12.1 () Fatigue

Question 1

List 3 key features of fatigue

Answer 1

Easy tiring - physical
Generalized weakness - emotional
Mental fatigue - cognitive

FS: TWM

Question 2

1. What is the prevalence of fatigue in cancer patients?
2. List 3 domains of QOL that may be impacted by fatigue

Answer 2

1. Most frequent and debilitating symptom in ADVANCED stage cancer (60-90%)
2. physical
   functional - social, work
   psychological - mood
   AND
   decision making capabilities, may lead to refusal of potentially curative Rx

FS:
Physical, emotional, functional, social

Question 3

Define “generalized weakness”

Answer 3

The anticipatory sensation of DIFFICULTY in initiating a certain activity.

Question 4

Define “mental fatigue”

Answer 4

Defined as the presence of impaired mental concentration, loss of memory, and emotional lability.

Memory
Emotional lability
Concentration

Question 5

Define cancer-related fatigue

Answer 5

A distressing persistent, SUBJECTIVE sense of
- physical, emotional and/or cognitive tiredness or exhaustion
- related to cancer or cancer treatment
- that is not proportional to recent activity and interferes with usual functioning

Question 6

List 4 conditions that fatigue should be distinguished from

Answer 6

Depression
Delirium (fluctuating LOC)
Drowsiness
Weakness (lack of physical/muscle/motor strength)

Question 7

List 2 ways in which tumours can directly cause fatigue

Answer 7

1. Lipolytic factors*
2. Proteolytic factors*
3. Pro inflammatory Cytokines* (!)
4. Tumour degredation products
5. Invasion of brain or pituitary gland (!)

* = tumour produced by products

Question 8

List 3 pro-inflammatory cytokines implicated in cancer-related fatigue.

Answer 8

1. TNF-alpha
2. IL-1
3. IL-6

Question 9

How can cancer-related treatments like radiation/chemo induce fatigue?

Answer 9

dysregulation of proinflammatory cytokines implicated in fatigue (TNF-a, IL-1, IL-6)

Question 10

What body systems do pro-inflammatory cytokines act on to induce fatigue? (4)

Answer 10

1. Brain (HPA axis, sleep, psych, dopamine changes)
2. Muscles (decrease mass/strength)
3. Metabolism
4. Immune system (cellular & humoral)

Question 11

What 3 host factors regulate pro-inflammatory cytokines implicated in fatigue?*

Answer 11

1. Genetic factors
2. Immune factors
3. HPA axis alterations

Question 12

What could be one of the main underlying mechanisms of fatigue?

Answer 12

Impaired muscle function

Unclear if fatigue related to muscle loss/altered muscle contraction VS. a central mechanism

Question 13

Contributors to Fatigue (14)

Answer 13

1. Cachexia (E)
2. Mood disorders (P)
3. Inflammation (I)
4. Neuroendocrine alterations (E)
5. Poly pharmacy (Iatrogenic)
6. Cancer-related symptoms (N)
7. Anemia (V)
8. Tumour by-products (N)
9. Infections (I)
10. Dehydration (D)
11. Anti cancer treatments (Iatrogenic)
12. Comorbidities (renal, hepatic, heart disease). (D)
13. Autonomic dysfunction (V)
14. Deconditioning (D)
15. Genetics (SNPs of proinflammatory cytokine genes)

Question 14

List 2 causes of muscle abnormalities due to cancer or it’s treatment.

Answer 14

1. Abnormalities in cytokine (pro-inflammatory) production*
2. Cachexia*
3. Increased lactate in muscle tissues
4. Atrophy* if type II muscle fibres
5. Myopathies* from anti cancer treatments
6. Loss of muscle mass* from corticosteroids

Question 15

1. What is the mechanism by which deconditioning leads to fatigue?
2. What is one treatment for this?

Answer 15

1. Prolonged bed rest + immobility = loss of muscle mass and reduced cardiac output

Deconditioning results in reduced endurance for exercise/ADLs
(may be compounded by muscle abnormalities)

2. Endurance exercise training can reduce fatigue and improve physical performance in cancer pts undergoing treatment/survivors

