David M. Parham

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 Ewings 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 Ewings 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. Local control using surgery and/or radiotherapy started at week 9 along with vincristine/dactinomycin. Maintenance included four alternating cycles of ifosfamide/etoposide and doxorubicin/CTX, with randomization to one of two CTX dose levels to determine the feasibility of dose-intensification during maintenance. RESULTS Patients had a median age of 13.4 years (range, 4.5 to 24.9 years); 34 patients were male and 43 patients were white. Nineteen patients presented with metastatic disease, 29 had tumors greater than 8 cm in diameter, and 26 had primary bone tumors. These patients received 155 induction cycles, 91% of which resulted in grade 4 neutropenia, 68% in febrile neutropenia, and 68% in grade 3 to 4 thrombocytopenia. During maintenance, grade 4 neutropenia and grade 3 to 4 thrombocytopenia occurred in 81% and 85% of cycles, respectively. Thirty-five patients (66%) completed all therapy, only 13 without significant delays; three developed secondary myeloid malignancies. The toxicity and time to therapy completion were similar in both CTX arms. Estimated 3-year survival and event-free survival were 72%+/-8% and 60%+/-9%, respectively. CONCLUSION Although intensifying therapy seems feasible for 25% of patients on this study, toxicity was considerable. Therefore, the noninvestigational use of dose-intensification in patients with EFT should await assessment of its impact on disease-free survival.

Treatment of children with peripheral primitive neuroectodermal tumor or extraosseous Ewing's tumor with Ewing's-directed therapy.

Purpose: We report the treatment and outcome of patients with peripheral primitive neuroectodermal tumor (PNET) and extraosseous Ewings tumor (EOE) using Ewings-directed therapy, including an ifosfamide and etoposide window. Methods: Seventeen pediatric patients with peripheral PNET (n = 14) or EOE (n = 3) were enrolled between 1988 and 1992 on our institutional Ewings protocol. Induction therapy comprised a 9-week “window” of ifosfamide and etoposide, followed by 9 weeks of therapy with cyclophosphamide and Adriamycin (Adria Laboratories, Columbus, OH). Response assessment after 17 weeks was followed by surgery and/or radiotherapy (doses based on tumor size and response to induction), repeat evaluation, and maintenance chemotherapy with alternating courses of vincristine/dactinomycin, ifosfamide/etoposide, and cyclophosphamide/Adriamycin for a total of 45 weeks. Results: At diagnosis, 8 patients had large lesions (>8 cm) and 3 had pulmonary metastases (1 with large tumor). Surgical resection was performed at diagnosis for 9 patients and after induction therapy for 5. During window therapy, all of the 9 evaluable patients responded (8 partial, 1 objective), and no patient without measurable disease developed disease progression. Responses were maintained or improved during subsequent induction in six of the patients with residual disease. Fourteen patients received local radiotherapy. At 49 to 94 months after diagnosis, 12 patients are disease-free (1 in second remission), 4 have died, and 1 is alive with disease. The five-year overall and progression-free survival rates are 77 ± 13% and 62 ± 16%, respectively. Conclusion: The use of consistent Ewings-directed combined-modality therapy for patients with soft tissue peripheral PNET/EOE results in survival similar to that of patients with osseous Ewings tumor. The combination of ifosfamide and etoposide appears active and should be incorporated in future treatment protocols.

Multifocal osteolysis following limb-sparing procedures: imaging findings and a review of the literature.

Limb-sparing procedures utilizing endoprostheses improve both the quality of life and functional level of patients treated for primary bone sarcomas. Herein, we present the imaging findings of an uncommon cause of prosthetic failure, i. e., foreign body reaction, manifested by progressive multifocal osteolysis along the prosthetic femoral shaft.