Mastering Cancer Treatment: Insights from medical oncologist Professor Tim Price

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Over the last three years, Aussie Med Ed has covered many medical topics and multiple cancer issues, which include renal, colorectal, skin, lung and pancreatic. Whilst individual treatment varies between the specialties, in all cases, an oncologist is often required to assist in providing further treatment and to help reduce the risk of recurrence. Today we're going to learn more about what that oncology treatment involves. Welcome to Aussie Med Ed. G'day and welcome to Aussie Med Ed, the Australian medical education podcast, designed with a pragmatic approach to medical conditions by interviewing specialists in the medical field. I'm Gavin Nimon, an orthopaedic surgeon based in Adelaide, and I'm broadcasting from Kaurna land. I'd like to remind you that this podcast podcast players and is also available as a video version on YouTube. I'd also like to remind you that if you enjoy this podcast, please subscribe or leave a review or give us a thumbs up as I really appreciate the support and it helps the channel grow. I'd like to start the podcast by acknowledging the traditional owners of the land on which this podcast is produced, the Kaurna people, and pay my respects to the Elders both past, present and emerging. I'd like to remind you that all the information presented today is just one opinion and there are various ways of treating all medical conditions. Therefore, you should always seek the opinion from your health professionals in the area in which you live. Also, if you have any concerns about the information raised today, please speak to your general practitioner or seek advice from a health organisation such as Lifeline in Australia. Well, it's my pleasure now to introduce Professor Tim Price. He trained in Medical Oncology at the Royal Adelaide Hospital and completed a Gastrointestinal Fellowship at the Royal Marsden Hospital in London. He's currently Head of Clinical Oncology Research and Head of Unit of the Combined Haematology and Non Medical Oncology Service at the Queen Elizabeth Hospital and holds visiting positions Both at the Calvary Hospital, North Adelaide, Western Hospital, Henley Beach, as well as the Lyall McEwen Hospitals. He's a clinical professor within the Faculty of Medicine at the University of Adelaide, along with all these accolades, he's also well known as being one of the nicest guys around the hospital. Welcome Tim. Thank you. Thank you. Thanks again for inviting me and I'm a pleasure to talk about medical oncology today. It's fantastic to have you on board. Look, I thought I'd just start off by asking you what your job involves. When I did my little bit of research, I realised how expansive it is. Perhaps you can describe it for the medical student and the GP who's listening. In yeah currently I have a few different roles, which is what you're probably alluding to. So I'm a medical oncologist, so I obviously see patients. I have two clinic days a week. I also am the head of the clinical research unit within the Cancer Centre here at Queen Elizabeth Hospital, so we run the clinical trials. And then I'm also currently involved in what's called the BRAG Comprehensive Cancer Centre, which is developing a Comprehensive Cancer Centre for South Australia, which is part of a national drive to have what are called Comprehensive Cancer Centres across the nation. So that's my various roles at the moment. I'm also involved in the Australasian Gastrointestinal Trials Group, which runs gastrointestinal trials across Australia. So my main interest is in gastrointestinal cancers. Well thank you very much for sparing some time. No problem. An oncologist, from my point of view, is someone who treats or looks after all the adjuvant and neoadjuvant therapies for cancers. And when you look at the different cancers that we've seen, in Aussie Med Ed, we've actually covered breast, renal, lung, prostate, melanoma. And all the individual specialists have to know those in quite deep detail, but you as an oncologist need to know all of them in perfect detail. How do you manage to learn all of this? Yeah so it's actually a good question because it is actually currently changing in terms of the way medical oncologists work. As you alluded to, there are different cancers within the community breast cancer. Colorectal cancer, prostate cancer in particular are the more common ones that are important to understand. And within that, there is now a great degree of complexity around the different treatments. So we'll talk a little bit later, about some of those treatments. But within colorectal cancer, for example, there are now at least six defined subgroups that all have different treatment pathways. For example, myself, I'm primarily a gastrointestinal medical oncologist, so that's all I do. So that's from the esophagus through to the anus and everything in between. And there is a lot of different treatments involved. Now, there are some medical oncologists who are generalists, who, as you say, have to treat all cancers, but that's becoming increasingly less common. Most oncologists will either have A fairly large tumor stream, which gastrointestinal is, or they may do breast cancer and gynae cancer, for example. So