Anorexia/Cachexia

Question 1

Presentation of anorexia-cachexia syndrome

Answer 1

• Chronic fatigue
• Anorexia
• Depression
• Early satiety
• Weight loss
• Loss of skeletal muscle (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support
• Leads to progressive functional impairment

Question 2

Pathophysiology of anorexia-cachexia syndrome

Answer 2

• Negative protein and energy balance
• Driven by variable combination of reduced food intake and abnormal metabolism
• Chronic inflammatory state likely drives much of the syndrome.

1. Muscle loss (hypercatabolism and hypoanabolism)
   - Inflammatory activity stimulates proteolytics systems resulting in increased enzymatic digestion of muscle tissue
   - Cytokines block anabolic effects of IGF and growth hormone, contributing to reduced muscle synthesis
   - Myostatins induce muscle proteolysis (upregulated in cachectic states)
   - Decreased ingestion of nutrients required for muscle anabolism (protein)
2. Anorexia (impaired PO intake)
   - Appetite governed by:
   a. Hypothalamus (loss of equilibrium between appetite stimulant and suppressor neurotransmitters due to cytokine stimulation and increased energy expenditure)
   b. Solitary tract nucleus (network in brainstem, regulating appetite and GI motility). Again, cytokine activity results in disequilibrium between appetite stimulation and suppression
3. Fat loss (hypermetabolism)
   - Lipolysis increases without concomitant increase in fat synthesis
   - Appears to be due to increased catecholamine activity
   - Obese patients may disproportionately lose muscle in comparison to fat, and may not appear underweight

Question 3

Lab features of anorexia/cachexia

Answer 3

• High CRP
• High LDH
• Low albumin (late)
• Low testosterone

Question 4

Difference between primary and secondary cachexia

Answer 4

Primary Cachexia
- Pervasive host-tumour relationship where there is a wasteful consumption of energy and altered metabolic processes leading to muscle and fat loss

Secondary Cachexia
- Due to other processes (e.g. depression, oral issues, dysphagia, nausea, etc.) that reduce nutrition and result in muscle loss

Often, patients will present with components of both.

Question 5

Correctable causes of cancer cachexia

Answer 5

1. Psychological factors
   - Anxiety, depression, family and/or spiritual distress
2. Difficulties with PO intake
   - Appetite
   - Disturbed taste or smell
3. Oral problems
   - Mucositis, denture issues, xerostomia, thrush
4. Dysphagia
5. GI issues
   - GERD, early satiety, N/V, Obstruction, Constipation, Diarrhea
6. Malabsorption
   - Fistulas, pancreatic insufficiency
7. Fatigue
   - Sleep disturbances, cognitive fatigue, physical limitations
8. Function
9. Pain
10. Metabolic disorders
    - DM, AI, Hypogonadism, Hypothyrodism

Question 6

Cancers most likely to cause cachexia

Answer 6

• Pancreas
• Lung
• Upper GI tract

Less common with early breast and heme cancers

However, anorexia-cachexia is considered a ‘final common pathway’ commonly encountered prior to death

Question 7

Assessment of anorexia-cachexia

Answer 7

1. Weight and height (standardised), BMI
   - No shoes, no outer garments, emptied pocket
   - Reliable scale with same one used for follow up
   - Note made of last BM and presence of pleural effusion, ascites, or edema noted
   - Weight loss history
2. History from patient
   - History and degree of weight loss
   - ESAS (for secondary cachexia components)
   - Patient-Generated Subjective Global Assessment (PG SGA) - patient reported food intake, weight loss, and symptoms affecting intake
   - Distress thermometer for factors influencing anorexia-cachexia
3. Functional assessment
   - Ability to walk over a timed period (2 or 6 minute walk)
   - Sit to stand time
   - Gait speed
4. Lab assessment
   - CRP (if elevated, in the absence of infection, suggests primary cachexia and is a predictor of reduced survival)
   - Albumin (typically only reduced if cachexia is advanced)
5. Psychosocial assessment
   - Isolation, family distress, ability to participate in social aspects of life, etc.

Question 8

Management of anorexia-cachexia

Answer 8

1. Determine whether primary or secondary
2. Aggressively treat any secondary causes
3. Involve multi-d team (dietician, PT, OT)
4. Discuss with family members and ensure they are active members of the team
5. Ensure appropriate diet

Question 9

Diet for patients with anorexia-cachexia

Answer 9

1. Ensure patient has an appropriate diet
2. Total protein intake of 1.5 g/kg if patient capable of ingesting this amount and malnourished
3. Consider alternative sources of protein (whey protein, nutritional supplements, etc.)

Question 10

Tips for food preparation for anorexia-cachexia

Answer 10

General tips for food prep:

• Experiment with spices and flavourings (lemon, orange, fruit, pickles, chutney)
• Sugar for bitter tastes
• Fruit based sauces for dry foods
• Marinate meats
• If meat aversion is present, use other high protein sources (fish, eggs, cheese)
• Plain milk can be made more palatable with fruit or chocolate syrup
• Sparkling water before eating can reduce bitter tastes
• Cold foods can be useful if odours are problematic
• Rinse mouth between meals with soda water or baking soda

Presentation:

• Vary colour of food and use garnishes
• Dine in area free of odours
• Serve small portions

Mealtimes

• Ensure meals are social
• Do not guilt or force patient with food
• Consider a small amount of alcohol if the patient is accustomed to this with meals (but limit or avoid during chemo)
• Breakfast should be largest meal of the day
• Small frequent meals

