Melissa M. Hudson, MDCancer Survivorship Division

Childhood Cancer Survivors:Evidence for Accelerated Aging

Overview of Aging

• Gradual, continuous process of natural change characterized by decline in many body functions– Process begins in early adulthood– Decline varies by time of onset among individuals

• chronological v. biological age – Factors influencing timing/rate of decline

• Heredity/genes• Lifestyle/health habits• Exposures to toxins• Health care

Conditions associated with aging: organ dysfunction

Hearing loss

Heart disease

Cognitive decline Dementia

CataractsFar-sightedness

Reproductive functionMenopauseOsteoporosis

Loss of muscle mass

Conditions associated with aging: Cancer

Conditions associated with aging: Cancer

1 in 2 men 1 in 3 womenACS Cancer Statistics 2015

Chronic disease in general population

• 4 of 5 adults age 50 or older suffer from at least one chronic condition – More than half have more

than one chronic condition• Common chronic diseases:

– High blood pressure– High cholesterol– Mental illness– Diabetes– Heart disease– Cancer

Health conditions in 1713 childhood cancer survivors undergoing comprehensive risk-based health testing in St. Jude Lifetime Cohort

Condition affecting cognitive skills

Condition affecting cognitive heart

Condition affecting endocrine function

Condition affecting hearing

Condition affecting lung function

At least one serious condition

At least one condition

0 10 20 30 40 50 60 70 80 90 100

Age at diagnosis: 6 yrs (range, 0-24)

Age at study: 32 yrs (range 18-60)

Time from diagnosis: 25 yrs (range 10-47)

Hudson et al. JAMA 2013

Normal ovarian reserve

AGE

FOLLICLE COUNT

25,000

37

1,000

51

Menopause

birth

1,000,000

12

Menarche

Acute ovarian failure in childhood cancer survivors

Follicle Count

25,000

(37)

1,000

(51)

Cancer Treatment

6.3% of women studied in CCSS Independent risk factorsIncreasing doses of abdominal/pelvic radiation >1,000 cGy to ovaries (OR 90.9) Alkylating agent exposure: Procarbazine (OR 2.6-3.2) Cytoxan at age > 12 (OR 4.9) High dose alkylators (BMT doses)

Chemaitilly et al, J Clin Endocrin Metab, 2006

Premature menopause in childhood cancer survivors

Follicle Count

25,000

1,000

Cancer Treatment

8% of women studied in CCSS•Approximately 30% treated with abdominal/pelvic radiation plus alkylators•Independent risk factors: Advancing age Increasing radiation dose to ovaries Increasing doses of alkylators Diagnosis of Hodgkin lymphoma

Sklar et al, J Natl Cancer Inst, 2006

Armstrong et al, J Clin Oncol , 2013

11.8%

6.8%

5.0%

0.3%

At 45 Years

Heart failure in childhood cancer survivors

Congestive Heart Failure

Armstrong et al, J Clin Oncol, 2013

180160

80

60

40

20

100

0

Ra

te R

ati

o RR=34.1

HTN,No

Anthracycline

RR=8.3

Anthracycline,No HTN

RR=88.5

HTN +Anthracycline

How much does high blood pressure contribute to development of heart failure

• Longitudinal evaluation• 10,724 survivors, CCSS• Hypertension potentiates

anthracycline-associated risk for heart failure

• Multiple traditional CV risk factors increase risk

• Prevention should be focus of future interventions

Relative excess risk due to interaction

= 44.5

Chronic health conditions

Breast cancer in Hodgkin lymphoma survivors

Bhatia S, et al. J Clin Oncol, 2003

Median time to diagnosis of breast cancer from radiation exposure is 15 to 20 years, with cases being diagnosed as

early as 8 years from exposure.

Start breast cancer screening at age 25 or 8

years after radiation

• Pre-frailty and Frailty are defined by a cluster of five measurements of physical state/abilities– Lean muscle mass – Exhaustion – Energy expenditure – Walking speed – Muscle weakness

Frailty as a measure of aging

Pre-frail = 2 items Frail = 3+ items

7.9

22.2

7.2

15.0

0.0

6.2

0

5

10

15

20

25

Frail Pre-frail

Percent

SJLIFE

CHS

Controls

• N=1922 (50.3% male)• Mean age at diagnosis

8.2±5.6 years• Mean age 33.6±8.1 years• Mean time since diagnosis

25.5±7.7 years• Frailty phenotype differed

by sex (females) , age (older), and diagnosis

CHS: Cardiovascular health study age range 65-101 yearsControl participants age range 18-50 years (mean 29.0±7.5years) Ness KK et al, JCO, 2013

Frailty in childhood cancer survivors

Evidence for accelerated aging?

• Yes: specific cancer treatments do cause organ dysfunction and can lead to diseases that typically develop in older individuals.

Important facts to consider:• The results presented reflect outcomes of older treatment

approaches that are no longer used. • Many changes have been made in cancer treatments to reduce

injury to normal organs and tissues.

Advice to cancer survivors: before and during therapy

• Talk to your care team about cancer treatment effects on health before therapy.

• Ask about ways to prevent or reduce chances of injury to healthy organs and tissues.

• Ask about how your health will be monitored during therapy to check for health effects.

Advice to cancer survivors: after therapy

• Know specific details about your cancer treatment.• Know the health risks linked to this treatment.• Know about the screening tests recommended to monitor

health risks linked to your treatment. • Have regular check ups to stay on

top of all health issues.• Understand how health habits can

modify the risk of organ injury and accelerated aging.

Practice health habits that protect against accelerated aging

• Smoking• Sun exposure• Diet• Physical activity• Alcohol intake

Thank you for your attention!

Acknowledgements•American Lebanese Syrian Associated Charities (ALSAC)•NCI Cancer Center Support (CORE) grant CA 21765