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besity, Insulin Resistance, and Cancerrognosis: Implications for Practice for Providingare among Cancer Survivors

IYATI PAREKH, PhD, RD*; TOMOKO OKADA, MS, RD, CNSC; GRACE L. LU-YAO, PhD, MPH

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he number of cancer survivors is steadily increasing.The American Cancer Society (ACS) recently reportedthat the 5-year relative survival rate for all cancers

ombined is 66% (1). The National Cancer Institute esti-ates that there are approximately 11 million cancer sur-

ivors, defined as individuals with a cancer diagnosis re-ardless of the course of the illness, until the end of their life2). These numbers are projected to double by 2050 (3).ancer is currently the leading cause of death among indi-iduals younger than 85 years of age (4,5). Overall, it is theecond leading cause of death, responsible for one in foureaths in the United States (4). In fact, cancer is expected toe the top cause of death in the United States by 2010,urpassing cardiovascular disease (6).

The prevalence of obesity has increased in parallel toancer, reaching epidemic proportions in the United States,ith approximately 70% of the population being obese orverweight (7). Scientific evidence suggests that obesity isredictive of poor cancer prognosis among cancer survivors.dipocytes, once thought of as passive depots of excess fat,re now collectively recognized as an active endocrine organhat secretes adipokines. Adipokines are a group of proteinsith signaling properties and include leptin, proinflamma-

ory proteins, and adiponectin, each of which is hypothe-ized to play a role in cancer biology (8).

Certified in India.. Parekh is an assistant professor, Department of Nu-

rition, Food Studies, and Public Health, New Yorkniversity, New York. T. Okada is a clinical dietitian,epartment of Food and Nutrition Services, Memorialloan-Kettering Cancer Center, New York, NY. G. L.u-Yao is an associate professor, Gallo Prostate Cancerenter, The Cancer Institute of New Jersey, New Bruns-ick; she is also an associate professor, University ofedicine and Dentistry of New Jersey–Robert Wood

ohnson Medical School, Department of Medicine, andhe School of Public Health, University of Medicine andentistry of New Jersey, Piscataway.Address correspondence to: Grace L. Lu-Yao, PhD,PH, The Cancer Institute of New Jersey, University ofedicine and Dentistry of New Jersey, 195 Little Albanyt, Room 5534, New Brunswick, NJ 08901. E-mail:

uyaogr@umdnj.eduManuscript accepted: March 13, 2009.Copyright © 2009 by the American Dietetic

ssociation.0002-8223/09/10908-0001$36.00/0

Fdoi: 10.1016/j.jada.2009.05.001

346 Journal of the AMERICAN DIETETIC ASSOCIATION

Insulin resistance, characterized by hyperinsulinemiand frequently accompanied by impaired glucose tolerance,s also associated with obesity (9). Insulin resistance is es-imated to be prevalent among approximately one in threemerican adults (9). Insulin has been implicated in cancerrogression by virtue of its proliferative and proinflamma-ory properties (8). Epidemiologic evidence collectively sug-ests that obesity and insulin resistance may be a high-risktate for disease progression among cancer survivors (dis-ussed later), implying that the trajectory of care within thisopulation needs urgent attention. The Institute of Medi-ine has identified cancer surveillance and control as a topublic health priority (10).Modifiable lifestyle interventions targeting energy bal-

nce and insulin resistance are measures that may besed as important cancer-control tools. The following sec-ions provide an overview of the hypothesized underlyingiological mechanisms that link obesity and insulin re-istance with cancer progression. Epidemiologic evidences presented from studies that have investigated thesessociations. Further, potential practice implications areuggested for all dietetics practitioners, board-certifiedpecialists in oncology nutrition, and other health-careroviders to alter dietary, lifestyle, and behavioral factorsn an attempt to delay cancer progression or mortalitymong the large at-risk population of cancer survivors.

