EORTC’s important work in implementing quality assurance (QA) in radiotherapy (RT) was further advanced with the recent publication of QA results from the STRASS trial (EORTC 62092-22092) in Cancer, the journal of the American Cancer Society. STRASS set out to investigate a potential benefit of RT given prior to surgery, as compared to surgery alone in patients with retroperitoneal sarcoma (RPS)1, a rare soft tissue cancer inside the abdomen. The rational of RT was not to devitalize the tumour, which will be removed anyway, but to sterilize the margins potentially left after surgery, affirm the authors.
Globally, trial results showed no advantage in terms of abdominal recurrence free survival (ARFS) for patients who underwent RT. Nevertheless the study is positive for the subgroup of well differentiated as Grade I and II dedifferentiated liposarcomas. A meticulous QA analysis aimed to investigate deviations from the RT protocols and their potential influence on the study results. Such deviations actually occurred in a substantial number of patients (28.8%). The authors observed that patients treated with protocol compliant plans had an 17 % increase in terms of ARFS compared to patients treated with uncompliant plans. Surprisingly this was not translated by increased local control. A possible reason for this finding could be that longer follow up is required to detect also a difference in LC, say the authors.
Since the STRASS trial opened in 2012, international consensus guidelines for the treatment of RPS have been published, and therefore fewer deviations from protocol would be expected today, say the authors.
QA was an important part of the trial as neoadjuvant RT in RPS was not considered standard of care. Given the fact that RPS are often not diagnosed until the tumour is very large, it is indeed challenging to make RT plans that cover the whole of the mass, while at the same time sparing internal organs not affected by the disease. It must be underlined that 95% of the patients in the RT arm received IMRT.
Until recently the RPS treatment guidelines related mainly to surgery; for example, that surgery should be carried out in centres with a high volume of sarcoma patients. But when RT is taken into the equation, what constitutes such a high-volume centre is still unclear, along with other uncertainties as the majority of centers included less than 10 patients. There are still useful lessons to be learned from the STRASS QA analysis, the authors say. “The reason for not reviewing all patients before starting RT was to optimise resources at the time of trial initiation. Therefore, one lesson of this trial should be that, in case RT represents the investigated treatment, a prospective review of all patients should be mandatory for future trials.”
Although there were several limitations to the analysis that may have affected the results, and which need further validation in an independent study, they underline the importance of redefining adequate RT volume delineations in patients with RPS in a collaboration between the operating surgeon and the radiation-oncologist, the authors say. It must be acknowledged that an underestimation of the extent of the well differentiated parts of retroperitoneal liposarcoma is frequently observed. They further emphasise the value of including RTQA in state-of-the art trial development.
An accompanying editorial makes the same point and calls for an improvement in the quality of RT delivered for rare tumours as for robust peer and expert review of RT plans to be carried out before treatment start. “Incorrect RT target delineation has significant implications and is not unique to STRASS.”
1.Bonvalot S, Gronchi A, Le Péchoux C, Swallow CJ, Strauss D, Meeus P, van Coevorden F, Stoldt S, Stoeckle E, Rutkowski P, Rastrelli M, Raut CP, Hompes D, De Paoli A, Sangalli C, Honoré C, Chung P, Miah A, Blay JY, Fiore M, Stelmes JJ, Dei Tos AP, Baldini EH, Litière S, Marreaud S, Gelderblom H, Haas RL. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1366-1377. doi: 10.1016/S1470-2045(20)30446-0. Epub 2020 Sep 14. PMID: 32941794.