Cancer/Transplant - Related Fatigue: What to Know, What to Do

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Cancer/Transplant-Related Fatigue: What to Know, What to Do

Thursday, April 22, 2021

Presenter: Ellen Manzullo MD, FACP, Professor of Medicine, The University of Texas, MD Anderson Cancer Center

Presentation is 38 minutes long with 10 minutes of Q & A.

Summary: Fatigue is the most common complaint of patients. It can continue for years after treatment. It may be due to the disease itself, or the chemotherapy, radiation, and other medications used to treat the disease. This presentation reviews the causes and complications of transplant-related fatigue and describes lifestyle changes and pharmacological interventions that can improve cancer-related fatigue.

Highlights:

• Sleep disorders, sleep apnea, and insomnia contribute to fatigue experienced by transplant patients. Practicing good sleep hygiene can be an effective response.
• Conserving energy, setting priorities, delegating chores, and scheduling activities for peak energy times are practical ways of minimizing the impact of cancer/transplant-related fatigue on everyday life.
• Exercise helps minimize cancer/transplant-related fatigue. It can begin with simple walking and gradually build up to aerobic exercise, resistance work, and strength training.

Key Points:

(01:19) Fatigue is a tiredness that is disproportional to recent activity and interferes with usual functioning.

(03:51) Fatigue has many causes that must be assessed for effective treatment.

(05:05) Heart, lung and liver problems can contribute to fatigue

(06:42) Medications, loss of muscle mass, poor nutrition and being overweight can contribute to fatigue.

(15:26) Cancer-related fatigue often occurs when the patient has pain, anxiety, depression, and sleep disorders.

(15:49) Lab evaluations can check for anemia, adrenal function, thyroid problems and other treatable conditions that contribute to fatigue.

(21:24) Conserving energy, setting priorities, and delegating chores can help with fatigue.

(22:35) Limiting daytime naps to thirty minutes or less can improve nighttime sleep.

(25:44) Physical medicine and rehab specialists can design a unique exercise program tailored to each person’s situation.

(30:55) Pharmacologic agents like methylphenidate or modafinil can help some people with fatigue.

Transcript of Presentation:

(00:00) [Marla O'Keefe]     Introduction. Hi, my name is Marla O'Keefe, and I'd like to welcome you to the workshop, Cancer and Transplant Related Fatigue: What to Know and What to Do. I'd like to introduce to you our speaker, Dr. Ellen Manzullo. Dr. Manzullo is a professor of medicine and the deputy division head of internal medicine at MD Anderson Cancer Center in Houston, Texas. She has published extensively on cancer-related fatigue and spearheaded the creation of a fatigue clinic at MD Anderson, where she evaluates and treats cancer patients and survivors who have cancer-related fatigue. Please welcome, Dr. Manzullo.

(00:42) [Ellen Manzullo]     Overview of talk. Thank you so very much for this introduction, and I'm really delighted to have this opportunity to speak to you today about cancer-related fatigue. So, what am I going to do to give you a snapshot. I'm going to begin by giving you the definition for cancer-related fatigue. Then we'll go ahead and discuss its various causes, and then describe to you the evaluation of patients with cancer-related fatigue, and then go through a variety of management strategies that we use.

(01:19) Fatigue is a physical symptom with emotional and cognitive dimensions.  So, to begin, I always like to begin with the official definition for cancer-related fatigue. And this is the definition that is used by the NCCN, which is the National Comprehensive Cancer Network. So, cancer-related fatigue is a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that's not proportional to recent activity and it interferes with usual functioning. So, this is the official definition. And I think it's really important to keep in mind that this is not only a physical symptom, but also one that has emotional and cognitive dimensions as well.

(02:09) Fatigue is the most common complaint of cancer patients. Very important to keep in mind is that fatigue is the most common complaint of cancer patients. And many times this is the most distressing symptom reported. And up to 30% of cancer survivors report fatigue even years after completion of treatment. And the fact of the matter is, that patients are often unprepared for this symptom.

(02:36) There are several barriers to recognizing and treating fatigue. Now, really there's a variety of barriers to the assessment and treatment of this symptom. First of all, it's the time constraints and busy outpatient practices. And this is just a reality. And over this past year, of course, with the pandemic, a lot more of these visits have been done via telemedicine, but still there are time constraints involved.

