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e-Session n 539001 - 9th September 2020

Cancer cachexia

Dr Arends: Hi, I am Jann Arends from Freiburg, Germany. Here are my conflicts of interest. I am a haemato-
oncologist, and because of my previous experience and work in gastroenterology and diabetology, I have a
longstanding interest in nutrition and metabolism in patients. This is highly relevant in cancer patients, and
let me show you briefly why. And while I'm presenting here, I will show you three faces of quite important
persons and experts in this field. And I will start with Vickie Baracos on the upper right-hand corner. And
Vickie Baracos is from Edmonton, Canada convened the group of experts worldwide, global group, and they
contributed more than 8,000 patients with advanced cancer, and she's showing, in this graph how body mass
index, body weight, as well as body weight-loss are important for overall survival in this group of patients.
And I show you that patients with a decreasing body mass index from the left to the right show a decrease in
overall survival given in months here, from 21.5 to 8.4 on the right side. And similarly, if you dropped down
on the left side from top to bottom, by increasing weight loss means survival decreases 21.5 months, in
patients without weight loss, if they are obese, BMI above 28, and this decreases to 7 months on the bottom
left corner for patients obese, but having lost more than 15% of body weight. And so, both of these factors,
body mass index, body weight and weight loss are quite important for survival in patients with advanced
cancer. My nutrition is frequent and there are old, nice data from the United States, but I'm showing you
here more recent data from Australia. And this is a contribution of several centers in Australia, outpatient,
inpatient chemotherapy, receiving patients, radiotherapy patients, and so on. And they contributed data
from 2012 in blue, and 2014 in orange, and looking at the different cancer entities from left, upper GI cancer
to right breast cancer, you see that malnutritional occurs between 15 and 61% of patients, then on average,
maybe, 30% of all cancer patients, outpatient, inpatient, and so on, do show signs of malnutrition. So, this is
frequent, and I've shown you before, this is relevant. How do patients lose body weight or come to
malnutrition? Sometimes it's postulated, it's the amount of energy expenditure, but data shows this most
probably is not the important thing. Patients with an active cancer have an increased resting energy
expenditure, the energy you need for just basic metabolism. However, with increasing activity of the cancer,
the patients also lose mobility and physical activity during the day, and they spend less energy for physical
activity. The total amount of energy appears to be quite similar to healthy controls. So, an excess of energy
expenditure is not the cause for losing body weight in cancer, increase in resting energy metabolism, but
decrease in mobility in these patients. However, if you go on and look for what patients eat and how much
energy they take in. These are data from Paula Ravasco, collected in Portugal. And she looked at different GI
cancer groups from head-neck to colon cancer patients, and she compared patients with early cancer stage
one or two to patients with advanced cancers, right column. And she looked at food intake from feeding,
from eating protocols compared to healthy controls, and she could see that, especially, in patients with
advanced cancer, these patients eat between 400 and more than 1000 kilocals per day less than healthy
subjects. So, this is a huge difference, and this is the major cause for losing body weight in cancer patients,
inadequate food intake. At the same time, these patients tend to be physically less active as I've said before.
These are data contributed by Feriolli and coworkers, and they compared healthy controls to patients with
early and with advanced cancer, three bars. And they looked at the number of steps taken by these patients,
and you see that advanced cancer patients move much less, on average like 4,000 steps per day, compared
to like almost 8,000 or 9,000 steps per day in healthy controls. So, almost half of the mobility. And at the
same time, they spend more time sitting or lying and they spend less time walking around, so, that's fairly
normal in advanced cancer patients. What is the consequence of this? Or maybe, there are several things
contributing? Let me first show this and remind you. You're welcome, and we would like you to ask questions.
We can talk about now, if Silvia Gonella will take the questions and put them to me, or at the end, whatever
you prefer.

Dr Gonella: But I think we can discuss something if you like.

Dr Arends: Sure.

Dr Gonella: So, first of all, I would thank you for this interesting presentation about data of malnutrition by
tumor type, and the impact of weight lost on the survival. Then, you have shown a picture that illustrate how
the rest energy expenditure may be increasing cachexia with a corresponding reduction in physical activity.
And I would ask you, if you better describe us how the relationship between the REE and physical activity
may be subjected to change across the disease trajectory, and which may be the role of muscle training
across the disease trajectory?

