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Hello and welcome to Bonus and mine, the bleep webinar. Um This is our first one of the series of oncology webinars. I'm really excited to have you join us today. I'm Taylor and I'm one of the co President's of Bonus and I'm joining Miranda today from mine, the bleep and our two speakers tonight, Doctor Rachel Broadband and Dr Rohan Shoten um from the Christie and they will be talking to us all about cancer diagnosis. Thank you very much for joining us today. We're really excited to have you talk and I'll pass over to you. Thanks Taylor. Um Thank you for the invitation to speak as well and for having us. Uh So as with all these things, despite it being three years of online talks and so on, we're still just wrestling. We're trying to get Rachel into the room as a speaker, so we'll keep an eye on that, but we'll start chatting in the meantime. Um So we are both S P R slash fellows at the Christie and the University of Manchester Rachel has just finished a really exciting phd looking at lung cancer screening in survivors of Hodgkin lymphoma. I'm also working with the lymphoma team at the Christie, uh working on a phd looking at a new biomarkers of cardiotoxicity caused by anthracycline chemo. Um This is a completely different uh sphere. This is the hard core nitty gritty of week to week MDT work in oncology, which is the bread and butter of what as uh on co enthusiasts, hopefully, what all of you will be doing in the future. So we'll start talking and if Rachel managers to join us in the next couple of minutes, she can take over. So the, the whole point of this talk is to just go really from symptom to treatment in a little bit more detail than what we might all have seen. I was undergraduates or uh early stages when we get to M D T s and so on. Uh It was something that I didn't really appreciate as a med student and then as an F Y one F two by and large, far too busy to do things like M D T s and clinics. So we'll talk about the principles of working up a suspected cancer. Uh Some common presenting symptoms and signs will work through one particular case that will hang most of the discussion for the hour or so on. Uh Then we'll talk through the role of imaging specifically and pathology uh in each of those things. So we'll start talking presenting symptoms. Now, obviously, these are many and varied. Primary tumor's can occur in just about any part of the body as you know, um can cause any number of symptoms. We'll see what Rachel's just messaging me. Oh, sorry, that looks. Um, so they can cause symptoms based on where an actual lump is growing, such as a breast cancer in the breast or lymphomas in nodes, anywhere through the body. Uh, some tumor's of course, are more prone to bleeding such as those in the gi tract and other tumor's are prone to obstructing or compressing important things that don't want to be obstructed or compressed. The communist of those are things like HPB cancers which very commonly of course present with painless jaundice. Um and equally the important point at the bottom, there is blood vessels causing external compression. This is something we see absolutely all the time in patient's with known cancer, but also new presentations of cancer is DVT and pe, these are absolute staples of presentations with cancer. So, if you're working in an acute medical setting and you see somebody who hasn't apparently unprovoked DVT or pe, you really need to be thinking carefully about whether this might be the first presentation of a malignancy primary tumor, as we've just said, can cause symptoms but clearly, so can metastases. Again, these vary enormously based on where they are in the body. Bone pain is a really common thing. It's unpleasant but pretty opiate responsive in general pathological fracture is an enormous problem for our patient's it can happen with no trauma whatsoever or it can be very low impact. And it's important that these patient's are worked up by orthopedic colleagues with expertise uh in managing pathological fractures. Of course, we see patients with breathlessness or cough frequently due to chest. Um and all of the others that you can see here, liver, brain nodal symptoms, the important ones at the bottom of these non specific systemic symptoms, uh constitutional symptoms of anorexia, fatigue, weight loss, nausea, of course, a huge number of the population of fatigued anyway, without having cancer. Uh, these are very common and I might add to that list as well be symptoms caused by lymphomas. We'll start talking about a particular case and, uh, see how far we get through before Rachel manages to join this case will take us through most of the talk for the evening. It's a 74 year old woman who turns up to see her doctor feeling breathless on further pressing her. She has had about four weeks of feeling out of breath. She has dry cough, occasionally some dull central chest discomfort and has lost a small amount of weight. She, uh, as per most patients in their seventies has osteoarthritis to some extent. High cholesterol COPD and glaucoma medications has shown here. Importantly, she has a fairly heavy x smoking history, a light drinker of alcohol lives with her husband and she was fit and independent until two weeks ago. There's a a family history of malignancy in her brothers and her mother. And that is what she presents to you. Systems review, I think is a really important and underrated part of the history. Sorry to teach you to suck eggs if this is all basic for you. But it's very much underappreciated and we all have to find our own way of tackling it. But in working up a patient with suspected malignancy, it's absolutely essential. So I think the key points are to look through all of the potential body systems that could be affected by the symptoms on the previous slides and take them off mentally. So, the salient points here are that this is a four week history, a relatively rapid acute history in that case of breathlessness in a woman with COPD and a strong smoking history who importantly again was fit and independent until two weeks ago. The key thing here is that she's gone from well to not well very, very quickly. When you examine her, she is in a wheelchair, her performance status is to, we'll return to that in a minute to explain what that means. Breathless at rest. She's hemodynamically about stable, has reduced breath sounds an adult percussion note throughout the left side of her chest. Otherwise, the examination is pretty unremarkable. Uh the uh otherwise, the features that we need to be looking for. Of course, in the respiratory exam is evidence of infusions, infections, obstructions and, and peripheral stick matter of COPD cardiovascular exam is perhaps less essential. That's more about guiding your view of patient's fitness for treatment rather than primary cancer diagnosis, abdominal features such as the city's Hepatomegaly. And I said at the beginning, absolutely essential that you don't miss a DVT or PE these are very, very common features. Of course, once we've got all of the clinical review, we then uh ask our healthcare assistants in clinic to provide us with bloods. These are just taken from a patient at the Christie that I saw a few weeks ago on the left, full blood count and on the right, the so called Christie profile, which is just a panel of UDINESE at the top, a bit of a bone profile. LFTs and for historic reasons, and LDH which gets done all the time as well. So important things that you might notice here is that this woman has a neutrophilia. She's hyponatremic, relatively good going hyponatremia. You noticed that her creatinine is fairly low, that suggests perhaps a low muscle mass and certainly in proportion, her urea is very high. It's disproportionately high. Isn't that that urea compared to her creatinine? So that might point towards gi bleeding or perhaps dehydration in the context of a woman who's actually of very slender muscle mass. Uh The LFTs of course, are important to uh keep an eye on as well. When we're thinking about assessment of fitness, it's really useful to have a framework to hang our opinion on and also to uh, I guess, track through a patient's journey from diagnosis and treatment which can go on for many, many years. Some of our patient's in uh lymphoma or breast clinics come with advanced uh incurable cancer but come to the clinics for more than a decade. So assessment fitness is, is absolutely essential. This guides chemotherapy decisions, radiotherapy, decision surgery, uh concurrent treatment such as chemo radiotherapy. of course rules exist to be broken. But as a general rule, chemotherapy would be very rarely offered when someone's performance status is three or four. I should say the performance status runs from one from 0 to 50 being completely fit and well unable to do all normal jobs and exercise, five being dead. Um So three and four at the shallow end of the performance status pool, you'd very rarely convince an oncologist to give you chemotherapy unless uh in a couple of very specific circumstances such as a rapid decline caused by a potentially reversible malignancy like lymphoma or a germ cell tumor. So is that there are various ways of measuring performance status. This Peacock Eastern Cooperative Oncology Group performance status is the commonest. Um The Karnofsky performance score is more complex. That's a percentage from 0 to 100 frailty score and co mobility index of course are important as well. This is the most important of them. Although the cog PS performance status, hopefully most of us here are 0 to 1. The difference between two and three is an important one to delineate. The key thing here is whether you're up and about for greater than or less than 50% of waking hours. So if someone is resting more than half of the day, they are by definition, performance status three. If they are up and about more than half the day, but not able to work, then they are performance status to a patient in bed or chair the entire day, entirely disabled or unable to look after him or herself, his performance status for as well as being useful for guiding us in treatment decisions. Performance status also correlates pretty neatly with overall survival for many if not all or most cancer types. This is a Kaplan maya plot showing the proportion of patient's alive for performance status. 0 to 4. And as you can see performance status four in blue, perhaps 50% of patient's, they're 0.5 are dead by four or five months which off the top of my head feels quite generous. Maybe it's three months, but it's, you know, bleak. Certainly. So the bottom line of this woman's presentation, if you were to give a one line summary to your professor in clinic after you've been to see her as a new referral is that she is a previously fit 74 year old presenting with rapidly progressing dyspnea, cough and weight loss in the context of a heavy smoking history. She is performance status to do to disappear with examination features suggestive of a left pleural effusion. She wanders off around the corner to the X ray department and she comes back with images on packs looking a little bit like this. The obvious finding of course, being a white out on the left hand side, which taken with your examination features of a dull percussion note and absent breath zones through the left is strongly suggestive of a large pleural effusion. There. You can see her media style um has been pushed away towards the right hand side. There's also a small patch of consolidation on the right here. She goes on to have a CT scan. Uh in this presentation mode. This isn't going to show us terribly well, but it's, I guess just to make the point that a CT chest abdomen pelvis is pretty well mandatory in the vast majority of patients with suspected malignancy. There are a couple of exceptions to that such as a very early stage, localized small low risk breast cancer such as an estrogen receptor positive, her two negative tumor in the breast, you might get away without a CT scan, but otherwise you won't go far wrong if you assume that uh someone with cancer needs CT chest to pelvis. Here's the bottom end of that CT scan showing the left sided pleural effusion. So the radiology consultant uh pines that this patient has multiple lesions throughout the liver, probably metastatic from a primary lung neoplasm, no surprises there from the history of breathlessness and smoking history. There are multiple enlarged para-aortic lymph nodes, a moderate left pleural effusion causing some collapse. Again, not uncommon. There is a subcarinal soft tissue mass density in a large left hilar mass with mediastinal extension, occluding the lobar bronchus of the left lower lobe, complete atelectasis of the left lower lobe and a moderate severe left side of pleural effusion with that Alexis. And she suggests that this is put through the chest radiology meeting sensibly enough. At this point, we'll just pause the case discussion to talk through the role of imaging in cancer diagnosis. Uh Imaging really is uh essential part of our day to day work. There isn't a day that goes by in clinical work where we don't request multiple CT scans, X rays, MRI S and pet scans. Broadly speaking, we need to know, firstly, is the cancer causing a patient symptoms? For example, if a patient turns up to clinic with a long history of breast cancer, but says that today she has backache, you need to know if it's cancer causing that or if it's just a longstanding uh muscular skeletal pathology. Um and secondly, is the cancer evident on examination or imaging or both it tells you the extent of disease. Therefore, what stage is the cancer? Therefore, how to treat the cancer and what the treatment intent should be on this point at the bottom for the vast majority of cancers. Sadly, again, there are exceptions. But the vast majority of cancers with advanced stage or metastatic disease, most will be incurable. That doesn't mean to say they have a short prognosis because many patient's uh for example, with breast cancer, uh prostate cancer, some lymphomas can live for years and years in excess of a decade with incurable cancer. So you will absolutely uh infuriate an oncologist if you uh in, in general medical circles, for example, if our colleagues decide that somebody should be for ward based care because they have advanced cancer when they might actually have a prognosis amounting to decades. Um So it's a really important thing not to assume that advanced cancer equals short prognosis tmm staging. A lot of you will be familiar with, of course, referring to the stage of the tumor, regional lymph nodes metastases. This varies hugely between different cancers. And there is of course, no way that you can remember this. And I'm not aware of any consultant oncologist, who knows the TNM system for anything but his or her own uh tumor site that he or she treats as a general rule. Though uh the T status, the smaller, the better T four typically indicates a large or locally invasive tumor. So for example, here in lung cancer, A T four tumor might be invading the mediastinum, the diaphragm, the recurrent laryngeal karina tricky esophagus, the nodal status typically goes for most cancers to end to lung is a little different and go to N three. And finally M status is either M zero or M one. And some cancers have an M one A one B one C. I think there's even an M one D in uh in Melanoma. But the key thing is basically a binary, are there metastases or are they're not the number categories of staging? You may also be familiar with these go from 1 to 4 for pretty well all tumor's. Um um and again, there are very dense tables that you can read when you come to sub specialize in whichever particular cancer you're most interested in the future, which will translate, for example, 80 uh to A N zero M zero tumor here tells us is a stage one B lung cancer. In this case, the important thing here is on the right hand side, if you've got an uh m one tumor. So, meaning metastases, that is by definition, stage four, in the vast majority of cancers, this describes limited stage small cell lung cancer. Um So stage 123, small cell lung cancer eligible for treatment of curative, used cautiously intent on the left hand side here. For example, it suggests that stage one and two, which is a tiny minority of patients with small cell lung cancer can be treated with surgical reception, followed by uh adjuvant chemotherapy plus or minus chemo radiotherapy uh up to stage three, you might consider in a fit patient, concurrent or simultaneous concurrent chemo radiotherapy or in a slightly less fit patient chemotherapy followed by radiotherapy. So again, here stage is absolutely vital and you'll see that the difference between two and three leads to entirely different treatment pathways. Sadly, uh stage also correlates closely with five year overall survival. As an example here, this is uh I think from memory for a small cell lung cancer. Um and of course outcomes as you'll know are pretty terrible with small cell lung cancer have been almost no um been very, very little progress in palliative immunochemotherapy in recent years. Um It remains a real challenge for us. There are of course different ways of imaging. Our patient's the commonest, the bread and butter of our day to day work. There is the CT scam which has now been around for several decades. It of course uses ionizing radiation to build cross sectional images. It relies on tissues varying in density. So energy beams pass through some tissues more easily than others. It's quick and easy. It's cheap. A CT head without contrast might take a minute or two. Uh CT chest, abdomen, pelvis with contrast might take a little longer but it's quick, it's cheap. Um Most patient's will not feel claustrophobic in a CT scan. Er It isn't so good for looking at tiny lesions in places like the brain or the liver. It's also a significant radiation dose and um, uh and really should be avoided in pregnancy. Um And we also have to bear in mind, of course, patient's with particular risk factors for future malignancies. IV Contrast is a controversial thing. It says here that it can lead to renal failure. It depends who you listen to. More recent research suggests that it probably doesn't, but you don't want to be that person that puts a patient onto dialysis after giving contrast, MRI of course, does not use ionizing radiation. It uses a huge magnet. The patient slides backwards on a bed into a much more claustrophobic tunnel. If you've ever had the misfortune to have an MRI scam yourself, then they're not the most pleasant of things. Um It however, does characterize soft tissue much better than the CT. And if you look, for example, at some of the images of em, our brains, it really is astounding the detail that we can see the more expensive they take longer. Some patient's simply cannot tolerate them at all. And MRI scanners clearly aren't compatible with some implants, foreign bodies. There's a very long safety checklist that you'll have to go through before you can have an MRI scan. Pet CT combined two different scams as the name suggest you get a pet scan and you also get a low dose CT scan. The idea here is to quantify the uptake of a radiopharmaceutical agent in combination with a CT scam. The radiopharmaceutical is fluoro deoxy glucose. So this is a radio labeled glucose. This is preferentially taken up by cancer cells which are rapidly a much higher metabolic activity than most non malignant tissues. The brain, perhaps the myocardium accepted, that's given as an IV injection. The scan takes place around 60 minutes later. And the uh the nuclear images are then overlaid on the CT scan to give a picture such as one of these, as I said, some tissues shine up on a pet scan entirely normally and physiologically such as the brain, the heart. Here, you can see the uh the trace of being excreted through the kidneys and into the bladder. So that's entirely normal and reassuring clearly. This on the right hand side though is highly suspicious of this patient with a highly FDG avid mass in the right lung and a suspicious avid uh node in the mediastinum as well. I think Rachel's still struggling to join. We'll continue. So pet scans aren't used as frequently. They are more challenging for a radiologist to interpret for all of these reasons here. Um some tissues shine up entirely normally mentioned the brain myocardium down at the bottom. Important to remember now, a young patient such as those coming through a teenage, young adult lymphoma clinic, that patient's with lots of brown fat will have high FDG uptake in other places as well. Clearly, a pet scan, I can't tell the difference between infection or abscess and inflammation and delinquency. They all appear much the same. You'll be asked to stop Metformin temporarily before a pet scan because it causes pretty spectacular bowel uptake. And some other things like granulomatous disease and fat necrosis can also cause false positives and therefore anxiety for patient's. So why, why my, why might we use a pet scan? Well, firstly, it gives us a pretty good idea. If a mass seen on a CT scan is malignant clearly. If it's an abscess, it might also be avid and some malignancies might not be FDG avid, but it's useful. It can guide response assessment in some cancers. And importantly, that's a whole, it's a whole body scan. It really does go from the vertex of your skull right down to the bottom of your feet. And so in a peripheral um cancer such as a sarcoma, it can be really useful for telling us if we've got disease uh elsewhere in the body, the CT chest to pelvis wouldn't show a radionuclide. Bone scan is used occasionally in some clinics to look specifically for bone metastases. Again, this uses a radionuclide agent here, Technetium 99. Um This is useful for detecting monitoring bone Mets usually picks up earlier than on A CC than, than on an X ray. So that's imaging in a nutshell. The headline news though is that a CT scan really is. The bread and butter is pretty mandatory MRI scan if you're wanting to look at soft tissue in awkward places like the liver or the brain, a pet scan. If you're wanting to look at some specific uh tumor types, lung cancer, lymphoma, to name a couple Melanoma. And otherwise your radiology colleagues will always be more than happy to guide you in which scan to request and are always delighted when their opinions are asked that takes us neatly to lab investigations in suspected cancer. As you'll know from ticking request forms at work or as you will come to know, there are of course, millions of tests available on just about every substance the body can produce. These can be used to a diagnosis to assess fitness and of course to plan treatment. Going back to our patient. At the beginning, she had a good going leukocytosis because of a neutrophilia in her case, that could be just a reactive picture because of her developing what's almost certainly a lung cancer. Um, it could equally be caused by steroids if someone has sensibly enough, given her a course of steroids to help her symptoms. And the hyponatremia again really is pretty common in patients with sometimes of lung cancer. Important to say though that these bread and butter blood test will very, very rarely confirm a cancer diagnosis. They may point you towards certain cancers, but a full blood count and set of biochemistry as a rule won't tell