 Hello and welcome to a brand new episode of White Court World. I am your presenter, Vasanthi Hari Prakash and our topic for the day is management of lung cancer, where we touch upon diagnostics, types of lung cancer, staging, treatment options, clinical trials, complementary medicine and so much more. Do not let these topics intimidate you because our guests today do the mighty job of simplifying complex jargon to simple things that we can digest. So let's kick start today's session, shall we? Hi, welcome to a brand new episode of White Court World by Manipal Hospitals. A podcast show by the doctors and for the doctors. I am Dr. Piyush Bajpayee. I am heading the department of medical oncology at Manipal Hospital daily. And I am Dr. Shubham Jain. I am head of the department and consultant surgical oncology at Manipal Hospitals daily. Today we will be discussing on lung cancer, what all advances have happened over the past decade. And it's really after 2010, lung cancer treatment has seen leaps and bounds advances in leaps and bounds. And so this is important that we talk about this disease pattern, especially just now on 9th of March was no smoking day. And we understand that lung cancer primarily is linked to tobacco consumption. It is definitely on the rise. India is facing around 13 lakh cases of cancer every year. So Dr. Shubham with this sort of lung cancer burden that India is facing with such a high mortality and most of our patients, they present in advanced stage lung cancer. What is your viewpoint on cancer screening, lung cancer screening specifically in this particular disease pattern? So a very valid question and a very important one, Dr. Piyush. Lung cancer screening has an established role in the West. Both in Americas and the Europe, there have been randomized trials which have shown the benefit of screening in early detection of lung cancer and their overall survival improvement for these patients. Unfortunately, in a resource constrained country like ours, it has not yet become the main scale public health policy. But I strongly believe that all the heavy smokers or all at risk people should opt for an annual low dose CT scan which can help us detect these cancers early enough to be able to offer an optimal treatment which can actually change the way the disease behaves for Indians as of now. It is important for our colleagues to understand that these are offered, this low dose CT scan is offered to people who are heavy smokers, mostly in the ages of 50 to 70 years, either current or just recently who stopped smoking. And it's a painless, non-invasive test, it's just a CT scan that needs to be done once a year which will help us detect any lesion and then it can trigger a chain of tests that can help us detect the cancer early. The challenges that our colleagues face and rightly so are the high false positive rate which means that there is a chance that something innocuous is picked up on the CT scan which needs to get investigated. The Western world is also trying to cope up with this. The more refined way we select our population who is undergoing the test, so it has to be high heavy smokers, a proper age, the lesser the chances of a false positive. But nevertheless, I would still stress on the fact that people should, our colleagues should identify people who are at high risk of developing such lung cancer and they should recommend a low dose CT scan for these patients. I absolutely agree, I think so with the sort of advanced stage lung cancers that we end up seeing, I think so high time that the concept of screening should be spread amongst the physicians because this is actually reducing the mortality as well. I agree. So what do you think is the role of the biopsy and what exactly is this liquid biopsy that we often heard here about? Okay, so you pointed out a very right and very important point that you brought out and that is biopsy in lung cancer. So biopsy as you just mentioned that sometimes with the sort of cases that we see, there could be tuberculosis mimicking lung cancer. So many times we have seen patients who have been treated for tuberculosis and then eventually we realize that this lesion is not responding on X-ray and then the biopsy is done. Sometimes we get to see that reports of FNACs are there and so what is now being realized that a good core biopsy is very important. A tissue is an issue in lung cancer actually and so because of the molecular diagnostics with what we as medical oncologists do after getting the small bit of tissue that is so important because you can actually analyze the DNA and realize which medicine you need to give to treat the patient better. So it is going to guide in precision medicine. Now unfortunately sometimes we do not get those type of tissues what I just mentioned because sometimes the background lung is diseased like as you know COPD or emphysema could be the background lung and sometimes pneumothorax could be a real problem if we enter the lung through a CT guided route and in my personal experience and also what we see is that peripheral lung cancers are actually difficult to approach by the central methods like the bronchoscopy but the CT guided biopsies really help but sometimes this all is very difficult and therefore the other way what you just alluded to was liquid biopsy and liquid biopsy is one way where the DNA of the tumor spills in the bloodstream and we then study this circulating free DNA the circulating DNA and analyze that what sort of tumor it is whether it can be treated with which tablet so this is stunning the DNA which is there in the bloodstream. So having said that Dr. Shubham after establishing the lung biopsy after knowing that it's