Transcript Slide 1

Optimizing the Life-long Health
of Childhood Cancer Survivors
Paul Nathan MD, MSc
Paediatric Oncologist/Associate Scientist
The Hospital for Sick Children
Toronto, Canada
Learning objectives
1. Explain why late effects of treatment occur and what
influences them
2. Discuss risk-based care and how it impacts long-term
follow-up
3. Examine current research and how it influences
survivorship
The childhood cancer
success story
% relapse free
•More intense therapy
2008: ~80%
90
80
70
60
50
40
30
20
10
0
•Better supportive care
•Rationalization of treatment (more in
some, less in others) – clinical trials
1960’s: ~10%
1960
1970
1980
1990
Year
•Some new treatments e.g. stem cell
2000
2005
transplant, molecularly targeted agents
How many survivors are there?
328,652
Mariotto AB, Cancer Epidemiol Biomarkers Prev. 2009
“It’s not over
when it’s over”
Patricia Ganz, Journal of Oncology Practice 2006
A “small” number of children have a
large lifetime impact
10,700 new childhood cancers in US in 2010
1,518,860 new adult cancers in 2010
Bleyer, 1990
Part 1
Why do late effects
occur?
What is the cost of cure?
Based on survivors treated between 1970-86:
•
By 30 years after their cancer:
•
3/4 have at least one chronic health condition
•
2/5 have a severe or life threatening condition
•
8 times more likely to have a severe or life
threatening health condition than their siblings
Oeffinger, NEJM, 2006
Armstrong, JCO, 2009
9
Risk of developing late effects
0.8
Any physical late
effect
Cumulative Incidence
0.7
0.6
0.5
0.4
Severe or life
threatening late
effect
0.3
0.2
0.1
0
0
5
10
15
20
25
Years Since Diagnosis
30
How much more likely is a cancer survivor to
develop a serious health condition?
Second cancer: 15
Heart failure: 15
Coronary artery disease: 10
Severe learning difficulties: 11
Ovarian failure – early menopause: 3 ½
Kidney failure/dialysis: 9
*compared to their siblings
What is the cost of cure?
Survivors are more likely than their siblings to report:
• Poor general health (2 ½x)
• Poor mental health (2x)
• Limitations in activities (e.g. personal care, shopping or
housework) (5x)
• Inability to attend school or work (6x)
12
But…
• Only 10% assess their health as poor
• An as yet unknown proportion are “thrivers”
• Many survivors are living happy, healthy lives
13
Principles of Survivorship
• Late effects are the price of success
• Late effects are a moving target
• Today’s treatments are the authors of tomorrow’s late
effects
• Specific exposures do not consistently result in particular
late effects
• Individual outcomes are difficult to predict
• Gene-environment interactions
14
What causes late effects?
•Radiation
•e.g. brain tumors,
bone tumors
•Chemotherapy
•Surgery
Tumor
Lifestyle and
health
behaviors
Treatment
Child’s attributes/
genetics
•Younger age at diagnosis
•Gender
•Genes (good and bad)
Chemotherapy  late effects
Drug
Late effect
Adriamycin
Heart disease
Cyclophosphamide
Infertility, secondary leukemia
Dexamethasone
Reduced bone density, osteonecrosis
Bleomycin, busulfan
Lung disease
Cisplatinum
Hearing loss, kidney disease
How do genes influence late
effects?
•Genes are the blueprint for all body processes
•4 nucleotides (A,T,C,G) are the template for making
proteins
•Humans can have minor differences in the code for certain
proteins (e.g. replace A with C)
•Single nucleotide polymorphism (SNP’s)
•This changes the way the proteins work  can make them
more or less effective
•Can change how the body processes chemotherapy 
increased or decreased toxicity
