month cone beam CT for a CT scan follow-up sorry all the nodules were well well covered by the ablation zone. There was one case where the patient had some mild hemoptysis again post-operatively in the ward that was self-limiting and four subjects who had some mild symptoms of low grade temperature was sometimes called post-ablation syndrome two pro-refusions and one some coughing and dyspnea and so on. They're fairly mild and there were no deaths or pneumothoraces in this prospective cohort. So these two papers really were some of the earlier studies and in select patients you can see who are surgically contraindicated to have poor premorbid. This approach for the bronchoscope is a novel and feasible approach and for these small lesions and may have fewer probe-based complications compared with percutaneous ablation approaches. Just to show a few cases this is a elderly gentleman over the right upper lobe adenocarcinoma biopsy proven. You can see the catheters through the lesion and the color circles are the predicted ablation zone for a given energy delivery and on the right side you can see this fairly classical halo effect showing the edge of the ablation zone at the edge of this sort of fried egg image. The tumor is the egg yolk if you like it's a shrunken size because of the heat and it's got a good margin. This is a younger patient 55 year old who's had a left pneumonectomy because of a very central tumor a couple of years ago with annual surveillance. Unfortunately he was found to have another right upper lobe nodule that was developing 1.5 centimeters that was biopsy proven to be a squamous cell carcinoma. Limited options he actually opted for ablation rather than radiation therapy and he was one of our earlier patients and you can see the ablation zone on the right side which is quite substantial. We managed to position the catheter through the tumor and at three years PET CT scan it just shows a scar without any activity where the ablations happen. So he's benefited from this therapy. Younger patients we see a lot of these with multifocal lung cancer already had multiple lung resection this one had a lobectomy and the segmentectomy on the right side and it's proven genetically genomically to be multifocal lung cancer and has two other GGOs in the left lung left upper lobe and left lower lobe. They are persistent and also a consistency which is compatible with a early lung cancer. So we gave her the option she probably could have had them wedged out or had segment taken out given her young age but she chose to have ablation in this particular case which we think were reasonable given the size of the GGOs and we could do a good job and you see the two post ablation changes on over there. So is ablating multiple lesions safe? This is a paper we just recently published showing that we were ablating two or up to four lesions in one general anesthetic session. So we were successfully able to ablate more than one nodule in one session and achieved all the ablations that we plan to do in those cases with a mean minimal margin of six millimeters in all the nodules. Several of them require double or triple ablation to ensure good coverage. The mean hospital stay when we compared with a cohort of single nodule ablation did not show that they had a longer hospital stay with multiple ablations and the inflammatory markers the simple CRP in a white cell count were not higher for multiple ablations compared with single ablations in historical data. So with multiple ablations actually the percentage of pain, fever, pleurifusion and hemoptysis were not more than for single nodule but the cases of pneumothorax was more. So if you did one nodule your risk of pneumothorax is around 4.5 percent but if you do two nodules is around eight percent so it's about double and that makes sense because you're navigating to another nodule and deploying all your tools again and catheters again in order to do ablation for another nodule. So doubling that percentage kind of makes sense. So with multiple ablations in fact in the same session it's technically feasible it requires fewer GA sessions obviously because you're doing more in one session saves OT and anesthetic time and saves costs and seems to be safe with no additional complications per nodule ablated. So far we've done around 210 nodule ablations over 4.8 years with a median imaging follow-up around 2.3 years with around 4 percent pneumothorax 1.7 percent effusion rate 3 percent infection rate either chest or pro space and 1.6 percent bleeding intraoperatively that required bronchoscopic management but that was dealt with before we extubated and sent the patient out of OR. Local recurrence is around 7.8 percent with a median image follow-up around two years as I mentioned and zero mortality so far in our cohort and the recurrence rate is not too dissimilar to SBRT when you look at SBRT one and two year local control rates is around 95 and 88 percent for tumor size of around two centimeters which is the size that we are ablating there about in our series. There are a number of FDA approved robotic assisted bronchoscopy machines that's shown here and the one that we have and have had experience of using is this one from it's called the Monarch from December 2021. We've been using this platform and in some ways we're thinking whether it'll be best to combine the both worlds of a you know a great navigational platform with a ablation catheter through that delivery platform such as a robotic bronchoscopy so we combine microwave ablation with robotic bronchoscopy and you'll see here this is the robotic bronchoscopy machine this cone beam CT machine and also the microwave machine that delivers the microwave down a catheter that you can see here that's gone down the robotic assisted bronchoscopy. We've done three cases of this robotic bronchoscopy microwave ablation for six metastases in three patients they were for lung colorectal metastasis to the lung and osteosarcoma metastasis to the lung as well all successfully ablated no blood loss or complications that we saw patients discharged home around one to two days after procedure one patient had a mild chest pain and two patients had no pain at all after the ablation. This is one image I just brought out to