1. 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

2. 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

3. 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)

4. 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 people died from cancer in 2001 (

5. 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

6. Theories of Nutrition & Cachexia

7. 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)

8. 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

9. 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)

10. 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)

11. 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)

12. 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)

13. 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)

14. 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)

15. 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)

16. 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

17. 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

18. 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

19. 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)

21. Nutritional Requirements in Cancer

22. 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)

23. 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 kcals per day
(Hyltander et al., 1991)
If not compensated by ↑ energy intake results in loss of kg muscle mass & 0.5 – 1.0kg body fat / month
(Bozzetti F et al.,1980)
The challenge is identifying which patients

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

25. 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

26. 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)

27. 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 ( g Nitrogen per kg)
(Elia, 1990)

28. 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)

29. 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

30. Aims of Nutritional Support

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

32. ‘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)

33. 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)

34. 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)

35. 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)

36. 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

37. 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)

38. 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)

39. Nutrition Support Throughout the Cancer Patient’s Journey

40. Nutritional Support – Pre / Peri - Operative
Patient’s with severe undernutrition benefit from NS 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

41. 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

42. 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

43. Interactive Case Study

44. 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

46. 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 kg
Ideal weight kg
BMI- 19.7kg/m2
No recent weight loss
Grip strength 28.5kg
(<69% of normal)

47. 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

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

50. 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

51. 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)

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

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

56. 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/ kg

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

58. 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)

59. Would you add 400kcal for weight gain?

60. 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

63. 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

64. 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

65. 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