Ernest U. Conrad

Osteosarcoma: A Randomized, Prospective Trial of the Addition of Ifosfamide and/or Muramyl Tripeptide to Cisplatin, Doxorubicin, and High-Dose Methotrexate

PURPOSE To determine whether the addition of ifosfamide and/or muramyl tripeptide (MTP) encapsulated in liposomes to cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) could improve the probability for event-free survival (EFS) in newly diagnosed patients with osteosarcoma (OS). PATIENTS AND METHODS Six hundred seventy-seven patients with OS without clinically detectable metastatic disease were treated with one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and HDMTX and underwent definitive surgical resection of the primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 double dagger 2 factorial design. The primary end point for analysis was EFS. RESULTS Patients treated with the standard arm of therapy had a 3-year EFS of 71%. We could not analyze the results by factorial design because we observed an interaction between the addition of ifosfamide and the addition of MTP. The addition of MTP to standard chemotherapy achieved a 3-year EFS rate of 68%. The addition of ifosfamide to standard chemotherapy achieved a 3-year EFS rate of 61%. The addition of both ifosfamide and MTP resulted in a 3-year EFS rate of 78%. CONCLUSION The addition of ifosfamide in this dose schedule to standard chemotherapy did not enhance EFS. The addition of MTP to chemotherapy might improve EFS, but additional clinical and laboratory investigation will be necessary to explain the interaction between ifosfamide and MTP.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

Survival of tumor megaprostheses replacements about the knee

Limb salvage surgery is an effective procedure with a low risk of tumor recurrence. In an attempt to define the incidence of implant failure at 2, 5, and 10 years postoperatively, we retrospectively reviewed implant survival in a group (n = 105) of pediatric (< 18 years of age) and adult patients who were treated with distal femoral and/or proximal tibial implants for extremity tumors. Issues regarding the timing of failure, reason for failure, and whether pediatric patients had higher rates of failure were posed as secondary questions. The median followup was 57 months (1-235 months). Thirty-two (32/105, 31%) patients had 42 implant failures. The mean prosthesis Kaplan-Meier survivorship of the index group was 84% at 2 years, 73% at 5 years, and 59% at 10 years. Forty-seven percent of all failures occurred within 2 years postoperatively, and 69% occurred within 5 years postoperatively. Pediatric patients had a higher failure rate than adults (42% versus 24%). Aseptic loosening was the most common reason for failure (n = 18/32; 56%). The incidence of failure in tumor megaprostheses is similar to early published literature and the incidence of these failures is highest within the first 3 years.Level of Evidence: Therapeutic study, level IV. See Guidelines for Authors for a complete description of levels of evidence.

Risk Assessment Based on FDG-PET Imaging in Patients with Synovial Sarcoma

AbstractSynovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent not all synovial sarcomas share the same tumor biology. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We therefore assessed the clinical value of 18F-FDG-PET-derived maximum standard uptake value (SUVmax) for predicting survival in patients with synovial sarcoma. 18F-FDG-PET was performed in 44 patients with synovial sarcoma before therapy and resection. SUVmax was calculated for each tumor and then evaluated for prognostic usefulness along with metastasis at presentation, tumor grade, histopathologic subtype, age, gender, postsurgical margins, anatomic location, and tumor size for overall survival and progression-free survival. SUVmax ranged from 1.2 to 13.0 (median, 4.35). Pretherapy tumor SUVmax predicted overall survival and progression-free survival. Patients presenting with a SUVmax greater than 4.35 had a decreased disease-free survival and were therefore at high risk for having local recurrences and metastatic disease. Level of Evidence: Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

The effects of freeze-drying and rehydration on cancellous bone

Processing technique significantly affects the strength and stiffness of bone for use as a structural alloimplant in reconstructive surgery. The effects of the rehydration of freeze-dried human cancellous bone were studied using 14-mm-diameter cancellous dowels taken from matched cadaveric sites. Three different methods of rehydration were evaluated and compared with unrehydrated freeze-dried and frozen grafts. All samples were biomechanically tested in anatomically matched pair groups to determine compressive strength and stiffness. The strength of each tested graft was expressed as a percentage of its matched pair control. Freeze-dried grafts rehydrated for 24 hours compared with frozen grafts showed no significant difference in mean compressive strength (92.6% +/- 13.3% of control). Analysis of in vacuo versus ex vacuo rehydration at one hour showed a 38% greater mean compressive strength and a 42% greater mean stiffness for the ex vacuo group. Unrehydrated grafts appeared to be both stronger and stiffer than their rehydrated counterparts. These results suggest that the rehydration of freeze-dried grafts may adversely affect graft strength and stiffness. Rehydration under a negative pressure may proceed more rapidly than the process at atmospheric pressures. These findings limit the acceptability of freeze-dried grafts as structural implants.

Pediatric spine tumors with spinal cord compromise

Twenty-nine pediatric spine tumor patients with neurologic deficit were reviewed retrospectively to evaluate tumor control, neurologic course, spinal deformity, and response to treatment. Diagnoses included 10 neuroblastomas, nine sarcomas, eight astrocytomas, and two lymphomas. Mean duration of symptoms at presentation was 8 weeks. Mean clinical follow-up was 7 years 4 months, with patient survival of 66% and a local recurrence rate of 34%. Twenty-four percent (seven of 29) of patients recovered minimal neurologic function with treatment, 76% (22 of 29) showed significant recovery, and two thirds (20 of 29) developed spinal deformity. The initial clinical response to chemotherapy appeared to be most pronounced in sarcoma patients (66% positive response).

Body mass index (BMI) at diagnosis is associated with surgical wound complications in patients with localized osteosarcoma: A report from the Children's Oncology Group†

Malnutrition is common at diagnosis and during treatment for sarcoma patients. Poor nutritional status is associated with increased risk of complications, particularly infections. We investigated the role of body mass index (BMI) on the incidence of surgical wound complications in patients with localized osteosarcoma treated on the Childrens Oncology Group (COG) legacy trial, INT‐0133.

Multiple myeloma: diagnosis and orthopaedic implications.

Abstract Multiple myeloma is a hematologic malignancy that commonly affects the skeletal system. The disease is primarily managed medically with chemotherapeutic agents. Pathologic fractures are common in patients with diagnosed and undiagnosed disease. The number of patients diagnosed with multiple myeloma is increasing, as is the incidence of associated pathologic fractures. Novel chemotherapeutic agents and radiation therapy protocols have been used to extend the average life span of patients with this disease. Various methods that allow for restoration of function and pain reduction can be used to stabilize and manage fractures associated with multiple myeloma. The orthopaedic surgeon and oncology team must work together to develop an individualized treatment plan to improve patient quality of life and provide pain relief.

Malignant progression in two children with multiple osteochondromas.

Multiple Osteochondromas (MO) is a disease of benign bony growths with a low incidence of malignant transformation. Secondary chondrosarcoma in children is rare even in children with MO. Making a diagnosis of malignancy in low-grade cartilage tumors is challenging and requires consideration of clinical, radiographic, and histopathological factors. We report two cases of skeletally immature patients with MO who presented with rapidly enlarging and radiographically aggressive lesions consistent with malignant transformation. Both underwent allograft reconstruction of the involved site with no signs of recurrence or metastatic disease at a minimum of four-year follow-up.

The Effect of Surgery With Radiation on Pelvic Ewing Sarcoma Survival

Pelvic Ewing sarcoma (ES) has poorer outcomes than extremity‐based lesions and the method of local control is controversial.