So hello everybody and welcome to this RSNA webinar. The topic today is the radiologist's role in diagnosing lung toxicity from anti-cancer drugs. Next slide please. I'm here together, my name is Nikolaus Gneidinger, I'm here together with Julian Professor Dinkel is a radiologist from the University of Munich. Maybe you want to say a couple of words, Julian? Yes, sure, sure. So thank you very much. It's a pleasure to welcome you in this webinar. So my name is Julian Dinkel. I'm an enthusiastic thoracic radiologist from France. I'm working at the Ludwig Maximilian University Hospital in Munich and I have the honor to work with Nikolaus. Nikolaus is a pneumologist and will introduce himself. Yes, Julian, thank you. My name is Nikolaus, as Julian said. I'm a pulmonologist. I was actually working in the same department or in the same hospital as Julian until a couple of months when I moved to Austria, where I'm currently heading the department for respiratory medicine. From my side. So we both will try to achieve the following aims today. For us, it is important that after this presentation, we could increase a bit of the understanding of lung toxicity from anti-cancer drugs. It will be important that we particularly focus on the role of radiology, identification, monitoring and management. And of course, with that, we want to improve early diagnosis of anti-cancer drug related lung toxicity via best practice and proactive communication between radiologists, oncologists and of course, pulmonologists. Please go on, Julian. So the agenda of today, I will start with a short overview about anti-cancer drugs related toxicities from the pulmonologist view. Then the most important part of today's webinar will follow from Julian. Then we will provide you some patient cases. And in the end, we hopefully can question and have a vivid discussion. So when we are talking about lung toxicity from anti-cancer drugs, we are mainly talking about interstitial lung diseases. And as you know, interstitial lung diseases are very heterogeneous group of diseases, actually, ranging from the idiopathic pulmonary fibrosis, which is something completely different what we are talking about today, to the most common form of drug-induced interstitial lung disease. And the pneumonitis is inflammation of the lung, which is not caused by an infection. This would be the pneumonia. But the mechanisms are quite similar. There is a hit, which is leading to an inflammation of the lung, followed by apparent repair and loss of function of the lung. There are different manifestations of pneumonitis caused by anti-cancer drugs, which we will see in the presentation. And of course, as you know, pneumonitis can develop very quickly and severe. That's why it is important that the management is done properly. ARD, and in particular pneumonitis, is characterized by four main manifestations. But it is important to understand that there is not a single clinical factor definitely confirming pneumonitis. This is a diagnosis of exclusion. But all of those four manifestations are important. Of course, most important from the pulmonologist's side is definitely the new onset of any respiratory symptoms. And the most common respiratory symptoms are dry cough and shortness of breath, where shortness of breath can be addressed, but can be also only present on exertion. Second, very important, and this is the main focus today of the webinar, are the radiological abnormalities. I don't want to go now into detail, because we will hear this in a moment. And of course, there are other manifestations like changes in pulmonary function testing, and maybe also some biopsies, histological or cytological findings. But in general, most important are the new onset of symptoms and the radiological abnormalities, which are usually the first thing which present. Please go on, Julian. This is very important, because this is important for understanding the role of the radiologist in the early identification of the pneumonitis. And it's important to say that monitoring of the pneumonitis should always occur alongside monitoring treatment response. This is quite clear. But if you have like a look here on the CTCA, so the Common Terminology Criteria for Adverse Events Classification, you see that the grade one of pneumonitis, the grade one toxicity, is characterized by being asymptomatic with radiological findings only. So this is the case where not the oncologist or the pulmonologist identifies that there is something wrong, it is the radiologist who is doing that by doing some follow-up CT scans, by monitoring treatment response or whatsoever. So this is very important, because in this case, the radiology is supposed to report the findings directly to the referring oncologist, and also to initiate a kind of follow-up discussion, and in particular multidisciplinary discussions with an idea going on. There are many other grades of the severity, but for now I think the most important is the grade one, because this is the most common form of pneumonitis which we see in daily routine. There are many drugs which have been reported to cause interstitial lung disease, to cause mainly pneumonitis, and most of them you have heard already. These are, for example, the anti-HER2, anti-cancer drugs, also mTOR inhibitors, virolimus, which with a quite high frequency of drug-induced