Kirsten Ness, PT, PhD AICR October · Kirsten Ness, PT, PhD AICR. October 2010. The Questions • How many childhood cancer survivors are there? • On average, are childhood cancer

Physical inactivity and body composition among childhood cancer survivors

Kirsten Ness, PT, PhD

AICR

October 2010

The Questions• How many childhood cancer survivors are there?

• On average, are childhood cancer survivors obese?

• Are childhood cancer survivors inactive?

• Why is a discussion of inactivity and obesity relevant for childhood cancer survivors? Information from the

Childhood Cancer Survivor Study

• What are the characteristics of the survivors who are at greatest risk for obesity and inactivity?

• Does diet play a role?

• Are there interventions available?

The Questions

• How many childhood cancer survivors are there?



• Why is a discussion of inactivity and obesity relevant for childhood cancer survivors –

information from the

Childhood Cancer Survivor Study?




Cancer incidence and mortality rates among U.S. children and adolescents

www.seer.cancer.gov

2010Mariotto, Cancer Epidemiol Biomarkers Prev. 2009

http://www.seer.cancer.gov/

The Questions










Obesity?

Body mass index in childhood cancer survivors

BMI < 18.5 BMI 18.5‐24.9 BMI 25‐29.9 BMI 30+

Females % % % %

General population 4.7 55.4 23.4 16.5

Acute lymphoblastic

leukemia

4.2 54.8 22.5 18.5

Other leukemia 7.4 53.4 23.9 15.3

Brain tumor 8.1 49.9 24.9 17.1

Hodgkin disease 8.1 61.4 17.8 12.6

Non‐Hodgkin lymphoma 8.7 58.0 26.1 7.2

Wilm’s tumor 12.3 68.9 10.5 8.3

Neuroblastoma 10.6 66.7 12.9 9.8

Soft tissue sarcoma 7.8 62.2 19.0 10.9

Bone tumor

Amputation 24.2 46.5 18.6 10.7

No‐amputation 9.8 65.9 16.4 7.9Meacham Cancer 2005

Body mass index in childhood cancer survivors

BMI < 18.5 BMI 18.5‐24.9 BMI 25‐29.9 BMI 30+

Males % % % %

General population 0.9 39.6 42.8 16.7

Acute lymphoblastic

leukemia

3.5 43.8 36.2 16.5

Other leukemia 2.1 49.6 36.4 11.9

Brain tumor 3.5 45.2 38.1 13.2

Hodgkin disease 3.6 48.0 35.5 12.9

Non‐Hodgkin lymphoma 3.8 49.6 36.5 10.2

Wilm’s tumor 8.1 57.1 26.6 8.1

Neuroblastoma 7.7 60.7 26.5 5.1

Soft tissue sarcoma 4.2 54.1 30.0 11.8

Bone tumor

Amputation 6.6 53.9 33.3 6.1

No‐amputation 2.5 51.2 34.8 11.4Meacham Cancer 2005

Altered body composition among childhood acute lymphoblastic leukemia survivors

Male participants

Male normative

values

Female participants

Female normative

valuesN=32 N=43

Mean SD Mean SD Mean SD Mean SDBMI (kg/m2) 26.8 5.3 27.5 0.3 27.9 8.1 26.8 0.3Bone mineral content %

4.0 0.6 3.8 0.5 3.6 0.6 3.8 0.5

Lean mass % 70.0 7.7* 74.7 8.4 58.0 10.0 60.2 5.3Fat mass % 26.0 8.0* 21.5 7.6 38.0 9.6 36.0 9.7*Skeletal muscle mass %

38.1 4.1* 40.7 4.7 30.1 5.0 32.3 5.7*

*p < 0.05

Ness PBC 2006

Altered body composition among childhood lymphoma survivors

• 44 HD or NHL survivors• Median age 22 years• Median time since

diagnosis 10.5 years• BMI calculated by

dividing weight in kilograms by height in

meters squared• Body fat analyzed via

DXA

Nysom PBC 2003

ALL survivors gain more body mass than siblings over time

Garmey JCO 2008

The Questions










Are childhood cancer survivors inactive?

Activity and inactivity in childhood cancer survivors

9,301 childhood cancer survivors 2,886 siblings 18+ years of age at questionnaire

Ness Cancer 2009

Activity and inactivity in childhood cancer survivors

Moderate physical activity

(Minutes/week)

Vigorous physical activity

(Minutes/week)Mean (SD) p-value‡ Mean (SD) p-value‡

BRFSS* 287 (451) 127(253)Siblings 216 (422) <0.001 108 (231) .011Survivors 208 (433) <0.001 98 (248) <.001‡Survivor, BRFSS comparisons from two sample t-tests or Chi squared statistics as BRFSS sample

frequency matched on age and gender. Sibling, BRFSS comparisons from linear or logistic regression models adjusted for age and gender.