Question 16

List 4 proposed mechanisms by which fatigue is perceived/induced in the CNS*

Answer 16

1. Primary or secondary CNS tumours
   -invasion of pituitary gland –> endocrine abnormalities
2. Cognitive dysfunction (from brain tumour/ n.t. &hormones from other primaries/cancer treatments) can be caused by or contribute to fatigue
3. Dysregulation of serotonin/its receptors in the brain due to cancer/treatments
4. circadian rhythm disruptions
5. dysregulation of HPA

n.t. = neurotransmitters

Question 17

1. When can fatigue occur with infections
2. What is the underlying mechanism

Answer 17

1. As a prodrome or may outlast infection by weeks/even months esp with recurrent or protracted infections
2. Thought to share the same mediators for fatigue as cancer

Question 18

6 causes of anemia in cancer pts

Answer 18

1. Myelosuppression by chemotherapeutic agents
2. Iron deficiency
3. Bleeding
4. Haemolysis
5. Nutritional deficiencies
6. Anemia of chronic disease

Microcytic: TAILS

Normocytic - high retic: bleeding or hemolysis

Normocytic - low retic: bone marrow suppression, renal disease, anemia of chronic disease

Macrocytic: liver disease, ETOH, B12/folate deficiency

Question 19

List 7 physical effects of autonomic dysfunction.

Answer 19

GI:
Malnutrition
Anorexia
Delayed gastric emptying
Chronic nausea

General:
Poor performance status
Fatigue

Vascular:
Orthostatic hypotension

feeling hot or cold in some parts of or all over your body, due to issues that cause the blood vessels to narrow or widen;

Skin:
excessive or decreased sweating, salivating, or eye-tearing;

bladder:
such as being unable to empty one’s bladder fully;

sexual problems:
such as vaginal dryness and difficulty maintaining an erection;

FS:
Vascular, GI, bladder, sexual
General
Skin

Question 20

List 3 psychological issues that can cause fatigue.

Answer 20

Depression
Anxiety
Adjustment reaction

Question 21

List 3 endocrine disorders that could be a cause of fatigue

Answer 21

1. Diabetes mellitus
2. Addison’s disease
3. Hypothyroidism
4. Testosterone/androgen insufficiency/hypogonadism
5. HPA axis abnormalities of corticotropin releasing factor

Question 22

1. List 4 signs/symptoms of testosterone deficiency
2. List 4 causes of testoterone deficieny in cancer patients
3. In cancer treatment-related testosterone deficiency, list 1 possible intervention and 4 of its benefits

Answer 22

1. loss of muscle mass
   fatigue
   reduced libido
   anemia
2. anorexia/cachexia sydrome
   chemotherapy
   radiation
   hormone ablative therapy
3. Androgenic anabolic steroids (i.e. testosterone + its derivatives)
   benefits: increase muscle mass/energy/libido/Hb

Question 23

List 4 electrolyte abnormalities that can cause fatigue.

Answer 23

Hyponatremia
Hypokalemia
Hypomagnesemia
Hypercalcemia

Question 24

List 6 cancer-related symptoms that can cause fatigue.

Answer 24

Pain
Psychological symptoms
Dyspnea
Sleep disturbances
Anorexia
Constipation

Question 25

List 9 paraneoplastic neurological syndromes associated with fatigue*

Answer 25

Progressive multifocal leucoencephalopathy Paraneoplastic encephalomyelitis Amyotrophic lateral sclerosis Subacute motor neuropathy Peripheral paraneoplastic neurological syndrome Ascending acute polyneuropathy Dermatomyositis polymyositis (neuromuscular) Eaton-lambert syndrome (neuromuscular) Myasthenia Gravis (neuromuscular) ## Footnote PML - usually with leukemia & lymphoma Paraneoplastic encephalomyelitis - 70% cases in lung cancer

Question 26

List 4 anti cancer therapies that commonly contribute to fatigue.

