Pranithi Hongsprabhas MD.

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Pranithi Hongsprabhas MD.

• Nutrition in Cancer

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Weight Loss in Cancer Patients

• 50 of CA pt lose wt
• 70 of terminal stage CA pt
• Wt loss is prognostic significant

Kondrup AJCN 2002, De Wys et al. Am J Med 1980,
Andreyev et al. Eur J Cancer 1998
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Frequency/Severity of Weight Loss Associated with
Cancer
DeWys et al. Am J Med 198069491
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Cancer Cachexia Myth

• Anorexia-cachexia syndrome is due to the host
  lack of appetite and or starvation
• Anorexia-cachexia happens because of tumor
  consumes the host nutrients

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Progression of Cancer-induced Weight Loss
Normal
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Cancer Cachexia

• Syndrome of combined physiologic, metabolic and
  psychological factors
• Manifestations
• anorexia
• progressive involuntary wt loss, wasting, tissue
  depletion
• Fatigue, poor performance
• Anemia
• More advance disease higher risk of wt loss

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Metabolic Response to Starvation

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Cancer Cachexia Anorexia Syndrome (CACS)
Abdominal pain
Malabsorption
Depression
Cachexia
Taste alteration
Constipation
Radio/chemotherapy, surgery side effects
Intestinal obstruction
Derangement of Metabolism

• Increased
• Lipolysis/lipid metabolism
• Proteolysis
• REE

• Decreased
• Lipogenesis
• LPL activity
• Protein synthesis

Lipolysis
TNF-?, IFN-?
increase of leptin altered orexegenic and
anorexegenic signals LIF, TGF-ß
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Does cancer influence energy expenditure?

• Cancer itself does not have consistent effect on
  REE
• Increased ¼ had 10 higher than predicted
• Unchanged
• Decreased ¼ had 10 lower than predicted

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Carbohydrate Metabolism

• 1925 Cori Cori demonstrate decreased glucose
  level
• High anaerobic glycolysis
• Glucose to lactate
• Increased lactate level
• Lactate
• Oxidized 15
• Regenerate to glucose 85

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CHO Metabolism

• Gluconeogenesis increased
• Lactate, glycerol, alanine
• Cannot be suppressed by glucose supplement
• Decreased glucose tolerance insulin resistance

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Lipid Metabolism

• Depletion of fat store
• The proportion of wt loss fat loss
• Associated with hypertriglyceridemia

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Mechanism

• Increased lipolysis
• Increased FFA and glycerol turnover
• Normal or increased lipid oxidation
• Decreased lipid clearance
• Decreased lipoprotein lipase (LPL) activity

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Protein Metabolism

• Increased protein metabolism
• Whole body protein turnover unchanged
• Muscle tissue largest pool
• Muscle protein loss, muscle wasting
• Decreased protein synthesis

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Liver Protein

• Increased hepatic protein synthesis
• Acute phase protein proportional to tumor growth

Intestinal Protein

• Decreased intestinal wt
• Net protein breakdown
• Decrease mucosal barrier intestinal permeability

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Protein turnover
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Cancer induced weight loss vs. other types of
weight loss
Adapt from Kolter DP, Ann Int Med 2000133622
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Does nutritional status influence the clinical
course and the prognosis?

• Reduce QOL
• Lower activity level
• Increase treatment related adverse reactions
• Reduce tumor response to treatment
• Reduce survival

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What are specific nutritional goals in cancer
patients?

• Prevent and treating undernutrition
• Enhancing anti-tumor treatment effects
• Reducing adverse effects of anti-tumor Rx
• Improve QOL

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Energy requirement

• If REE cannot be measured, use rule of thumb
• Ambulant pt 30-35 kcal/kg/d
• Bedridden pt 20-25 kcal/kg/d

• Oncological Rx may modulate EE

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Do cancer patients require a distinct nutrient
composition?

• Standard formula are recommended for EN of cancer
  pt
• Protein 1 g/kg/d (minimum)
• 1.2-2 g/kg/d
• Supplement with electrolyte, vitamins and trace
  element acording to RDA

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When should EN be started?

• If undernutrition already exists
• If it is anticipated that Pt will be unable to
  eat for 7 d
• If an inadequate food intake (
  10 d

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Can EN maintain or improve nutritional status in
cancer patients?

• Yes In wt lost patients from insufficient
  intake
• Gain more wt, lost less wt1
• improve or maintain nutritional status2
• maintain QOL

1. Systematic review of ONS, counceling Baldwin
et al, 2004 2. Cancer cachexia and GI cancer
Bozzetti F1989 and Lindh A 1986. 3. GI and H
neck cancer. Isenring EA, 2004
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Can EN maintain or improve nutritional status in
cancer patients?