*Behavioral Risk Factor Surveillance System

Ness Cancer 2009

The Questions




• Why is a discussion of inactivity and obesity relevant for childhood cancer survivors? Information from the

Childhood Cancer Survivor Study.




Childhood cancer survivor studyChildhood cancer survivor study

Created to take advantage of: – The opportunity to gain new knowledge about the long‐

term effects of cancer and therapy, knowledge that can be used to help design treatment protocols and

intervention strategies that will increase survival and minimize harmful health effects.

– The obligation to educate survivors about the potential impacts of cancer diagnosis and treatment on their

health, and to provide follow‐up care, for example, by treating and implementing programs for the prevention

and early detection of late effects.

www.ccss.stjude.org

http://ccss.stjude.org/

Coordinating CenterSt. Jude Children’s Research Hospital

Original Contributing Clinical Centers

Resource Centers

New Clinical Centers (Expansion Cohort)

Univ. So. CaliforniaFollow‐up Center

MD AndersonRadiation Physics Ctr.

Cincinnati Children’sBiorepository

Ohio State Univ.Biopathology Center

Fred

Hutchinson

Statistics and Data

Center

Participating Centers




Study design• Retrospective cohort• 5‐Year cancer survivors,

diagnosed 1970‐1986• < 21 years old at diagnosis• 26 institutions • Health outcome data

collected in a series of

surveys 1995, 2000, 2003,

2005, 2007• Medical record abstraction• Comparison group of 3,899

siblings • Expansion cohort currently

being enrolled (diagnosed

1987‐1999)

• 20,632 Eligible

Lost

(n=3058)

• 17,574 Contacted

Refusal

(n=3216)

• 14,358 Participants


Diagnoses



Participants(N=14,358)

Siblings(N=3,899)

N (%) N (%)

Sex

Male 7713 (53.7) 1875 (48.1)

Female 6645 (46.3) 2024 (51.9)

Age ‐

questionnaire

< 20 years 3156 (22.0) 803 (20.6)

20‐29 years 5446 (38.0) 1273 (32.6)

30‐39 years 4628 (32.2) 1293 (33.2)

40‐49 years 1110 ( 7.7) 489 (12.5)

50‐59 years 18 ( 0.1) 41 ( 1.1)

Characteristics Characteristics



N (%)Age at diagnosis

0‐4 years 5754 (40.1)

5‐9 years 3200 (22.3)

10‐14 years 2913 (20.3)

15‐20 years 2491 (17.3)

Therapy

Radiation 33 ( 0.2)

Chemotherapy 816 ( 5.7)

Chemotherapy & radiation 1459 (10.2)

Chemotherapy, radiation, surgery 5550 (38.7)

Radiation & surgery 1479 (10.3)

Chemotherapy & surgery 2274 (15.8)

Surgery 909 ( 6.3)

CharacteristicsCharacteristics



0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 5 10 15 20 25 30

Years From Original Cancer Diagnosis

Cumulative Incide

nce

Grade 1-5

Grade 3-5

Oeffinger NEJM 2006

Chronic conditions



Survivors(N=9,308)

Siblings(N=2,951)

OR 95% CI

Obesity 20.6% 20.8% 1.0 0.9-1.1Medication for Hypertension 8.8% 5.7% 1.9 1.6-2.2Medication for Dyslipidemia 5.2% 4.0% 1.6 1.3-2.0Medication for Impaired Glucose Tolerance

2.5% 1.7% 1.7 1.2-2.3

CVRFC (Any 3) 1.3% 1.2% 1.3 0.9-1.9Adjusted for age (median=32 years), sex, ethnicity and intra‐family correlations

Relative odds of cardiovascular disease risk factors among survivors compared to siblings

Meacham PBC 2010



Cumulative Incidence of Cardiac Outcomes

Cumulative incidence of reported cardiac outcomes at

30 years from diagnosis

Congestive Heart Failure 4.1% (3.2 ‐

5.0)

Myocardial Infarction 1.3% (1.0 ‐

1.7)

Atherosclerosis 2.1% (1.4 ‐

2.7)

Pericardial disease 3.0% (2.1 ‐

3.9)

Valvular disease 4.0% (3.1 ‐

4.9)

Angiography 3.4% (2.5 ‐

4.3)