it is not quite as broad as your concern in terms of the breadth of knowledge needed. It's a bit like in in your specialty, orthopaedics. I mean, there are now, knee specialists, hand specialists, et cetera, et cetera. So it is becoming subspecialized even within the specialty. right. And when does your role start? Does it start from initial diagnosis when a specialist refers a patient to you and you join a multidisciplinary team? Yeah, so commencement of meeting a patient with cancer very variable, so it may be a referral directly from the GP, so for example, they may find that they've done a scan and there's lesion in the bowel and also, unfortunately, metastasis in the liver, and that Patient may be referred directly to me and then I will then, as you say, coordinate that multidisciplinary management, which will of course include a surgeon and sometimes radiation oncologist. A lot of the referrals though have come via the surgeon, so the GP will have picked up bowel symptoms, bleeding for example is a common one for colon cancer, and they'll have had surgical workup, diagnosis, potentially surgery, and then they'll come to the medical oncologist to consider the chemotherapy part of the treatment. It is, a fair point to make that, the medical oncologist often has the most prolonged contact with a cancer patient, so a surgeon will operate. Recover, that might be a few weeks but a medical oncologist can be six months if they're having adjuvant therapy and it could be lifelong if they're having treatment for more advanced disease. who do you depend upon predominantly as part of your support team? Yeah, so the crucial team within a medical oncology unit will be the the chemotherapy nurses are particularly important because obviously that's what our main tool of our trade is delivering chemotherapy and particularly intravenous chemotherapy. Highly trained chemotherapy nurses who understand the treatments, side effect screening and just being there to deliver the safe chemotherapy access and so forth. The other crucial thing in today's practice is what are called cancer care coordinators or sometimes they're termed nurse navigators, but that can be more broad in terms of different specialties. But they're really increasingly important because of the multidisciplinary nature of cancer care. So patient may have a medical oncology appointment, they may have a surgical appointment, radiation. And, For a patient, coordinating all those appointments, understanding why they have them, trying to make sure they flow with their investigations, so often they'll have CT scans, different x rays, and so navigating through and coordinating that sort of sequential approach so that the management There's a pathway is often importantly guided by those cancer care coordinators or nurse navigators. I mean, more broadly you know, cancer is a. Upsetting diagnosis, so psychologists are really important in a cancer centre. Dieticians are really important because with particularly more advanced cancer the nutritional changes that can occur because, people don't have an appetite and weight loss and trying to manage that. And then, of course, patients are admitted to a ward and often have cancer specific symptoms. So having, cancer trained nurses on a cancer specific ward are also important. So many different specialties and clinical practitioners that are involved in the care of cancer. And I guess just as I'm talking through, the other one is nowadays increasingly is physiotherapy or exercise physiologists. So trying to maintain, we know exercise has a positive impact on cancer outcomes, particularly in breast and colon cancer. And focusing on that exercise and keeping people well and active is also increasingly important. So there's lots of, people that are involved in that cancer team beyond our surgeons and radiation oncologists. Yeah. I suspect the palliative team will also have a role at some stage in some of those patients, hopefully not as many as we might Yeah. So that's a very important point. As you alluded to with the way you asked the question, when patients ideally will be on chemotherapy and tolerating that we'll be keeping their disease under control, which nowadays can be for years rather than months. Historically, advanced Disease was often measured in months in terms of median survival. Nowadays it's often in many years. So those patients remain well and we need to manage their symptoms and side effects. But as the treatments start to become less effective or patients become resistant to treatments, then the palliative care team becomes a crucial partner in managing those patients as they develop symptoms, particularly pain. Weight loss nausea, which is probably what precipitated your question, because they are symptoms of the later phases of cancer. So yeah, we work closely with palliative care, particularly towards the later part of patients, pathway and and then often that is a transition to palliative care being the primary caregivers. That said, the general practitioner can be incredibly important in that phase not only through the whole pathway of cancer treatments and support, but particularly in those later stages when patients are having symptoms and the general practitioner understands the family, they may have known that patient for many years. The husband or wife, etc. So I think it's a partnership of a number of different teams, but certainly palliative care is very important. When I think about treatment of cancer, I think of surgery, Oncology and Radiotherapy. Are there any other modalities I need to think about part of the treatment process of cancer. So just in terms of your, the definitions there it's really important to to sometimes define that. So adjuvant therapy, neoadjuvant therapy are primarily in the curative setting, and in that setting often surgical intervention and radiation intervention are core component of that whole treatment pathway. So the adjuvant is obviously when patients have had surgery, either their breast cancer removed completely and then adjuvant therapy is aimed at reducing risk future recurrence based on micrometastatic disease that we can't measure. I guess to your question about what are the other things we need to be aware of, so that just makes me think of the new sort of We're probably going on a little tangent to your question, but in terms of new technology, what is increasingly being explored is whether you can actually tell which patient requires adjuvant therapy. By definition, a patient who comes to you to discuss adjuvant therapy is not because they definitely have cancer. It's a potential that they may have microscopic disease, and then you're giving all of the patients you see of which there may be, let's say, for example, there's a 30 percent risk that they may have microscopic cells that cause a problem in the future. But you'll see 10 patients, there'll be 3 who may benefit because they're at risk and the other 7 won't. But all of those patients are getting chemotherapy. So that's a fair proportion of patients who are getting chemotherapy for essentially no reason at all. So what we're now seeing is that we can potentially differentiate between the 7 who do not require it, and the three who do, by measuring by what's called a liquid biopsy, seeing whether there are circulating tumor DNA measurable, which then indicates there's residual disease, and those patients then would ideally then be advised to have adjuvant chemotherapy. And if we can show the reliability, the sensitivity of those tests it is still very investigational, but the sensitivity and specificity is increasing. Ultimately, We should be able to do a blood test if you like. to then tell whether a patient actually needs adjuvant therapy or not. So that, is a significant change. In terms of, I think you're asking around what sort of changing that multidisciplinary space. The other thing that comes to mind in terms of a major change in my specialty is that patients who have low bowel cancer, rectal cancer, for example. If you think of bowel cancer, the typical response would be you need an operation or surgery. For Rectal cancer now. What we now do is look at a combination of chemotherapy and radiotherapy as a neoadjuvant, so pre surgical intervention in the curative setting, and then an additional round of chemotherapy, so roughly five, six months of therapy, and what we can see is that around 40 to 50 percent of patients actually have a complete response response. without needing surgery. So rectum, preserving the rectum is now becoming increasingly an option for patients who have rectal cancer. So that's quite a different way of practicing. So historically they would have gone straight to surgery or they may have had some radiotherapy before but then always had surgery. And now nearly half of patients potentially may actually not need to go to surgery. And of course, for rectal cancer, the requirement of a stoma and the impact on the patient is really quite significant. So that's a major change, looking at the whole three specialties. So radiotherapy, chemotherapy, and then potentially, in fact, not needing the surgeon aside from very close surveillance after that. So that's, one of the key things I'd say the other way of answering your question is looking at beyond chemotherapy. So in that adjuvant setting, so in that precautionary, postoperative setting, the other big change is that in, particularly in melanoma, where now we know that immunotherapy, which has a, been a game changer for melanoma overall, but even in the adjuvant setting, we're now seeing that we can prevent recurrence. Melanoma when it recurs historically is not a good thing. Although immunotherapy has changed that as well, but. We now can give adjuvant post, removal of a melanoma lesion immunotherapy. And then there's a significant reduction in the risk of then recurrence in the future. So that's a big change. It's not just chemotherapy given in the adjuvant therapy setting. It's also immunotherapy. And then there are some other targeted agents that. What are called targeted agents, which are also used in the adjuvant setting for lung cancer, for example. So yeah, it has moved beyond just standard chemotherapy. In the years since I've trained, the stuff you're talking about is just like science fiction when I went through and it's just amazing you can do that. I'm in awe of how things have progressed. What agents do you generally tend to use when it comes to chemotherapy? And are there a few ones that the medical students and GPs should know? Is there broad headings, just the basics to go so I think, what I would suggest is important is really understanding the differentiation today between chemotherapy, often called molecular or targeted agents, or immunotherapy. Because if you see have a patient who presents to the new clinic, or into emergency, identifying the differences between those is really important in terms of particularly the potential side effects. and how they're managed. So if we start with chemotherapy, there are lots of different mechanisms of how chemotherapy work. They can be direct DNA damaging agents, or they might impact on the cell cycle, but ultimately they're cell killers. They're essentially killing the cancer cells by whatever mechanism they're delivered. And therefore, they typically have fairly broad, recognisable side effects, which are important to understand. The risk of nausea, which nowadays is actually far less because we have medications to prevent that. But the risk of gut toxicity, so diarrhoea, mucositis is pretty common. Alopecia is what we always that's actually very dependent on the type of drug. So, anthracyclines, for example, will cause hair loss, as would what we call taxanes, that's another class agent, but essentially, alopecia is one, one side effect that we need to be aware of but particularly in terms of managing things, gut toxicity is one. Mucosal damage from the chemotherapy, the toxicity, and obviously hematological toxicity is the other one that's very important to be aware of with chemotherapy. So when someone presents with, they say they're on chemotherapy and they have a fever, it's very important to understand what their white cell count or their neutrophil count is. count is because if they have a neutropenia, then their risk of sepsis and potentially dying from that is actually then quite high untreated. So the need for early intervention, early intravenous antibiotics for someone who's neutropenic and has fever is very important to understand. Fatigue, all of those sort of other general side effects are important. I guess they're the key ones that, you should always be aware with chemotherapy. And I think, chemotherapy's been around for many years. I think most people know those key side effects and potentially know how to manage those. The ones that are different though are the, particularly immunotherapy. Immunotherapy does not cause typical chemotherapy like side effects. Essentially, the main side effects of immunotherapy are autoimmune processes. iNflammatory bowel like syndromes where you get colitis from an autoimmune process. Hypothyroidism hypophysitis is actually quite common with immunotherapy and needing thyroid replacement or cortisol replacement, for example. Pneumonitis hepatitis, all from an autoimmune mechanism are the side effects that you see with immunotherapy. And essentially, all have the same treatment, which is steroid. So as you would with a autoimmune disease, the crucial thing is to recognize that someone who's on immunotherapy and potentially has a autoimmune process needs steroids, and they often need them in high dose. and ideally need that early. So, that's a, a really important understanding broadly as to what you need to think about when someone has immunotherapy and unusual toxicity. So myocarditis, pericarditis, those sort of things. So if people, patients present with syndromes that you might think are a diagnosis, but it's linking that to that autoimmune process and then starting steroids, which is really important. And then the molecular drugs often have. Fairly specific side effects depending on the class. For example, there are what are called anti EGFR, or epithelial growth factor receptor antibodies. Patients will often confuse those and call them immunotherapy. But they're not. They're antibodies against growth factors. And they have, for example, a particular side effect with a rash. And it's often an acne like rash. So it's often facial, chest requires steroid cream, antibiotics and advice about sun and creams. And so that's, an unusual side effect, somewhat unexpected and certainly not one you'd see with chemotherapy and is specific to, to that class of agent. Some of the other drugs have other types of rash. Some drugs cause a lot of arthralgia, joint symptoms, and they require physiotherapy and so I guess just being mindful that there are these differences between standard chemotherapy, which often cause, people think about diarrhea. Effect on blood counts, nausea, fatigue, that's chemotherapy. Immunotherapy is very much autoimmune processes, which have a very specific treatment as in steroid. And then some of the other sort of what are called targeted drugs have relatively specific side effects depending on what the target is. The reason the anti GFR drugs cause a rash is that the receptor is actually quite common in the skin. In fact, the rash is a good signal that the drug is working. So if you get a really bad rash, it's probably working because it's hitting the target. But it's a it is a distressing symptom and it's a shame it has to occur, but. But it is one specific to that sort of target. The other one which is quite common in what are called anti angiogenic drugs. So they're targeting the vascular endothelial growth factor. Those drugs cause hypertension and proteinuria. So they're, again, someone who's on a anti angiogenic drug and might turn up to the clinic or to emergency with very high blood pressure. It's important to identify that. Probably related to the chemotherapy treatment. So again, it's not one that you would think of as being chemotherapy. It's related to the Targeted drug and because of the works on blood vessels and then managing that hypertension somewhat aggressively is appropriate because it is drug driven and the antibodies have longer half life so it's not going to go away quickly. So they're just a few examples, of the different. agents and then therefore the different side effects that we need to be aware of. So it's not just classic chemotherapy anymore with those typical side effects. There's a number of differing side effects we see from those different, differing types of drugs nowadays. Brilliant. Great summary. Thoughts come to mind. When a patient presents a casualty and is assessed by an intern, or comes with a GP practice, and they've got neutropenia from a chemotherapeutic agent, how do you determine it's actually sepsis? If they've got a high fever but you can't see a raised white cell count, they may not have a ESR or CRP response because of their reduction in cells and things. Apart from being aware of it and just treating it on spec, are there any other things that these doctors should look out for? Yeah, so the crucial message that there is that if a patient presents with a fever and you've done a blood count and they're neutropenic let's say their neutrophil counts 0. 3 or 0. 2, the crucial thing there is that irrespective of whether they're unwell or not, they should go probably to their cancer centre or to an emergency because they are at risk because they've already had a fever. Obviously something's going on, and they need then to be assessed and potentially put on intravenous antibiotics. Now, there are protocols, sorry I'm slightly diverging from your question, but there are protocols for what are called low risk neutropenia, and sometimes patients can be sent home. with oral antibiotics, but it does depend on the protocol. So how long you predict the patient will be neutropenic. So the longer, if a particular chemotherapy protocol means that you're likely to be neutropenic for a prolonged period of time, you would always admit that patient for intravenous antibiotics because there's a high risk that fever is predicting for deterioration. So I guess that's the crucial message. If someone has a fever, even if they're not unwell at the time, they probably need to have assessment at the cancer center because they're at risk of deteriorating. in Terms of telling the sepsis there are the classic symptoms are still there. If they're developing hypertension, tachycardia, et cetera they would be the clinical findings. The other point to make sometimes though, is that if a patient on chemotherapy presents unwell and particularly unwell, and then you've and then they're neutropenic, they may in fact not mount a fever, so they might be hypothermic, which again comes back to your question about sepsis, so those patients are obviously at very high risk of deteriorating. So CRP generally does still become elevated in the setting of infection even if you are neutropenic, so those investigations are still relatively informative but obviously the crucial thing is understanding that neutropenia. Yeah. The other question that comes to mind is use of immunotherapy. You talked about an autoimmune reaction. Now, obviously, rheumatologists treat these autoimmune type conditions nowadays with biologic agents. Can you use the immunotherapy and then a biologic agent to treat autoimmune reaction, or you still stick with the standard steroids? You're absolutely right. So the first line therapy is steroid. And often, as I mentioned before, high dose steroid. But then if you have an autoimmune persistent colitis, then that's right. You can come in with some of the other agents that are used for inflammatory bowel disease, for example and rheumatoid cetera. So they are the next step up. They're relatively expensive and has complicated the way we treat some of these toxicities and so I guess one of the other things to talk about, which is actually quite important around modern treatments for cancer is, the financial toxicity of some of these agents. So they're not always available on the PBAC. So we need to then work with how we fund these agents and immunotherapy historically has been very expensive and then you add in a toxicity that then has if you don't Respond to steroid, a very expensive biologic to try to treat that autoimmune syndrome, that makes things quite complex, particularly as patients are generally admitted to the hospital and then the funding the budget around trying to support the immunotherapy toxicity has been something that's been a concern of recent years. That said, the modern the new generation immunotherapy drugs have far less common. Risk of these autoimmune conditions and therefore, the need for some of those biologics is less, but you're right, steroid and then a biologic if that's failing. And going back to the nausea agents we're talking about, is ondansetron still the one that's predominantly used for chemotherapy and other nausea conditions associated with this, or is there newer agents again? Yeah, so there's NK inhibitors, which is a different