lung toxicities, but also anti-CDK4-6 inhibitors, and of course, last but not least, there are some new drugs which are the immune checkpoint inhibitors, anti-PD-1 and anti-PD-L1, which are known to cause pneumonitis. But there are also a new group of drugs which you can find here, this is DDM1 and DDXT, these are antibody drug conjugates, trastuzumab, teruxtecan, which have been, where it has been reported that mild ILDs are very common, and that's why we are here, to get more awareness for this problem and to prevent further progression of those mild pneumonitis to severe cases. Please go on. So there are several risk factors for drug-related interstitial lung diseases, and most important is definitely a history of having a lung disease, in particular having an interstitial lung disease is a risk factor, but not only having an interstitial lung disease, also having milder forms, for example, like interstitial lung abnormalities, are already risk factors for getting a drug-related ILD. But also poor overall health status, smoking status, advanced age, being Japanese or African ethnicity, being male, sex, or having received prior medical therapy, or also radiation are risk factors for developing drug-related ILD. Please go on, Julian. So, therefore, it's important, or in particular, in those patients with risk factor, but not all, but actually in all patients, it's very important that you do, or the oncologist, alongside with you as radiologists, do a careful monitoring of patients by not only CT scans, but also by other tests. What, so what can be, or how can be an ILD pneumonitis suspected? Of course, when you have like new onset of symptoms, dyspnea, cough, fever, hypoxemia, if you have new signs on physical examinations, for example, by having crackles on the lung exam, but also, again, by having interstitial changes on the chest imaging. If you have one of those three components present, it's important that to immediately interrupt the anti-cancer drugs and that you start differential diagnosis. And for those differential diagnosis, it's also very important that the oncologist has an intense discussion with you as a radiologist to get an idea of what are, what is more likely and what is less likely regarding differential diagnosis. If you are very confident that you have an ILD, which is caused by the anti-cancer drugs, you should definitely immediately start with steroids. If you're not so sure, need more time, you also can start with steroids, but you also should in parallel start your differential diagnosis testing. On the right side of the slide, you can see some remarks. It's important to keep in mind that patients who are under intense chemotherapy or in particular who have brain metastasis and are under steroid treatment, they have a higher risk for opportunistic infections, for example, like pneumocystis, Yerovetsi pneumonia, but also some other infections, which should be taken into account when you do your differential diagnosis. In general, there are many other comorbidities which can be present. This is not always easy to rule out all of those, but together with your radiologist or with your oncologist as a team, you mostly can narrow it down to some diagnosis actually. Please go on, Julian. So, once again, here you have a kind of a scheme how this could look like. Again, we start with step one. If you have like some suspicion of interstitial lung disease, as I said, just repeat it by new onset of symptoms, new onset of clinical signs, but also new signs on CT imaging, then stop your drug and then you move or your oncologist or pulmonologist will move to step two. If you didn't do the chest imaging so far, you have to do it now. Of course, you always do take a history and you always do your physical. What is not so important in my opinion is doing a respiratory function test in this situation, but it's very important to do some laboratory tests to get some ideas if you have some comorbidities present, if you have like, if this is a pneumonia or infection, what you see, if you have lung edema or if you have a progression of the underlying disease. Sometimes you need to do or it's helpful to do some bronchoscopy, doing a bronchial veular lavage or doing a biopsy, but this is not always necessary. But in the end, you as a team together with your oncologist or the oncologist together with you should come up with any kind of differential diagnosis with a bit of confidence actually, and then you should know or should have an idea if this is maybe progression of the underlying disease. For example, when you have like lymphangiosis, carcinomatosis present, if you have an infection, if you have any other pulmonary disorders, or do you think that it is really drug-induced hyperlipidemia. Please go on, Julian. And this is very important because now we are coming to the very busy slide here. This is the management guidance and we just focused here on the role of the radiologist. And as you see again, the grading is very important and I'm repeating myself, but I think this is important to understand. If you have an asymptomatic patient with radiographic findings only, you as a radiologist are the one who is suspecting the drug-induced ILD, who is the one who is reporting it to the oncologist and maybe initiating a multidisciplinary discussion. Of course, then your oncologist or