UTATIVE BIOLOGICAL MECHANISMSeveral adipocyte-derived cytokines have been suggestedo act as a link between obesity, insulin resistance, andancer. The potential biological role of insulin and thesedipokines in cancer progression, and how they mightork in concert to promote tumor growth, are summa-

ized in this section (Figure 1).

nsulin, Insulin-Like Growth Factor-1 (IGF-1), and IGF-1 Bindingrotein 3 Axis (IGFBP-3)nsulin is an anabolic hormone that may stimulate cellroliferation and cancer progression via multiple path-ays: (a) Insulin may increase production of IGF-1 via

he growth hormone mechanism (8). (b) Insulin mightncrease free IGF-1 levels, making more IGF-1 availableo bind to its receptors on normal and cancer cells. Thiseceptor-bound IGF-1 modulates cell proliferation andurvival. (c) Together, insulin and IGF-1 may stimulateroduction of adipocyte-derived vascular endothelialrowth factor (VEGF), a critical angiogenic factor thatnfluences endothelial cell survival and migration (11).

urthermore, IGFBP-3, the most predominant IGF bind-

© 2009 by the American Dietetic Association

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ng protein in serum, regulates the function of IGF-1hrough the inhibition of the IGF-1 receptor (12). IGFBP-3s hypothesized to act as a tumor suppressor and inhibitell growth by sequestering free IGFs as well as by inhib-ting IGF-independent effects on cell growth (12).

The interplay of several factors seem to contribute tonsulin resistance and may include sedentary lifestyles,ody weight, high-calorie diets, saturated fat intake,igher socioeconomic status, and inflammation, specifi-ally tumor necrosis factor-� (TNF-�) and existing cancer13,14). In addition, higher concentrations of free fattycids among obese individuals have also been implicatedn decreasing insulin sensitivity (15).

eptineptin, an adipokine found among obese individuals atigher concentrations, is the key player in energy balancend appetite control (16). Leptin induces expression ofEGF, which is responsible for cancer progression via itsotent proangiogenic effect (11) and has been shown tonduce cell migration and expression of growth factors inuman prostate cancer cells in vitro (17). Laboratoryvidence shows that leptin promotes proliferation and

Lifestyle modificati

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igure 1. Potential mechanisms of obesity, insulin resistance, anddipocyte-derived cytokines (adipokines), inflammatory factors, insulinromote tumor growth. Insulin resistance seems central to the pathwahrough lifestyle modification, specifically consumption of healthier dietNF-��tumor necrosis factor �; PGE2�prostaglandin E-2; IL-6 ,-8,CP-1�monocyte chemoattractant protein 1; VEGF�vascular endoth

rowth factor binding protein 3.

nvasiveness of endometrial cells (18). Furthermore, it t

nterferes with insulin signaling and is associated withigher concentrations of circulating insulin (19), whichas proliferative properties.

roinflammatory Adipokinest has been hypothesized that cancer progression is closelyelated to chronic inflammation and impaired cytokineunctioning (20). Furthermore, obese individuals haveigher levels of inflammatory markers accompanied by de-angements of insulin metabolism (21). Proinflammatoryactors produced by adipocytes include prostaglandin E-2,NF-�, interleukin (IL)-6, IL-8, IL-10, macrophage inflam-atory protein-1, and monocyte chemoattractant protein-1

22,23). These factors produce a cellular environment con-ucive to survival and growth of cancer cells. In addition,NF-� stimulates VEGF production, which is key to tumorrowth, via angiogenesis (8). One epidemiologic study sup-orts the link between cancer mortality and higher levels ofnflammatory markers (24).

diponectindiponectin, another major adipokine that plays a role in

iet and physical activity

adipose tissue

sistance

Free fatty acids Leptin

VEGF

↑ Angiogenesis1:IGBP3 ratio

r growth

ted biomarkers in cancer progression. This figure illustrates howthe insulin-like growth factor-1 (IGF-1) axis, might work in concert tomoting tumor growth. Management of insulin resistance and obesityincreased physical activity, may prevent or delay cancer progression.interleukin-6, -8, -10; MIP-1�macrophage inflammatory protein 1;growth factor; IGF-1:IGBP3�insulin-like growth factor 1:insulin-like

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August 2009 ● Journal of the AMERICAN DIETETIC ASSOCIATION 1347

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ator of inflammatory response and insulin sensitivity.diponectin concentrations are inversely associated with

nsulin resistance, body weight, and inflammatory re-ponse (23). Recent evidence from laboratory studies sug-ests that adiponectin is an important inhibitor of prolif-ration, either through its anti-inflammatory role,nfluence on insulin sensitivity, or by acting directly onancer cells to increase apoptosis (25). Some studies sug-est that adiponectin might have an antiangiogenic po-ential (25). Evidence from human studies, although lim-ted, is consistent with the laboratory evidence. Forxample, results from several small case-control studiesn�30 to 236) revealed that lower adiponectin concentra-ions were associated with more advanced breast cancer26) and prostate cancer (27,28).