class and then there's and then there's the ondansetron or Palonosetron but they're the same class as as odantetron and now there's actually a combination of the NK inhibitors and ondansetron like drugs which we give pre chemotherapy and then that's often combined with steroid, with dexamethasone so it's really what you'd call a triplet, combination of drugs to minimize the risk of nausea. And nowadays, nausea becomes less of a problem. in fact, what we see more often is that patients complain of the post chemotherapy fatigue or tiredness for two or three days after. And I think it's because the nausea is better controlled that, probably fatigue's always been there, but that's really what they're now. And and that's, yeah, so those new anti nausea medications have really changed things, just going back to one of your, the earlier questions around side effects and what people what, clinicians should be aware of. It just made me think about neuropathy. Nausea we've controlled even alopecia nowadays, we have cold caps to reduce that risk. But one of the, one of the more concerning longer persistent side effects of chemotherapy is neuropathy and certainly cisplatin, so the platinum class drugs can cause neuropathy. A drug that I use commonly, oxaliplatin, has a very, it's a very effective drug for bowel cancer, and in fact all GI cancers nowadays. buT it has this risk of causing an unusual cold sensitivity, so that if you touch something cold, or walk on cold tiles, or even drink a cold drink, it feels like your throat's closing up, or you've got pain in your hands and feet. And that can transition into actually a painful peripheral neuropathy that persists. And that can be quite problematic, and I think, A lot of general practitioners see these patients who have had their treatment and they're in their, if you like, their survivorship period, and they come with that neuropathy, and they're obviously wanting some answers and some treatment, and unfortunately, in some patients develops. into an irreversible, uncomfortable neuropathy, which in fact has no treatment. And there's been lots, a lot of investigation research around trying to prevent that neuropathy, giving calcium magnesium infusions, for example using early anti epileptic drugs to see if it reduces the neuropathy. But unfortunately it's a very persistent problem. It's one that I see general practitioners refer patients back for Is there some way we can improve this? And unfortunately there's not. So that being aware of that neuropathy I think is probably also something that would be useful. On that aspect, obviously sometimes, not commonly, but occasionally we'll see a patient for carpal tunnel or some other nerve entrapment type condition who is having chemotherapy. Is that contraindicated to do a release or would you still recommend trying a release to try and help as much nerve entrapment as possible in that situation? Yeah, if they've got a, it's separate syndrome like carpal tunnel, then that, That would certainly be appropriate to manage that as necessary. And I guess that's why I mentioned that neuropathy because it is a side effect that that's out there. It tends to resolve but trying to differentiate between the chemotherapy neuropathy that may be persisting and then other syndromes as in carpal tunnel is really important. And and does that neuropathy affect the optic nerve as well? Obviously it's more of a central nerve, a cranial nerve. No, so it's purely a peripheral nerve peripheral neuropathy. Now that said delving into the sort of the less common here but when you have an oxaliplatin infusion as I mentioned, this cold sensitivity comes on quite quickly. It can be a very difficult drug to give in winter, for example. I think if you lived in the UK, it'd be a terrible drug because it's always cold there, but if you go from the warmth of the chemotherapy suite and you go out into the cold, you get this cold air into your mouth and it feels like it's closing over, you get the hands and feet. But some people do get some funny jaw symptoms. Some people get some visual changes. So going back to, it doesn't affect the optic nerve, but it creates this sort of sensitivity, which I think is not well understood. It's transient, it goes away. And in fact, some people develop some tongue symptoms, they have a bit of trouble with their speech, and then some patients even describe this sort of jelly legs, they physically can't actually walk. And they need to stay in overnight. It all goes away but there are some unusual sort of spectrum within this sort of nervous system effect that oxaliplatin causes. But typically it's that cold sensitivity. Your predominate gut oncology. How often would you need to see a patient after a with a gastrointestinal cancer? And what's the sort of normal follow up period and how do you evaluate them when you do see them? Yeah, so it depends a little bit on the situation. So an adjuvant patient, for example, will come to us after their surgery. They'll then have generally three to six months of chemotherapy as an adjuvant precautionary treatment. And then generally those patients will then go back to their surgeon for surveillance. And that might be the colorectal surgeon or the breast endocrine surgeon, if it's a breast cancer, etc. If a patient has metastatic disease, then