Everyone, thank you for joining us tonight for our CyPath Lung in Practice webinar. My name is Julie Anne Overton, and I'm the Director of Communications here at bioAffinity Technologies. Before we begin the webinar, I have a few housekeeping items to go over. This session is being recorded and will be available for viewing on our website at www.cypathlung.com. Regarding tonight's setup, all of the attendees are muted by default, and your cameras will remain off throughout the session. Dr. Gordon Downie, who is our Chief Medical Officer here at bioAffinity Technologies, is going to moderate the conversation, and he will introduce our panel of pulmonologists. You may submit a written question at any point during the webinar through the Q&A panel at the bottom of your screen. Dr. Downie will direct the questions to our panelists during our question-and-answer periods throughout the program.
If we don't get to all the questions, we're going to try to follow up with an email after the fact. For our healthcare professionals who are joining us tonight, you will receive your DoorDash voucher on the same email that you used to register for the webinar. With that, I'm going to hand things over to Dr. Downie and our panel of physicians. Thank you again for being here.
Thank you, Julie Anne. My name is Dr. Gordon Downie. I welcome you, audience, tonight for our CyPath Lung Testing, A Simpler Path Forward. I'd like to thank bioAffinity Technologies for providing this platform for our audience and for our panelists. I'm a first-generation interventional pulmonologist. I trained at UNC Chapel Hill. I've mostly published in photodynamic therapy, early lung cancer diagnosis, and bronchoscopy education. I joined CyPath as their Chief Medical Officer about 12 months ago, and I've had a wonderful year working with them and talking about our product. Tonight, we're going to have an in-depth discussion about the clinical burden of processing early lung cancer and pulmonary nodules in high-risk individuals, either by screening or surveillance in survivorship or incidentally found pulmonary nodules. I'll be asking our expert panel to share their experiences with diagnosing lung cancer and assessing pulmonary nodules.
There will be two question-and-answer periods. We're fortunate tonight to have a wonderful expert panel who have significant experience in this arena and have added CyPath Lung to their clinical practice algorithms. We have Dr. Guda joining us from San Antonio. He's an interventional pulmonologist and specializing in robotic bronchoscopy, airway stenting, and minimally invasive diagnostics in lung disease. We have Dr. Michael Nicholson joining us from New Jersey, Robert Wood Johnson practice in New Jersey. He trained at Temple, and he does pulmonary and critical care. Lastly, we have Dr. Greg White joining us from Texarkana, Texas, at CHRISTUS St. Michael Hospital. He specializes also in pulmonary and critical care. He assesses about 500 pulmonary nodules every year. Very expert panel. Tonight, our clinical problem is basically how we treat and how we assess patients who are involved with pulmonary nodules.
Every clinician who's joining us tonight is in a unique region that have different ways of defining the components of pulmonary nodules and the clinical challenges that assessing lung cancer, diagnosing lung cancer, and assessing pulmonary nodules. As an interventional pulmonologist, at one time, the vice chair of the ACCP committee on intervention, and now as a practicing pulmonologist and CMO, I have heard from clinicians all over the country about the challenges of dealing with pulmonary nodules. I'd like to ask our panelists to talk about some of their challenges that they face in this interesting arena of assessing pulmonary nodules. Dr. Guda, perhaps you can start our discussion.
Thank you again, Dr. Downie, for introducing me and bringing me in to talk about this. As an interventional pulmonologist and as somebody that does quite a bit of robotic bronchoscopy for diagnosis of these small nodules that we previously could not get to, it's raised a very interesting question as to what we do with the smaller, if you're able to access smaller and smaller nodules, or we're able to go to those portions of the lung with a robot that we have never previously been able to get to, the question is, well, if you can do it for every single patient, should every single patient actually get that procedure that comes with a lot of risks associated with it?
In our practice, we have a very robust practice, and we do quite a few number of pulmonary nodules as well as advanced interventional procedures, including laser stenting, debulking, pleural biopsies. A lot of times, the type of patients that we are seeing come in quite apprehensive because they either have a history of smoking or they know somebody that has had lung cancer, or they've had family history of lung cancer, and now they've got this abnormal spot that is there in their lung, and they are unaware as to how they want to proceed with it. One of the methods in assuaging some of the grief that the patient may experience with that initial diagnosis, shock diagnosis of, "Hey, there is something here on this CT scan that's concerning," is to help risk stratify them, and that's essentially the biggest portion of why CyPath works.
There are certain patient populations that do better with risk stratification and there are certain patient populations that just want to go forward and get a biopsy and be done with it. Either way, this piece of data informs us as to with what clinical confidence I can go in when I'm performing the biopsies to help answer those questions. In most of our patients that are coming in, our practice is predominantly an oncology-driven practice. We have a lot of oncologists that refer to us, but we have a not insignificant number of patients that come to us through the ER, through primary care, through general pulmonary, and all of those nodules that we see can have a varying degree of risk.
