Transcript presentation ( format)

Adult Survivors of
Childhood and Adolescent
Cancer
Anna T. Meadows, MD
Children’s Hospital of Philadelphia
University of PA School of Medicine
Cancer Survival, 0-14 Years of Age
SEER Program 1976-1997
100
Proportion Surviving
90
80
1990
70
1985
60
1980
1976
50
40
• Over 250,000 childhood cancer survivors in the US
• 1 in 1,000 is a childhood cancer survivor
• 1 in 570 is a childhood cancer survivor (ages 20 to 34 yr.)
30
20
10
0
0
2
4
6
8
10
12
14
16
Years from Diagnosis
18
20
22
Advances in Treatment for
Pediatric Cancer
• Chemotherapy responsiveness
• Multi-agent chemotherapy protocols
• Adjuvant and neoadjuvant therapy
• Improvements in surgery and anaesthesia
• Supportive therapies: Blood products,
broad spectrum antibiotics, antifungals
Late Mortality
Sex-specific survival (CCSS)
Survival function estimate
US Female
1.00
US Male
0.96
0. 92
Female
0.88
•Relapse
•Treatment-related
•Non-treatment-related
0.84
Male
0.80
5
10
15
20
Years since diagnosis
25
Mortality in Survivors of
Childhood Cancer
• Surveillance and End Results data
for 5 years survivors
• Diagnosis 1974-1980
– 7% mortality
• Diagnosis 1995-2000
– 4% mortality
Evolution of Survivorship
Research
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Anecdotal Reports
Case Series
Prospective Studies
Multivariate Analyses
Mathematical Modeling
Surveillance and Counseling
Intervention
Late Complications of
Childhood Cancer Therapy
• Growth and
Development
– linear growth
– intellectual function
– sexual maturation
• Reproduction
– fertility
– health of offspring
• Vital Organ Function
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cardiac
pulmonary
renal
gastrointestinal
• Second Neoplasms
– benign
– malignant
• Psychosocial adjustment
Neurocognitive Late Effects
• Radiation induced
– dose related
– age related
• Chemotherapy induced
– Methotrexate
– Intrathecal therapy:
• Triples > single agent
• Surgical resection
Prevention of Cognitive
Dysfunction
• Eliminate or reduce cranial irradiation
• Substitute chemotherapy with CNS
penetration
• Avoid parenteral methotrexate after radiation
• Monitor educational performance
• Provide early intervention
Gonadal Failure
• Males and females are different
• Fertility and hormone production are not
synchronous males, unlike females
• Radiation and alkylator agent
chemotherapy (cyclophosphamide,
ifosfamide, cisplatin, procarbazine,
nitrosoureas, mustard) are responsible;
doses are critical
Prevention of Gonadal Toxicity
• Eliminate or reduce radiation to the
gonads
• Design gender-specific protocols
• For males, avoid or reduce total dose
of alkylating agents
Cardiac Late Effects
• Anthracyclines
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Gender
Age
Dose
Latency
• Radiation
• > 25 - 30 Gy
• Cardiomyopathy
• Ventricular
dysfunction
• Pericarditis
• Rhythm
abnormalities
• Pericardial damage
• CAD
Prevention of Cardiac Toxicity
• Limit total dose of anthracyclines
• Infuse anthracyclines slowly
• Evaluate cardiac function during therapy
• Avoid concomitant radiotherapy
• Use the cardioprotectant dexrazoxane
Factors Predisposing to
Second Neoplasms
• Treatment
– radiation therapy
– chemotherapy: alkylating agents;
epipodophyllotoxins
• Genetic Conditions
– genetic retinoblastoma
– neurofibromatosis
– Li-Fraumeni Syndrome
Radiation Therapy and
Second Neoplasms
• bone and soft tissue sarcomas
– doses >40Gy; adolescents
• carcinomas of the breast
– doses >30Gy; adolescents
• thyroid adenomas and carcinomas
– young children; dose-effect
• basal cell carcinomas
Relative Risk of Thyroid Cancer
by Age and Radiation Dose
30
<5 years
5 - 9 years
10 -14 years
>=15 years
Relative Risk
25
20
15
10
5
0
10
20
30
40
Dose (Gy)
50
60
70
Chemotherapy and Second
Neoplasms
• Alkylators: myeloid leukemia and MDS
– chromosomes 5 and 7 abnormalities
– latent period 3 to 7 years
– dose relationship
• Epipodophyllotoxin:monocytic leukemia
– chromosome 11q23 abnormality
– dose and schedule dependent
– short latent period
Cumulative incidence
0.0
0.10 0.20 0.30
LESG - Second Malignant Neoplasms
0.0
10.0
20.0
Years since diagnosis
30.0
Subsequent Neoplasms following
update of LESG cohort
250
200
150
100
50
0
All Neoplams
1985
Solid Tumors
1994
2000
AML/NHL
Breast Cancer After Thoracic
Radiation in Childhood
• MEDLINE, EMBASE, Cochrane Library and
CINAHL search – 1966 to 2008
• Cumulative incidence 40-45 years 13-20%
• SIR 13.3-55.5
• Incidence increased linearly with RT dose
• ~13% Bilateral; most metachronous
• Benefits of targeted surveillance screening
Second Cancers in
Genetic Retinoblastoma
• Pineal gland
- familial cases at greater risk
• Bone and soft tissue sarcomas
- 6 to 10% up to 20 years without radiation
- increasing frequency with time after
radiation
• Malignant melanoma; leiomyosarcoma
Cumulative Incidence of a Second Cancer
Percent Cumulative Incidence, %
40
36.0%
Hereditary Retinoblastoma
30
20
10
5.69%
Non-Hereditary Retinoblastoma
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0
10
20
30
40
50
Time After Retinoblastoma Diagnosis, yrs
Hereditary
963
760
615
401
147
30
570
500
317
134
46
Non-Hereditary
638
Number of Patients at Risk
Percent Cumulative Incidence
Cumulative Incidence of a Second
Cancer Following Hereditary Rb
40
30.4%
30
20
9.4%
10
0
0
10
20
30
Survival (Years)
Radiotherapy
No Radiotherapy
40
NEUROFIBROMATOSIS TYPE 1
GORLIN SYNDROME
Radiation for Medulloblastoma
Psychosocial Late Effects
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Fear of recurrence and death
Adjustment to physiological late effects
