melissa m. hudson, md cancer survivorship division childhood cancer survivors: evidence for...
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Melissa M. Hudson, MDCancer Survivorship Division
Childhood Cancer Survivors:Evidence for Accelerated Aging
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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
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Conditions associated with aging: organ dysfunction
Hearing loss
Heart disease
Cognitive decline Dementia
CataractsFar-sightedness
Reproductive functionMenopauseOsteoporosis
Loss of muscle mass
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Conditions associated with aging: Cancer
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Conditions associated with aging: Cancer
1 in 2 men 1 in 3 womenACS Cancer Statistics 2015
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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
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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
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Normal ovarian reserve
AGE
FOLLICLE COUNT
25,000
37
1,000
51
Menopause
birth
1,000,000
12
Menarche
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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
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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
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Armstrong et al, J Clin Oncol , 2013
11.8%
6.8%
5.0%
0.3%
At 45 Years
Heart failure in childhood cancer survivors
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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
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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
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• 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
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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
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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.
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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.
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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.
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Practice health habits that protect against accelerated aging
• Smoking• Sun exposure• Diet• Physical activity• Alcohol intake
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Thank you for your attention!
Acknowledgements•American Lebanese Syrian Associated Charities (ALSAC)•NCI Cancer Center Support (CORE) grant CA 21765