Dr Arends: Thank you very much. So, these are extremely important and very relevant questions. However,
at this time there are basically no data. This sounds like fantastic studies to do, to look at patients with
different physical activity. We will still talk about this later-on with different degree of systemic inflammation,
with higher resting energy expenditure. Probably, less physical activity, and there might be a continuum of
patients going from perfectly normal, to very much in a bad shape. But at this time, we can just propose this
and ask interested experts to try to do studies, just like you're asking for, and just try to get a better hold on
this, but this is just hypothesis. There are some data from a British group around Moses and coworkers, but
again, much more could be done to make much better data of this. So, I'm sorry, but that's the situation at
this time.

Dr Gonella: Okay. Thank you.

Dr Arends: You think I should move on?

Dr Gonella: Sure.

Dr Arends: Okay. [Audio Not Clear] So, patients being physically inactive, probably, will lose muscle mass, like
you just referred to, muscle training would be good to maintain or even increase muscle mass. If we go one
step ahead from just looking at body weight or loss of body weight, and look at body compartments, it
appears to us that muscle mass is a quite important compartment in everybody, and muscle mass is about
80% of physically active, or let's say, metabolically active body-cell mass. So, it is quite relevant in terms of
mass. And there are very, let's say, maybe simple, but not easy to be done at this moment, but very nice
mechanisms to study muscle mass, and the easiest thing at this time, or the most at the highest quality at
this time, is looking at routine CT scans of cancer patients, looking at a certain height at lumbar 3, L3, and
just take a cross-section, and try to find the muscle mass by looking at the density of the bodies. The
Hounsfield units for muscles are very well known, and just color these Hounsfield units corresponding to
muscle. And you see, you can color it by any color, but usually red is used, and you look at two patients with
obesity, BMI of 30 kilograms per square meter. They have the same body mass index, the same body weight,
but there is a vast difference in muscle mass, looking at the red area on the left and on the right side. So, just
looking at BMI or body weight, does not tell you whether there is a lot of muscle in this patient or whether
there's just little mass of patient? And the term used for this is sarcopenia. There are several different cutoffs
or defining levers, but quite often it's the fifth percentile of a healthy reference population. If muscle mass is
below this fifth percentile, the term sarcopenia is used. And in fact, because all cancer patients undergo CT
scans regularly, we hope this will turn out to be a routine measurement available to all oncologists in,
hopefully, the near future. If we look at the muscle mass derived from this CT scans, you can rank patients
according to their muscularity, with a lot of muscles on the right side, 100% the highest muscle mass in this
group of patients, to the lowest muscle mass which would be sarcopenia. Then again, these are data
contributed by Vickie Baracos, who published this in a review. And you see that the hazard risk of death
increases as muscularity decreases below about 30%. So, very low muscle mass is associated with a high risk
of death. So, looking at muscle mass should be quite important for all cancer patients. And in fact, there are
systematic reviews and meta-analysis by now, and I just show you this. This study is looking at 38 trials with
more than 7,000 patients included, and they could show that muscle mass, as calculated from CT scan that
the height of L3, is highly significantly correlated with poor overall survival, with poor cancer specific survival,
and also with disease free survival. So, muscle mass is extremely prognostic for these patients. And what is
quite important also, of course, for our daily oncology, if you have obese patients. I've shown you those with
a high BMI above 28 in my first slide. If you have obese patients, they might be sarcopenic. They might have
a very low muscle mass because they already have lost weight. And this loss of weight, the sarcopenic obesity,
is associated with a quite significantly increased risk of those limiting toxicity during chemotherapy in a
number of different cancers, as collected here in this review, again contributed by Vickie Baracos and Arribas.
So, loss of muscle mass is important for outcome in these patients, even if they're obese and they appear to
be overweight. Let me come to another quite important topic, and that is systemic inflammation. And we
know that systemic inflammation occurs in wounds in healthy patients, but if you look at tumor tissue locally,
like the tumor stroma, this is usually composed not only of malignant cells, but also by immuno-active benign
cells of the host of this tumor. And in fact, very similar things go on in the tumor and in wounds, especially,
there is a high secretion of local pro-inflammatory mediators, that may spill out into the systemic circulation
and contribute to systemic inflammation in these hosts. And in fact, this is a long time ago, like 1986, Dvorak,
called "tumors wounds that do not heal." There is a constant seeping of pro-inflammatory mediators into the
systemic circulation. Well, we'll go on in a second, this is just a reminder. Maybe, Silvia.

