Medical Late Effects of Childhood Cancer

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1 Medical Late Effects of Childhood Cancer Robert Goldsby Associate Professor of Clinical Pediatric UCSF Late Mortality in 5+ Year Survivors 1.00 US Female US Male Survival function estimate Cumulative mortality 14% at 25y Female Male Years since diagnosis Mertens, et al, JCO, 2000 Mertens, et al, ASCO,

2 What about Mortality by Specific Diagnosis? Wilms % survival estimates Hodgkins Leukemia 84 CNS Years since diagnosis Cause-Specific Late Mortality Cumulative probability of cause-specific mortality (%) Recurrence SMN SMR (95% CI) Cancer 16.6 ( ) Cardiac 10.4 ( ) Pulmonary 8.2 ( ) Years since diagnosis JCO 19:3163,2001 Cumulative Incidence of Health Conditions in Survivors Cumulative Incidence Yrs. From Original Cancer Diagnosis Grade 1-5 Grade 3-5 Oeffinger et al. N Engl J Med

3 Relative Risk of Health Conditions by Original Diagnosis All estimates are significant at p < * Adjusted for age, sex, and race Oeffinger et al. N Engl J Med 2006 Other % N=817 Breast % Lymphoma 28 3% Melanoma 36 5% Leukemia 29 4% Bone 38 5% Sarcoma 81 10% Meningioma / Benign 66 8% Thyroid % Malig. CNS 60 8% Overall: SIR = 5.2 (Increasing with time) With updated numbers since JNCI, 2001 Risk of SMN by Original Diagnosis Cumulative Incidence% (20 Yrs) Standardized Incidence Ratio Leukemia CNS Hodgkin Non- Hodgkin Wilms NBL ST Sarcoma Bone 3

4 Risk of Breast Cancer and Effect of Radiation Kinney et al. Ann Intern Med 2004: 141: Heart Damage X From COG health-links Anthracyclines Radiation Other factors Young age Types of damage Cardiac cell damage with ventricular dysfunction (Cardiomyopathy) Arryhthmias Cardiovascular Disease in Survivors Condition reported RR Congestive heart failure (CHF) 5.7 Myocardial Infarction 4.9 Atherosclerosis 10.2 Pericardial Disease 6.3 Valvular disease 4.8 Procedures Coronary angiography 8.2 Anthracycline exposure > 250 mg/m2 increased the risk Radiation to the heart also increased the risk J Clin Oncol 26:

5 Attempts to reduce risks and follow-up Avoid cumulative dose over mg/m2 Avoid the combination of anthracyclines and radiation to the heart Use of cardioprotectants. Dexraxozane Follow-up dependent on cumulative dose and radiation exposure Effect on the Lungs Therapy specific: Radiation to the chest Chemotherapy: Bleomycin Cyclophosphamide Busulfan CCNU and BCNU Lung Surgery COG Health Links Pulmonary Complications in Survivors 3.5% incidence at 20 years with chest xrt Cancer 95: ,

6 Follow-up care PCP should monitor for symptoms May need imaging or pulmonary function tests Must avoid smoking Avoid other lung trauma (ex. scuba diving) Cleveland Clinic J Med 75:531, 2008 Endocrine Outcomes is Related to Diagnosis and Treatment Survivors of Brain Tumors are at highest risk 43% report at least one late endocrine condition Hypothyroidism, RR = 14 Growth Hormone deficiency, RR = 280 Received GH injections, RR = 360 Meds to induce puberty, RR = 86 Osteoperosis, RR = 25 Risk higher for patients treated with surgery and radiation and higher still for patients who received adjuvant chemotherapy. Cancer 97:663 73, 2003 Risk of Thyroid Disorders XRT Dose Dependent Hodgkins survivors 34% had at least 1 thyroid abnormality 27 fold increased risk of thyroid nodule J Clin Endocrinol Metab 85: ,

7 Growth Identical twins 6 years after bone marrow transplant Photo from A Ablin Factors influencing growth Cranial radiation Can cause growth hormone deficiency. Increased risk with increased dose. Risk of early puberty after cranial XRT and this shortens the growth period. Radiation to spine or long bones damage to bones prevents growth. Chemotherapy alone has least (if any) impact on final height. Effect on fertility Depends on therapy, dose, timing and gender Gonadotoxic Chemotherapy Alkylating Agents Cyclophosphamide Ifosfamide Others: Busulfan, Melphalan, Thiotepa Nitrosoureas (CCNU, BCNU) Cisplatin Others (Cytarabine, Vinblastin, Etoposide) Best Pract Res Clinic Endocrinol Metabol,

8 Techniques to reduce risk of infertility Males Females Sperm banking Oophopexy Embryo cryopreservation Gonadotrophin suppression Advances: Cryopreservation of oocytes, ovarian tissue, testicular tissue or immature spermatocytes Best Pract Res Clinic Endocrinol Metabol, 2002 Minimal Impact on Pregnancy Outcomes Birth weight with (hatched) and without (solid) pelvic XRT Offspring of women who received pelvic irradiation are at risk for low birth weight. Am J Obstet Gynecol 187:1070, 2002 No adverse preganacy outcomes for partners of male survivors J Clin Oncol 21:716,2003 No Significant Increased Risk of Congenital Malformations The frequency of congenital anomalies is ~8 to 9% among live-born children. Not greater than that observed in the general population. No cases of childhood cancer observed in these studies with short follow-up. NEJM 325:141, 1991 Arch Pediatr Adolesc Med 151:379,

9 What about the siblings? Drinking Behaviors in Adult Siblings of Childhood Cancer Survivors Behavior Peer Survivor Sibling (OR) Current drinker Risky drinker Heavy drinker Adult siblings of childhood cancer exhibit higher rates of current, risky and heavy alcohol consumption compared to both peers and survivors. Addiction, 103: , 2008 Association of SMN in Survivor and Cancer Risk in Sibling Survivor: SMN No SMN Sibling (SIR) P< % of siblings had same cancer as first or second proband cancer Cancer Epidemiol Biomarkers Prev 14:1922 7,

10 Other local effects: Scoliosis after XRT Photos from A.Ablin Post Radiation Consequences Unable to raise arms Patient ultimately died of respiratory failure due to lung fibrosis Photo from A. Ablin Local Surgical Issues 10

11 Dental Issues Identical twins No cancer therapy After BMT for relapsed ALL Survivor Passport a Creditcard Sized Summary 11

12 Credit-card Sized Passport Just a reminder! Brian s story Diagnosed with metastatic Ewing Sarcoma Treated with very intensive multiagent chemotherapy and limb-salvage surgery. Completed therapy ~ 4 years ago. He is a Junior at UCSB. He spent his summer working at UCSF and is applying for medical school next year! And and he is enjoying life!!!! 12