Nutritional Management of the Cancer Patient

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Nutritional Management of the Cancer Patient

• Joel Mason, M.D.
• Associate Professor of Medicine and Nutrition,
  Divisions of Gastroenterology and Clinical
  Nutrition, Tufts University

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topics of discussion

• The extent of protein-calorie malnutrition (PCM)
  among cancer pts
• The clinical ramifications of PCM
• How to detect clinically significant levels of
  PCM
• Is it worthwhile addressing the issue in the
  cancer patient and, if so, how?

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Survey of 477 cancer patients prevalence of
protein-calorie malnutrition(PCM)
site malnourished (gt10 loss of
UBW) stomach 89 esophagus 78 pancreas
58 colorectal 36 head neck 52 lung
31 breast 10 ovary 25 prostate 17
uterus 31 overall
30 Ann Oncol 2007
odds ratio of PCM with cancers of digestive tract
or head neck 3.2 (C.I. 2.0-5.2)
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Adverse clinical consequences of weight loss in
cancer case-control and prospective cohort trials

• outcome study
• diminished survival Ann Surg. 2004 240(4)
  719
• Am J Med 198069491
• Eur J Cancer 199834503
• Cancer 199986519
• Hepatogastro 199946103
• decreased response to chemoRx Arch Otolaryngol
  Head Neck Surg
• and XRT 1998124871875
• Eur J Cancer 199834503
• increased perioperative morbidity J Surg Oncol
  199249163
• worse quality of life Eur J Cancer 199834503
  

5
Adverse clinical consequences of weight loss in
cancer case-control and prospective cohort trials

• outcome study
• diminished survival Ann Surg. 2004 240(4)
  719
• Am J Med 198069491
• Eur J Cancer 199834503
• Cancer 199986519
• Hepatogastro 199946103
• decreased response to chemoRx Arch Otolaryngol
  Head Neck Surg
• and XRT 1998124871875
• Eur J Cancer 199834503
• increased perioperative morbidity J Surg Oncol
  199249163
• worse quality of life Eur J Cancer 199834503
  

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Factors that contribute to the development of
protein-calorie malnutrition in the cancer
patient

• Alterations in metabolism
• increases in protein catabolism
• inefficiency in energy consumption/increases in
  overall caloric expenditure

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Factors that contribute to the development of
protein-calorie malnutrition in the cancer
patient

• Alterations in metabolism
• increases in protein catabolism
• inefficiency in energy consumption/increases in
  overall caloric expenditure
• Alterations in physiology
• malabsorption/maldigestion due to tumor or to
  therapy
• constipation/gastrointestinal dysmotility due to
  surgical ablation of autonomic innervation of gut
  or to narcotics and sedatives
• Insufficient dietary intake
• suppression of appetite
• mediated by cytokines, other humoral factors
• mediated by emotional depression
• mediated by loss of taste sensation (neural
  destruction, drug effects, paraneoplastic
  syndrome)
• learned aversion to eating due to adverse
  symptoms
• nausea, vomiting, other symptoms due to surgery,
  radiation, or chemotherapy
• Physical impairment of deglutition
• effects on chewing or swallowing mechanisms
• reduction in saliva production (tumor invasion,
  effects due to surgery, radiation, or drugs)
• mass effect of tumor
• radiation- or chemotherapy-induced mucositis
• surgical interruption of swallowing mechanism

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normal
body protein pool
catabolism (250 gms protein/day)
synthesis
amino acid pool
dietary replacement
gluconeogenesis urea
Wasting in cancer
body protein pool
catabolism (up to 700 gms protein/day)
synthesis
amino acid pool
dietary replacement
gluconeogenesis urea
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Protein-calorie malnutrition a body compartment
perspective
Fat mass somatic lean mass visceral lean
mass Simple starvation
/-
Wasting in cancer
/
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Relationship Between Body Weight Loss and Loss of
Total Body Protein
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(No Transcript)
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gt10 unintentional loss of usual body weight a
convenient and suitable means of defining
substantial malnutrition

• Associated with a 15-20 loss of body cell mass
• Beyond this threshold, physiologic functions are
  adversely affected
• Beyond this threshold, clinical outcomes are also
  significantly worse

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• Creatinine-height Index a
• measure of skeletal muscle
• mass and a means of detecting PCM
• calculation 24 hour urinary creatinine/ideal
  value for height and gender
• values lt80 of ideal moderate-to-severe PCM

JPEN J Parenter Enteral Nutr 197711122
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Alterations in Energy and Protein Metabolism
During Wasting in Cancer Mediators

• Cytokines immune cells activated by neoplasm
  TNF-?, interleukin-1, 2 and 6, gamma-interferon
• ? peripheral lipolysis and hepatic lipogenesis
• ? energy expenditure, increased proteolysis
• Proteolysis-inducing factor
• glycoprotein produced by the cancer cells, found
  in urine of cachectic cancer pts but not those
  w/o cachexia, and not those whose cachexia is due
  to other diseases
• ? reproducibilty
• Lipid-mobilizing factor
• ? peripheral lipolysis (release of fatty acids
  and glycerol)
• ?peripheral lipogenesis
• produced both by neoplastic cells, which can also
  stimulate its expression in adipocytes
• Nature 1996379739742
• Br J Cancer 200184 1599-1601
• Proc Natl Acad Sci USA 2004101 2500-05

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How does one determine whether a given patient
warrants intensive nutrition support?
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How does one determine whether a given patient
warrants intensive nutrition support?