share of one of the osteosarcoma metastasis and this is the microwave ablation catheter we're not able to penetrate this particular metastasis because it was osteosarcoma we laid it on either side and did a what's called a you know a bracket ablation of this nodule and this is one month post ablation imaging using this combination of system on the right side with a good margin and well ablated area. So in the future there are a lot of other energies that are you know including steam from vapor steam energy and also PEF ablation energy. These will be described by subsequent speakers as well as direct drug delivery to the nodule that may add value for the patient in terms of managing complex lung nodules and lung cancer. Essentially providing a bronchoscopic microwave ablation approach for patients with lung tumors allow them to have a more personalized and a tailored treatment and therapy. It potentially allows them to have more choice in terms of selecting the best therapy and also it preserves goes towards lung preservation in patients with multiple lesions or multifocal lung cancer. It may also allow early treatments in the future as we see more early disease being discovered. So and the bronchial microwave ablation in summary for treating small select lung tumors is feasible and safe. The approach is relatively non-invasive has low complication rates and reasonable midterm results. We obviously need a lot more high quality data and longer follow-up. We need more granularity in our data as well. Robotic bronchoscopy may achieve more quicker accurate navigation to the lesion that needs to be ablated and to create a more precise ablation. So thank you all for the kind attention and listening to this lecture. So in fact the next speaker is Dr. Michael Pritchard. So Dr. Michael Pritchard is going to be telling us about the U.S. experience ablation experience of transbronchial ablation. He really needs no introduction. He's an advanced bronchoscopist who's board certified in pulmonary disease and critical care medicine. Was trained in Mount Sinai Medical Center in Florida and also in St. Elizabeth Medical Center in Boston, Massachusetts. He's basically really a pioneer as director of thoracic oncology at the center in Pinehurst Medical Clinic. And he's also a founding member and past president of Society of Advanced Bronchoscopy as well as in the board of region for World Association for Bronchology Intervention and Pulmonology. He has a number of publications particularly in use of cone beam CT navigational platforms in ablation as well as techniques in reducing atelectasis to improve the procedure and is instrumental in writing a lot of the protocols and guidelines. And he recently did the first U.S. intuitive ion endoluminal robotic platform procedure as well as enrolled patients in the affinity trial of PEF. So without further delay I'm going to stop sharing and allow Dr. Michael Pritchard to share his slides and enlighten us on his experience. Thanks so much Calvin. I appreciate being asked by ISLC to speak with you today about our experience in the United States regarding ablation. We'll talk first about microwave ablation and this was something that we started in 2018. Also with a similar product to what Calvin has used with the Monarch platform. And this was our publication of this just last year but these cases started in 2018 before we had robots. We had 11 tumors that were treated in 10 patients. This was both at the Mayo Clinic as well as my institution. We had 100% technical success and 100% technical efficacy. Patients were all discharged within 24 hours. We did have a COPD exacerbation within the first 30 days at our site and there was a death at 15 days that we'll talk about at a patient that was treated at the Mayo Clinic. Excellent quality of life indicators. No improvement or sorry no decline in pulmonary function and actually we found that a lot of these patients had some improvement in their pulmonary function and we'll take a look at that. This was a summary of the lesions that were treated at our hospital and all these had to be biopsy proven. Interestingly in our study we chose patients not only that were inoperable but patients also who chose not to have surgery. And what you'll see there was about half and half also in terms of those who chose not to have surgery and those who could not have surgery. This was a summary of the cases that were treated at the Mayo Clinic, and you can see the dates that they were treated there. You know, I want to urge some caution in this as well, just because we're still learning about this technology. Just like in the early days of SBRT, we really had to learn where we can treat, we can treat what's the best energy, what is the best catheter, what's the best cooling method. And so everybody has their take on this, and so this is something that we're learning. And again, about two weeks after this, the patient had a sudden death event, and we don't know the exact cause. We were not able to get an autopsy, but you can see that there was a large cavity formation there in this case. So something to explore. All the details are in that publication. For the sake of time, we're not gonna go into those, but I would like to review some cases with you. Calvin has also presented some of the data that we've published outside of this as well. This was one of the early cases. This was a squamous cell carcinoma in a patient who was a borderline candidate for surgery. And you can see the probe in this. And again, all of this was done with electromagnetic navigation bronchoscopy with a steerable catheter. Once you start using robotics, the word steerable catheter doesn't mean quite as much as it used to. But here you see the nice ablation zones. We treated this at 100 watts for 10 minutes and you see large ablation zones, which gives you a satisfactory margin on all sides of the tumor. And you can see that in other planes. You can ablate right up against pleural surfaces in the diaphragm. You may get some, this patient had some slight right shoulder pain after her procedure. Lasted for about 24 hours and was treated easily with NSAIDs. So this is what it looks like pre-ablation and then post-ablation. You can see that halo around it, similar to what