Patients with advanced Chronic Obstructive Pulmonary Disease (COPD) are at increased risk of lung cancer, and should be screened with low-dose CT. The diagnosis of COPD also influences the diagnostic approach and treatment options if solitary pulmonary nodules (SPN) are identified during screening. This webinar discusses the link between COPD and lung cancer, and how early diagnosis can improve survival. Case studies will be presented.
Hello and welcome from Temple Health in philadelphia. Today we welcome dr gerard Criner professor and chair of the department of Jurassic medicine and surgery at the Lewis Katz School of Medicine at Temple University and director of the Temple lung center at Temple University Hospital. Our topic today for live discussion is lung cancer screening and diagnosing solitary pulmonary nodules in patients with COPD sometimes at advanced stages. Dr Criner, you're known for your work and leadership in the area of COPD and currently you're expanding on that experience and performing more advanced bronchoscopy. I'm sure we all want to hear and learn about how these areas intersect and the current steps towards the best outcomes in that patient population. So dr Criner please take it away. Good afternoon and thanks TK for the introduction. As TK mentioned, I'm going to talk about lung cancer screening and how to handle solitary pulmonary nodules and patients with advanced lung disease. These are my disclosures and there's nothing really in conflict with the content I'm going to present to you today. So the importance of COPD and lung cancer is they are both common global causes of morbidity and mortality COPD overall has a worldwide prevalence of 7 to 19% and it's the third leading cause of death. There's over 65 million people who suffer from moderate to severe COPD worldwide And approximately 25 million people in the United States COPD caused about 3.23 million deaths in 2019 lung cancer is also a very common problem. As you all know, It's one of the most frequently diagnosed cancers worldwide. It's about 12% of all cancers. It's the most common cancer diagnosed in men. It's the third most common cancer diagnosed in women. So unfortunately, it's a very prevalent malignancy in both genders, And lung cancer is the leading cause of all cancer deaths, about 18.4% or 1.74 million worldwide. In fact, more people die from lung cancer on an annual basis than people who die from colon, breast or prostate cancer. And this number unfortunately, is expected to increase to 2.45 million patients worldwide by 2030, which is almost a 40% increase since 2016. So, although the cases for cancer have decreased in the United States more recently, probably deaths because of the advent of lung cancer screening, it's still a growing and important problem worldwide. So what are the important features of COPD and lung cancer? Well, because of the frequent occurrence of either COPD or lung cancer in patients who have common predisposing risk, the two diseases can occurs simultaneously in susceptible patients. So, patients who have COPD who smoke have up to a six fold risk of lung cancer compared to smokers without airflow obstruction and lung cancer and COPD as you well know, share common risk, such as exposure to cigarette smoke or biomass fuel exposure and in some parts of the world, and lung cancer increased incidents increases as air flow, as if everyone declines or airflow obstruction increases regardless of the cigarette smoke exposure that the subject is exposed to. And another important feature is the structural presence of emphysema without any evidence of airflow obstruction also increases lung cancer risk. So as you can see a patient with COPD smokes can have airflow obstruction can have emphysema. These are both independent risk factors for patients to develop lung cancer. Not only is it important for COPD increasing the risk of lung cancer, the diagnosis of COPD, as you well know, has important implications for the target patient population that we screen for lung cancer with L. D. C. T. Or low dose ct scans. And it also influences our diagnostic approach and treatment options for patients who have nodules that are considered suspicious for lung cancer. So it affects our approach to diagnosis and and really has significant implications in terms of COPD and our patient prognosis from a significant co morbid problem as well as how we treat these patients and manage them with lung cancer. So what are some of the factors that go into this pathologic or pathogenic link between COPD and lung cancer? Some of them are shown in this paper here from a couple of years ago to the top left? You see patients that have genomic transcriptome and proteome IQ sort of predisposition, perhaps the to developing cancer or COPD. And then there is a shared environmental risk factors such as smoking in or outdoor pollution and a microbiome that we know is distorted in patients with COPD compared to the non COPD population. And this can then result this intersection of genetic factors and environmental factors can affect the host in terms of the inflammatory injury or repair processes that can occur. And along and the way our immune response, both innate and adaptive as well