Nutritional requirements in long term conditions - Cancer Rachael Donnelly & Rachel Barrett Highly Specialist Oncology Dietitians Guy’s & St Thomas’ NHS Foundation Trust PEN Group Summer Meeting August 1st 2006

Aims Promote further understanding of cancer cachexia & cancer as along term condition Review current evidence base for nutritional requirements & the provision of nutritional support for cancer patients Acknowledge the practicalities of providing such requirements through an interactive case study

What is Cancer? ‘… the disordered & uncontrolled growth of cells within a specific organ / tissue type …. they often produce secondary growths / metastasis … this is the central & most threatening feature of malignant disorders….’ ‘… cancer is a collection of diseases with the common feature of uncontrolled growth … there are several causes, but ‘lifestyle’ factors are a major influence … several cellular changes are required to generate cancer …. invasion & metastasis distinguish cancers from benign growths ….. cancers are not always lethal…’ (Brennan, 2004)

Cancer – UK Facts & Figures 1 in 3 will get cancer at some stage of their lives 250,000 diagnosed with cancer per annum (Equivalent to 684 diagnoses daily) In the UK 154 460 people died from cancer in 2001 (www.cancerresearchuk.org)

Considerations in managing a cancer patient Site of cancer Type Stage of cancer Multi-modality treatment i.e. chemotherapy, radiotherapy, surgery & biological therapies Side effects of treatment & disease Co-morbidities Age of patient Social circumstances i.e. alcohol / drug & nicotine dependency Cachexia syndrome

Theories of Nutrition & Cachexia

Cancer Cachexia - What it is not? Due to starvation Due to malnutrition Due to competition by the tumour Restricted to cancer Reversed by nutritional support (Regnard, 2004)

Cancer Cachexia - Definitions Derives from the Greek ‘kakos’ meaning bad & ‘hexis’ meaning condition (Shaw, 2000) A physical fading of wholeness Syndrome of decreased appetite, weight loss, metabolic alterations & inflammatory state

Cancer Cachexia - What it is? An extreme on the continuum of weight loss in cancer Seen in cancer, cardiac disease & chronic infection but not neurological disease Due to a systemic inflammatory response Mediated through cytokines & other factors such as proteolysis inducing factor (PIF) & lipid mobilising factor (LMF) (Regnard, 2004)

Cancer Cachexia - Features Some or all of the following features are exhibited in varying degrees: Hypophagia / anorexia Early satiety Anaemia Weight loss with depletion & alteration of body compartments Oedema Asthenia (weakness) (Freeman & Donnelly, 2004)

Cancer Cachexia - Prevalence Occurs in ~ 70% of patients during the terminal course of disease Weight loss > 10% pre illness weight occurs in up to 45% of hospitalised cancer patients Cancer of the Upper GI & lung have the highest prevalence of weight loss Lung cancer patients with 30% weight loss show 75% depletion of skeletal muscle Breast cancer, sarcomas & NHL show the least weight loss (Payne-James et al., 2001)

Cancer Cachexia - Aetiology Understanding is limited & based upon the knowledge of abnormalities in nutrition behaviour & metabolic patterns Appears as a classic case of malnutrition 3 theories have been suggested: Metabolic competition Malnutrition Alterations of metabolic pathways (Payne-James et al., 2001)

Cancer Cachexia - Metabolic Competition Neo-plastic cells compete with host tissues for protein, functioning as a ‘nitrogen trap’ In experiments where tumour is a high % of animal weight this theory holds, but in human tumours – even patients with a very small tumour can have severe cachexia (Morrison, 1976)

Cancer Cachexia – Malnutrition (1) Upper aerodigestive disease is an obvious cause of malnutrition Regardless of tumour location, anorexia is the most common cause of hypophagia & usually consists of a loss of appetite &/or feelings of early satiety Hypophagia has been related to the presence of dysgeusia Diminished ability to perceive sweet flavours leads to anorexia (Payne-James et al., 2001)

Cancer Cachexia – Malnutrition (2) Reduced threshold for bitter flavours linked to an aversion to meat Dysosmia is also related to an aversion to food Malnutrition leads to secondary changes in the GI tract which may be responsible for the feeling of fullness, delayed emptying, defective digestion & the poor absorption of nutrients However, malnutrition alone is not thought to be the main cause of cachexia (Payne-James et al., 2001)

Metabolic Alterations in Starvation V. Cancer Cachexia – CHO Metabolism Glucose tolerance Insulin sensitivity Glucose turnover Serum glucose level Serum insulin level Hepatic gluconeogenesis Serum lactate level Cori cycle activity Decreased Increased Unchanged Adapted from Rivadeneira et al.,1998

Metabolic Alterations in Starvation V Cancer Cachexia – Fat Metabolism Lipolysis Lipoprotein lipase activity Serum triglyceride level Increased Unchanged Decreased Adapted from Rivadeneira et al.,1998

Metabolic Alterations in Starvation V Cancer Cachexia – Protein Metabolism Protein turnover Skeletal muscle catabolism Nitrogen balance Urinary nitrogen excretion Decreased Negative Increased Unchanged Adapted from Rivadeneira et al., 1998