•SNP’s have been shown to impact heart problems,
hearing, attention …
17
Does gender make a difference?
• Females at slightly higher risk for:
•
•
•
•
•
Lower IQ after ALL therapy
Heart disease after anthracyclines
Overweight after cranial radiation
Hypothyroidism after neck radiation
Steroid-induced osteonecrosis
• Impact on fertility different in females vs. males
Lifestyle
• Exercise, diet
• Lifestyle habits – smoking, sun tanning,
regular medical care
• Important and (unlike prior treatment) can
be modified by the survivor
Part 2
Risk-based care
Risk-based care
A prescription for lifelong health care focused
on ensuring each survivor’s best health
outcomes based on their past treatment
Cancer survivors – a focus of national
and international attention
2003
2006
Risk-based survivor-focused care after
the completion of therapy
All survivors require a systematic plan for periodic
assessment and surveillance aimed at prevention
or early diagnosis and management of late
effects.
Care should be adapted to the risks arising from the
cancer, its therapy, genetic predispositions, lifestyle
and co-morbid health conditions.
23
The purpose of risk-based
care
To PREVENT late effects before they happen
To IDENTIFY late effects before they cause problems
To MODIFY existing late effects
To use the lessons from survivors to influence the care
of NEWLY DIAGNOSED PATIENTS
24
http://www.survivorshipguidelines.org
For example: 28 yr old woman treated for Hodgkin’s
lymphoma at age 14 yr with chemotherapy and chest
radiation
Every 6 months
• Breast exam  breast cancer
Yearly
• Visit to physician with complete check-up
• Thyroid examination  thyroid cancer
• Thyroid function tests  hypothyroidism
• Mammogram (or breast MRI)  breast cancer
Every 2 years
• Echocardiogram  early signs of heart failure
27
Where do survivors get their care?
100.0%
80.0%
100.0%
85.4%
80.0%
60.0%
40.0%
20.0%
60.0%
%
0.0%
40.0%
20.0%
14.6%
0.0%
Cancer center
Primary care facility
Cancer center visits and the development of
late effects in the years after diagnosis
1
0.9
GRADE
Chronic1-5
health conditions, any grade
Prevalence or cumulative incidence *
0.8
CCFU
Visit to cancer center within past two years
0.7
*
0.6
0.5
0.4
0.3
0.2
0.1
0
0
5
10
15
Interval from cancer diagnosis, years
20
25
The majority of adult survivors of childhood
cancer are seen by a family physician in
their community  not at a cancer center
Do survivors seen outside of a cancer center
get “risk-based” care?
Screening
• Women who receive radiation (>20 Gy) to the breast
need an annual mammogram (+/- MRI) starting at age
25 (or 8 years off therapy)
• Any patient treated with an anthracycline +/- chest
radiation needs an echocardiogram every 1, 2 or 5
years
Optimal screening practices
Mammogram
169/414 (41%)
Echocardiogram
511/1810 (28%)
Surveillance tests according to care at a
cancer centre vs. community
Observations
Majority of adult survivors of childhood
cancer receive care from a primary care
physician
Primary care physicians less likely to
provide guideline recommended screening
tests than cancer centers
Surveillance for new cancers
• ~9% of survivors will develop a new cancer within 30 years
of their original diagnosis
• A further 7% will develop a new skin cancer (usually in an
area of previous radiation)
• This risk is 9x greater than the general population
• Survivors at risk for a new cancer need regular
surveillance!
Meadows, JCO; Mertens JCO
What can be done to prevent new
cancers or detect them early
Breast cancer screening

