Late Effects of Cancer Therapy

1. Late Effects of Cancer Therapy Lillian R. Meacham, MD Kathelen V Amos Children’s Chair for Cancer Survivorship Medical Director of Cancer Survivor Program Professor of Pediatrics/ Emory University

2. Why Do We Need Specialized Medical Care for Survivors? 5 year survival rate for cancer Childhood cancer is 80% Adult cancer is 60% There are 10 million cancer survivors in the US 1 in 640 people is a survivor of pediatric cancer In adult survivors of pediatric cancer 75% have a chronic health condition 42% of those conditions are severe, disabling, life threatening or result in death

3. National Survivorship Prioritiesare being Established

4. Key Survivorship Publications The President's Cancer Panel annual report 2003-2004 Living Beyond Cancer: Finding a New Balance. Institute of Medicine Reports (IOM) In 2003 Childhood Cancer Survivorship: Improving Care and Quality of Life In 2006 From Cancer Patient to Cancer Survivor: Lost in Transition In 2007 Implementing Cancer Survivorship Care Planning The Centers for Disease Control and Prevention – 2006 A National Plan for Cancer Survivorship: Advancing Public Health Strategies.

5. Lost in Transition

6. National Key Recommendations 1. Survivor care is a distinct phase of cancer care Education 2. Raise awareness of the needs of cancer survivors 3. Educational opportunities to health care providers Clinical Care 4. Models of coordinated interdisciplinary 5. Comprehensive care summary and follow-up 6. Evidence-based clinical practice guidelines 7. Access to adequate and affordable health insurance. 8. Eliminate discrimination and minimize adverse effects of cancer on employment, Research 9. Survivorship research 10. Quality of survivorship care measures

7. Snapshot of Survivors

8. Health status of adults who are long-term childhood cancer Survivor Childhood Cancer Survivor Study (CCSS)

9. CCSS Childhood Cancer Survivor Study 26 institutions <21 at time of diagnosis Diagnosed between 1970-1986 Survived 5 years 14,000 survivors / 3,500 siblings Medical Record Abstraction Questionnaires

10. Health Status of Adults who are Long-Term Childhood Cancer Survivors Childhood Cancer Survivor Study (CCSS) Survivors (9535) vs Siblings (2916) Functional Impairment Self-care Needing help with personal care needs, such as eating, bathing, dressing or getting around your home Routine chores/ business Needing “ help in in handling routine needs, such as everyday household chores, doing necessary business, shopping or getting around for other purposes” Job/ school “keeping you from holding a job or attending school” Activity limitation Moderate activity- moving a table, carrying groceries or bowling Walking upstairs or climbing a few flight of stairs Walking 1 blockFunctional Impairment Self-care Needing help with personal care needs, such as eating, bathing, dressing or getting around your home Routine chores/ business Needing “ help in in handling routine needs, such as everyday household chores, doing necessary business, shopping or getting around for other purposes” Job/ school “keeping you from holding a job or attending school” Activity limitation Moderate activity- moving a table, carrying groceries or bowling Walking upstairs or climbing a few flight of stairs Walking 1 block

11. 400 Long-term survivors and 560 controls Long Term Survivors no difference Quality of life Level of self esteem Female LTS had more cancer specific worries than male LTS Long Term Survivors less worried about Self image Dying Several areas of general health Long Term Survivors more worried about Fertility Getting / changing jobs Insurance 

12. 321 Long-Term Adult Survivors 1/3 of survivors worry about Recurrence Second cancer Symptoms they have may be related to cancer Cancer related health worries are a significant predictor of Depression Anxiety Most consistent predictor of psychosocial distress is dispositional optimism Less cancer –related health worries Lower levels of anxiety Lower levels of depression Cancer Related Health Worries and Psychological Distress

13. Childhood Ca Surv Study 10,397 survivors and 3,034 siblings Calculated the frequency of chronic conditions Common Terminology Criteria for Adverse Events v 3.0 (NCI) 1 is mild 2 is moderate 3 is severe 4 is life threatening or disabling 5 is death Cumulative incidence @ 30 years 73.4 % for a chronic health condition Survivor vs siblings RR=3.3 (95% CI 3.0-3.5) 42.4 % for severe, disabling, life threatening condition or death. Chronic Health Conditions in Adult Survivors of Childhood Cancer

14. These too are Snapshots of Survivors

15. Late Effects of Cancer Therapy

16. Late Effects of Cancer Therapy Cognitive/Learning Psychosocial Mental Health Disorders Fatigue Seizures Neuropathies Cataracts Ototoxicities Dental Caries Tooth/Root Agenesis Chronic Sinusitis

17. Late Effects of Cancer Therapy Poor Growth/GHD Thyroid Problems Adrenal Insufficiency Ovary and Testes Early Puberty Hypogonadism Infertility Osteopenia Obesity Metabolic Syndrome

18. Late Effects of Cancer Therapy Pulmonary Toxicity Fibrosis Interstitial Pneumonitis Restrictive Disease Obstructive Disease Impaired Diffusion

19. Late Effects of Cancer Therapy Cardiomyopathies Congestive Heart Failure Arrhythmias Valvular Disease Vascular Disease Atherosclerotic Disease Myocardial Infarction Moyamoya Stroke Dyslipidemia Metabolic Syndrome

20. Late Effects of Cancer Therapy Liver Toxicity Hepatic Fibrosis Cirrhosis Veno-Occlusive Disease Cholelithiasis Functional Asplenia GI Strictures Bowel Obstruction Fistulas / Strictures

21. Late Effects of Cancer Therapy Renal/ GU Toxicity Tubular Glomerular Renal Insufficiency Hypertension Hemorrhagic Cystitis Bladder Fibrosis