as our response to injury can occur that can result in the development of either COPD lung cancer, pulmonary fibrosis or in some patients. The combination of all these factors, as you'll see later in some of the patients that I describe, you can see the overlap of these different disorders that can occur in individual patients. So one of the important factors that we know is that the stage of what you diagnosed lung cancer has an important implication on the patient's outcome. And this is the data from the seer cancer population in the U. S. From 2000 and 9 to 2000 and 15. Almost a quarter million people that looked at the stage of presentation in the five year survival. And as you can see if you have localized disease, although not terrific at that time, your five year survival was much better than if you had distance disease. Unfortunately in this outlook or this. Look at patients from this time period, most of these patients, the majority had evidence of widespread disease at the time that they were diagnosed well lung cancer screening has been shown by two large population based studies both in the U. S. And N. S. T. And the nelson study that was done outside the U. S. That you can stage patients that are earlier period in the evolution of their disease. If you do routine lung cancer screening with low dose ct scans and as you can see, you can flip the seer data by now, more people are presenting at an earlier stage of the disease than a later stage of disease by using this tool and you can see here that the improvement in survival is about a 20% survival that you can see and it has a durable effect on patients outcome when patients are followed either from up to six years and an L. S. T. Up to in the nelson study up to 10 years. So lung cancer screening has an important part to play in improving the paradigm of management of patients with with lung cancer. This use of LDC T however poses a problem for the patients that were trying to diagnose and therefore treat That these earlier stage lung cancers are usually found more than 70% of them. And this is data from the Nelson trial um are in the lower third of the lung and in the tropical regions of both the upper and lower lobes which in some cases are not only peripheral but they're in difficult to reach locations. So this poses somewhat of a challenge to be able to diagnose the patient appropriately. And there's some other features that um are important to realize. When we're trying to diagnose a patient with a small peripheral nodule that you find from lung cancer screening. These lesions less than two cm have an important bearing on our ability to diagnose if there flora skopje cle invisible if they don't have an airway that leads to the path of the of the tumor. And if it's in a peripheral location, there's also an element that when you do a planning ct and then you try to do the procedure. The planning cT is done while the patient's awake and spontaneously breathing. The procedure is done while the patient is sedated in some cases paralyzed and laying recumbent for a period of time on enriched oxygen. And then you have the CT two body divergence, which means whether you thought the CT scan was and planned it on some sort of imaging platform for virtual navigation. Then when you actually do the procedure, it's slightly off the mark because of these other factors that occur and then to go out into the periphery, you must have the tools to drive you there as well as the biopsy tools that can operate in smaller or more torturous airways and then finally, and most importantly, when we're talking about patients with COPD and other forms of significant lung co morbid problems post characteristics if they have advanced underlying lung disease or co morbid conditions limits your ability to take approaches. Either transfer drastically or endoscopic lee as well as the period of time that patients can tolerate general anesthesia. So these are all factors that go into play. We can diagnose a patient with a lesion. But how do we no really uh execute our ability to find out what that lesion is and find out if it's cancer or not and get the patient effective treatment plan. Well these are some of the approaches for solitary pulmonary nodule diagnosis. TTN is shown to the left C. T. Guided needle biopsies which In the past was the mainstay. Um the diagnostic Dilfer for tumors that are less than two cm is good. It's 92% complication rate is about 24% with a fine needle and 38% with a core needle so a little bit higher. With a larger needle. A pneumothorax rate All comers is about 25% but 5% of those less. About a quarter of them require an intervention with a chest a chest tube place so by 5% of them have a complication that requires an a different additional intervention for treating the the complication that occurs during a biopsy, flexible bronchoscopy with electromagnetic navigation diagnostic yield is 73% which is lower than we get with um transfer drastic approach. The pneumothorax rate is less in terms of the overall rate of 4% compared to 25 less patients need a chest tube 3% about compared to five and a half percent of patients who have a T. T. N. A. So yield is much less and pretty much not acceptable when