The retroperitoneal space is the site of origin for about 15% of soft tissue sarcomas [
1]. Complete excision with wide margins represents the mainstay of treatment, however even gross total resections are possible only in about 50% of the patients [
2,
3] because of the often locally advanced tumors which frequently already involve vital structures at time of diagnosis [
3]. Even if gross total resection is possible, margins are typically narrow because of the normal tissue limitations [
3,
4] consequently the local failure rate after surgery alone remains high [
5‐
7]. In accordance to extremity soft tissue sarcomas (STS), where randomized trials have demonstrated improved local control by the addition of radiation [
8,
9], considerable interest has been paid in the use of postoperative radiation approaches in retroperitoneal STS also. However, the efficacy of postoperative external beam irradiation (EBRT) is limited because of the inability to deliver adequate doses in account for the tolerance limits of stomach, small bowel, kidney, liver and spinal cord [
10], especially when conventional radiation techniques are used. Because of the known dose-relationship resulting in improved local control rates if doses beyond 55–60 Gy are used [
11,
12], some centers including ours investigated the use of an intraoperative radiation therapy (IORT) boost to overcome the dose limits of postoperative EBRT [
3,
10,
13‐
15]. The only randomized trial reported so far [
13] found a significantly improved local control rate of 60% using a combination of 20 Gy IORT and 35–40 Gy EBRT compared to 20% control with 50–55 Gy postoperative EBRT alone. The reduction of local failures was even accompanied by a lower rate of gastrointestinal toxicities with the use of IORT, but neuropathy emerged as a dose-limiting side effect. [
13]. However, it has been shown, that neurotoxicity is hardly increased if the intraoperative dose is limited to less than 15 Gy [
16]. Given the necessity of a slightly lowered intraoperative dose and the aim of a further improvement in local control, it seems reasonable to investigate an increased EBRT dose component in the combined treatment approach. Compared to the postoperative approach, preoperative radiation therapy and the use of improved irradiation techniques seem favourable for the following reasons : Preoperative radiation therapy allows for a more precise target volume definition and delineation with smaller safety margins, reduces toxicity to adjacent organs at risk because of their displacement through the tumor itself, may lead to a devitalisation of tumor cells including a down-sizing effect, and may avoid a treatment delay due to postoperative complications. Considering improved irradiation techniques, intensity-modulated radiation therapy (IMRT) has been shown to result in improved target coverage and reduced dose to adjacent organs at risk compared to conventional irradiation, as shown in several diseases including retroperitoneal sarcoma [
17,
18], especially if complex shaped target volumes have to be treated [
19]. Further on, IMRT offers the opportunity to reduce overall treatment time using an integrated boost concept with simultaneously increased dose per fraction in parts of the target volume which are at increased risk for incomplete resection during planned surgery.
Therefore, the primary aim of this trial is to investigate the value of dose-escalated preoperative IMRT followed by surgery with an intraoperative electron boost to reduce the local recurrence rate without a markedly increased toxicity. This combination yields total doses which should be able to control even microscopic residual disease without harm to the adjacent organs at risk.