Calvin showed in his cases there. You can see the ablation zone 10 minutes afterwards. And this is the importance of Conebeam CT scan in these cases for both placement as well as assessment of the ablation zone. And here's what this looks like after four years. This patient's done very well. It's actually now been five years. She's done very well. No evidence of recurrence and no evidence of any new tumor. And you can see that in all three planes just shrunk down into a small scar there. And you can see her pulmonary function tests after one year have actually slightly improved a bit. And so there's no decline in lung function. One of the things that we do sometimes get frustrated with, with SBRT and surgery obviously, is that you will lose some lung function. A second case quickly was an adenocarcinoma in the left lower lobe. With this one after a month, we did not get a big ablation response, but just a very small amount of ablation zone there at the one month. And then you can see this did not have a big cavity or anything like that. Just a very small, well-controlled ablation zone that continued to shrink over time. You can see it pulls the fissure over there. And you can see this in all planes. And it's just shrunk down into a little bit of a linear scar. We did a PET scan after six months, and you can see that even though you have a small area there where the tumor used to be, there's no metabolic activity there at all. And you can see that in multiple planes. This is what it looks like after four years. And interestingly, just earlier this week, I saw this patient back for his five-year follow-up. And I'll show you those images as well. But here you can see that it's just shrunk down into a nice, small scar. This patient was actually a good surgical candidate, and he chose not to have surgery. This is what his CT scan looks like now five years later. So we've been able to cure him of this cancer bronchoscopically. Again, no decline in his lung function. All right, and then the third case just shows, Calvin had mentioned that sometimes you'll bracket these tumors. This was a larger tumor. And in this trial, we were only treating lesions up to two centimeters. And so this was at the maximum amount of that. And you can see these two ablation zones around the tumor in the middle, but at the top there is a little invagination where there was going to be a close margin. And so we decided to place the ablation catheter right through that small area and do a short third ablation for five minutes. So what you're seeing is you can start to be a little artful about this, and you can have these overlapping ablation zones with the tumor in the middle and get very good coverage in bracketing. When we start talking about robotics, we're not going to have as much need for this because we have the ability to really position things exactly where we want to and not be at the mercy of the catheter. And again, four years later, you can see that this has just shrunk down into a very small scar. He's also doing very well now, five years out. Pulmonary function testing, again, has some clear obstruction there, but his pulmonary function testing actually improved. Whether we're getting a little bit of a lung volume reduction with these procedures or what remains to be seen, our numbers are still very small. So clearly we have some gaps in terms of why can't everybody do this? Well, we need more access to ConeVM CT scan. We have some gaps in software. Only the FIC systems have augmented fluoroscopy and the better resolving power to show very small ground glass lesions like what Calvin showed earlier. We need to train more physicians with these skills and robotics is going to play a key role there. So here's the integration with robotics. And Calvin talked to you a little bit about the Monarch platform. This is the intuitive ion platform that we use. And this is all done in a hybrid suite, very similar to Calvin's. He has a Siemens setup. We have a Phillips setup. So again, any FIC system can really help you do this. This is what a ConeVM scan looks like. It takes five seconds to do a spin. You see the robot is locked in place. And then you're able to do segmentation. So you can pick and choose where the lesion is and you tell the computer where the lesion is. And then that is automatically overlaid and that's called augmented fluoroscopy. So no matter what angle or plane you move your fluoro in, you'll see that lesion. So here's how we're able to make these minor adjustments. You can see that I'm right on this lesion that's barely wider than that 3.5 millimeter robotic catheter. And I don't need to move any medial or lateral. But when we look at a lateral view, we can see I'm actually slightly posterior to the lesion. And so I know that I need to move slightly anterior and with our robotic platforms now, we can pick and choose very specific directions. I can move slightly anterior and now I'm in the center of the lesion. So with augmented fluoroscopy, we're able to make these adjustments and limit the number of combium CT scan spins that we do in these. And you can see how precise you can be, putting your needle in a very small lesion that's located on the pleura and confirm that in all three planes. Here's another example of lesion. This is not for ablation. This is not a candidate for ablation due to location, at least not microwave ablation. And we'll talk about another form in a minute. This is just showing you how accurate you can be when you combine combium CT scan with robotics. So the newest technology that we're working with in the newest energy form is called pulsed electric field. And so again, this is exactly what it states, which is doing pulse electric field. This is built similar to irreversible electroporation technology, but there's been some changes. It makes it incredibly safe because it's a non-thermal energy. You don't see cavities. You don't even see ablation zones after the procedures. So planning becomes very important. And the idea behind this is that you get cell death, but it preserves the extracellular matrix. And that's where you get the immunogenicity. And so the promise of this is that you're able to form an immunogenicity to the tumor and not to your own body. And so this