you what cancer a patient has. We commonly see anemia. The vast majority of our patients with advanced cancer have subnormal hemoglobin. As I mentioned about leucocytosis a moment ago. Lots of patient's similarly can have a thrombo cytosis due to inflammatory states. Liver enzymes of course can be deranged in obstructive or hepatic patterns. And hyperbilirubinemia can follow either of those hypercalcemia is a common presenting feature of cancers. Um really does imply either bone metastases or apparently a plastic phenomenon. The LDH is an interesting one. It's uh it's done to a crazy degree at our hospital at the Christie where every bio chemistry panel will come with an L D H in other hospitals. It's done very, very rarely. It's a pretty crude marker of high cell turnover. So as a very hazy idea of treatment response, it can be very useful, but it's not the greatest uh test by any means. And some apparently a plastic conditions can cause hyponatremia or calcemia. As I said, tumor markers are perhaps more interesting, but they're also a bit of a dark art and we all have to resist the temptation to be too taken with just requesting a panel of tumor markers for everybody with a lump where there shouldn't be a lump. And there is fairly specific guidance for GPS and Secretary care clinicians on which tumor markers to request. And when the reason for the caution and hesitancy with tumor markers is the right hand column in in red here, which is that there is a significant risk of false positives and false negatives So in red here, all these conditions can cause false positive tumor marker rises. Uh and equally not all patient's, for example, with colorectal cancer will have a raised C E A to go through this very briefly vote. The most important ones that you'll come across in undergrad exams, finals or M R C P will be things like the alpha feta protein in uh some germ cell tumors and hep a tele about cellular cancer. However, of course, also we have to be aware of the patient with cirrhosis pregnancy and some other cancers, calcitonin from medullary thyroid cancer, see a 15 3 is secreted in a small proportion of patient with advanced breast cancer and has a pretty limited use in uh in diagnosing breast cancer to almost no use but is useful in monitoring treatment response in a known secreta. So there's no point going on and on requesting it in a patient with advanced breast cancer if she's never had a raised 15 3, but if it was raised from the outset, then it's useful to follow it on serial testing. See a 19 9 much the same applies. But for pancreatic or biliary tract cancers, see a 1 to 5 with ovarian cancers, the C E A in colorectal cancer. HCG in uh some germ cell tumors, gestational trophoblastic disease. And of course, ps PSA and prostate cancer of all of those on the table. Ps PSA is probably the most useful in the widely used again though. It's important that we're all aware that PS psa is not specific for prostate cancer. And there are any number of things which will put your PS A up and cause a huge amount of anxiety and worry for a patient. So take home message, there is to be careful with and be cautious. Don't just tick all the boxes because you'll end up with a panel of results that you really can't explain and a scared patient, we'll move on to talk about uh pathology in cancer diagnosis. Uh Our histopathology colleagues are uh really are the absolute salt of the hospital. We couldn't work without them. They do a heroic job behind the scenes. They are very much the unseen heroes of the, the the whole process of diagnosis. Going back to our 74 year old with breathlessness, weight loss and the mass in the lung and in the liver, the pathologist is sent a sample described as this. So this is pleural fluid cytology from a plural tap or a chest drain. So the history given is a metastatic lung cancer, query, small cell query, lung cancer, urgent please. Pathologist says, well, it's 40 mL of cloudy red fluid and then goes on to say it's a sample containing cohesive groups of malignant cells. They have an increased nucleocytoplasmic ratio, loaded nuclei with salt and pepper chromatin. Clearly a malignant sample morphologically meaning purely on basic H and E stain. It looks like it may be a small cell carcinoma, but immunohistochemical tree will be done and a further report will follow. So that kind of cytology or histology report you'll see very commonly and we'll talk through what that all means shortly, shortly afterwards. Supplementary report comes back with the results of the immunohistochemical tree. Neoplastic cells are positive for C D 56 synaptophysin with punctate positivity for cam 52 T T F one is negative ki 67 80 to 90%. The immuno profile confirms the diagnosis of small cell lung cancer. So it's beautifully wrapped up in a package for you. So we'll talk through what each of those bits mean. This is something that I really did not appreciate to any extent at all as a med student, as an F Y trainee, as a core medical trainee. And it's only in more recent years as oncology spr that I've, I've read more pathology reports in detail, been two MG T S and and got friendly with some pathologists. Um pathologist on that point are a very friendly bunch and will almost always invite you into their office for cake and microscopy if you happen to be lacking friends as uh some of us are, this is a chandy stain him, a toxin, Ersin stain of a patient with small cell lung cancer. So this is the bread and butter of morphology. The process of selecting a biopsy site, however, needs to be taken into account based on a few factors shown here. So the commonest way to approach this is based on the history, the exam and the imaging and then to select a biopsy site based on, well, what is easy and safe to access? What's the most clinically concerning lesion and what does the patient want? So