Predicting the effect of indirect cell kill in the treatment of multiple brain metastases via single‐isocenter/multitarget volumetric modulated arc therapy stereotactic radiosurgery

Abstract

Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m-bm) when using singleisocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT-VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions. Material and Methods: Nine complex patients with 61 total tumors (2-16 tumors/patient) were planned using SIMT-VMAT with geometry similar to Hyper-Arc with a 10MV-FFF beam (2400 MU/min).Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02-11.5) and 1.9 cc (0.11-18.8) with an average distance to isocenter of 5.4 cm (2.2-8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2 o ] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m-bm via SIMT-VMAT. Results: Patient setup errors of 1.3 mm /1.3 • in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2 • showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed. Conclusions: Radiosurgery of m-bm using SIMT-VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Assessment of PTV margin adequacy for single isocenter multiple brain metastases using genetic algorithms

“…However, it should be considered that using wider margins improves quality indices, but increases the risk of necrosis [43] by increasing indicators such as V 12 . The PTV coverage applying translations and rotations was studied and it was shown that dosimetric changes [48] and tumor control [49] followed a complex function of the displacement's combination. This effect may be related to a previous computational work where it was shown that applying rotations in diverse combinations showed different final displacements [16].…”

Multicomponent mathematical model for tumor volume calculation with setup error using single-isocenter stereotactic radiotherapy for multiple brain metastases

“…Rojas et al derived the optimal planning target volume (PTV) margin required to meet the tolerances [13]. Although there have been evaluations of the target's tumor control probability (TCP) and normal tissue complication probability (NTCP) in the presence of some setup errors, most of those studies performed only physical evaluations [14,15]. Mathematical models have long been used to elucidate physiological and pathological processes in humans, and the models have been extended to many areas of medicine [16,17].…”