creates a very small ablation zone, only about one centimeter for now. And in future versions, that'll be increased to two. But what we're seeing is this is creating tertiary lymphoid structures. And using this in combination with certain therapies like immunotherapy really has a lot of promise. And we're seeing some very good early results. This was a patient that had a soft tissue sarcoma of the leg and also lung metastasis. They treated the leg sarcoma with pulse electric field therapy and no treatments for the lungs. And you see this abscopal effect on the post PEF PET scan that shows resolution of the lung mets. And after six months, you see a decrease in the size of the left thigh lesion. And again, still stable chest findings at that time. Here's an example of a primary lung cancer that was treated with PEF. This got six different treatments. You can do this percutaneously, or obviously the whole reason for doing this talk is that we can do it bronchoscopically. There are a few studies that are ongoing to look at this. This is basically doing PEF at the time of biopsy and then continuing on with the checkmate protocol. And this is in progress. And then the affinity trial, which we're doing really more of a safety and feasibility to do this bronchoscopically in patients that have either stage four lung cancer or a ligamentostatic disease from another site. We've completed about 10 of these cases and we're expanding that to 30 at sites like the Mayo Clinic, Cornell University, and our site. This is how we can work together. This was one of the first patients we treated. This was a male with breast cancer. And in the same procedure, I navigated to the lesion, established that this was a malignancy in his lung. He was a never smoker. And under the same anesthesia, we also worked with our interventional radiology colleagues and we treated liver metastasis and his lung metastasis all in the same anesthesia. And this was the first affinity patient. This was a patient with renal cell carcinoma. You can see the two small metastatic lesions there. And that left lower lobe lesion, we actually treated it with three different activations. So that's how precise we can be with these overlapping zones. And then you see a very small four to five millimeter lesion on the right side. And you see the combium CT scan of our needle right in the middle of that. And we treat that with a single activation. And this is what it looks like in the room when we're doing these procedures using augmented fluoroscopy. And then now we have some four month follow-up data. Again, all this is very early, but you actually see a decrease in the size of the left lower lobe lesion. This patient has had no other therapies at all and stability, if not maybe very slight decrease in the right lower lobe lesion. So this is another ablation technology that's coming down the road that we're excited about to be able to do studies on and see if we have another option to help our patients. That's where we're at with things in the United States right now. And so I'll stop there. And I'm very happy to have Calvin introduce our next speaker. Thank you very much, Mike, for a fantastic talk. And our final presenter is Dr. Agathe-Sacan Givelay. And she's the head of thoracic surgery from the Institute Bijeliz Monzuri. And she graduated from the University of Paris and was awarded a DPhil for her research into tracheal replacement, thanks to a fellowship over in Minneapolis, Minnesota. She's worked for over 10 years as a thoracic and vascular surgeon at the Avocent Hospital and decided to focus on thoracic surgery and mainly lung tumors. And before she moved to the current Institute and became the head of the department from 2020, she has deep involvement in innovative and robotic programs and has one of the largest experience of segmentectomies in the continent over there. And she leads a IM and thoracic team to organize successful international sub-global conferences for a number of years. And her interests really are in image guided thoracic surgery and also guided bronchoscopy for therapy. And she then went on to perform one of the first in the European continent and the bronchial microwave ablation in December, 2022. So it's a great pleasure to have Agathe telling us about her experience over in her center. Thank you, Agathe. Thanks Kelvin for this kind of introduction and invitation for this webinar. So I just want to share with you our early experience and the main topic is how to start an ablation program. I will just go through rapidly with the material because all the speakers as yet discuss about it, how you can select your first patients and what the challenges you will have to face. So as we yet said, the first things you need to get, it's an accurate bronchoscopic navigation platform to reach the lesions. You will have to learn to work on an hybrid OR because you will need a high quality imaging to assess that your tools, whatever you use for biopsy or after for ablation is in correct position. And also after the ablation to assess the effect of the ablations and to be sure that you get correct margins. And also you will have to decide which energy source you want to use for your patients and that could be delivered down the bronchoscope to ablate the tumor. And you yet hear that you can use different energies. So what we've decided in our institution is that we were yet performing some bronchoscopic biopsies with a navigation platform that was a super dimension one. It was used by ophthalmologists for biopsies but we were using it as surgeons for doing labeling before weight resections to assess metastatic disease or perhaps sometimes to assess non-small cell cancer before matropulmonary resections. And we upgrade the system with the Illumisite systems to correct the CT to body divergence two years after. So the first perhaps key message it's you need to be used to your navigation platform before going through an ablation program. And that's what we have done with all the surgical teams. In the future, what I would request from this navigation platform it's perhaps to get a continuous direct visions to have these target deviation corrected to have a more ergonomic systems. We all struggle with the catheter deformations and we