Pediatric Oncology. Vlad Radulescu, MD
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1 Pediatric Oncology Vlad Radulescu, MD
2 Objectives Review the epidemiology of childhood cancer Discuss the presenting signs and symptoms, general treatment principles and overall prognosis of the most common pediatric malignancies Present the late effects of therapy in cancer survivors
3 Epidemiology 8,000 cases per year in the United States For ages 1-15: 14 new cases per 100,000 children each year The overall 5 year survival of pediatric cancer patients is currently at approx. 75% Estimated 250,000 Americans are survivors of childhood cancer
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6 Epidemiology Others Leukemia Sarcomas Wilms Tumor Lymphoma Neuroblastoma Brain tumors
7 Childhood Cancers Usually originate from stem cells Predominance of hematopoietic malignancies, sarcomas Gene mutations in childhood cancer are usually not acquired through interaction with environment Better cure rates compared to adult cancers
8 COMMON PEDIATRIC MALIGNANCIES
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10 Acute Lymphocytic Leukemia (ALL) Malignancy of bone marrow Normal hematopoiesis disrupted by blasts derived from lymphocytes of T or B lineage Peak age 3-5 years; increased risk in certain genetic syndromes: Down s syndrome, ataxia-telangiectasia, congenital immunodeficiencies
11 Acute Lymphocytic Leukemia (ALL) Most common cancer in children less than 15 years ( cases/year) 75% of all childhood leukemias
12 Clinical Manifestations Bone marrow failure Anemia -Pallor, fatigue Thrombocytopenia -Purpura Neutropenia -Fever, Infections Organ infiltration by leukemic cells Hepato-Splenomegaly Lymphadenopathy Bone pain
13 ALL- diagnosis Bone marrow aspiration Microscopic exam Flow cytometry Cytogenetics
14 Childhood ALL Therapy Induction 1-6 weeks Vincristine; L-Asparaginase; Prednisone Consolidation 6-8 weeks Interim maintenance 6-8 weeks Delayed intensification 6-8 weeks Continuation 120 weeks (maintenance)
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16 Lymphoma Presenting Signs and Symptoms Peripheral lymph node enlargement Mediastinal adenopathy Cough, difficulty breathing Mesenteric adenopathy Abdominal pain, intestinal obstruction Splenomegaly Systemic signs fevers, weight loss, night sweats
17 Lymphoma Hodgkin s Disease More common in adolescents Treatment chemotherapy radiation therapy Prognosis Stg I III >90% Stg IV 80-85%
18 Lymphoma Non- Hodgkin s Lymphomas Four morphologic subtypes are common in children Aggressive clinical course Require intense chemotherapy Overall survival - 80%
19 Neuroblastoma Most common malignancy in infants < 1 yr age Most common extracranial solid tumor of childhood Derived from primordial neural crest cells Arises anywhere along the sympathetic nervous ganglia
20 Presenting Signs/Symptoms of Neuroblastoma Common Large asymptomatic abdominal mass Posterior thoracic mass on chest x-ray Intermittent fever, weight loss, vague general pain Occasional Horner s syndrome Spinal cord compression Periorbital ecchymoses
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24 Age at presentation Staging Histology Neuroblastoma clinical variables Shimada classification Tumor biology n-myc amplification
25 Neuroblastoma treatment and outcome Low risk disease Surgery +/- chemotherapy > 90% overall survival at 4 years Intermediate risk disease Surgery + chemotherapy 80-90% overall survival at 4 years High risk disease - includes 50% of patients Surgery, chemotherapy, autologous stem cell transplant, radiotherapy, immunotherapy 30-40% overall survival
26 Wilms Tumor 5% of childhood cancers Median age at diagnosis 3 years Associated congenital anomalies Derived from primary metanephric blastema Usually unicentric lesions involving one kidney (5% of cases are bilateral)
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28 Signs/Symptoms of Wilms Tumor Incidence Asymptomatic abdominal mass 60% Microscopic or gross hematuria 15% Weight loss, malaise 5% Hypertension 8-25% Fever, n/v, abdominal pain <10%
29 Therapy for Wilms Tumor Stage I Surgery, no RT, VCR/ ActD DFS 90% Stage II Surgery, no RT, 15 months intensive DFS 90% VCR/ ActD Stage III Surgery, RT to tumor bed, DFS 76% triple drug chemo (15 months) Stage IV Surgery, high dose RT, DFS 69% triple drug chemo (15 months)
30 Brain tumors Virtually all CNS tumors are primary brain tumors in children (in contrast to adults)
31 Brain tumors Posterior fossa tumors - most common in children > 1 yr. Medulloblastoma Cerebellar astrocytoma Ependymoma Supratentorial tumors: Gliomas; Craniopharyngiomas Pineal tumors
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33 Clinical presentation Signs of increased intracranial pressure Neurologic deficits Seizures
34 What headaches suggest intracranial pathology? Occur in the morning Aggravated by sneezing, coughing, or straining Recurrent and localized Increasingly frequent or severe Unresponsive to medication Complicated migraine (associated with transient neurological symptoms)
35 Associated Signs & Symptoms Neurologic abnormalities altered mental state nuchal rigidity hemiparesis Presistent vomiting Diplopia or papilledema Neurocutaneous syndromes Macrocephaly Growth abnormalities Head tilt
36 Brain Tumors: treatment Treatment modality and prognosis are determined by: Location and size of the tumor Pathology Age of the child
37 LATE EFFECTS OF CHILDHOOD CANCER
38 Late Effects of Childhood Cancer The overall 5 year survival of pediatric cancer patients is currently at approx. 75% 250,000 childhood cancer survivors in the US The childhood cancer survivors have specific medical problems related their previous cancer therapy : late effects
39 Late Effects of Childhood Cancer Second cancers Organ system dysfunction
40 Second Cancers - causes Radiation Breast, thyroid cancer, bone & soft tissue sarcoma CNS Tumors Chemotherapy: alkylating agents, epipodophylotoxins, anthracyclines Leukemia and myelodysplastic syndrome Genetic predisposition Li-Fraumeni sdr. Fanconi anemia
41 Organ System Late effects Cardiovascular Cardiomyopathy Coronary artery disease Pulmonary Pulmonary fibrosis Endocrine Growth hormone deficiency Hypothyroidism
42 Organ System Late effects Growth disturbances Short stature Obesity Central Nervous System Neuro-cognitive impairment Hearing loss Reproductive system Infertility
43 Follow-up care of childhood cancer survivors Systems of care Pediatric oncologist / primary care physician Comprehensive long term follow-up clinics
44 Follow-up care of childhood cancer survivors Comprehensive Clinical evaluation Comprehensive treatment summary Thorough physical examination Diagnostic and screening tests Assessment and follow-up plan
45 Conclusions Childhood cancer is rare, but the primary care physician needs to maintain an index of suspicion; follow-up is critical to reaching a diagnosis Primary care physicians are going to need to become familiar with long term effects of cancers and their therapy, as the survivor population increases
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