Cancer Cachexia - Cytokines Produced by host in response to tumour Cytokines regulate many of the nutritional & metabolic disturbances in the cancer patient leading to: Decreased appetite Increase in BMR Increased glucose uptake Increased mobilisation of fat & protein stores Increased muscle protein release (Tisdale, 2004)

Nutritional Requirements in Cancer

Energy Expenditure Cancer itself does not have a consistent effect on resting energy expenditure (REE) Oncological treatment may influence energy expenditure (Arends et al., 2006)

Resting Energy Expenditure In cancer patients, REE can be: Unchanged Increased Decreased Many cancer patients are mildly hypermetabolic with an excess energy expenditure of between 138-289 kcals per day (Hyltander et al., 1991) If not compensated by ↑ energy intake results in loss of 1.1 - 2.3kg muscle mass & 0.5 – 1.0kg body fat / month (Bozzetti F et al.,1980) The challenge is identifying which patients

When working out the energy requirements for a patient with cancer, would you add a stress factor?

Energy Requirements (1) Assume energy requirements are normal unless data available to say otherwise (Arends et al., 2006) It is not appropriate to add calories for weight gain when calculating requirements for cancer patients

Energy Requirements (2) For non obese cancer patients total energy expenditure is approx: 30-35kcal/kgBW/d in ambulant patients 20-25kcal/kgBW/d in bedridden patients Assumptions are less accurate for underweight individuals (TEE per kg is higher in this group) (Arends et al., 2006) Published reference calculations are more accurate for underweight cancer patients (Harris & Benedict 1919, Schofield 1985)

Protein Requirements Optimal nitrogen supply for cancer patients can not be determined at present (Nitenberg et al., 2002) Protein requirements are calculated as per published reference calculations (0.17-0.2g Nitrogen per kg) (Elia, 1990)

Vitamin and Mineral Requirements (1) Vitamins & Minerals – lack of evidence surrounding requirements in oncological disease Base requirements on UK RNI’s (PEN Group, 2004) For EN recommendations are based on RDA’s (ASPEN, 2002)

Vitamin and Mineral Requirements (2) Markers of oxidative stress are increased & levels of anti-oxidants are decreased in cancer patients (Mantovani et al., 2003) Inclusion of increased doses of anti-oxidant vitamins could be considered but at present lack data to demonstrate clinical benefit (Arends et al., 2006) In reality, not routinely measuring vitamin & mineral status in such patients

Aims of Nutritional Support

‘An improvement in survival due to nutritional interventions has not yet been shown’ (Arends et al., 2006)

‘Unintentional weight loss of ≥ 10% within the previous 6/12 signifies substantial nutritional deficit & is a good prognostic indicator of outcome’ (DeWys et al., 1980)

Cancer - Aims of Nutritional Support (NS) (1) Improve the subjective quality of life (QoL) Enhance anti-tumour treatment effects Reduce the adverse effects of anti-tumour therapies Prevent & treat undernutrition (Arends et al., 2006)

Cancer - Aims of Nutritional Support (2) ‘…the principle aim of nutritional intervention with cancer patients will be to maintain physical strength & optimise nutritional status within the confines of the disease…’ (van Bokhorst de van der Schueren et al., 1999) ‘…nutritional intervention should be tailored to meet the needs of the patient & realistic for the patient to achieve…’ (Mick et al., 1991)

Aims of Nutritional Support (3) Optimum nutrition improves therapeutic modalities & the clinical course & outcome in cancer patients (Rivadeneira et al., 1998) Numerous studies strongly suggest substantial weight loss >10% leads to adverse consequences: Reduced response to chemotherapy & radiotherapy Increased morbidity Poor quality of life (QoL) Increased mortality rate (Van Bokhorst de van der Scheren et al., 1997)

When should Nutritional Support be started? If undernutrition is already present If inadequate food intake is anticipated for more than 7 days It should substitute the difference between actual intake & calculated requirements Inadequate nutrition throughout treatment course leads to increased morbidity & mortality, & reduced tolerance to treatment (Arends et al., 2006) Inadequate nutrition throughout treatment course leads to increased morbidity & mortality, & reduced tolerance to treatment – toxicities – dose reduction, delays in treatment, treatment change/termination

Can Nutritional Support improve Nutritional Status in Cancer? Yes, in patients whose weight loss is due to insufficient nutritional intake secondary to obstruction e.g. upper GI, head & neck In cachexic patients it is virtually impossible to achieve whole body protein anabolism Goals of NS are therefore different (Arends et al., 2006)

Does Nutrition Support Feed the Tumour? There is no reliable data to support the effect of nutrition on tumour growth ‘Feeding the tumour’ should have no influence on the decision to feed a cancer patient (Arends et al., 2006)

Nutrition Support Throughout the Cancer Patient’s Journey

Nutritional Support – Pre / Peri - Operative Patient’s with severe undernutrition benefit from NS 10-14 days prior to major surgery, even if surgery has to be delayed (Meyenfeldt von., 1992) All patients undergoing major abdominal surgery, NS (with immune-modulating substrates) is recommended for 5-7 days independent of nutritional status (Braga et al. 1999) Second point: based on current literature – grade A literature

