PEDIATRIC MALIGNANCIES

Transcription

1 PEDIATRIC MALIGNANCIES Martin Brecher, MD Roswell Park Cancer Institute Women & Children s Hospital of Buffalo! Oncology for Scientists

2 Epidemiology 10% of childhood deaths, most common cause of death from disease 10-12,000 new cases/yr in US

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7 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

8 Etiology (cont) Viral Oncogenesis EBV in Burkitt s, Hodgkin s Immune deficiency increase in lymphoid malignancies with congenital immunodeficiency cancer in AIDS patients

9 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

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

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12 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,

13 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

14 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

15 ALL (cont) Intensification/Consolidation Maintenance - outpatient CNS prophylaxis - IT meds vs CSXRT 80% cure overall

16 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

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18 AML (cont) Treatment induction -Dauno, AraC, 6TG intensification - HD AraC Allo BMT vs chemo Cure rates % sib allo BMT vs 30-40% chemo only

19 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

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21 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

22 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

23 Non-Hodgkins Lymphoma Very different from adults - nearly all high grade Small noncleaved (undifferentiated) - Burkitt s Lymphoblastic Large cell

24 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

25 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

26 NHL (cont) Therapy - Chemotherapy XRT no benefit chemo differs, based on cell type intensive, multiagent CNS prophylaxis

27 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

28 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

29 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

30 Wilms Tumor Most common malignant renal tumor in children 460 cases/yr Mean age 3-4 yrs WAGR Syndrome - del 11p13 Beckwith-Wiedemann

31 Wilms Tumor (cont) Abdominal swelling mass Abdominal pain, hematuria, fever Imaging US, abdominal CT MRI for caval patency CXR for pulmonary mets

32 Wilms Tumor (cont) Surgery upfront -nephrectomy Chemotherapy - VCR, actino +/- doxo XRT for advanced stages 65-90% RFS, overall 80% 5-7% bilateral

33 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

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

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

36 Bone Tumors 7th largest, 3rd largest group in adolescents Osteosarcoma distal femur, proximal tibia, proximal humerus metaphysis RB gene deletion pain, soft tissue mass

37 Bone Tumors (cont) Osteosarcoma (cont) 20% dx - lung, bone Codman s triangle stage - MRI primary, CT chest, bone scan Neo-adjuvant chemo - limb-sparing surgery 80-90% RFS

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40 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

41 Bone Tumors Ewings Sarcoma (cont) plain film - onion skin XRT effective chemotherapy - VAC, doxo, Ifos, VP16

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43 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

44 Late Effects (cont) Infertility - MOPP, XRT, BMT Secondary malignancies - XRT, cytoxan regimens, intensive VP16, BMT