Question 11

Dietary supplements for anorexia-cachexia and lifestyle interventions

Answer 11

1. Commercially available supplements (e.g. Ensure) - but should complement rather than replace regular food intake
2. Omega 3 fatty acids, 2 - 2.5g/daily of EPA, may reduce inflammation. Avoid in patients receiving therapies with significant thrombocytopenic risk or at risk of bleeding from other causes. Weak evidence.
3. Vitamin D - common deficiency in Northern hemisphere populations. Patients at high risk of hypercalcemia probably should not take Vit D
4. Multivitamins and Vit C - weak evidence, may interfere with chemotherapy.
5. Exercise program according to capability and safety profile
   - Improves function
   - Decreases inflammation
   - Best therapy for fatigue

Question 12

Pharmacologic interventions for anorexia-cachexia

Answer 12

1. Corticosteroids
   - Appetite stimulants, but increase muscle breakdown. Improve QoL and appetite, but not weight.
   - Avoid long term use (e.g. use short term to boost appetite or in patients with baseline limited mobility where appetite is the prime concern)
   - Dex is more likely to result in muscle catabolism - prednisone is safer, but more likely to cause electrolyte imbalance
2. Progestational agents (Megestrol acetate)
   - Increases appetite and weight gain, though almost entirely fat rather than muscle
   - Some degree of muscle catabolism (less so than steroids), overall found equivalent to steroids
   - Use is advised for short term, combined with exercise
   - Risk of VTE (low risk, but avoid in patients with a history of VTE)
3. Cannabinoids
   - Enhance taste and smell, making food more palatable
   - Limited evidence, but may be a good option for some patients
4. Anabolic steroids
   - Many patients are hypogonadal (especially if elderly or on opioids), confirmed by low levels of bioavailable testosterone
   - Limited evidence, but can use replacement testosterone doses in wasted, hypogonadal patients with a detailed discussion of adverse effects
5. Gastric stimulants and laxatives
   - Ensure patients are on a bowel protocol as constipation will diminish appetite
   - If there are features of early satiety and bloating, a trial of maxeran is worthwhile

Question 13

Gastric stimulants and laxatives for anorexia-cachexia

Answer 13

Gastric stimulants and laxatives

• Ensure patients are on a bowel protocol as constipation will diminish appetite
• If there are features of early satiety and bloating, a trial of maxeran is worthwhile

Question 14

Anabolic steroids for anorexia-cachexia

Answer 14

• Many patients are hypogonadal (especially if elderly or on opioids), confirmed by low levels of bioavailable testosterone
• Limited evidence, but can use replacement testosterone doses in wasted, hypogonadal patients with a detailed discussion of adverse effects

Question 15

Cannabinoids for anorexia-cachexia

Answer 15

• Enhance taste and smell, making food more palatable

- Limited evidence, but may be a good option for some patients

Question 16

Progestational agents for anorexia-cachexia

Answer 16

Progestational agents (Megestrol acetate)

• Increases appetite and weight gain, though almost entirely fat rather than muscle
• Some degree of muscle catabolism (less so than steroids), overall found equivalent to steroids
• Use is advised for short term, combined with exercise
• Risk of VTE (low risk, but avoid in patients with a history of VTE)

Question 17

Steroids for anorexia-cachexia

Answer 17

Corticosteroids

• Appetite stimulants, but increase muscle breakdown
• Avoid long term use (e.g. use short term to boost appetite or in patients with baseline limited mobility where appetite is the prime concern)
• Dex is more likely to result in muscle catabolism - prednisone is safer, but more likely to cause electrolyte imbalance

Question 18

Enteral or parenteral feeding for anorexia-cachexia

Answer 18

• Role for cancer patients who are malnourished during aggressive therapy or pre-op, there may be a role
• Less clear in advanced cancer with anorexia-cachexia and no clear benefits with significant risk

Consider when:
- Cachectic patients with normal CRP (look for secondary causes of malnutrition)
- Patients with well-maintained muscle strength
- Life expectancy > 6 months
E.g. bowel obstruction or malabsorption

Question 19

Patient Generated Subjective Global Assessment

Answer 19

• Validated tool for patients with cancer
• Several elements are useful for assessment of anorexia-cachexia (includes weight loss history, dietary intake component, checklist of ‘nutritional impact’ symptoms, and functional capacity assessment)

Question 20

Interventions appropriate for patients with anorexia-cachexia, ECOG PS 0-3

Answer 20

• Dietary consult
• Physio for exercise plan
• Consider NSAID or fish oil for an anti-inflammatory (no clear evidence)
• Consideration of other pharmacotherapy

Question 21

Interventions appropriate for patients with anorexia-cachexia, ECOG PS 4

Answer 21

• Consider non-pharm interventions if survival >2-3 months

- Consider steroids for improved energy and appetite

Question 22

Interventions for patients with anorexia-cachexia and HIV

Answer 22

• Anabolic steroids may be particularly useful in HIV
• Consider megestrol acetate
• Dronabinol has some evidence, but was associated with a higher frequency of CNS adverse effects compared to placebo

Question 23

Interventions for patients with anorexia-cachexia and COPD

Answer 23

• Anabolic steroids have some evidence, though were typically combined with an exercise or rehab program
• Pts treated with Megestrol acetate showed improvements in PaO2, body image, and appetite scores, but distance walked in 6 mins and dyspnea scores were worse
• Polyunsaturated fatty acids were shown to be beneficial in a single centre trial with improved peak workload, but no significant differences in body composition, muscle strength, or lung function