Results of the RENEW trial

(1)

Wendy Demark-Wahnefried, PhD, RD

Professor and Webb Endowed Chair of Nutrition Sciences

Associate Director for Prevention, Control and Population Sciences The University of Alabama at Birmingham (UAB) - USA

UAB Comprehensive Cancer Center

Home-based Diet-Exercise Interventions to

Improve Health Behaviors, Body Weight, & Functional Status in Cancer Survivors:

Results of the RENEW trial

(2)

Objectives

• Brief overview of issues in survivorship

and potential role of nutritional status, diet and exercise.

• What factors need to be considered in delivering dietary interventions that

promote dietary change and healthier eating patterns over the long-term?

• Discuss lessons learned and findings of

the RENEW trial

(3)

Cancer Survivorship:

The Good News!

About 25 million survivors worldwide

(Parkin et al. CA- Cancer J Clin. 2005)

(4)

Cancer Survivors at greater risk - Progressive disease

- Second primaries

- Cardiovascular Disease - Diabetes

- Osteoporosis - Sarcopenia

- Functional decline

- Subsets prone to depression &

fatigue

- $219 Billion annually on cancer in the US: 2/3’s of these costs due to downstream effects

Cancer Survivorship:

The Bad News!

(5)

Possible Solutions

Diet Exercise

Depression  

Fatigue  

Adverse Body Composition Change  

Functional Decline  

Comorbidity  

Recurrent/Progressive Disease 

Growing!



Growing!

 Possible benefit Probable benefit  Convincing benefit

(6)

Change in BMI after Diagnosis of Breast Cancer

& Association with Recurrence & Mortality

Data from Cohort of 5204 Breast Cancer Survivors in Nurse’s Health Study

0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8

>0.5 loss maintain 0.5-2.0 gain >2.0 gain

recurrence

breast cancer mortality

all cause mortality

Change in BMI

Kroenke et al. JCO 23: 1370-8, 2005

Relativ e Ris k

(7)

Exercise & Association with Recurrence &

Survival - CALGB 89803 (Stage III CRC) N=832

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

<3 3-8.9 9-17.9 18-26.9 27+

recurrence

recurrence + deaths due to other causes

overall mortality

Level of Exercise (MET hrs/week)

Re lativ e Ris k

Meyerhardt et al. JCO 24:3535, 2006

(8)

0 5 10 15 20 25

All Patients ER positive ER negative

Low Fat Diet Regular Diet

Results of the Women’s Intervention Nutrition Study (WINS) Show Reduced Rates of Recurrence

in Patients Assigned to a Low Fat Diet (n=2,437)

Chlebowski et al. JNCI 98:1767, 2006

P =.034 P =.277

P =.018

Recurrence Rates (% of population)

(9)

Diet & Physical Activity Guidelines for Cancer Survivors

World Cancer Research Fund-American Institute for Cancer Research 2^ndExpert Research Report, http://www.aicr.org

World Cancer Fund - American Institute for Cancer Research (2007)

Weight Be as lean as possible without becoming underweight Physical Activity Be physically active 30+ min/day – aim for 60+ min/day

Limit sedentary habits such as watching television

Dietary Pattern Avoid sugary drinks. Limit energy-dense foods (foods high in sugar & fat, and low in fiber)

Eat more of a variety of vegetables, fruits, whole grains and legumes

Limit consumption of processed & red meat Other Limit consumption of salty foods

Alcohol If drink limit to 1-2 drinks/day

Supplements Don’t use supplements to protect against cancer

(10)

What are the Lifestyle Practices of Cancer Survivors?

Behavior %

Overweight or Obese 59-71%

Eat < 5 Daily Servings of Fruits & Vegetables 52-58%

Moderate-to-Heavy Alcohol Intake 16%

Takes Supplements 70-80%

Sedentary ~70%

(11)

Levels of Interest in Diet & Exercise Interventions (978 Breast and Prostate Cancer Survivors)

0 10 20 30 40 50 60

Diet Exercise

Extremely/Very Somewhat/A Little Not at All

Demark-Wahnefried et al. Cancer 88:674, 2000

(12)

Levels of Interest in Various Intervention Modes of Delivery

(% of sample indicating “extremely or very interested”)

Demark-Wahnefried et al. Cancer 88:674, 2000/103:2171-80, 2005

38 53

38 49

44 33

60 70 80 90 100

Adult Survivors 0

10 20 30 40 50 60

1 2 3 4

Adult Survivors (978 breast & prostate, Duke 2000 survey)

Teen-Young Adult Survivors (209 Duke Sheet1!$B$3

Series3

0 10 20 30 40 50 60

% of sample

978 Breast & Prostate Cancer Survivors (2000 Duke survey)

209 Teen/Young Adult Childhood Cancer Survivors (2003 Duke survey)

180 Teen/Young Adult Childhood Cancer

Survivors (2009 MDACC survey)

Mailings Clinic Telephone Computer

Counseling

(13)

• Test the impact of a diet-exercise mailed material/telephone counseling program on weight loss & physical functioning in 640

prostate, colorectal & breast cancer survivors

• 65+ years of age & overweight

• 5+ years out from diagnosis

Reach Out to ENhancE Wellness in Older Survivors

(R01 CA106919)

(14)

% with Limitations:

Survivors vs. General Population

0 10 20 30 40 50 60

Psych.

