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