pulmonologist will initiate some clinical examinations, some differential diagnosis, but again, you as radiologists are very important for those differential diagnosis because many of them you can rule out or rule in by looking on the CT scan. If you have this grade one, you stop your anti-cancer drug temporarily, you may initiate some steroids, but it's important that you monitor your patient closely, that you repeat the chest CT scan to look if the ILD has resolved or maybe just remained stable or progressed. If you are in a situation where you decide that your patient remains on the anti-cancer drugs, it is very important that you closely monitor with HRCT before you do the next cycle of therapy. If you have a resolution on the HRCT of your findings and your patient is not anymore on the drug, you can re-initiate the drug. Once more, grade two is also important because in grade two, usually the patient is asymptomatic, so the oncologist will call you and say, we have a symptomatic patient, I suspect an ILD, a pneumonitis, then you will do the CT scan and will again have the intense discussion with your referring physician what is a likely diagnosis. But otherwise, it's important to say that in grade two, it is recommended to discontinue immediately the drug and it's actually not recommended to start the drug again, but this is something your oncologist will deal with. Please go on, Julian. So, thank you. Thank you, Niklaus, for this nice overview and I will focus on the radiologist's role in optimizing patient care for drug-related ILD pneumonitis and as Niklaus said before, you will not perform the CT and do the diagnosis without further information, but the good thing that we have in oncological cases is that we always have a baseline CT and the baseline CT goes beyond the oncological staging. Sure, you will look at the tumour, you will look at lymph nodes and that's the baseline for the treatment, but you have to look at the status of the lungs before therapy because it's very easy, especially in asymptomatic patients, that would be a great one, to see something new appearing after therapy and in these cases, it's probably easier for us to suspect and suggest this drug-induced pneumonitis. So, look at the baseline CT, the status of the lungs before therapy. The CT, if you have these follow-up CTs that will be probably oncological CTs, then you should do construction with a thin slide thickness to look at the lung parenchyma, but if you are not able to do the diagnosis because you think that the examination is not done properly, it's probably easier to do the examination with a HRCT, meaning that you will have a very thin slide thickness, inspiration scan, high-resolution control kernel. The field of view should be adapted to the lung anatomy to get the maximum of the resolution and I would recommend to use high pitch and short rotation time because the patient, especially with new respiratory symptoms, they tend to have difficulties to do this examination in breath-hold, so keep the examination time as short as possible. So, I would say that the structure approach is very interesting, especially by dealing with the differential diagnosis. So, there is no free lunch in ILD diagnosis, it's only some kind of assumption due to dominant pattern. So, look first at the dominant high-resolution pattern that you see on the CT scan. Is it reticular? Is it high attenuation? In high attenuation, you have to differentiate between ground glass spasticities and consolidations. Do you see nodular pattern or low attenuation pattern? Then you have to look at the location within the secondary lobule. Is it centrolobular, perilymphatic? Is it random? And then where is it situated in the lung? Do we have additional findings like pleural fluid, lymphadenopathy, bronchiectasis, sign of volume loss indicating some kind of fibrosis? Then that would be all the signs that we are looking for. So, the normal secondary lobular anatomy is depicted on the right side and you see that the size of the object is very small. So, you should not see that much. You can see some pulmonary veins and you will see some pulmonary arteries, but the typical septal bronchial wall thickness is too small for the CT scans. So, when you can see the structure, it means that it's pathological. So, that's the location of centrolobular and that would be a perilymphatic pattern. And the key fact is the drug-induced pneumonitis has heterogeneous radiological presentation. The patterns are mostly cryptogenic organizing pneumonia pattern. That would be a cryptogenic, well, actually it's not cryptogenic in this case, that's the pattern, but it will have some organizing pneumonia pattern. And sometimes it has NSIP or HP pattern. Rarely, fortunately, it will have some acute interstitial pneumonia in sarcoid-like reaction. It's quite rare. So, mostly you will have hytenuation pattern and reticular pattern. That's a slide about the immune checkpoint inhibitor-related pneumonitis. And as I said before, it exhibits radiographic patterns. Most of the cases are organizing pneumonia pattern, but as I said before, a lot of pattern, minority of cases have this acute interstitial pneumonitis pattern, which is associated with the ARDS and it's a very severe form of pneumonitis. The patient are not asymptomatic in this case. So, I have collected some