Nutritional Management of the Cancer Patient

1. Nutritional Management of the Cancer Patient Joel Mason, M.D. Associate Professor of Medicine and Nutrition, Divisions of Gastroenterology and Clinical Nutrition, Tufts University

2. topics of discussion • The extent of protein-calorie malnutrition (PCM) among cancer pts • The clinical ramifications of PCM • How to detect clinically significant levels of PCM • Is it worthwhile addressing the issue in the cancer patient and, if so, how?

3. Survey of 477 cancer patients: prevalence of protein-calorie malnutrition(PCM) site % malnourished (>10 loss of UBW) stomach 89% esophagus 78 pancreas 58 colorectal 36 head & neck 52 lung 31 breast 10 ovary 25 prostate 17 uterus 31 overall = 30% Ann Oncol 2007 odds ratio of PCM with cancers of digestive tract or head & neck = 3.2 (C.I. 2.0-5.2)

4. Adverse clinical consequences of weight loss in cancer: case-control and prospective cohort trials outcome study diminished survival Ann Surg. 2004; 240(4): 719 Am J Med 1980;69:491 Eur J Cancer 1998;34:503 Cancer 1999;86:519 Hepatogastro 1999;46:103 decreased response to chemoRx Arch Otolaryngol Head Neck Surg and XRT 1998;124:871–875 Eur J Cancer 1998;34:503 increased perioperative morbidityJ Surg Oncol 1992;49:163 worse quality of lifeEur J Cancer 1998;34:503

5. Adverse clinical consequences of weight loss in cancer: case-control and prospective cohort trials outcome study diminished survivalAnn Surg. 2004; 240(4): 719 Am J Med 1980;69:491 Eur J Cancer 1998;34:503 Cancer 1999;86:519 Hepatogastro 1999;46:103 decreased response to chemoRxArch Otolaryngol Head Neck Surg and XRT1998;124:871–875 Eur J Cancer 1998;34:503 increased perioperative morbidityJ Surg Oncol 1992;49:163 worse quality of lifeEur J Cancer 1998;34:503

6. Factors that contribute to the development of protein-calorie malnutrition in the cancer patient • Alterations in metabolism • increases in protein catabolism • inefficiency in energy consumption/increases in overall caloric expenditure

7. Factors that contribute to the development of protein-calorie malnutrition in the cancer patient • Alterations in metabolism • increases in protein catabolism • inefficiency in energy consumption/increases in overall caloric expenditure • Alterations in physiology • malabsorption/maldigestion due to tumor or to therapy • constipation/gastrointestinal dysmotility due to surgical ablation of autonomic innervation of gut or to narcotics and sedatives • Insufficient dietary intake • suppression of appetite • mediated by cytokines, other humoral factors • mediated by emotional depression • mediated by loss of taste sensation (neural destruction, drug effects, paraneoplastic syndrome) • learned aversion to eating due to adverse symptoms • nausea, vomiting, other symptoms due to surgery, radiation, or chemotherapy • Physical impairment of deglutition • effects on chewing or swallowing mechanisms • reduction in saliva production (tumor invasion, effects due to surgery, radiation, or drugs) • mass effect of tumor • radiation- or chemotherapy-induced mucositis • surgical interruption of swallowing mechanism

8. normal body protein pool catabolism (~250 gms protein/day) synthesis amino acid pool gluconeogenesis + urea dietary replacement Wasting in cancer body protein pool catabolism (up to ~700 gms protein/day) synthesis amino acid pool dietary replacement gluconeogenesis + urea

9. Protein-calorie malnutrition: a body compartment perspective Fat mass somatic lean mass visceral lean mass Simple starvation +++ + +/- Wasting in cancer +++ +++ +/++

10. Relationship Between Body Weight Loss and Loss of Total Body Protein

12. >10% unintentional loss of usual body weight: a convenient and suitable means of defining substantial malnutrition • Associated with a 15-20% loss of body cell mass • Beyond this threshold, physiologic functions are adversely affected • Beyond this threshold, clinical outcomes are also significantly worse

13. Creatinine-height Index: a • measure of skeletal muscle • mass and a means of detecting PCM • calculation: 24 hour urinary creatinine/ideal value for height and gender • values <80% of ideal = moderate-to-severe PCM JPEN J Parenter Enteral Nutr 1977;1:11–22

