PEDIATRIC MALIGNANCIES

Martin Brecher, MD Roswell Park Cancer Institute

Women & Children’s Hospital of Buffalo !

Oncology for Scientists

Epidemiology

• 10% of childhood deaths, most common cause of death from disease

• 10-12,000 new cases/yr in US

Etiology

• Unknown • Genetics

– incidence increased with some chromosomal abnormalities

– identical twins - 20% concordance rate for leukemia if < 6 yrs

• Environmental - prenatal vs post natal – radiation – chemical carcinogens – diet - no evidence in children

Etiology (cont)

• Viral Oncogenesis – EBV in Burkitt’s, Hodgkin’s

• Immune deficiency – increase in lymphoid malignancies with

congenital immunodeficiency – cancer in AIDS patients

Signs & Symptoms

• Solid tumors – lump, mass, pain in area of growth

• Leukemia – related to abnormal blood counts – infections/fever - WBC – fatigue, lethargy - anemia – bruising, bleeding - platelets

• Brain tumor – headache, vomiting, neurologic signs

Acute Lymphoblastic Leukemia

• Most common pediatric malignancy • 80% of pediatric leukemias • 1/25,000 • peaks at 3-5 years • boys>girls

ALL (cont)

• Presentation – bleeding/bruising, fever, irritability, bone pain,

adenopathy – high or low WBC, anemia, thrombocytopenia,

elevated LDH, elevated uric acid • Differential diagnosis

– Mono, CMV, ITP, JRA, aplastic anemia, neuroblastoma,

ALL (cont)

• Diagnosis - bone marrow – morphology, histochemistry, flow cytometry,

cytogenetics • LP for CNS disease, prognosis, prophylaxis • Prognosis

– WBC > 50K, age <2 or >10 worse – DI > 1.16 favorable – chromosomes

ALL (cont)

• FAB Classification - L1, L2, L3 • Markers - Tcell, B cell, B-lineage • Treatment based upon risk category -

standard vs high risk • Induction - clear marrow of evidence of

leukemia (CR) – 3 drug - VCR, pred, asp – 4 drug - add anthracycline

ALL (cont)

• Intensification/Consolidation • Maintenance - outpatient • CNS prophylaxis - IT meds vs CSXRT • 80% cure overall

Acute Myelogenous Leukemia

• 500 new cases/yr • No age, sex preference • FAB classification dependent upon lineage • presentation - similar to ALL, DIC,

gingivitis, chloromas • 20% with WBC > 100,000

AML (cont)

• Treatment – induction -Dauno, AraC, 6TG – intensification - HD AraC – Allo BMT vs chemo

• Cure rates - 60-70% sib allo BMT vs 30-40% chemo only

Hodgkins Disease

• Peaks in adolescence, 20’s in US, rare < 5 years

• More common in immunodeficiency • Pathology - 4 types, NS most common • Painless adenopathy -supraclavicular,

cervical • firm, rubbery nodes • 2/3 mediastinal involvement

Hodgkins Disease (cont)

• Spreads via contiguous nodal groups • Lungs, pleura, pericardium • Spleen, liver. marrow • “B” symptoms -fever, weight loss, night

sweats • Stage with CT neck/chest/abdomen,

gallium scan

Hodgkins Disease

• Bone marrow aspirate/biopsy if advanced disease

• Staging laparotomy • Therapy

– traditionally -skeletally mature, local disease - XRT

– advanced disease - chemo -MOPP, ABVD – Trend toward low dose chemo + low dose XRT

in local disease

Non-Hodgkins Lymphoma

• Very different from adults - nearly all high grade

• Small noncleaved (undifferentiated) - Burkitt’s

• Lymphoblastic • Large cell

NHL (cont)• Small non-cleaved - “Burkitt’s”

– endemic vs sporadic – B cell, express surface immunoglobulin, usually IgM – abdominal mass +/- ascites – abdominal pain/swelling – intussception, right iliac fossa mass, confused with

appendicitis – inguinal, iliac adenopathy

• Large cell – usually B cell phenotype – presentation similar to small noncleaved