cases, actually four cases with reticulation. And we will go on this, well, this scans and that actually can happen in any of our oncological patients. So, you have a follow-up scan and you see suddenly this type of pattern beginning with this one. But this one has reticulation, but you see as well that we have some nodular pattern. The thickening of the interlobular septa is usually irregular with some nodule pattern as well. It is sometimes unilateral in 50% of the case. And usually you will have other signs that the patient has a relapse or a progressive disease like a new lymphadenopathy or pleural effusion. So, this is a case of progression of disease, of oncological disease with lymphogenic carcinomatosis. In this one, you have a very similar pattern, reticulation, which is located in the interlobular septa. It's bilateral, smooth. Sometimes you will have a kind of ground glass opacity, perihela, and you have some gravitational distribution. And the additional findings in these cases are cardiomegaly and pleural fluid. So, that's typical cases for cardiogenic pulmonary edema. And in the CT scan on the upper screen, you see that the patient has a very small pneumothorax because he had a pleural fluid and a catheter and had a very small pneumothorax after that. So, this case is indeed a drug-induced pneumonitis. The pattern here is an NSIP pattern. You can discuss that it's a bit of HP as well because we have some ground glass opacity and some mosaic distribution. But the predominant findings is GGO and reticulation. And if you don't have any kind of treatment, the patient might evolve with some subtle traction bronchiectasis indicating fibrotic changes. And this case is very rare. It's, again, bilateral, smooth interlobular thickening, but you see that the patient has no cardiac disease. Actually, the echocardiography was completely normal, but it was interesting that the patient had a high erosinophilic count in the blood sample, and it was an acute erosinophilic pneumonia, which was drug-induced. So, the high attenuation pattern. So, again, five cases that could happen to your oncological patient, and we will go on. So, I will take a bit of time for this one. So, the first one is actually very often seen in this patient, but they will have a clinical presentation most of the time with a fever. We will discuss that with Nicholas. So, in this patient, when you see these unspecific findings with some TGO, interstitial reticulation, but clinical presentation indicating some infection, then think of atypical pneumonia. And this one is much more impressive with the very important patchy consolidation. Sometimes you see some crazy paving, grown glass opacity, but here in this example, I focused on the soft tissue window, so you see only the very large opacification. But the important thing is we had this examination with contrast agent because the first diagnosis suspected was pulmonary embolism, and it was no pulmonary embolism. It was a rapid progressive. It was a drug-induced acute interstitial pneumonitis, and the patient unfortunately died a few days later. So, this one is a typical aspect of a pulmonary embolism. I wanted to have this kind of mixed window where you see here the thrombotic changes and the infarct pneumonia. And this case is what you will see most of the time in this drug-induced pneumonia, organizing pneumonia. So you see some bilateral peripheral conciliation. They are usually sharply demarcated. You see some perilobular thickening with atal sign and palm chemo bands. So that is something that you might pick up in a follow-up scan as an asymptomatic patient is coming for this scan. And it has to be really reported and you should make this differential diagnosis that it could be drug-induced organizing pneumonia. And lastly, this case of HP pattern, you see much more bronchial aspersity with a mosaic pattern. Some secondary lobules are not affected by bronchial aspersity. And that is a pattern that you might see as well in this patient. So radiology should be vigilant, especially, as I said, during the follow-up scans. So you will do the tumor response monitoring, sometimes using Resist, iResist, but be careful, look at the lungs as well. Not only for lung metastasis, pulmonary embolism, but as well for ILD pneumonitis, drug-induced pneumonitis. And if the patient has new onset of dyspnea, look at the spine, because sometimes it's only a spine fracture and the patient has some pain and cannot breathe accordingly. And, but it is a very complicated diagnosis. And you might need to work collaboratively with your MDT to rule out different troubles. And actually in Munich, we have this ILD and Pneumology Board where we can discuss these complicated cases, cases that are not straightforward. Indeed, the key is early identification, because if you do that, you will have the drug cessation, you might have some time to rule out differential diagnosis. And sometimes, well, you have to be very pragmatic and consider antibiotic therapy when an overlapping infection cannot be ruled out. That's sometimes the case, but the pneumologists and oncologists are very pragmatic as well. And sometimes they will treat both. And that is something that we will discuss together with Niklaus in the next cases. Jos Kees. Yes, Julian. And I will quickly present the case. Thank you very much. Yeah, you