We do utilize it in those patients whose Mayo Clinic model is insufficient in giving you the information, or you have got a nodule that does not meet Lung-RADS 4B, and then you are thinking, "You know what? I need to do a biopsy of this." Maybe, but there are risks associated with it. The patient may not be the best patient take for anesthesia. Well, we definitely have a role for CyPath there to help risk stratify, and then the patient's own sputum gives us the information, and then we proceed with the next steps, whether it's management with biopsy or management with imaging at a reasonable cadence. That is all something that is informed because we have another tool to help us with risk stratification there.
Absolutely. Dr. White, you have a very busy practice in northeast Texas. Maybe you could describe the challenges that you face in dealing with pulmonary nodule assessment.
Well, kind of echoing what Dr. Guda was saying. In my simplistic way I think about it is not every patient needs a procedure, and not every nodule needs a biopsy. It's just kind of an easy way to think about it. There's always risk anytime you put somebody under for a procedure, there's always a scary thing if you have biopsy. That being said, risk stratification is always great. It's encouraged me to go after procedures, had patients get procedures. It's encouraged me not to go after patients for procedures. I've even used it sometimes when the patient was high risk for a procedure and the PET scan was positive and this was positive. I've had radiation oncologists go ahead and start treating based off of that risk stratification. What I'm seeing with nodules is we've had a huge influx of low-dose screening CTs through our hospital system.
We're doing about 120-150 a month now, not counting what I'm already tracking, and I'm getting more and more nodules coming in, and you just can't spend all day bronching and finding a way where these things settle out at.
Dr. Nicholson, you're on the East Coast in New Jersey. Can you talk a little bit about your practice challenges with pulmonary nodule assessment?
Absolutely. I think one of the biggest things is I try to keep up to date on a lot of medical literature, podcasts, webinars, and things, and I'm inundated with mediastinal cryobiopsy, MONARCH first Ion, all of these new tools and tricks, and everything is about how do we biopsy better, but not who is the better person to biopsy. I think that's a really important thing for us to focus on because the prevalence of lung nodules is increasing, and we need to utilize the resources correctly. My fellowship was at Temple Lung Center. The bronchoscopy suite was two ORs that both had Ions and Cone beam CTs. Every millimeter nodule, someone wanted to take a poke at it. Now I'm in a community-based practice with an academic affiliation.
Several groups, high volume of nodules, smaller amount of Ion time, and we have to find out who are those patients that are the best suited for it. Everything in medicine is about pre-test probability. Before you go into a biopsy, who are the patients with the highest pre-test probability to actually have a cancer? That's who you want to biopsy. Our current tools for that are not great. We have multiple calculators. In the ViewMedica talk, we showed how multiple calculators show different scores, and some say biopsy, some say don't. So what are you trusting? When you have a non-invasive diagnostic test like CyPath, it helps you to have a better pre-test probability before you make a decision like that, because this burden of nodules is only going to increase.
Right now, most insurances and Medicare will cover the USPSTF guidelines, which say former smoker or current smoker are those who have quit within the last 15 years. For several years, the American Cancer Society has been encouraging people to remove that quit within the last 15 years and just anyone who smoked for more than 20 pack years. If you've got a chance to review the new cholesterol guidelines from cardiology, they are really encouraging the use of coronary artery calcium scoring. I have a lot of incidental nodules in my practice found on coronary artery calcium scoring. There's just this real need to figure out who are the right people and optimize that pre-test probability.
Absolutely. For our audience, I know a lot of the clinicians that are listening tonight have similar problems and feelings that our panelists touched on. Just to review again very quickly, there's a rapidly evolving increased burden to all clinicians based on what you just heard from Dr. Nicholson, Dr. Guda, and Dr. White. Why is this burden exploding? Increasing screening. Finally, we're hardwiring a lot of family practice doctors, internal medicine doctors, and hospital systems are hardwiring their screening for the high-risk individuals. Also, what the definition of high risk is expanding every year. We're finding out that non-smoking related lung cancers are increasing in the population. We have now probably 10-20 carcinogens that most of the US population is exposed to. Who's at high risk? That's an expanding population.
Now with AI-driven mining of EMRs, there's more and more hospital systems that are finding every time a pulmonary nodule, quote-unquote, is mentioned in an EMR. As pulmonologists and clinicians dealing within this area, we are getting the full burden of this. Dr. Guda, I'd like you to talk a little bit about how you receive your referrals. Do you receive them from hospital systems, from internal medicine docs, family practice docs? How do you receive these referrals, and how are you told, or how are you directed by those referring people about your next step in the process?
I alluded to this earlier today, earlier in this meeting where I said a lot of our clinical practice is kind of directed by the presence of oncology. We have about 34 different oncologists that feed into our practice. Essentially, these oncologists, they are looking for answers. Our clinic is essentially a procedurally-driven clinic because these patients have already been seen by oncology. Either you're looking for metastatic disease or you're coming in with a higher clinical gestalt than you typically get from a primary care physician or a pulmonologist. Our clinic is pretty much directed by that kind of a burden. From the community also, we just reviewed some of our numbers, and we are seeing an increasing awareness in the community about screening. It's a great point that Dr. Nicholson made, is the 15-year mark benchmark is an arbitrary number.
