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

Abstract

BACKGROUND:The European Organization for Research and Treatment of Cancer 22092-62092 STRASS trial failed to demonstrate the superiority of neoadjuvant radiotherapy (RT) over surgery alone in patients with retroperitoneal sarcoma. Therefore, an RT qualityassurance program was added to the study protocol to detect and correct RT deviations. The authors report results from the trial RT quality-assurance program and its potential effect on patient outcomes. METHODS: To evaluate the effect of RT compliance on survival outcomes, a composite end point was created. It combined the information related to planning target volume coverage, target delineation, total dose received, and overall treatment time into 2 groups: non-RT-compliant (NRC) for patients who had unacceptable deviation(s) in any of the previous categories and RT-compliant (RC) otherwise. Abdominal recurrence-free survival (ARFS) and overall survival were compared between the 2 groups using a Cox proportional hazard model adjusted for known prognostic factors. RESULTS: Thirty-six of 125 patients (28.8%) were classified as NRC, and the remaining 89 patients (71.2%) were classified as RC. The 3-year ARFS rate was 66.8% (95% confidence interval [CI], 55.8%-75.7%) and 49.8% (95% CI, 32.7%-64.8%) for the RC and NRC groups, respectively (adjusted hazard ratio, 2.32; 95% CI, 1.25-4.32; P = .008). Local recurrence after macroscopic complete resection occurred in 13 of 89 patients (14.6%) versus 2 of 36 patients (5.6%) in the RC and NRC groups, respectively. CONCLUSIONS: The current analysis suggests a significant benefit in terms of ARFS in favor of the RC group. This association did not translate into less local relapses after complete resection in the RC group. Multidisciplinary collaboration and review of cases are critical to avoid geographic misses, especially for rare tumors like retroperitoneal sarcoma.

Is quality related to quantity: Interpreting the results of STRASS in the context of noncompliant radiotherapy

“…Similarly, Peters and colleagues also observed that RT noncompliance was associated with a 20% decrement in overall survival at 2 years in a phase 3 head and neck cancer study 14 . The findings by Haas and colleagues in the current study are consistent with these prior reports 8 . Noncompliant RT plans were correlated with a less favorable ARFS and a trend toward poorer overall survival.…”

“…14 The findings by Haas and colleagues in the current study are consistent with these prior reports. 8 Noncompliant RT plans were correlated with a less favorable ARFS and a trend toward poorer overall survival. However, it was surprising that RT compliance was not associated with a lower rate of local recurrences.…”

“…As part of the trial, the authors astutely had the foresight to incorporate a robust RTQA program, which included both prospective and retrospective plan review, and an analysis of that experience by Haas and colleagues is published in this edition of Cancer. 8 Here, Haas and colleagues report that nearly 35% of the RT plans in the investigative arm of STRASS were noncompliant at first review (defined by planning target volume coverage, target delineation, total dose received, and overall treatment time), and, ultimately, 29% of delivered RT plans were deemed noncompliant based on prospectively identified parameters. The most common cause of RT noncompliance was incorrect target delineation, which was observed in 66% of deviations and, interestingly, RT noncompliance was associated with a poorer 3-year ARFS.…”

“…The recently reported STRASS study (European Organization for Research and Treatment of Cancer Trial 62092), 7 a randomized trial evaluating the role of preoperative RT for patients with RP sarcomas, failed to demonstrate a benefit of preoperative RT compared with surgery alone in reducing abdominal recurrence‐free survival (ARFS). As part of the trial, the authors astutely had the foresight to incorporate a robust RTQA program, which included both prospective and retrospective plan review, and an analysis of that experience by Haas and colleagues is published in this edition of Cancer 8 …”

Radiotherapy in Retroperitoneal Liposarcoma: Are We Looking for an Answer in the Wrong Place?

“…This flaw is particularly important if we think of the recent report from the STRASS RT quality-assurance program that showed a direct correlation between RT compliance and abdominal recurrence-free survival (ARFS) in patients treated in trial, or if we look at the growing evidence regarding the importance of the quality of surgery and center volume on surgical and oncological outcomes. 3,4 Third, information about post-surgical events different from patient death are not available. Thus, the direct effect of RT on local control or disease-specific survival are not measured.…”