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Adult Survivors of Childhood and Adolescent Cancer

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. 1990. 1985. 1980. 1976. Over 250,000 childhood cancer survivors in the US

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Adult Survivors of Childhood and Adolescent Cancer

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  1. Adult Survivors of Childhood and Adolescent Cancer Anna T. Meadows, MD Children’s Hospital of Philadelphia University of PA School of Medicine

  2. 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.)

  3. 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

  4. 5 10 15 20 25 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

  5. 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

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

  7. 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 Late Complications of Childhood Cancer Therapy

  8. Neurocognitive Late Effects • Radiation induced • dose related • age related • Chemotherapy induced • Methotrexate • Intrathecal therapy: • Triples > single agent • Surgical resection

  9. 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

  10. 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

  11. 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

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

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

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

  15. 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

  16. Relative Risk of Thyroid Cancer by Age and Radiation Dose

  17. 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

  18. LESG - Second Malignant Neoplasms

  19. Subsequent Neoplasms following update of LESG cohort

  20. 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

  21. 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

  22. Cumulative Incidence of a Second Cancer 36.0% Hereditary Retinoblastoma 5.69% Non-Hereditary Retinoblastoma Hereditary 963 760 615 401 147 30 Non-Hereditary 638 570 500 317 134 46 Number of Patients at Risk

  23. Cumulative Incidence of a Second Cancer Following Hereditary Rb 30.4% 9.4%

  24. NEUROFIBROMATOSIS TYPE 1

  25. GORLIN SYNDROME Radiation for Medulloblastoma

  26. 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

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

  28. 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

  29. 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

  30. Survivors’ Needs Education Treatment Risk factors Surveillance Surveillance Early detection of problems Anticipatory guidance Modifiable risk factors Empowerment/Advocacy Education Awareness

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

  39. Obstacles to TransitionAdult Caregiver Lack of familiarity with childhood cancer and late effects Heightened perception of care demands Lack of institutional support Economic concerns

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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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