PIDEMIOLOGIC EVIDENCE OF OBESITY AND INSULINESISTANCE AND CANCER PROGRESSION, DISEASEECURRENCE, AND MORTALITYbesityvidence suggests that obesity is associated with cancerrogression, recurrence of disease, and mortality. Perhapshe best evidence of obesity and cancer mortality comesrom a large prospective national study (n�900,000) in anCS cohort with a 16-year follow-up. This study reported anpproximately 50% to 60% higher prevalence of mortalityrom all cancers combined and multiple site-specific cancersmong morbidly obese (body mass index [BMI] �40) partic-pants vs those within the normal weight range, after ad-usting for demographic, dietary, and lifestyle factors (29).imilarly, in another study of two large ACS cohorts of men

n�816,268), there was an approximately 25% increase inrostate cancer mortality in obese (BMI �30) vs nonobeseen, after adjusting for age, race, exercise, smoking status,

nd family history of prostate cancer (30).Furthermore, a 35-year prospective cohort study

mong London-based men (n�18,403), noted an in-reased risk of dying from cancers of the colon, rectum,iver, and lymphoma among men with increased bodyeight, with hazard ratios ranging from 1.3 to 2.9 afterdjusting for a range of covariates, including socioeco-omic status and physical activity, although not alwaystatistically significant (31). Studies have suggested thatxcess body fat is a negative prognostic factor for prostateancer progression, with patients having faster biochem-cal failure (measured using prostate-specific antigen con-entrations over time, as a surrogate for disease recur-ence), positive surgical margins, and mortality (32-34).

nsulin Resistancelthough there are several plausible biological mecha-isms that link insulin resistance to cancer progressionr mortality, there are fewer epidemiologic studies thatave investigated these associations. The existing evi-ence collectively reports detrimental associations be-ween insulin resistance and cancer biology. For example,here is robust evidence from the Risk Factors and Lifexpectancy Project (1978-1987), a prospective studymong adults age 20 to 69 years, pooled from nine largepidemiologic studies (N�62,285), suggesting an approx-

mately threefold increased risk (hazard ratio: 2.99; 95% c

348 August 2009 Volume 109 Number 8

onfidence interval [CI]: 1.27 to 7.02) of colorectal cancerortality among participants with insulin resistance or

ssociated biochemical abnormalities after adjusting forge, alcohol consumption, and smoking (35).Similarly, findings from the Chicago Heart Associationetection Project in Industry reported a 50% increased

isk of colon cancer mortality among participants havinghe insulin resistance syndrome (�3 of 5 biochemicalbnormalities) after adjusting for race, age, education,ex, and height (36). In a prospective cohort study eval-ating the late effects of cancer among 512 women withreast cancer, insulin resistance was associated with awo- to threefold increased risk of distant recurrence ofisease (hazard ratio: 2.0; 95% CI: 1.2 to 3.3) and deathrom the disease (hazard ratio: 3.1; 95% CI: 1.7 to 5.7)fter adjusting for tumor and treatment-related variables37). Similarly, in a 10-year prospective Korean studyn�1,298,385), after controlling for smoking and alcoholse, individuals with higher vs lower fasting serum glu-ose concentrations (proxy for insulin resistance) werepproximately 30% more likely to die of cancer (all can-ers combined) (hazard ratio: 1.29; 95% CI: 1.22-1.37),nd these detrimental associations persisted across allMI categories, suggesting an independent role of insulineyond excess body weight (38).In summary, large well-powered studies collectively

uggest that both obesity and hyperinsulinemia may beigh-risk conditions for the late effects of cancer. It isoteworthy that the detrimental direction of the associa-ions were not limited to site-specific cancers, but ob-erved for most cancers (except lung cancer because of theonfounding effects of smoking). These associations mayossibly be explained by the biochemical reverberationsf obesity and insulin resistance, which create an envi-onment conducive for cancer cells to proliferate and sur-ive, regardless of cancer type.However, the existing literature on obesity, insulin resis-

ance, and cancer does not answer some important ques-ions about cancer survivorship. Although there is convinc-ng evidence in the literature that obesity is associated withncreased risk of developing cancer and death from it, thempact of obesity among cancer survivors is not well-stud-ed. The relationships of insulin resistance and cancer pro-ression or recurrence require additional studies amongurvivors. Further, insulin resistance is the hallmark ofetabolic syndrome, a constellation of related biochemical

bnormalities, which may act synergistically to influenceumor growth. At this time, the relationships of the fulletabolic syndrome with cancer progression are unclear. In

ddition, the majority of the studies have used mortality asproxy for long-term or late consequences of cancer.Overall, obesity, insulin resistance, and metabolic syn-

rome, all of which are current public health concerns inhe United States, warrant further investigation in theontext of surveillance of cancer survivors and cancerrognosis. Addressing these issues may teach importantessons to health professionals at cancer centers and mo-ivate them to design and implement special lifestyle andeight-management intervention programs to prevent

ate consequences of cancer among the large population of

ancer survivors.