need a better accuracy and a better positioning of our tools as Michael said or Calvin said sometimes you need to bracket ablations and perhaps there is some technology that would come and would avoid to navigate twice or three times to the lesions. And also we need these real time imaging during all the process. So that's why I really think the robotic platform could be the next platform to be chosen for your ablation program. If you are thinking about starting an ablation program because it can give you more articulation a better visualization and also a superior stability of your tools. The next things you need is a hybrid OR. So we get discussed about these high quality imaging to assess the correct positioning and the ablation effects of your ablations. And it's also help you to combine some approaches. For example, in our institution we start doing some labeling percutaneously and also by an endocrine shall way in the same anesthetic sessions depending on the location of the tumor. So for metastatic disease, for example. At the beginning, if you do not have an hybrid OR usually you can borrow the hybrid OR from your interventional cardiologist and that's how we start. And after that being used with the hybrid OR we build a multi-programme shared hybrid OR with their specialty and with our own access for the thoracic surgical team. I will not go through what it can help you but you know that you can navigate to the lesions do the segmentation, adjust the placement of your tools and after start your ablations and assess the correct positions. The key messages when you start an ablation programme is that you need to learn to work with these new images. It's a new task. You're not always very familiar with that. You need to have some dedicated peoples. What we found in our institution is that sometimes at the beginning it could be better to be two surgeons one at the head of the patients and one working with the radiological images. And also you need to train yourself inside this hybrid environment before the ablation programme. So we were using all the cross-country techniques or the CanBeam CT techniques even for labelling with the objective to be inside the target as we were doing ablations to be trained with all the hybrid environments. So you can use a CanBeam CT but there's also some others good quality images that can be done with the mobile CT scanners. The key messages is to work on the high quality images real-time images, the one that will give you the margins assessment and the 3D view and also starting thinking about radiation doses not only for the patients but also for you and also for your team. So you can use the mobile CanBeam CT also here mobile CT scanner and you will have to think about your robotic platform because everything needs to fit inside the same room and that's not so easy when you think about the CanBeam CT the navigation platform, the robotic platform and so on. The last thing that you need to think about is the energy source. So we've gone through a different one and we spoke a lot about microwave ablation and also the PEF ablation that just Mike spoke about. We start with the microwave ablation only because at the beginning it was the one that was really used inside our hospital. So we had good relationship with our interventional radiologists. We could rely on the microwave ablation experience that could be very helpful at the beginning of your own experience to have better interpretation of the margins. And to be aware also of complication that could occur. And also what could be difficult is that you need to work for my sides in France we see e-marked technologies and efficacy proven on human line. So at that time we were just using microwave ablation. So selection of your patients you need, we think that at the beginning the hyper selection of the patients is the key. So we were selecting very good patients PS0 fit for both techniques, meaning that if there was any problem with the androbronchial way we could switch during the same session time for a packet in this way because we wanted to treat the patient that was the main objective. We were taking only patient with unique lesion and the easy ENB access to have less challenges at the beginning. How were indications with three different one, non-synthetic disease, not small cell lung cancer. If there was no surgery possible or no asperity indicated. And we were not working with GGO lesion at that times. And all these patient was validated with an interventional radiologist. So we start one year, there's only eight patients for nine lesions. The median lesion size is one centimeters because we wanted to start with very little lesions. And finally we just treated only metastatic disease. All the margins was more than one centimeters because the lesion was not very big. And we switched from a manual task that was very difficult to do with a prototype done by GE that helped us to have all these tasks to put the ellipse, assess the margins automatically done by the software. And that could be the first challenges it's to improve the process of your ablations process. Also, the second challenge was to accept the learning curve. I think we are still in the learning curve even if we may know that the endovascular route give less pneumothorax, we had yet two pneumothorax, the first patient and the last one. The first one because the cross country go through the visceral pleura, and the last one because we were doing the new challenges that was two lesions at the same time and during the navigation on the other side, the patients encounter pneumothorax on the first side yet treated. The length of hospital stay was even with these two pneumothorax only one day. We have one readmission at the hospital and that was for a new pneumothorax on the last patients at that time, but we have only one year follow up. There's no recurrence and to assess and to try to get the learning curve as short as possible, I think we really need to be proctored and I'm really thankful for the proctoring by Kelvin Law. So we've done some immersive journey at St. Barthes Hospital with some ablation cases that we have seen with all our teams, meaning the pneumologists, the radiologists, interventional radiologists and the surgical