Dr Gonella: Yes.

Dr Arends: You have another question?

Dr Gonella: There is a question by one participant, and then one more by myself. This participant asks you if
we need to always look at the muscle mass at the lumbar region, or if we can do on other sides.

Dr Arends: Well, of course. Basically, you can do a lot of things, but to standardize this lumbar 3 is the most
widely used at this time. And in fact, the group starting this a couple of years ago, looked at lumbar 4 and 5,
and a little bit above that. Lumbar 3 has been grown to be the standard that is used almost globally, but if
you look at thoracic tumors, if you have repeated CT scans, they might not really include lumbar 3, and so,
there were some groups starting to have standards for thoracic 10 or 12 to look at these. But again, it should
be a standardized height to not go anywhere, because, of course, the body shape depends on where you're
measuring, and lumbar 3 is the most widely used standard at this time. And looking at tumors in the head-
neck region, it might be quite important to look at other standards higher up, but then again, whoever wants
to do a trial should look at what's important in the region you are looking at. And, of course, what we like to
have every CT scan to be converted to muscle mass at the same time, and you might not use it, but it might
be important for the patient.

Dr Gonella: Okay. Thank you. And then you have just said that sarcopenic obesity is associated with a higher
mortality and higher rate of complications, but I would ask you if you had any hypothesis about the
mechanism that underlines such a relationship, according to your experience, long experience, in nutrition?
 Dr Arends: Again, the connection, the association between which two things? Maybe it was a little bit too
low, the voice, sorry. I've put it up now.

Dr Gonella: If you have any hypothesis about the mechanism that underlines the relationship between
sarcopenic obesity and the high rate mortality?

Dr Arends: In fact, I think there is a lot of trials that are going on. Basically, it might be a marker, just showing
that your basic energy, your basic resources are being lost. We can catch this by looking at muscle mass, at
the same time, you will lose immunocompetent, you will be more prone to have repeated infections, and
just be not resilient enough to survive longer. So, I think there is a lot of things going on, and of course, muscle
mass is not the first thing fighting cancer, but it's probably a marker of our resources being available at this
time. And if we lose more, we're losing other things as well, and just this all will contribute to you being at a
higher risk to die.

Dr Gonella: Thank you for your answer.

