Proposal of an Alternative Near-Minimum Isodose Surface DV-0.01 cc Equally Minimizing Gross Tumor Volume Below the Relevant Dose as the Basis for Dose Prescription and Evaluation of Stereotactic Radiosurgery for Brain Metastases.

Abstract

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.