It is based on old data that doesn't really have the same kind of consensus as smoking history positive, smoking history negative. There is an increased awareness in the community as well, where we have a larger population of patients that do get sent to us from the primary care physicians, and those patients have variable risk factors. There are also physicians that say, "Hey, I've got a three-millimeter nodule. I do not know what to do about it. I am just going to go ahead and send this to the lung clinic for management." Then the patient comes in quite worried, "I have a three-millimeter nodule. Are you going to biopsy this? Is this cancer or not?" Right. That is where the patient population variance comes.
Now, with oncology, patients that have had breast cancer five years ago or cervical cancer 10 years ago, and they are being monitored for something or the other. They have had abdominal pain. They do a CT scan of the lung. They see a small nodule, get a dedicated CT scan, and then you get a small nodule on that. Then what do you do with a six-millimeter nodule? How do you risk stratify somebody who has had a history of solid organ cancer, and you have a six-millimeter nodule that is there on their lung, and now you are to choose, do you biopsy, do you not biopsy? Right?
Absolutely. I'm sorry to interrupt. The American Cancer Society is really wanting to focus on not just screening, but the survivorship and surveillance side, the off-ramping from treatment of lung cancer after lung cancer has been diagnosed and treated. Could you talk a little bit about CyPath Lung and your clinic, and how you deal with survivorship and surveillance?
We use it in moderate amount. I would say that a lot of our patients that do come in with nodules that may not be amenable to biopsy, but you still have enough of risk factors, which is the point I was about to make next, is those patients, we do have them get us CyPath samples, sputum samples, to send for CyPath for us to be able to say, "Hey, this is the risk factor. This is what we see on the data coming out from them now. The nodules have not changed in a year. Let's repeat it again and see how we can assess it." Now, that volume is small. It is not the bulk of the patients that we have. For every 10 patients that for CyPath, one of them is going to be for the surveillance in our practice right now.
Dr. Nicholson, maybe you could comment about nodules, how they come into your practice and your practice algorithm, and how you employ CyPath in your practice.
Absolutely. I think Dr. Guda had touched on something important there when he said the anxious patient, right? We'll talk a lot tonight about data and about workflows and things, but at the end of the day, a lot of times there's a patient with a five-millimeter nodule sitting in front of you, and you as a clinician knows that this is probably nothing, but then as a patient with ChatGPT thinks that this is the end of their life. Having CyPath as a way to bridge that gap between when is the repeat CAT scan, if you're not going to go after this for any reason, and relieve that anxiety for patients is a huge part of it that I wanted to bring up as well.
For me, I'm in a practice with 10 other pulmonologists ranging in age from me, who's out of fellowship recently, and pulmonologists who finished med school in 1984. We're all over the place, and me and one other physician does most of our biopsies. A lot of our referrals come from the community cardiologists who get CACs and primary care doctors who do a lot of screening. We also have a very large patient panel who's doing LDCTs every year.
I receive a lot of the referrals to do the biopsies. Basically, all of my colleagues who have patients who have a nodule, they will send me, say, "What do you want to do? Do you want a biopsy? Do you want to do a PET? Do you want to do." I say, "Well, let's start off and let's get a CyPath. It'll take us a few days to get the results. The patient just gives a sputum sample, and then we're going to know a better pretest probability of what the best next steps are." It works in very early to my algorithm in a lot of these nodules, especially the ones that are less than 1.2 centimeters and the ones where PET is more unreliable, seven, eight, six, things like that.
Dr. White, we're both from Northeast Texas, and we've been colleagues for a long time, and we've talked about our individual clinics. I know we've discussed anxiety, patient stigma, patient nihilism, and how anxiety and fear affects the process. You want to touch on that a little bit?
Absolutely. Our patients, I imagine like most patients that live in the community, they're all a little headstrong and stubborn. Most people here smoke. I still have an ashtray outside my front door in my office because I got tired of people throwing cigarette butts in my bushes. They know that. They know they're smoking and there's a risk associated with it. They're like, "Ah, I'm fine. It's not bothering me." Somehow they get a CAT scan, they find a nodule that makes them cough up some blood. Oh, it's okay, the blood has stopped, or it's still coughing up blood, and they'll just kind of kick the can down the line for a little bit. They can be very scared, even though it's six millimeters, they're just fretful about it. Those people, CyPath gives them peace of mind, just like it's negative.
If it's positive, we should probably do something sooner. That's kind of upfront with CyPath. The other thing, I kind of use CyPath a little bit downstream. I've seen Dr. Guda's bronchoscopy suite, and Dr. Nicholson sounds like he's got a pretty good bronch suite. Ours still has not been updated yet. Our comfortability for what we have for our navigational bronchs, I'm always kind of on the fence on. If I get a negative biopsy from a nodule and the lymph nodes are negative and the CyPath is positive, I have a more stronger clinical indication, especially if it's high risk, to actually go into resection or talk with a radiation oncologist sooner than later.
It's just kind of an added, for me, it's a downstream piece, so knowing that, well, was it truly negative or was it truly positive and it truly is a true negative. There's some upstream value to it and some downstream value with respect to these nodules in terms of biopsies.