Mulrooney BJC 2010



Relative Risk* (95% CI) of Cardiac Outcomes Compared to Sibling Controls

CHF

Myocardial Infarction

Atherosclerosis

Pericardial Disease

Valvular Disease

Coronary Angiogram

5.0

10.3

6.34.8

8.35.9

1

10

100

Relative

Risk *

* Adjusted for age at diagnosis, gender, race, income, education, smoking

Relative Risk of Cardiac Outcomes Compared to Siblings

Mulrooney BJC 2010



Kurt ASCO 2009

Hospitalizations by attained age



7.0

2.6

6.7

5.0

3.4 3.5

1.1

10.1

2.41.7

16.815.7

14.113.2

8.7 8.7

7.1

4.84.1

3.5

0

2

4

6

8

10

12

14

16

18

Exte

rnal

Neop

lastic

Gastr

ointe

stina

lGe

nitou

rinar

yCa

rdiov

ascu

larPu

lmon

ary

Neuo

rlogic

alPs

ycho

logica

lEn

docri

neInf

ectio

us

Rate pe

r 1000

person years US population

Survivors

Kurt ASCO 2009

Cause specific hospitalizations



Mertens JNCI 2008



The Questions










No CNS No CNS

RxRxYes CNS Yes CNS

RxRx

MeanMean MeanMean pp‐‐valuevalue

Waist circumference (cm) Waist circumference (cm) ––

MalesMales 92.692.6 93.493.4 0.890.89

Waist circumference (cm) Waist circumference (cm) ––

FemalesFemales 84.184.1 95.495.4 0.040.04

BMI (kg/mBMI (kg/m22) Males) Males 26.826.8 26.826.8 0.990.99

BMI (kg/mBMI (kg/m22) Females) Females 24.124.1 30.330.3 0.010.01

Cranial radiation and female gender are associated

with obesity in ALL survivors

Gurney Cancer 2006



OROR 95% CI95% CI

ALL survivor vs. siblingALL survivor vs. sibling 1.6 (1.4‐1.8)

Astrocytoma survivor vs. siblingAstrocytoma survivor vs. sibling 1.4 (1.2‐1.7)

Cranial radiation vs. no cranial radiationCranial radiation vs. no cranial radiation 1.6 (1.2‐2.0)

< $40,000 annual income vs. $40,000+ annual income< $40,000 annual income vs. $40,000+ annual income 1.4 (1.2‐1.7)

Black vs. Caucasian raceBlack vs. Caucasian race 1.5 (1.1‐2.1)

No activity in the past month vs. any activity/past monthNo activity in the past month vs. any activity/past month 1.3 (1.1‐1.5)

Cranial radiation, black race, lower income, a sedentary

lifestyle and a diagnosis of ALL or Astrocytoma are

associated with obesity in the entire CCSS cohort

Meacham CEBP 2010



0 10 20 30 40 50Percent (%)

Other radiationNo radiation

Cranial radiationChest radiation

No chemotherapyOther chemotherapy

Anthracyclines

No surgeryOther surgery

Amputation 1.5*1.1

1.01.0

1.4*1.01.0

†RR adjusted for age and gender

*p < 0.05

Percent of those with

an inactive lifestyle,

relative risks†

of

inactive lifestyle by

treatment

Cranial radiation and amputation are associated with

inactivityNess Cancer 2009


RR” 95% CI*

ALL 1.8 1.6‐2.0

AML 1.5 1.1‐1.9

Astrocytoma 1.9 1.6‐2.2

Medulloblastoma, PNET 2.6 2.2‐3.2

Other CNS tumors 2.3 1.8‐2.9

Hodgkin lymphoma 1.3 1.1‐1.5

Non‐Hodgkin lymphoma 1.7 1.4‐2.0

Wilms Tumor 1.6 1.3‐1.9

Neuroblastoma 1.4 1.2‐1.8

Osteosarcoma 1.8 1.5‐2.1

Ewing sarcoma 1.4 1.1‐1.9

Soft tissue sarcoma 1.6 1.4‐1.9

Inactivity by cancer type


Ness Cancer 2009


Other correlates of inactivity in the CCSS cohort

• Female gender

• Black race• Less than a high school education• Unemployment

• BMI < 18.5 kg/m2 or 30+ kg/m2

• Smoking

• Depression


Ness Cancer 2009


The Questions











Nutrient Intake Mean ( SD)Energy (kcal) 2215.0 (1182.4)Fat (g) 74.4 (40.6)Energy from fat (%) 30.6 (8.2)Energy from saturated fat (%) 10.4 (2.7)Protein (g) 83.9 (48.6)Carbohydrate (g) 290.5 (187.7)Energy from sugar (%) 16.6 (11.6)Total Fiber (g) 17.3 (11.0)Sodium (mg) 3113.4 (1502.1)

There is scant information on diet in this cohort

Robien J Pediatr Hematol Oncol 2008


Daily food group servings Mean (SD)

Fruit 2.9 (4.9)Vegetables 3.2 (2.3)Total grains 5.2 (3.1)Whole grains 1.3 (1.4)

Dairy 2.6 (2.5)Meat, poultry, fish (oz) 4.6 (3.7)

In this small group of 72 ALL survivors, daily intake is not optimal

Robien J Pediatr Hematol Oncol 2008

The Questions










Intervention

Diet*

and activity interventions during treatment

• Referral rate– Only 10% of those with musculoskeletal conditions are

referred for rehab

(Gohar SK Pediatr Hematol Oncol. 2010 27:179‐87.)

