Critical impact of radiotherapy protocol compliance and quality in the treatment of retroperitoneal sarcomas: Results from the 62092-22092 STRASS trial.

Abstract

11566 Background: The EORTC 22092-62092 STRASS trial failed to detect a superiority of neoadjuvant radiotherapy in patients with retroperitoneal sarcoma as compared to surgery alone. As radiotherapy (RT) was the experimental treatment, a comprehensive quality assurance program (RTQA) has been included in the study protocol in order to detect and correct potential RT deviations. We report here the overall trial RTQA results and its potential impact on patient’s outcomes in this international phase III trial. Methods: Plans from all patients randomized to the experimental preoperative RT arm were submitted to a multidisciplinary RTQA team, consisting of medical physicists and radiation-oncologists. Target volume parameters and tumor dose coverage were prospectively reviewed by the RTQA team but not all plans were made compliant. In order to evaluate the impact on oncological outcomes, a composite endpoint, overall RT compliance status, was created; patients were classified into two major groups: RT compliant (RC) group and non-compliant (NRC) group, defining whether RT was as concisely per protocol or not. This composite endpoint combined the information related to PTV coverage, target delineation, total dose received and overall treatment time. Both abdominal recurrence-free survival (ARFS) and OS were compared between RC and NRC patients using Cox’s proportional hazard model adjusted for age, sex, WHO performance status, tumor grade, histological subtype and tumor size at baseline (millimeters). Results: After final review, 75.2% (94 out of 125) of patients had compliant RT plans (65.6% were already compliant at first submission to RTQA team and 9.6% were made compliant after review). Most patients in the NRC (77.4%) had deviations linked to incorrect target volume delineations. 3-year ARFS was 67.2% (95% Confidence interval (CI): 58.0 – 77.8%) and 48.4% (34.3 – 68.2%) for RC and NRC group, respectively (adjusted HR: 2.64, 95% CI: 1.38 – 5.07, p = 0.003). Corresponding OS at 3 years was 89.9% (95% CI: 83.6 – 96.3%) and 75.4% (95% CI: 61.9 – 91.8%) in the RC and NRC group with a trend in favor of RC (adjusted HR: 2.76, 95% CI: 0.91 – 8.43, p = 0.074). Conclusions: To our knowledge, this is the first RTQA evaluation of a phase III sarcoma trial. The data suggests a significant benefit in terms of ARFS and a trend for OS in favor of the RT compliant group. RTQA in prospective clinical trials, investigating new RT techniques, dose levels and indications, continues to be an important and integral part of trial designing. Funding Source: EORTC, EORTC Cancer Research Fund, EUROSARC FP7 278472 and Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society.