Absolutely. As far as in my practice, patient stigma was a big deal. COPDers blaming themselves and not really wanting to pursue it. The fact that CyPath could be mailed to them privately in their home, and they didn't have to travel, it could be done at their own time and their own pace, that was a big deal. You touched on something very important, all three of you did, that it's a data point that each clinician can add to their armamentarium when talking to patients to relieve anxiety and relieve fear, because there are mixed messages. Dr. Google is alive and well, and a lot of patients will come in having consulted Dr. Google.
Having an additional data point with a high sensitivity, 92%, negative predictive value 99%, for nodules under 20 millimeters really helps in these discussions and quells anxiety and fear. I think at this point, before we break for questions, I would love to hear from Dr. Guda, maybe with a case that you've had, and then Dr. White, maybe you could follow that with one of your cases.
Absolutely. Do we want to break for questions, or do we want to do the case first?
Well, so far there are no questions. There are no questions yet, so I think we can go straight to your case. I do invite the audience, absolutely, to please submit your questions.
Okay. This is actually one of the first cases where it was like the first use case for CyPath for me, because I'm a skeptic at heart. I like a very healthy dose of skepticism with my morning coffee. Whenever there is something, any new piece of technology that comes through, I like testing it and making sure that it actually works. From what I see, this is actually a very interesting patient. She's a 66-year-old female who's known former history of smoking, quit about five years ago, and she developed abdominal pain, some discomfort. She has got some vasculopathy in the abdomen, so they thought there was some sort of an obstruction taking place or essentially ischemia. They did a CT scan of the abdomen and pelvis, and they noticed some ground glass changes in the base.
The next thing they did after that was, hey, we're not sure what this is, but let's get a CT angio also because we think that our CTA of the aorta, just to make sure that there is no evidence of vasculopathy. They caught what's highlighted here in the red circle is this schmutz, as the best way of some of the radiologists describing it. It's essentially some ground glass nodules for us who are more technical. It's ground glass nodularity in the right upper lobe with other ground glass nodularity throughout the entire lung. Now, based on her history, it is not a very solid nodule. At the most, in the greatest dimension, about 13 millimeters.
It's not very suspicious, but it is a little bit suspicious, where you are considering, and based on the history and the surrounding emphysema in a patient that had quit smoking just recently, that maybe there's something more to this. How do you risk stratify based on all the other modalities that Dr. Nicholson was touching on? Every single modality that you put in for risk stratification, it gives you a different number. The benchmark, the goalpost keeps changing, right? In those situations, we thought maybe we should do a PET scan because the patient got sent over to us from the ED for this nodule. The patient was quite nervous about it, obviously. She had some family members and some, not immediate relatives, but friends, have lung cancer, developed lung cancer. She was worried.
PET scan wouldn't be very informative because the solid component is less than six millimeters. We looked at what the follow-up options were available to us, which was both a six-month CT scan and watchful waiting for three to five years. The patient, given that she has family members who developed cancer, and now we are worried about something that's going on in the lung. She's aware of what that means and what that looks like. We decided to go forward with CyPath. This was, I think, our third or maybe fourth patient that we had set up for CyPath. The pre-screening risk was low, and the CyPath results came back at 0.8. Sorry, not 0.8. At 0.7. We, at that point, were quite surprised. We proceeded with discussing risks and benefits of a biopsy.
We did a robotic bronchoscopy and performed a cryobiopsy, which is where you freeze the tissue and you pull that and you get a larger chunk of tissue. Lo and behold, it was positive for adenocarcinoma. She was sent for tumor board review. We reviewed her case, and it was early invasive adenocarcinoma. She had a PET scan done, the full gamut, and because the ground-glass nodules were only isolated to the right upper lobe, they elected to go forward with doing a full right upper lobectomy on her because of all the other. This patient, I think this was about a year and a half ago, and she's had follow-up CT scans that have been clear thus far. She did not need any further testing. Sure enough, it was early invasive adenocarcinoma in this patient.
This was one of those first patients that made me a believer, I would say, that there is a modality out there that can be reliable in comparison to some of the other modalities that are there, where this patient profile doesn't fit under those models, that other risk stratification profiles are available. Right? This profile of this patient fit just with this or biopsy or watchful waiting. Sorry. When we are nervous about following through and just doing watching for somebody who has risk factors, and the biopsy maybe seems too aggressive because of the surrounding emphysema, risk of pneumothorax, all those things, this really is helpful.
This CyPath really was helpful to push us into the direction of doing a biopsy, where I, at the time of evaluating this patient in the clinic, was not convinced one way or the other that we should be doing a biopsy. I'm glad we did, because now she is potentially lung cancer-free.
Before we head over to Dr. White's case, I did receive a question just now to go over some of the statistics of our clinical trial. Our clinical trial for CyPath Lung was peer-reviewed published, and we reported a 92% sensitivity, a 87% specificity. We provide data as a binary, either likely or unlikely. This is based on our negative predictive value, which for nodules less than 20 millimeters is 99% positive predictive value. Dr. Guda's case, based on the specificity and positive predictive value of 61%, obviously, the patient, Helen, benefited from that positive predictive value. We have a very robust clinical trial demonstrating, I think, best in industry sensitivity area under the curve of 89% and specificity as well as the positive and negative predictive values.
