pranithi hongsprabhas md. nutrition in cancer. weight loss in cancer patients 50% of ca pt lose wt ~...
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Pranithi Hongsprabhas Pranithi Hongsprabhas MD.MD.
Nutrition in Nutrition in CancerCancer
Weight Loss in Cancer PatientsWeight 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 Frequency/Severity of Weight Loss Associated with CancerLoss Associated with Cancer
0
10
20
30
40
50
60
70
80
90
100
Colon Prostate SCLC NSCLC Pancreas Nonmeasurable
gastric
Mesurablegastric
Severe
Moderate
Minimal
DeWys et al. Am J Med 1980;69:491
CancerCancer Cachexia: MythCachexia: 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 Progression of Cancer-induced Weight LossWeight Loss
Normal
Mild Weight Loss/ Anorexia
Moderate Weight Loss/
Reduced activity
Severe Weight Loss/
Cachectic State
Death
Metabolic Changes
Below IBW Muscle Wasting Obvious
Reduced Survival
Initiating Factors
Cancer CachexiaCancer 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
Long CL et al. JPEN 1979;3:452-456
010 20 30 40
Partial Starvation
Days
Nitr
ogen
Exc
retio
n (g
/day
)
12
8
44
Total Starvation
Normal Range
Energy Expenditure in Starvation
Metabolic Response to Metabolic Response to StarvationStarvation
Hormone
Norepinephrine
Norepinephrine
Epinephrine
Thyroid Hormone T4
Source
Sympathetic Nervous System
Adrenal Gland
Adrenal Gland
Thyroid Gland (changes to T3 peripherally)
Change in Secretion
Landberg L, et al. N Engl J Med 1978;298:1295.
Hormonal Response to Starvation
Cancer Cachexia Anorexia Cancer Cachexia Anorexia Syndrome (CACS)Syndrome (CACS)
Cachexia
Abdominal pain
Depression
Constipation
Radio/chemotherapy, surgery side effects
Taste alteration
Malabsorption
Intestinal obstruction
Derangement of Metabolism
Lipolysis
TNF-, IFN- increase of leptin & altered orexegenic and anorexegenic signals
LIF, TGF-β
Increased
• Lipolysis/lipid metabolism
• Proteolysis
• REE
Decreased
• Lipogenesis
• LPL activity
• Protein synthesis
Does cancer influence energy Does cancer influence energy expenditure?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 MetabolismCarbohydrate Metabolism
1925 Cori & Cori demonstrate decreased glucose level
High anaerobic glycolysis Glucose to lactate
Increased lactate levelLactate
Oxidized 15 % Regenerate to glucose 85%
CHO MetabolismCHO Metabolism
Gluconeogenesis: increasedLactate, glycerol, alanineCannot be suppressed by glucose supplement
Decreased glucose tolerance: insulin resistance
Lipid MetabolismLipid Metabolism
Depletion of fat storeThe proportion of wt loss:
fat lossAssociated with
hypertriglyceridemia
MechanismMechanism
Increased lipolysis Increased FFA and glycerol
turnoverNormal or increased lipid
oxidationDecreased lipid clearance
Decreased lipoprotein lipase (LPL) activity
Protein MetabolismProtein Metabolism
Increased protein metabolismWhole body protein turnover:
unchangedMuscle tissue: largest pool
Muscle protein loss, muscle wasting
Decreased protein synthesis
Cancer induced weight loss vs. Cancer induced weight loss vs. other types of weight lossother types of weight loss
Cancer induced
Caloric deficiency
Body weight Lean body mass Body fat Caloric intake TEE REE Protein degradation
Acute phase response
--
Proteolysis inducing factors (PIF)
--Adapt from Kolter DP, Ann Int Med 2000;133:622
Does nutritional status influence Does nutritional status influence the clinical course and the the clinical course and the prognosis?prognosis?Reduce QOLLower activity levelIncrease treatment related
adverse reactionsReduce tumor response to
treatmentReduce survival
What are specific nutritional What are specific nutritional goals in cancer patients?goals in cancer patients?
Prevent and treating undernutrition
Enhancing anti-tumor treatment effects
Reducing adverse effects of anti-tumor Rx
Improve QOL
Energy requirementEnergy requirement
If REE cannot be measured, use rule of thumb
Ambulant pt: 30-35 kcal/kg/dBedridden pt: 20-25 kcal/kg/d
Oncological Rx may modulate EE
Do cancer patients require a Do cancer patients require a distinct nutrient composition?distinct nutrient composition?
Standard formula are recommended for EN of cancer ptProtein 1 g/kg/d (minimum)1.2-2 g/kg/dSupplement with electrolyte,
vitamins and trace element acording to RDA
When should EN be When should EN be started?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 Can EN maintain or improve nutritional status in cancer nutritional status in cancer patients?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, 20042. 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 Can EN maintain or improve nutritional status in cancer nutritional status in cancer patients?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 challengesTherapeutic challenges
Cancer induced weight loss Metabolic
abnormalities
Other types of weight loss (caloric deprivation) Mechanical causes Treatment related causes Pcycholocical issues
Provision of energy and protein can
promote weight gain
No weight gain, even when added energy and protein provided
Ottery FD Cancer Practice 1994;2:123
Can metabolic modulators Can metabolic modulators increase nutritional intakeincrease nutritional intake
Steroids (short term) Improve appetite Nausea Pain
Mechanisim: TNF-, IL-1ADR: PUD, osteoporosis
Progesterone Improve appetite Wt gain QOL
Megestorol acetate, Medroxy- progesteone acetate
ADR: fluid retention, thromboembolism
Can metabolic modulators Can metabolic modulators increase nutritional intakeincrease 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
Can metabolic modulators Can metabolic modulators increase nutritional intakeincrease nutritional intake
Does supplementation with Does supplementation with ωω-3 fatty -3 fatty acid have beneficial effect in cancer acid have beneficial effect in cancer patients?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 situationSpecial situation
Perioperative ENRadiotherapyChemotherapyTransplantationAdvance stage/ incurable
PerioperativePerioperative
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
RadiotherapyRadiotherapy
-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
34 2000 137 168Critical Reviews in Oncology:Hematology ( ) –
Is there indication for EN during Is there indication for EN during radiotherapy (XRT)or combined radiotherapy (XRT)or combined radiotherapy(cXRT)?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
NoRoutine EN during CTX has no
effect on tumor response nor CTX associated unwanted effects (b)
Is there indication for EN Is there indication for EN during chemotherapy?during chemotherapy?
ESPEN guidelines on EN Clin Nutr 2006
Bone Marrow Bone Marrow TransplantationTransplantation 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 Is there an indication for EN in advanced stages of incurable advanced stages of incurable cancer patients?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 ENRisk of EN
Does EN feed the tumor?No reliable dataTheoretical considerations
shouldNo influence of the decision to
feed a cancer patient
ConclusionConclusion
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
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