Pediatric Solid Tumors
Summary of Key Points
Osteosarcoma
Primary Therapy
• The primary tumor is managed surgically with a limb-sparing operation or amputation.
• Adjuvant chemotherapy incorporating high-dose methotrexate is used preoperatively for presumed micrometastatic disease; response will guide further therapy.
• Methotrexate responders have a more than 80% chance of cure.
• Primary pulmonary metastatic disease is managed surgically, although adjuvant chemotherapy may reduce the extent of resection.
Ewing Sarcoma Family Tumors
Differential Diagnosis
• Osteomyelitis must be ruled out, especially when the patient has a fever.
• Lesions to be excluded include benign tumors of bone that manifest as lytic lesions (e.g., eosinophilic granuloma, giant cell tumor), malignant tumors (e.g., osteosarcoma, primary lymphoma of bone), and metastatic lesions from a nonosseous tumor (e.g., neuroblastoma).
Primary Therapy
• The primary tumor should always be treated with multimodality therapy consisting of chemotherapy, radiation therapy, surgery, or a combination of these treatments.
• Specific local treatment depends on the primary site. Surgical extirpation may be considered with tumors in expendable bones (proximal part of the fibula, rib, clavicle, iliac wing).
• Unresectable tumors generally necessitate a combined approach of chemotherapy, radiation therapy, and surgery.
• Localized disease is curable with combined therapy in more than 70% of cases. Metastatic disease is curable in 30% to 40% of cases.
Neuroblastoma
Differential Diagnosis
• Disseminated bone disease can resemble systemic infection, inflammatory disease, osteomyelitis, or rheumatoid arthritis.
• Paraneoplastic syndromes associated with neuroblastoma (vasoactive intestinal peptide syndrome, opsoclonus-myoclonus-ataxia syndrome) must be differentiated from primary inflammatory bowel disease and neurologic disease.
• Neuroblastoma must be differentiated from other small, round, blue cell neoplasms of childhood (e.g., Ewing sarcoma, primitive neuroectodermal tumor, non-Hodgkin lymphoma, undifferentiated soft-tissue sarcoma).
• In as many as 10% of tumors, catecholamines are not produced. In 1%, the absence of an obvious primary lesion confounds the diagnosis.
Staging Evaluation
• Staging evaluation includes a complete history and physical examination, CBC, serum chemistry analysis (including determination of lactate dehydrogenase level), quantitative urine catecholamines, bone marrow examination, radionuclide scintigraphy, and imaging studies of the primary tumor and chest.
Primary Therapy
• Specific treatment depends on stage of disease, age of the patient, and biological features of the tumor.
• With few exceptions (completely resected primary tumor, localized tumor with/without complete excision and favorable tumor biological features, infants with stable stage 4S disease), multiple-agent chemotherapy is the backbone of multimodality treatment.
• Survival depends on stage and biological features of the tumor (e.g., histopathological subtype, MYCN gene amplification).
• The overall survival rate for asymptomatic patients with favorable biology stage 1, 2a, or 2b tumors is greater than 90%.
• Overall survival among patients with advanced-stage 3 or 4 with MYCN gene amplification disease is poor. Less than one-third of children with high risk disease are long-term survivors.
Wilms Tumor
Etiology and Epidemiology
• Mean age at diagnosis is 44 months for unilateral tumors and 31 months for bilateral tumors.
• Familial cases account for 1.5% of cases of Wilms tumor.
• Associated with Wilms tumor is a syndrome comprising aniridia, genitourinary anomalies, and mental retardation (WAGR syndrome); Denys-Drash syndrome; and Beckwith-Wiedemann syndrome.
• No firmly established environmental factors have been identified.
Pathology and Tumor Biology
• The main histologic subtypes are favorable and anaplastic.
• Major implicated genes and loci include WT1 (11p13), IGF2 (11p15), FAM123B/WTX (Xq11), and CTNNB1/β-catenin (3p22).
• Mutations of the p53 gene (TP53) are associated with anaplastic tumors.
• Loss of heterozygosity (LOH) at chromosomes 1p and 16q and gain of chromosome 1q are associated with adverse prognosis.
Differential Diagnosis
• Neuroblastoma is the main consideration in the differential diagnosis.
• Other tumors to be excluded are renal neoplasms (clear cell sarcoma, rhabdoid tumor, congenital mesoblastic nephroma, renal cell carcinoma).
• Benign renal processes (nephrogenic rests, multicystic or polycystic kidneys, hydronephrosis, renal carbuncles, hemorrhage) also should be ruled out.
Staging Evaluation
• Evaluation begins with complete history and physical examination, with careful attention to blood pressure and assessment for associated congenital anomalies.
• Other components of the staging evaluation include CBC, serum chemistry analysis, urinalysis, abdominal ultrasonography, abdominal/pelvic computed tomography (CT) or magnetic resonance imaging (MRI), and chest CT.
Primary Therapy
• Surgery: Surgical resection of the primary tumor usually precedes chemotherapy in the approach taken by the Children’s Oncology Group (COG). Presurgical chemotherapy is used in the approach taken by the International Society of Pediatric Oncology (SIOP).
• Chemotherapy: Agents used depend on disease stage and favorable versus anaplastic histology: stages I and II, favorable histology—vincristine, actinomycin D; stages III and IV, favorable histology, and stage I, anaplastic histology—vincristine, doxorubicin, actinomycin D; stages II through IV, anaplastic histology—vincristine, cyclophosphamide, doxorubicin, carboplatin, etoposide.
• Radiation therapy: Radiation therapy is included in management for stages III and IV, favorable histology, and stages II through IV, anaplastic histology.
• Recurrent disease is effectively managed with radiation therapy and chemotherapy with agents not used for initial treatment.
• Patients who initially received aggressive treatment may respond to cyclophosphamide or ifosfamide-, carboplatin-, and etoposide-based regimens.
Complications
• Renal failure is seen in less than 1% of patients with unilateral tumors and 12% in patients with bilateral tumors.
• Congestive heart failure may occur in patients who receive doxorubicin (occurs in 4.4% of patients).
• Pregnancy-related complications in adulthood have occurred in girls who receive flank irradiation.
• A second malignant neoplasm also may develop (6.7% cumulative incidence of solid malignancies at age 40 years).
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