Fatigue: what do we know?

Fatigue

Ollie Minton

Fatigue: what do we know?

• Impact of fatigue

• Mechanism

• Intervention

-Non-pharmacological -Pharmacological

• Where do we go from here?

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Fatigue is…

a subjective, unpleasant symptom which incorporates total body feelings ranging from tiredness to exhaustion creating an unrelenting overall condition which interferes with

individuals’ ability to function to their normal capacity

Ream and Richardson (1996)

Part of the modern condition?

Subjective vs Objective

• Difficult to link performance to specific complaints

• Cognitive testing in fatigued breast cancer – reduced verbal fluency & general processing speed

Prevalence

• Cancer-related fatigue:

– 40% at diagnosis

– 60-90% of those on treatment – 30-75% of cancer survivors

Prevalence declines over time

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Patient perception

Multicentre patient survey

consecutive patients with cancer attending OPD and chemotherapy day units -

•56% experienced fatigue on most or every day

•52% rated fatigue as biggest problem

Measuring fatigue

• Specific aspects of fatigue to assess

• Unidimensional vs multidimensional

• Patient population

Examples:

• Visual analogue/numerical scale

• FACIT- fatigue Scale

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Mechanisms

Technology allows measurement

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Cytokines driving symptoms

• Inflammatory low grade myositis

• Muscle inflammation in advanced disease with creatinine kinase rise

• B cell mediated cytokines causing macrophage proliferation.

• Access across blood brain barrier causing central symptoms

• Exact mechanism still unclear.

Pro-inflammatory response in cancer fatigue?

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Symptom clusters

• Patients on treatment:

• Cancer centre study N= 650

• Confluence of pain , depression and fatigue

• More highly correlated than by chance

• Related to physical functioning but not CRP

• Disease free survivors (successfully treated for breast cancer)

• N= 278 (105 fatigued vs. 173 controls) based on diagnostic process akin to CFS

• 5 independently associated variables

• Hospital anxiety and Depression (HADS) score , pain ,insomnia , systemic side effects of

treatment and plasma sodium

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Cancer fatigue syndrome

• N=300 breast cancer vs n=300 connective tissue disorders

• Specific elements of concentration & short term memory associated with cancer (&

treatment)

• Prevalence similar – 30% in both groups

Interventions

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National Comprehensive Cancer Network Guidelines (2013)

• Screening

• Evaluation

• Interventions

– Energy pacing and distraction

– Activity enhancement, psychosocial, nutritional, physical, CBT

– Psychostimulants: methylphenidate or modafinil

Proof of principle for CBT

Non-pharmacological interventions

• Exercise: aerobic exercise

• Psychosocial intervention

• Education programme

• Acupuncture

• Chinese Herbal medicine

Exercise for cancer fatigue

• Aerobic exercise only effective

• Mainly during or after treatment

• Breast and Prostate cancer N= 4000

• Resistance exercise does not improve fatigue

• Classes and subsidised gym memberships

• Optimum dose, type, or frequency still unclear

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NHS Physical activity care pathway

“Let’s Get Moving”

Interventions

• Brief 30 second flag

• 5 minute advice

• 30 minute meeting with e.g. physiotherapist

• But Key is repetition for at least 3 months and regular follow up for 12 months to affect

behavioural change.

• Objective monitoring feedback

Meta-analysis of Acupuncture

• 5 weakly positive trials improving during treatment

• Ginseng 8 weeks improved in post treatment phase

• No severe adverse events reported but high frequency of minor adverse effects

Herbal Medicine

• 10 trials in total

• Qualitative analysis using Cochrane methodology

Trial Data

• 177 trials for cancer related fatigue ( up to end of 2013) – across all types of intervention

• No superiority of any one intervention

• All effect sizes small

• Evidence still in favour for methylphenidate and exercise

Challenges of research in this area

• High attrition

• Complex phenomenon – biological, physical, psychosocial

• Patient’s own attitude – ‘just part of the condition’

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Conclusions

• Significant clinical problem during and after treatment

• Options for treatment limited but could include drugs and/or exercise

• Clearer mechanisms would lead to more

targeted treatment and objective monitoring and screening

• Suggestion that more severe fatigue might

Future directions

• Adding fatigue measurements to routine treatment monitoring (standardised across tumour groups) – use of registries

• Identifying those at high risk – genetic susceptibility

• Matching the symptoms to underlying pathological changes

• Further development of individualised approach

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