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A large study conducted of 8249 patients with soft tissue sarcoma of any anatomic location from Aldosterone the Florida Cancer Data System confirmed that low-grade tumors demonstrated a significant survival advantage compared to other sarcomas [22]; they also found that there was no survival benefit with the addition of radiation therapy, though they did not specifically examine by location. A study by Pisters et al. included a cohort of 46 patients with well-differentiated soft tissue sarcomas receiving brachytherapy [9]. Their findings indicated that well-differentiated soft tissue sarcomas exhibited no improvement in local tumor control with the addition of brachytherapy. In contrast, a study by Yang et al. (n = 55) found that external beam RT improved the rates of local control in well-differentiated STS of the extremities [8]. Regardless of the impact on local control, neither study showed a survival benefit with the addition of radiation therapy following surgery. Additionally, the studies that demonstrate LR to be an independent risk factor for metastasis and death have not looked specifically at well-differentiated tumors. Some authors have questioned whether or not well-differentiated tumors are even likely to respond to RT, given their latent biology. With these points in mind, one might wonder why adjuvant RT would be considered at all for patients with well-differentiated tumors. At our institution, adjuvant RT is MLN8237 chemical structure reserved for those patients with well-differentiated STS-E in whom the morbidity of a subsequent resection would be unacceptable. Therefore, we were surprised to find that 27% of all patients with well-differentiated C59 STS-E in the NCDB were treated with adjuvant radiation therapy. One might expect that this would result from patients with challenging or high-risk disease being disproportionately treated with adjuvant RT. Yet this was not the case. Patients with positive margins received RT 36% of the time and patients with tumors >5?cm received RT 32% of the time. In a separate analysis of the NCDB focusing exclusively on patients with high grade STS-E, we found that RT was utilized only 62% of the time (Hou et al., in press). These data suggest that adjuvant RT is underutilized in patients with high grade STS-E while being overutilized in patients with low grade STS-E. We did find that the use of adjuvant RT for well-differentiated sarcomas was associated with a significantly lower rate of limb amputation as the index procedure (0.8% in the RT group versus, 4.1% in the surgery alone group, p