clearly, a large lump in the neck is pretty easy to get to with an ultrasound probe and a big fat needle compared to a tiny lung nodule, the size of a pea right in the middle of the chest, which is dangerous and unpleasant to get to, which is the most concerning lesion is a slightly different thing. So for example, if you've got a patient with suspected bowel cancer, but also a suspicious lump in deliver, well, clearly, in that case, yes, you could get tissue from the colon via a colonoscopy. But if this is a liver metastases that completely changes your treatment intent from curative to palliative probably um and changes how you're going to treat the patient. So, in that case, you may well want to go after the liver lesion first. Some patient's may simply not be fit for certain biopsies or procedures or may not be all that enthusiastic to undergo them. There's a subtle difference between histology and cytology. Histology refers to a solid uh sample, a needle biopsy, ideally a core needle biopsy or an excisional biopsy even better. This can be done uh via a needle uh externally by a radiologist, for example, can be done by an endoscopy or laparoscopy thoracoscopy or perhaps in a more dramatic situation as a laparotomy. So sometimes, for example, if a patient goes for a laparotomy for their bowel cancer or their pelvic malignancy, then very frequently suspicious lesions on the liver might be quickly excised, biopsied and sent off to the lab cytology. On the other hand, refers to uh diagnosis from fluids, urine sputum, CSF, pleural fluid pericardium. Others, this is usually a fine needle aspirate of any of those places or brushing such as from the biliary tree in an ERCP as a general rule, if you can get histology, a solid lump of cancer, you'll have a much happier pathologist than cytology. It's far harder to diagnose cancer confidently from a few cells sloshing around in a liter or two of pleural fluid compared to a solid lump of lung cancer who gets the tissue. Well, commonly a physician such as Augusta enterologist or a respiratory physician, uh a surgeon or a gynecologist or a radiologist using ultrasound probe or a CT guided biopsy. Here's an example of a patient undergoing a kidney biopsy, probably by a radiologist. The ultrasound transducer is held in close proximity and then under close monitoring to make sure that the uh the needles going into the area of concern within the kidney. Some cause will be taken by a coaxial needle looking something like this in breast cancer. You probably will have come across the term sentinel lymph node biopsy. This refers to a radioactive substance or die being injected directly or adjacent to a tumor. And then a couple of hours later in theater, looking at the lymph nodes within the axilla, um exercising the sentinel lymph nodes for staging purposes. The principle here being that the sentinel lymph node or the first lymph node acts if you will like a gatekeeper. And you can fairly confidently say that if a sentinel lymph node is negative from a breast lump, meaning if the first lymph node is negative, there probably aren't involved lymph nodes downstream of that. So you can probably spare that patient and unpleasant, full axillary node clearance. Here's a CT guided lung biopsy being done. So the patient will be carefully positioned in the scan, er uh will be marked up on the skin. Usually with some felt tip pens will go I/O of the scan. Er whilst the radiologist where's lead apron and ducks behind the the lead screen for for the protection of their own safety very slowly and carefully, the needle will be advanced into the tumor and then they'll usually do a post biopsy check to make sure that for example, they haven't popped new math oryx. So the radiologist does her procedure and copies and pastes the clinical history from the request card for the CT guided biopsy onto the histology request form. Um And the question then is, well, where does it go? It magically turns up in the lab, of course, and once it gets to the lab, they'll do various things to it. It will be very finely sliced, um then undergo a number of stains. These are just some common stains used in hodgkin lymphoma. And again, just as with staging, you wouldn't be expected to know the minutiae of staging for multiple tumor's. You similarly wouldn't, similarly wouldn't be expected to know the immunohistochemical three profile of different tumor. But it's interesting and worthwhile having a vague idea. So here's an H and E slide first on the top left, this shows the classic owl eyes appearance. Hope you can see that this big lump in the middle. So Hodgkin lymphoma read Sternberg cells, as you may remember, characteristically have this owl I appearance. Then you'll notice that on these subsequent IHC stains that particular read Sternberg sell in the middle has taken up the C D 15 and CD 30 markers but not the others. So that profile there is very much in keeping with a hodgkin lymphoma other tests available. Well, it's an ever expanding field fish fluorescence in situ hybridization is useful for chromosomal analysis. So, if you're trying to subtype a particular cancer. So here for as an example, a mantle cell lymphoma characteristically has the T 11 14 Q 13 Q 32 snappily named translocation, which is a hallmark of mantle cell lymphoma fish in that case is going to be a clincher of a diagnosis molecular tests, which we'll talk about in the next couple of slides again, really useful in some selected cancers for guiding treatments. So some common examples here, for example, estrogen receptor, her to alk and rose one E G F R P D L1 that should be rather than PDL exclamation mark. Even oncologists get excited sometimes uh be rough and many, many more. So here's an example going back to colorectal cancer. So here's a patient who's got a liver fairly sadly, chock full of suspicious