The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence.

The charts of 423 patients with localized extremity soft-tissue sarcoma treated at our institution over a 10-year period (1968-1978) were reviewed. Data were subjected to both univariate and multivariate analysis, with independent variables in the multivariate analysis appearing in capital letters. Factors associated with an increased risk of local recurrence included the following: AGE greater than 53; PRESENTATION WITH RECURRENT DISEASE; HIGH TUMOR GRADE; positive regional nodes; TREATMENT BY LIMB-SPARING SURGERY (LSS); invasion of vital structures (LSS only); INADEQUATE MARGINS; and biopsy with delayed definitive resection. Survival was adversely affected by the following: AGE greater than 53; PAINFUL MASS; PROXIMAL SITE; SIZE greater than or equal to 10 cm; HIGH TUMOR GRADE; POSITIVE NODES; invasion of vital structures; TREATMENT BY AMPUTATION; INADEQUATE MARGINS; and local recurrence after treatment at our institution. Significant variations in both local recurrence and survival according to histopathology were also observed, with EMBRYONAL RHABDOMYOSARCOMA, ANGIOSARCOMA, and MALIGNANT PERIPHERAL NERVE TUMORS emerging as independent predictors of local recurrence. Using the Cox models for local recurrence and survival, patients were stratified into high-, intermediate-, and low-risk categories based on the presence or absence of each variable. Risk factor analysis should be part of the overall evaluation of each patient with extremity sarcoma.

A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72‐hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high‐grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P < 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study.

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