LC was superior for extremity lesions compared with trunk tumors and HDR and EBRT compared with BT alone (odds ratio = 0.21; 95% confidence interval: 0.026, 0.651, p = 0.013). LC was also improved with doses greater than 65 Gy. A Japanese group reported their experience of HDR and EBRT. Their inclusion criteria were (1) high tumor grade, (2) low-grade

tumor ≥10 cm, (3) recurrent tumor, (4) tumor abutting or invading critical structures, and (5) positive margins. They prescribed 2–3 Gy/fraction × 6, BID combined with EBRT (36–60 GSK J4 clinical trial Gy). After a median followup of 31 months, there was no local failure within the radiation field (25). San Miguel et al. (23) combined 45 Gy of EBRT with 16 or 24 Gy HDR BT depending on the margin status. LC at 9 years was reported as 77.4%. Positive margins had a 4.4-fold risk of local failure compared with close or negative margin (p = 0.036). They

report 30% Grade 3–4 toxic events, with the majority related to wound healing. Despite this relatively high rate of toxicity, the reoperation rate was comparable to other series at 10%. Lower limb location and volume of the 150% isodose (TV150 >27 mL) combined predicted for Grade 3 complications (p = 0.003). There is no randomized comparison of HDR and LDR BT. Pohar et al. (27), however, published a historical control comparison in 37 patients treated between 1995 and 2004. Twenty-seven patients had LDR and 17 patients HDR (since 2001). The mean EBRT dose this website was approximately 50 Gy. The LDR dose was 15 Gy prescribed at 6-mm depth (0.42 Gy/h) based on the Paris system of loading. The mean HDR dose was 13 Gy (10.2–18 Gy) over three to four fractions BID. They noted an increase in toxicity in patients receiving >15 Gy HDR and adopted a standard HDR dose of 4.5 Gy × 3 (13.5 Gy). LC was 90% with LDR and 94% for HDR. There was a trend of decreased

Dipeptidyl peptidase occurrence of severe complications (Grade 3–4) in the HDR group (30% LDR vs. 6% HDR p = 0.06). Laskar et al. (44) retrospectively reviewed their pediatric data for patients who underwent WLE with BT with or without EBRT. Both LDR and HDR were in their cohort. Of 50 patients, 30 had BT alone (LDR or HDR). They concluded that LC related to size of tumor and grade (better control for tumors <5 cm and low-grade tumors). LC for BT and EBRT was comparable to BT alone (78% vs. 84%, p = 0.89), and there was no difference in LC between LDR and HDR either as monotherapy or in combination with EBRT (77% vs. 92%, p = 0.32; 67% vs. 100%, p = 0.17). We concluded, therefore, that HDR is also a valid approach to source loading for STS. The radiobiology of large fraction sizes and the potential for creative combinations of HDR BT with systemic therapy is yet to be explored. HDR has some functional and radiation safety advantages for pediatric patients. There are a limited number of reports on the use of PDR BT in STS [28], [51] and [52].