On the acceptance, commissioning, and quality assurance of electron FLASH units.

Background & Purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an example of commissioning. Methods: A protocol for acceptance, commissioning, and QA of UHDR linear accelerators was established by combining and adapting standards and professional recommendations for standard linear accelerators based on the experience with UHDR at four clinical centers that use different UHDR devices. Non-standard dosimetric beam parameters considered included pulse width, pulse repetition frequency, dose per pulse, and instantaneous dose rate, together with recommendations on how to acquire these measurements. Results: The 6- and 9-MeV beams of an UHDR electron device were commissioned by using this developed protocol. Measurements were acquired with a combination of ion chambers, beam current transformers (BCTs), and dose-rate-independent passive dosimeters. The unit was calibrated according to the concept of redundant dosimetry using a reference setup. Conclusions: This study provides detailed recommendations for the acceptance testing, commissioning, and routine QA of low-energy electron UHDR linear accelerators. The proposed framework is not limited to any specific unit, making it applicable to all existing eFLASH units in the market. Through practical insights and theoretical discourse, this document establishes a benchmark for the commissioning of UHDR devices for clinical use.

Dual beam-current transformer design for monitoring and reporting of electron ultra-high dose rate (FLASH) beam parameters.

PURPOSE: To investigate the usefulness and effectiveness of a dual beam-current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real-time, and to inform on the usefulness of this design for future eFLASH beam control. METHODS: Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam parameters such as pulse width (PW), pulse repetition frequency (PRF), and dose per pulse (DPP), and in combination to determine beam energy using the ratio of the lower-to-upper BCT signal. RESULTS: A linear relationship was observed between the absorbed dose measured on Gafchromic film and the BCT signals for both the upper and lower BCT (R2  > 0.99). A linear relationship was also observed in the BCT signals as a function of the number of pulses delivered regardless of the PW, DPP, or PRF (R2  > 0.99). The lower-to-upper BCT ratio was found to correlate strongly with the energy of the eFLASH beam due to differential beam attenuation caused by the secondary scattering foil. The BCTs were also able to provide accurate information about the PW, PRF, energy, and DPP for each individual pulse delivered in real-time. CONCLUSION: The dual BCT system integrated within the FLASH Mobetron was shown to be a reliable monitoring system able to quantify accelerator performance and capture all essential physical beam parameters on a pulse-by-pulse basis, and the ratio between the two BCTs was strongly correlated with beam energy. The fast signal readout and processing enables the BCTs to provide real-time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams.

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

PURPOSE: Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m-bm) when using single-isocenter/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 HyperArc 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, ±2o ] 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. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation-induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m-bm using a SIMT-VMAT plan.

Management of multiple brain metastases via dual-isocenter VMAT stereotactic radiosurgery.

Single-isocenter volumetric modulated arc therapy (VMAT) stereotactic radiosurgery (SRS) techniques to treat multiple brain metastases simultaneously can significantly improve treatment delivery efficiency, patient compliance, and clinic workflow. However, due to large number of brain metastases sharing the same MLC pair causing island blocking, there is higher low- and intermediate-dose spillage to the normal brain and higher dose to organs-at-risk (OAR). To minimize this problem and improve plan quality, this study proposes a dual-isocenter planning strategy that groups lesions based on hemisphere location (left vs right sided) in the brain parenchyma, providing less island blocking reducing the MLC travel distance. This technique offers simplified planning while also increasing patient comfort and compliance by allowing for large number of brain metastases to be treated in 2 groups. Seven complex patients with 5 to 16 metastases (64 total) were planned with a single-isocenter VMAT-SRS technique using a 10MV-FFF beam with a prescription of 20 Gy to each lesion. The isocenter was placed at the approximate geometric center of the targets. Each patient was replanned using the dual-isocenter approach, generating 2 plans and placing each isocenter at the approximate geometric center of the combined targets of each side with corresponding non-coplanar partial arcs. Compared to single-isocenter VMAT, dual-isocenter VMAT plans provided similar target coverage and dose conformity with less spread of intermediate dose to normal brain with reduction of dose to OAR. Reduction in total monitor units and beam on time was observed, but due to the second isocenter setup and verification, overall treatment time was increased. Dual-isocenter VMAT-SRS planning for multiple brain metastases is a simplified approach that provides superior treatment options for patient compliance who may not tolerate longer traditional treatment times as with individual isocenters to each target. This planning technique significantly reduces the amount of low- and intermediate-dose spillage, further sparing OAR and normal brain, potentially improving target accuracy though localization of left vs right-sided tumors for each isocenter set up.

Dynamic conformal arcs-based single-isocenter VMAT planning technique for radiosurgery of multiple brain metastases.