can go on. This was a 55 year old woman with a triple negative breast cancer without having any comorbidities. And in December 2022, she presented to the Multidisciplinary Tumor Board. She had a mediastinal lymph node relapse in the triple negative breast cancer, which was previously treated with lumbectomy and adjuvant radiation. According to that, she then received a triple therapy with buccaldexal, carboplatin, and pembrolizumab and developed then in February, 2023. After the first restaging, after having had like two cycles of this chemotherapy, she reported rapid progression of dyspnea. And she was admitted to the emergency department with an oxygen saturation of only 90%, which is quite low already. And the CT scan was performed. Julian, please go on, and maybe you can comment already on what we have CT scan-wise. Yeah, that's true. And that's the baseline CT. And well, in the presentation, you didn't say if the patient had breast cancer on the right side or the left side, but we can look at the baseline CT and see the scar here after the lymph node dissection and the lumbectomy on the right side. And after adjuvant radiation, you will sometimes see this tiny reticulation in green glass opacities in the subplural pattern here. So basically we have this post-therapeutic treatment changes on the chest wall and subplural within the right lung. Sorry, and we have indeed some lymph node relapse with enlarged suspicion lymph nodes. And that's why the patient had this new therapy. And well, she was then scanned, after this episode of brightness. And what we see now is this extensive ground glass opacity on both sides. But you might notice that we see much more ground glass on the right side than the left side. And interestingly, you have some paramediastinal as well here and probably a little bit more subplural here on the right side ventral. So in this context, we immediately thought that the patient had a drug-induced pneumonitis. And we know that sometimes the pneumonitis can be associated with all radiation pneumonitis. So that the pneumonitis area that were affected by prior radiation, even though the radiation was sometimes 10 years before. So that was the idea that we had some kind of recall pneumonitis drug-induced by this new treatment. Thank you, Julian. I think this is a very, very interesting case. And this was a severe form of pneumonitis where it is definitely important to start immediately with treatment sometimes, or most of the time in such a situation, you cannot wait till everything is done what you need for ruling out every other differential diagnosis. That is very important that you as a radiologist together with your oncologist discuss these cases and establish kind of a likelihood for having a pneumonitis. As I said previously, very often you cannot rule out that there is not also a kind of infection. But in clinical practice, this does not matter. You should treat this patient with steroids. And if you suspect a concomitant infection or if you cannot rule out that it is infection at all, you also treat antimicrobial in parallel. And of course you do your differential test for later but you should not waste time. You should initiate a treatment. Please go on, Julian. I think this is- Yes, sure. Yeah, second case. Yeah, we have a second case. Actually, this is a 46-year-old woman. Please go on to the history. 46-year-old woman with triple negative multifocal breast cancer. She was treated already with neoadjuvant chemotherapy with four times iverubicin and cyclophosphamide followed by four times baclidaxel, carboplatin, and pembrolizumab. And in June 2022, lumpectomy was performed. Adjuvant radiation was performed. Adjuvant pembrolizumab was then applied. And actually, yeah, half a year, eight months later, the patient reported about rapid progression of dyspnoea. You see, this is the most common manifestation of an ILD, pneumonitis, was then admitted again to the emergency department. Please go on, Julian. Yeah, and you see that we perform the CT scan with contrast agent because due to this onset of dyspnoea, we wanted to rule out a pulmonary embolism, and we were able to rule out, but we saw this extensive new consolidation and ground glass opacities, sometimes with the nodular aspect, and you see some atoll phenomenon. And it's quite rare to see these numbers of atolls and nodules, but in this patient who had actually not really signs of infection, we thought that the patient had, well, some drug-induced pneumonitis with an organizing pneumonia pattern. Due to this very nodular aspect, we thought that it could be some manifestation of acute fibrinose organizing pneumonia, which is interesting that can occur sometimes 12 months after the introduction of the drug, but usually much sooner, and it's usually three to six months. And interestingly, while you perform the bronchoscopy in this patient, I think it was heroic, probably. Yes, definitely, as we are, but this is actually, to be honest, in most cases, you do not need invasive testing. This is my experience. So if you have a patient like this admitting on Friday evening, please don't wait till Monday till finally your pulmonologist shows up again. The time is very important in this setting. Please initiate a treatment, and sometimes it can be helpful, but this patient actually, this patient we would have treated