Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

I'm gonna cover these three learning objectives, implementing multi mo multimodal interventions, coordinating multidisciplinary team management and monitoring outcomes and adjusting plans. This is a companion talk. My previous talk looks at um methods of cachexia diagnosis and screening. So principles of life, as we've learned from my previous lecture, cancer, cachexia is a multimodal um problem by that. I mean, the biology that's surrounding it is complex. It's not just simple, um lack of nutritional intake, it's not just simple loss of muscle, it's not just simple metabolism changes, it's all of these things together. So when you have a complex problem with multiple different pathways that will result in it and different, different types of clinical phenotypes, it's really important that we address all these factors in unison together. So it's rare that we're gonna have one single medication or tablet that's gonna fix this problem. Second thing is our goals. Well, ideally, we'd like to people to gain weight, gain function and improve their quality of life and independence. Our goal can also be to preserve function, preserve quality of life and preserve independence. And I think that's a, a reasonable thing to aim for. It might be always difficult to stop people losing weight and reducing their physical function. But it's a maybe AAA, you know, less advertising aspirational to go for something that's preserving function. It don't be too hard if you're looking for increases in weight and increases in physical function. And also it's important to think about stage specific interventions. So, what's right for somebody at the start of their um cachexia trajectory wouldn't have a pre cachexia phase. Might be quite different from somebody in the refractory cachexia stage near the end of life. So what we're very good at doing in oncology is we're very good at staging cancers and treating cancers. And in the last 10 or 15 years, there's been a huge step change in the positive improvement outcomes of multiple cancer types. So we think of hither to cancer type 24 such as um lung cancer, lung cancer is a great example. Um myeloma, for example, patients now with these diseases are living for many years, patients with stage four lung cancer are now living for, you know, two or three years, which was unheard of, you know, five years ago. So we're really getting good at treating cancer, staging the tumor and treating the tumor. But what we're not very good at staging the horse and treating the host. Now, by staging the horse, I mean staging the patient, what stage is that patient at? Is that patient lost a lot of weight? Are they functionally compromised? Are they very weak? Have they got a reduced appetite? Have they got multiple symptoms such as pain will move to constipation? So we have to think what is the patient like? How are we gonna stay to the patient? There's various ways to do this. We can do it through a a functional status such as ecog performance status. You can do a biochemical status such as using a inflammatory score such as the Glasgow score. The important thing is that we should be staging the horse or staging the patient alongside as we see you in to. And if we're gonna stage the horse, we should treat the horse as well. So what I'm gonna do in the next section of this talk is talk about some different modalities to try and treat the horse to treat catholic aia. And really, if you think about it, if we do these things together, treating the host and the tumor in in unit, I think we're led to get better outcomes for all involved in this. So actually optimizing the condition of the patient will hopefully result in a more efficacious cancer therapy. So let me give an example of some multi modal interventions. So I sent it to you that as a, as a complex biology, it's, it's schematic here, a very simple sort of um depiction of that. But on the top, you've got the tumor and how that reacts with the host and that releases lots of side kinds. So, inflammatory hormones protecting factors and also it produces the endocrine dysfunction. You'll see here, this is a wide reaching effect reading from the brain to in a tissue, to muscle tissue, to liver, to gut an affected glucose metabolism. I'm not gonna touch on all these. But one of the key aspects is it's affecting the brain. Now, you wouldn't think the brain would be involved in something that really was a weight loss thing. You would think that was more sort of, you know, gastrointestinal, but actually a lot of cachexia is driven from the brain. Brain can result in anorexia. Changes in anorexia. Chemosensitive changes are generic activation and increased hypogonadism. And they all result essentially in muscle tissue loss and adipose tissue loss as well. So really the brain is one of the key drivers in cancer cachexia. Another key driver is the liver. Uh liver really acts as a biofire in cancer cachexia, taking a lot of these inflammatory signals and enhancing them and amplifying around the body. So it's a complex phenomenon and results in essentially people with reduced food intake, reduced muscle, increased inflammation. Now, if you think about a simple way of doing this and breaking it down, well, if somebody's um you know, not gaining weight with giving them some increased nutrition. So, a study was done called The Man trial, which is multimodal evidence, nutrition and anti-inflammatories for where we get patients in a randomized trial. A multimodal intervention, diversity, standard care and the intervention involve dietary counseling, exercise, both aerobic and resistance exercise. Ibuprofen to downregulate inflammation. So simple Ibuprofen, omega three oral nutritional supplements. So, fish oils, which again are naturally anti-inflammatory, but all importantly, alongside systemic anticancer therapy, treating the treating the cancer at the same time as you treating the cachexia not afterwards. But in uh in um in line, in parallel with treating the cancer. So this main act trial, as I say, we, we, we diagnosed people with incurable non small cell lung or pancreatic ductal adenocarcinoma. They were starting systemic cancer therapy. And unfortunately, we didn't have to have people losing weight to take the trial. We made the assumption that these patients were at high risk of cancer cachexia and were going to lose weight. So we thought we were going to try and prevent the development of it or, or slow at risk, slow its progression. We did a study that people randomized equally between the intervention arm, which is a multimodal treatment or standard cancer here and that we assess patients after just six weeks. Our premier outpoint outcome was difference in weight change and our secondaries were difference in muscle mass and physical activity. So these are results of, of those two aspects and the, and the in terms of gaining weight. The P so bars on the chart are the multimodal treatment. In other words, that's intervention of the Ibuprofen and nutritional supplements, et cetera. Theres this treatment as usual, which is a blue line. And if you see here, there's a clear difference in the percentage weight change between those two groups to labels of statistical significance. Now, with, regarding our secondary employs, there was no statistical different changes in muscle, muscle mass or also their physical activity. Um and there can be many reasons for that. But the other aspect to say is the drug, the the whole process was relatively safe. So this trial really was the first big trial to try and sort of target this multimodal biology of cancer cachexia intervention, prevented weight loss. And it was a real world data and a pragmatic trial on the background of changing cancer treatments. So we would wonder if this actually could be a background for optimal cancer care and new therapies in the future. Now, in terms of nutritional interventions, II spoke to you at the start to see that some people um there are people with cachexia simply giving the nutritional supplements was not, was not enough. There's a lot we know about nutritional interventions. There's a lot we don't know this. Um this chart here you shows uh patients um patients with cancer across different tumor types. And that just shows you across all these tumor types, different numbers of patients who had um nutritional problems, unintentional weight loss or they felt they had lost muscle. So it's quite high, it's specifically high in some groups such as the lung groups and the head and neck cancer groups, you can see it across it occur across all cancers. And what is interesting if you think about the nutritional care people get, it's not really based on any high degree of the evidence and there's no standard of care. So if you're a breast cancer patient in one hospital versus a breast cancer patient in another hospital, it doesn't mean you have the same nutritional interventions. You might not even get any nut interventions at all. Studies of nutritional interventions have produced mixed results and an hour screen for nutritional status in body comp conversation has been inconsistent and there's no real minimal cut offs or, or um screening questions for this. The other thing to know is that sarcopenia, so loss of muscle is associated with increased toxicity from chemo or immunotherapy so called systemic anticancer therapy. But research and nutritional interventions in cancer malnutrition is limited. There's no coherent intervention and we don't know, you know, if what works well and breast cancer works for gastric cancer. We don't know when we should give it. Should we give it before treatment after treatment during treatment? And should we try to tailor our interventions? In other words, if somebody's lost a lot of muscle and should we think about giving them an intervention?