2168 - Clinical Outcomes of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy for Brain Metastases
Presenter(s)
L. Pari Mitre1, L. Zhao1, L. G. Schmitt1, A. Chung1, S. Stojadinovic1, M. Youssef2, E. Noch2, E. Maher2, T. Patel3, A. R. Patel3, M. Z. Sun3, H. Gao1, J. Li1, M. Lee4, R. D. Timmerman1, J. B. De Vis1, X. Cai1, T. Dan1, Z. Wardak1, and M. Dohopolski1; 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, 3Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, 4School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX
Purpose/Objective(s): Gamma Knife fractionated stereotactic radiotherapy (FSRT) is a standard approach for treating brain metastases (BMs), yet concerns persist regarding toxicity and optimal fractionation. Personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) is an emerging paradigm. We hypothesized that PULSAR would provide local control comparable to FSRT with lower clinically significant toxicity, defined as grade =3 vasogenic edema, according to the Common Terminology Criteria for Adverse Events, particularly for larger lesions and in patients receiving concurrent or adjuvant CNS-active systemic therapy (CNSaD). Primary outcomes were local failure (LF) and vasogenic edema.
Materials/Methods: We performed a retrospective cohort analysis of BMs treated with FSRT or PULSAR between January 2018 and December 2025 at our institution. Postoperative radiation cases were excluded. Inclusion required =4 months post-treatment follow-up. In total, 560 lesions in 247 patients met criteria. Cumulative incidence of LF was compared using Gray’s test with death as the competing risk. Toxicity associations were assessed using hazard ratios. To mitigate confounding, propensity score matching was performed, including prespecified subgroup analyses (lesions >2 cm in diameter, CNSaD and extracranial disease control status).
Results: 251 lesions (134 patients) received FSRT and 309 lesions (113 patients) received PULSAR. Median age, lesion size, dose per fraction, prior radiotherapy, and histology distributions were similar between groups. Two-year LF cumulative incidence was comparable between FSRT (12.6%) and PULSAR (11.9%) (p=0.83). Lesions >2 cm demonstrated numerically lower LF rates with PULSAR, particularly with concurrent CNSaD, with no observed LF at 2.5 years with PULSAR. Grade =3 vasogenic edema occurred in 18 FSRT-treated lesions and 10 PULSAR-treated lesions. Two-year toxicity incidence was numerically lower with PULSAR (2.6%) compared to FSRT (6.9%), though not statistically significant (p=0.094). Adjuvant CNSaD use was independently associated with increased toxicity risk (HR 3.0, p=0.038), whereas treatment type was not. After 1:1 propensity score matching, edema incidence was significantly lower in PULSAR + concurrent CNSaD than FSRT + concurrent CNSaD among patients with lesions >2 cm (p<0.001). Additionally, patients without extracranial control of disease developed less edema in the PULSAR subgroup versus FSRT (p=0.03).
Conclusion: PULSAR achieved LF comparable to FSRT and showed numerically lower rates of vasogenic edema, with the most pronounced differences observed in patients with lesions >2 cm receiving concurrent CNSaD. The association of CNSaD with toxicity highlights the importance of treatment-drug interaction in toxicity mitigation. These findings support further investigation of PULSAR as a strategy to preserve efficacy while potentially reducing clinically significant edema in high-risk subgroups.