Dr Arends: Okay. So, looking at systemic inflammation, the spillover of these compounds into the systemic
circulation. This is a German slide, but I think we can go through this. And I'm just comparing here the
situation of pure starvation, losing body weight by not eating, having enough access to food, to cachexia in
the right column. And what is important in both situations, there is inadequate energy getting to the body,
but if you have a hunger situation, the appetite is maintained, the mobility is maintained, and the metabolic
pattern is ketosis to maintain your protein pool as best as possible. However, in cancer patients, they don't
eat enough, but also they are anorectic, they don't have appetite and they have fatigue, and they don't move,
and they're inactive, and the metabolic pattern is systemic inflammation. And so, this is important to realize,
cachexia and malnutrition in cancer patient is not starvation, this is quite different, and the important thing
that makes the difference probably is systemic inflammation. And I've shown you what we consider to be the
cause for this. And here it is the second face. This is Donald McMillan from Glasgow, and he contributed a
very easy and simple score to look at systemic inflammation, which is present in many patients. And this is
Donald McMillan from the UK, and these are data from Freiburg in Germany. And these are 250 patients with
advanced cancer. And just looking at two important peptides, CRP as acute phase reactant and albumin as a
negative, more chronic systemic inflammatory marker. And as you can see, a lot of patients have raised CRP
above one, which is our standard for normal, and at the same time, these patients tend to lose serum
albumin, drop below the normal threshold. And what McMillan did is, he said, I am giving a score with three
different groups, the first score is the best score, which is said it is Glasgow Prognostic Score because he's
from Glasgow. Score of zero is all patients with normal CRP, normal CRP best score. If you have a raised CRP,
but still normal albumin, you get a score of 1, and if raised CRP, but already decrease in albumin, you have a
worst score of GPS of 2. And this very simple score has been shown to be predictive of clinical outcome in a
huge number of trials. And Donald McMillan collected this and published this already in 2012, almost 10
years ago, and more than 20 trials with surgical cancer patients, 11 trials with patients undergoing radio-
chemotherapy, inoperable cancer, mixed cancer patients, and in all of these patients score zero, one or two
correlates with clinical outcomes. So, this is quite convincing and very good. And I'll just show you one
example. This has been published in 2014. Survival in patients after treatment mainly of colorectal cancer,
and these are five years of observation, so quite long survivor. Primary treatment. If you look at the groups
separated by GPS, normal CRP at the top, and raised CRP and decrease albumin at the bottom, you see a
significant separation of these groups and GPS tool is very bad for survivor, and can be shown early, but also
after five years after primary surgery. And this is not just one trial, you can look at more trials, and this is a
systematic review and meta-analysis of different trials looking at survival in colorectal cancer patients, and
you can see all of these show the same thing. If you have raised systemic inflammation, raised Glasgow
prognostic score, you have an increased risk of death in these patients. So, this is very relevant and this is
quite significant also, and the degree of increasing hazard ratio. And—
 Dr Gonella: Okay, Jann, we had a question regarding the previous set of slides about the role of CT scan, and
we would like to know if the measurement of muscle mass at lumbar 3 is compared to a normal range of
values, or if it needs to be compared to the patient's own values of previous CT scan?

Dr Arends: Well, I think... All right, so as soon as we talk about this, everybody gets a lot of ideas. So, this is
a brilliant idea, and we would like to have of course, a time evolution of muscle mass in patients. At this time,
this still is like a wish. At this time, we don't have muscle mass in almost in any patient, and this has been
used in trials looking at the ones... There are some data for successive measurements, but not so very many.
But of course, it would be the thing. At this time, we look at reference groups, look at the fifth percentile in
healthy patients, or healthy subjects, and if somebody is below this fifth percentile, his term is to be
sarcopenic, but of course, it would be better to have the evolution and look whether a patient has lost muscle
mass, but again, this is still a development process and we don't have everything we want to have. And that's
the benefit of these sessions, I think, to alert, interested physicians and expert oncologist, hematologist to
start trials and try to work on this.

Dr Gonella: Okay, thank you. We can move.

Dr Arends: And just as the things I've just shown you before, this has been incorporated, and this, again, is
published already almost 10 years ago, and the most prominent cancer cachexia definition used globally at
this time, published by a consensus group, convened by Ken Fearon, the late Ken Fearon, and published in
2011. And they used to define cachexia to combine weight loss and systemic inflammation. And what is
important, beside this definition of full-blown cachexia, to see that there is a pre-stage, there is a time
evolution of cachexia going on, patients first, having metabolic derangement of low degree, maybe no
significant weight loss yet, but they might be anorectic, and they are prone to develop cachexia. And we
should try to detect patients as early as possible to start treatment as early as possible. And of course, there
might be a late stage called refractory cachexia with a brief survival, expected survival, and it is important to
realize that, at this phase, it might not be helpful to just introduce very invasive interventions to these
patients, like maybe parenteral nutrition, and you might be well-off to be very reluctant to be invasive at this
later stage. So, this is important to just understand early phase of cachexia and maybe, a late phase, which is
not so easy, or maybe impossible to treat. And what I just wanna do now, just because maybe if you have
never talked about this, this maybe sounds a little bit complicated to make it as easy to understand as
possible. Our body resources require energy and nutrients, and they require anabolic agents to maintain our
resources, and they are endangered by catabolic drivers that might occur during any acute or chronic illness.
And these three components working on our body are important to understand. And we know that in cancer
patients, intake of energy and nutrients is compromised by anorexia, dysphagia, nausea, pain, obstruction,
other things going on by the tumor or by our treatment, so, that's important to realize. We need to counteract
it. There is a lot of catabolic drivers by systemic inflammation induced by the tumor, by the cancers I have
shown, but repeated infections, pneumonia, other things, wound, surgery, maybe catabolic drugs being given
to the patient. And our anabolic agents, physical activity, sufficient adequate protein intake may be not
available as the patients are fatigued, they have pain, they don't wanna move, they don't eat enough, so,
anabolic agents are decreased. That's a problem. In pure starvation, energy intake is decreased, but anabolic
agents and catabolic drivers usually are not changed, they are still in a normal balance for the body, and it is
easy to counter starvation by just replenishing energy and nutrients. You need to be careful, but that's an
easy treatment in the end. If you look at cachexia, we have an increase of catabolic drivers. We have systemic
inflammation as one of these doing this, and that compromises our body resources, muscle mass, fat mass
being broken-down. At the same time, patients feel fatigued and they have less anabolic agents, and at the
same time, they don't take-in food enough because of all the compromising factors. And we have a complex
situation, and it's not as easy to treat as simple starvation. So, these arrows I've shown you are also our
treatment targets. We need to improve energy and nutrient intake, we need to support anabolic agents, and
we need to try to decrease catabolic drivers, catabolic agents, either symptomatically or by treating
infections, wounds, and other things. Try to enable the patient to eat, treat anorexia, treat dysphagia, and if
the patient still cannot eat enough, you might use a dietary counseling or a nutritional supplement, enteral
nutrition, parenteral nutrition, whatever is available at the center. And to increase anabolism, we need to
include exercise training in our treatment concept. This needs to be an essential component. Adequate
protein, not only energy and fat, but protein to allow body proteins to be maintained, or even to be built-up.
Maybe this is just a reminder and I stop and I can stop here briefly.