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MPLICATIONS FOR PRACTICEdentification of High-Risk Cancer Survivorsecause high BMI and insulin resistance are predictive ofoor cancer prognosis, the multidisciplinary health careeam, including oncologists, primary care physicians, andegistered dietitians (RDs) or board-certified specialistsn oncology nutrition should identify obese patients andcreen for insulin resistance to stratify individuals by riskf cancer progression. In addition to the traditional bodyeight assessment and laboratory tests, assessment of

ome obesity-related phenotypic manifestations may alsoe done. These include hyperpigmentation of the skin,pecifically on the back of the neck, (a condition known ascanthosis nigricans) (39), caused primarily by insulinesistance, or the presence of the “buffalo hump” (or cer-ical lipomatosis) and a double-chin, which has beenhown to be predictive of the insulin resistance syndrome40). It seems reasonable to offer appropriate counselingeferrals to RDs and fitness experts for dietary, behav-oral, and lifestyle changes (specifically weight loss), asn integral part of the therapy for patients in the high-isk strata. This could serve as an important secondaryancer-control measure. In addition, promotion of life-tyle changes maybe the key to improved treatment out-omes and successful therapy among individuals under-

American Cancer Society Guidelines (56)

1. Maintain a healthy weight throughout life.● Balance caloric intake with physical activity.● Avoid excessive weight gain throughout the life cycle.● Achieve and maintain a healthy weight if currently

overweight or obese.

2. Adopt a physically active lifestyle.● Adults: Engage in at least 30 minutes of moderate to

vigorous physical activity, above usual activities, on 5 ormore days of the week. Forty-five to 60 minutes ofintentional physical activity are preferable.

● Children and adolescents: Engage in at least 60 minutesper day of moderate to vigorous physical activity at least5 days per week.

3. Consume a healthy diet, with an emphasis on plant sources● Choose foods and beverages in amounts that help achieve

and maintain a healthful weight.● Eat five or more servings of vegetables and fruits each day.● Choose whole grains over processed (refined) grains and

sugars.● Limit consumption of processed and red meats.

4. If you drink alcoholic beverages, limit consumption.● No more than two drinks per day for men and one drink a

day for women.

igure 2. Current guidelines on nutrition and physical activity for canceournal for Clinicians, Vol. 56, No. 5, 2006, pp 254-281. Copyright 200iley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc. (56). Adaptedancer Research. Food, Nutrition, Physical Activity, and the Prevention

oing cancer treatment (41). m

ancer Control through Lifestyle Modifications: Implications forhe RDhe RD or board-certified specialist in oncology nutritionlays a pivotal role in the care of cancer survivorshrough the course of the disease and during routineollow-up care. The Institute of Medicine report outlineshree “seasons” of cancer survivorship: (a) “acute sur-ival,” which begins with cancer diagnosis, and consistsrimarily of cancer therapy, (b) “extended survival,”hich is a post-treatment period during which a personoes into remission, and (c) “permanent survival,” whichs usually tantamount with “cure” (10). During these pe-iods of survival, individuals may live cancer-free foreveral years or with intermittent bouts of cancer, haveersistent disease, or die rapidly of late disease. RDs andoard-certified specialists in oncology nutrition are keylayers in improving survival and quality of life as wells in reducing complications and risks that may ariseuring these “seasons” of survival, during and after treat-ent from comorbidities associated with being over-eight or obese, through dietary and lifestyle modifica-

ion. In fact, a recent ACS report identified that morehan 50% of cancer deaths could be prevented by modifi-ble lifestyle factors, including diet and exercise (42). Inddition, evidence from two large studies suggests that

erican Institute for Cancer Research/World Cancer Researchnd Guidelines (57)

Body Fatness● Be as lean as possible within the normal range of body weight.

Physical Activity● Be physically active as part of everyday life.

Foods and Drinks that Promote Weight Gain● Limit consumption of energy-dense foods. Avoid sugary drinks.

Plant Foods● Eat mostly foods of plant origin.

Animal Foods● Limit intake of red meat and avoid processed meat.

