Robert S. Bell

Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.

PURPOSE: The purpose of this critical appraisal was to determine the prognostic factors that influence survival in patients with nonmetastatic, high-grade osteosarcoma of the extremities. DESIGN: A computerized literature search of reports published from January 1973 to March 1992 was conducted to determine those eligible for inclusion in the review. Reports were reviewed blindly by two of the authors; inclusion and scoring were determined according to preestablished criteria. RESULTS: Eight reports were included in the appraisal. The prognostic variables evaluated were age, sex, anatomic tumor location, tumor size, and tumor necrosis. Tumor size and necrosis following preoperative chemotherapy were significant prognostic variables in relation to survival in univariate analysis. However, only tumor necrosis maintained its significance in multivariate modeling. CONCLUSION: The most important prognostic variable for patients with osteosarcoma of the extremity was tumor necrosis evident following preoperative chemotherapy. There is no consensus as to any prognostic variable that might be used to stratify patients before the onset of therapy.

A multicentric retrospective study of giant cell tumor of bone was conducted among Canadian surgeons. The hypothesis was that no differences would be found in health status, function, or recurrence rate irrespective to the nature of filling material or adjuvant used in patients treated with curettage. One hundred eighty-six cases were collected. There were 96 females and 90 males. The mean age of the patients was 36 years (range, 14-72 years), the minimum followup was 24 months, and the median followup was 60 months. Sixty-two percent of the tumors involved the knee region. One hundred fifty-eight were primary tumors and 28 were recurrences. Campanacci grading was as follows: Grade 1, seven patients; Grade 2, 100 patients; Grade 3, 76 patients; and unknown in three patients. Fifty-six patients had a pathologic fracture. Resection was done in 38 patients and 148 patients had curettage. The latter was supplemented with high speed burring in 135 patients, cement in 64 patients, various combinations of autograft or allograft bone in 61 patients, phenol in 37 patients, and liquid nitrogen in 10 patients. Structural allografts were used in 25 patients. The overall recurrence rate was 17%, 18% after curettage, and 16% after resection. Patients with primary tumors treated with curettage had a 10% recurrence rate. For recurrent lesions treated by curettage, the recurrence rate was 35%. The nature of the filling material used or the type of adjuvant method used or any combination of both failed to show any statistical impact on the recurrence risk. The results from the Musculoskeletal Tumor Society rating from 1987 were significantly lower in patients who sustained a displaced fracture. Results from the bodily pain section of the Short Form-36 also were found to be lower when a pathologic fracture was present. Results from the Musculoskeletal Tumor Society Rating 1987, the Short Form-36, and the Toronto Extremity Salvage Score did not show differences when either cement or bone graft were used after curettage.