Abstract
BackgroundFollowing surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death. Radiotherapy is utilized to reduce recurrence rates but the efficacy of this strategy has not been definitely established. As treatment tolerability is more favorable with preoperative radiotherapy, normofractionated neoadjuvant treatment is the current approach. The final results of the prospective, randomized STRASS (EORTC 62092) trial, which compared the efficacy of this combined treatment to that of surgery alone, are still awaited; preliminary results presented at the 2019 ASCO Annual Meeting indicated that combined treatment is associated with better local control in patients with liposarcoma (74.5% of the cohort, 11% benefit in abdominal progression free survival after 3 years, p = 0.049). Particles allow better sparing of surrounding tissues at risk, e.g., bowel epithelium, and carbon ions additionally offer biologic advantages and are preferred in slow growing tumors. Furthermore, hypofractionation allows for a significantly shorter treatment interval with a lower risk of progression during radiotherapy.Methods and designWe present a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the retroperitoneum will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5–6 fractions per week] in each arm). The primary objective is the safety and feasibility based on the proportion of grade 3–5 toxicity (CTCAE, version 5.0) in the first 12 months after surgery or discontinuation of treatment for any reason related to the treatment. Local control, local progression-free survival, disease-free survival, overall survival, and quality of life are the secondary endpoints of the study.DiscussionThe aim of this study is to confirm that hypofractionated, accelerated preoperative radiotherapy is safe and feasible. The rationale for the use of particle therapy is the potential for reduced toxicity. The data will lay the groundwork for a randomized phase III trial comparing hypofractionated proton and carbon ion irradiation with regard to local control.Trial registrationClinicalTrials.gov NCT04219202. Retrospectively registered on January 6, 2020
Highlights
Following surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death
Retroperitoneal sarcomas show a lower risk for distant metastases; local control is crucial as the primary cause of death in these patients is local disease recurrence [4,5,6]
Preoperative radiotherapy seems to be able to reduce the risk of local recurrence based on data from small sample sized studies and retrospective analyses [1]; at many centers, external beam radiotherapy is combined with an intraoperative radiotherapy [7]
Summary
Following surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death. Retroperitoneal sarcomas show a lower risk for distant metastases; local control is crucial as the primary cause of death in these patients is local disease recurrence [4,5,6]. The special physical and biological properties of protons and carbon ions lead to a superior dose distribution [8, 9] This allows a better sparing of the surrounding organs at risk, with chances to reduce treatment-related side effects and even potential for dose escalation. The standard neoajuvant normofractionated radiotherapy consists of 25 fractions with 2-Gy single dose over 5 weeks; the special properties of particles allow hypofractionation resulting in a reduced treatment total time of 3 weeks
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