Looking Out for Changes: Cancer-Related Anorexia and Cachexia Syndrome

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology.

Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase 1 and Cleveland Clinic sarcoma programs. Today, I'm happy to be joined by Dr. Adriana Alvarez, a regional oncologist and palliative medicine physician in our regional oncology network. She's here today to talk to us about cancer-related anorexia and cachexia syndrome. Welcome, Adriana.

Adriana Alvarez, MD: Hi, thank you very much for having me. It's really a pleasure to be here.

Dale Shepard, MD, PhD: Absolutely. Tell us a little bit about your role. In the region you see, you're a medical oncologist, you have training in palliative medicine. Tell us a little bit about your role.

Adriana Alvarez, MD: I started this path in oncology as a palliative care physician, and then I continued my passion about taking care of patients following hematology/oncology fellowships. Right now, I'm kind of happy I can wear these two hats in my daily practice. Also, patients are a continuum. They're moving targets, so sometimes I need to do more of the role of an oncologist, sometimes I need to be more of palliative care. Sometimes I need to be more optimistic, sometimes I need to be more pessimistic, so I kind of like this balance. I'm able to be with my patients through the whole continuum of care.

Dale Shepard, MD, PhD: And then as a regional oncologist, are there particular types of patients that you see more often than not, or you kind of see the spectrum?

Adriana Alvarez, MD: I see the spectrum. I kind of prefer a little bit more lung cancers and GI cancer, but I see a little bit of everything. I'm very happy that I'm able to work with the team at the main campus, and we have fluid communication to better serve our patients.

Dale Shepard, MD, PhD: Excellent. Well, today, we're going to focus on cancer related anorexia-cachexia syndrome, and so let's start off. What is that? We have a lot of people that might be listening from a lot of backgrounds, so maybe just as a backdrop, what exactly is that?

Adriana Alvarez, MD: Well, there are many definitions. I would like to start with something that I recently hear about, that this is from ancient times, so from Greece. Hippocrates actually invented the word "cachexia". It's very humbling, because look how many more years we are after that, and we are still talking about the topic. At the time, it was sign of impending death. Now when a patient is cachectic, that's what it looks like, that is close to death. It's very humbling, after all this year, we are still talking about the topic, and we don't have a clear solution. But to define this, I could say that it's a complex syndrome in patient with cancer that is characterized by weight loss, sarcopenia, also loss of lean muscle mass, weight loss that is not simply taken care of by nutrition, so it's more complex than that.

If we go by also definition how we in the clinical definition, it's a patient that has lost more than 5 percent of their body weight in the last six months, or in patients that are skinner, body mass index of 20 when it's a weight loss of 2 percent. That is very important, I think, for us as an oncology of palliative care to identify it because, especially in the United States, our populations are overweight. We can have an overweight patient that is cachectic, and we cannot identify that. One of the things I do in my daily practice, one of the first questions when I go to review a symptom is, "How's your weight? How's your appetite?" Or if I have a patient, the first time I'm introducing them, "Okay. How do you feel like you're doing with your appetite? Have you lost weight?" Patients try to underestimate whether or not they reveal all the symptoms at the same time. They want to look strong when they see an oncologist. We are able to give treatment, so it's very important for us to try to identify that because there's a prognosis sign too.

Dale Shepard, MD, PhD: It's often shocking how much weight loss people will come in with and say things like, "Oh, but I was trying," and it's so traumatic compared to what they would ever be able to have done previously.

Adriana Alvarez, MD: Actually, some of them are happy, like, "Yeah, I lost weight. I was trying this diet." Then unfortunately, we had to break the news, "Well, something else was going on."

Dale Shepard, MD, PhD: Again, just so people can think about terms properly, because I think people kind of interchange, anorexia versus cachectic?

Adriana Alvarez, MD: Well, anorexia is lack of appetite, basically, and can be associated with many illnesses. HIV, infections, sometimes psychological disorders, and so forth. But cachexia is a more complex syndrome, and right now we are looking into pathophysiology. It's not about just intake, as I mentioned before, and that is important to take into consideration when we talk to our patient. We do education to our colleagues and patient family members, but it is state where there is an interaction between the cancer cells and the host that ultimately will lead to hyper-metabolism, so patients are spending more energy that they can't afford and hypo anabolism, so basically more.

That is why it's very important to look at muscle loss, because that is kind of a sign of hyper-metabolism. In pathophysiology, there are many cytokines, interleukins, hormones that play a role, so they're not that simple to fix. Sometimes, we think that this is related to treatment or the patient not eating, but appetite, actually appetite loss or anorexia, is a consequence of the cachexia and not necessarily the cost. That I think is the important point too, as a take-home message for everybody to remember.

