Impact of Distance From the Isocenter on Local Control and Toxicity for Zero Margin, Single-Isocenter Multitarget Volumetric Modulated Arc Therapy-Based Stereotactic Radiosurgery for Brain Metastases

Luke A Moradi; Richard A Popple; Roman L Travis; Samuel R Marcrom; Kristen O Riley; James M Markert; Christopher D Willey; Drexell H Boggs; Rodney J Sullivan; Joel A Pogue; John B Fiveash

doi:10.1016/j.ijrobp.2026.05.031

Impact of Distance From the Isocenter on Local Control and Toxicity for Zero Margin, Single-Isocenter Multitarget Volumetric Modulated Arc Therapy-Based Stereotactic Radiosurgery for Brain Metastases

Int J Radiat Oncol Biol Phys. 2026 Jun 2:S0360-3016(26)00772-8. doi: 10.1016/j.ijrobp.2026.05.031. Online ahead of print.

Affiliations

¹ Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: lukemoradi@uabmc.edu.
² Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.
³ Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama.

PMID: 42235693
DOI: 10.1016/j.ijrobp.2026.05.031

Abstract

Purpose: Radiosurgical treatment of multiple intracranial targets using a single isocenter is more efficient than sequential isocenter treatment. The primary concern with single-isocenter, multitarget (SIMT) stereotactic radiosurgery (SRS) is that rotational error may cause underdosing of peripheral lesions and/or increased normal tissue toxicity, particularly for targets distant from the isocenter. Many centers mitigate this risk by adding a planning target volume (PTV) margin, which increases dose to normal brain tissue. This study examined whether distance from the isocenter affects local tumor control or toxicity in patients treated with SIMT SRS using a 0-mm PTV margin.

Methods and materials: We retrospectively evaluated 429 patients with 3039 intracranial tumors treated with SIMT SRS or fractionated SRS using single-isocenter volumetric modulated arc therapy plans with a 0-mm clinical target volume/PTV expansion from gross tumor volume. All treatments used the Varian HD-120 multileaf collimators on a 6-degree-of-freedom couch. Local failure was defined as ≥25% increase in maximum tumor diameter (minimum 3 mm) or viable tumor cells at salvage surgery. Toxicity was defined as National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 central nervous system grade ≥3.

Results: Of the 3039 tumors evaluated, 1510 and 1034 tumors had clinical and radiographic follow-up at 6 months and 1 year, respectively. Median distance from the isocenter was 4.9 cm (range, 0.04-13.4 cm) and 70% of tumors in this study were ≥4 cm from the isocenter. One-year local control was 95.1% (95% CI, 94.0-96.1) and freedom from grade ≥3 toxicity was 98.4% (95% CI, 97.8-99.0). Larger tumor volume correlated with both worse local control (hazard ratio, 1.017; 95% CI, 1.000-1.034; P = .047) and higher toxicity (hazard ratio, 1.088; 95% CI, 1.056-1.121; P < .001). Increased distance from the isocenter was not associated with worse local failure or toxicity on multivariable analysis.

Conclusions: In this retrospective analysis of SIMT volumetric modulated arc therapy radiosurgery using HD-120 multileaf collimators, 6-degree-of-freedom couch, intrafraction surface monitoring, and 0-mm clinical target volume/PTV margin, increased distance from the isocenter did not adversely impact short-term local tumor control or increase high-grade toxicity. These findings are currently being tested in a prospective randomized trial.