As you know, everybody's prevalence in regional United States is slightly different, and that's why the negative and positive predictive values are so important. I hope that answers the question from the audience. Dr. White, would you like to talk about your case, Samuel?
Not yet. I actually want to talk about the statistics real quick, because you raised a good point that I always think is important for me. Out of the statistics, the positive predictive value is actually the weakest statistics there, at 60%, but the negative predictive value is really high. Going back to my statement that not everybody needs a procedure, not everybody needs a nodule. If I can give somebody peace of mind that this is truly not likely cancer, there's no reason for them for a procedure. That being said, it's also all-comers. When they cough up their fluid, they're identifying cancer cells. We're not saying it's a squamous cell or an adeno, a prostate, whatever other lung, breast cancer. It's all-comer cancers that is coming out when they cough up.
You're saying, yes, it's going to be a cancer, or it's not, with the final results with the biopsy. The positive predictive value is about 60%, so you still ultimately have to get a biopsy if it's positive. Even then, it's not always going to be a cancer, but it kind of gives you a risk stratification on who you need to watch closer, who do you need to pursue quicker. If it's truly negative, I feel much more comfortable let things ride. That's what's, kind of, nice about it. Yeah. Now I can talk about my patient.
Now, in the meantime, we've gotten several more questions. Before we go to your case, I'm going to answer some of these questions. The next question is: What are the biochemical markers of the CyPath test? Can you please elaborate a bit more on what it looks like and how it detects malignant cells? Excuse me. The reason I became interested in CyPath Lung testing was my background in photodynamic therapy, which uses porphyrin biochemistry as its core technology. We're a diagnostic test, a supplemental diagnostic test, that uses sputum, which goes through flow cytometry, which is AI machine-driven for amplifying those results. There are basically four main data points that go into our algorithm. We incubate the sputum and porphyrin, which stains the malignant cells. We identify pulmonary macrophages with receptor stains, so we know we're getting a good lung sample.
We filter every sputum sample that comes in that gets rid of debris. We identify apoptotic cells, which we found extremely important for the flow cytometry. We also special stain immune-active inflammatory cells within the lungs. It isn't just the cancer cells we're looking at to give us our likely or unlikely diagnosis or probability. We are also looking at the microenvironment within the lung. You can imagine that the small tumors are producing a unique immune response that we'll be able to see in the sputum. These four data points, the macrophages, the immune cells, the tumor cells, and the apoptotic cells, are assessed in flow cytometry and gives us our results. I hope that answers that question.
The next question is: What patient populations have you found that CyPath may be more likely to give false positive results in, or in what situations would you not recommend using it? That is an excellent question. We have a huge study that we've started with 2,000 patients, and I think we'll better answer that when that study is at completion. Clearly, what we see for the negative predictive value is we had an interesting case where someone had florid thrush, and that sample turned out to be unlikely. Then we realized in our lab that all of the patients, when there's a heavy population of yeast, we were getting negative values. We realized that the yeast was blocking the gating and the flow cytometry. Now that is one of our exclusion criteria, active thrush.
I think we're going to find more and more about what we need to exclude and include as we go through our bigger study. The positive predictive value of 61% is very competitive. It's comparable to the Cologuard test for colon cancer, and certainly stands up to imaging mammography for breast cancer. Even though that sounds like a weak number, it's actually very predictive. I do think, again, the bigger study will show some of the reasons for positive predictive value being at 61%. All right, Dr. White, go ahead. Your case, Samuel, is up.
Okay. Well, this guy's been kind of a classic patient. He's 68 years old, still smoking. He was referred by a primary care doctor for coughing up blood. Primary care doctor treated him with some antibiotics and some steroids. He was such an active smoker, he was smoking in the parking lot when I walked in to see him coming from the hospital. Smoker, coughing up blood. Between when he saw the primary care doctor and saw me, his bleeding had stopped. Kind of this stoic kind of guy, "Just leave me. I don't want to be a problem to anybody. I'm happy just being who I am and just leave me alone," kind of attitude. Wife was there. She was kind of worried. He didn't want a biopsy, and he was willing to do a CAT scan in three months. Well, the CAT scan to me screamed cancer.
He looked like he had cancer. Still smoking on top of cancer. Then I was like, "You know, we can do that, but let's do a CyPath. And if it's positive, then we can talk about biopsying. If it's negative, we'll watch." He was okay doing that. Sent it out. Came back, it was positive on the CyPath. We biopsied him, Stage 1 cancer. He's gone under resection at this point. He's doing well. He's still smoking, but we're just watching for new things to grow at some point. He's done well with this. This encouraged a reluctant patient to actually get something done that needed something done.
Perfect. Dr. Nicholson, I don't believe we have a slide for you, but I think you have an interesting case also that you'd like to discuss.