cancer and nearly 30% of the cases 20 to 30% we do get to see some early stages at well how would you stage a patient in your you know practice before surgery? So Dr. Piyush staging is and you would agree one of the most important markers of how the patient is going to progress in his natural history and what the treatment options are so there is no replacement for a good staging before planning the treatment. Now conventionally for any cancer the nodal assessment and a metastatic disease evaluation both are very important more so for lung cancers because we have seen in the past that the occult spread to either bones or brain is so often placed in our patients that there is no way that this metastatic workup should be avoided in any patient unless and until it's a very rare case of a very early disease so because of that reason the metastatic evaluation should include a PET CT scan and an MRI brain there have been many instances where the patient otherwise seemed to be fine but we picked up an incidental lesion on MRI of the brain and these the stage changed remarkably for the patient and the disease outcomes. So really there is no shortcut I feel for the metastatic workup similarly for the midiastinal staging or this to identify a spread of cancer to the lymph nodes in the chest there are various modalities PET CT for one does give us some idea of whether the nodes are involved or not but for majority of the tumors we would need ebus FNAC which is basically an endobronchial ultrasound guided FNAC wherein a scope is inserted into the airway and the pulmonologist helps us in identifying any enlarged nodes and a sample is taken which the pathologist then tells us whether it's involved or not but the chances of ebus coming giving a false report is also reasonably high so when the clinical suspicion is good or if we are planning for a surgical resection of any lung cancer I do prefer in going for a midiastinoscopy which basically is insertion of scope into the chest through a small insertion in the neck to evaluate the nodes at large we are able to draw bigger samples of these nodes and the pathologist is then able to comment more confidently whether these nodes are involved or not you would agree to me that the management of the disease with the knowledge that it has spread to the lymph nodes in the chest differs drastically and changes a lot so that's my view on this what do you think about the metastatic workup and the staging? I agree with you that the surgical workup should include all the thorough midiastinal staging when you are seeing a chest limited or midiastinal limited disease pattern and you are absolutely right that the management should change management could change if there is a you know high nodal burden especially the N2 and N3 so there are definitely different ramifications and of course when most of the times when we see on a thoracic CT or a chest x-ray a lung limited disease a PET CT has rarely gained the ground as you just mentioned that PET CT is now being done and it really helps not only in the metastatic disease workup and if my radiation colleague would have been there he would have definitely agreed that the feel of radiation definitely gets affected by the PET scan and a thorough midiastinal staging so that of course metastatic workup definitely the PET CT helps over there and of course the local staging again the PET CT helps over there as well. Likewise for the brain MRI has gained importance especially in early stage as well as now in advanced stage lung cancer as well because any local therapy you go for you must have a MRI brain done because of high propensity of these lung cancers especially the adenocarcinoma small cell carcinomas to go into the brain so definitely a baseline MRI of the brain is very important because PET CT does not throw much of light on the small lesions in the brain therefore MRI needs to be done before we start treatment. Now as we are talking about treatment so Dr. Shubham what are the advances what have happened over the past few years what are your comments on the minimal invasive procedures that are happening? Well that's the most important exciting part for a surgeon in the management of lung cancer that you've now come to. Lung cancer treatment has seen a paradigm shift in the last decade or so the minimally invasive surgery with the help of laparoscope which is called a VATS or the robotic platform which is called a RATS has actually now come into the mainstream and it's very well acceptable we are able to go give good results to the patients especially with the improvement in the ancillary surgical techniques that is the staplers the improvement in the critical care and these actually help us in delivering the same oncological safety to the patient which is removing the lobe that is affected by the disease and in turn it has also improved our short-term outcomes the patients are able to go home faster they have shorter scars they have lesser pain because of chest surgery it has overall reduced the morbidity a lot so that has been a game changer in the management of lung cancer surgically also another important advance is the uh acceptability of segmentectomy for lung screening detected lesions so when the lesion that is detected is too small the old concept of doing a lobectomy is now being challenged by the surgeons wherein a smaller segment of the lobe that is taken out is being debated as being oncologically equivalent to a lobectomy there are more randomized data trials that are still awaited but in the times to come it is likely to change that the lobectomy that is a standard of care right now measuring further to a segmentectomy having said that how do you prefer