NHL (cont)

• Lymphoblastic – T cell phenotype – mediastinal mass, pleural effusion – SVC syndrome, dyspnea – cervical adenopathy – abdominal involvement uncommon

• Staging - CT chest/abdomen, bone marrow, LP

• Prognosis - tumor burden

NHL (cont)

• Therapy - Chemotherapy – XRT no benefit – chemo differs, based on cell type – intensive, multiagent – CNS prophylaxis

Brain Tumors

• Most common solid tumor (1200/yr) • Associated with phacomatoses • Presentation dependent upon site of origin,

not histology • Obstructing, increased ICP - classic triad

(morning HA, vomiting w/o nausea, diplopia

Brain Tumors (cont)

• Subacute ICP - poor school performance, fatigue, personality change, HA

• Infants, toddlers - irritable, anorexia, developmental delay, loss of milestones, optic pallor, macrocephaly

• Infratentorial -balance, truncal instability, UE coordination, gait disturbance, CN findings

Brain Tumors (cont)

• Supratentorial - seizure, hemiparesis, hemisensory loss, visual field defect

• Staging - MRI brain, spine for mets, LP for cytology, +/- bone scan, BMA/bx

• Treatment - SURGERY -prognosis better • XRT • Chemo - less of role for many types

– advanced, metastatic – attempt to decrease XRT dose

Wilms Tumor

• Most common malignant renal tumor in children

• 460 cases/yr • Mean age 3-4 yrs • WAGR Syndrome - del 11p13 • Beckwith-Wiedemann

Wilms Tumor (cont)

• Abdominal swelling mass • Abdominal pain, hematuria, fever • Imaging

– US, abdominal CT – MRI for caval patency – CXR for pulmonary mets

Wilms Tumor (cont)

• Surgery upfront -nephrectomy • Chemotherapy - VCR, actino +/- doxo • XRT for advanced stages • 65-90% RFS, overall 80% • 5-7% bilateral

Neuroblastoma

• Most common extracranial solid tumor (525 cases/yr)

• Histology – Small round blue cell tumor – derived from post ganglionic sympathetic

neuroblasts • Arise in any site along sympathetic chain

Neuroblastoma (cont)

• Most primaries - abdomen (adrenal) • Infants - thoracic, cervical • < 5yrs, rare > 10 yrs • Metastasis - lymphatic, hematogenous • Infants more localized vs older children

more metastatic

Neuroblastoma

• Surgery - pivotal role • Chemotherapy - aggressive, multiagent • XRT for advanced stages • High-dose chemo with auto BMT? - delay

recurrence?

Bone Tumors

• 7th largest, 3rd largest group in adolescents

• Osteosarcoma – distal femur, proximal tibia, proximal humerus – metaphysis – RB gene deletion – pain, soft tissue mass

Bone Tumors (cont)

• Osteosarcoma (cont) – 20% metastatic @ dx - lung, bone – “Codman’s triangle” – stage - MRI primary, CT chest, bone scan – Neo-adjuvant chemo - limb-sparing surgery – 80-90% RFS

Bone Tumors (cont)

• Ewings Sarcoma – any bone - pelvis, femur, tibia, fibula, scapula,

spine, ribs (axial) – diaphysis – t(11:22) – pain, swelling, fever – mets - lungs, bone, marrow

Bone Tumors

• Ewings Sarcoma (cont) – plain film -”onion skin” – XRT effective – chemotherapy - VAC, doxo, Ifos, VP16

Late Effects

• Increasing survivors of childhood cancer • Growth abnormalities

– direct effect on bones -short stature, scoliosis – hormonal - GH from cranial XRT

• Organ damage - lung, heart, kidney, thyroid – anthracycline - cardiotoxic - late, cumulative – bleomycin -pulmonary

Late Effects (cont)

• Infertility - MOPP, XRT, BMT • Secondary malignancies - XRT, cytoxan

regimens, intensive VP16, BMT