Is the Thickness of the Margin Associated With Local Recurrence and Survival in Patients With Myxofibrosarcoma?

Background: Myxofibrosarcoma (MFS) is a spectrum of aggressive soft tissue fibroblastic neoplasms characterized by variable myxoid stroma, pleomorphism, and a distinctive curved vascular pattern; these tumors are associated with a high likelihood of recurrence. Better local tumor control (a tumor-free margin) is believed to be important to minimize the risk of recurrence, but the effect of surgical resection margin status on local recurrence and survival in MFS is not as well-characterized as it might be.

Questions/purposes: (1) Is margin width associated with local recurrence? (2) Is there a relationship between greater margin thickness and improved overall and disease-free survival (DFS)? (3) Is worsening French Federation of Cancer Centers grade associated with local recurrence and poorer overall survival?

Methods: Using a database of patients with bone and soft tissue tumors at a tertiary university hospital, we retrospectively reviewed the medical records of 282 patients who had soft tissue sarcomas and who had been surgically treated by a multidisciplinary bone and soft tissue tumor care team between January 2010 and December 2021. Of these 282 patients, 38 were identified as having MFS. Patients who received surgical care for MFS outside our institution (unplanned resection) (four patients) and whose surgical margins were not reported as microscopic numerical data (10) were excluded from the analysis. We estimated survival and local recurrence and examined factors potentially influencing these outcomes. Patient demographics, tumor characteristics, surgical margin distance (in mm), and disease-related outcomes were recorded. The minimum follow-up was 3 months (median 41.5 months, range 3 to 128 months).

Results: Overall 1-year local recurrence-free rates were 66.7% (95% CI 50% to 88%). Patients with positive margins were more likely to have local recurrence than patients with negative margins (HR 10.91 [95% CI 2.61 to 45.66]; p = 0.001). Patients with an inadequate margin (positive margin or a negative margin of 1 mm or less) had a greater risk of local recurrence (HR 9.96 [95% CI 1.22 to 81.44]; p = 0.032). Patients with positive margins or margins less than or equal to 1 mm had worse 2-year local recurrence-free survival than did those with margins of greater than 1 mm (46.9% [95% CI 16% to 76%] versus 91.7% [95% CI 75% to 100%]; p = 0.005). The mean overall survival was 98 months (95% CI 77.2 to 118.8). The Kaplan-Meier overall 1-, 2- and 5-year estimated rates of survival were 88% (95% CI 75% to 100%), 79.2% (95% CI 64.5% to 97.2%), and 73.5% (95% CI 57.2 % to 94.5%), respectively. Positive surgical margins were associated with decreased overall survival (HR 6.96 [95% CI 1.39 to 34.89]; p = 0.018). There was a mean DFS time of 4.25 months (95% CI 0.92 to 7.59) in microscopically positive patients, 75.5 months (95% CI 37.47 to 113.53) in patients with margins 1 mm or less, and 118 months (95% CI 99.23 to 136.77) in patients with margins over 1 mm. There was a statistical difference between DFS times according to surgical margin classification (p < 0.001). With the numbers we had, we could not detect any difference between the histologic grades determined by the French Federation of Cancer Centers grading system in terms of local recurrence (HR 3.80 [95% CI 0.76 to 18.94]; p = 0.103) and overall survival (HR 6.91 [95% CI 0.79 to 60.13]; p = 0.080). Tumor size was the prognostic factor associated with a higher local recurrence rate among all factors analyzed as univariate (HR 1.18 [95% CI 1.05 to 1.32]; p = 0.004).

Conclusion: A surgical procedure with a sufficient negative surgical margin distance appears to be associated with a lower proportion of patients who experience a local recurrence and is associated with overall patient survival. It is difficult to define what a sufficient margin is, but in our patients, it appears to be greater than 1 mm.Level of Evidence Level III, therapeutic study.