Dale Shepard, MD, PhD: Yeah. Oftentimes, as you say, because of their disease or because of their treatments, patients may not be eating as well. What's the best way for someone to tease out why people aren't eating? Really, if in fact cachexia is the cause, or if it's just they're not eating, as an example?

Adriana Alvarez, MD: That's an excellent question, because there's some people who also are trying to classify pre cachexia, cachexia, and then a cachexia that we cannot fix anymore, refractory cachexia, so there is a syndrome complex. Cachexia/anorexia don't come alone. They usually come also with other symptoms that we have to take and pay attention to, so that's why our palliative care team is so important. What if the patient is depressed, and not eating because of depression? What if the patient is constipated or has nausea for other reasons that we can fix? If the patient has, for instance, GI cancer, are they having a bowel obstruction? Are they having a malabsorption situation? Are our patients with head and neck cancer undergoing significant mucositis that they cannot swallow? So, I think that proper history will help us to take care of other symptoms that may contribute to increased nutrition, because nutrition could be a part of it on the context, so pay more attention to the patients, patient reported outcomes. Making sure that the patient feels comfortable, sharing this and working as a team will help us to try to identify what is going on.

Dale Shepard, MD, PhD: You mentioned a lot of different reasons why people might not be eating, and that would lead to loss of weight and things. Is there something specific that can be done to diagnose this anorexia/cachexia syndrome, or is it more of a diagnosis of exclusion and sort of optimizing symptoms and seeing what's left?

Adriana Alvarez, MD: I think a little bit of both. There is not a standardized way to diagnose anorexia/cachexia. There are some markers that we're looking into. For instance, C-reactive protein as a sign of inflammation. Hypoproteinemia, so loss of proteins. Those are things that we can check and see. If I see a patient that is having these issues, I can think about that. Also, sometimes checking some hormones. Testosterone especially in males because cachexia seems to be affecting that cortisol levels, and things like that can help. Something that we don't use in the practice, but we could, and I think we should, is we use CAT scans all the time to evaluate a follow-up or a response to treatment. There is a way to look into the lean muscle, especially when we do CAT scans. They have the intelligence to look at the L3 level and see the characteristics of the muscle. So that if we see sarcopenia, that is the loss of the muscle, then that can help us to identify those patients, so to be more assertive in that case.

Dale Shepard, MD, PhD: And so, we've identified a patient, we know they have cachexia. Of course, there's an importance to treat the underlying cancer in most cases. What else could we do to treat? Is there anything that's been developed specifically to help?

Adriana Alvarez, MD: Unfortunately, there are no FDA-approved drugs. Recently, in recent years, they have brought attention from many organizations, like ASCO made recently a guideline about cachexia/anorexia. We're having a prime time in this topic, I'm glad to hear that. Even ESMO, the European Society of Medical Oncology, to give some recommendations. In terms of medications, the only two that are kind of recommended in certain situations are progesterone analogs, like Megestrol acetate and also steroids. However, those also have side effects and only fix a little bit of the problem. Megestrol acetate also comes with significant side effects in the long term, and much of the weight gain that we're looking for is fat, not necessarily lean muscle mass. I'm focusing a little bit more on lean body mass, because that will give the patient functionality. More strength to do the same thing that they want to do. We're talking about quality of life.

These two agents are the one. There are also have been many studies, so if we go into pathophysiology, there are situations where, in some cases, testosterone can be maybe recommended in combination with medication. Like for instance, magistrate acetate and Olanzapine have been also used. Cannabinoids is kind of a great topic because there are groups that say yes, there's some groups that say no. We need to still research, so I don't want to endorse that. We know that cannabinoids are more helpful in patients with HIV and not that clear with cancer. However, I think it's an area to explore. Then if we have a patient with early satiety, like we talk about, sometimes the patient says, "Well, I'm pooping," but we take an x-ray and they're full of poop, then prokinetics can help, like metoclopramide. That's why we should pay attention to what other things we can do to help. Some patients, some antidepressants can help with appetite Mirtazapine, so those are things that we can consider at some point.

Dale Shepard, MD, PhD: Tell me a little bit about the best ways to manage patients, and particularly family, expectations. I mean, it seems like sometimes there's battles in families, like they're not eating. Eating is such a culturally important, sharing meals and having people eat. Sometimes patients with advanced cancer just don't eat and they don't gain weight. How do you set those expectations and have those family discussions?

