Malignant fibrous histiocytoma: Outcome and prognostic factors following conservation surgery and radiotherapy

Purpose: Malignant fibrous histiocytoma is the most common type of soft tissue sarcoma. This communication presents an analysis of outcome and prognostic factors based on a retrospective review of patients with this disease treated by conservation surgery and radiotherapy. Methods and Materials: From 1966 to 1991, 271 consecutive patients with malignant fibrous histiocytoma were treated with conservation surgery and radiotherapy. The outcome with local control, metastatic relapse, and survival as end points was evaluated by univariate and multivariate statistics to delineate independently significant prognostic factors. Results: Postoperative radiation at a mean dose of 62.8 Gy was used in 195 patients and preoperative radiation at a mean dose of 50 Gy was used in 76 patients. At a median follow-up of 7.3 years, 123 patients (45%) developed disease relapse at some site. Fifty-seven (21%) developed local recurrence leading to an actuarial local relapse rate of 26% at 10 years, 83 (31%) developed metastatic relapse for a 10-year actuarial metastatic rate of 33%, and the 5-, 10-, and 15-year survival rates were 68, 60, and 46%, respectively. For local control, prior local recurrence (in 53 patients) was identified as an adverse factor, yielding a 10-year recurrence rate of 42% compared to 22% for 218 patients without prior disease (p < 0.01). Also, a positive surgical margin (in 46 patients) was adverse with a 10-year local recurrence rate of 39% compared to a recurrence rate of 17% with negative margins (167 patients) (p = 0.01). Patients with pathologically undocumented resection margins (58) had a local recurrence rate similar to those with positive margins (41% at 10 years). Tumor site (extremity vs. nonextremity), location (proximal vs. distal), size (less than or equal to 5 cm vs. > 5 cm), and histology (myxoid vs. nonmyxoid) were not significant determinants of local outcome. For metastatic relapse, the major determinants of outcome were histology (myxoid vs. nonmyxoid) and tumor size. Myxoid tumors (59 patients) had a low metastatic propensity (13% 10-year metastatic rate) compared to nonmyxoid tumors (212 patients) (40% 10-year metastatic rate) (p < 0.01). Size was an important covariate for metastases for both myxoid and nonmyxoid tumors. For nonmyxoid tumors the 10-year metastatic rates were 23 and 51% for lesions less than or greater than 5 cm. For myxoid tumors a significant metastatic rate appeared only for tumors exceeding 10 cm (10-year metastatic rates of 8% vs. 44% for tumors less than vs. greater than 10 cm). In this retrospective review we found no evidence that adjuvant chemotherapy decreased the metastatic rate. In multivariate analysis for metastatic relapse and survival, tumor histology (nonmyxoid vs. myxoid) and size (< 5 cm vs. > 5 cm) were the only independent determinants of outcome. Conclusion: Malignant fibrous histiocytoma is a heterogeneous disease and its myxoid variant must be recognized as a distinct entity. Both variants are locally aggressive and require equally aggressive local therapy. Conservation surgery striving for negative margins with radiation therapy provides acceptable local control and is the treatment of choice for this disease. Patients with myxoid tumors do not require systemic therapy; patients with nonmyxoid disease exceeding 5 cm are at significant risk for metastases and the development of effective adjuvant treatment is an important research goal.