Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial

BackgroundSurgery is an important therapeutic option for brain metastases. Currently, postoperative stereotactic radiosurgery (SRT) leads to 6-month and 1-year local control estimated at 70 and 62% respectively. However, there is an increased risk of radio-necrosis and leptomeningeal relapse. Preoperative SRT might be an alternative, providing local control remains at least equivalent. It is an innovative concept that could enable the stereotactic benefits to be retained with advantages over post-operative SRT.MethodsSTEP has been designed as a national, multicentre, open-label, prospective, non-randomized, phase-II trial. Seventeen patients are expected to be recruited in the study from 7 sites and they will be followed for 12months. Patients with more than 4 distinct brain metastases, including one with a surgical indication, and an indication for SRT and surgery, are eligible for enrolment. The primary objective of the trial is to assess 6-month local control after preoperative SRT. The secondary objectives include the assessment of local control, radio-necrosis, overall survival, toxicities, leptomeningeal relapse, distant control, cognitive function, and quality of life. The experimental design is based on a Flemming plan.DiscussionThere is very little data available in the literature on preoperative SRT: there have only been 3 American single or two-centre retrospective studies. STEP is the first prospective trial on preoperative SRT in Europe. Compared to postoperative stereotactic radiotherapy, preoperative stereotactic radiotherapy will enable reduction in the irradiated volume, leptomeningeal relapse and the total duration of the combined treatment (from 4 to 6weeks to a few days).Trial registration numberClinicaltrials.gov: NCT04503772, registered on August 07, 2020. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N degrees ID RCB 2020-A00403-36, registered in February 2020. Protocol: version 4, 07 December 2020.

Automated summary

BackgroundSurgery is a crucial treatment for brain metastases, but postoperative stereotactic radiosurgery (SRT) comes with risks. Preoperative SRT is proposed as an alternative to reduce risks, and the STEP trial is the first prospective study in Europe to assess its effectiveness.