team. And also Kelvin was very kind to come for the first eight patients and each patients had after been discussed and debriefed to try to improve everything inside the OR. The next challenges we have faced with the ventilation protocol and perhaps we can have a discussion with the other experts, but it was very difficult to assess which ventilation protocol was the really good one for these ablation process. At the beginning, we were using a very high PEEP, but we had a CT two body divisions. So at the last three patients, we adopt the Kelvin's protocol where there's only a 12 positioning and we also do the positioning and the ablation during apnea to avoid any movement of the lung. So just a quick overview of the first case to let you to see, but it's just like Kelvin or Mike images how the scar is getting. And the last challenge is for me is perhaps the main difficult point to bring together a multidisciplinary team in this program because it changed your anesthesiologist protocol. It changed the nurse task. It changed your own surgical task. And these new tasks, it's just like you can have some breaks and you need to assess who does what. And that's not so easy at the beginning. And the last but not the least problem in France is the financial problem. Perhaps it's very different in Asia or in America, but in France, there's no money for these new innovation treatment. And that's very difficult. And I'm thankful for my establishment who is very involved in innovative treatments. So the last one will be to increase the difficulty. So we are thinking about doing multiple lesions and combining also ablation and surgery when some of the metastatic disease is more for wet resection, for example. We want to test some other energy and we are very interested in the electroporation. Like Mike said, we want also perhaps to move to a robotic bronchoscopy navigation platform, but we need to wait for the CE mark. So thanks to ION, there's one coming in the European market. And perhaps we would have to think about enlarging our indications and perhaps to treat some GGOs. European people are very different than the ASEAN ones, but we sometimes face also some multiple adenocarcinoma, not small cell lung cancer. And perhaps we would have also to rely on the experience of Calvin and all the ASEAN experts on these fields. And as Yed said, we need for trial to assess that there is no more local recurrence, that there's no other long-term complications. So my conclusion is that sometimes we need to be pioneers. We need to cross some roads to see outside the guidelines, but with the main objective to be beneficial for our patients. And I really think we need to believe in it because I'm quite sure that the first results are very good on that ablation program. So thanks for my team and save the date. As Calvin said, you are all invited at the next Bronchoscopy Ablation Summit in Paris. Thanks. Thank you very much indeed, Agathe, for a fantastic talk. So what I'm going to do is to, I think what I'm going to do is put up this Q&A slide here. And we do have actually a few questions from the audience and we have five minutes, which is perfect to address some of these questions. The first question from Dr. Baldwin is, are you concerned about over-diagnosis and treating five millimeter ground glass opacities as it's generally not recommended in guidelines? So perhaps I can take on this question given that I probably ablate more ground glass opacities than anyone else. So the cohort that we normally ablate in terms of these small GGOs are not the ones that just found to have a ground glass opacity on the screening CT scan. It's not that group patient. It's actually for patients who already had diagnosed multifocal lung tumors. So they may have had a lobectomy, a segmentectomy or lobectomy then found to have several multifocal tumors within that lobe. And on another lobe, the patient has these other small GGOs. Now we don't routinely say that you must have them treated. We actually give them choices and present to them the guidelines that you should observe them perhaps for a period of time until they grow, until they have more solid components. But we also do tell them our current data of ablation of how successful it is. And they can be treated at this stage with these potential complications. So we present to them the options out there basically. And some of them will, given that they've already had diagnosed multifocal lung cancer, they will take on the treatment while it's still a small ground glass opacity. And the ablation zones will be smaller as well, you know, and before they start growing to a larger size. I don't know whether that addresses some of those, the question. We also have our own data in our center. So we often go in to do a lung resection for a two centimeter adenocarcinoma like a lobectomy or segmentectomy. And in another lobe, there'll be a GGO and we normally die mark that GGO to wedge it out because it's in the same operation, right, in the same side. And we have data that in our center for persistent GGOs less than seven millimeters, persistent meaning on two consecutive CT scans at least six months apart, that over 70% of them are AIS or already adenocarcinoma. So the fact that, you know, having small GGOs is not lung cancer, it doesn't fare well in Asia. We've resected two millimeter, multiple two millimeter invasive adenocarcinomas in our surgery in conjunction with a segmentectomy or lobectomy for concomitant nodules as well. So we have our own data we present to the patient and we have a discussion with them with all of that. The second question is how did you evaluate the therapeutic effect after the ablation? Can I give this question to the other two speakers, perhaps start with Mike, your take on that? Yeah. Yeah. So the therapeutic effect is really we're following with CT scans. So similar with what you would do with, you know, SBRT or, you know, surgery looking for surveillance CT scans. So these patients got a one month follow-up scan and then six months and 12 months and then yearly thereafter. And then after that, we just followed the NCCN guidelines and most of these patients got CT scans every six months for the first two years and then yearly thereafter to five years. There