Fractures in pediatric Ewing sarcoma.

Purpose: To determine the incidence, timing, and clinical significance of long-bone fractures in children with Ewing sarcoma family of tumors (ESFT).

Patients And Methods: We retrospectively reviewed 93 consecutive cases of ESFT of the long bones seen at a single institution over the course of a 37-year period.

Results: Fracture occurred in 14 (15%) of 93 patients with long-bone ESFT, most commonly in the femur.

Primary Ewing tumor of the vertebrae: clinical characteristics, prognostic factors, and outcome.

Background: Fewer than 10% of Ewing family of tumors (EFT) arise in the vertebrae. Little information is available regarding the clinical presentation and outcome of these tumors.

Procedure: We reviewed the clinical features, prognostic factors, and outcome of EFT of the spine identified at our institution between 1962 and 1999.

Circulating concentrations of IGF-I and IGFBP-3 are not predictive of incidence or clinical behavior of pediatric osteosarcoma.

Background: Preclinical studies suggest a role of insulin-like growth factor-1 (IGF-1) in the proliferation of osteosarcoma cells in vivo. The purpose of this study is to address the relationship between serum levels of IGF-1 and its binding protein (IGFBP-3), and the clinical behavior and outcome of osteosarcoma in children, and to compare those levels present in osteosarcoma patients with a normal population.

Procedure: Serum IGF-1 and IGFBP-3 levels were determined by ELISA in 37 patients with osteosarcoma treated on the same treatment regimen (OS-91 protocol), and who had available serum samples from diagnosis.

Development, characterization and therapy of a disseminated model of childhood neuroblastoma in SCID mice.

Purpose: To develop a highly reproducible model of disseminated childhood neuroblastoma in mice to allow secondary evaluation of therapeutics against microscopic disseminated disease.

Methods: CB17/Icr SCID were injected i.v.

Use of reverse transcriptase polymerase chain reaction for diagnosis and staging of alveolar rhabdomyosarcoma, Ewing sarcoma family of tumors, and desmoplastic small round cell tumor.

Purpose: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT).

Materials And Methods: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3-FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures.

Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis.

Purpose: The benefit of whole-lung irradiation (WLI) for patients who have pulmonary metastases (PM) of Ewing sarcoma family tumors (ESFT) is unclear. At our institution, WLI is reserved for patients with PM that do not respond completely to induction chemotherapy. We reviewed our experience to assess the impact of WLI on clinical outcome.

Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.

Purpose: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin.

Patients And Methods: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3).

Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models.

The activity of temozolomide combined with irinotecan (CPT-11) was evaluated against eight independent xenografts (four neuroblastomas, three rhabdomyosarcomas, and one glioblastoma). In all studies, temozolomide was administered p.o.

Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors.

Purpose: Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies.

P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines.

Background: The p53 tumor suppressor gene is the most commonly mutated gene in human cancer, and mutations arise in a wide variety of tumor types. Wild-type p53 functions as a regulator of apoptosis, so mutations in the p53 gene are generally associated with aggressive tumors and a poor prognosis.

Procedure: We have investigated the p53 mutation and MDM2 amplification frequencies in biopsies from pediatric rhabdomyosarcoma (RMS) tumors and cell lines by SSCP and Southern analyses.

Nonrhabdomyosarcoma soft tissue sarcomas in children: is age at diagnosis an important variable?

Purpose: The associations between age at diagnosis, tumor characteristics, and outcome in children diagnosed with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) were studied.

Methods: Retrospective review was conducted of 192 children from 1962 through 1996. Patients were divided into groups: birth to 1 year (n = 13), 1 to 5 years (n = 26), 5 to 10 years (n = 49), 10 to 15 years (n = 55), and older than 15 years (n = 49) of age at diagnosis.

Bone sarcomas of the head and neck in children: the St Jude Children's Research Hospital experience.

Background: Bone sarcomas of the head and neck are difficult to resect. The authors reviewed their institutional experience with these tumors to characterize patients' clinical findings and to assess the impact of surgical resection on outcome.

Methods: The records of the 28 patients with bone sarcomas originating in the head and neck treated at St.

Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas.