Multiple small beamlets in the delivery of highly modulated single-isocenter HyperArc VMAT plan can lead to dose delivery errors associated with small-field dosimetry, which can be a major concern for stereotactic radiosurgery for multiple brain lesions. Herein, we describe and compare a clinically valuable dynamic conformal arc (DCA)-based VMAT (DCA-VMAT) approach for stereotactic radiosurgery of multiple brain lesions using flattening filter free beams to minimize this effect. Original single-isocenter HyperArc style VMAT and DCA-VMAT plans were created on 7 patients with 2 to 8 brain lesions (total 35 lesions) for 10 MV- flattening filter free beam. 20 Gy was prescribed to each lesion. For identical planning criteria, DCA-VMAT utilizes user-controlled field aperture shaper before VMAT optimization. Plans were evaluated for conformity and target coverage, low- and intermediate dose spillages to brain volume that received more than 30% (V30%) and 50% (V50%) of prescription dose. Additionally, mean brain dose, V8, V12 and maximal dose to adjacent organs-at-risk (OAR) including hippocampi were reported. Total monitor units, beam modulation factor, treatment delivery efficiency, and accuracy were recorded. Comparing with original VMAT, DCA-VMAT plans provided similar tumor dose, target coverage and conformity, yet tighter radio-surgical dose distribution with lower dose to normal brain V30% (p = 0.009), V50% (p = 0.05) and other OAR including lower dose to hippocampi. Lower total number of monitor units and smaller beam modulation factor reduced beam on time by 2.82 min (p < 0.001), on average (maximum up to 3.8 min). Beam delivery accuracy was improved by 8%, on average (p < 0.001) and maximum up to 13% in some cases for DCA-VMAT plans. This novel DCA-VMAT approach provided excellent plan quality, reduced dose to normal brain, and other OAR while significantly reducing beam-on time for radiosurgery of multiple brain lesions-improving patient compliance and clinic workflow. It also provided less MLC modulation through the targets-potentially minimizing small field dosimetry errors as demonstrated by quality assurance results. Incorporating DCA-based VMAT optimization in HyperArc module for radiosurgery of multiple brain lesions merits future investigation.

Single-Isocenter Volumetric Modulated Arc Therapy (VMAT) Radiosurgery for Multiple Brain Metastases: Potential Loss of Target(s) Coverage Due to Isocenter Misalignment.

Purpose A single-isocenter volumetric modulated arc therapy (VMAT) treatment to multiple brain metastatic patients is an efficient stereotactic radiosurgery (SRS) option. However, the current clinical practice of single-isocenter SRS does not account for patient setup uncertainty, which degrades treatment delivery accuracy. This study quantifies the loss of target coverage and potential collateral dose to normal tissue due to clinically observable isocenter misalignment. Methods and materials Nine patients with 61 total tumors (2-16 tumors/patient) who underwent Gamma Knife® SRS were replanned in Eclipse™ using 10 megavoltages (MV) flattening-filter-free (FFF) bream (2400 MU/min), using a single-isocenter VMAT plan, similar to HyperArc™ VMAT plan. Isocenter was placed in the geometric center of the tumors. The prescription was 20 Gy to each tumor. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02-11.5 cc) and 1.9 cc (0.11-18.8 cc), respectively, derived from MRI images. The average isocenter to tumor distance was 5.5 cm (1.6-10.1 cm). Six-degrees of freedom (6DoF) random and systematic residual set up errors within [±2 mm, ±2o] were generated using an in-house script in Eclipse based on our pre-treatment daily cone-beam CT imaging shifts and recomputed for the simulated VMAT plan. Relative loss of target coverage as a function of tumor size and distance to isocenter were evaluated as well as collateral dose to organs-at risk (OAR). Results The average beam-on time was less than six minutes. However, loss of target coverage for clinically observable setup errors were, on average, 7.9% (up to 73.1%) for the GTV (p < 0.001) and 21.5% for the PTV (up to 93.7%; p < 0.001). The correlation was found for both random and systematic residual setup errors with tumor sizes; there was a greater loss of target coverage for small tumors. Due to isocenter misalignment, OAR doses fluctuated and potentially receive higher doses than the original plan. Conclusion A single-isocenter VMAT SRS treatment (similar to HyperArc™ VMAT) to multiple brain metastases was fast with < 6 min of beam-on time. However, due to small residual set up errors, single-isocenter VMAT, in its current use, is not an accurate SRS treatment modality for multiple brain metastases. Loss of target coverage was statistically significant, especially for smaller lesions, and may not be clinically acceptable if left uncorrected. Further investigation of correction strategies is underway.