Problems

1+

ADL/IADL

1+

functional

Work

General Survivors

Hewitt, Rowland, Yancik. J Gerontol. 58:82, 2003

(15)

Estimated associations between health behaviors & physical function (n=688)

Health Behavior Point increase in SF36

Physical Function Subscale

P-value

Affirmative response to

vigorous exercise 20 min at least 3 x weekly

15.4 ^P<.0001

One daily serving

increase in F&V 0.9 ^P=.0049

1% decrease in

total energy from fat 0.2 ^P<.0001

Demark-Wahnefried et al. Intl J Behav Nutr Phys Act 1:16, 2004 (www.ijbnpa.org/content/1/1/16).

(16)

Effect of Weight Change on Physical Function in Women Age 65+

-15 -10 -5 0 5 10

<25 25-29.9 30-34.9 35+

20+ lb gain 5-19 lb gain 5-19 lb loss 20+ lb loss

Fine et al. JAMA. 282:2136, 1999

Modest weight loss improves function

in those who are overweight/obese

(17)

Overview: Accrual & Screening

Self-Referrals N=107

NC Cancer Registry N = 67,054

Potential N = 37,054

Omit decedents, duplicates, 2^nd primaries,contact info Confirm case status w/MD

Approached N = 26,031 N = 107

Mailed letter of invitation

and a screening survey

Undeliverable n = 6,030 Returned survey/consents

White, males, younger & more proximal to dx more likely to respond

n = 86

80% response n = 1147

6% response n = 1233 Ineligible n = 567

641 Enrolled

Randomization: cancer site, gender, age (65-74 years vs 75+ years), and race Immediate Intervention (319) Delayed Intervention (322)

1-yr Follow-up (269) 1-yr Follow-up (289) 2-yr Follow-up 2-yr Follow-up

76 Drop-outs 77 Drop-Outs

(18)

Geographic Distribution of Participants

Accrued for the RENEW Trial (n=641)

(19)

11

39 0 5 10 15 20 25 30 35 40 45 50

Project LEAD RENEW

# of Letters of Invitation Mailed to Ascertain 1 Analyzable Participant Project LEAD vs. RENEW Telephone Counseling/Mailed Material

Diet & Exercise Interventions aimed at Elderly Cancer Survivors

Recruited within 18M of diagnosis

Recruited at least

5-yrs after diagnosis

(20)

Age 73.1 (5.1) (range 65-87)

% Male 45%

% Caucasian 89%

Education 33% < HS

30% Some College 37% > College Grad

Type of Cancer ^{45% Breast}

41% Prostate 14% Colorectal

% Cancer Registry 92%

Years since Dx 8.6 (2.7) (range 5-26)

# of Comorbidities 2 (1.2)

Current Smoker 6%

Physical Function (SF 36) 75.7 (18.9) (range10-100)

RENEW Study Sample Characteristics (n=641)

(21)

Intervention Mean (SE)

Wait List Control

Mean (SE) P-

value SF-36 Physical Function -2.55 (1.07) -5.39 (1.01) .034 Basic Lower Extremity – LLF +0.41 (0.71) -2.11 (0.67) .005 Adv. Lower Extremity – LLF +0.44 (0.60) -2.55 (0.61) .015 Strength Exercise (min/d) +22.2 (2.8) +0.5 (3.0) <.0001 Strength Exercise

(session/w) +1.4 (2.6) +0.2 (2.5) <.0001

Endurance Exercise (min/d) +43.1 (5.7) +26.1 (6.3) <.0001 Endur. Exercise (session/w) +1.6 (3.9) +0.5 (4.1) .005 F&V Intake (servings/d) +1.48 (0.16) +0.15 (0.12) <.0001 Saturated Fat Intake (g/d) -3.64 (0.61) -1.19 (0.55) .002 Healthy Eating Index +7.1 (0.9) +1.4 (0.8) <.0001

Weight (kg) -2.45 (0.22) -1.03 (0.2) <.0001

BMI -0.82 (0.07) -0.035 (0.08) .0002

Quality-of-Life (Total SF-36) +0.91 (0.86) -2.17 (0.90) .025

Results

JAMA 301: 1883-91, 2009.

