Lecture 14 Childhood Cancer Did you know Cancer claims the lives of more children than all other childhood diseases combined Childhood Cancer Rates Number of childhood cancer diagnoses per year total 15 700 Incidence Prevalence Cancer in adults is fairly common 1 to 3 It is extremely rare for children 1 in 600 Causation Survivability Approximately 90 of adult cancers can be attributed to environmental factors Most childhood cancers have no clear causation Most striking difference between childhood cancer and adult cancer is childhood cancer is much more curable 2 3 children survive and live healthy lives Adult survivability for cancer overall is less than 50 What are the most common types of childhood cancers The types of cancers that occur most often in children are different from those seen in adults Leukemia Brain Lymphoma Acute lymphoblastic Leukemia ALL 20 25 of childhood cancers Uncontrolled growth of white blood cells that would normally become B and T cells starts in bone marrow Acute Mylelogenic Leukemia AML 5 of childhood cancers Uncontrolled growth of white blood cells that normally would become macrophages and granulocytes starts in bone marrow And other nervous system tumors often in lower parts of the brain cerebellum and brain stem 20 of childhood cancers and most common solid tumor Uncontrolled growth of B and T cells in lymph tissues lymph nodes thymus Hodgkins more common in young adults large abnormal B cells Non Hodgkins younger children aggressive ASAP treatment Most common solid cancer occurring outside of the brain in childhood cancer of nerve tissue associated with sympathetic nervous system adrenals and stomach Neuroblastoma Wilms Tumor Kidney cancer swollen belly Prognosis largely depends on microscopic characteristic of cells especially nuclear shape and size Rhabdomyosarcoma Arises from skeletal muscle precursors most common soft tissue cancer sarcoma can occur anywhere in body Bone Cancer More common among teens Osteosarcoma teens where rapid growth occurs painful Ewing Sarcoma young teens painful hip and chest wall Stem Cell Lineage Leukemia Blood stem cell should become mature blood cells but instead they do not Retinoblastoma Retinoblastoma is a relatively uncommon tumor of childhood cancer that accounts for about 3 of the cancers in children under the age of 15 Can strike from time a child is in the womb up to 5 years of age 87 of the children stricken with this disease worldwide die mostly in developing countries In developed countries 97 of those who do live have moderate to severe visual impairment Possible Causes of Childhood Cancer The best established environment cause of childhood cancer is ionizing radiation High dose radiation exposure linked to ALL AML osteosarcoma thyroid cancer and soft tissue sarcoma Viral infections might be involved in certain Non Hodgkin s lymphomas and Maternal use of alcohol during pregnancy is associated with a 2 6 fold increased leukemia risk of ALL Pregnant Ladies may not want to Eat predatory fish mercury Lick or remediate surfaces pained with lead paint Drink well water with high levels of arsenic Eat or work with pesticides Work with or around solvents paint thinners Clean ovens with oven cleaners Signs of Childhood Cancer Increased swelling or persistent pain in bones joints back or legs Continual unexpected weight loss Headaches often with vomiting at night or early morning Lump or mass especially in the abdomen neck chest pelvis or armpits Development of recessive bruising bleeding or rash Constant infections A whitish color behind the pupil Nausea which persist or vomiting with nausea Constant tiredness or noticeable paleness Eye vision changes which occur suddenly and persists Recurrent fevers of unknown origin Incidence vs Mortality of Childhood Cancer An estimated 11 900 children and adolescents under the age of 20 were diagnosed with cancer in 2001 Leading types of cancer diagnosed in U S children and adolescents 2001 Cancer Among Children and Adolescents Differ Common Cancers Ages 0 14 Leukemia 26 Brain CNS 21 Neuroblastoma 7 NH Lymphoma 6 Common cancers ages 15 19 Hodgkin Lymphoma 15 Thyroid Carcinoma 11 Brain CNS 10 Top Three Cause of Cancer Death in Children 0 14 Brain ONS Leukemia Soft tissue including heart In adolescents 15 19 Leukemia Bone and joint Brain ONS Treatment of childhood Cancers and Long Term Problems Treatment efficacy has improved survivors pay a high price in side effects Secondary cancers Heart damage Lung damage Chronic hepatitis Alterations in growth and development Infertility Impaired cognitive abilities and psycho social impact Typical Treatments treatments Childhood cancers are uncommon and rarely have a tried and true set of More than 60 of children younger than 15 years old with cancer are treated as part of a clinical trial Pediatric Cancer Centers Children s Hospitals with multidisciplinary care Surgery often with post chemotherapy Chemotherapy Radiation Leukemia bone marrow transplant post Chemo therapy Immunotherapy Emily Whitehead At age 5 one night she complained of bag leg pain was given pain killers she woke up and said it still hurt was given more pain killers Happened again the next night Went to the ER she was diagnosed with Leukemia was treated with chemotherapy Went into remission then cancer came back Another round of chemotherapy Went into remission again cancer came back and she was treated again Leukemia became so bad she was given days to live Went in for a clinical trial she was the first child in the study She is now cured Emily Whitehead and T Cell Therapy Cart Therapy In depth Chimeric Antigen Receptor Antibody for B cell leukemia antigen and protein domains that tell T cells to kill tumor cells and proliferate 1 Extracting T Cells A patient is hooked up to a machine akin to a centrifuge that separates out white blood cells including T cells and return red blood including T cells and returns red cells and platelets to the patient The resulting paink bag of cells is sent to the manufacturing facility for reprogramming 2 Reprogramming At the manufacturing facility a viral vector inserts into T cells the genes carrying the instructions for a chimeric antigen receptor or CAR The CAR consists of an antibody domain that can recognize specific cancer cells a hinge and trans membrane domain that tethers the antibody to the cell and costimulatory and essential activity domains which together signal the cell to divide 3 Manufactoring To elicit a powerful
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