Anthony Bozzo MD MSc1, Aaron Gazendam MD1, and Kurt R. Weiss MD2 1 Division of Orthopaedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada 2 University of Toronto, Toronto, ON, Canada Radiation‐induced cell death is brought about by direct DNA damage and the production of free radicals. Tumors with varying DNA concentrations and local oxygen tensions respond differently to identical doses of radiation. The presence of prior surgery also affects tumor cell sensitivity.1 The exact timing, sequence, and dose of XRT remain controversial. A recent population‐based review of over 8000 soft tissue tumors documented the distribution of soft tissue sarcomas (STS) to be the lower extremity (32%), upper limb (13%), and axial (55%).2 In patients undergoing wide resection for soft tissue sarcoma, does the use of XRT result in better local control and overall survival compared to surgical resection alone? STS constitute 1% of all cancer diagnoses and the incidence is estimated at 1 per 30 000. The mainstay of treatment is wide surgical excision. XRT is used in the management of STS, with the goal of extending the virtual margin to the surrounding tissues.3 Limb‐sparing surgery plus XRT is as effective as amputation for the local control of STS. STS are rare and there is a paucity of level I evidence upon which to base treatment decisions. There is agreement that local control is important, and some authors have correlated local recurrence with diminished overall survival. Most studies are retrospective with small (average 182, range 41–517) numbers of patients. There are two systematic reviews that included 4579 patients, and there is significant overlap between these reviews. There are three randomized controlled trials (RCTs) that evaluated 298 patients. A systematic review concluded that XRT in addition to limb‐sparing surgery improves local control for extremity STS over surgery alone, but does not affect overall survival.4 A review of RCTs in extremity STS found that limb‐sparing surgery plus XRT is equivalent to amputation for local control.5 Furthermore, adding XRT to surgical resection significantly improves local control over surgery alone but does not improve overall survival. The first RCT compared limb‐sparing surgery plus postoperative XRT to amputation in 43 patients.6 At the time of this study, amputation was the standard of care for local control of STS. The authors found no significant differences in local recurrence (p = 0.06; odds ratio [OR] = 6.32; 95% confidence interval [CI]: 0.32–125.52) or overall survival (p = 0.99; OR = 0.86; 95% CI: 0.13–5.89) at five years. They concluded that limb‐sparing surgery plus XRT is a reasonable alternative to amputation. The next two RCTs compared limb‐sparing surgery alone to limb‐sparing surgery plus postoperative RT. Pisters et al. (n = 164 patients) reported a significant improvement (p = 0.002; OR = 0.23; 95% CI: 0.08–0.66) in local control with surgery plus brachytherapy compared with the surgery alone in patients with high‐grade tumors.7 Brachytherapy did not provide an advantage in patients with low‐grade tumors. There were no differences between the two treatment groups in terms of metastatic disease (p = 0.60; OR = 0.74; 95% CI: 0.35–1.56) or five‐year survival (p = 0.65; OR = 0.8; 95% CI: 0.35–1.81). Yang et al. stratified 141 patients into high‐ and low‐grade tumors.8 All patients had surgery and were randomized to receive external beam XRT or not. XRT significantly improved local control in both high‐grade (p = 0.003; OR = 0.05; 95% CI: 0.00–0.81) and low‐grade (p = 0.02; OR = 0.08; 95% CI: 0.01–0.70) tumors. However, there were no differences in overall survival at 10 years (p = 0.71; OR = 0.93; 95% CI: 0.40–2.15). An outcomes study involving 8249 patients using the Florida Cancer Registry demonstrated that surgical resection (p <0.001) and XRT (p <0.001) were the only treatment variables to improve survival.9 The findings of earlier studies from the 1980s and 1990s are in line with the newer RCTs and systematic reviews.10–17 In patients receiving XRT for management of their soft‐tissue sarcoma, does preoperative XRT result in better survival outcomes compared to postoperative XRT? Sarcomas are best treated by multidisciplinary teams and individualized treatment plans. The relative advantages and disadvantages of pre‐ versus postoperative XRT must be related to each patient. There are potential advantages and disadvantages to both pre‐ and postoperative XRT. Both strategies are successfully used to treat patients. Preoperative XRT is associated with a higher rate of wound complications but better long‐term functional outcomes. High‐quality evidence exists to answer this question. Advantages and disadvantages
167 Radiation Therapy in Soft Tissue Sarcoma
Clinical scenario
Importance of the problem
Top three questions
Question 1: Is there evidence to use XRT in the management of STS?
Rationale
Clinical comment
Available literature and quality of the evidence
Findings
Resolution of clinical scenario
Question 2: What are the relative advantages and disadvantages of pre‐ versus postoperative XRT?
Rationale
Clinical comment
Available literature and quality of the evidence
Findings
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