Purpose: Patient setup errors are of major concern for stereotactic radiosurgery (SRS) of multiple brain metastases (m-bm) when using SIMT-VMAT treatments. However, recent clinical outcome studies show high rates of tumor local control for SIMT-VMAT. This could be from contributions of both direct cell kill (DCK) and indirect cell kill (ICK) via devascularization for a single-dose of 15Gy or more. This study quantifies the role of ICK in dosimetric errors as a function of spatial patient setup uncertainty.
Methods: Nine patients with 2-16 metastases (61 total) were planned using SIMT-VMAT with HyperArc planning geometry using a 10MV-FFF beam with a 20Gy prescription to each lesion. Isocenter was placed at the geometric center of all tumors with an average distance to isocenter of 5.4 cm (2.2-8.9cm). Plans were recalculated with clinically realistic patient setup errors [±2mm, ±2o] in all 6-directions. Boolean structures were generated to calculate the effect of DCK as 20Gy isodose volume (IDV) and ICK as 15Gy minus 20Gy IDV. Contributions of DCK and ICK to PTV coverage were analyzed along with brain toxicity. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum acceptable patient setup errors to utilize ICK for SIMT-VMAT.
Results: Patient setup errors of 1.3mm/1.3°in all 6-directions must be maintained to achieve PTV coverage of 15Gy for ICK with SIMT-VMAT. Setup errors of 2mm/2° showed clinically unacceptable loss of PTV coverage of 29.4±14.6% even accounting for ICK–suggesting repositioning the patient. However, no significant effect on normal brain toxicity was observed.
Conclusion: SRS of m-bm using SIMT-VMAT treatments have shown positive outcomes even with patient setup errors. These clinical outcomes, while largely due to DCK, are also due to ICK. Mechanisms, such as devascularization, should be explored to provide better understanding of the radiobiological response of SRS of m-bm using SIMT-VMAT.
Radiosurgery, Setup Errors, Linear Quadratic Model