Introduction In stereotactic radiosurgery (SRS) for brain metastasis (BM), the prescribed dose is generally reported as a minimum dose to cover a specific percentage (e.g. D98%) of the gross tumor volume (GTV) with or without a margin or an unspecified intended marginal dose to the GTV boundary. In dose prescription to a margin-added planning target volume (PTV), the GTV marginal dose is likely variable and unclear. This study aimed to revealmajor flaws of dose prescription to a fixed % coverage of a target volume (TV), such as GTV D98% or PTV D95%, and to propose an alternative. Materials and methods Seven quasi-spherical models with volumes ranging from 1.00 to 15.00 cc were assumed as GTVs. The GTVs and the volumes generated by adding isotropic 1- and 2-mm margins to the GTV boundaries (GTV + 1 and 2 mm) were used for SRS planning, dose prescription, and evaluation. Volumetric-modulated arcs with a 5-mm leaf-width multileaf collimator were used to optimize each SRS plan to ensure the steepest dose gradient outside each TV boundary. In dose prescription to the GTV D98%, 0.02-0.3 cc of the GTV is below the prescribed dose, and the volume increases with larger GTVs. The volume below the prescribed dose should be less than the equivalent of a 3-mm-diameter lesion, i.e. 0.01 cc. Therefore, DV-0.01 cc was defined as an alternative near-minimum dose for which the TV below a relevant dose is less than 0.01 cc. Four different dose prescriptions, including the GTVDV-0.01 cc, were compared using specific doses in 1, 3, and 5 fractions, equivalent to 80, 60, and 50 Gy, respectively, as biologically effective doses (BEDs) to the boundaries of GTV, GTV + 1 mm, and GTV + 2 mm, respectively. Results Dose prescription to the GTV DV-0.01 cc corresponds to 95.0, 98.0, and 99.0-99.93% coverages for the GTV of 0.20, 0.50, and 1.00-15.00 cc, respectively. The GTV DV-0.01 cc varied substantially and decreased significantly as the GTV increased in dose prescriptions to the GTV D98%, GTV + 1 mm D95%, and GTV + 2 mm D95%. The GTV + 2 mm DV-0.01 cc increased significantly as the GTV increased, except for the dose prescription to the GTV + 2 mm D95% with a decreasing tendency. When comparing BED-based specific dose prescriptions, dose prescription to the GTV DV-0.01 cc was optimal in terms of the following: 1) consistency of the near-minimum dose of GTV; 2) the highest BED at 2 mm outside the GTV, except for 1.00 cc GTV, and the rational increase with increasing GTV; and 3) the highest BED at 2 mm inside the GTV. In dose prescription with the BED of 80 Gy in 1 fraction and 5 fractionsto the GTV DV-0.01 cc, the GTV limits were ≤1.40 and ≤8.46 cc, respectively, in order for the irradiated isodose volume not to exceed the proposed thresholds for minimizing the risk of brain radionecrosis. Conclusions Dose prescription to a fixed % coverage of a GTV with or without a margin leads to the substantially varied near-minimum doseat the GTV boundary, which significantly decreases with increasing GTV.Alternatively, GTV DV-0.01 cc with a variable coverage (D>95%) for >0.20 cc GTV and fixedD95% for ≤0.20 cc GTV is recommended as the basis for dose prescription and evaluation, along with supplemental evaluation of the marginal dose of the GTV plus a margin (e.g. GTV + 2 mm) to demonstrate the appropriateness of dose attenuationoutside the GTV boundary.
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