The Late Effects Study Group. Sherry L. Bayliff, MD, MPH Assistant Professor of Pediatrics Division of Pediatric Hematology/Oncology

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1 Sherry L. Bayliff, MD, MPH Assistant Professor of Pediatrics Division of Pediatric Hematology/Oncology Family Medicine Review November 4, 2009 Aziz & Rowland, Sem Rad Oncol 2003; 13:248 To understand the multiple long term health issues our pediatric cancer survivors face. To appreciate the services that can be provided by Long-Term Follow-Up Care. To recognize the importance of Risk Based Care. To recognize the challenges/barriers faced when trying to deliver survivorship care. ~20,000 new pediatric cancer diagnoses/year ~80% of pediatric cancer patients will become long term survivors ~270,000 childhood cancer survivors ~1 in every 250 adults (by 2010) Hewitt, Weiner, & Simone, 2003 The Late Effects Study Group early 1970s international consortium Cooperative Groups NWTS, POG, CCG, COG The Childhood Cancer Survivor Study (CCSS) A study of 10,397 participants in the CCSS (compared with 3,034 of their siblings) 73% with at least 1 chronic health condition by 40 yrs old 42% categorized as severe, life-threatening, or fatal 3.3x more likely to have a chronic health condition and 4.0x more likely to have 2 or more chronic health conditions than their sibling counterparts Incidence of chronic conditions increases over time (no plateau) Oeffinger et al

2 Cardio-pulmonary Abnormalities Autoimmune Dysfunction Endocrine Dysfunction Eye Problems Bone/Joint Problems Kidney and Genitourinary Dysfunction Secondary Malignancies Psychosocial/Cognitive Effects recurrence heart problems second cancers obesity GI problems skeletal problems sexual problems infertility poor quality of life cognitive problems school/work issues depression Underlying Diagnosis bone cancer, CNS tumors, Hodgkin's highest risk Intensity of Treatment Regimens radiation doses, accumulative chemo doses Transplant Related conditioning therapies, chronic GVHD Multifactorial genetic predisposition, age at time of dx, immunodeficiency, health behaviors A cooperative team effort Majority of CCSs continue care not at cancer center Lack of knowledge by provider Lack of understanding and risk awareness on part of the survivor Recognition of the need for Risk Based Care a systematic plan for lifelong screening, surveillance, and prevention that incorporates risks based on the previous cancer, cancer therapy, genetic predispositions, lifestyle behaviors, and comorbid health conditions Oeffinger, 2004 only 53% of cancer centers had a developed LTFU program as of 1997 care provided by PCPs lack of communication lack of educating materials small percentage of the PCP s practice large investment of resources Annals of Family Medicine Oeffinger et al,

3 monitor for/manage physical late effects provide health education provided referrals to specialists and resources encourage wellness/health promotion activities address psychosocial needs assess/provide intervention for educational/vocational needs assist with financial/insurance issues guide transition: pediatric adult-focused care empower survivors to advocate for their own needs facilitate research Cancer Center Models Primary Oncology Care Specialized LTFU Clinic Shared Care Young Adult Transition Models Formalized Transition Programs Adult Oncology-Directed Care Community-Based Care Models Need-Based Models close contact with the pediatric oncology team (consultative basis) individual risk factors updated screening recommendations transition at specific time points for continued care provision of primary care most common model transition w/in same cancer center examines/evaluates the patient risk-based screening recommendations education about potential late effects encourages primary care continuum No matter what model is chosen, an educated survivor who is empowered to be an active participant in their own life long care is the cornerstone of all successful survivorship care Surgery Chemotherapy Radiation --in Establishing and Enhancing Services for Childhood Cancer Survivors: Long-Term Follow-Up Program Resource Guide; COG