was two patients in our cohort that got a PET scan, one at six months, as I showed you there, and one at seven months because we were possibly concerned about recurrence. Neither one of those PET scans showed evidence of recurrence. So similar to SBRT, sometimes it may be difficult to tell if there is going to be local recurrence. If there's any question, you can always do a PET scan. So very similar to what you would do with SBRT in terms of your follow-up. Great. Thanks, Mike. I have a question here, which is maybe best for Agat, which is how to start the ablation program in a developing country? How would you suggest? So I would probably not suggest to start with the robotic platform because it could be probably a financial problem. I would suggest to get a good navigation platform, but you really need to have an hybrid OR. I mean, you can't do that program without assessing margins and correct positioning of your tools. So perhaps in developing countries, you need to share some platform between different countries and to have some programs where there's one leading country where you can try and develop this program. But I really think that we need to stick about navigation platform and hybrid OR to assess the correct position of your probe. Thank you very much. I see in one of the earlier questions actually says, could we find out the reasons why the patients decline SBRT, which is less invasive and opt for endobronchial ablation instead? It's an interesting question. I mean, I think I put that slide up as one of the indications for some of my patients and maybe I can start off answering and supplement by my other experienced ablation speakers as well. So some patients are really not for SBRT anymore because they've had some radiation, as I mentioned, they've had some chest radiation because they've had breast surgery, breast cancer. And although it's not direct radiation into the lung, but our radiation oncologists are reluctant to give further radiation to that side of the chest. So ablation for small lesions that are in the lung seems quite appropriate. There are also lesions that, in fact, in ablation, we can ablate multiple lesions in different lobes. So we have the slight, I would say advantage, but slight indication and the ability to ablate spread out lesions in large areas that our radiation oncologists are reluctant to give large area radiation to both lungs for small lesions, whereas the small lesions are perfect for us because our ablation zone is not as big and we are not so good at dealing with larger lesions. We also have patients who prefer to come in for one treatment, which is what it is for us. We do a general anaesthetic, which can be considered invasive by some people. The bronchoscopy is not so invasive, really, there's no scars and 89% of patients have no pain. So they go home the next morning. So they prefer one treatment for their one, two or three lesions, metastases, nodules, rather than coming in for multiple treatments to the hospital. So some prefer that as well. And some patients just feel they're a little bit uncomfortable with the idea of radiation and they do ask, you know, what happens? We have to, you know, talk to them after the MDT that radiation carries a certain recurrence rate. Our ablation also carries a certain recurrence rate after ablation. But they ask what happens after the recurrence. And we say for ablation, we can ablate again, it's thermal ablation, we can ablate as many times and touch up the areas that recur as many times as we want, whereas the radiation oncologist would tend not to be able to give additional radiation if it recurs. So we tend to ablate lesions now and for some of our recurrence, we refer those to the radiation oncologist to deal with, or some of them we would re-ablate if appropriate. So it's a very, actually, friendly atmosphere in our MDT in discussing all of these treatment modalities headed by our head of MDT. Some of you may know Tony Mok, who is actually buying into this idea of having an additional choice for our patients and within the MDT setting. So it answers a little bit of perhaps what you're looking for. Any additional comments from the US or the European continent in terms of patients preferring ablation rather than radiation? Yeah, at this point in the US, this was all under the auspices of a clinical trial. And so you'll always have patients who are interested in participating in a clinical trial, want to be part of clinical research, do something new. They were all presented all options if they were appropriate. One of the patients that we did treat in that trial had SPRT, was referred to us by his radiation oncologist because he had local recurrence in that area. So again, some of that is personal preference. And at least in the US in those studies, it was because they desire to participate in a clinical trial. Thank you. Agat? No more comment from the European side, same things. Thank you. Thank you very much. So in one of the earlier questions, we have a question saying, any concerns with autoimmunity with the PEF treatment? Mike, would you know that? Yeah, so that's a great question. When we first started talking about this energy, it's the exact same thing that I thought was like, okay, well, can we generate autoimmunity? Are we going to flare up autoimmune conditions that they may have? The short answer to that is no. This is such a small ablation zone and you're ablating tumors. So the whole idea is for it to be tumor specific immunogenicity and not systemic. So if we were treating a huge volume of lung, normal lung with this, then perhaps you could see some stimulation of innate immunity or some autoimmunity, but we're not seeing that in any of the human cases treated either with PERC or with an endoluminal approach. Thank you. And there's a question on cryotherapy. It asks, can you expand on the information on cryotherapy? I can't remember, Agathe, did you mention cryotherapy? Have you any? I mentioned that it could come, but I have no data on it, but I think it could be an option. I think every energy source will probably come by the androvoncular way and we will have some specific indication for each of one. Mike, yeah, it was expanded. Yeah, I the only thing that I am aware of in