we look at this. If we're trying to go to the next level and duplicate what we have with T. T. N. A. If we look at um the prevalence of use of E. M. N. It's growing overall but it's still relatively low. And if we look at the ability and people in the community by the host acquired data registry five years ago. Now in less than two cm it's less than half the patient population. Were they able to make a diagnosis? So it's not always effective when you go outside of clinical trials or out of specialized centers to mimic with use of this technology was found in um in the clinical trials with more skilled observers. There's also somewhat of a time delay uh and variable pathways where patients go through to get A. S. P. N. That's identified to be diagnosed to finance its treated and you can see some of these different pathways that occur after the L. D. C. Occurs and it goes to the general practitioner. They might send them to interventional radiology. They could send them to a pulmonologist. They may send them especially in the United States to an interventional pulmonologist or an advanced bronc ologists. And then there's inter discipline of these sub specialist referrals in some cases based on patient's anatomy. All this in some degree may delay somewhat the effective ability to diagnose the patient and render them treatment. Um So what we'd like to do is take the screening, streamlined a diagnosis so patients can have a more streamlined approach to treatment. So let me talk to you about some approaches that have been published in the literature by others and which I think are very applicable to patients who have COPD and other advanced lung diseases. And really this is something that I think people that have standard skills and bronchoscopy could be able to apply at their institution and do so. This is one of them. This is using a blend of technologies as they will show you. Which is a combination of robotic bronchoscopy, cone beam ct augmented Flora Skopje and radio E bust. This 62 year old female who was referred by one of our thoracic surgeons who previously had breast cancer that was treated with a lumpectomy and Adjuvant XRT and was on Arimidex and she had a incidental L. O. L. Um left upper lobe Ggo identified for an observational clinical trial that she was in and she had a faint G oh that was Pet positive at 1.8. So very mildly pet positive. So we use this combined technology with her um to guide ourselves to this lesion and what we found endoscopic lee. You can see this pulmonary artery but we also could identify the lesion next to the pulmonary artery that was there. And when you can use these combined technologies, you're out in the periphery of the seventh generation. You could identify this pulsating vessel and stay away from it. So you could biopsy a lesion and avoid a complication by doing this. So with the T. T. N. A. We're able to diagnose a low grade and a carcinoma. Beit needle biopsy patient was discharged home posted procedure and the patient underwent curative uh radiotherapy for this. She wasn't deemed to be a surgical candidate for other factors in her condition. And the patient responded to that treatment. Well, there's another case of a patient that presented to community physician. Um and she had advanced emphysema. She was sent for consideration of bronchus, coptic lung reduction. She had this speculated solid nodule in the right upper lobe that was 12 by um 10 by 11 millimeters. This was pet avid at 7.8 suv. She wasn't a candidate for TNA because she had advanced emphysema that would be a greater risk of a more prolonged air leak. And this was planned to be out in the 7th a generation. You see the pet scan down at the bottom. Right? So she underwent this combined approach with robotic bronchoscopy with use a cone beam cT augmented flora's copy as well as radio the bus. You can see, we were uh drove to the television were a little bit off from what we found fluoroscope quickly by a couple of degrees from the planned image. This is the ct body divergence while you're actually doing the case. Um And then with rotating mildly you can see this radio E bus. We can't identify the lesion, but by rotating about two degrees, you can find that we have now a concentric lesion on biopsy for which we were able to effectively diagnose and biopsy in a short period of time. This navigation takes a couple minutes and then looking at the constructing the cbc T. And carving out the lesion and put an augmented Flora Skopje and making the minor manipulations with the radio E. Bus takes about several minutes in this case. And then what we found in this case is patient by Rose had squamous cell carcinoma. Were then able to plan the patient's case which she ended up getting a right robotic assistant risk opic resection of the lesion plus L. VRS and media sentinel lymph node dissection. This is her final pathologic diagnosis that the patient had. So she was able to get a combined procedure with L. V. R. S. And a curative resection for lung cancer. There was another case of a patient that was again referred to our Thoracic surgeons who was a 69 year old female who had moderate emphysema had hefty f. She was a little bit overweight and she had obstructive