Definitely. I know Dr. Downie and I have discussed many different cases and utilizations of CyPath. Actually a couple of days ago, not a case I was planning on coming here to talk about, but something that struck me as so interesting, and I was so happy that I had the ability to use CyPath now when before I would have not known what to do in this situation. It's actually a patient who is currently being worked up for a heart transplant, with obviously severe heart disease, not someone you want to put under general anesthesia. Throughout the workup, former smoker, had a CAT scan done, showed a six-millimeters nodule plopped right in the middle of the right upper lobe. IR can't touch it with a TTNA. Doesn't look like a great area going to for a navigational with someone with my experience.
Obviously someone you don't want to put under general anesthesia. Heart failure is saying, "We need to know about this nodule before we pursue doing a heart transplant on this patient." I was like, "Well, what if I told you I could send a sputum kit to the patient's house and they can do a non-invasive diagnostic test with a 99% negative predictive value?" It was just such a unique situation. Obviously, most of us are not going to encounter something like this really frequently, but Dr. Guda, Dr. White, and myself can go over tons of cases like the ones they just presented. I want to kind of add that unique perspective of something that came up also about how simple it is to do. There are so many things in healthcare now.
When you tell the patient, you have to get this test, you have to get this product. They have to make phone calls, their insurance, they have to schedule appointments. It's difficult. CyPath, I tell them, "The company's going to contact you. I'm going to fill out the paperwork. They're going to send it to you. They're going to call you and instruct you on how to do it. And then they're going to come pick it up from you and bring it back to their lab and send me the results." The patient's like, "So what do I have to do?" You have to answer the phone, and you have to give us some sputum. They're really relieved to see something so simple that they can do, and especially a patient like this who has all the anxiety going on of doing a heart transplant evaluation.
To have something that's so easily accessible and valuable is really phenomenal.
I had two questions, almost identical, asking about the low percentage of screening that we see in the United States. We touched on the fact that patient nihilism has a lot to do with it, that patient stigma, blaming themselves, has a lot to do with not wanting to pursue that. As a corollary in these questions, they said, "Well, do you think CyPath Lung can help with the screening process, improving those screening numbers?" I'd like each of the panelists to maybe comment. Do you think CyPath as a adjuvant supplemental test will allow us to do better with screening?
I have a very interesting take on this because, or at least I think it's interesting. Patients, when you tell them you have got to go and get screened to find out if you have cancer, immediately go, "Well, I don't want to know," or, "I don't think I have cancer. I don't feel bad. I don't want to go through with the testing," because you're unsure. At the end of the day, I like the colonoscopy where you go in there and you see a polyp, you resect a polyp, you've essentially taken out the pre-cancerous lesion, and you've also screened them at the same time. An imaging study like this, it's different, right?
In patients that when they are going to go get a CT scan done, shell out so much money, most of them living very much under their means, giving them a test that says, "Hey, listen, you meet several risk criteria. Doing a screening for you is going to tell us something, whether it's really bad emphysema or you've got pulmonary nodules that need to be evaluated." Maybe doing this sputum testing may help them understand the importance of it, because you're doing more than just screening them for the nodule that they have, but you're also going to risk stratify them, not at the same time, but in sequence.
Sometimes patients may seem a little bit more willing to go forward and get a CT scan done if they have a known higher risk, not just by numbers, by saying, you're a smoker, or you had quit smoking 15 years ago or 12 years ago, you still may be at risk for developing this. While you want to have a nodule when you're performing this, I wonder, it's a question, I wonder if those patients that get screened with a sputum test first, you define whether or not they're having an increased risk based on their sputum analysis, and then they do the CT scan. Will that increase the number of patients that we actually collect for biopsy that are going to be positive down the line just because you've had a risk stratification test done first? It's an interesting take.
It's not imaging and then you do the risk stratification, but it's like putting maybe the cart in front of the horse kind of a method. I wonder if that is something that might help improve the screening of patients that are already at risk at all?
Dr. Guda, I've heard similar questions along that line, so that's an excellent point. Dr. Nicholson, what are your thoughts on this?
Yeah, I think even our scopes we steal from our GI colleagues. Now I think on the Varian talk, they talked about the similarities between FIT testing and this, finding the ways to identify those patients who otherwise would not be screened and use some kind of screening for them in terms of this testing. There's a lot of concern in my area and my practice from patients with radiation, and it's a true concern from them. They don't want to be getting CTs every year. A nodule pops up, you have to follow it again in three months.
I had one gentleman who said, "If I didn't have cancer before, I have it now from all the CAT scans people are ordering for me." To have a radiation-free way to try to risk stratify somebody, I think that's the future of all early detection all across all medical specialties is to do it in the most effective and least invasive way possible for the patient safety, for healthcare utilization and cost, and to figure out how to increase that pretest probability, like I mentioned, to find the patients who really do need a CAT scan and really do need a biopsy.
Dr. White?