Answer 26

Cytotoxic therapeutic agents Radiotherapy Biological response modifiers (i.e interferon) Targeted therapy (I.e tyrosine kinase inhibitor) (but rule out endocrinopathies from immunotherapy PD-1 inhibitors)

Question 27

List 11 medication classes commonly used in palliative care that can cause fatigue.

Answer 27

Opioids Anxiolytics Anticholinergics Antiepileptics Neuroleptics Alpha-adrenergic blocking agents Diuretics SSRIs TCAs Benzos ## Footnote compounded by polypharmacy!

Question 28

6 components to assessment of fatigue

Answer 28

Severity Duration Onset Level of interference with ever day life Associated psychological or social problems Possible underlying causes FS: OPQRSTUV - DIMS

Question 29

Name 3 clinical assessment tools for fatigue.

Answer 29

Visual analogue scale* ! Numerical rating scales* ! Functional assessment of cancer therapy-fatigue* Brief Fatigue Inventory* ! Piper Fatigue Scale* Fatigue Questionnaire** Multidimensional Fatigue Inventory** Pearson and Byars Fatigue Feeling Checklist ## Footnote * = subjective tools ** = multidimensional tools

Question 30

List 3 specific assessments for fatigue in the clinical setting.

Answer 30

Subjective assessment tools (VAS, NRS, FACT-F, Piper, BFI) Performance status Functional capacity (assess task: walking, driving, cycling) Task-related fatigue (VAS, NRS, Pearson&Byars) ## Footnote VAS= visual analogue scale NRS = numerical rating scale

Question 31

List 3 "dimensions" of fatigue that can be assessed

Answer 31

1. Physical 2. Cognitive 3. Emotional

Question 32

List 3 tools to assess performance status

Answer 32

Karnofsky performance status European Cooperative Oncology Group score (ECOG) Edmonton functional assessment test

Question 33

3 questions to consider in the assessment of fatigue*

Answer 33

1. Is fatigue a symptom of primary concern to the patient? 2. What are the major, probable causes? 3. Are there therapeutic measures available that have reasonable cost/benefit ratio?

Question 34

List 5 non-pharm measures to manage fatigue.

Answer 34

PT OT Acupuncture Exercise if deconditioning (early cancer and cancer survivors… not so much late stage)… best evidence. CBT Education about fatigue + instruction in self-care, coping techniques, activity management

Question 35

List 3 classes of medications that can help manage fatigue.

Answer 35

1. Corticosteroids (dex) 2. Progestational agents (megastrol acetate)/ other anti-cachexia agents 3. Psychostimulants (methylphenidate) (Lack of compelling data to support any of these other than very short term corticosteroids)

Question 36

List 10 specific measures to address in the evaluation and management of fatigue.*

Answer 36

Psychological issues Cachexia Anemia Infection Autonomic failure Metabolic and endocrine disorders Opioid induced sedation Hypoxia Dehydration Deconditioning

Question 37

List 3 ways corticosteroids are thought to help combat fatigue.

Answer 37

Inhibition of tumour induced substances Central euphoriant effects Improvement of physical symptoms | *probably not through appetite stimulation as steroids not shown to impr

Question 38

List 8 potentially reversible causes of fatigue in palliative care patients.*

Answer 38

Infection Anemia Autonomic factors Psychological factors Sleep disturbances (daytime sleepiness and/or insomnia) Metabolic disorders Drug induced Nutritional deficiency Dehydration Hypoxia optimize underlying cardio-resp conditions

Question 39

List 5 ways to manage fatigue caused by autonomic dysfunction. (Name 2 drug names)

Answer 39

Midodrine (alpha-1 sympathomimetic agent) Consider mineralocortocoid if indicated (fludrocortisone) Adjust doses of meds contributing to fatigue Decrease poly pharmacy Encourage exercise Increase salt intake Avoid triggers of autonomic insufficiency.

Question 40

List 4 triggers of autonomic insufficiency

Answer 40

Heat Motionless standing Large morning meals Etoh

Question 41

What is one common nutritional deficiency in patients with advanced cancer?

Answer 41

Carnitine (but in RCT, supplementation did not improve fatigue)

Question 42

List 2 nutritional supplements that may help combat cancer-related fatigue.