Purpose: The aim of this study was to assess renal tubular toxicity (RTT) of ifosfamide-containing regimens (ICR) in patients with newly diagnosed sarcomas at St. Jude Children's Research Hospital.

Methods: The authors reviewed the records of 199 patients receiving ICR at St.

Biochemical correlates of temozolomide sensitivity in pediatric solid tumor xenograft models.

The antitumor activity of the methylating agent temozolomide has been evaluated against a panel of 17 xenografts derived from pediatric solid tumors. Temozolomide was administered p.o.

Hemangiopericytoma in children and infants.

Background: Hemangiopericytoma (HPC) is a soft-tissue neoplasm most commonly seen in adults; only 5-10% of cases occur in children. Childhood HPC comprises two distinct clinical entities. In children older than 1 year, it behaves in a manner similar to adult HPC.

Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts.

Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3). Topotecan was given by i.v.

Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital.

Purpose: The rarity and heterogeneity of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) has precluded meaningful analysis of prognostic factors associated with surgically resected disease. To define a population of patients at high risk of treatment failure who might benefit from adjuvant therapies, we evaluated the relationship between various clinicopathologic factors and clinical outcome of children and adolescents with resected NRSTS over a 27-year period at our institution.

Patients And Methods: We analyzed the records of 121 consecutive patients with NRSTS who underwent surgical resection between August 1969 and December 1996.

Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children.

Purpose: In a preclinical model of neuroblastoma, administration of irinotecan daily 5 days per week for 2 consecutive weeks ([qd x 5] x 2) resulted in greater antitumor activity than did a single 5-day course with the same total dose. We evaluated this protracted schedule in children.

Patients And Methods: Twenty-three children with refractory solid tumors were enrolled onto a phase I study.

Brain metastases in pediatric Ewing sarcoma and rhabdomyosarcoma: the St. Jude Children's Research Hospital experience.

Purpose: Although brain metastases rarely occur in children with solid tumors, pediatric Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) are among those most likely to metastasize to the brain. The authors review their institution's experience of brain metastases of ES and RMS.

Patients And Methods: The clinical characteristics, therapy, and outcome of all patients treated at St.

Chemotherapy dose-intensification for pediatric patients with Ewing's family of tumors and desmoplastic small round-cell tumors: a feasibility study at St. Jude Children's Research Hospital.

Purpose: To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors.

Patients And Methods: From February 1992 to June 1996, we treated 53 consecutive patients on our Ewing's protocol. Induction comprised three cycles of ifosfamide/etoposide on days 1 to 3 and cyclophosphamide (CTX)/doxorubicin on day 5, followed by granulocyte colony-stimulating factor.

Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience.

Background: Because the natural history of pediatric patients with metastatic nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) had not been well described, we retrospectively reviewed our single-institution experience with these tumors.

Procedure: We identified 26 patients with metastatic NRSTS who were treated at St. Jude Children's Research Hospital from December 1971 through July 1995.

Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin's disease at St. Jude Children's Research Hospital.

Objective: To assess disease control, patterns of relapse, factors predictive of relapse, and late effects of treatment, we reviewed all cases of supradiaphragmatic (SD) Hodgkin's disease (HD) treated with primary radiation therapy (RT) at our institution.

Methods: We retrospectively reviewed the disease characteristics, treatment history, and long-term outcome of the 106 patients with Stage I and II supradiaphragmatic HD who received definitive irradiation at St. Jude Children's Research Hospital between 1970 and 1995.

Increased mortality after successful treatment for Hodgkin's disease.

Purpose: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease.

Patients And Methods: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated.

Bax is an important determinant of chemosensitivity in pediatric tumor cell lines independent of Bcl-2 expression and p53 status.

Susceptibility of a tumor cell to undergo chemotherapy-induced apoptosis appears to be dependent upon the balance of proapoptotic and survival factors that are expressed within any given cell. We have chosen to evaluate how expression of several of these proteins influences chemosensitivity of a panel of 10 pediatric tumor cell lines chosen from three tumor histiotypes: neuroblastoma, rhabdomyosarcoma, and pediatric glial tumors. The proteins evaluated were p53 and six members of the Bax/Bcl-2 family: three proapoptotic proteins (Bax, Bak, and Bcl-xS) and three survival factors (Bcl-2, Bcl-xL, and Mcl-1).