Dr Gonella: Okay. We have a question regarding sarcopenic obesity. A participant has noted that obesity has
been shown to be a poor prognostic factor in breast cancer patients, and he would like to know if sarcopenic
obesity can explain this.

Dr Arends: Tell me again, sarcopenic obesity should explain what? This is associated with decreased survival
also in breast cancer, yes.

Dr Gonella: Yes, so, okay.

Dr Arends: The question is what is the cause again? But I think it's similar, losing body mass, losing muscle
mass, body-cell mass is an increased risk of infections of not being able to tolerate treatment long enough,
increased treatment toxicity, decreased compliance with treatments, shorter treatment and so on.

Dr Gonella: Okay. And then I would ask you about treatment strategies. Literature has shown an important
role of the dietary counseling, in improving weight gain and in increasing the dietary intake. Instead, the oral
nutritional supplements were shown not to be so effective without a dietary counseling. So, dietary
counseling is suggested to be the primary choice for nutritional support. So, according to your great
experience in nutrition, I would like to ask you, when is the best time to start to offer dietary counseling?
And who should offer these counseling?

Dr Arends: Well, one thing is, of course, cancer is a huge spectrum of different things. This is during primary
treatment, this is treatment or counseling of survivors, this is counseling of recurrence of cancer, palliative
setting and so on. So, all of these situations would require different counseling, and we suggest to do a
screening for risk of malnutrition or for malnutrition in every cancer patient. If there is no problem, you don't
need, you might, but you don't have to counsel because we have limited availability of persons and time, but
if in screening there is a risk detected, these patients should be counseled repeatedly, and they should be
counseled by an expert in this topic. So, this should be a professional nutrition expert. And the terms, how
you call these persons always is different in different countries, but it should be a professional doing these
counseling.

Dr Gonella: Thank you. And then our participants would like to go more in depth about the pharmacological
intervention, and they are asking you about the use of Progesterone acetate for outstanding patients. What
do you think?