Alcoholic Drinks● Limit alcoholic drinks.

Preservation, Processing, Preparation● Limit consumption of salt. Avoid moldy cereals (grains) or

pulses (legumes).

Dietary Supplements● Aim to meet nutritional needs through diet alone.

Breastfeeding● Mothers to breastfeed; children to be breastfed.

vention and survivorship. [Adapted with permission from: CA: A Cancererican Cancer Society. This material is reproduced with permission ofpermission from: World Cancer Research Fund/American Institute forancer: A Global Perspective. Washington, DC: AICR, 2007 (57).]

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iets and increased physical activity to control weight,ay prevent cancer progression and mortality (43,44).Cancer patients may also have weight-management

hallenges due to disease- or treatment-related weightain. During treatment, patients may experience fatigue,epression, neutropenia, insomnia, decreased oral in-ake, side effects of medication, and changes in bodyomposition. This may lead to decreased physical activityevels, resulting in an involuntary weight gain (45). Cer-ain chemotherapy regimens, hormone therapy, and ste-oid medications can also cause changes in body compo-ition and undesirable weight gain (45,46). Afteronsidering all the clinical aspects and the potential forisease-related weight loss, a customized plan with annergy deficit of 500 to 1,000 kcal per day may be recom-ended by an RD, with the expectation of a weight loss ofto 2 lb per week per the American Dietetic Association

uidelines (47). This regimen must be followed in con-unction with the physician’s care plan, provided it doesot interfere with treatment or coincide with periods ofime during treatment deemed high-risk for any involun-ary weight loss. Cancer survivors should be encouragedo follow the current guidelines on nutrition and physicalctivity proposed by the American Institute of Canceresearch (48) and the ACS (45) (see Figure 2). Figure 3ummarizes some practice points for RDs (45,47).Prolonged hyperinsulinemia may be caused in part by

pecific types of carbohydrates and fatty acids. Quickerbsorption of dietary glucose into the bloodstream fromhe intestines results in a stronger stimulus for insulinecretion (49). Typical American diets, characterized byigher intakes of red and processed meats, high-fat dairy,esserts, refined grains, and lower intakes of fiber, aressociated with hyperinsulinemia (50). Saturated and

● Recommend that cancer survivors follow American CancerSociety and/or American Institute of Cancer Researchguidelines on nutrition and physical activity for cancerprevention and survivors and encourage adherence to healthylifestyle behaviors (see Figure 2 for more details).

● Considering all clinical aspects of treatment-related sideeffects and the potential for disease-related weight loss, createan individualized nutritional care plan for appropriate weightmanagement:� Energy deficit of 500-1,000 calories for a weight loss of 1-2

lb per week may be recommended

● Collaborate with physicians and exercise physiologists tocustomize a safe exercise program. Decisions on the type,frequency, duration, and intensity of physical activity wouldvary depending on the following:� Survivor’s age� Previous fitness activities� Type of cancer� Stage of treatment� Type of therapy� Presence of comorbid conditions

igure 3. Practice points for registered dietitians and board-certifiedpecialists in oncology nutrition, for weight management of cancer survi-ors (data from [45,47]).

rans-fatty acids may increase insulin levels, whereas s

350 August 2009 Volume 109 Number 8

olyunsaturated fatty acids, especially n-3 fatty acids,eem to be protective against hyperinsulinemia (51).owever, it is more likely that the overall dietary patternould influence insulin levels.Existing evidence suggests that exercise is safe and

easible for patients during cancer treatment (45). Phys-cal activity and survival have been investigated in breastnd colon cancers and seem to reduce the risk of mortality52,53). The Nurses’ Health Study, consisting of womeniagnosed with breast cancer between 1984 and 1998n�2,987), noted that physical activity reduced the risk ofecurrence and death from the disease, with the greatestenefit occurring in women who walked 3 to 5 hours pereek (43).In addition, a prospective randomized study among

atients with advanced colorectal cancer (n�832) foundhat increasing levels of physical activity reduced risk ofecurrence and cancer mortality in a multivariate analy-is including adjustment for disease-free survival andhemotherapy (52). Findings from a previous laboratorytudy suggest that a more healthful diet and physicalctivity reduced tumor growth and increased apoptosis byodulating the insulin/IGF-1 pathway (54). For counsel-

ng purposes, decisions about the type, frequency, dura-ion, and intensity of physical activity should be individ-alized to the survivor’s age, previous fitness activities,ype of cancer, stage of treatment, type of therapy, andomorbid conditions (45).Although cancer diagnosis is described as a “teachableoment” to empower cancer patients to make lifestyle

hanges, a recent study found that only a minority ofancer survivors are meeting the ACS guidelines forhysical activity and consuming the recommended 5 orore servings of fruits and vegetables daily (55). A major

hallenge for the RD/board-certified specialist in oncologyutrition is to plan the trajectory of care among cancerurvivors with a vision of both the long- and short-termonsequences of cancer diagnosis, while empoweringhem to adhere to more healthful diets and lifestyles.

