Adult Survivors of Childhood and Adolescent Cancer

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Adult Survivors of Childhood and Adolescent
Cancer

• Anna T. Meadows, MD
• Childrens Hospital of Philadelphia
• University of PA School of Medicine

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Cancer Survival, 0-14 Years of Age SEER Program
1976-1997
1990
1985
1980
1976

• 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.)

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Advances in Treatment forPediatric Cancer

• Chemotherapy responsiveness
• Multi-agent chemotherapy protocols
• Adjuvant and neoadjuvant therapy
• Improvements in surgery and anaesthesia
• Supportive therapies Blood products, broad
  spectrum antibiotics, antifungals

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Late Mortality Sex-specific survival (CCSS)
US Female
1.00
US Male
0.96
0. 92
Survival function estimate
Female
0.88

• Relapse
• Treatment-related
• Non-treatment-related

Male
0.84
0.80
Years since diagnosis
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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

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Evolution of Survivorship Research

• Anecdotal Reports
• Case Series
• Prospective Studies
• Multivariate Analyses
• Mathematical Modeling
• Surveillance and Counseling
• Intervention

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Late Complications of Childhood Cancer Therapy

• Growth and Development
• linear growth
• intellectual function
• sexual maturation
• Reproduction
• fertility
• health of offspring

• Vital Organ Function
• cardiac
• pulmonary
• renal
• gastrointestinal
• Second Neoplasms
• benign
• malignant
• Psychosocial adjustment

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Neurocognitive Late Effects

• Radiation induced
• dose related
• age related
• Chemotherapy induced
• Methotrexate
• Intrathecal therapy
• Triples gt single agent
• Surgical resection

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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

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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

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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

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Cardiac Late Effects

• Anthracyclines
• Gender
• Age
• Dose
• Latency
• Radiation
• gt 25 - 30 Gy

• Cardiomyopathy
• Ventricular dysfunction
• Pericarditis
• Rhythm abnormalities
• Pericardial damage
• CAD

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Prevention of Cardiac Toxicity

• Limit total dose of anthracyclines
• Infuse anthracyclines slowly
• Evaluate cardiac function during therapy
• Avoid concomitant radiotherapy
• Use the cardioprotectant dexrazoxane

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Factors Predisposing to Second Neoplasms

• Treatment
• radiation therapy
• chemotherapy alkylating agents
  epipodophyllotoxins
• Genetic Conditions
• genetic retinoblastoma
• neurofibromatosis
• Li-Fraumeni Syndrome

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Radiation Therapy and Second Neoplasms

• bone and soft tissue sarcomas
• doses gt40Gy adolescents
• carcinomas of the breast
• doses gt30Gy adolescents
• thyroid adenomas and carcinomas
• young children dose-effect
• basal cell carcinomas

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Relative Risk of Thyroid Cancer by Age and
Radiation Dose
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Chemotherapy and Second Neoplasms

• Alkylators myeloid leukemia and MDS
• chromosomes 5 and 7 abnormalities
• latent period 3 to 7 years
• dose relationship
• Epipodophyllotoxinmonocytic leukemia
• chromosome 11q23 abnormality
• dose and schedule dependent
• short latent period

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LESG - Second Malignant Neoplasms
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Subsequent Neoplasms following update of LESG
cohort
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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

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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

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Cumulative Incidence of a Second Cancer
36.0
Hereditary Retinoblastoma
5.69
Non-Hereditary Retinoblastoma
Hereditary 963 760 615 401 147 30 N
on-Hereditary 638 570 500 317 134 46 Number
of Patients at Risk
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Cumulative Incidence of a Second Cancer Following
Hereditary Rb
30.4
9.4
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NEUROFIBROMATOSIS TYPE 1
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GORLIN SYNDROME Radiation for Medulloblastoma
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Psychosocial Late Effects

• 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

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Symptoms of PTSD

• Hypervigilance for threat
• Avoidance of traumatic reminders
• Recurrent intrusive memories
• Reckless behavior
• Regressive dependency
• Affective blunting/numbing
• Irritability
• Sense of isolation

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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

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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

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Survivors Needs

• Education
• Treatment
• Risk factors
• Surveillance
• Surveillance
• Early detection of problems
• Anticipatory guidance
• Modifiable risk factors
• Empowerment/Advocacy
• Education
• Awareness

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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

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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

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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

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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

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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

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Obstacles to TransitionPatient

• Dependent Behavior Immaturity
• Severe Illness/Disability
• Lack of support systems
• Lack of trust in caregivers
• Poor adherence to treatment regimes
• Psychological Issues

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Obstacles to TransitionFamily

• Emotional dependency
• Excessive need to control
• Heightened perception of disability
• Lack of trust in caregivers
• Mistaken perception of potential survival
• Psychological Issues

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Obstacles to TransitionPediatric Caregiver

• 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

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Obstacles to TransitionAdult Caregiver

• Lack of familiarity with childhood cancer and
  late effects
• Heightened perception of care demands
• Lack of institutional support
• Economic concerns

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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

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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

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Research Principles

• Hypotheses
• Supported by clinical observations
• Involve important outcomes
• Availability of preliminary information
• Methods
• Retrospective or prospective
• Availability of necessary sample size
• Avoidance of selection bias
• Sufficient resources for completion of study
• Follow-up is adequate

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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

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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.

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