Adriana Alvarez, MD: Well, that's very difficult. Sometimes, it's not a conversation that happens in one site, and that is a message. It's something I learned that sometimes it takes multiple conversations, time, and that's why it's very helpful to work in a team that will reinforce that. I try to explain in a gentler way what is going on, and like I mentioned before, not just the nutrition. I said, "Well, the factory is on strike." The factory is your body, so no matter how much element you give to construct, in this case it could be muscle proteins, things like that, the body is in a strike, so actually feeding you or feeding our loved one make more symptoms. Of course, this conversation will be different at the beginning, right? Where, again, we have to explore other things. I have a diagnosis of cancer, very depressed, I don't want to eat.

Okay. That is different than if I have a patient that has gone to two or three lines of therapy and is actually dying. The conversation will shear, will take other turns. I try to explain, as well, that sometimes more food can cause more symptoms. The patient can feel more uncomfortable. Nausea, vomiting, bloating. Some more discomfort. Also, sometimes I kind of play the devil advocate. I look at the patient, and I try to be on their side, and I say to the patient, "Well, now I'm going to try to be a mediator here." You go, "What do you think?" Because sometimes patients are really bothered, because it seems like it's the only topic of conversation, so like, "You're not eating, you're not eating." I said, "Well, okay, let's stop that. What is concerning you," and try to find other ways to take care of our loved one.

The symbolic meaning of the meal maybe can be shifted to, "Okay, let's do a massage. Let's get together for a talk. Let's try to make momentum of your life. Let me put some lip moisturizer on your lip." There are other ways to take care of them, because I think that the issue with a patient taking care of their loved one is that they want to do everything possible. They see a patient, a person that is changing in front of their life. It's very distressing, so they want to do everything possible. What is humanly possible to do is nurturing. We learn to nurture from the time we're born, right? I think that the shift, and we have to be very humble when we have these conversations, a lot of silence. I sometimes tell the stories about some patients that, towards the end of life, were kind of faking they were sleeping because they didn't want to talk with the patient about the food.

They knew that relatives were going to come in to visit them, and they just played, "I'm sleeping. I don't want to talk about this, I don't want them to offer me a meal." Try to explain to families that we can take away precious moments if we are really focusing on that. As the team, we're going to evaluate everything, and I try to support and say, "Well, let me talk to a nutritionist to see if we can talk about more dense, nutritious meals." Maybe more quantity, more calories, or things that you can enjoy. Things like that. But again, it's not easy. It takes more than one talk. Sometimes, we're not successful, I'm going to be honest with you, but it's clear I think that we have to have professionals. I mean, it's an indication for TPN, it's an indication for the tube feeding.

Those questions are going to arise, and we have to be kind of firm, gently again, but that is not going to create a benefit. Actually, they have been reviewed. There were many trials in the eighties and the nineties with TPN, and patients actually, the survival was shorter. Patients died from infections, complications from TPN, and things like that. Now if you're telling me a patient has a short bowel syndrome or an obstruction, let's suppose ovarian cancer, transitory time, of course that could be indicated at the time. Or if I have a patient with a head or neck cancer with a curative intent, that I know that it's not cachexia just because of the syndrome. It's also what I'm doing to them with the radiation, the chemotherapy, and all that. Certainly, those patients can benefit from those interventions, but we have to be clear when and how.

Dale Shepard, MD, PhD: I'm glad you mentioned the whole supplemental nutrition, and things like TPN and things, because that does seem like it comes up as sort of a grab to try to get that nutrition in people sometimes and stop weight loss. You, of course, have the advantage of having training in hem onc and palliative medicine, but I'm guessing that in most cases that would be an ideal setting for a referral to palliative medicine or nutrition, to have those discussions as a multidisciplinary approach?

Adriana Alvarez, MD: Yes, absolutely. I actually want to mention that one of the studies that came a few years back by Dr. Tamil from Harvard. When they were analyzing intervention, palliative care in lung cancer, and the patient have a better survival, many of the intervention help actually to live longer and to live better. I try to encourage a referral to palliative care from day one, so the patients are familiar with it, so they see you as a part of a team from the beginning and not like, "Okay. After six months, I'm going to send you right now to palliative care." Because they seem like, "Oh, you're abandoning me. What is going on? I'm doing worse." From day one, I think it's very important that we identify that to help us with this. Not only the conversation, but to talk about that complex syndrome that goes along with cachexia/anorexia in cancer are the things that we have to take a look at.