(03:03) Also, patients are reluctant many times to mention that they have fatigue due to concern that they don't want to do anything that might have a potential impact on their overall treatment plan. And also, clinicians on the other hand, many times feel uncomfortable discussing this symptom due to a lack of knowledge in this area. Cancer-related fatigue is a phenomenon and there is aspects of it, that really further research is required.

(03:36) And then finally, another barrier is that some patients think it's just an expected outcome of their cancer and their treatment, and they simply discuss it, and they don't really bring it up when they see their physician.

(03:51) Fatigue has many causes. Now, I work at the fatigue clinic here at MD Anderson Cancer Center, and one of the common questions that I get is, well, what causes cancer-related fatigue? And what you can see with this diagram is that there are many causes of cancer-related fatigue. It's not only the cancer, but also the treatment that has been received, whether it's chemotherapy, radiotherapy, stem cell, or bone marrow transplant, that's very important. But also, we have to keep in mind, other medical conditions are important for cancer-related fatigue. And I'll go into this in more detail.

(04:33) Medications can contribute to fatigue. Also just overall deconditioning and a loss of muscle mass, poor nutrition. And then also fatigue commonly clusters with other symptoms, such as pain, anxiety, depression. And these symptoms also contribute to the patient's cancer-related fatigue. So, as you can see, many causes for cancer-related fatigue.

(05:05) Heart, lung and liver problems can contribute to fatigue.  So, to begin with, as far as the comorbid conditions, or other words, other medical conditions, for example, anemia is an important one. And many times, cancer patients when their hemoglobin level goes below 10, they'll begin to experience fatigue. Also neurologic disorders. And then of course, any sort of heart problem. And as an internist, this is something I really keep in mind because in the evaluation of a patient with fatigue, I don't want to miss any underlying coronary artery disease, for example.

(05:44) So, it's very important that when you have fatigue, you undergo a very complete medical evaluation because coronary artery disease or congestive heart failure, even arrhythmias can contribute to symptoms. Also, lung disease, any sorts of liver problems, kidney disease, arthritis. And when I say arthritis, I include other rheumatologic problems. So, for example, lupus or Sjogren's, those would be also possible contributing factors, and any type of infectious process. And then of course, hormonal disease and a common one, and one that we always check for is thyroid disease. Both hypo or hyperthyroidism can contribute to fatigue. And then of course, graft-versus-host disease.

(06:42) Medications, sleep and pain medications can contribute to fatigue. So, in addition to these other co-morbid conditions, something that's extremely important is to have an accurate medication list. And I always encourage my patients to always have an accurate medication list with them, because there are a variety of medications that contribute to fatigue, such as beta blockers. And patients can be on this medication such as Atenolol, Carvedilol, and Metoprolol for their heart disease.

(07:13) Also, a variety of sleep aids can contribute to fatigue. Patients will say that when they use it, that when they get up in the morning, they can have a feeling of hung over. And then of course, medications for nausea and vomiting, and then also pain medications. So, these are all medications that can particularly contribute to fatigue.

(07:41) Overall conditioning, nutrition and weight can be factors. So, other causes for cancer-related fatigue are your overall conditioning, and as well as your nutrition. And I think probably as you all know, that as one goes through their cancer treatment, it's easy to have decreased physical activity and subsequently decreased physical conditioning. And as a result of that, you have physical function changes, which could then contribute to fatigue.

(08:08) And then of course, nutritional balances, weight change is an important one, or if any patients have any sort of motility disorders. And then of course, dehydration with both fluid and electrolyte balances. And so, I always emphasize to the patients or my patients, the importance of good nutrition. And we usually consider that five servings of fruits and vegetables on a daily basis, but also to make sure that you don't get dehydrated.

(08:42) Now, another important cause of cancer-related fatigue are these associated symptoms. And I had mentioned that earlier, for example, pain, anxiety, depression, and sleep disorder, these can all contribute to the severity of the fatigue.

