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Adult Survivors of Childhood and Adolescent Cancer

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Title: Adult Survivors of Childhood and Adolescent Cancer


1
Adult Survivors of Childhood and Adolescent
Cancer
  • Anna T. Meadows, MD
  • Childrens Hospital of Philadelphia
  • University of PA School of Medicine

2
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3
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.)

4
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

5
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
6
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

7
Evolution of Survivorship Research
  • Anecdotal Reports
  • Case Series
  • Prospective Studies
  • Multivariate Analyses
  • Mathematical Modeling
  • Surveillance and Counseling
  • Intervention

8
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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11
Neurocognitive Late Effects
  • Radiation induced
  • dose related
  • age related
  • Chemotherapy induced
  • Methotrexate
  • Intrathecal therapy
  • Triples gt single agent
  • Surgical resection

12
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

13
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

14
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

15
Cardiac Late Effects
  • Anthracyclines
  • Gender
  • Age
  • Dose
  • Latency
  • Radiation
  • gt 25 - 30 Gy
  • Cardiomyopathy
  • Ventricular dysfunction
  • Pericarditis
  • Rhythm abnormalities
  • Pericardial damage
  • CAD

16
Prevention of Cardiac Toxicity
  • Limit total dose of anthracyclines
  • Infuse anthracyclines slowly
  • Evaluate cardiac function during therapy
  • Avoid concomitant radiotherapy
  • Use the cardioprotectant dexrazoxane

17
Factors Predisposing to Second Neoplasms
  • Treatment
  • radiation therapy
  • chemotherapy alkylating agents
    epipodophyllotoxins
  • Genetic Conditions
  • genetic retinoblastoma
  • neurofibromatosis
  • Li-Fraumeni Syndrome

18
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

19
Relative Risk of Thyroid Cancer by Age and
Radiation Dose
20
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

21
LESG - Second Malignant Neoplasms
22
Subsequent Neoplasms following update of LESG
cohort
23
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

24
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

25
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
26
Cumulative Incidence of a Second Cancer Following
Hereditary Rb
30.4
9.4
27
NEUROFIBROMATOSIS TYPE 1
28
GORLIN SYNDROME Radiation for Medulloblastoma
29
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

30
Symptoms of PTSD
  • Hypervigilance for threat
  • Avoidance of traumatic reminders
  • Recurrent intrusive memories
  • Reckless behavior
  • Regressive dependency
  • Affective blunting/numbing
  • Irritability
  • Sense of isolation

31
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

32
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

33
Survivors Needs
  • Education
  • Treatment
  • Risk factors
  • Surveillance
  • Surveillance
  • Early detection of problems
  • Anticipatory guidance
  • Modifiable risk factors
  • Empowerment/Advocacy
  • Education
  • Awareness

34
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

35
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

36
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

37
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

38
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

39
Obstacles to Transition Patient
  • Dependent Behavior Immaturity
  • Severe Illness/Disability
  • Lack of support systems
  • Lack of trust in caregivers
  • Poor adherence to treatment regimes
  • Psychological Issues

40
Obstacles to Transition Family
  • Emotional dependency
  • Excessive need to control
  • Heightened perception of disability
  • Lack of trust in caregivers
  • Mistaken perception of potential survival
  • Psychological Issues

41
Obstacles to Transition Pediatric 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

42
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

43
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

44
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

45
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

46
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

47
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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