ONCLUSIONShe prevalence of obesity and cancer have been increas-

ng in parallel. The number of cancer survivors has in-reased in the past 3 decades, with a projected doublingy 2050 (3). Furthermore, approximately one third of theS population has insulin resistance. Biochemical rever-erations of both obesity and insulin resistance, specifi-ally higher concentrations of leptin, proinflammatoryactors, and a disturbed insulin-IGF-1 axis, may cooper-tively contribute to tumor growth and cancer progres-ion (8). Although additional studies are warranted tonvestigate this issue specifically in the context of surveil-ance of cancer survivors and cancer prognosis, existingpidemiologic evidence supports the poor prognostic po-ential of obesity and hyperinsulinemia with cancer biol-gy, suggesting a need for updated clinical guidelines.This has several implications for the RD and certified

pecialist in oncology nutrition for behavioral counselingnd weight management among cancer patients throughhe course of the illness, after treatment, and throughoutine follow-up care (Figure 4). Clinicians should worklosely with RDs to identify obese cancer survivors and

creen for insulin resistance during treatment and fol-

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Patient referred to dietitian

Screen for appropriateness for weight loss/management:

Assess appropriateness of any change in weight as it relates to

timing of cancer treatments

Screen for:•Eating disorder

•Pregnancy• Receiving chemotherapy, radiation

Weight loss/management appropriate?

Assess measures of adiposity: •Body mass index (BMI)

•Waist circumference (WC)

Treat for primary nutritional problem or refer back to healthcare practitioner

BMI 25OR

WC > 102cm (females)WC > 88cm (males)

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active treatments (eg, hormone therapy, chemotherapy)

Recommend weight loss/management treatment

Patient motivated to lose weight?

Commence comprehensive weight loss/management

program (diet, physical activity,behavioral therapy)

Individualized goals of weight loss: •Reduce body weight at optimal rate of 1-2 lbs/wk for

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from baseline

Individualized reduced calorie diet:Caloric deficit of 500-1,000 kcalsbelow estimated energy needs

Pay special attention to maintaining adequate intake of

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appropriate physical activity level

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igure 4. Weight loss/management screening and treatment algorithm for cancer survivors. This flowchart is to serve as a guide to registeredietitians/board-certified specialists in oncology nutrition to counsel cancer survivors for weight management. Patient needs for weight loss as wells the appropriate level of intervention can be assessed using this chart. (Adapted from the American Dietetic Association Adult Weight Management

vidence Based Nutrition Practice Guideline Screening and Treatment Algorithms.)

August 2009 ● Journal of the AMERICAN DIETETIC ASSOCIATION 1351

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ow-up visits to identify individuals who are at potentiallyigher risk of cancer progression. These cancer survivorshould be offered appropriate counseling referrals, spe-ifically for weight management, to prevent repercus-ions of obesity on their existing cancer. The Americanietetic Association, ACS, and American Institute of Can-

er Research guidelines on diet and physical activity shoulde referred to by RDs, board-certified specialists in oncologyutrition, and health care professionals to delay or preventevelopment of new cancers, disease recurrence, or mortal-ty.

In conclusion, increased body weight and prolongednsulin resistance, both associated with chronic low-gradenflammation, have been implicated in poor prognosismong the rapidly increasing population of cancer survi-ors. It is time to consider management of these modifi-ble risk factors through more healthful lifestyles as anmportant secondary cancer-control tool.

TATEMENT OF POTENTIAL CONFLICT OF INTEREST:o potential conflict of interest was reported by theuthors.FUNDING/SUPPORT: This study was supported by

he National Institutes of Health Award 1R03CA132127.ACKNOWLEDGEMENTS: We would like to thank

hanusha Puvananayagam, our research assistant at theancer Institute of New Jersey, for her technical anddministrative support, and to Maya Vadiveloo, re-earch assistant, at New York University, Department ofutrition, Food Studies, and Public Health, for her re-

earch and administrative support toward preparing theanuscript.

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