lumps that look very much like metastases on both sides of the liver. So we consider, well, what will change management management and what's the safest to access patient has the biopsy? It goes off to the path lab for immunohistochemical tree with conventional stains, pathologist then says, well, actually, this looks like a colorectal cancer. And uh I know that we can now do these additional uh status is why don't we request a few further tests that are particular to that particular cancer? So here colorectal cancer, if it was a lung cancer, though there would be different uh particular tests. And again, PCR that is useful for some further testing. Again, really to get down to the nitty gritty. The purpose of this is to really do a deep dive into. Well, yes, this may be lung cancer. But what flavor of lung cancer it is, you know, lung cancer is a capsule term for a tumor in the lungs. It doesn't tell you anything about how you're going to treat it, how long the patient will live, whether they'll live or whether they'll die. And so we absolutely must. It's absolutely mandatory that these specific further tests are done on pathology sample for, for whichever cancer. It, maybe there'll be particular tests that you need to do to run with the colorectal example. For a minute. Here's the CT scan again, here's some uh some immunohistochemical tree staining on the top, right, that I've just pulling from the internet. So you'll see it's pretty small, but you'll see C E A carcino embryonic antigen, the same as the tumor marker, but also done on a pathology specimen is useful. And then the key one here will be C K seven and 20. We'll get a characteristic pattern. So I H C is absolutely vital. Then looking at molecular testing. Well, we want to know in colorectal cancer what the raz status is, rows is a gene and uncle gene that codes um for particular proteins which will guide us in uh choice of treatment for patients with colorectal cancer. So it's really vital that we know there're as status, whether they have a mutation or whether they are wild type. We also want to know whether there is a be rough mutation in colorectal cancer these days. That's a fairly recent innovation as of about five years ago, the her two status is also applicable to colorectal cancer. You'll know it from, from breast cancer. But about five or 5% or so of patients with colorectal cancer will be her two positive and NTRK fusion uh in a small number of cancers as well. So again, these can be mutually exclusive. So generally a be rough mutated tumor will almost never be also rather mutated that they tend to be exclusive. There's only a tiny crossover between the two as an example. Uh But it's important that the take home message here is that it's really important that for whichever particular cancer you're looking at in a given case that you have a careful idea of. Well, exactly what flavor of bowel cancer is that? What kind of lung cancer is it? Once we've got all of that information back from the pathologist, that will usually be a fairly lengthy report for most cancers that for some will amount to several sides of a four paper for others. It'll just be a short paragraph or two. Of course, the case needs to go through an M D T. This is again, non negotiable. This must happen for all new cases of cancer nationally. It typically happens once a week, it can take anything from one hour to half a day or longer. And some of the grimmer MDT S, I've had the misfortune to sit through. Well, generally list all new cancer diagnoses and any particularly challenging cases for which we'd like a radiology or pathology review or just some 2nd, 3rd, 4th or fifth opinions from colleagues in the room typically attended by consultant, physician surgeons, a radiologist and pathologist. Some senior nurses who know the patient's well and actually often chip in with some of the most important things in MDT such as. Oh, well, you know, Mr Jones is currently nursing his wife through the last stages of dementia and will very unlikely want any investigations for the suspected cancer that's clearly essential. Um, a slaughter as oncology, trainees or surgical trainees will usually turn up in MG T as well and sit at the back. There'll be an M D T coordinator who writes minutes and uh keeps everybody on track with the correct notes. There will be a brief discussion of each case led by the chair. The decision making process needs to be really carefully documented. It's always a headache in clinic on the rare occasion that you get a poor documentation from the MDT. Um It's an absolute headache. If then two weeks later, you're trying to think back and say, well, why did we recommend this treatment? And you're trying to explain that to a patient. So clear documentation is important. So at the bottom that it must always be professional though, clearly, discussion's can get very robust or even heated. Um Sadly, I'm sure you will all see pretty um ugly scenes in M D T s at some stage in your career where it turns unpleasant happily, the, uh without exception, every time I've seen that in an MD tea in the past, it hasn't been because of particular egos, but rather because everyone wants to do the best for a patient, they're having a sporting disagreement and they all kiss and make up afterwards usually. Um But we just have to be a little bit thick skinned and M D T s. So this woman going back to the kind of the index case this 74 year old woman where the four week history of dyspnea and cough and a history of COPD. We know she was independent two weeks ago but is now severely dyspneic and wheelchair bound. The radiologist pipes up that she has a large left hilar mass causing obstruction of the left lower lobe bronchus. There is a large left side of pleural effusion, multiple liver mets and this is clearly stage four disease. The pathologist confirms that