Nutritional Support – Chemotherapy Currently, there is no strong evidence for routine NS during CT as it has no effect on tumour response to CT, nor on CT related associated unwanted side effects Symptom control is vital prior to any NS i.e. adequate anti-emetic control of nausea & vomiting Timely NS is necessary in many patients undergoing chemotherapy (Arends et al., 2006) Conditioned nausea, 56% of pts have food aversions by cycle 3 chemo Nutrition not relevant in stopping side effects Highlight that patients can get worse with each cycle of chemo S/E of chemo are dynamic and specific to time and change with drugs altering with each cycle of chemo

Nutritional Support – RT / Chemo-RT Intensive dietary counselling or NS prevents therapy associated weight loss & interruption of RT when compared to normal food Routine NS is not indicated in abdominal RT Nor is there any suggestion that routine NS is beneficial during RT to any other part of part of the body other than the head & neck & oesophageal (Arends et al., 2006) Significant weight loss can lead to Interruption in RT (moulds not fitting) can lead to a decrease in cure Some pts have daily visits to hospital for 5-7 weeks  need the energy

Interactive Case Study

Case Study (Background) Male- Mr D 52 yrs Diagnosis- T4N3M0 SCC Left Floor of Mouth (FOM) PMH- CABG x 3 ’99 & Hypertension Social History Lives alone above a pub Alcohol intake approx. 63 units/week Smokes 50g tobacco/week Security Guard

Initial Nutritional Assessment Diet History 4 strong black coffee’s each with 2 sugars 1 meal daily, early evening, takeaway Cornish pasty & chips Approx. 5 pints strong lager +/- 2-3 double vodkas per night Weight on referral- 55kg 17/05/05 Usual weight- 55-60kg Ideal weight- 56-69kg BMI- 19.7kg/m2 No recent weight loss Grip strength 28.5kg (<69% of normal)

Oncological Treatment 23/05/05 resection of FOM with DCIA flap Hemi-glossectomy Left radical neck dissection Right neck dissection Dental clearance Nil by mouth & tracheostomy in situ 13/06/05 debridement of DCIA flap 15/06/05 PEC major flap after failure of DCIA flap 04/08/05 post surgery 6/52 radiotherapy

When calculating Mr D’s energy requirements post operatively what stress factor would you use?

What actually happened Requirements calculated using 10% stress factor (SF) & 20% activity factor (AF) – approx. 2000kcal, 60-70g Protein Fed 2000ml Nutrison Multi fibre (2000kcal, 80g Protein) Weight increased 61.2kg- oedematous, 5 days later 55.3kg

What happened next Withdrawing from alcohol – confused & AWOL from ward Changed feed 1000ml Nutrision Energy Multi Fibre & boluses 2 x 200ml Fortisip Not meeting requirements due to compliance issues Flap failure & need for further surgery Remains NBM & PEG placed 19/07/05 Weight 52.1kg (2.9kg (5%) weight loss in 2/12)

What happened next Commenced radiotherapy 04/08/05 Weight 49.5kg Remained an inpatient Refusing pump feeding – bolusing only

Mr D’s requirements were re-calculated- what SF & AF would you use?

What actually happened Energy requirements were calculated with no SF & 25% AF – approx. 1800kcal, 50-60g Protein Feed regimen 6 x 200ml Fortisip bolused daily – provides 1800kcal, 72g protein Only taking 4 x 200ml Fortisip daily- provided 1200kcal, 48g protein Weight 07/09/05 47.5kg

Mr D was discharged home post radiotherapy, his weight dropped to 47kg & his requirements re-calculated. What activity factor would you use?

What actually happened Energy requirements were calculated using a PAL factor (1.5 – moderately active in a light occupation) & not an activity factor as this patient was now in the community Feed switched to 4 x 237ml cans of Two CalHN bolused in an attempt to meet requirements in a minimum volume Oral diet resumed (alcohol only)

Would you add 400kcal for weight gain?

What actually happened (1) In this case, no, in light of compliance issues & problems meeting baseline requirements Mr D has since had multiple admissions with acopia, continued weight loss, deterioration of swallow – now NBM, & undergone further surgery for wound dehiscence Dietetic intervention has incorporated both social & medical aspects of care

What actually happened (2) Taken 18 months to fully heal wounds, weight gain has just begun in conjunction psychological & psychiatric support & re-housing Highlights the need for regular dietetic review & consideration of the wider issues

Conclusions If the patient remains cachectic adding additional kcal for weight gain is unlikely to be of any clinical benefit Our opinion is if the tumour has been removed/ treated/ controlled & you meet nutritional requirements (BMR + adequate AF/ PAL factor) & weight continues to decline, consider additional kcal for weight gain BUT, this is unlikely as few patients are entirely disease free/ controlled & ongoing weight loss is often a sign of disease progression/ recurrence

Summary Cancer is increasingly becoming a chronic / “long term” condition The evidence for the nutritional requirements of this patient group is limited & are reliant on estimation Dietetic interventions need to be individualised as no two cancer patients journey are the same Regular reassessment is vital in order to maximise the therapeutic potential of nutritional support