Well, I'm glad both of you guys mentioned gastroenterology. The way I look at it, this is actually more kind of my vision of where I see pulmonary going. I think we're in an amazing time for pulmonary. We're actually finally doing some stuff. Historically, pulmonary is kind of like the closet in the end of the hall that people were doing bronchoscopies in for pneumonias, maybe a cancer. We're in the age of robotics, where we're going after lesions that are less than one centimeter, which is phenomenal and amazing if you think about it. We're going to the age of therapeutics, just starting that. Going back to the GI doctors, they've done an incredible job marketing themselves. You used to be 50 years old, you blow out your candles, you got yourself a colonoscopy. Now it's moved up to 45. We're starting to do low-dose screening CTs.
Those are going to start finding more and more nodules and polyps, or more nodules. Going to the GIs, they have your colonoscopy. My brother had his done. He had three polyps. He didn't see a frigging polyp. My thought for the next five-10 years, pulmonologists won't be treating lung cancer anymore. We're going to be treating nodular lung disease. We're going to have tools that will say high risk lesion. We're going to do biopsy, man, real-time pathology reads in the room. Then we can go ahead and treat it with whatever therapeutic is going to be out there. We're getting really close to that. CyPath is kind of going to be, in my mind, will be kind of the starting line to get this whole process started, going from where we're treating lung cancers and start paying attention to more nodular lung disease.
Yeah. One of the questions that I have not answered asked about, and we're reading as clinicians and healthcare providers about potential screening tests for lung cancer, blood tests for lung cancer, you name it. There's certainly a lot of data out there and a lot of newsworthy data out there. The question was specifically why sputum? Why not blood, or some other mode, or direct biopsy? The great thing about the CyPath Lung test is that it's a real-time cancer test. It is looking at the microenvironment of the lung at that time that the sputum is produced. When we say that something is unlikely or likely in our binary result, we are talking about real-time changes that are occurring in the lung. You can use this in patients that have had previous cancers anywhere in the body, previous lung cancer.
Unlike blood tests, which have echoes of the cancer floating around as proteins in the blood, and usually, these tests restrict, cannot be used whenever there's been a cancer within five years, including lung cancer. The real-time exam of the sputum, I think is a huge benefit that favors a sputum analysis over the blood, and obviously not compared to going in and biopsying. As all of our three panelists have mentioned, the risk in a bad lunger of a percutaneous needle biopsy or even a robotic biopsy is tremendous. We haven't really talked about the finances yet of these high-end robotic procedures, but it is a very expensive test. We're in an era of financial crisis and trying to figure out the best use of our money.
Having a cost-effective test like CyPath as compared to going after low probability, as Dr. White just said, low probability nodule with a very expensive test. Just I don't think makes sense to me. I also wanted to mention, early on when I was introducing Dr. Guda, I was looking cross-eyed, and I said he was from San Antonio. He's actually practicing in Fort Worth, so I apologize, Dr. Guda, about that, and he can be contacted through his office.
At the end of our talk, all the attendees will be receiving an email from us with contact information of Dr. Guda, Dr. Nicholson, Dr. White, and also our reps around the country. Our contact with Dallas Coleman, who's the head of our marketing department, because I also got several questions about the logistics of how to order the test and how to go through the test. I think at this point, we've caught up on questions.
I would like each of the panelists to kind of summarize their thoughts. We'll go in reverse order. Dr. White, you actually gave a really good insight into the future of where pulmonary is going. The future and CyPath, you mentioned it, but just kind of restate that in a sentence or two.
Well, I'll just state what I like about CyPath. It's an easy test. Its pathology is agnostic. It doesn't matter if it's a squamous cell adeno, breast cancer, prostate cancer, it's whatever malignancy is in the lung. Gives lots of peace of mind to the patients if it's negative. It encourages me that we should probably biopsy or watch it more aggressively if the CyPath is positive. I've had patients get procedures that they didn't want it. I've had patients not get procedures that they wanted it because the CyPath was negative. It's a good clinical decision tool to use. Downstream also, again, I think there's a huge place for it too. If you do a biopsy and it's negative, is it truly a true negative, or do we need to do something different? Do we need to go to the surgical approach?
I've had patients get treated for a cancer that was a lesion that was positive on CyPath, weakly avid on PET, and is a high-risk patient for any procedure. Just go ahead and do some SBRT. It's a nice easy test that gives you a lot of clinical data.
Dr. Nicholson?
Yeah. I would close by saying that when I was a fellow and a new attending, nodules were probably one of my least favorite patients to see in clinic. I was constantly stressed about whether or not I was making the right decision and overwhelmed by the amount of risk stratification tools that I didn't feel like actually helped me make a better decision and didn't help me to communicate with the patient. I think having a tool that, A, helps me to make the right clinical decision, and B, makes the conversation with the patient more on their level and able to tell them, like kind of pull back the curtain and say, "Hey, this is the data that I'm going on and this is why we're doing this test." It's made me so much more confident in my ability to deal with these nodules in the office.
Every pulmonologist that I've talked to or worked with, like I said, I have 10 who work out of my practice. I was the first to start utilizing CyPath, and every single one of them who used it once, after one use now incorporates it into their practice because they see how useful it is both to them as the clinician and also on the patient end of things. When you get that, while you're waiting for the next CT scan in three months, you get that sigh of relief from the patient when you call them and say, "Hey, the CyPath sputum was negative." They say, "Oh, thank God, now I won't be thinking about this CT scan every day for the next three months.