• Intervention data (randomized) is limited to ALL– Hartmann 2009 (N=51)

• Compliance < 36% with exercise• No improvements

– Marchese 2004 (N=28)• Improved dorsiflexion and knee extension

– Moyer‐Mileur 2009 (N=13)*• Improved physical activity levels

Diet*

and activity interventions among survivors

Diagnosis Age Timing Duration Frequency

Components Number Results

Takken

2009

ALL 6‐14

years

12

months

post

chemo

12 weeks 2

times per

week plus

home

exercises

Strengthenin

g, aerobic,

interval

training

9 enrolled4

completed

No effect

Blaauwbro

ek 2009

Multiple,

mostly ALL

18‐61

years

5+ year

survivor

10 weeks1 home

visit, 3

phone calls

Pedometer

feedback for

step goal

setting

46

enrolled,

38

completed

Increased

steps

Keats 2008 Multiple,

mostly

leukemia

and

lymphoma

14‐18

years

5+ year

survivor

16 weeks 1X

weekly in

hospital

training and

education

Education,

aerobic

training,

flexibility and

core strength

10 Improved

activity

+fitness –

declining

with

follow‐up

Diet and activity interventions among survivors

Diagnosis Age Timing Duration Frequency

Components Number Results

Collett*

2007

Adolescent

survivors

Mean

18

years

Mean 12

years

post dx

12 weeks Training with

exercise

physiologist –

center based

36(half

controls)

Null

Hudson*2002

Multiple Mean

15

years

Mean 10

years

post dx

1 in person

counseling

and goal

setting

session, 2

follow‐up

calls to

reinforce

Selected

health

behaviors

including diet

or physical

activity

266 (half

controls)

Null

Childhood cancer survivors have unique needs


Ness Ann Intern Med 2005; Kadan Lottick JNCI 2010; Gurney Ann Epidemiol 2007

Childhood cancer survivors have unique needs


Survivor Reported Barriers to Exercise

• Too tired• Too busy• Do not belong to a gym• Rather watch television

or read• No one to exercise with• Bad weather• Feel self‐conscious• Do not enjoy it

• Friends do not exercise• No willpower• No access to equipment• Worry about injury• Do not like to sweat• No support• Do not want to be sore• Unsure how to exercise• No place to exercise

Arroyave Oncol Nurs Forum 2008

Survivor reported barriers to adopting a healthy diet

To eating more fruits/vegetables

• Hard to get when dining out

• Do not like the taste• Not available at home• Cost too much• Take too long to prepare• Hurt stomach• Friends do not eat them• Family does not like them

To eating more whole grains

• Hard to get when dining out

• Do not like the taste• Family does not like them• Not available at home• Friends do not eat them• Cost too much• Take too long to prepare• Hurt stomach


To limiting high‐fat foods• Commercials make high‐fat foods

tempting• Hard to get low‐fat foods when

dining out• Friends eat a lot of high‐fat foods• Family eats a lot of high‐fat foods• Low‐fat foods do not taste good• No willpower• Low‐fat foods do not fill me up• Do not know how to choose

lower‐fat foods• Low‐fat foods not available at

home

To eating more high‐calcium foods• Hard to get when dining out• Hurt stomach• Not available at home• Do not like the taste• Friends do not eat them• Family does not like them

Survivor reported barriers to adopting a healthy diet


Summary• There are increasing numbers of childhood

cancer survivors

• Childhood cancer survivors have altered body composition

• They are inactive

• They are at increased risk for cardiac disease and early death

• Cranial radiation, amputation, female gender, and black race contribute to a poor outcome

Summary

• Altered body composition and inactivity are correlated

• Social correlates include lower income and lower educational attainment

• Smoking is associated with inactivity

• Dietary habits appear to be sub‐optimal

Summary

• Interventions are beginning to emerge

• There are problems with intervention participation and retention

• Additional work is needed that addresses the unique physical and cognitive needs of cancer survivors

• Perceived barriers to change need to be considered when designing interventions

• The interventions need to be portable

Childhood Cancer Survivor Study

•

The Childhood Cancer Survivor Study is an NCI‐ funded resource (U24 CA55727) to promote and

facilitate research among long‐term survivors of cancer diagnosed during childhood and

adolescence.

•

Investigators interested in potential uses of this resource are encouraged to visit:

www.ccss.stjude.org


http://www.ccss.stjude.org/


Documents

Kirsten Ness, PT, PhD AICR October · Kirsten Ness, PT, PhD AICR. October 2010. The Questions • How many childhood cancer survivors are there? • On average, are childhood cancer