Intraoperative radiotherapy for brain metastases after surgical resection a systematic review and meta-analysis

Brain metastases (BMs) are common in advanced cancers such as lung, breast, and melanoma, and carry a poor prognosis with high morbidity and local recurrence rates after surgery alone. Intraoperative radiotherapy (IORT) has emerged as a promising adjuvant treatment, delivering radiation directly to the resection cavity to reduce recurrence and minimize delays to systemic therapy. IORT also demonstrated more favorable dose homogeneity than single-fraction stereotactic radiosurgery, with fractionated IMRT achieving the highest uniformity. However, evidence regarding its efficacy and safety compared to non-IORT approaches remains limited. This meta-analysis synthesized data from 16 studies (2006-2023) involving 966 patients undergoing surgical resection of brain metastases, comparing outcomes between IORT (n = 616) and non-IORT (n = 350) groups. Key outcomes assessed included local control, overall survival (OS), distant brain control (DBC), postoperative complications, and adverse events. Meta-regression was used to explore associations between clinical factors and outcomes. IORT patients had significantly lower postoperative complication rates than non-IORT patients (risk ratio 0.52, 95% CI 0.43-0.62, p < 0.00001). Pooled local necrosis and postoperative mortality rates after IORT were low at 4.6% and 5.0%, respectively, with no significant variation by radiation dose or duration. The pooled local control rate (LCR) across eight studies was 92.5% (95% CI: 88.1-96.8%), despite moderate heterogeneity (I² = 65.4%, p = 0.005), highlighting IORT's effectiveness in local tumor control. IORT was also linked to shorter hospital stays (mean 8.8 vs. 19 days) and comparable or improved local recurrence rates. Meta-regression showed a positive correlation between lesion size and mortality (p < 0.05). Distant brain control averaged 52.4%, with moderate-to-low risk of bias across studies. IORT following surgical resection of brain metastases is a safe and effective modality, offering reduced postoperative complications and promising local control while enabling faster initiation of systemic therapy. Delivering adequate radiation doses tailored to tumor biology and size is critical to minimize local recurrence. Future clinical trials should focus on optimizing IORT parameters and establishing standardized guidelines to improve patient outcomes.