83%, p = 0.15). However, in univariate analysis of Stage III patients, the LC was improved if treated with EBRT and BT (100% vs. 62%, p = 0.03). Also high-grade lesions tended to have improved LC with EBRT and BT (100% vs. 74%, p = 0.09). No factors predicted for improved LC on multivariate analysis, possibly because of the small sample size. In a review by Laskar et al. (42), 155 patients (98 treated with LDR and 57 with HDR) had WLE of the primary tumor with BT alone (55 patients) or with EBRT (100 patients). In their cohort, the disease-free survival (DFS) and OS were superior in superficial tumors less Epacadostat solubility dmso than 5 cm. Dose greater than 60 Gy was found to favorably

impact LC, DFS, and OS. They found fewer complications with BT monotherapy compared with BT and EBRT. The justification for LDR BT for STS rests

on these outcome reports and is supported by radiobiologic theory, which predicts for tumor control and normal tissue tolerance when sufficient and properly distributed radiation doses are applied. The limitations of LDR are radiation exposure to personnel, patient isolation for prolonged periods, limitations on nursing care, and potential for unrecognized catheter or source displacement. HDR BT with remote afterloading has become increasingly prevalent (Table 2) Tacrolimus in vitro because of improved radiation safety and better control of the dose distributions associated with a stepping source. There are several reports on HDR monotherapy [10], [24], [45], [46], [47] and [48]. Itami et al. (24) reported on 25 patients (26 lesions) treated with 36 Gy in six fractions of HDR (a dose that would be predicted to control microscopic disease). Their overall 5-year local regional control was 78%. LC in patients with positive margins and previous surgical resections was only 43.8% compared with 93% for patients with negative margins and no previous resections. All local recurrences were outside the treated volume. They concluded that EBRT should be added for patients with Teicoplanin previous surgery or positive margins as most of the recurrences would have fallen within a traditional EBRT volume. Koizumi et al. (47)

reported on 16 lesions treated with HDR 40–50 Gy in 7–10 fractions over 4–7 days twice a day (BID) prescribed at 5 or 10 mm from the source. LC was 50%. Of the eight uncontrolled lesions, 63% had macroscopically positive resection margins that may explain the relatively low LC rate. Although not strictly comparable to results in adults, Nag et al. (48) reported 80% long-term LC in children treated with HDR monotherapy (36 Gy in 12 fractions) with 20% Grade 3–4 long-term complications. Most of the reported HDR experience is with combined EBRT [10], [23], [25], [39], [46], [49] and [50]. Petera et al. (10) retrospectively reviewed 45 patients with primary or recurrent STS who either underwent HDR monotherapy (30–54 Gy) or HDR (15–30 Gy) and EBRT (40–50 Gy). The use of EBRT was at the discretion of the treating oncologist.