Nutrition referral? Yes. Not only for the recommendation that we talked about before, but about those dense, high calorie foods. So, what could be gentle on your stomach, what you can create, but also to educate our patients. Because sometimes they do these diets that are detrimental, and they don't have a scientific base. I have a patient that's already deteriorating in catabolism, and then I have these diets that are super extremes. I don't want to go into details. Keto diets or microbiotic diets. I mean, it might have a role in certain circumstances, but not in the general population, so sometimes having a specialist in nutrition that can explain those things.

I try not to use the word "educate" that much because I don't feel like I need to educate, but kind of showing the patient the other side of the coin of the complications. I have patient that, they'll come in and say, "Keto diet. I'm very happy, I'm losing 15 pounds," on treatment. Okay, I'm a little bit disturbed by that, so I'll, "I think that this is not the time to do this. Let's wait and see, because maybe it's not the right thing for you at this point."

Dale Shepard, MD, PhD: It's usually well-intentioned, it's just not the right goal.

Adriana Alvarez, MD: Correct. Sometimes they don't hear from us directly as an oncologist, but they can hear from another member of the team. Sometimes having our team, our nurse, our nutritionist, our palliative care, so everybody in the same kind of mindset will help to reinforce that information to the patient.

Dale Shepard, MD, PhD: It's important you mentioned nurses, because sometimes it might be the care coordinator nurse and sometimes it's the infusion nurse that tells us about things that perhaps the patient or family won't tell us.

Adriana Alvarez, MD: Absolutely. That's why it's very important they report the patient to us. An oncologist is not that great sometimes. It could be us, because we're busy. It could be the patient. That they want to, "I'm doing super well. I want more chemo." But yes, I take the time to ask the nurse, "Hey, what do you see? What do you like? How did the patient look?" I think that those are important things to pay attention to.

Dale Shepard, MD, PhD: I guess just to wrap up from a treatment standpoint. You mentioned before about, we're learning more about pathophysiology and cytokines and things that might be important. Anything exciting from a trial standpoint? We don't have anything currently FDA approved, but is there anything that looks promising that might be available soon?

Adriana Alvarez, MD: Yeah. Actually, knowing more about pathophysiology has shown us several pathways that we could potentially interact with. For instance, there's a cytokine, myokine, is kind of a situation where we can intersect to improve anabolism of muscle that is an investigation. They are selective. The androgen receptor modulators are also in research right now. Also, I think the one that's bringing more attention is Agrylin. One of those is Anamorelin, and they have been studied in two recent trials, ROMANA 1 and ROMANA 2. Actually, Dr. Tamil have been one of the leads on those trials. Have not been approved here. However, have been approved in Japan. In some areas, our world is being used now. It has been shown. Basically, this medication is oral, so that is easy to take. No significant side effects but improve anabolism and improve also appetite.

Now one of the two things that the drug had to prove, to be approved perhaps. One was the, okay, the weight gain, the increase in lean muscle mass, but they were not able to, they didn't succeed, improve activity. Like hand grip was one of the things that they were measuring, and it didn't meet that end point. However, I think that we're getting martyrs in the way that the FDA now is looking at quality of life too as an endpoint, so I'm hopeful that they will look into more that, at least to give an opportunity. They were two quite big trials in lung cancer, so I'm hoping that they can be better explored. Another thing I wanted to mention about the importance of the research and all that, especially because you're in phase one and clinical trial, is that sarcopenia is also associated with significant increase in side effect from chemotherapy.

So, maybe one of the things too, especially when we are in certain trials where we're looking for toxicity, maybe evaluating the sarcopenia levels in patients can help us to determine the dose for that particular population. Many of our patients that go to phase one had exhausted many lines of treatment, so cachexia will be a little bit more prominent. So, I think that it is something that some researchers are looking into, and it's not that difficult to get. Nowadays, with the CAT scan, they're able to measure that. [inaudible] is not that expensive, easy, non-invasive to see the composition of the body. I think that that is an area to investigate, along with other endpoints, because that can help determine who is going to have more side effects or not. The same way that we sometimes measure, "Okay. Are you a low metabolizer, high metabolizer? How's your sarcopenia level, internal toxicity?"

Dale Shepard, MD, PhD: That's great. Well, this is a really important topic, and I appreciate all your insights. Thanks for being with us.

Adriana Alvarez, MD: Well, thank you so much for having me. It was very humbling, especially coming from the region. I'm not like a main leader, a main campus like you guys is, but we all work as a team. I wanted to recognize also our excellent palliative care team, which has been one of the pioneers in the country. We're growing in the region too, so I have a very close relationship with them, my best memories, and I really appreciate everything I learned from them because my patients have benefited from it.

Dale Shepard, MD, PhD: That's excellent. Well, thank you.

Adriana Alvarez, MD: Okay. Thank you.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

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