• In the presence of inflammation
• Extremely difficult to achieve anabolism
• Without effective antitumor Rx ?
  impossible to reverse process
• At least to maintain wt or minimize wt loss
• Additional intervention pharmacological effort
  recommended to modulate inflammatory response

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Therapeutic challenges

• Cancer induced weight loss
• Metabolic abnormalities

• Other types of weight loss (caloric deprivation)
• Mechanical causes
• Treatment related causes
• Pcycholocical issues

No weight gain, even when added energy and
protein provided
Provision of energy and protein can promote
weight gain
Ottery FD Cancer Practice 19942123
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Can metabolic modulators increase nutritional
intake

• Steroids (short term)
• Improve appetite
• Nausea
• Pain
• Mechanisim ? TNF-?, IL-1
• ADR PUD, osteoporosis

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Can metabolic modulators increase nutritional
intake

• Progesterone
• Improve appetite
• Wt gain
• QOL
• Megestorol acetate, Medroxy- progesteone acetate
• ADR fluid retention, thromboembolism

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Can metabolic modulators increase nutritional
intake

• ? 3 fatty acid
• ? 3 fatty acid less active pro-inflammatory
  midiators
• Improve appetite and body weight
• Antagonized Lipid mobilizing factors,
  proteolysis inducing factors

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(No Transcript)
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Does supplementation with ?-3 fatty acid have
beneficial effect in cancer patients?

• RCT contradictory/controversial
• Evidence level C
• RCT
• improve survival/Non significant effect on wt
• Did not improve wt or appetite
• Non RCT improve survival, side effect of CTX
• Recent RCT high dose EPA wt stabilization, wt
  gain
• Unlikely to prolong survival in advance cancer
• The result of further trials are awaited

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Special situation

• Perioperative EN
• Radiotherapy
• Chemotherapy
• Transplantation
• Advance stage/ incurable

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Perioperative

• Severe nutritional risk benefit from SNS 10-14 d
  prior to major surgery even if surgery has to be
  delayed (A)
• All CA pt undergoing major abdominal surgery,
  preop EN preferably with immune modulating
  substreates 5-7 d independent of nutritional
  status (A)

ESPEN guidelines on EN Clin Nutr 2006
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Radiotherapy

• -ve effect of XRT on oral feeding
• early SNS may lead to complete course of Rx ?
  reduce morbidity in Rx of head neck cancer
• PN failed to improve survival, infectious
  complication and noninfectious complication in
  abd XRT
• EN reduce wt loss, digestive intolerance to abd
  and pelvic XRT

Critical Reviews in OncologyHematology 34 (2000)
137168
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Is there indication for EN during radiotherapy
(XRT)or combined radiotherapy(cXRT)?

• Yes, use intensive counceling and ONS to increase
  intake (A)
• to prevent Rx associated wt loss
• To prevent interuption of XRT
• in GI, head and neck area
• If obstructive HN or esophageal CA interferes
  with swallowing tube feeding is preferred
• TF is preferred if local mucositis is expected
  (c)
• Routine EN is not indicated during XRT of other
  body regions (c)

ESPEN guidelines on EN Clin Nutr 2006
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Is there indication for EN during chemotherapy?

• No
• Routine EN during CTX has no effect on tumor
  response nor CTX associated unwanted effects (b)

ESPEN guidelines on EN Clin Nutr 2006
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Bone Marrow Transplantation

• Nutritional consequences of BMT
• NV, mucositis, diarrhea
• Venooclusive disease (VOD)
• Graft vs. host dis (GVHD)
• Metabolic abnormalities
• Increased protein metabolism
• Hyperglycemia
• Hypertriglyceridemia
• Electrolyte abnormalities
• TPN indicated

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Is there an indication for EN in advanced stages
of incurable cancer patients?

• EN should be provided in order to minimize wt
  loss, as long as pt consents and the dying phase
  has not started (c)
• When EOL is very close, most pt require only
  minimal of food and water to reduce thirst and
  hunger (b)

ESPEN guidelines on EN Clin Nutr 2006
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Risk of EN

• Does EN feed the tumor?
• No reliable data
• Theoretical considerations should
• No influence of the decision to feed a cancer
  patient

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Complementary and alternative mdicine (CAM)

• Current evidence CAM is more effective in
  relieving cancer-related symptoms in slowing
  disease progression.
• acupuncture for CTx related NV or for pain
• massage (except deep tissue or forceful) for
  anxiety or pain
• moderate exercise to minimize fatigue
• psychological and mind-body techniques
• reduction of animal and SFA, and addition of soy
  in the diet of well nourished men with prostate
  cancer.

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An CAM Rx should be discouraged if

• Delays conventional Rx
• No scientific prove
• Provided by unlicensed practitioner
• Require injection of substances not approved by
  FDA

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Conclusion

• Complete improvement of nutritional state is not
  attained in short time
• Cancer Rx should not be postponed until
  nutritional rehabilitation achieved
• Nutritional Rx should be incorporated in to the
  overall Rx as early as possible
• Effort to improve nutritional and metabolic
  status may ? morbidity and mortality in pts who
  need surgery, XRx, XR-CTx