to manage the patients in the adjuvant period after the surgery for lung cancers please share us your insights into how that has changed and evolved definitely that area of adjuvant treatment for lung cancer chemotherapy did come up you know and there was meta-analysis to prove that after you have done the surgery the surgeon has done their job then chemotherapy was being discussed in stage one be an above stages up to stage three so their chemotherapy definitely had established its role with various old trials and meta-analysis showing that there is an incremental almost five percent benefit absolute benefit if chemotherapy is given in a adjuvant setting additionally to surgery so adjuvant chemotherapy was there for a very long time and now what we are seeing is that now with the targeted drugs being available so if we are doing this particular mutation earlier on the sample that the surgeon gives us the pathologist you know after proving that it's adenocarcinoma or squamous cell carcinoma so we can then accordingly most of times in adenocarcinoma send this sample for mutation testing and EGFR is one particular mutation where now the drug is established in the adjuvant setting as well and giving some great results so ozimertanib is the drug which is actually showing in data in adjuvant setting and is impacting hugely on the survival also likewise now there is a thought process before you operate Dr. Shubham there is now this concept coming of near-juvant chemotherapy and near-juvant chemotherapy rather so there is this keynote 816 trial which recently got approved for the drug combination through the FDA that you know you use nivolumab and chemotherapy together you are actually getting some great pathological complete responses as in there is a lot of necrosis happening cell death happening before the surgery and then the surgeons are finding it easier to reject the it is more of a less blood spill and post-op recovery is better likewise the responses are so good sometimes we are able to predict how would the patient do once we have some good pathological complete responses so this is a very exciting field which is coming up near-juvant chemotherapy so but as we just discussed that it is metastatic primality but there is now a window of small metastasis happening and that is oligometastasis what are your comments on management of oligometastatic disease so oligometastatic is an entity that is actually a creation of our medical advances many a times as I was saying because of the advancements in diagnostic techniques we are able to detect patients who are not full-blown metastatic with a widespread disease and we have detected a few restricted lesions so it may be in the brain it may be in the adrenal now what the trials in the data has shown is that if we are treating these patients with the curative intent that is we remove the metastatic lesion as well as the primary lesion these patients have benefited and behaved much more like primary lesion which is localized or at least local original rather than behaving as a fully metastatic disease so that is the benefit obviously it comes with its own caveats that the patient's mediasthenal nodes should be negative wherein these patients before being offered treatment with a curative intent a mediasthenoscopy is done we also should be able to tackle with these metastatic sites with curative intent we should be able to get an R0 over there whether it's the adrenal gland or the brain and only then do we offer these patients the surgery for the lung primary but we do come across such patients many a times who are just on the verge of getting a full-blown metastatic disease and they were just one or two restricted sites so if these patients are fit I definitely see a point in treating them with the curative intent rather than what used to be the norm previously of labeling them as a metastatic disease and just giving up on them having said that even the locally advanced lung cancers that we see that's an evolving area and what are your thoughts on the immunotherapy that goes on for these locally advanced diseases yeah so locally advanced lung cancer again and there is there has been primarily the role of chemo radiation in patients who were unrejectable stage 3b especially specifically so there post chemo radiation there was a dilemma that eventually we were actually waiting for the patient to relapse there was the relapse free survival was actually you know almost one and a half years but now there is immunotherapy coming into play and this particular immunotherapy Darvalumab actually has you know rekindled hope of better treatment outcomes so definitely it is increasing the survival by almost another 12 months rather slightly more so definitely in adjuvant setting post chemo radiation Darvalumab if given for one year is now a hope for these patients having said the locally advanced and I do understand locally advanced is one particular complex disease pattern what are your thoughts on some very complex surgeries involved in these locally advanced tumors so locally advanced lung cancer can be both challenging and at the same time complex surgical options for the patient we call this disease locally advanced primarily whether it's involving the airway a more central airway or supposedly if it's involving the chest wall or the muscles of the respiration so these are cases wherein it's just there we can remove these organs and safely but obviously the thought is of how the setup is going to be and how the patient is going to behave so choosing your patients who are fit enough to undergo such procedures is the most important thing there are peripheral centers across our country which will not