Sexuality/intimacy issues
Changes in social support
Employment discrimination
Insurance discrimination
Financial issues
Quality of life issues
Symptoms of PTSD
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Hypervigilance for threat
Avoidance of traumatic reminders
Recurrent intrusive memories
Reckless behavior
Regressive dependency
Affective blunting/numbing
Irritability
Sense of isolation
Positive Psychosocial Late Effects
• Greater appreciation for life
• Increased life satisfaction
• Renewed spirituality or religiosity
• Improved self-acceptance & self-awareness
• Strengthened relationships with significant
others
• Increased ability to cope with adversity
• Present-centered awareness
Reduction in Psychosocial
Morbidity
• Individual and group support during therapy
• Incorporate family members in education and
counseling
• Identify families at high risk requiring
additional intervention
• Continue support after completion of therapy
Survivors’ Needs
• Education
• Treatment
• Risk factors
• Surveillance
• Surveillance
• Early detection of problems
• Anticipatory guidance
• Modifiable risk factors
• Empowerment/Advocacy
• Education
• Awareness
Transition from Pediatrics to
Adult Focused Care
• Determining readiness for transition
• Providing comprehensive care that is user-friendly
in an adult-centered environment
• Transmitting information from pediatrics to adult
setting
• Development of a stable infrastructure for ongoing
care and research
Ideal Follow-up Program
• Coordinated, comprehensive care
• Multidisciplinary; culturally and socially
appropriate
• Health education and anticipatory guidance
based on therapy and other risk factors
• Transition to adult health care system
Survivor Intervention to Reduce
Late Effects
• Health education re: exercise, diet,
sun, smoking cessation
• Reproductive counseling
• Psychosocial support
• Education regarding previous
disease history
• Discussion of risks associated with
treatment
Provider Education to Reduce
Late Effects
• Increase knowledge of late
effects of cancer therapy
• Improve ability to recognize and
treat subclinical late effects
• Detect second cancers early
– Screening of high risk patients for
RT-associated cancers
– Counseling of survivors with
genetic predisposition
Transitional Care Models
• Disease Specific: disease specific where individuals
move from pediatric specialist to adult specialist.
• Generic: adolescent focused, move from pediatric,
adolescent to adult services with disease specialist as
part of the team.
• Primary Care: use a family practitioner, with
specialist as consultants*
• Single Site: use same clinical environment and
moves from pediatric to adult with specialist as
consultants
Obstacles to Transition
Patient
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Dependent Behavior; Immaturity
Severe Illness/Disability
Lack of support systems
Lack of trust in caregivers
Poor adherence to treatment regimes
Psychological Issues
Obstacles to Transition
Family
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Emotional dependency
Excessive need to control
Heightened perception of disability
Lack of trust in caregivers
Mistaken perception of potential survival
Psychological Issues
Obstacles to Transition
Pediatric Caregiver
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Concerns about the program
Emotional bond with patient and family
Perceptions of own skill as caregiver
Distrust of adult caregiver
Ambivalence towards transition
Economic concerns
Obstacles to Transition
Adult Caregiver
• Lack of familiarity with childhood
cancer and late effects
• Heightened perception of care
demands
• Lack of institutional support
• Economic concerns
Research Questions
• Incidence and prevalence of late effects
of cancer treatment
• Relationship between treatment
modality, including dose, and late effects
• Ways to reduce the physiological and
psychosocial morbidity of cancer
treatment
• Interventions to improve the quality of
survival throughout the lifespan
Research Questions
• How best to provide comprehensive care
throughout the life span of survivors
• What is the best venue for follow-up care
• Will insurance cover necessary care
• How to monitor changes in survivors as they
age
• How to determine readiness to transition
• Does systematic evaluation and follow-up
care reduce late effects
Research Principles
Hypotheses
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Supported by clinical observations
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Involve important outcomes
Availability of preliminary information
Methods
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Retrospective or prospective
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Availability of necessary sample size
Avoidance of selection bias
Sufficient resources for completion of study
Follow-up is adequate
Clinical Care/Research
Conflicts
• Procedures
– Interventions based on clinical need
• Reimbursement for studies
– Some not clinically indicated
• Investigator interest, time, expertise
– Acute care needs take priority
Conclusions
As survivors enter the third and fourth decade of life they will need to
cope with the normal demands of young adulthood while dealing
with possible physical and psychological effects of their cancer
treatment.
Transition programs for young adult survivors should determine
readiness for transition, develop/interpret guidelines, and provide
research opportunities that test the appropriate venues for care
and the effectiveness and efficiency of surveillance guidelines.