PEDIATRIC ONCOLOGY

Childhood Cancer:

Only 2% of all cancer occur before 15 years of age

Cancer is the second most common cause of death (10%) in children

Incidence: 130 per million children 0-14 years of age per year in U.S

Childhood Cancer is Unlike Adult Cancer:

Majority of adult cancers are carcinomas

Leukemia, lymphoma and brain tumors account for almost two-thirds of childhood tumors

Many embryonal cell tumors are similar in appearance (small round cell tumor)

Cancer in Children:

Leukemia, Lymphoma (39%)

Brain tumor (20.7%)

Neuroblastoma (7.3%)

Wilm's tumor (6.1%)

Osteosarcoma, Ewing's sarcoma (4.7%)

Rhabdomyosarcoma (3.4%)

Retinoblastoma (2.9%)

Germ cell tumor and others (16.4)

The Cause of Childhood Cancer:

Inherited predisposition

Environmental exposure

Hereditary Predisposition to Pediatric Cancer:

Down syndrome child has a 20 fold increase chance to develop leukemia

50% of optic nerve glioma are associated with neurofibromatosis; 40% of Retinoblastoma are hereditary, 3-5% of Wilm's tumor are associated with genetic disorders

Retinoblastoma:

Autosomal dominant

2-hit hypothesis

In hereditary form, the first mutations is in a germ cell, present early in life, often bilateral and multiple primary tumors, increases risk to develop Osteosarcoma and melanoma

Molecular Basis of Retinoblastoma:

Loss of 2 copies of RB1 gene

RB1 gene; tumor suppressor gene, located on chromosome 13q14, encodes a regulator of G1 to S cell cycle transition

Neurofibromatosis Type 1:

A common genetic disorder affecting 1 in 2500 people

Features: Café-au-tait spots axillary freckling, neaurofibromas, lisch nodules

Predispose to schwannoma, optic giloma, JMML, pheochromocytoma etc.

NF1 gene encodes neurofibonin stimulator of RAS-specific GTPase activity

Li-Fraumeni Syndrome:

Family with clustering of multiple cancers, including pediatric sarcoma, breast cancer, leukemia, brain tumors and adrenocortical carcinoma

P53 germ line mutation

P53 gene, a tumor suppressor gene located on chromosome 17p13, encodes a transcription factor, regulate G1-S checkpoint

Environmental Factors in Development of Childhood Cancer:

Ultraviolet radiation

Ionizing radiation

Chemical agents

Electromagnetic fields

Molecular Basis of Childhood Cancer:

Chromosome aberration

Loss of tumor suppressor gene

Aberrant control of the cell cycle

Defects in mismatch recognition and repair

Telomerase

Treatment of Childhood Cancer is tailored to:

Histopathology

Favorable, unfavorable histology

Cytogenetic and molecular markers

Staging

Age and gender

Early tumor response

Slow responder receives more intensive therapy

Genetic Prognostic Factors:

ALL t(4,11), t(9,22), t(1,19) are associated with poor prognosis, consider BMT in 1^st remission

Neuroblastoma

N-Myc oncogene amplification is associated with poor prognosis

Trk-A receptor over expression is associated with better survival

Age Affecting Cancer Treatment:

ALL - over 10 years of age treated on high risk protocol

Brain cancer - delay or avoid radiation therapy in infants

Neuroblastoma - better prognosis for infant under 1 year of age

Bone cancer - age affects the decision of amputation of limb salvage surgery

Treatment affected by Gender:

ALL - on CGG studies, boy receives 3 years therapy and girl receives 2 years therapy

Hodgkin's Disease - avoid mediatinal radiation in females, minimize alkylating agent exposure in males.

Side Effects of Chemotherapy:

Anemia

Bleeding

Constipation or Diarrhea

Electrolytes abnormalities

Hair loss

Infection

Kidney damage

Liver damage

Mouth sores

Myocardial injury

Neurotoxicity

Ototoxicity

Pulmonary fibrosis

Skin rash

Advances in Cancer Therapy:

Blood & Marrow Transplant (BMT)

Source of donors: autologous, allogeneic related and unrelated, matched or mismatched

Source of stem cells: bone marrow, peripheral blood stem cells, cord blood

Pre-BMT conditioning

Pre-BMT immunomodulation

Pre-BMT immunotherapy

New Treatment Approach:

Immunotherapy

Differation therapy

Gene therapy

Therapy targeting at oncogene pathway

Childhood Cancer Survivors:

1 in every 900 individuals between 16-44 yr. of age will be a survivor of childhood cancer

They will at increased risk for second cancer because of genetic predisposition and previous exposure to irradiation and chemotherapy

Late Effect Follow up on Hodgkin's Disease Survivors:

In a cohort of 1380 childhood Hodgkin's

Disease survivors, the estimated incidence of second cancer 15 years after the diagnosis of H.D. was 7%

Incidence of solid tumor was 3.9%, leukemia 2.8%

He most common solid tumor was breast cancer, increased in women treated with high dose radiation for H.D.