be able to offer such complex surgeries and these patients then go for a chemo radiation but at a center like ours the comprehensive cancer center there are facilities with the help of other departments like the critical care the blood medicine and everything with the cooperation of all these we can offer the patients a surgical cure and obviously the surgical cure is the best option for the patient in any solid organ cancer so that's it and removing the airway and doing sleeve resections is feasible at times it is feasible through a wads or a wads approach also and obviously adding the adjuvant chemo radiation for such patients would still be the norm but the outcomes definitely improve much more rather than just giving these patients a definitive chemo radiation do you agree to that Dr. Pugh? Oh absolutely I mean wherever the window of opportunity of doing a local resection or any local therapy definitely one should have a tumor board meeting a comprehensive multidisciplinary inputs should be taken for each patient of lung cancer I think so the patient would hugely benefit with these sort of inputs I absolutely agree with you on that okay that's what we do agree over here but sometimes we do different tumor boards so that's absolutely fine so it's always in the best interest of the patient and these ones you put are you know these are different opinions we gain more inputs and we actually debate through for each patient yeah absolutely and speaking of advanced cancers coming back to metastatic lung cancers the scenario has evolved and evolved drastically can you please share your thoughts and insights into how it has changed over the last few years and how you see it evolving in the coming years so what I remember is that you know going back some 14 years back when we were doing a I was doing my DM course at that time there was this particular drug jeffitinib which was being discussed you know Tony mock paper where this particular drug was used in a specific subset of population on clinical characteristic it was female edinocarcinoma non smokers or relatively lighter smokers asian and these patients were actually doing great on this particular drug jeffitinib they were doing better than what conventional chemotherapy was so somewhere there was this realization that something would be peculiar for these patients and eventually thanks to precision medicine thanks to analysis of DNA mutations by various platform like next generation sequencing it became hugely possible to detect such mutations and this was realized that's EGFR mutation which is definitely one of the biggest chunk of mutations in lung cancer this is druggable and there are most of times the 90% or 80-90% of mutations found in this particular domain of tyrosine kinase is basically druggable and jeffitinib was the first generation a lot and it was the first generation and now we are talking about the third generation EGFR blockade and that's ozimutinib and now what's the difference between the generation is that there is better brain penetration and there is more evid binding to the receptor more specific binding to the receptor so this has definitely increased you know the cell kill the apoptosis and also it is this is realizing now into better survivals so definitely precision medicine has brought in this and then the realization that it's almost 50% of the more than slightly more than 50% are mutations in lung cancer where you need not give chemotherapy and you can keep chemotherapy as a reserve so there are ALC inhibitors and now there are BRAF inhibitors and then you name receptor and now there is some clinical trial going all over the world for these oral tablets actually and they're doing much much better than chemotherapy also then there was this realization that immunotherapy is something that is a programmed death ligand binding agent and this immunotherapy is actually activating our immune responses against cancer which is which the cancer actually nullifies our immune system in terms of inhibiting our immune system this immunotherapy drug like a pembrolizumab or nivolumab they are actually uplifting that immune system and making our body capable enough to fight against cancer so what we are seeing is patients are doing much better we are able to give this in elderly sometimes weak individuals where we had you know to think twice whether we'll be really able to deliver chemotherapy so definitely this is a real game changer. Having spoken about these recent advances what is your take on palliative medicine Dr. Shuman? So the harsh reality Dr. Pugh still is that majority of our patients do present in metastatic stage and unfortunately in a country like ours majority of our patients still are not able to either afford the medicines the recent advances that you were talking about or they don't have access to the healthcare facilities such as complex surgical resections or these options of surgery or early detection so that is why in the management of lung cancer palliative medicine or end-of-life care still hold a very central role patients who are detected and diagnosed at advanced stages of cancer do need to be discussed in a multidisciplinary tumor board such as ours and a palliative specialist who can address at least the basic issues for such patients such as pain, feeding these should be addressed and there is absolutely no second thought on this that it is a very important component of any lung cancer management or lung cancer program that any hospital has. With this I think we'd like to close the session. It was wonderful talking to you Dr. Pugh. Thank you so much. We hope you'll be watching the next white coat world episode. Thank you and bye till then.