Pranithi Hongsprabhas MD. Nutrition in Cancer

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 DeWys et al. Am J Med 1980;69:491

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 Normal Mild Weight Loss/ Anorexia Moderate Weight Loss/ Reduced activity Severe Weight Loss/ Cachectic State Death Metabolic Changes Below IBWMuscle Wasting Obvious Reduced Survival Initiating Factors

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

Long CL et al. JPEN 1979;3: Partial Starvation Days Nitrogen Excretion (g/day) Total Starvation Normal Range Energy Expenditure in Starvation Metabolic Response to Starvation Hormone Norepinephrine Epinephrine Thyroid Hormone T4 Source Sympathetic Nervous System 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 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 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 lipoprotein lipase (LPL) activity

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

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

Protein turnover Muscle breakdown Gut permeability

Cancer induced weight loss vs. other types of weight loss Cancer inducedCaloric 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 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 anti- tumor Rx Improve QOL

Energy requirement If REE cannot be measured, use rule of thumb Ambulant pt: kcal/kg/d Bedridden pt: 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) 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 ( 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 wt 1 improve or maintain nutritional status 2 maintain QOL 1. Systematic review of ONS, counceling Baldwin et al, Cancer cachexia and GI cancer Bozzetti F1989 and Lindh A 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 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 increase nutritional intake Steroids (short term) Improve appetite Nausea Pain Mechanisim:  TNF- , IL-1 ADR: PUD, osteoporosis

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 Can metabolic modulators increase nutritional intake

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 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

No Routine EN during CTX has no effect on tumor response nor CTX associated unwanted effects (b) Is there indication for EN during chemotherapy? 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

Complementary and alternative mdicine (CAM) Current evidence: CAM is more effective in relieving cancer-related symptoms > in slowing disease progression. acupuncture for CTx related N&V 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.

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

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