Pediatric Oncology
Jeffrey S. Dome, MD, PhD
Chief, Division of Oncology
Children’s National Medical Center
Professor of Pediatrics
George Washington University
School of Medicine and Health Sciences
Outline
Epidemiology of pediatric cancer
Common pediatric malignancies
Chemotherapy
Oncologic emergencies
Childhood Cancer: Statistics
Ages 0-15 yr 9000 cases/yr
Ages 15-19 yr 3700 cases/yr
Ages 19-21 yr 1500 cases/yr
Total 14,200 cases/yr
Childhood Cancer Deaths: 2,500-2,800/yr
Cancer is leading cause of disease-related
death in children in United States SEER
Annual USA Cancer Mortality Rate
Children 50 y.o.
• Fever, weight loss, night sweats
• Biopsy: Reed Sternberg Cells
• 5-year survival >90%
Hodgkin Lymphoma: Late
Effects
Second malignant neoplasms- 20% at 20 years
AML: (4%) within first 10 years of
diagnosis, chemotherapy, poor
survival
Solid tumors (16%): breast cancer,
bone sarcomas, thyroid carcinoma,
soft tissue sarcomas
Fertility
Cardiopulmonary
Non-Hodgkin Lymphoma
• Classification
Lymphoblastic 30%
Small non-cleaved (Burkitt) 50%
Large cell, immunoblastic 20%
• Can arise anywhere
Abdomen (35%)
Mediastinum (25%)
Head and neck (13%)
Peripheral nodes (14%)
Other sites
• 5-year survival: 75%
Soft Tissue Sarcomas
• Rhabdomyosarcoma (pre-school/school
age)
• Non-rhabdomyosarcoma (adolescence)
• Synovial cell sarcoma
• Malignant peripheral nerve sheath tumor
• Fibrosarcoma
• Liposarcoma
• Desmoplastic small round cell tumor
Rhabdomyosarcoma
• Can occur anywhere
• Orbit
• Paratesticular
• Extremity
• Pelvis
• Vagina
• Prostate
• Bladder
• Treat with surgery/chemo/radiation
• Survival: 70-75%
Germ Cell Tumors
• Gonadal (adolescents)
• Germinoma—testes
• Dysgerminoma-ovaries
• Extragonadal
• Yolk sac tumor- sacrococcygeal
• CNS tumors
• Mediastinal
• Tumor Markers
• AFP: elevated in yolk sac tumors
• HCG: elevated in embryonal carcinoma
• Treatment
• Mature teratomas: surgery only
• Malignant elements: surgery/chemotherapy
Neuroblastoma
• Originates from neural crest cells
• Adrenal (most common)
• Paraspinal (sympathetic gangion)
• Most common extracranial solid tumor
• Most common neoplasm in first year of life
Neuroblastoma: Signs/Symptoms
• Abdominal mass with pain
• Respiratory distress, dysphagia,
• or cough (thoracic mass)
• Cord paralysis - bowel, bladder
• Bone Pain (distant spread)
• Periorbital Ecchymoses (distant spread)
• Opsoclonus/myoclonus
• Diarrhea (from catecholamine secretion)
Neuroblastoma: Physical Findings
• Abdominal mass
• Neurologic deficits
• Opsoclonus/myoclonus
• Raccoon eyes
• Hepatomegaly
• Skin nodules
• Horner’s syndrome (anhidrosis, miosis, ptosis)
Neuroblastoma-Workup
• CT, MRI, ultrasound of primary
• Bilateral bone marrow aspirates/biopsies
• Bone scan, MIBG scan
• CXR and Chest CT
• Urine catecholamines
• Tumor for biology studies: MYCN, DNA ploidy,
LOH 1p, 11q
Neuroblastoma Treatment/Outcomes
• Surgery
• Chemotherapy
• Radiotherapy
• Autologous stem cell transplant
• Retinoic Acid
Low Risk Tumors: Survival >90%