4 overall incidence 12.6% yrs) fold lifetime risk compared to age matched controls leading cause of death behind recurrence multifactorial in etiology AML most common almost always preceded by myelodysplasia, genetic abnormalities Solid tumors associated with history of XRT Chemotherapy Alkylating agents delay to onset 5-10 yrs dose related Topoisomerase II Inhibitors delay to onset 2-3 yrs correlates with dose intensity and schedule Combination therapy increased risk with increased number of cycles Radiation risk peaks at 4-9 yrs inverse relationship with dose doses chemo family history 1 o cancer was soft tissue sarcoma, Hodgkin s lymphoma, or bone tumor other secondary cancer Radiation (>30 Gy highest risk) 9-fold higher incidence than age matched controls delay to onset peaks > 10 yrs post XRT (no plateau) Breast Cancer XRT rates by 10-20% at 20 yrs cumulative yrs post is 35% volume of radiation delivery risk begins to increase 8 yrs after XRT risk decreased if other therapies induce premature menopause Mammography, breast exam, MRI Chemotherapy Anthracyclines & hi-dose Cyclophosphamide cumulative dose related >450 doxorubicin has 5-11% risk cardiac dz risk is nearly 23% >800 risk is 100% Asymptomatic ventricular dysfunction Radiation coronary artery dz, pericarditis, ventricular dysfunction, valvular disease risk decreases as patient ages Chemotherapy-related (rare) Bleomycin, nitrosurea, CTX, Ciplatinum, MTX pneumonitis, fibrosis, acute hypersensitivity, noncardiogenic pulmonary edema cumulative dose relationship risk further increased by supplemental O 2, older age, smoking, renal dysfunction, infections, prior mediastinal XRT Radiation 5-15% risk of pneumonitis after XRT for lung cancer with concomitant chemo, prior XRT, steroids, young age Increased w/higher cumulative doses and daily fractions 4

5 Hx & Physical Exam Review of Systems ECHO/MUGA every 2-5 years Normal: FS > 29%; LVEF > 55% Abnormal: decrease of 10% of previous or < nl EKG findings late and nonspecific careful evaluation during 3 rd trimester of pregnancy Hx & Physical Exam Review of Systems PFTs baseline 6-23 months after end of therapy repeat q 2-5 years if normal at baseline Imaging Lung biopsy most commonly growth hormone deficiency and thyroid dysfunction present as decreased linear growth, abnormal musculoskeletal maturation or signs/sxs of thyroid dz greatest risk associated w/xrt to Hypothalamic-Pituitary-Growth Hormone axis or neck may occur w/o growth hormone deficiency cancer free for 1-2 years may worsen degree of scoliosis or induce benign intracranial hypertension controversial risk of inducing second cancer incidence 10-28% with low dose XRT to neck delay to onset of 5 years, increases until 20 yrs XRT > Gy to neck greatest risk palpable thyroid is abnormal Ultrasound and nuclear scanning Biopsy if nodule found screening TSH yearly FT3/FT4 if TSH increased Brain tumors (greatest) and ALL neurocognitive dysfunction greatest morbidity female, < 3 years, increased time from therapy 4 primary therapy induced pathologies: leukoencephalopathy mineralizing microangiopathy subacute necrotizing leukoencephalopathy secondary brain tumors 5