sleep apnea with this 11 by 12 right middle of nodule that was right on the pericardium. Um And was not a candidate obviously for T. T. N. A. Because of the location and the dynamic changes that occur with you know, cardiac ostentation. She was also on 4 to 6 liters of auction with exertion and about two liters of auction. Aggressed so marginal in terms of like gas exchange and tolerance. Again using combined modality procedures, the patient had some attempts to try to minimize the development of ad electrolysis during the case with a higher title volume, higher peep and a low level of F. I. 02. But this patient required still about 50% oxygen because of her underlying lung disease. And so she developed some add electricity as you can see here during the case. Around this right middle lobe nodule. And this is the planning nodule that we had in the path that we had overall. You can see again we had some divergence of where the plan not to was. And even as the case arise from where we could see what the comb being case and then to where the virtual image was, where the lesion was actually here. Uh And then made fine adjustments to augment and overcome the C. T. The body the version that occurs and can do this with minute movements when you have a robotic bronchoscopes up and be able to do further live imaging. So in that patient's case she ended up having adenocarcinoma. And she was treated with S. P. R. T. Because of her poor risk for surgery. So is this just flukes for a couple of cases or can you do this in a broader patient population? So we reviewed our first about 70 cases that we've done with this one. Selected consecutive cases or 69 cases using this kind of technology that was with uh just outlined for you. Um and looked at what our yield was as well as our complication. Right. This is our patient population. Patient population was late sixties. Um There was uh most of them were smokers in the past. Current smokers and 25% former smokers. And about three quarters patients had significant co morbid conditions, 68% had COPD of moderate to very severe airflow obstruction as you can see here. The f 81 mean was 56% the delta was 23% and most of the patients were on supplemental auction. The mean use of auction was one leader overall In six minute walk distance was limited in this patient population. Besides COPD patients, about 27% of the time underlying coronary artery disease, heart failure, asthma and 17% interstitial lung disease and 9% and about 7% of these patients had a prior single lung transplant and in the native lung ended up developing a lesion. So these are patients that either had I. L. D. Or COPD as a cause of their need for transplant. I can see our nodule distribution most of them just had one but about 25% of them had to or greater and uh 50% of them had a Bronc assigned 50% did not. Most of them were in the upper lobes, either right upper lobe or left upper lobe. Less of them were in the lower lobes or middle lobe And a nodule size and about 70% was less than 20 or or two centim and 57% of them were pet avid. Most of these were peripheral away from the floor. It was about 16 mm. So most of these were in the beyond the sixth generation seventh generation of greater in about 50% of these cases. And radio E. Bus was able to be used in about 95% of the cases by using kind of approach that I've outlining those selected cases before. These patients, 74% had one nodule biopsied Us and able to use the rebus to identify the cases, 95% of the time and I told you that they were in a peripheral airways. The importance of this is about half of these patients were malignant and half were not. So just treating everybody the same with the peripheral nodule sending them to surgery or sending them to get pureed. Radiotherapy would mean over treating the patients for something that they didn't need. Almost half of the time when the patients however were found to be malignant. No surprise, since these are peripheral lesions for the most part, about 64% of these or adenocarcinoma. And we weren't able in these 69 cases to do three of the cases. Because with the that approach that I said because we weren't able to calculate the airway because of the acute bending radius and we had to use other techniques to be able to put either a small brush out into the area and those were considered to be technical failures. Um We had fork nodules that we couldn't diagnose appropriately because of an atomic problems. And those patients had follow up either open biopsy or T. T. N. A. And those patients were found to be malignant. So our overall accuracy was about 94% of the population. And 6% of the time patients had to have because of the suspicion that indeed we did not disprove that it wasn't malignant and it was benign. They went on to further diagnostic work up and then were treated for a malignancy. So I think the point of this is that we now have tools that I think are much better in terms of satisfying some of the concerns that are raised with lung cancer imaging, how to prevent the morbidity of spurious and non diagnostic techniques and some patients that that may have a lesions suspicious for cancer without undoing more morbid procedures that might not be needed. I