High Risk Tumors: Survival 40%
Wilms Tumor
• 6% of all pediatric cancers
• 500 cases/year in North America
• Peak 2-4 years old, 90% 10 years old
• Bilateral in 5%
• Syndromes or congenital anomalies in 10-15%
Beckwith-Wiedemann
Hemihypertrophy
Organomegaly
High birth weight
Omphalocele
Neonatal
hypoglycemia
Wilms tumor,
hepatoblastoma (5%)
11p15 Loss of
imprinting
IGF2/H19 genes
WAGR Syndrome
Wilms tumor
Aniridia
GU Malformations
Hypospadias
Undescended testes
Mental Retardation
30% chance of
Wilms
11p13 deletions
WT1 gene
Wilms: Clinical features
• Asymptomatic abdominal mass
• Hypertension (25%)
• Hematuria (25%)
• Fever (25%)
Wilms Tumor Work-up
• Ultrasound of abd and IVC
• CT of abdomen and chest
• CBC and UA
Wilms tumor therapy
• Surgery
• Chemotherapy
• Radiotherapy
Survival Rate:
Favorable Histology- 90%
Anaplastic Histology- 60%
Neuroblastoma Wilms
Age Peak 2 2-4
90% females
• Pubertal growth spurt
• Pain ± swelling
• Associated with radiation
Ewing Sarcoma
• Can occur in long or short bones
• diaphysis
• Primitive neural tissue
• No association with radiation
• Rare in Blacks and Asians
• Associated with t (11;22) (q24q12)
Evaluation
• Plain film of bone
• MRI/CT of primary
• Chest CT
• Bone scan
• Bone marrow (Ewing)
• Biopsy
Bone Tumors: Treatment
• Surgery (limb-sparing)
• Radiation (Ewing)
• Chemotherapy (Neo-adjuvant)
• Survival 70% (localized)
Retinoblastoma
• 70% unilateral/30% bilateral
• Bilateral associated with hereditary
predisposition: Rb mutations
• Presenting feature: leucocoria, eye deviation
• Treatment
• Unilateral: enucleation
• Bilateral: Chemo/laser therapy
• Survival rate: >95%
Hepatoblastoma
• Occurs in toddlers/infants
• Elevated AFP
• Associated with prematurity, Beckwith-
Wiedemann Syndrome, Familial
Adenomatous Polyposis
• Treatment: surgery, chemotherapy,
sometimes liver transplant
• Survival rate: 70-75%
Question 1
11 year old Caucasian boy has had increasing
pain and swelling over his left thigh over the past
2 weeks. He is afebrile. His peripheral blood
count is normal. Radiograph demonstrates a
lytic lesion in the midshaft of the femur with
surrounding soft-tissue mass.
Of the following the most likely diagnosis is:
A. Leukemia
B. Aneurysmal bone cyst
C. Osteosarcoma
D. Ewings sarcoma
E. Non-accidental trauma
Question 2
A 4 year old boy presents with bruising, pallor,
intermittent “achy” pain in the extremities,
and intermittent low grade fever of 2 weeks’
duration. Findings on laboratory studies
include hemoglobin 6.5 gm/dl, WBC
2,200/cu mm, platelets 30,000.
Of the following the most likely diagnosis is:
A. acute lymphoblastic leukemia
B. transient erythrocytopenia of childhood
C. infectious mononucleosis
D. parvovirus infection
E. ITP
Question 3
A 3-year-old girl is in your office for her annual
visit. You notice that her blood pressure is
130/80, pulse is 80 beats/min. A large
nontender mass is palpated in right upper
quadrant. Urinalysis is unremarkable except
for the presence of 7 RBC’s.
The most likely diagnosis is:.
