“SCOPES”, towards a reduced treatment burden for soft tissue sarcoma patients
Currently, most sarcoma reference centers prefer a conventionally fractionated preoperative radiotherapy (RT) schedule (25 x 2 Gy in 5 weeks) over postoperative RT to 66 Gy for extremity soft tissue sarcoma patients. This preference is based upon a more favorable long-term toxicity profile after prolonged follow up of the Canadian SR-2 phase III, randomizing pre- to postoperative RT [O’SULLIVAN 2002]. Ever since, 50 Gy in 5 weeks is considered the golden standard. However, this dose level does not come forth from any preoperative comparative testing nor from knowledge on sarcoma radiosensitivity. There are several reasons to initiate clinical studies to deviate from this golden standard of 50 Gy. Our own preclinical radiobiological investigations [HAAS 2021] have shown a biological rationale for hypofractionation, now ready to be carefully tested in the clinic. Although quality of life of sarcoma patients on treatment has not been widely investigated yet, in daily practice, patients perceive this 5 week period as long. Hypofractionation offers potential benefits for patients by decreasing the overall treatment time of preoperative RT further enabling to perform surgery 2 weeks sooner. Finally, in the current COVID-19 pandemic it is important to down-scale the management of cancer patients maintaining treatment efficacy and normal tissue toxicity. An iso-toxic and iso-effective regimen of 14 x 3 Gy has been calculated, on radiobiological parameters, as study schedule. In the past, several clinical studies been designed, investigating various RT schedules but they all lack randomization to the standard 50 Gy regimen and none of them explored quality of life nor patient reported outcomes. Sarcomas are rare, representing only 1% of all adult cancer patients. Formal phase III randomized trials, e.g. with a non-inferiority statistical design, are logistically almost impossible to perform in the setting of rare cancers. In this project, we propose to prospectively randomize the 50 Gy golden standard in a randomized, pick-the-winner, phase II design to the new hypofractionated 14 x 3 Gy regimen and to compare toxicities and local control.