Cachexia -anorexia represent a broad multi-organ syndrome seen in several chronic diseases. Cancer cachexia (CC ) is a paraneoplastic syndrome whose outbreak is governed and driven by inflammation.
Complex syndrome that combines weight loss , lipolysis , loss of muscle and visceral protein , anorexia , chronic nausea and weakness Criteria for recognition - most definitions state a drastic loss of body weight for e.g > 10 % Lancet oncology in 2011 defined cachexia as ○ weight loss of greater than 5 % over the last 6 months OR ○ BMI < 20 and weight loss of > 2 % ○ appendicular skeletal muscle index consistent with sarcopenia (muscle wasting ) and weight loss of more than 2 %
Anorexia – A reduction in appetite which can be psychogenic ( anorexia nervosa ) or due to an underlying advanced illness as cancer.
Malnutrition – NICE describes malnutrition as “ state in which deficiency of nutrients as energy , protein , vitamins ad minerals causes measurable adverse effects on body composition , function or clinical outcome “. BAPEN recommends using the MUST ( Malnutrition Universal Screening Tool ) which consists of BMI , an unintentional weight loss hx of > 10 % in the last 3-6 months and acute disease effect associated with being acutely ill and unable to eat for > 5 days to recognise malnutrition.
Cancer cachexia – Prevalence varies across cancer types and ranges from ○ 60% among lung cancer patients ○ 80 % among GI cancers ( pancreas , colorectal, stomach and oesophagus ) Egidio et al in The Journal of Palliative Medicine in 2006 quoted that ○ cachexia may occur in up to 80 % of patients with advanced cancer ○ it is the main cause of death in 20 % of patients ( ie mortality is a result of cachexia rather then the tumour burden itself ) ○ cachexia is a marker of poor prognosis and is associated with anorexia , asthenia and changes in body image three stages of cancer cachexia have been described ○ precachexia – less than 5 % weight loss with other features as glucose intolerance or anorexia ( early metabolic dysregulation as proteolysis , lipolysis , glucose intolerance , insulin resistance , ↑ gluconeogenesis and ↑ ed resting energy expenditure ) ○ cachexia -as described above ○ refractory cachexia – cachexia which does not response to treatment , these patients have a low performance score and a life expectancy of less than 3 months Cachexia is also seen in people with AIDS and chronic forms of kidney disease , heart failure , people who have suffered severe burns and trauma.
What happens – A form of metabolic mutiny which tilts body’s metabolism towards catabolism Body’s immune response to cancer results in production of pro-inflammatory cytokines Several pathophysiological derangements can lead to weight oss which can happen together as impaired food intake , reduction in physical activity and associated anabolic effects as well as metabolic changes leading to systemic inflammation and activation of catabolism Several cytokines are thought to play role in the etiology of cancer cachexia Persistent inflammatory and stress responses coupled with tumour derived factors result in increased resting energy expenditure and net loss of lean tissue Cachexia leads to metabolic abnormalities as ○ synthesis of acute phase proteins in the liver at the expense of muscle protein ○ proteolysis ○ lipolysis ○ insulin resistance ○ decreased lipogenesis ○ elevated triglycerides ○ decreased HDL The net result is a negative protein and energy balance driven by a variable combination of reduced nutritional intake and abnormal metabolism.
Why important- Has a profound impact on quality of life , symptom burden and a patients sense of dignity Anxiety and distress for the patient and carers ↑↑ ed risk falls , ↑ healthcare use , ↓ self confidence , ↓ functional abilities Treatment related complications due to weight loss as fewer completed cycles of chemotherapy and decreased survival rate ↓↓ survival.
observe energy levels ability to perform ADL’s strength , mobility and wasting of skeletal muscles skin tone , turgor , colour , integrity features suggestive of dehydration as ○ increased thirst ○ dry mouth ○ decreased urine output ○ decreased skin turgor ○ weakness , dizziness , confusion ○ ↑ pulse ↓ BP ○ postural hypotension most common GI symptoms in cachectic patients are early satiety , nausea , bloating , taste alterations , xerostomia , dysphagia and constipation severe fatigue and breathlessness can be 2ary nutrition impact symptoms.
Potential causes – pain fatigue breathlessness ascites drugs as opioids ( e.g SEs of anticancer medications ) Intra- oral infections electrolyte imbalance as raised calcium nausea constipation dysphagia gastritis impaired gastric emptying ○ e.g due to local disease ○ autonomic neuropathy causing early satiety and vomiting of undigested food that relieves nausea poor oral hygiene / candidiasis / ill fitting dentures , ulcers /mucositis altered taste or smell depression and anxiety.
Note examine – Body weight Weight change during preceding months Body composition with a focus on muscle mass Oral cavity / swallow Abdomen Check available lab results Calorific intake with a focus on energy and protein intake Mid arm circumference Whole body impedance and electroconductivity
An assessment may focus on aspects as nutritional status metabolic status functional status nutritional barriers GI dysfunction distressing symptoms psychological and social distress adverse effects from medications tumour status.
