Transcript Update in Clinical Nutrition

Nutrition in Cancer
Pranithi Hongsprabhas MD.
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
Frequency/Severity of Weight
Loss Associated with Cancer
100
Severe
90
Moderate
80
Minimal
70
60
50
40
30
20
10
0
Colon
Prostate
SCLC
DeWys et al. Am J Med 1980;69:491
NSCLC
Pancreas
Non
measurable
gastric
Mesurable
gastric
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
Progression of Cancer-induced
Weight Loss
Initiating
Factors
Normal
Mild Weight
Loss/ Anorexia
Metabolic
Changes
Moderate
Weight Loss/
Reduced activity
Below IBW
Severe Weight
Loss/ Cachectic
State
Muscle Wasting
Obvious
Death
Reduced
Survival
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
Metabolic Response to
Starvation
Hormonal
Response
Starvation
Energy Expenditure
in to
Starvation
Nitrogen Excretion (g/day)
Hormone
12
Source
Change in Secretion
Norepinephrine
Sympathetic Nervous System
Norepinephrine
Adrenal Gland
Epinephrine
8
Thyroid Hormone T4


Normal Range
Adrenal Gland


Thyroid Gland (changes to T3
peripherally)
Partial Starvation
4
Total Starvation
0
10
20
Days
30
40
Long CL et al. JPEN 1979;3:452-456
Landberg L, et al. N Engl J Med 1978;298:1295.
Cancer Cachexia Anorexia
Syndrome (CACS)
Abdominal pain
Malabsorption
Taste alteration
Depression
Cachexia
Constipation
Radio/chemotherapy,
surgery side effects
Intestinal
obstruction
Derangement of
Metabolism
Increased
Decreased
• Lipolysis/lipid metabolism
• Lipogenesis
• Proteolysis
• LPL activity
• REE
• Protein synthesis
Lipolysis
TNF-, IFN-
LIF, TGF-β
increase of leptin
& altered orexegenic and
anorexegenic signals
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
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%
CHO Metabolism
Gluconeogenesis: increased
 Lactate,
glycerol, alanine
 Cannot be suppressed by
glucose supplement
Decreased glucose tolerance:
insulin resistance
Lipid Metabolism
Depletion of fat store
The proportion of wt loss: fat
loss
Associated with
hypertriglyceridemia
Mechanism
 Increased lipolysis
 Increased
FFA and glycerol
turnover
 Normal or increased lipid oxidation
 Decreased lipid clearance
 Decreased
activity
lipoprotein lipase (LPL)
Protein Metabolism
 Increased protein metabolism
 Whole body protein turnover:
unchanged
 Muscle tissue: largest pool
 Muscle
protein loss, muscle wasting
 Decreased protein synthesis
Cancer induced weight loss vs.
other types of weight loss
Cancer induced
Caloric deficiency


Lean body mass
Body fat
Caloric intake
TEE








REE
Protein degradation
Acute phase response





Body weight
Proteolysis inducing
factors (PIF)

Adapt from Kolter DP, Ann Int Med 2000;133:622
-
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
What are specific nutritional goals
in cancer patients?
 Prevent and treating undernutrition
 Enhancing anti-tumor treatment
effects
 Reducing adverse effects of antitumor Rx
 Improve QOL
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
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
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 (<60%) to
eat for > 10 d
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
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
Therapeutic challenges
 Other types of weight
loss (caloric
deprivation)



Mechanical causes
Treatment related causes
Pcycholocical issues
Provision of energy
and protein can
promote weight gain
Ottery FD Cancer Practice 1994;2:123
 Cancer induced weight
loss

Metabolic
abnormalities
No weight gain, even
when added energy
and protein provided
Can metabolic modulators
increase nutritional intake
Steroids (short term)
 Improve
appetite
 Nausea
 Pain
 Mechanisim:  TNF-, IL-1
 ADR: PUD, osteoporosis
Can metabolic modulators
increase nutritional intake
Progesterone
Improve appetite
 Wt gain
 QOL

 Megestorol acetate, Medroxy- progesteone
acetate
 ADR: fluid retention, thromboembolism
Can metabolic modulators
increase nutritional intake
 ω 3 fatty acid
 ω 3 fatty acid: less active pro-inflammatory
midiators
 Improve appetite and body weight
 Antagonized: Lipid mobilizing factors,
proteolysis inducing factors
Does supplementation with ω-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
Special situation
 Perioperative EN
 Radiotherapy
 Chemotherapy
 Transplantation
 Advance stage/ incurable
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
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 Oncology:Hematology 34 (2000) 137–168
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 H&N 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
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
Bone Marrow Transplantation
 Nutritional consequences of BMT
N&V, mucositis, diarrhea
 Venooclusive disease (VOD)
 Graft vs. host dis (GVHD)
 Metabolic abnormalities





Increased protein metabolism
Hyperglycemia
Hypertriglyceridemia
Electrolyte abnormalities
 TPN: indicated
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
Risk of EN
 Does EN feed the tumor?
 No
reliable data
 Theoretical considerations should
 No influence of the decision to feed
a cancer patient
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