terms of endoluminal was really what was presented at your meeting that we were all at in Hong Kong. I think that you had someone, maybe he was from mainland China, who was using some cryo transbronchially to treat some tumors. Obviously, there's some limitations there with being able to get a catheter, a larger catheter to the position, being able to get a large enough ice ball to treat tumors. Technically, I guess if you can go multiple places like we do with PEF, it's theoretically possible. Obviously, percutaneous cryo has been around for a long time and can be quite useful, too. Yeah, that's also my understanding as well, Mike, I think cryo is great for, you know, critical, neocritical structures because, you know, obviously preserves the architecture a lot. And but I think my understanding is it does take repeated cycles of freezing and thawing. And it does take a long time for two or at least two cycles and some would say three cycles. And I think a percutaneous approach, you say, is more popular. I think they're able to put bigger needles through the chest, you know, into the tumor to get a bigger ice ball. I mean, for us, the technology, my understanding is still not quite there yet to create a good, you know, cryo zone. Would you say that? Yeah. Yeah, great. So let me see. There are a lot of questions actually coming in now. I'm not sure how many we can actually deal with. One question I think is of interest is mobile cone beam CT sufficient or do we really need fixed cone beam CT? Maybe from the two speakers. I guess. Yeah, perhaps a mobile cone beam CT could probably be used to. But I think we really need and it's answer a second question, the augmented fluoroscopy. And that's sometimes what is lacking. And it could spare some cone beam CT and also some radiation. So for me at that time, without the fluoroscopy, the augmented fluoroscopy, I will use the fixed one. So, Mike, what is your opinion? Yeah, so I think that you have better resolving power with a fixed system. And Calvin, you published that study looking at a small ground glass lesion that you could see with a fixed system and couldn't see with with a mobile system. However, I think that as you know, I think you could safely do ablation now with mobile cone beam CT scan. I do. I think that you may have challenges in terms of ground glass lesions. You may have challenges in terms of seeing the ablation zone afterwards and knowing that you got treatment. And then the obvious points that you mentioned about not having augmented fluoroscopy right now in the clinical trials that are ongoing in the United States, the FDA is mandating that you have a fixed cone beam system and augmented fluoroscopy that may change in the future. And then the follow up question to that is, is tomosynthesis good enough to do that? Right now, the answer is no. I don't think that that's a good idea. There are some platforms on the horizon that I've seen have some pretty amazing images. But right now, the systems that are out there, I don't think are appropriate for doing ablation, particularly microwave ablation. Yeah, I tend to agree with you that I think in the not too distant future, probably a mobile CT would would have the software, the tools to to deal with an ablation. The limited experience I have is that it's still because of the lower power that it delivers with the imaging with smaller GGOs, it's can be a little bit challenging to to identify, particularly with the tool near the GGO in my practice that causes some artifacts. And so that that could be a problem. But for more solid lesions, I think the images are pretty good with the Conebeam CT. Another question as we come close to the end of our session. Do you think microwave ablation therapy can be suitable to treat lymphadenopathy? Mike. Yeah, so right now the answer is no, but it does bring up the idea of the possibility of using other treatments in lymph nodes. So I've done PEF treatment in lymph nodes. We can deliver that with EBUS. There are drug delivery trials, radio sensitizers, things like that, you know, that may be on the horizon, oncolytic viruses, things like that that you can. But you cannot ablate inside of a lymph node because you'll basically you'll burn a tract. So the the activation end of that is is several centimeters. And so you can't heat the entry into that. And that's the problem that they have with percutaneous. They have to sometimes take very indirect routes because you can puncture the pleura, but you can't puncture it and ablate it. You will create a bronchopleura fistula. So that would be a limitation of treating inside of the lymph node, at least with thermal energy. But for non-thermal, it may be an attractive option in the future for drug delivery or PEF. Thanks, Mike. So there's a question of do you offer these treatments as part of standard of care or only as a research protocol? I think Mike's answer to that, you know, mainly is the research in the U.S. How about you, Agathe, in your center, is is it part of a standard of care patients can choose? For metastatic disease, if the multidisciplinary board decide a local treatment and a non-surgical treatment, it can it could be offered as a standard of care. But for not small cell cancer surgery, it's if there's no more option, meaning no surgery, no SBRT, because it's not standard of care and we are not at that moment treating GGOs. And that's that's something that we're doing now with PEF is that we are treating it under clinical trials, but we're also offering it in salvage cases as well, just like you mentioned you're doing there in France. Thank you to both our speakers, I think we've come to the end of our session and we must bring it to a close, although there are more questions to answer, so I just want to thank both speakers today for their excellent talk and really informative Q&A session. To discover more education activities being offered by ISLC, you can consider visiting their website at ISLC.org. So thank you all very much for joining us today and I hope you enjoyed this webinar. Thank you.

webinar transcript

bronchoscopic ablation therapy

lung malignancies

procedure

patient selection

microwave ablation

PEF ablation

follow-up evaluations

implementation challenges

lymphadenopathy