2596 - The association between time to postoperative radiotherapy, local control, and symptomatic adverse radiation effect in patients with resected brain metastases

M. A. Salans¹, A. Lui¹, T. Catalan¹, M. K. Aghi², P. V. Theodosopoulos², S. E. Braunstein³, R. A. Morshed², and H. Vasudevan³; ¹University of California San Francisco, San Francisco, CA, ²University of California San Francisco, Department of Neurological Surgery, San Francisco, CA, ³Department of Radiation Oncology, University of California San Francisco, San Francisco, CA

Purpose/Objective(s): Postoperative stereotactic radiosurgery (PORT) improves clinical outcomes after resection of brain metastases (BM) yet the optimal timing of PORT remains unclear. Materials/

Methods: We retrospectively identified 161 consecutive patients with 177 resected BM who underwent resection followed by PORT at a single institution between 2006-2022. Patients who underwent prior radiation to the resected lesion were excluded. Clinical characteristics were obtained from the medical record and compared between patients who received early versus late PORT based on median time to PORT (=28 days vs. >28 days) using Student’s t- and chi-square tests. Local control (LC), intracranial CNS progression-free survival (CNS PFS), and overall survival (OS) were assessed with the Kaplan-Meier method. Univariable and multivariable associations between clinical characteristics and LC and CNS PFS were assessed with the Fine-Gray subdistribution hazard model with death as a competing risk. Associations between clinical characteristics and OS were evaluated with the Cox proportional hazards model.
Results: Median follow-up was 28 months (95% CI 21-36 months), and median time to PORT was 28 days (interquartile range 21-40 days). 89 patients (52.4%) received PORT =28 days after surgery. The most common primary tumor histologies were non-small-cell lung (NSCLC) (n=53, 31.2%), melanoma (n=34, 20.0%), and breast (n=34, 20.0%). Most patients had a single BM (n=90, 52.9%) at the time of surgery and underwent fractionated stereotactic radiosurgery (median 24 Gy in median 3 fractions) (n=96, 56.5%). One-year rates of LC, intracranial CNS PFS, and OS were 78.1% (95% CI 71.3%-85.5%), 50.1% (95% CI 42.7%-58.9%), and 70.7% (95% CI 63.7%-78.5%), respectively. Early PORT (=28 days) was associated with improved LC (one-year LC 83.6% vs. 71.8%, p=0.03) but not intracranial CNS PFS (subdistribution hazard ratio [SHR]=0.97, p=0.9) or OS (hazard ratio=1.2, p=0.4). On multivariable regression analysis, only time to PORT was associated with local recurrence (>28 days SHR=2.1, p=0.04). Patients who received early PORT (=28 days) were more likely to have >1 BM (55.1% vs. 38.3%, p=0.04) and receive immune checkpoint inhibition (ICI) after PORT (25.8% vs. 12.3%, p=0.04). Postoperative complication rates were 2.2% (n=2) and 6.2% (n=5) in the early and late PORT groups, respectively (p=0.37). Time to PORT was not associated with volume of tumor resected (Spearman’s r=-0.03, p=0.69). Twelve (7.1%) patients developed symptomatic adverse radiation effects (sARE) after PORT. There was no difference in the rates of sARE between patients who received early versus late PORT (7.9% vs. 6.2%, p=0.90) or among patients who received concurrent (0% vs. 22.2%, p=0.45) or postoperative (0% vs. 10%, p=0.66) ICI.
Conclusion: Early PORT for resected brain metastases is associated with improved LC, underscoring the importance of timely PORT following brain metastasis resection.