the pleural cytology is in keeping with small cell lung cancer. And in this case, it's a fairly clear, open and shut case that this needs a referral to a medical oncologist for palliative chemotherapy if it hasn't been stage four disease and perhaps hadn't been small cell, there's been a stage one lung and no carcinoma. Uh huh, squamous cell carcinoma. Then it might have been a referral to a cardiothoracic surgeon for consideration of surgery. Sadly, in this case, though this patient needs to come and see a medical oncologist that takes me to the end of a really whistlestop tour from presenting symptoms to diagnosis. We've spoken about huge amount, I'd be really interested in any questions or comments you might have. Um, this whole process is an art rather than a sigh ins. And I guess the important thing that we haven't touched on at all is the human aspect of it in the sense that uh the heart of all of this process is a terrified patient who during this period, which might take anything from 1 to 6 weeks to do that whole process, that patient will be thinking about whether they have to say their goodbyes to their loved ones, sell the house. It's a terrifying time and it, it really is non negotiable that they're supported through that period by a good clinical nurse specialist. Um So with that point, thoughts on the postcard, any questions I'd I'd be really happy to take. Thank you very much for the talk. It was really, really great. It was really interesting and our apologies for not getting Rachel to be able to join. Um We still haven't got to the bottom of it, but we'll work out in the future and sort that out for the future. But thank you very much, Rohan. It was really great talk and I've just got one question and anyone else, any questions feel free to pop them on the chat and I can go through them. I've just got one question quickly more about your career path. Really? So, what, what drove you into oncology? And how did you get there? What? Absolutely. Um, well, the first thing to say is that I absolutely love my job. I'm doing a phd at the moment and that's very different. But when doing normal day to day medical oncology, spr, you know, the vast majority of the time, I absolutely love it. Clearly. We all have bad days. But, um, I wouldn't do any other job in the world. And, uh, you know, I would happily talk to all of you for hours and try and convert you to come and be medical or clinical oncologist because I think it's a fantastic career. Um, in my case, I, um, suddenly, um, kind of thought as 1/4 year medical students sitting on a bus and thought, hang on a minute. I want to be an oncologist and, uh, didn't change my mind after that. So I picked out placements, um, from there on where I'd get lots of exposure to oncology. Uh, I made sure that my non oncology placements I was looking out for patients with cancer. For example, when I did elderly medicine, yeah, you can usually find an audit or something to do on elderly people with cancer or in surgery. Uh, I made sure that I got two MG T S and made friends in clinics and so on with some oncologists and found some good mentors. Um When I, then, so then I chose a foundation program that had a job at the Christie in which I absolutely loved. Uh You know, I was lucky that my, my first supervisor as an F Y two was fantastically inspiring. Uh And I still work closely with that professor. No. Um uh Then again, I chose a core medical training path that had an oncology job elsewhere in the country which I enjoyed and I wouldn't want to do anything else so that the pathway now if you're interested is to do your F Y one F two, then to go and do two years of internal medicine training rather than three as it stands. So if you want to be a cardiologist or a gastroenterologist, you do three years. But for oncology, you can duck out after two as it stands that may change, you then apply to be oncology. Spr either a clinical oncologist or a medical oncologist. If anyone doesn't know the difference for that is simply that clinical oncologists deliver radiotherapy as well as um systemic therapies, chemotherapy. Whereas medical oncologist, we are much more now reminded and only deal in systemic therapies. Uh so that you can apply for an S T three job. As of a couple of years ago, there is now a common ST three years shared between clinic and Meadowbank. So regardless of which one you have been allocated by the interviews and selection process, you do the same sort of year, you do some basics of chemo and radiotherapy and common tumor sites like breast lung and colon. And then after that, you diverge and we do slightly different exams. Medoc training is four years as an S P R A majority tend to do phds or higher degrees as well. But not everyone, it isn't mandatory by any means. Clinical oncology is five years of training. Still plenty to higher degrees. Perhaps not, not quite as many though. That's great. Thank you very much. It's really interesting um, to hear about your group health. Um, I don't think there's any questions in the chat at the moment. Um, but I'm sure if anyone's got any, I'm sure you won't mind them emailing you. Not really happy to. Uh, yeah, please do pass on my email address. If anyone wants, uh, advice about careers or applications. These kinds of things were really help. Uh, can't, can't recommend it enough as a, as a career. Really fantastic mix for me. Of clinical medicines are good medicine, good signs and good pathology research and kind of the, the human aspect of really developing good relationships with our patient's. Uh, I promise you, it is not as depressing as you think. And we give a lot of really good news as well as bad news. Of course. Thank you very much. Thank you for a great talk and we'll just see you at future events. Not, thanks very much. Bye for now. Thanks everyone for attending. Thank you.