they're probably going to see you for a long time, hopefully. In the metastatic setting what would be termed palliative chemotherapy schedules will be given. And when I use that it's very important to understand that it's just the terminology. So we're not in a palliative setting, but they, because they're aimed at controlling disease, controlling symptoms, preventing symptoms, et cetera. That's the terminology. And so in, in that sort of setting, patients will have a course of chemotherapy, which is generally about six months. Then hopefully they're in a type of remission or disease control and they'll be monitored. They'll then have regular scans every two to three months. And then when they have activity again, they would recommence chemotherapy schedule. And you'd be seeing patients, roughly every three months when they're not on chemotherapy. During chemotherapy though, it would depend on the schedule. So Some chemotherapy schedules are every week, some are every two weeks, and then some are every three weeks. That's probably the biggest gap. And then you would see those patients essentially before each chemotherapy. You assess their blood count, so going back to the neutropenia point before, you would need to make sure that they've had hematological recovery, so their neutrophil count and platelet count is adequate, and then they would proceed with chemotherapy. I think you've basically touched upon the newer agents, but where are things heading? What's the innovations that are coming in the area of oncology treatment? Is there anything on top of immunotherapy and other agents that you've talked about already that's actually quite exciting? yeah, so the other sort of class of drugs that are coming through are what are called ADCs which antibody drug conjugates and they're quite interesting in that they're basically an antibody to a receptor that's quite common on a cancer. So, the antibody is not the treatment part. So the antibodies I talked before, the EGFR, or the vascular factor I described before, the antibody is directed at those receptors as a part of its treatment mechanism. The antibody drug conjugates are drugs that will bind to a a receptor that's not necessarily related to the cancer process, but it's common on a cancer cell. It may be overexpressed, but not necessarily driving the cancer. And then there's what's called a drug payload, so the, to the antibody is then linked essentially a chemotherapy drug. Heat seeking missile? exactly, so exactly, so what you're doing there is you're trying to deliver the chemotherapy drug directly to the cancer cell by using the overexpressed antibody. Now, in theory, those drugs will be more targeted it is still chemotherapy, it's still cytotoxic, killing those cells But it is, yes, exactly as you described. So that's, one exciting change that's that's been occurring. The other one is what's called CAR T cells. Now, this is more commonly used in hematology, but is increasingly being used. It's a type of immunotherapy and again, based on the particular receptors or behavior of certain cancer cells. For example, there are CAR T cell trials for bowel cancer. They are particular bowel cancers that have particular receptors, which then allow, t cell manipulated T cell, which is part of a CAR T infusion to then be delivered to again hone in on, on those cancer cells. Cancer vaccines, I had a patient who chose to travel to the U. S., to the Mayo Clinic in the U. S. to have a personalized vaccine developed. Now, I'm not. Quite across the technology of some of these things, because they're really now, getting into the field of true immunology specialised cancer therapy, and there are particular clinicians who do that, particularly the haematologists but it is looking like CAR T therapy and vaccine therapy, personalised vaccine therapy will have a place in the solid cancer setting. And that's a very strong area of research moving forward. And so there, I guess there, there are two examples of technology that's really developing, becoming quite intricate and complex around the understanding of the cancer cell and the individual's immune system and then trying to use that to drive the therapeutic approach. That would be the two , changes that would come to mind. And then there are, changes to the to just immunotherapy. As I mentioned before, they're a first generation, they're a new generation of drugs. As we understand how we manipulate the immune system. Immunotherapy essentially turns our immune system back on. That's essentially what it's doing. So we're actually. Fighting the cancer off ourselves by having these antibodies turn our own immune system back on. Or stopping the process that occurs where the body becomes fatigued. So have lots of abnormal cells in our body all the time, but we often clear those. But if the population reaches a point where the immune system is overcome or fatigued, then it switches itself off. And what we need to do is then switch it back on, which is one of the key principles of immunotherapy. Understanding how we can turn that back on is really an important part of researching new generation immunotherapy. Two questions come out of that . First one is, with the idea that, normally our own immunology kills the cells that are floating around, but this new immunotherapy