Guda?
This is actually a great conversation because we're not just talking about lung screening, we're not just talking about biopsies, but we're talking about risk stratification. Where do you start? What type of, what size of nodule do you take? For CyPath, I found it reliable to be from six millimeters or greater, right? For those patients that have already had a previous history of lung cancer, other risk stratification modalities may not be useful because they've already had previous history of other cancers or organ tumors. The future is very wide. It's very bright. You can develop it in whichever way you need to. A lot of this, to piggyback on what Dr. Nicholson said, when I was in IB training, we were the goers. We were walking around with a scalpel, a figurative scalpel in our pocket, right?
We're trying to go in and do the biopsies. This tells us when to not, which is great, because then you can tell a patient, like Dr. White said, "The chance of you having a negative test from a biopsy is very high based on this other test that we have done, based on the sputum that you have given us," not some arbitrary number based on age or your height and your weight and what the nodule looks like. It's a much more reliable tool, in my opinion, when you're having a conversation with people. We use it. I mean, I ordered it a couple of times just today on patients that have six and 6.5, seven-millimeter nodules, and they have history of other cancers.
It's not really looking like a full nodule, like a ground-glass nodule, and I'm expecting it to help me make a decision whether I go after that and do perform a biopsy or not. Can we do the biopsy? Sure. Should we? It answers that, should we?
Should we? Absolutely. Julie Anne or Lexi, if we could put up the algorithm. I have two more questions. Okay, I hope that comes up pretty clear. This is the algorithm that CyPath Lung has developed, and I'm going to walk through it as I answer the two questions, which one was about the Ohio River Valley, Indiana and Cincinnati and histoplasmosis and the fact that probably 90%-95% of CT scans of patients over 60 will have pulmonary nodules. All three of our panelists mentioned the impact of the negative predictive value for nodules under 20 millimeters being 99% in our clinical trial. That is a huge positive when you want to talk to your patient that has these small sub 2-centimeter nodules, probably sub 1-centimeter nodules, in these high endemic areas of fungi.
You can go by society-recommended CT scans if you do a CyPath, and it's unlikely, because the negative predictive value is 99%. That is a very powerful test.
Hey, Dr. Downie, I have a bunch of histo out where I'm at as well, and I haven't seen any problems in terms of the CyPath having a bad result in the histo, because I see a lot of histo out here.
Yeah. The Red River Valley also is an endemic area, absolutely. There was a question about what is the smallest size. Well, I'm going to go and talk about surveillance. I think we have utility, and we've shown utility in radiologically occult disease, having a negative predictive value and a positive predictive value even in radiologically occult disease. Clearly there is utility in the sub-10-millimeter all the way down to six millimeters. I have personally used it in five millimeters and four millimeters with success. Maybe the panelists, have you used it as small as four millimeters?
Absolutely.
Yeah. I think four millimeters is probably a pretty good cutoff for its utility. If you go below four millimeters, all of the pulmonary nodule calculators don't even bother with a probability. I think you can follow society guidelines for follow-up CTs at that point. You have the algorithm that we're suggesting, and I'm going to start by giving the disclaimer, which is the little clear box at the very bottom that says, "The provider, the patient conversation, and the clinical experience outweighs any data point." In the end, as a clinician, you will have a gestalt. You'll have a feeling about that nodule based on your clinical experience and your clinical wisdom. That trumps any data point that we can come up with.
That being said, I particularly find. If you have a patient that's at high risk, and they have a low-dose CT scan and you're sub 15 millimeters, so the right-hand side of our algorithm. You get a CyPath test. If the CyPath test is likely, then even though this is a small nodule, the positive predictive value is 61%. We're going to recommend in our algorithm a biopsy. Again, clinical gestalt might say, well, positive predictive value of 61%, that means that 39 x out of 100, that will be a false positive. If you have the nodule and even with a likely result, if you want to maybe do a closer follow-up with CT scan, that is certainly reasonable. Maybe one of the panelists can comment on that.
Could you clarify the question again, Dr. Downie?
Yeah. You know what? I've just seen that we're approaching. I was very verbose with all that, and we're approaching the 0700HRS time limit. We're definitely getting near wrap-up time. I'll restate the question, and then I think we'll call it after somebody answers that question. If you have a likely result, and it is in a smaller lesion, can you wait and do a follow-up CT scan, or should you go with a biopsy?
Our practice is to biopsy. The smallest lesion I've ever biopsied was four millimeters for metastatic cancer, and that patient did receive a CyPath, and it was positive. That's why we biopsied. Four millimeters is pretty small, but we have done a biopsy of it with successful results. In our practice, we can get after those, and so we perform a biopsy on those patients.
Again, we're at the top of the hour. I'd like to thank the audience for joining us and the excellent questions. I'd like to thank our panelists who really have given insight. I will mention that Dr. Nicholson has done a wonderful ViewMedica talk on the CyPath test, which, if you can follow the ViewMedica, it is very informative and very complete. Thank you, panelists, and thank you, audience, for being involved tonight. Thank you.
Thank you.