Starting at puberty
Breast self exam monthly
Clinical breast exam yearly
Age 25 (or >8 years after
radiation)
Clinical breast exam every 6 months
Mammogram every year (+/- breast MRI)

Thyroid cancer: Annual thyroid exam

Skin cancer: Sunscreen, sun avoidance, annual skin
examination

Lung cancer: Smoking cessation programs (peer to peer; direct
or internet)
36
Screening in survivors at average risk for a new cancer (USPSTF)
Breast
Cervix
Mammography every 1 to 2 years for
Pap smear every 3 years starting at age
women aged ≥40 y
21 years
Surveillance in survivors at high risk for a new cancer (COG)
Breast
Colorectal
Skin
≥20 Gy radiation therapy to ≥30 Gy radiation therapy Any radiation therapy
the chest
to the abdomen, pelvis,
or spine
Annual mammogram
Colonoscopy every 5
Annual skin examination
starting 8 years after
years starting at age 35
of radiated areas
radiation or age 25 years,
years
whichever is last
Compliance with recommended
screening tests – average risk
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
81%
67%
Mammography
Pap smears
% complying with guidelines
Compliance with Recommended Surveillance
Tests – high risk
100%
80%
60%
46%
40%
20%
27%
12%
0%
Colonoscopy
Mammography
Skin exam
Observation
• Survivors are reasonably compliant with
population screening but not with high-risk
surveillance
• Suggests “lack of knowledge” rather than
“lack of motivation”
Survivor-related barriers to riskbased care
• Feel invulnerable to late effects or do not perceive them as
serious
• Lack of knowledge about treatment received
• Lack of awareness of potential late effects/future risks
• Other factors: economic (missing work, cost of travel,
childcare), culture, spiritual belief
Zebrack et al., 2004
Mertens et al., 2004
Survivor care plans
Barriers to risk-based care: Physician
and health care system-related factors
• Lack of capacity for survivor care within cancer treating
institutions
• Primary care physicians unfamiliar with population
• Poor communication between cancer centers and primary
care physicians
• Lack of health insurance or coverage of recommended
screening tests
Part 3
Current survivorship
research
What we have and have not
researched
• Several long term cohort studies
• Late Effects Study Group
• Childhood Cancer Survivor Study (CCSS)
• British Childhood Cancer Survivor Study (BCCSS)
• St. Jude Life
The Childhood Cancer Survivor
Study
• Established in 1994
• 26 institutions (25 US, 1 Canada)
• National Cancer Institute funded study
•
•
•
•
5-year survivors of selected childhood cancers
Diagnosed 1970-1986
<21 years at diagnosis
Alive, regardless of disease status
46
CCSS – US participants
(N=13,277)
47
Topics studied by the CCSS
• Specific late effects (heart, fertility, 2nd cancer
etc.)
• Health care and cancer screening
• Survivor knowledge
• Psychological outcomes
• Insurance, marriage, employment etc.
• Physical activity, obesity etc.
48
New CCSS cohort
• Can’t always apply knowledge about survivors
treated in 70’s/80’s to today’s children
• We need to learn about survivors treated more
recently
• Recruiting 20,700 new survivors treated between
1987-1999
• Increased focus on minorities
49
What we have and have not
researched
• Modification of therapy during treatment
• Elimination of cranial radiation therapy
• Dexrazoxane to protect the heart
• Hearing protectants (e.g. sodium thiosulfate)
What we have and have not
researched
Single nucleotide polymorphisms (SNP)
associated with:
• Cisplatinum-induced hearing loss
• Obesity after cranial radiation (leptin receptor)
• ADD after MTX therapy for ALL
• Anthracycline cardiomyopathy
Ross et al. Nature Genetics 2009
Ross et al. JCO 2004
Krull et al. J Peds 2007
Blanco et al. Cancer 2008
What we have and have not
researched
• Few studies of interventions after therapy:
• Difficult to target adult survivors since most no longer
in “cancer system”
• Difficult to test preventive strategies in children
• Limited collaboration between oncologists and other
researchers
What we have and have not
researched
• St. Jude Consortium for Pediatric Research
• Low dose tamoxifen to prevent breast cancer
• Physical activity intervention in children on ALL
treatment
• Beta blockers/ACE inhibitors after anthracyclines
• COG Outcomes and Survivorship Committee
Part 4
Resources for survivors
and their families
Provides information and resources for pediatric
cancer survivors.
56
Programs include equipment and supplies, support groups,
educational literature, and summer camps for childhood
cancer survivors.
57
Online information and electronic support groups for
pediatric cancer survivors and their caregivers
58
Provides resource guides, quarterly newsletters, referrals,
information, and publishes books for pediatric cancer
survivors, including ‘Educating the Child with Cancer’.
A non-profit organization that offers extensive
education, advocacy and public health resources.
61
Answers for Life After Cancer
Has a comprehensive website, dedicated to issues that may occur after
treatment and offers suggestions to deal with the long-term effects of
treatment, tips for healthy living and archived teleconferences/web
conferences.
Provides web conferences for professionals and families on medical late
effects, health insurance, nutrition, sibling concerns and educational late
effects.
Sponsors survivorship conferences throughout the country.
Distributes educational material for parents, young adults and teens
addressing issues and concerns that may occur after treatment.
Web access to the Late Effects Assessment Tool, a free interactive tool
designed to prepare survivors for potential medical issues that may arise
after treatment has ended and to offer strategies for maintaining overall
health.
www.beyondthecure.org
Childhood Cancer
Ombudsman Program
[email protected]
Provides help for survivors experiencing
problems getting access to appropriate
education, medical care, health care cost
coverage, and employment.
Federation for Children
with Special Needs
http://www.fcsn.org
Federally funded organization providing
information on special education rights and
laws, conferences, referrals for services,
parent training workshops, publications, and
advocacy information.
National Center for
Learning Disabilities
http://www.ncld.org
Offers extensive resources, referral services,
and educational programs related to learning
disabilities.
US Department of
Justice
ADA Information Line, Civil
Rights Division
http://www.usdoj.gov
Answers questions about the Americans with
Disabilities Act, explains how to file a
complaint, and provides dispute resolution
information.
Questions