Dr Arends: Well, basically, I'm not finished with my talk, but we can just put this in between. These progestins
have been quite... Well, not quite widely, but they have been used during the 1980s, 1990s. They are not, at
least as far as I see it in my country, and other countries, not being used too much at this time. We know that
progestins, and this has been noted in breast cancer patients, they gain body weight when they were treated
during a certain period. I think this is not done so much anymore with progestins in endocrine responsive
breast cancer, but taking progestins increases fat mass, it doesn't really, as far as the trials available can show,
most previous tries didn't look at body composition, but progestins don't appear to increase body cell mass,
muscle mass, but more probably fat mass, incorporation of water. Still, this does not need to be a bad thing,
but there are no real data that survival is increased by these agents. Some show that quality of life improves
a little bit, but there is a high risk of prothrombotic events, and so, we always suggest to be careful if you
consider using progestins, especially in cancers like pancreatic cancer or others who have a high risk primarily
of thrombosis and lung embolisms. So, they are not really used quite broadly. They're not really available to
treat cachexia, they're not really cheap, they're expensive, and so, well, there are trials on this, but we've
published guidelines, we are working on this guideline from ESMO, and we say, it's possible to use these
agents, and we know there are very few agents looking at everything around, but then again, they are not
really the best agents we could dream of, let's put it this way.

Dr Gonella: Okay. And we would also know your opinion about the role of nutritional supplements enriched
with the EPA in providing nutritional support and counteracting inflammation.

Dr Arends: Yes, I think this is, let's say it's an interesting topic. It is also a very controversial topic. Data
available are hydrogenous, it's not really going in one direction. If you look at the evolution of guidelines on
this topic, you see that some guidelines give recommendation like, it is possible to recommend, or at least to
try omega-3 enriched supplements, other guidelines are a little bit more reluctant. There are some data that
show, and there is some pathophysiological argument that because we have systemic inflammation, omega-
3 fatty acids might be competitive and agonists of arachidonic acid and thus maybe decrease systemic
inflammation, and then might potentially be helpful in conservation. But again, we are really lacking a large
number of convincing trials in this direction. There is some data, some pathophysiological argument. These
supplements are not very tasteful to say minimum, so, we always hope for the industry to develop better
tasting supplements, especially with omega-3 fatty acids. We might use them to drink some, much cool them
down, so you don't have the taste so much, try to take a very energy dense supplement so, you don't have
to drink large amounts. So, there are some things to use it, and we're also waiting for more and better, and
more convincing trials at this time.

Dr Gonella: Thank you, Jann, we can move on.

Dr Arends: Okay. So, I think I'm also going to define the chapter of what I wanted to tell you. I've shown you
what we need to do, have a complicated situation with cancer cachexia, many things to do. There is not one
person who can do it by herself or himself, and I think there is a large group of experts that need to be
available, let's say, not every patient will require every expert to work with her or him, but all of these experts
might, at one time or another, be important for patients with malnutrition. These, of course, are dieticians,
nutritionists, of course, nurses, we need the pharmacists, the radio oncologists, physiotherapists,
psychologists, social workers. A lot of things may be invalidated by the patient going home and not being
able to do all the special things we suggest or recommend to do, so, we need social care and social support
quite importantly, and speech therapists. For head and neck cancer is pain experts. And we need somebody
to lead a group and call these different experts to the special situation of an individual patient, and we need
either a patient manager, or the oncologist might do it, maybe the gastroenterologist. This is just a
suggestion, but at every center, the optimal situation would be to have a group of experts available and
somebody to lead this group, and call upon the different selection of experts who might be required to
support the individual situation of a special patient. And of course, to build this, there are some strategies
put up, and we've published this in clinics and clinical nutrition and a guideline by the society of clinical
metabolism and nutrition in Europe, and to say, all cancer patients at every time should be screened for the
risk of malnutrition using a standard tool, published to be valid and available. And if patients are at risk of
malnutrition, they need to be followed-up more closely. They need to undergo a thorough assessment of
nutrition, impact symptoms like anorexia, dysphagia, pain, need to be monitored for food intake, for the
availability of body resources like muscle mass, fat reserves. Physical activity needs to be assessed, and the
degree of systemic inflammation, maybe by using the Glasgow prognostic score. And then based on the
individual set up of different problems in each patient. They will all be different. We need an individualized,
multi-targeted treatment approach. And this again, needs to be guided by somebody in this group, but that's
the thing. Repeated screening for those at no risk and follow-up assessment and treatment for those patients
with the risk of malnutrition. And the treatment strategy, of course, should be providing adequate energy
and nutrient intake using omega-3 fatty acids and supplements if available and adequate. But you should
always start with nutrition counseling, and I know that a lot of dietitians say, it's more important to try to eat
normally with the food available, before you switch and go on to oral nutritional supplements, but if normal
food doesn't allow adequate intake, then, of course, also use nutritional supplements. Try to alleviate all
defects in the GI tract that might impair the ability to eat, to swallow, to chew and so on. And try to decrease
catabolic drivers and increase anabolic stimuli by including exercise training in these patients. And the bottom
graph, I think is important because as patients approach the end of life, which is very important thing in our
cancer patients, and the palliative situation, the importance of anti-cachexia interventions will go down. We
don't need to treat a patient until the last day or week with intravenous nutrition and do intense exercise
training. We have to adjust this to the situation of the patient of the expectation of life ahead. So, let me just
close at this time, that nutrition concepts and oncology do have a limit. We should not underfeed any
patients. So, we have to screen all patients and we have to repeat screening those patients that have not
developed malnutrition so far. Screen all patients. But if they approach the end of life, we should not
overfeed, we should individualize at the end of life and just look at what the patients need at his position or
her position, during when we say the journey of the patient through this cancer disease. Thank you.

