L12.1 Cancer cachexia

Question 1

Cancer Cachexia definition

Answer 1

Multifactorial syndrome characterised by ongoing loss of skeletal muscle mass with or without loss of fat mass that leads to progressive functional impairment

Question 2

Diagnosis of cancer cachexia

Answer 2

• >5% weight loss over 6 months
• BMI<20 + weight loss >2%

Question 3

Prevalence of cancer cachexia?

Timeline of cancer cachexia development

Answer 3

• Cachexia affects 80% of cancer patients
• More common in children & elderly
• Weight loss ↑ with duration/severity of cachexia

Precachexia → Cachexia → Refractory cachexia → Death

Question 4

Consequences of cancer cachexia

Answer 4

• ↓40% physical activity (↑fatigue) → ↓quality of life
• ↓chance of improving tumour mass after chemotherapy (imparied response)
• Respiratory failure (↓diaphragm force & ↓TV)
• Cardiac failure (↑Cardiac fibrosis, ↓heart mass, structural remodelling & dysfuntion)
• ↑Susceptibility to chemotherapy toxicity → induce cardiactoxicity

Question 5

Muscle mass as an indication?

Answer 5

• 15% ↓ in muscle mass → ↓ function
• 25-30% ↓ in muscle mass → death
• Muscle str → is also a predictor of survival

Question 6

Treatment: 1) Understand pathogenesis & Identify therapeutic targets

Answer 6

Question 7

Treatment: 2) Develop suitable pre-clinical models & tests

Answer 7

Use mice instead of rats

Question 8

Treatment: 3) Test efficacy of tests

Answer 8

• Target anorexia → ↑food intake but no effect on muscle mass/↑ in quality of life
• Target Cytokines (using anti-inflammatories) → have ↑ side effects
  
  • Many only target 1 cytokines → other released cytokines still have adverse effects
• Protein changes
  
  • Myostatin (causes atrophy)
    
    • Anti-myostatin → improvement
  • Activin (causes greater atrophy)
    
    • Inhibit activin & myostatin → ↑ beneficial effects
  • ANG pathways → signalling causes muscle wasting
    
    • ACE inhibitors (prevents ANG 1 → 2) → no improvement in body & muscle mass but ↑ muscle function & fatigue
  • TWEAK pathway (TNF-α pathway) → causes atrophy
    
    • Fn14 inhibitory antibodies → prevents loss in body & muscle mass, also ↑ muscle str
• Combination therapy → well tolerated & ↑ benefits
• Exercising with cachexia → ↓body mass & muscle mass ∴ bad

Question 9

Treatment: 4) Test efficacy in clinical trials

Answer 9

• Often shows efficacy in preclin trials → but none in clinical trials
• Lack of standard & appropriate tests
  
  • Need to examine FATIGUE & loss of MUSCLE FUNCTION not only the change in BODY MAS & APPETITE