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Location: Marriott Marquis
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PQA 04 - PQA 04 Palliative Care and Central Nervous System Poster Q&A

2506 - Exploring the Impact of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy for the Treatment of Brain Metastases

Monday, September 30, 2024
10:45 AM – 12:00 PM ET
Location: Hall C

Screen: 3

M. Dohopolski1, S. Anand2, S. Stojadinovic1, L. Giuliani Schmitt1, M. L. Aliru1, T. Patel3, A. R. Patel3, S. Barnett3, M. Youssef4, N. Shaikh4, X. Cai1, T. Dan1, R. D. Timmerman1, and Z. Wardak1; 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 2University of Texas Southwestern Medical Center, Dallas, TX, 3Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, 4Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX

Purpose/Objective(s): Brain metastases (BMs) affect ~30% of cancer patients. Fractionated stereotactic radiosurgery (FSRS) is a static treatment paradigm for managing large BMs. Here, we evaluate the impact of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR), our institutional adaptive paradigm delivering high-dose radiation over extended intervals, on patient outcomes in the era of blood-brain barrier (BBB) penetrating drugs. We hypothesize that PULSAR+BBB drugs will offer improved tumor control compared to FSRS. Materials/

Methods: We evaluated patients with BMs treated on our non-invasive stereotactic radiosurgery instrument who received FSRS or PULSAR from 1/2018-1/2024. Demographics, tumor, and treatment characteristics were collected. Characteristics were compared using the chi-square or Fisher exact test and the two-sample t-test or Mann-Whitney as appropriate. Kaplan Meier analysis with log-rank and cumulative incidence with completing risk of death using Fine-Gray were used to analyze overall survival (OS) and local (infield and marginal) failure/grade 3+ toxicity stratified by clinical variable using R statistics software. Multivariate Cox proportional hazard models were used for local failure and toxicity. P-value <0.05 used as significance cut-off.
Results: One hundred sixty-six (166) lesions (92 patients) and 85 lesions (46 patients) were included in the FSRS and PULSAR cohorts. Ages ranged from 57-72 and 56-67, respectively. Median initial size were similar (4.0 vs 3.4 cc), and the most common histologies were non-small cell lung cancer and breast for both groups. Concurrent BBB (cBBB) drug use was more common in the PULSAR cohort (55 vs 29%) but adjuvant BBB (aBBB) drug use was similar (~70% each). Median follow-up and OS were 1.7 years and 1.5 years; no difference is OS between groups. Two-year failure rates were 14.2 and 9.4%, respectively; rates were lowered when stratified by cBBB drug use (~13% vs 5% at 1 year). CBBB drug+PULSAR, aBBB, smaller size, gyn/melanoma/lung cancers were associated with fewer local failures on multivariate analysis. Two-year grade 3+ toxicity rates were similar (12.9 vs 7.6%) and were not affected by cBBB drug use.
Conclusion: PULSAR is a promising adaptive treatment paradigm for treating BMs, suggesting enhanced efficacy without increased toxicity compared to traditional treatments. While the reductions in local failures and grade 3+ toxicity were not statistically significant, the combination of PULSAR with concurrent BBB drugs showed promise in improving tumor control. Prospective trials are needed to confirm these preliminary findings and to establish PULSARs role in the treatment of BMs in the era of BBB penetrating drugs.