(22)

Changes in Lifestyle Behaviors

69

33.3

101.1

100.9

37.5

107.5

0 20 40 60 80 100 120

65.2 66.4

59.6

61.1

66.2

58 59.3 60 62 64 66 68

Weekly Minutes of Exercise

Healthy Eating Index

Baseline

1-yr 2-yr

Immediate RENEW Intervention Delayed Intervention

Minutes of Physical Activity

Diet Quality

Baseline 1-year 2-years

1-year 2-years

Baseline

(23)

Change in BMI

28.3 28.2 28.2

29.1 28.8 29.1

28 28.2 28.4 28.6 28.8 29 29.2

29.4 Body Mass Index (kg/m

²

)

BaselineBaseline 1-year1-yr 2-years2-yr

(24)

Change in Physical Function (SF-36)

Baseline 1-yr 2-yr

70.6 76.1 74.4

69.4 70.5

65 60

65 70 75 80

BaselineBaseline 1-year1-yr 2-years2-yr

(25)

Summary

The RENEW exercise-diet intervention that was delivered via mailed materials & telephone

counseling was successful in…

- improving diet and physical activity - improving weight status

- reorienting physical functioning

- improving overall quality of life

- DURABLE and REPLICABLE

(26)

Areas for Future Research

• To determine optimal timing of interventions

• To determine optimal channels and modes of delivery for interventions

• To determine the optimal target (survivors alone or survivors and family/friends)

• To determine optimal means of addressing content in multi-component interventions

• To determine means by which effective interventions

are sustainable

(27)

Collaborators

Thanks to all survivors who participated in this research!

Miriam Morey, PhD Elizabeth Clipp, PhD

Bercedis Peterson, PhD Carl Pieper, PhD

Harvey Cohen, MD

Denise Snyder, MS, RD Richard Sloane, MS, MPH

National Cancer Institute R01-CA106919

Results of the RENEW trial

Home-based Diet-Exercise Interventions to

Improve Health Behaviors, Body Weight, & Functional Status in Cancer Survivors:

Results of the RENEW trial

Objectives

• Brief overview of issues in survivorship

and potential role of nutritional status, diet and exercise.

• What factors need to be considered in delivering dietary interventions that

promote dietary change and healthier eating patterns over the long-term?

• Discuss lessons learned and findings of

the RENEW trial

Cancer Survivorship:

The Good News!

About 25 million survivors worldwide

(Parkin et al. CA- Cancer J Clin. 2005)

Cancer Survivors at greater risk - Progressive disease

- Second primaries

- Cardiovascular Disease - Diabetes

- Osteoporosis - Sarcopenia

- Functional decline

- Subsets prone to depression &

fatigue

- $219 Billion annually on cancer in the US: 2/3’s of these costs due to downstream effects

Cancer Survivorship:

The Bad News!

Possible Solutions

Diet Exercise

Depression  

Fatigue  

Adverse Body Composition Change  

Functional Decline  

Comorbidity  

Recurrent/Progressive Disease 

Growing!



Growing!

Change in BMI after Diagnosis of Breast Cancer

& Association with Recurrence & Mortality

Relativ e Ris k

Exercise & Association with Recurrence &

Survival - CALGB 89803 (Stage III CRC) N=832

Re lativ e Ris k

Results of the Women’s Intervention Nutrition Study (WINS) Show Reduced Rates of Recurrence

in Patients Assigned to a Low Fat Diet (n=2,437)

Diet & Physical Activity Guidelines for Cancer Survivors

What are the Lifestyle Practices of Cancer Survivors?

Behavior %

Overweight or Obese 59-71%

Eat < 5 Daily Servings of Fruits & Vegetables 52-58%

Moderate-to-Heavy Alcohol Intake 16%

Takes Supplements 70-80%

Sedentary ~70%

Levels of Interest in Diet & Exercise Interventions (978 Breast and Prostate Cancer Survivors)

Levels of Interest in Various Intervention Modes of Delivery

(% of sample indicating “extremely or very interested”)

• Test the impact of a diet-exercise mailed material/telephone counseling program on weight loss & physical functioning in 640

prostate, colorectal & breast cancer survivors

• 65+ years of age & overweight

• 5+ years out from diagnosis

Reach Out to ENhancE Wellness in Older Survivors

(R01 CA106919)

% with Limitations:

Survivors vs. General Population

Estimated associations between health behaviors & physical function (n=688)

Health Behavior Point increase in SF36

Physical Function Subscale

P-value

Affirmative response to

vigorous exercise 20 min at least 3 x weekly

15.4 P<.0001

One daily serving

increase in F&V 0.9 P=.0049

1% decrease in

total energy from fat 0.2 P<.0001

Effect of Weight Change on Physical Function in Women Age 65+

Modest weight loss improves function

in those who are overweight/obese

Overview: Accrual & Screening

Self-Referrals N=107

NC Cancer Registry N = 67,054

15.4 ^P<.0001

increase in F&V 0.9 ^P=.0049

total energy from fat 0.2 ^P<.0001

Type of Cancer ^{45% Breast}