think that we can approach T. T. N. A diagnostic yields um Hopefully uh with a broader therapy that has less risk of pneumothorax. Um And I think that others as others have shown the use of these combined modalities increases our diagnostic approach with acceptable morbidity to detect spN and patients with advanced COPD and other forms of lung disease. I also think for the future that this provides a pathway for future development of a blade of therapies for high risk patients for treatment of malignant spN that in the future that we might be able to treat after we diagnose an spn to be found malignant and the bronchial E at the same setting under anesthesia and selected appropriate patients. So with that I'll end and I'll be happy to take any questions that people may have arrest those. So dr crider. What are some of the other complications of TTN? A needle biopsy beyond pneumothorax, there might be some bleeding but that's pretty uncommon and rare. So most of it is related to um really the the pneumothorax overall um TK and as you're you know defining like the best timing for screening and to to meet that early diagnosis. Um What what's the key to look at smoking history? Current COPD diagnosis? Still smoking uh symptomatic patients. What do you recommend most? Mhm. Well I you know fortunately for us the U. S. P. S. A. T. S. As the United States preventative services Task force has just released updated recommendations based on two things meta analysis they did of the published literature. Um as well as a says net which is an arm of the um uh en ci who did a risk assessment for lung cancer screening and patients at risk. And they give us good indication for patients that smoke 20 pack years of history or greater who are between the age of 50 and 80 and have uh smoked within the last 15 years or current smokers that those are the patients that are at highest risk for development of lung cancer. Where annual screening is warranted for these patients to look for a solitary pulmonary nodule and determine their risk. And that's based on their analysis. As I said in modeling that suggests that the benefits of screening outweigh any of the risk that we've talked about in the last half hour. So that is the best I think evidence to support right now. Big thanks. And how has this changed your practice? Well, I think um it's a lot of us have a pathway that we feel comfortable that we can take patients who have a problem discussed with the patient with to expect in terms of the likelihood of yield on a diagnostic biopsy with the acceptable like risk of complication. I mean none of this is a complication free. But it's less than what it's been reported in the past decade. So I think that gives us a good way to talk to patients about informing them further when we do shared decision making about what to expect and why we would want to do lung cancer screening. And if we find something that needs to be followed up on how would we approach the follow up with that? Mhm. And in that regard, how important is navigation? You know, for these patients as far as you know, decreasing their time to diagnosis and that not straight line that you showed in some of the current pathways. Yeah. I think all of us who have had, you know know somebody or personally have been told well you might have something that's cancer or whatever organ it is obviously the anxiety with that is high. Um and showing a patient and and putting them in a pathway where they have someone that's guiding them throughout and expeditiously taking them through the pathway of trying to find out what needs to be done for them or not. That is I think the most reassuring thing for a patient and I think all of us would want that to be done for ourselves agreed definitely. And thanks everybody for the questions. Please keep them coming. Um dr Criner you showed That 25% of patients had two or more nodules. Does this factor into that repeat the need for repeat, rancorous copies and some patients that one may be reachable. Others are more distal and hard to reach and patient has to come back into the Bronx sweet for a second advanced procedure. Yeah it's a good questions. Uh Some of the patients can be we've done multiple lesions in the same setting so depending on what you're doing for a patient you know and ask optically you can do this. That's somewhat of a the difference between doing it with C. T. Guided needle biopsy because you're obviously only going to be able to for most cases biopsy one lesion and um only ever one side at the same setting. Where and the broccoli bronchus copy cle you could potentially biopsy multiple lesions, multiple lobes in different size of the lung so that are different lungs at the same setting. So that one's itself to be able to biopsy more lesions at one setting from the bronchus coptic standpoint depending on the individual patients. Um And one thing that I think everybody knows that we'd like to minimize the number of diagnostic procedures that you put a patient through. Especially ones that you know the cohort that I presented people who have significant underlying lung disease. It's not you really have to be um conscious of that. Okay what are the limitations of the technique? Which