(09:02) Sleep disorders are common causes of fatigue in cancer patients. And one that I really want to go ahead and spend some time on is talking to you about sleep disorders. And a sleep disorder is often defined as any disorder that affects, disrupts or involves sleep. And it's very important to keep in mind that sleep is really essential for life. And sleep disorders are very common in cancer patients. And approximately 30% to 88% of cancer patients have sleep disorders.

(09:39) And I think as we can all relate, a lack of sleep is associated many times with symptoms of depression, anxiety, decreased cognitive function. Also, it can have an effect on impairing one's immune system, and then just also decreased quality of life. And poor sleep can last far beyond the cancer treatment.

(10:06) Sleep apnea and insomnia are more common among cancer patients. In addition, sleep apnea has been found to be more common among cancer patients than the general population. And so, that's why when I see a patient in the fatigue clinic, I will ask their spouse, if for example, they have noted that the patient has loud snoring, or if they have witnessed that the patient stops breathing while they sleep, because those could be very important clues that the patient can have a potential sleep disorder and would benefit from being seen by a sleep specialist.

(10:43) And also, cancer patients are twice as likely as people without cancer to experience insomnia. So, really, sleep disorders are very important in cancer patients.

(11:00) Biomarkers and genetic factors are also associated with poor sleep. Now, I always like to add this slide into my talk because this is an area where there's really a need for further research, and this is the whole area of biomarkers. And so, it's thought that cancer-related fatigue is linked to a variety of biomarkers that are, for example, immune, inflammatory, metabolic. And that would refer to, for example, any types of hormonal disease.

(11:30) And then also, there's thought that there are genetic factors that are related to this symptom. And I have the reference down there for you in case you are interested in searching this out. But I think what's really important to keep in mind is really further research is needed in this area.

(11:55) Diagnosing cancer-related fatigue requires a detailed history, physical exam, and fatigue assessment.  So, as far as the evaluation of the patient with cancer-related fatigue, to begin with, a very detailed history and physical exam is required. And with the history, it's really important for all of you to have an in-depth fatigue assessment. And so, what this means is, obtain the history as far as when the fatigue began. When did it start? What is its pattern? For example, is it more in the morning, more in the afternoon, or is it all day? Some patients say they've not been able to see any pattern. And then actually, how long have you had it? Because that can be very important to know how long have you had this symptom? Did it begin in fact, even before your cancer diagnosis or did it happen for example, after your stem cell transplant?

(12:55) Also, an important factor is how the fatigue has changed over time. For example, have you noticed that it's been getting better the further away you get from your stem cell transplant? Also, what are the associated or alleviating factors? For example, have you noticed, for example, exercise will result in improvement in the fatigue?.

(13:20) And then also, assessment of how does this fatigue interfere with daily functioning. And this really varies from patient to patient because some patients, for example, are simply just struggling with the activities of daily living, while others are in their jobs, working full time and have a lot of responsibilities as far as child care or care of elderly parents. So, it's important to have an assessment of how this fatigue interferes with daily functioning.

(13:59) And so, also functional status is important to know. What are your routine activities that you do. Also, do you have an exercise program? And I always ask patients, are they exercising and what are they doing? And then also to describe a typical day, and this would include getting up in the morning, go to bed at night, and then do you, for example, do you work? How is this symptom impacting your daily life?

(14:34) And then also, have you noticed any memory changes? Because as you can remember from the first slide that I showed, cancer-related fatigue, not only has a physical component and an emotional component, but also cognitive component. And patients can have memory changes as part of their cancer-related fatigue.

(15:01) So, then when we evaluate the patient in the fatigue clinic, we always do a complete review of past medical history, looking for some of those other medical conditions, and really want to make sure that they're adequately treated, as well as making sure that the patient does not have any other new medical conditions that haven't been diagnosed.

(15:26) Cancer-related fatigue often clusters with pain, anxiety, depression, and sleep disorders. Also, it's very important to have an accurate medication list, and then also do a complete review of systems to assess other symptoms that are being experienced, keeping in mind that cancer-related fatigue, commonly clusters with those other symptoms, such as pain, anxiety, depression, and sleep disorders.