anyway with steroids, and this is most important because if you do not treat, these patients can deteriorate very rapidly. In general, even those cases, both cases were quite severe cases, and in both cases, actually you would, as an oncologist, or now from the oncologist-pulmonologist side, you would not reintroduce your treatment, but there are now plenty of recommendations out which show and recommend that if you have a very mild form of pneumonitis, which is quite common, actually, you can reintroduce your anticancer drug, and this is particularly important if you have a patient which, like the second patient, I think, who is responding very well tumor-wise to the therapy, then you have to have like a kind of a risk-benefit balance, and sometimes reintroducing the drug again is definitely worth to do, but this is only recommended if you have grade one and you remember grade one is the pneumonitis, which is only seen on imaging, which doesn't come along with any complications. I think there's a question on that in the chat, and we will hopefully answer in a minute, but close monitoring is definitely important, but not only doing regular CT scans and doing regular lung function tests and doing regular history taking and physical exam, but there is a lot more. Please go on, Julian. And for me, also important, maybe not for you, so as a radiologist, as a treating physician, envision this, that you educate your patient or the oncologist patients or whomever patient, but that patients are educated, that they know that those drugs they receive have side effects, and those side effects can come along with symptoms for ALD, and if the patients have those symptoms, they definitely should request an immediate reporting. So education, advice for self-monitoring and requesting immediate reporting is very helpful, and also provide some written information, because sometimes you have patients who are then admitted to a hospital which does not have the experience, maybe not the experience with the provided prescribed drug, then it's very helpful that patients have kind of written information with them. Yeah, Julian, any comments on that? So, yes, well, actually, I think, indeed, that this patient interaction is probably different between radiologists and patients, and that is something that is more important for the oncologist. I think what is really relevant is that the oncologist, when sending a patient for a follow-up, write the type of drug, especially if the drug that is applied to the patient might induce some interstitial lung disease. So if you don't know, well, you can always say, okay, it looks very peculiar, and maybe it's drug-induced, but if you know exactly that the patient is having some treatment, is becoming some treatment with a drug, inducing lung toxicity in 4% of the cases or 10% of the cases, then just from a statistical point of view, you will have much more confidence in your differential diagnosis. So now we have some time for questions from the audience. Yeah, we have already, like, two questions. To be honest, I do not understand the first question completely. Maybe, Julian, you can have a look on that. Oh, yes, okay. Well, I think, yes, there was the question about the dose, yeah, the fact that we have many scans and there will be a dose accumulation. So we are dealing now with the patient with some cancer, and oncological treatment, and they will have a follow-up treatment, and this follow-up CT is recommended by national guidelines. So you don't have to care that much about the doses of the scans, because the guidelines are written, and indeed, the question of doses and the benefits of the scans is much higher than the risk of some secondary radiation-induced damage. So in this type of patient, I would not really be scared about that. If you don't, if you cannot do a diagnosis because you think that your oncological follow-up CT is not good enough from a quality point of view, then I think it is really totally fair to reduce the CT with HRCT, even though you can use low dose, so typically 1.5 millisieverts, and I think it's not a problem. If you need that for the diagnosis, it's absolutely not a problem. Great. So a couple of questions are popping up, so we have to hurry up, Julian. The next question is, thank you, John, for the nice word. The next question is, do you believe that it is very important to stop anticancer treatment in grade one ALDI, or would the mild cases possibly resolve spontaneously? This is a good question, which we cannot answer yet. It is indeed the case that you have grade one ALDIs, which resolve by their own, and you do not have to introduce steroids. But what you definitely do, you should wait at least the time until the next cycle, which is usually three weeks, and before you provide the next cycle DDXT, you should definitely do a CT, a re-CT, and look if the ALDI resolved, if it remains stable, or if it got worse. In my opinion, if it did not resolve, you should not give the next cycle. If it is resolved, you can, within 28 days, you can give it the same dosage. If it took a little longer, you can try a lower dosage, but if it did not go away, you shouldn't do it again. And Julian and I have been in an education committee of one of those studies, and we have seen that patients who have DDXT-associated ALDI, which resolved, they are at risk