Answer 42

L-carnitine Ginseng Co-Enzyme Q-10 Guarana | *more studies needed re: efficacy & safety

Question 43

What are common changes associated with cancer related fatigue? (6)

Answer 43

Decreased cognitive function Decreased muscle endurance Decreased sleep quality Decreased control over body processes Increased social withdrawal Increased emotional reactivity

Question 44

What is the pathophysiology of cancer related fatigue?

Answer 44

Proposed mechanisms include energy imbalance caused by a variety of mechanisms including: Pro-inflammatory cytokines HPA axis dysregulation Circadian rhythms desynchronization Persistent immune system activation Establishment of a chronic inflammatory state.

Question 45

Describe the brief fatigue inventory?

Answer 45

0-10 numeric scale rating fatigue over designated time period. 0-3 mild 4-7 moderate 8-10 severe

Question 46

List 4 psychosocial interventions to manage cancer related fatigue.

Answer 46

CBT Behavioural therapy Psychotherapy Support groups Changing coping strategies Relaxation Energy conservation Stress management

Question 47

What are 4 considerations when prescribing/recommending exercise to patients?

Answer 47

Frequency Intensity Time Type (FITT)

Question 48

What advice would you give a patient to manage fatigue in advanced cancer? (6)

Answer 48

1. Plan activities during times in the day when pt is least tired. 2. Integrate regular, gentle activities into the day (stretching, sitting at table for meals). 3. Avoid stress and include relaxation/meditation techniques throughout the day. 4. Suggest multiple short naps throughout the day. 5. Limit visiting hrs for family and friends. 6. Look into home meal delivery options. FS Physical fatigue - Physical activity (pacing) - Nutrition Mental fatigue - Relaxation - Meditation Emotional fatigue - Social - Avoid stress

Question 49

What are the five elements of the definition of fatigue according to the NCCN?*

Answer 49

Distressing Persistent Physical tiredness Emotional tiredness Cognitive tiredness

Question 50

List 4 CNS abnormalities that may contribute to fatigue

Answer 50

Primary and secondary tumours* Anti neoplastic tx Drugs used to treat complications of cancer (ie opioids) Dis regulation of seretonin and or its receptors in the brain due to cancer tx.* Circadian rhythm disruption* Dysregulation of the HPA axis*

Question 51

What is the relationship between fatigue and cachexia?

Answer 51

Fatigue can be caused by muscle weakness and malnutrition which are characteristic of cachexia. But profound fatigue can exist in the absence of cachexia.

Question 52

On a numerical rating scale what value has been shown to suggest clinically relevant fatigue?

Answer 52

> 5

Question 53

3 benefits of exercising to manage fatigue.

Answer 53

Maintain muscle mass Improved self-reported physical functioning Improved sense of wellbeing Improved self esteem Improved outcomes (ie maintaining independence)

Question 54

List 4 lifestyle modifications that can be undertaken for management if fatigue and which can be explored in counseling.

Answer 54

Adapting activities Spending more time in bed or exercise if deconditioned. Rearranging schedules with respect to fatigue patterns. Change causative medications

Question 55

Treatment for what level of anemia is associated with improved fatigue in palliative care?

Answer 55

<80

Question 56

List 4 disadvantages of epo for treatment of fatigue.

Answer 56

1. Increased thrombotic events* 2. It may decrease survival time 3. 4-8 weeks before hgb increases* 4. Tumour growth (via angiogenesis)* 5. High cost*

Question 57

What is the typical dose of corticosteroids for fatigue?

Answer 57

Prednisone 40mg daily (about Dex 6 mg) *corticosteroid effects usually only last 2-4 weeks * long term risk of osteoporosis, myopathies, infections

Question 58

You have a patient with major depression and cancer-related fatigue. List 1 pharmacological treatment option for both issues

Answer 58

Major depression could be treated with anti-depressant but this has not been found to be effective for cancer-related fatigue Consider psychostimulant for rapid anti-depressant effect + helpful with fatigue, opioid-induced sedation