(15:49) Lab evaluations can check for anemia, adrenal function, and related conditions. Then also important is a laboratory evaluation. And when we see a patient, we always do within a month a CBC with differential looking to see if there's any evidence for anemia. Also, a comprehensive metabolic panel, looking to see if there are any electrolyte abnormalities or any hepatic or renal dysfunction. And then also, endocrine studies. And as I mentioned, both hypo as well as hyperthyroidism can contribute to cancer-related fatigue.

(16:24) And then also some patients can have some adrenal dysfunction. And then also measurement of fatigue, pain, depression, anxiety, and sleep disturbance are also looked at. And we actually use questionnaires in our clinic to assess each one of those symptoms.

(16:46) Severity of fatigue can be measured with a Brief Fatigue Inventory score. And one of the very important tools that we have is the Brief Fatigue Inventory score. And this was a tool developed by a faculty member here at our institution. And this is an important way that we put a number to the patient's fatigue. And it is a questionnaire, nine to 10 questions that we have the patient complete, prior to the first consult, as well as each follow-up visit. And this gives us, the medical team a good sense of the severity of the fatigue. So, if it's mild, the patient on this fatigue inventory score will have a score of zero to 3.9. If it's moderate, it's four to 6.9. And if it's fatigue, it's seven to 10. So, this is a great way to assess the severity of this symptom, not only at the initial consult, but with each subsequent clinic visit.

(17:53) Patients need unique treatment plans for fatigue that also address other existing medical conditions. So, a very important question as well, how do we manage cancer-related fatigue? And so, what's important is, first of all, is optimizing the treatment of any existing medical conditions. That's really important. And as a general internist, I look at this as the number one priority. But then also it's important to keep in mind that many times there are several causes just like that pinwheel that I showed earlier, frequently many causes.

(18:29) And so, each individual patient is unique. And so, we try to come up with an individualized treatment plan for each patient. And then of course follow them with time. And so, for example, possible causes will be anemia. So, it'd be important to make sure that patient doesn't require a blood transfusion. Or if they have hypothyroidism, making sure that they're on adequate dose of thyroid supplementation.

(19:01) As I mentioned, sleep disorders are very important. And if a patient has, for example, obstructive sleep apnea, we want to make sure that they have the adequate equipment that they need, for example, CPAP.

(19:18) And then also, make sure that the patients have optimum treatment of other poorly controlled medical conditions such as their heart disease and diabetes. And in fact, diabetes is a very important one, because of the increase in obesity in our country, we are seeing more and more patients also with diabetes. And so, adequate treatment of that medical condition is really important. And then also, another important aspect to management is adjustment of medications, looking at potential side effects.

(20:01) Depression often accompanies fatigue but is helped by antidepressants and exercise. Now, as I mentioned, other symptoms commonly cluster with cancer-related fatigue, of course, depression is one of them. And studies have shown that actually depression correlates with the degree of fatigue, many times in cancer patients. And some patients benefit from antidepressants.

(20:21) Also, exercise can have a positive effect on depression. And that's why I really work with patients, trying to make sure that if they're not exercising, to begin an exercise program, keeping in mind, the overall goal is 30 minutes exercise, five days a week. And then in those patients where their depression is really severe, then we will consider possible referral to psychiatry clinic.

(20:51) Treating underlying pain may alleviate fatigue symptoms. Another important symptom that our patients experience is pain. And it's very important to evaluate the severity of the pain, and of course, prescription of medication to help alleviate that. And some patients, when they have improvement in their pain, they also experience improvement in their fatigue. And then also, possible referral to the pain clinic can be very helpful as far as alleviating the symptoms.

(21:24) Conserving energy, setting priorities, and delegating chores can help with fatigue. So, in all patients, I review general strategies, what I call lifestyle strategies for cancer-related fatigue. And a very important one is energy conservation. What I tell patients is to think of their energy like a bowl of candy, and then to think about what they need to do over the course of the week, and to ask themselves that, do they have enough energy for everything that needs to be done over the week? If not, then think about what activities can be omitted or perhaps delegated to someone else.

(22:04) And I think this is important for all of us to think about how can we conserve our energy? And this means setting priorities, pacing yourself. And then as I mentioned, delegating chores that can be done by someone else.

