Purpose

Mesenchymal stromal cells (MSCs) are an attractive choice for regenerative medicine. We previously showed that MSCs enhance wound healing in animals after radiotherapy. The effect of MSCs on tumor growth is not well understood. The potential use of MSCs to enhance wound healing after radiotherapy (RT) and resection of soft tissue sarcoma (STS) is dependent on a satisfactory safety profile to ensure that tumor proliferation does not occur and recurrence is not increased.

To determine if rates of local recurrence and metastasis differ in upper versus lower extremity sarcomas.

Prospectively collected data relating to patients undergoing limb-sparing surgery for extremity soft tissue sarcoma between January 1986 and April 1997 were analysed. Local recurrence-free and metastasis-free rates were calculated using the method of Kaplan and Meier. Univariate and multivariate analyses of potential predictive factors were evaluated with the log-rank test and the Cox proportional hazards model.

Of 480 eligible patients, 48 (10. 0%) had a local recurrence and 131 (27. 3%) developed metastases. Median follow-up of survivors was 4. 8 years (0. 1 to 12. 9). There were 139 upper and 341 lower extremity tumours. Upper extremity tumours were more often treated by unplanned excision before referral (89 vs 160, p< 0. 001) and were smaller (6. 0cm vs 9. 3cm, p< 0. 000). Lower extremity tumours were more often deep to or involving the investing fascia (280 vs. 97, p< 0. 003). The distribution of histological types differed in each extremity. Fewer upper extremity tumours were treated with adjuvant radiotherapy (98 vs. 289, p< 0. 000).

The 5-year local recurrence-free rate was 82% in the upper and 93% in the lower extremity (p< 0. 002). Local recurrence was predicted by surgical margin status (hazard ratio 3. 16, p< 0. 000) but not extremity (p=0. 127) or unplanned excision before referral (p=0. 868).

The 5-year metastasis-free rate was 82% in the upper and 69% in the lower extremity (p< 0. 013). Metastasis was predicted by high histological grade (hazard ratio 17. 28, p< 0. 000), tumour size in cm (hazard ratio 1. 05, p< 0. 001) and deep location (hazard ratio 1. 93, p< 0. 028) but not by extremity (p=0. 211).

Local recurrence is more frequent after treatment for upper compared with lower extremity sarcomas. Variation in the use of radiotherapy and differences in histological type may be contributory. Metastasis is more frequent after treatment for lower extremity sarcomas because tumours tend to be large and deep.

We considered whether a positive margin occurring after resection of a soft-tissue sarcoma of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection.

Of 566 patients in a prospective database, 87 with positive margins after limb-sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection.