INTRODUCTION TO PEDIATRIC ONCOLOGY Prof.Dr.Reha Cengizlier

Epidemiology of Childhood and Adolescent Cancer Malignant neoplasms remain the second most common cause of all deaths (12.8%) among persons 1–14 yr of age in the USA Relative 5-yr survival rates have improved from 56% in 1974 to >81% in 2000 Pediatric cancers differ markedly from adult malignancies in both prognosis and distribution by histology and tumor site

Lymphohematopoietic cancers (i.e., acute lymphoblastic leukemia, lymphomas) account for approximately 40%, Nervous system cancers ( 30% ) Embryonal and sarcomas ( 10% ) In the pediatric age group, with two peaks—the first in early childhood and the second in adolescence

Age distribution During the first year of life, embryonal tumors such as neuroblastoma, nephroblastoma (Wilms tumor), retinoblastoma, rhabdomyosarcoma, hepatoblastoma, and medulloblastoma are most common Acute leukemias, non-Hodgkin lymphomas, and gliomas peak in incidence from 2–5 yr of age Bone malignancies, Hodgkin disease, gonadal germ cell malignancies (testicular and ovarian carcinomas), and other carcinomas increase in pre/adolescent

The most notable genetic conditions that impart childhood cancer susceptibility are: Neurofibromatosis types 1 and 2 Down syndrome Beckwith-Wiedemann syndrome Tuberous sclerosis von Hippel-Lindau disease Xeroderma pigmentosum, ataxia-telangiectasia Nevus basal cell carcinoma syndrome

Mechanisms of syndromes are associated with an increased risk of developing malignancies Inactivation of tumor suppressor genes –Familial retinoblastoma, - Neurofibromatosis Defects in DNA repair –Bloom syndrome (short stature, photosensitive telangiectatic erythema), –Ataxia-telangiectasia (childhood ataxia with progressive neuromotor degeneration) –Fanconi anemia (short stature, skeletal and renal anomalies, pancytopenia) Defects in immune surveillance (lymphoma, leukemia), –Wiskott-Aldrich syndrome –Severe combined immunodeficiency, –Common variable immunodeficiency, –X-linked lymphoproliferative syndrome.

Environmental exposures that have been studied without convincing evidence for a causal role include non-ionizing power frequency electromagnetic fields, pesticides, parental occupational chemical exposures, dietary factors, and environmental cigarette smoke Viruses have been associated with certain pediatric cancers, such as polyomaviruses (BK, JC, SV40) associated with brain cancer and Epstein-Barr virus with non-Hodgkin lymphoma, but the etiologic importance remains unclear

Alteration in the regulation of tumor suppressor genes Tumor suppressor genes are important regulators of cellular growth and programmed cell death or apoptosis They have been called recessive oncogenes Because; Inactivation of both alleles of a tumor suppressor gene is required for expression of a malignant phenotype

In familial cases, children inherit an inactivated allele from one parent, and consequently require the inactivation of the only remaining normal allele. This helps explain why familial cases of retinoblastoma present earlier in childhood than sporadic cases, since only one “hit” is required

Other factors associated with oncogenesis VIRUSES –Epstein-Barr virus (EBV) and Burkitt lymphoma and nasopharyngeal carcinoma –Hepatitis B infection (HBsAg-positive), the risk of developing hepatocellular carcinoma –Human papillomavirus (HPV) and cervical carcinomas Human herpesvirus 8 (HHV8) is associated with Kaposi's sarcoma

Other factors associated with oncogenesis TELOMERASE –Telomeres are a series of tens to thousands of TTAGGG repeats at the ends of chromosomes that are important for stabilizing the chromosomal ends and limiting breakage, translocation, and loss of DNA material –In some instances telomerase, an enzyme that adds telomeres to the ends of chromosomes, becomes active –Consequence; these cells may have a survival advantage. (Therapy aimed at inhibition of telomerase activity)

Potential adverse late effects of curative therapy with chemotherapy, radiation, and/or surgery Subsequent malignancy, Early mortality, Infertility, Reduced stature, Cardiomyopathy, Pulmonary fibrosis, Osteoporosis, Neurocognitive impairment, Affective mood disorders, Altered social functioning