22. Late Effects of Cancer Therapy Alopecia Skin Fibrosis Premature Aging Osteonecrosis Exostosis Limb Loss / Dysfunction Hypoplasia Limb length discrepancy MSK growth disorders Scoliosis / Kyphosis Fractures

23. Late Effects of Cancer Therapy Bone Cancer Breast Cancer CNS Cancer Thyroid Cancer Skin Cancer Leukemia Lymphoma Bladder Cancer Colorectal Cancer

24. What every survivor should know? What kind of Cancer did you have? What kind of chemotherapy did you receive? What kind and how much radiation did you receive? What kind of late effects are you at risk for? How should you be monitored for late effects? Nina Kadan Lottick – JAMA 2002 CCSS Cross sectional survey of 635 consecutive survivor (5%) of 12,156 surv 72% reported their diagnosis with precision 19% were accurate but not precise Brain tumors and NB were less likely to know their diagnosis Treatment history 94% accurate for chemotherapy 89% accurate for Rt but only 70% accurate for site of RT 93% accurate for spleenectomy Receiving a LTFU summary did not improve accuracy.Nina Kadan Lottick – JAMA 2002 CCSS Cross sectional survey of 635 consecutive survivor (5%) of 12,156 surv 72% reported their diagnosis with precision 19% were accurate but not precise Brain tumors and NB were less likely to know their diagnosis Treatment history 94% accurate for chemotherapy 89% accurate for Rt but only 70% accurate for site of RT 93% accurate for spleenectomy Receiving a LTFU summary did not improve accuracy.

25. Survivor Healthcare Plan (SHP) AKA Passport to Care Roadmap to Survivorship

26. Survivor Healthcare Plan (SHP) Treatment Summary Cancer Diagnosis Chemotherapy – Agents and Doses Radiation – Site and Dose Surgery Bone Marrow Transplant Individualized Risk Profile Individualized Monitoring Plan

31. Screening and Management Guidelines Organized by Agent Evidence Based Recommended by a Multidisciplinary Taskforce Consensus by COG – Late Effects Committee

32. Example

33. Applied to the first 500 patients in the Cancer Survivor Clinic / Aflac Cancer Center Questions: How many patients have Late Effects? What kind of Late Effects are we seeing?

35. Late Effects Severity Score - Aflac Common Toxicity Criteria Adverse Events v 4.3

36. Late Effects Severity Score - Aflac Common Toxicity Criteria Adverse Events v 4.3

37. Late Effects Severity Score - Aflac Common Toxicity Criteria Adverse Events v 4.3

39. Endocrine Disorders in 1st 500 Aflac CSP

40. Endocrine Disorders in 1st 500 Aflac CSP

41. Endocrine Disorders in 1st 500 Aflac CSP

42. Endocrine Disorders in 1st 500 Aflac CSP

44. Neuropsychological Disorders in 1st 500 Aflac CSP Miscellaneous Fatigue 3% Speech problems 3% Developmental Disorder 3% Adjustment disorder 1.8% Sleep disorder 1.8% Substance abuse 0.7% Schizophrenia 0.4%Miscellaneous Fatigue 3% Speech problems 3% Developmental Disorder 3% Adjustment disorder 1.8% Sleep disorder 1.8% Substance abuse 0.7% Schizophrenia 0.4%

46. Georgia Pediatric Alliance Cancer Survivors

47. The Goal of the GPACS Every Pediatric Cancer Survivor in Georgia Receives a Survivorship Healthcare Plan

50. Goals of Survivorship Care are: Awareness Medical goals Early recognition and treatment of Late Effects Improve the Quality of Life Decrease Healthcare Costs Psycho-social Goals Establish the “New Normal” Social life School and Work

51. Surveillance Over Screening Undue Fear Unnecessary screening Higher cost Under screening Missed LE Potentially life threatening Missed early intervention Missed chance to minimize morbidity Long run – higher healthcare costs

52. Essential Content of Survivorship Training IOM Prevention of secondary cancers General discussion of survivorship Long-Term Complications/sequelae of treatment Trends and statistics in health care access Health care systems/quality assurance/models of care Rehabilitation Services Quality-of-life issues in survivorship Detection of recurrent and secondary cancers Pain management Palliative care /end-of-life care Short term complications Treatment of recurrent cancer

53. Amsterdam

54. Quality of Life Among Long-Term Adolescent and Adult Survivors of Childhood Cancer (Canada) Childhood Cancer Survivors 1,334 Age and sex matched general population controls 1,477 Questionnaire that included SF -36 and measures of self esteem, optimism and life satisfaction

55. Limitations on Physical Performance and Daily Activities among Long-Term Survivors of Childhood Cancer Childhood Cancer Survivor Study (CCSS) Survivors (11,481) vs Siblings (3,839) Physical performance (6 areas) – over the past 2 years how long has your health limited you in 1. Vigorous activities like lifting heavy objects, running strenuous sports 2. Moderate activities moving a table, carrying groceries or bowling 3. Walking up a flight of stairs 4. Bending lifting or stooping 5. Walking 1 block 6. Eating dressing, bathing or using the toilet Participation restrictions 3 categories Because of limitation of health did you need help with: Limited personal care Limited routine activities of daily living Preventing school or workPhysical performance (6 areas) – over the past 2 years how long has your health limited you in 1. Vigorous activities like lifting heavy objects, running strenuous sports 2. Moderate activities moving a table, carrying groceries or bowling 3. Walking up a flight of stairs 4. Bending lifting or stooping 5. Walking 1 block 6. Eating dressing, bathing or using the toilet Participation restrictions 3 categories Because of limitation of health did you need help with: Limited personal care Limited routine activities of daily living Preventing school or work