KEY POINTS
- This Strahlentherapie und Onkologie commentary reviews preliminary results from the single-centre randomized phase III trial NCT03741673, which enrolled 103 adults scheduled for resection of at least one brain metastasis.
- Patients were randomized to preoperative SRS/FSRT followed by surgery within 30 days or surgery followed by postoperative SRS/FSRT within 30 days. Radiation consisted of 15–22 Gy in one fraction or 21–30 Gy in three to five fractions, with technique and fractionation selected by the treating physician.
- Both protocol treatments were completed by 45 of 51 patients (88%) in the preoperative arm versus 38 of 52 patients (73%) in the postoperative arm, suggesting that delivering radiation before surgery reduced the risk of never receiving the planned postoperative treatment.
- Median time between the two interventions was 6 days with preoperative radiation versus 22 days after upfront surgery (p < 0.001). Median time from randomization to completion of both local treatments was 10 versus 32.5 days, respectively (p < 0.001).
- Thirty-day postoperative morbidity was similar: 48.9% after preoperative radiotherapy versus 44.7% after postoperative radiotherapy (p = 0.87). No significant differences were identified in neurological, infectious, respiratory, vascular, gastrointestinal, cardiac, or genitourinary complications.
- Treatment delivery was imbalanced: Gamma Knife was used in 84% versus 50%, and single-fraction treatment in 51% versus 29%, in the preoperative and postoperative groups, respectively. These differences complicate direct attribution of all findings to treatment sequence alone.
- The phase III primary endpoint is one-year leptomeningeal disease-free survival, and the analysis was not mature for leptomeningeal relapse, local control, radiation necrosis, progression-free survival, or overall survival. Postoperative stereotactic radiotherapy therefore remains the standard pending final oncologic results.
CLINICAL TAKEAWAY
Preoperative SRS or FSRT appears logistically feasible, improves completion of combined local therapy, and does not increase early postoperative morbidity in appropriately selected patients. It remains investigational because the outcomes that could justify changing sequence—especially leptomeningeal disease and local control—have not yet been reported.