nodules or locations locations or patient types might you avoid? Yeah so patients that have lesions that are really um on the pleura in a difficult to articulate position would probably be better served with T. T. N. A. Especially ones that are highly articulated in like RB one posterior medial. Those are a little bit hard to get to. So with those patients in those circumstances they might be better served with Aetna. Those patients where there's no peripheral airway that's really no airway signed, leading to the lesion where there's a larger swath of peron coma that you have to go through to get the lesion that might have a vessel that you can see that's interfering with your path if you're going to do a per cutaneous approach through the airway wall. Those are patients also that you might want to avoid. So it depends on some an atomic concerns and how much the capabilities of our current tools to be able to to navigate to the periphery And um really uh if your path is kind of like obscured by vessel overlay, Great, thank you. Are there other comorbidities that cause similar challenges to COPD diagnosing these patients? Well, interstitial lung disease is problematic because of the oxygen the patients require. And also from some patients of fiber optic traction that occurs. So that makes it somewhat challenging to like navigate to some of those patients. Um Those are probably the two most common co morbid conditions pulmonary Hypertension would be a 3rd. Although personally we haven't encountered patients with severe pulmonary hypertension that we've done but that would be a third. It's always a challenge for bronchus ka pik biopsies in patients with a higher degree of pulmonary hypertension. Um, those would be the three things that would come to the forefront. Gotcha. And I think that someone may have had their hand raised if I didn't see that. I apologize. Please try that again. In addition to the Q and A questions. So there we go. So I see Dr roman. Petrov has his hand raised jess. If you could please allow DR Petrov to ask a question. Okay. Yeah. Dr Greiner, thank you for the very interesting talk and thank you for the leading the effort. So the results that you share the astonishing and I think it is a game changer. What would you see as the barriers to implementation? It's uh, sort of, uh, system wide and, and then the community, because frequently new technologists, um, impaired by the reimbursement and do you see this as a problem? And this technology as well? Yeah. Thanks roman for that. Well, the most common, I guess obstacles to this technology is, um, robotic platforms. There's two that are FDA cleared and commercially available. They're both not inexpensive. So an institution, you know, has to factor that in when they're Putting out capital outlines. So that's one a cone beam cT scanner also is a precious commodity that's not routinely available at war. Not always readily accessible because most of cone beam cT s are an outgrowth of vascular surgery or CT surgery. And those are the most institute for neurosurgery. Those are shared commodities. So they're not always readily accessible and some institutions, smaller community hospitals might not be able to put out the outline for that. And so those are two that being said using robotic platforms have been advocated by others just by using um, C arm fluoroscope E um and using multiple planes of Flora Skopje and using radio E bus. There's other navigational platforms that have been used with tips, sensors on tops of tools and devices to kind of avoid the need for cone beam cT. Um, and the costs that would go along with that. So, those are other um, imaging modalities that might be useful real time to try to handle some of these problems. But in my experience where I find the greatest use is being able to cut down the time under general anesthesia for a patient who has compromised with advanced lung disease. That to me, is the greatest benefit for this with an acceptable diagnostic yield. With less complications. So, um, I think that's the limitations. But to me at institutions like ours, the benefit is, is what I said, it allows us to do something simpler quicker with less complications in a sick patient. Doctor kroner, this has been extremely useful. Um, and again, a very important patient type, you know, those that if we can decrease the time to diagnosis and lung cancer and some of the specifics that that folks need with advanced lung disease, I'm glad that you're here as a resource Before we wrap up. If there's any other final questions we're happy to ask. Um but I will also put in a bit of a plug for the international COPD conference. The gold meeting coming up next month, november 16th, um is also going to include a a portion on the COPD and lung cancer and opportunities and challenges. So Please try to log into that virtual event on November 16 as well. We appreciate everybody taking time to join us today. Uh, there's actually a link to the registration site for gold here in the chat. Thank you heather. And again, thanks for joining us here live from Temple Health and Dr Criner. Thanks again for your time and we're here as you need us. Thanks TK Thanks heather for putting us together