• using whatever practical means is necessary to
  adequately meet the nutritional needs of the
  patient

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Under what conditions does aggressive nutrition
support benefit the cancer patient an
evidence-based approach

• The malnourished patient about to undergo major
  surgery
• A patient (malnourished or not) about to undergo
  bone marrow transplantation
• A patient about to undergo XRT or chemotherapy
• improved quality of life proven but not a
  decrease in morbidity or mortality

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Cumulative Incidence of Complications Within 30
Days After Randomization VA Cooperative Study
Adapted from New Engl J Med 1991325525
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A randomized clinical trial of perioperative TPN
in malnourished patients with GI cancers
undergoing curative resection, n90
non-infectious cxs mortality
TPN 12?? 0? Control 34
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10 days of pre-op tpn/9 days of postop tpn
versus ad lib pre-op/1000 kcal/d 85 g protein/d
postop ?p 0.05 ??p 0.02
J Parent Ent Nutr 200024 7
Similarly, in a RCT of 124 pts undergoing
curative resection hepatocellular CA, the
group receiving pre- postop TPN had a RR of
overall cxs of 0.66 (CI0.45-0.96), and a RR of
infectious cxs of 0.57 (CI0.34-0.96). NEJM
19943311547
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Does use of TPN (vs. no nutritional support) in
ill patients benefit their hospital course a
meta-analysis of 26 randomized controlled trials
TPN possesses significant benefit
J.A.M.A 19982802013
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Enteral vs. parenteral nutrition in malnourished
cancer patients a multicenter trial
317 malnourished patients about to undergo
curative resection for GI cancers at 10 centers,
randomized to isocaloric and isonitrogenous
regimens, to begin within 24 hours after
surgery overall postop cxs infectious
cxs postop LOS enteral 34, RR0.7,
plt0.01 16, RR0.59, plt0.02 13.4 d,
plt0.01 parenteral 49 27
15.0
Lancet 20013581487
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Aggressive nutritional support in cancer
patients additional features

• Initiating nutritional support prior to surgery
  (typically gt7 days) is superior to starting
  postoperatively. If the latter is pursued,
  nutritional support must begin within 24 hours
  after surgery to demonstrate a benefit.
• Studies with stable isotopic labelling of amino
  acids demonstrate that significant and
  substantial improvements of protein synthesis are
  achieved in patients with cancer
• Studies in animals show tumor growth can be
  stimulated by provision of nutrition (and human
  studies confirm increased proliferation in the
  tumor) but this should not present a problem if
  patient is undergoing curative Rx, and may even
  present an advantage

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Characteristics of immunomodulatory enteral
formulas (Impact?, Immun-Aid?)

• functions
• delivers nutritional requirements
• modulate immune system (neutraceutical)
• nutritional ingredients present in pharmacologic
  quantitites
• arginine
• ?-3 fatty acids
• glutamine
• nucleotides

Impact Advanced Recovery is the only product
that can be used orally
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A meta-analysis of malnourished cancer patients
undergoing elective surgery
9 randomized controlled trials, conducted
1992-1999, comparing preop use of IEFs to
standard enteral formulas
mortality infections hospital stay 0.99
(0.42-2.34) 0.53 (0.42-0.68) -3.4d (-4.6--2.2)

JAMA 2001286944
In a large RCT (n305), pre-operative
administration with 1 L/day for 5 days prior to
surgery was as effective in reducing postop
infections and LOS as same regimen given for
additional 9 days after surgery. Both were far
superior to standard IV therapy. Conducted in
pts with lt10 weight loss! Gastroenterology
2002 122763
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Summary

• Protein-calorie malnutrition is common amongst
  cancer patients and is associated with poorer
  outcomes. GI and head neck cancers have the
  highest prevalence
• The cause of the malnutrition is multifactorial
  but, like malnutrition in the acutely ill
  patient, it is characterized by disproportionate
  contraction of lean mass
• Stratification of the cancer patient by
  nutritional status is easily done, and is
  constructive since the provision of aggressive
  nutritional support will improve outcomes in
  select groups of malnourished patients
• The use of immunoenhancing formulas is indicated
  in malnourished preoperative cancer patients
  since it diminishes perioperative complications