A. Hepatoblastoma
B. Neuroblastoma
C. Pheochromocytoma
D. Wilms Tumor
E. Pyelonephritis
Oncologic Emergencies
Tumor Lysis Syndrome
Associated with leukemia, non-Hodgkin
lymphoma
Caused by lysis of tumor cells and
release of salts and metabolites of
purines
Crystallization of uric acid, xanthine,
hypoxanthine, calcium phosphate in
kidneys causes renal failure—patients
may need dialysis
Management of Tumor Lysis
Syndrome
Monitor K+, Phosphorous, Calcium, uric
acid, creatinine frequently (q6-q8 hours)
Give allopurinol—reduces uric acid
Hydrate-2X maintenance, no potassium
Alkalinize urine to prevent formation of uric
acid crystals
Keep pH 7-8
If too alkaline, CaPO4, xanthine, hypoxanthine
crystals precipitate
Rasburicase (urate oxidase) can be used
for patients with high uric acid
Spinal Cord Compression
Associated with neuroblastoma,
lymphomas, sarcomas
Spinal Cord Compression:
Presentation
Back Pain: suspect cord compression
when pain not relieved in supine position
or back pain has a radicular component
Weakness, sensory abnormalities, and
paresis
Urinary and fecal incontinence if lesion at
conus medullaris level
Paraplegia and quadriplegia can occur
rapidly
Spinal Cord Compression:
Management
MRI stat
Dexamethasone
Consult neurosurgery and neurology:
Surgery if diagnosis unknown
Tumor not chemo/radiation sensitive
Spine unstable
Radiation or Chemotherapy
Increased intracranial
pressure
Increased ICP: Presentation
Headache
Nausea
Vomiting
Parinaud’s syndrome: setting-sun sign,
large pupils, impaired reflex constriction to
light but not to accommodation, IV nerve
palsy
Cranial nerve palsies, nystagmus
Personality/behavior changes
Increased ICP: Treatment
CT or MRI scan
Dexamethasone
Consult neurosurgery—may need VP
Shunt or tumor removal
Fever/Neutropenia
Definitions
Fever: temperature of 38.3o C (101oF) taken orally
once or a temperature of 38.0o C (100.4o F) persisting
for one hour or more
Neutropenia: absolute neutrophil count less than
500/ul or less than 1000/ul when counts are falling.
Patients typically neutropenic 5-10 days after receiving
chemo
Associated with life-threatening infections
Gram negative and positive organisms
Management of Fever
Get CBC: assess whether patient is
neutropenic
Draw blood culture—one from each
lumen
1 ml blood for each year of age up to 10 ml
Immediate antibiotic IV
ceftazidime if well-appearing
ceftazidime/vancomycin/gentamicin if ill-
appearing
Admit to hospital-ICU if hypotensive
Mediastinal Mass/
Airway Compression
Management
Airway: alleviation of respiratory distress
Avoid sedation without anesthesiologist
least invasive method possible with the least
anesthesia possible for diagnosis
Tumor:
Steroids
Chemotherapy
Radiation Therapy
Question
A 4 year old girl who has ALL develops a fever of
38.5 o C (103.6 o F). Findings include slight
irritability and clear rhinorrhea. She has a total
neutrophil count of 100/mm3 following recent
chemotherapy.
Which is the most appropriate management?
A. Blood culture, ceftriaxone, follow-up as
outpatient in 24 hours
B. Blood culture, ceftazidime, admit for
observation
C. Sudafed for rhinorrhea
D. Ceftazidime first, then blood culture
Chemotherapy
Side effects of treatment
Chemotherapy preferentially effects rapidly
growing cells
Hair
GI mucosa
Bone Marrow
Anemia
Thrombocytopenia
Leukopenia
Neutrophils and Lymphocytes
Side Effects of Specific Drugs
Cyclophosphamide: hemorrhagic cystitis,
infertility
Ifosfamide: hemorrhagic cystitis, infertility,
Fanconi syndrome (bicarb, protein,
phosphorous wasting), infertility
Cisplatin: hearing loss, renal damage,
magnesium wasting
Doxorubicin: cardiac damage (CHF)
Etoposide: secondary leukemia
Side Effects of Specific Drugs
Methotrexate: renal toxicity, mucositis,
neurologic toxicity
ARA-C: fevers, conjunctivitis
Asparaginase: thrombosis, diabetes,
allergic reactions, pancreatitis
Vincristine: peripheral neuropathy,
constipation
Question
Identify the correct associations:
A. Nephrotoxicity: cisplatin, methotrexate,
ifosfamide
B. Infertility: Vincristine and doxorubicin
C. Hemorrhagic cystitis: cyclophosphamide and
cisplatin
D. Hearing loss: doxorubicin and asparaginase
THE END
(on to Dermatology!)