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Background The use of radiation therapy to treat metastases in patients with metastatic Ewing sarcoma (MES) has been controversial and variable. The authors report outcomes and patterns of failure after metastatic site irradiation (MSI). Procedure A total of 27 pediatric patients with MES were treated with chemotherapy and received radiation therapy to their primary site. Ten patients additionally received MSI, which consisted of whole-lung irradiation (WLI) in patients with lung metastases. Metastatic sites were followed from diagnosis to the first relapse. Results Median follow-up was 29 months. Seventy-eight percent of patients relapsed. Two-year progression-free survival (PFS) and overall survival with and without MSI were 30 versus 29% (log rank P=0.38) and 60 versus 70% (log rank P=0.11), respectively. The median time to relapse among patients who relapsed was 19.5 versus 12.3 months for those receiving MSI versus those who did not (P=0.04).Seven of 20 (35%) patients with lung metastases received WLI±other MSI. Two-year PFS with and without MSI was 43% versus 23% (log rank P=0.02). Among patients with a complete response to computed tomography, 5 of 14 (36%) patients received MSI. Two-year PFS with and without MSI was 60% versus 33% (log rank P=0.04).In the cohort of patients who relapsed, among all metastatic sites at diagnosis, the disease recurred at 15% of irradiated sites and 31% of unirradiated sites. On logistic regression, no factors were statistically associated with increased risk of recurrence at initial sites of metastases. Conclusions Relapses frequently occur at sites of prior unirradiated disease in patients with MES. WLI may improve 2-year PFS, regardless of chemotherapy response. Further investigation of the role of MSI is warranted.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor characterized by aggressive local invasion and a syndrome of platelet trapping known as Kasabach-Merritt phenomenon that, through deposition of platelet derived growth factors, may perpetuate the growth of the tumor. Although many cases of KHE are successfully treated with local control or low-intensity chemotherapy, some cases are often refractory even to aggressive treatment. Herein, we describe a patient with a refractory, recurrent KHE despite multiple attempts at local control and intensive chemotherapy, that ultimately was successfully treated with rationally designed and low-intensity combination therapy of sirolimus and aspirin.

Purpose: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. Patients and Methods: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. Results: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P 0.043; OS: 55% vs. 27%; P 0.012). Conclusions: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IEcontaining regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

The past year has seen a greater understanding of the means by which the alveolar rhabdomyosarcoma gene fusions (PAX-FKHR) lead to the malignant phenotype. The treatment of the primary tumor in rhabdomyosarcoma has been reexamined, with the roles of surgery and radiation expanding in American studies and decreasing in European ones. "Megatherapy" approaches with stem cell or bone marrow autologous transplants still have not found a role in the treatment of metastatic rhabdomyosarcoma. Our understanding of the natural history of nonrhabdo soft tissue sarcomas in children has increased, and molecular diagnosis is becoming established. The role of chemotherapy in treatment remains controversial.

The clinical course of a 31-month-old patient with advanced (stage IV) rhabdoid tumor of the kidney (RTK) and an analysis of treatment variables that may impact survival are presented. Treatment included complete resection of abdominal disease, radiation therapy to the abdomen and chest, and chemotherapy on a schedule of dose intensification by reduction of the interval between cycles. Inclusion of doxorubicin in treatment was associated with survival among patients in published series (P = 0.002). The patient was in continuous complete remission 60 months from diagnosis. Stage IV rhabdoid tumor of the kidney can be effectively treated with intensive multimodal therapy. Doxorubicin may be an important component of a successful therapeutic regimen.

Nine patients who had an osteosarcoma that had developed as a second malignant neoplasm in a previously irradiated site were managed at a major center for the treatment of tumors in children. The doses of radiation had averaged 4144 centigray (range, 2300 to 8000 centigray) and chemotherapy had been administered, when appropriate, for the primary malignant lesion (Ewing sarcoma, malignant fibrous histiocytoma, Hodgkin lymphoma, neuroblastoma, neurofibrosarcoma, rhabdomyosarcoma, and Wilms tumor). The interval between the initial treatment and the diagnosis of the secondary sarcoma averaged ten years and one month (range, five years and ten months to twenty-one years and nine months). Three patients were alive, two of them with active disease, at the time of writing. The other six had died within three years (average, fifteen months) after the second diagnosis. The prevalence of secondary osteosarcoma is increasing as the survival of children who have a malignant lesion increases. Plans for tumor therapy should take into account the risk of this complication, which is usually fatal.

Aggressive fibromatosis is a rare fibroproliferative disorder with a variable biologic potential that is locally morbid but does not metastasize. Eighteen patients with extraabdominal fibromatosis were treated with a multidisciplinary approach over a 27-year period. Our observations, coupled with a review of the literature, suggest that conservative surgery with the goal of a wide margin coupled with adjuvant therapies may result in adequate control of disease from infancy to adolescence. Amputation should be reserved for cases in which the disease or its treatment have resulted in a nonfunctional or chronically painful extremity. Radiation should be used as a last resort in the skeletally immature because of the risk of growth disturbance, contracture, and secondary malignancy. Chemotherapy may have a role in children with inoperable disease, in those who have gross residual tumor after an intralesional procedure, for disease progression or recurrence, and neoadjuvant therapy should be investigated as a means to achieve a wide margin in some cases.

New knowledge in cell and molecular biology has begun to expand the understanding of the biology of osteosarcoma and Ewing's sarcoma. Studies on osteosarcomas have revealed abnormalities in the growth-inhibiting retinoblastoma gene, which may release cells from normal growth control. Abnormalities in growth factor production or response tend to inappropriately activate cell growth. Tumor cell DNA content and cytogenetics may affect the diagnosis and prognostic grouping of osteosarcomas. In Ewing's sarcomas, a characteristic translocation between Chromosomes 11 and 22 has been identified; this translocation is also found in malignant neuroepitheliomas. A variety of studies point to both neuroectodermal and mesenchymal origins for Ewing's sarcomas. Applications of new biologic knowledge and technology to clinical problems will lead to significant changes in the diagnosis, and perhaps in the treatment, of these tumors in the coming years. Collaborations between community and referral center physicians and scientists are critical for continued progress.