Nutritional screening – Consider carrying out regular nutritional screening in all cancer patients undergoing anti-cancer treatment and in those with an expected survival of more than a few months Patients with an expected survival of less than a few months screening for eating related distress should be carried our
No general agreement as to the best screening tool – the following can be used PG- SGA ie scored Patient-Generated Subjective Global Assessment available via www. pt-global.org MNA – mini nutritional assessment short form MUST -malnutrition Universal Screening Tool Nutrition Risk Screening 2003 ( NRS 2002 ) Short Nutritional Assessment Questionnaire ( SNAQ ) Malnutrition Screenint Tools ( MST )
Personalized , Multi targeted and Multimodal approach.
aim is to alleviate or improve the consequences of cachexia and to → relieve symptoms impacting on food intake → adequate energy and nutrient intake → minimise catabolic alterations → support muscle training ( exercise ) → psychological and social support consider reversible causes interventions can be nutritional , pharmacological , exercise , psychosocial.
professional nutritional counseling cancer patients who cannot eat adequately should get nutritional support combination of dietary advice and oral nutritional supplements for e.g ○ high energy , high protein foods ○ fortification ( enriching foods by adding fat / oils , protein powder ) ○ ONS ( oral nutritional supplements ) ONS are a balanced mixture of macro and micro-nutrients in the form of liquid feeds , puddings and powdered formulations reconstituted with milk and water ONS available as fibre containing and milk- juice – yoghurt like products n-3- fatty acids have been used due to their anti-inflammatory properties tube feeding particularly for patients with head & neck , upper GI cancers where dysphagia may happen due to an obstructing tumour or severe mucositis. parenteral nutrition – weak evidence base and can be associated with severe complication which can include catheter related infections , occlusion and thrombosis, derangements of substrate and electrolyte levels , refeeding syndrome , exsiccosis , fluid overload and chronic hepatopathy and osteopathy
Pharmacotherapy- This is an area of ongoing research with corticosteroid being the most common option used in the primary care , other agents would be initiated under the advice of the specialist primary care team. Todate no consensus exists on a single effective or standard treatment of cachexia Corticosteroids ○ useful in the short term – most widely used appetite stimulant ○ can help reduce nausea , improve energy levels and feeling of general well-being ○ short term benefit is primarily due to potent anti-inflammatory activity whereas long term use is associated with side effects as rapid loss of muscle mass , insulin resistance and ↑↑ ed likelihood of infections as candida and stomatitis , further worsening the state of an already cachexic patient ○ length of response tends to decrease ( time frame described is 3-6 weeks ) ○ long term use is associated with significant/ multiple SEs ○ typical example -dexamethasone 4 mg po od x 1 week and then reduce to lowest effective dose 0.5 to 2 mg od Megace ( megestrol acetate ) and medroxyprogesterone acetate ( MPA ) are orally active derivatives of progesterone and have appetite stimulant and antigonadotropic activities. ○ takes about 2 weeks to work ○ pills are large but water soluble – may ↑ appetite and BW but not muscle mass ○ more suitable for long term use ○ main side effects include nausea , fluid retention and ↑ ed risk thromboembolism Ghrelin – endogenous ligand for growth hormone secretagogue receptors , it stimulates GH secretion and works to influence food intake regulation , GI motility and acid secretion. NSAIDs -particularly celecoxib has been considered to counteract the chronic inflammation in CC . Trials have been conducted with use of celecoxib© in combination with others as supplement L-carnitine and megesterol Prokinetics as metoclopramide / domperidone may help with early satiety , delayed gastric emptying , gastroparesis , nausea While several agents are being studied as cannabinoids , melanocortin antagonists , thalidomide and etanercept , bete 2 adrenergic drugs, olanzapine – treating CC remains a challenge with low evidence base of use and the multisystem pathways that lead to CC
- Aoyagi, Tomoyoshi et al. “Cancer cachexia, mechanism and treatment.” World journal of gastrointestinal oncology vol. 7,4 (2015): 17-29. doi:10.4251/wjgo.v7.i4.17
- Advani, Shailesh M et al. “Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials.” BMC cancer vol. 18,1 1174. 27 Nov. 2018, doi:10.1186/s12885-018-5080-4
- AUTHOR Marceca Gioacchino P., Londhe Priya, Calore Federica
TITLE=Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options JOURNAL=Frontiers in Oncology VOLUME 10 YEAR 2020 PAGES=298 URL https://www.frontiersin.org/article/10.3389/fonc.2020.00298 DOI=10.3389/fonc.2020.00298
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- BAPEN Introduction to malnutrition Introduction to Malnutrition (bapen.org.uk)
- NICE Malnutrition via Introduction | Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition | Guidance | NICE