for getting further ALDs that follow up. Julian, can we differentiate a typical viral infection from drug-induced pneumonitis? Frankly, just by looking at the picture, you cannot. It's sometimes very difficult to do that. So sometimes, indeed, the appearance of the drug-induced pneumonitis is so odd, so peculiar, that you think it's probably not an atypical infection, but no, it's very complicated. The good thing is, most of the patient, we have a clinic symptoms and drug samples, so you have to dig a little bit in the history of the patient, in the blood sample, in everything, and then you are more confident if the patient has nothing, no signs of infections, that is probably drug-induced. Yeah. There are two questions concerning the similar topic. So average range of time to develop ALD after oncology treatment, and in which timeframe can a therapy-induced pneumonitis occur after last cycle? I think, Julian, we have seen, actually, both pneumonitis developing already after the first cycle of an anticancer treatment, but, and we have also seen cases where ALDs develop months after the last cycle. So it's, for me, it's hard to say, actually, but what we have seen, for example, for drastotumab deruxedecan, that the risk is highest in the first 12 months, so in the first year of treatment. After that, the likelihood is getting quite low, actually. Julian, eosinophilic pneumonia, considered, is eosinophilic pneumonia considered as drug-related ALD? Yes, I would say yes, as you have shown in the case. Yeah, well, yes, it depends. In this case, it was an acute one, and it was related to the drug, but usually, in acute eosinophilic pneumonia, you don't know the trigger. That's a problem. Yes, there's a question on contrast dye, contrast agent. What about the contrast agent? I mean, there will be probably, most of the time, in oncological patient, your follow-up CT with a contrast agent. I think, indeed, that can be sometimes difficult to diagnose very fine ground-glass opacities, especially if you have some mosaic perfusion. So yeah, sometimes, a contrast agent is a problem, and you have to perform a CT scan again in HRCT condition, meaning without contrast agent. And sometimes, the contrast agent is requested because you want to rule out realism, and that's why we do it sometimes with a contrast agent. And if the CT scan is really straightforward with some pulmonary afflictions and opacities, then we won't do the exam again with HRCT. If there is still some kind of uncertainties, then you do an HRCT. It's very rare that we do both at the same time, but sometimes, the pneumologist is requesting, first, an HRCT, and then a CT scan with a contrast agent to rule out pulmonary embolism. Good. There's a question. In the asymptomatic phase and in the absence of other signs or differentials, what do you do? Stop or change the treatment? Steroids? Question mark. Follow-up CT? And what interval? PET CT? Thank you. So in the asymptomatic phase, in grade one, it's actually up to the treating physician if you apply steroids or not. I usually tend to do it because my gut feeling, and it's not more than that, is that the outcome is better, and getting the ALDI resolved is faster with a bit of steroids. If you have steroid-associated comorbidities, like diabetes or osteoporosis, of course, you should take this into account, and you can also do it without steroids. If you have a drug which you give every three weeks, you have the time, and before you give the drug again, you do a CT scan and then decide. If you have another drug, like, for example, the TKI-Diuretic Kindness Inhibitor, which you give orally every day, of course, you have to decide what to do with the drug. Then I would definitely also stop the drug until you have seen that the CT scan is resolved. PET CT in this situation is not necessary, in my opinion. Can drug-related ALDI develop after years of treatment? Stop. After years, I don't think so. It's a bit different. If you had, like, radiation therapy years ago, this is what Julian showed us, like, recall pneumonitis, that patients develop pneumonitis in the area of radiation therapy years after radiation was stopped. Is this right, Julian? Short answer? Yeah, sure. Yeah, yeah. But indeed, after years after stop of the therapy, there is no pneumonitis. It can occur 19 months after the beginning of the treatment, but not after the stop of the treatment. And I think, well, we will have to wrap up the webinar. I'm so sorry. We had a few questions, but we are running out of time. I thank you for all these questions, for, and I thank AstraZeneca for the support. And, well, I thank the organizing commission, indeed, for this fantastic organization and the opportunity to talk to the RSNA during the RSNA webinars. And I thank you, Nikolaos, for your support as well as a pneumologist to radiologists. So thank you very much. Also from my side, it was an amazing discussion. I see there are many questions, so there is definitely a need for discussing those questions and those topics. And thank you, everybody, for being here. I wish you a nice day. For us, it's already evening. We are going to bed soon, so take care. And nice having you here. Bye-bye.

radiology

lung toxicity

anti-cancer drugs

pneumonitis

early diagnosis

multidisciplinary approach

CT scans

case studies

drug-induced lung diseases