(22:20) Scheduling activities for peak energy times can also help. Also, a very important tip is to try to schedule activities at times of the day when you know when you will have peak energy. And this does vary from patient to patient.

(22:35) Limit naps to thirty minutes to not interfere with nighttime sleep. Another important aspect of energy conservation is to postpone non-essential activities. And then, if you're going to take a nap, try to do naps that do not disrupt your nighttime sleep. And these typically would be naps that would be no more than 30 minutes at a time. Because when, for example, if I have patients that will sleep for two to three hours, the potential of that interfering with their sleep at night is very high. So, try to limit your naps. And if you need to take a nap in the day, try to limit it to 30 minutes.

(23:17) Another important way to conserve one's energy is to have a structured daily routine, and also to attend to one activity at a time. And I know that's a challenge because we are all in a society where we all multitask. And it's good to try to focus on attending to one activity at a time.

(23:40) Exercise is extremely important and simple walking is a good way to start. I think as far as our toolbox is concerned, exercise is extremely important. Exercise can improve your functional performance, decreasing your fatigue. And we try to focus on individualizing the exercise program for each patient. And as I mentioned, a good goal is 30 minutes of exercise, five days a week. And I tell patients where, if they're not exercising at all, we'll just begin slowly, even if it means walking around the house, for example, a hundred more steps per day, that's fine. And just gradually try to increase your extra exercise ability, your ability to walk on a daily basis, keeping in mind the overall goal is eventually 30 minutes of exercise, five days a week.

(24:36) And as I mentioned, walking, I think is one of the best forms of exercise. And there's many reasons: that usually it's safe, it's convenient and it stimulates one's energy, helps maintain balance, mobility. And it's also just a major component of the activities of daily living. So, walking is, I think a very important type of exercise that we can do. And it's easy, particularly in patients who have not been exercising, and it's a great way for them to begin their exercise program.

(25:16) Aerobic exercise, resistance exercise and strength training are all valuable. Now, I'm showing you a study on this slide that was done by an exercise physiologist. And this is looking in more depth as far as modes of exercise. And of course, there's aerobic exercise, resistance exercise and flexibility. And with the aerobic exercise, as I mentioned, the overall goal is 30 minutes of exercise, five days a week.

(25:44) Physical medicine and rehab specialists can design a unique exercise program. Also, resistance exercise can be very helpful, and that would be strength training exercises, two to three times per week. And what you're trying to do is increase your muscle mass. And then of course, flexibility exercises, which would be stretching exercises. And for those of my patients who really have not been exercising, and they really need help, many times I'll refer them to physical medicine and rehab, and they can be very helpful as far as an exercise prescription. And I like to always emphasize that what we want to do is try to resume normal activity as soon as possible during cancer and following cancer treatment.

(26:37) Some exercise is better than none. You want to start slowly and progressively increase and strive to achieve recommended levels of exercise. And like I mentioned, physical medicine and rehab consultants can be very helpful as far as coming up with an exercise program.

(27:01) Several practices can improve sleep hygiene and lessen fatigue. Another important tool, as far as cancer-related fatigue is good sleep hygiene. And a part of that is to set a constant sleep schedule. And what I tell patients is, try to go to bed at the same time, get up at the same time and have regular bedtime rituals. And so, I'll encourage patients to think about taking a warm bath or listening to soothing music, or reading an inspirational book.

(27:33) It's important also as far as with regular exercise, to do it at least two hours before bedtime. Because if you do rigorous exercise before bedtime, that can go ahead and sometimes wake you up and interfere with your ability to sleep at night. And then also, trying to avoid large meals before bedtime. Some patients find that small snacks will tend to promote sleep.

(28:07) An important thing with good sleep hygiene is also to limit caffeine. And a good rule of thumb is to limit, take less than two servings per day and try not to drink caffeine after noon. Also, avoiding nicotine. And tobacco users who stopped smoking are usually able to fall asleep faster and sleep actually better once the withdrawal symptoms subside.

(28:37) Another good rule of thumb is to avoid alcohol four to six hours before bedtime. And then as I mentioned, limit afternoon naps to less than 30 minutes. And then also, very important, is use your bedroom for sleep only. And I think in this day and age, many times patients are using their laptops when they're in bed or they're watching TV. And I think it's very important that as you begin to think about going to bed, to try to go ahead and decrease all these other activities.