6 age and gender specific many survivors are unaware of their risks Ovaries: greatest ovarian risk: postpubertal + hi-dose alkylators standard chemo doses: retain/recover function increased risk w/increased number cycles of combination therapy > 20 Gy pelvic XRT permanent ovarian failure Assess bone age, U/S ovaries, thyroid studies, hormonal evaluation boys much more sensitive age and pubertal status little impact CTX mg/kg sterility 20% may recover after combo tx; 50% remain sterile XRT 1-3 Gy reversible; > 3 Gy irreversible Leydig cell function preserved usually PE, Tanner stage, bone age, sperm analysis, hormonal evaluation markedly reduced by chemoprotectant drugs and limited cumulative dosing acute tubular dysfunction w/alkylating agents or XRT Gy to kidneys Fanconi renal wasting hypo-phosphatemic rickets dribbling and nocturnal enuresis Radiation TBI most common association >50 Gy: neovascularity, glaucoma, atrophy of iris, retinal infarction, exudates, hemorrhage, optic neuropathy, decreased tearing and fibrosis of lacrimal glands >40 Gy: ulceration, neovascularization, keratinization, edema of the cornea Cataracts Corticosteroids and/or XRT Gy chronic OM with Gy to middle ear Sensorineural hearing loss Gy radiation to middle ear cisplatin exaggerated by aminoglycoside use continue Audiology plan made during therapy Radiation > 40 Gy enteritis esophagus through colon hepatitis/fibrosis/cirrhosis Intensified by concurrent use of dactinomycin/adriamycin Early colorectal screening Pelvic or abdominal XRT >25 Gy Start 15 yrs post treatment or age 35 yrs (later event) 6

7 fear/anxiety of another cancer; a wish to leave it all behind; and unresolved feelings Interventions discuss LTFU plans before treatment ends familiarize the survivor with the plan for transition encourage survivors to be proactive self care encourage healthy lifestyle behaviors Unemployed=uninsured; mobility due to school/employment; childhood cancer as a preexisting condition; survivors may age out of existing insurance coverage; restriction of coverage; outright cost of healthcare prohibitive in the uninsured Interventions provide information regarding government programs related to special needs/disability develop a directory of community resources and referrals provide financial/insurance counseling August 16 th, 2007 >5 years off therapy Oncologist, Nurse Coordinator, Social Worker more than 100 survivors waiting collaboration with the UK Med/Peds Clinic, Pediatricians, Family Practice Groups, etc. Pre-Clinic Questionnaire Physical and Psychosocial Assessment Educational Materials LAF Survivors Handbook Individualized Health Links Resource Directory Cancer Treatment Summary Visit Summaries Referral to Subspecialists SUMMARY OF CANCER TREATMENT Demographics Name: Sex: Date of Birth: Address: Phone: SS# Race/Ethnic ity: Alternate conta ct: Rela tionship: Phone: Cancer Diagnosis Diagnosis: Date of Diagnosis: Age at Diagnosis: Date Therapy Completed: Sites involved/stage/diagnostic details: Laterality: Hereditary/congenital history: Pertinent history: Past medica l history: Family history: Treatment Center #1: Medical Record #: MD/APN Contact Information: Treatment Center #2: Medical Record #: MD/APN Contact Information: Relapse(s) Date: Site(s): Laterality: Date Therapy Completed: CANCER TREATMENT SUMMARY Protocol Acronym/Number Title/Description Initiated Completed On-Study Surgery Date Procedure Site (if applicable) Laterality Surgeon/Institution Chemotherapy Drug Name Route Cumulative Dose Children s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers Health Links Summary of Cancer Treatment template Late Effects Directory of Services Long-Term Follow-Up Program Resource Guide 7

8 Survivors of Childhood and Adolescent Cancer: A Multidisciplinary Approach; Heidelberg: Springer, 2005 Late Effects of Childhood Cancer; London: Arnold, 2004 Childhood Cancer Survivorship: Improving Care and Quality of Life; Washington, DC: The National Academies Press, 2003 Childhood Cancer Survivors: A Practical Guide to Your Future (2 nd Edition); Sebastopol, CA, O Reilly Media, Inc., 2007 ( Children s Oncology Group Health Links, 2006 ( to better understand identified late effects i.e. metabolic syndrome and obesity to identify newly occurring late effects to better understand quality of life issues to develop targeted therapies to reduce/prevent late effects Stacy Peach, RN, CPON Nurse Coordinator Kim Cron, MSW Clinical Social Worker Treacy Regan Administrative Clinical Research Assistant Pediatric H/O Division physicians, nurses, research & administrative staff Karen Lommel, MD Child Psychiatry Wendy Landier, RN, MSN, CPNP, CPON City of Hope National Medical Center 8