helps turn it back on. Does that explain why, as we age, risk of cancers get greater, because we don't have as good an immunity, and therefore we're not keeping the cancer in check, and therefore they can get out of control as we get older. Is that the thought that widely occurs, or is that just me making it simplified there's no doubt that that is part of the, process. There's the aging process itself, which puts, the cells at greater risk of not. Repairing properly, et cetera. Greater exposure to carcinogens, et cetera, over time. But certainly that modification of the immune system is probably a factor in that as well, as we age. Yeah, And the other question that came into mind was the personalised vaccinations. Is that on the back of this mRNA vaccination that's COVID era, or was this well before all that? so the mRNA research that's come out of the COVID vaccine, I think, is increasingly a component of these personalized vaccines. As mentioned, I'm not entirely across that technology, because It is very highly specialized. Very few of those trials exist. As I say, my patient went to the U. S. to seek out one of those. But there is various mechanisms of developing those personalized vaccines. They are very investigational but yes, that's the interesting thing, isn't it? The mRNA technology was being investigated in the background, particularly around the cancer space. And then because of that , that's why it was being able to be transferred into the COVID situation so quickly, because it was a technology that was already understood and then transferring it very quickly. So we were lucky in a way that was being developed. Excellent. My final question for you, but a year ago we had an interview with a couple of researchers on artificial intelligence and I would have thought there'd have to be a role of AI in your area for designing or working out which algorithms or which protocols work better for different patients? Is that the case or is it not yet incorporated into oncology? Yeah, it's going to be really interested where AI fits in terms of, predicting a or trying to guide a patient's pathway. Currently it's relatively straightforward because based on those biomarkers that we get, mutation testing, et cetera. But I think where it's going to have a huge impact is in the diagnostic setting. You look at, so for example, for immunotherapy, we need to understand what's called the PD L1 count, which is essentially what the antibodies for immunotherapy target. And so there are a number of different scoring mechanisms to give you your PD L1 percentage on the immunohistochemistry of the, specimen or biopsy. And that takes a lot of time, so the pathologist has to count a certain number of cells, and then how many are PD L1 positive and would think that AI training that occurs with. to be able to then read those pathology slides and give you a score will be a huge sort of time saving. A lot of the cost in some of what we do. So when you have a new drug that requires a PD L1 score, that then requires funding for the pathologist to do that. If you can automate it, if you can just, have it read then some of those funding issues which often delay our access to some of these interventions can be overcome. Obviously, there's a cost to developing the AI, but, I think there's a longer term trade off in terms of something that can automate it. And then, of course, in the radiology field, I think that's the other area where. AI is being seen, but that's predominantly around screening, particularly, lung screening, for example, is coming into play, whether you can read the scan by AI. So I think definitely AI will have a place particularly in, in some of the diagnostic settings. In terms of being able to, I guess the other part is, it's again diagnostic, so the molecular screen, when you look at these mutations, being able to look at this huge amount of data that comes out when you do a next generation sequencing, which is the NGS, which is the way the molecular testing is done, and looking for the mutations, the mutation count burden, if that can be automated by AI, that's also going to give us a faster, I suspect, and also the decision making ability. Lower time intervention to get those results. So certainly in the diagnostic setting, I think there'll be a huge impact of AI. I don't think AI will take away from the clinical perspective of explaining what we need to do and those sort of things. Yeah. It's been brilliant, absolutely brilliant having you on. I'm honestly in awe of what you're doing. It's been fantastic hearing about it all, Tim. Really appreciate your time. You're a very busy gentleman. And once again, thank you very much for coming on Aussie Med Ed. No worries, it's been a pleasure. Hopefully it's been of some interest. Thank you. Oh, I'm sure it will be, so thank you very much. Thank you very much for listening to our podcast today. I'd like to remind you that the information provided is just general advice and may vary depending on the region in which you are practicing or being treated. If you have any concerns or questions about what we've discussed, you should seek advice from your general practitioner. I'd like to thank you very much for listening to our podcast and please subscribe to the podcast for the next episode. Until then, please stay safe.