(29:19) Relaxation and self-hypnosis brings multiple benefits while also improving fatigue. And then also, relaxation and self-hypnosis are also very important. And actually, a new alternative therapy for the treatment of fatigue is both of these items. And what it does is it provides tranquility, less pain, helps with concentration and just gives a feeling of hope, and helps with relaxation, and then it gives a sense of wellbeing, which could be very important for the treatment of cancer-related fatigue.

(29:56) Good nutrition can decrease or prevent fatigue. Also, nutrition is extremely important. And what I really emphasize to all my patients is to try to maintain good nutrition because this can actually decrease or prevent fatigue. And as I mentioned, the goal is five servings of fruits and vegetables. Of course, I realized some patients do require special diets, and this is where a good dietician can come in.

(30:25) Also, we want to minimize other gastrointestinal side effects patients can experience such as nausea, vomiting, and diarrhea. And then it really cannot be over overstated, the importance of good dental care. And I really encourage patients to see their dentist on a regular basis because this can be very important as far as one's nutrition.

(30:55) Drugs like methylphenidate can help some people with fatigue. So, in addition to all of these lifestyle measures that I have mentioned, there are some patients that definitely will benefit from pharmacologic agents. And so, what we do use in our fatigue clinic is stimulant therapy. And one of the stimulants that we use is methylphenidate. And I found that a number of my patients are familiar with this because they're familiar with it due to, for example, children who are on this medication for ADHD.

(31:33) So, methylphenidate is a CNS stimulant. It has a short plasma half-life of about two hours, rapid onset of action. And its duration of hours is usually three to six hours. Baseline dose or a good starting dose is usually five milligrams in the morning and five milligrams at noon. And the maximum dose is usually around a milligram per kilogram per day. And I can tell you, usually we start very conservatively, usually like starting five in the morning and five at noon.

(32:12) And in patients who are really concerned about this medication or after a detailed discussion, really want a conservative dose, then some patients I'll use five milligrams in the morning. And then I'll tell the patient to contact me in about two weeks to let me know how they're doing on this medication.

(32:36) Evaluating pre-existing or existing conditions and monitoring side-effects is important with such medications. Now, prior to prescribing this medication, I want to make sure that the patient does not have any pre-existing or existing medical conditions, for example, that would be a contraindication. And that would be, for example, any significant coronary artery disease.

(32:57) And I also have a detailed conversation with the patient about possible side effects, such as palpitations, or maybe increase in anxiety or difficulty with sleep, or perhaps even decreased appetite. And what I do want to stress is that these side effects are usually very rare. Many times these medications are very well tolerated. And I start on a low dose. And then depending on how the patient responds, then can gradually increase the dose of this medication. And this actually is a very important medication and very valuable as far as tools that we have that can help with cancer-related fatigue.

(33:51) Modafinil can be another helpful medication. So, in addition to the methylphenidate, which I just mentioned, another stimulant that we use is Modafinil. Now, Modafinil is a CNS stimulant and it's approved for the treatment of narcolepsy. The usual dose is a hundred to 200 milligrams in the morning, with the second dose at noon. And the maximum dose is typically 400 milligrams per day.

(34:20) And similar to the muscle methylphenidate, I always want to make certain that the patient doesn't have any medical contraindications and they are aware of potential side effects. And then after starting this medication, I'll have the patient, as I mentioned, contact me in two weeks to let me know how they're doing.

(34:46) Education is crucial so people can learn how to recognize and treat cancer-related fatigue. I always like to mention that education is so extremely important as far as the treatment of cancer-related fatigue. And really, I think all cancer patients and their families should be educated on the phenomenon of cancer-related fatigue and management strategies. And it's really important to keep in mind that this is such an important part, an essential component of total health care, extremely important. And this is why I'm always delighted to give talks like this, because I think fatigue is the most common and most distressing symptom in cancer patients. And it's many times, this is a fact that's not well recognized, and there are things that can be done as I've mentioned to help with this symptom.