14. Alterations in Energy and Protein Metabolism During Wasting in Cancer: Mediators • Cytokines: immune cells activated by neoplasm: TNF-, interleukin-1, 2 and 6, gamma-interferon •  peripheral lipolysis and hepatic lipogenesis •  energy expenditure, increased proteolysis • Proteolysis-inducing factor* • glycoprotein produced by the cancer cells, found in urine of cachectic cancer pts but not those w/o cachexia, and not those whose cachexia is due to other diseases • ? reproducibilty • Lipid-mobilizing factor# •  peripheral lipolysis (release of fatty acids and glycerol) • peripheral lipogenesis • produced both by neoplastic cells, which can also stimulate its expression in adipocytes *Nature 1996;379:739–742 *Br J Cancer 2001;84: 1599-1601 #Proc Natl Acad Sci USA 2004;101: 2500-05

15. How does one determine whether a given patient warrants intensive nutrition support?

16. How does one determine whether a given patient warrants intensive nutrition support? *using whatever practical means is necessary to adequately meet the nutritional needs of the patient

17. Under what conditions does ‘aggressive nutrition support’ benefit the cancer patient: an evidence-based approach • The malnourished patient about to undergo major surgery • A patient (malnourished or not) about to undergo bone marrow transplantation • A patient about to undergo XRT or chemotherapy* *improved quality of life proven but not a decrease in morbidity or mortality

18. Cumulative Incidence of Complications Within 30 Days After Randomization: VA Cooperative Study Adapted from: New Engl J Med 1991;325:525

19. A randomized clinical trial of perioperative TPN in malnourished patients with GI cancers undergoing curative resection, n=90 non-infectious cx’s mortality TPN* 12% 0% Control 34% 11% *10 days of pre-op tpn/9 days of postop tpn versus ad lib pre-op/1000 kcal/d + 85 g protein/d postop p = 0.05 p = 0.02 J Parent Ent Nutr 2000;24: 7 Similarly, in a RCT of 124 pts undergoing curative resection hepatocellular CA, the group receiving pre- + postop TPN had a RR of overall cx’s of 0.66 (CI=0.45-0.96), and a RR of infectious cx’s of 0.57 (CI=0.34-0.96). NEJM 1994;331:1547

20. Does use of TPN (vs. no nutritional support) in ill patients benefit their hospital course: a meta-analysis of 26 randomized controlled trials **TPN possesses significant benefit J.A.M.A 1998;280:2013

21. Enteral vs. parenteral nutrition in malnourished cancer patients: a multicenter trial 317 malnourished patients about to undergo curative resection for GI cancers at 10 centers, randomized to isocaloric and isonitrogenous regimens, to begin within 24 hours after surgery overall postop cx’s infectious cx’s postop LOS enteral 34%, RR=0.7, p<0.01 16%, RR=0.59, p<0.02 13.4 d, p<0.01 parenteral 49 27 15.0 Lancet 2001;358:1487

22. ‘Aggressive’ nutritional support in cancer patients: additional features • Initiating nutritional support prior to surgery (typically >7 days) is superior to starting postoperatively. If the latter is pursued, nutritional support must begin within 24 hours after surgery to demonstrate a benefit. • Studies with stable isotopic labelling of amino acids demonstrate that significant and substantial improvements of protein synthesis are achieved in patients with cancer • Studies in animals show tumor growth can be stimulated by provision of nutrition (and human studies confirm increased proliferation in the tumor) but this should not present a problem if patient is undergoing curative Rx, and may even present an advantage

23. Characteristics of ‘immunomodulatory’ enteral formulas (Impact, Immun-Aid) • functions • delivers nutritional requirements • modulate immune system (‘neutraceutical’) • nutritional ingredients present in pharmacologic quantitites • arginine • Ω-3 fatty acids • glutamine • nucleotides *Impact Advanced Recovery is the only product that can be used orally

24. A meta-analysis of malnourished cancer patients undergoing elective surgery 9 randomized controlled trials, conducted 1992-1999, comparing preop use of IEFs to standard enteral formulas mortality infections hospital stay 0.99 (0.42-2.34) 0.53 (0.42-0.68)* -3.4d (-4.6--2.2)* JAMA 2001;286:944 In a large RCT (n=305), pre-operative administration with 1 L/day for 5 days prior to surgery was as effective in reducing postop infections and LOS as same regimen given for additional 9 days after surgery. Both were far superior to standard IV therapy. Conducted in pts with <10% weight loss! Gastroenterology 2002; 122:763

25. Summary • Protein-calorie malnutrition is common amongst cancer patients and is associated with poorer outcomes. GI and head & neck cancers have the highest prevalence • The cause of the malnutrition is multifactorial but, like malnutrition in the acutely ill patient, it is characterized by disproportionate contraction of lean mass • Stratification of the cancer patient by nutritional status is easily done, and is constructive since the provision of aggressive nutritional support will improve outcomes in select groups of malnourished patients • The use of immunoenhancing formulas is indicated in malnourished preoperative cancer patients since it diminishes perioperative complications