Dr Gonella: Thank you, Jann. So, we all agree on the point that all patients with metabolic alteration should
be identified as early as possible during the disease trajectory, and the best will be to identify them during
the pre-cachexia stage, but this may be extremely challenging for the oncologists and for all the healthcare
professionals. So, in addition to screen and the rescreen at periodic time, do you have any further suggestions
for the oncologist to early intercept patients with metabolic alteration, in order to offer both the nutritional
support, but also psychosocial support to patients and their family?

Dr Arends: Well, I think there are several things. One is, every oncologist, every hematologist should be
aware of this set of problems of this thing that nutrition, or let's say malnutrition, is important. So, awareness
is the first thing. The second thing is, be also aware that you can't do it yourself. You have to have a team,
maybe small, maybe larger, and also you need some standard operating procedures. Who is doing screening?
Where does the screening results end-up? Who is looking at them? Who is taking care of assessment? Who
is collecting the sum of problems in an individual patient? Who is responsible for treatment of these patients?
Who is responsible for followup? So, it's quite important to have the setup done, probably, because if you
have to invent the wheel every time you see a new patient, you will get lost. So, awareness of the problem,
awareness that you need a structure in your, either it's a private outpatient setting, or whether it's a hospital,
there needs to be a structure to attacking this problem, otherwise, you will get lost and lose time, and don't
really come to help your patients enough. So, I think these are the most important things. Setup a structure,
and then work with your group of experts interested in treating. Well, cachexia is the word, fatigue is the
same, you're just looking from a different angle at the problem of the host losing energy, losing body
resources, losing motivation. So, cachexia is looking from the nutritional point of view, fatigue is from another
point, but there are some social aspects, there are psychological aspects. It's a complicated thing, and you
need a group of experts, and it's very difficult to do this all by yourself.

Dr Gonella: Thank you, Jann. I think that we can stop now, or if you have a bit more time, we have still a
question that asks us, "What should the screening of patients include?"

Dr Arends: Yes, so this is just one session where you can talk about certain things. Screening, I've mentioned
there's NRS, which means Nutrition Risk Screening suggested by the ASPEN Society. This can be looked-up in
the literature. And usually, you're looking at body mass, body weight, you're looking at loss of body weight,
you're looking at food intake, you're looking at systemic inflammation, but screening needs to be easy
because this shouldn't be done by the expert, but by somebody not really focusing on nutrition, this might
be the nurse, this might be some other person, just going through the ward. We are doing this giving a patient
just this score, and they really fill it out and we just get the answer by digital. They do it by tablet. We just get
the answer and then everything needs to be done by the expert, but the screening should be easy and
standard tool should be followed like the NRS, so, there's the MST, there is a number of scores. And if you
look at our guidelines, they're all listed there. And in the end, it doesn't matter so much which screening tool
you use, because this should just alert you that this patient has a problem.

Dr Gonella: Thank you, Jann for this accurate overview about cachexia and the nutritional issue in cachexia.

Dr Arends: Thank you for guiding this. Thank you. So, maybe we say goodbye and hi to everybody, and wish
good success with following-up on this at every situation where patients will be malnourished and are waiting
for treatment.

Dr Gonella: Thank you again and bye.

Dr Arends: Goodbye.