(35:40): Caregivers are crucial partners in managing cancer-related fatigue. Then in addition, I always have a shout out for the caregivers. Caregivers are such an important part of this whole entire journey. I tell the caregivers, it's important to take quality time for yourself. Schedule time off during the day, for example, at home, where you can just relax, and also to watch for any signs of stress. Don't be afraid to ask for help from family and friends. There are a variety of resources that are out there for caregivers. And it's overall very important to ventilate your feelings. And you are such an important part of the whole journey. And you also are important and also need to watch out for yourself, and your own levels of stress.

(36:38) A summary of how to treat cancer-related fatigue.  So, in conclusion, so fatigue, this is the most common and the most distressing symptom in cancer patients and survivors. And patients with cancer-related fatigue, really require a complete medical evaluation. And as I mentioned today, looking for any medical problems that are undiagnosed or inadequately treated, and then also looking for any other possible associated symptoms, such as pain, anxiety, depression, sleep disturbance, because these symptoms will need to be addressed because by addressing them, potentially, this can decrease the severity of the fatigue.

(37:23) So, then the treatment for cancer-related fatigue really consists of a variety of both nonpharmacologic and possible pharmacologic interventions. And each patient should have a treatment plan tailored to them. And in all patients with cancer-related fatigue, really should be educated on the lifestyle measures that I've reviewed with you today.

(37:50) And finally, continued research is necessary to better define this phenomenon, to look at what are the pathologic or pathophysiologic mechanisms for cancer-related fatigue. And then I think also, this research will help us with further development of treatment strategies. And so, I'm going to go ahead and now turn it over to our moderator.

(38:23) [Marla O'Keefe]      Thank you, Dr. Manzullo. That was an excellent presentation. And you certainly generated a lot of good questions here. So, we'll now go to the questions. As a reminder, if you have a question, please type it into the chat box in the lower left-hand corner of your screen.

Question & Answer Session

(38:40) Our first question today is, how big of a role do medications play in fatigue like tacrolimus or Jakafi, for example?

(38:51) [Ellen Manzullo]      Right. It can be quite significant. I have had patients, a number of patients over the years on both of those medications, and they have been able to tell me how adjustments in that medication do have an effect on their cancer-related fatigue. I mean, I think something that we all realize is that these are necessary medications. And so, we keep that in the back of our mind. And then that's why we work on all the other things that I've mentioned to you today, but they can have an effect.

(39:32) [Marla O'Keefe]      Thank you. "I am 24 years out from an autologous stem cell transplant. And my red blood cell count still isn't in the normal range. Is there a way to raise my red blood cell count?"

(39:47) [Ellen Manzullo]      Yeah. So, basically I know when I see patients in the fatigue clinic, this is like the first thing that I look at is what their hemoglobin level is. And so, typically patients when their hemoglobin level is 10 or less, they will be experiencing fatigue. And so, I think the big question is, and one that we're faced with is, does the patient require a blood transfusion?

(40:19) I know at our institution here at MD Anderson, typically we give blood transfusions if the patient has a hemoglobin level of about seven or less. And so, really, that probably is one of the most effective interventions would be a blood transfusion. But the big question is, is it indicated, is the hemoglobin level low enough?

(40:44) Another important thing is to make sure that there are not any other causes of anemia, for example, iron deficiency or B12, or folate deficiency, because if that's the case, well then perhaps supplementing those could potentially help the anemia. And so, that's why it's always good to have an evaluation of the anemia to see, could there be any of these other causes such as iron deficiency, B12 or folate deficiency?

(41:19) [Marla O'Keefe]      Thank you. Next question is, "I was diagnosed with chronic fatigue syndrome and myalgic encephalomyelitis. I still deal with this 16 years post-transplant and it significantly impacts my daily life. How common is this? And could it also be called cancer-related fatigue?"

(41:42) [Ellen Manzullo]      So, this is an excellent question. And this is why when I see a patient, I always get an assessment as far as when did the fatigue begin? And so patients, for example, there are patients that are diagnosed with chronic fatigue syndrome, and if it was like, for example, five to 10 years before the cancer diagnosis, most likely there is some other etiology for your fatigue. And so, that's why I always ask, when did your fatigue begin?

(42:21) Sometimes for example, those patients who do have these chronic fatigue syndrome, for example, they will experience worsening fatigue with their cancer treatment. So, we'll still use the same principles that I've described to you today. But it can be quite challenging, especially if you've had this chronic fatigue syndrome, for example, a few years prior to your cancer diagnosis.

(42:54) [Marla O'Keefe]      Thank you. Would you recommend drinks with electrolytes over water to increase hydration?

(43:02) [Ellen Manzullo]      Yeah. So, that's an excellent question. Those drinks are not a problem. I always, as a general rule of thumb, I tell patients to try to drink six to eight glasses of water a day, at least. And as far as these drinks, the only caution that I would have, is to look at what sorts of electrolytes are in these drinks, for example, that's very important.

(43:36) Also, patients many times are having these energy drinks and they're in all of our grocery stores. One thing you have to keep in mind is, some of these drinks also are high in glucose. And in patients, for example, that are drinking a lot of them on a daily basis, and if they're a diabetic, they can have trouble with their blood glucose control. So, that would be something to keep in the back of one's mind if, for example, you're a diabetic. And it's really important to have good control of diabetes because that also, that alone can have improvement in fatigue.

(44:22) [Marla O'Keefe]      Thank you. And this tags along with the last question, are supplements like iron and B12 effective for fatigue?

(44:31) [Ellen Manzullo]      Yeah, especially the supplements will be important in patients with anemia, where we find, for example, there is iron deficiency or B12, or folate deficiency. Yes, if we can give these supplements to a patient and they have improvement in their hemoglobin, they could potentially have improvement in their fatigue.

(44:59) [Marla O'Keefe]      The next question is, are there any CNS stimulants that are over the counter?

(45:06) [Ellen Manzullo]      No, actually the CNS stimulants, these are the ones that, for example, I described to you are controlled substances. Almost all the times we just give a 30 day supply, and these are controlled substances. As far as supplements out there that are CNS stimulants, no, I do not think so. And I'm not aware of any.

(45:37) [Marla O'Keefe]      How do you balance dehydration with kidney dialysis?

(45:44 [Ellen Manzullo]      So, that can be a challenge. Actually, so for example, this is where, with cancer-related fatigue, I often tell patients it's a multi-disciplinary approach. And it is something that where we work with, sometimes as a general internist, I will work with a variety of specialists. And I will go ahead at times and work with patient's nephrologist to see what can be done as far as a patient's volume status. It is a challenge because I know patients with end stage renal disease, who require dialysis, can experience worsening fatigue the day of, and the day after. And so, this is something where working with a nephrologist can be helpful.

(46:45) [Marla O'Keefe]      Thank you. What do you know about effectiveness of acupuncture for fatigue?

(46:52) [Ellen Manzullo]      Right. As far as acupuncture is concerned, really there are some pilot studies out there that are suggestive, that they are helpful. However, this is an area that I think further research is needed. So, I think this is an area where studies are being done, pilot studies are out there. And I think it's a promising area and one that we need to keep our eye on.

(47:25) [Marla O'Keefe]      Okay, thank you. And this is going to have to be our last question. We've had a lot of good ones. "I have found that drugs, I have taken to treat neurological conditions such as Neurontin and Lyrica to cause fatigue. Is this common?"

(47:41) [Ellen Manzullo]      Yes. Actually, so we can go ahead and we can see that in our patients. And this is where we weigh the benefit and the risks of these medications. And that's why it's so important that medication list that I mentioned. Sometimes patients will have improvement in their fatigue with perhaps some decrease of that medication. But there are quite frankly, some patients that I've seen where they needed just another medication.

(48:14) For example, I know patients who have fibromyalgia, they could be on one of those medications, and it can be a challenge as far as weighing the risk and the benefits of stopping that medication. But yes, that is, it has been observed and it is in fact the case.

(48:35) [Marla O'Keefe]     Closing. Okay. Dr. Manzullo, thank you very much. It was a wonderful presentation and some great questions. On behalf of BMT InfoNet and our partners, we'd like to thank you for your helpful remarks. And thank you, the audience, for your excellent questions.