Part 2: Dynamic mixed beam radiotherapy (DYMBER): Photon dynamic trajectories combined with modulated electron beams.

The purpose of this study was to develop a treatment technique for dynamic mixed beam radiotherapy (DYMBER) utilizing increased degrees of freedom (DoF) of a conventional treatment unit including different particle types (photons and electrons), intensity and energy modulation and dynamic gantry, table, and collimator rotations. A treatment planning process has been developed to create DYMBER plans combining photon dynamic trajectories (DTs) and step and shoot electron apertures collimated with the photon multileaf collimator (pMLC). A gantry-table path is determined for the photon DTs with minimized overlap of the organs at risk (OARs) with the target. In addition, an associated dynamic collimator rotation is established with minimized area between the pMLC leaves and the target contour. pMLC sequences of photon DTs and electron pMLC apertures are then simultaneously optimized using direct aperture optimization (DAO). Subsequently, the final dose distribution of the electron pMLC apertures is calculated using the Swiss Monte Carlo Plan (SMCP). The pMLC sequences of the photon DTs are then re-optimized with a finer control point resolution and with the final electron dose distribution taken into account. Afterwards, the final photon dose distribution is calculated also using the SMCP and summed together with the one of the electrons. This process is applied for a brain and two head and neck cases. The resulting DYMBER dose distributions are compared to those of dynamic trajectory radiotherapy (DTRT) plans consisting only of photon DTs and clinically applied VMAT plans. Furthermore, the deliverability of the DYMBER plans is verified in terms of dosimetric accuracy, delivery time and collision avoidance. For this purpose, The DYMBER plans are delivered to Gafchromic EBT3 films placed in an anthropomorphic head phantom on a Varian TrueBeam linear accelerator. For each case, the dose homogeneity in the target is similar or better for DYMBER compared to DTRT and VMAT. Averaged over all three cases, the mean dose to the parallel OARs is 16% and 28% lower, D2% to the serial OARs is 17% and 37% lower and V10% to normal tissue is 12% and 4% lower for the DYMBER plans compared to the DTRT and VMAT plans, respectively. The DYMBER plans are delivered without collision and with a 4-5 min longer delivery time than the VMAT plans. The absolute dose measurements are compared to calculation by gamma analysis using 2% (global)/2 mm criteria with passing rates of at least 99%. A treatment technique for DYMBER has been successfully developed and verified for its deliverability. The dosimetric superiority of DYMBER over DTRT and VMAT indicates utilizing increased DoF to be the key to improve brain and head and neck radiation treatments in future.

Mueller S ，Manser P ，Volken W ，Frei D ，Kueng R ，Herrmann E ，Elicin O ，Aebersold DM ，Stampanoni MFM ，Fix MK ... -  《-》

Part 1: Optimization and evaluation of dynamic trajectory radiotherapy.

Although volumetric modulated arc therapy (VMAT) is a well-accepted treatment technique in radiotherapy using a coplanar delivery approach, VMAT might be further improved by including dynamic table and collimator rotations leading to dynamic trajectory radiotherapy (DTRT). In this work, an optimization procedure for DTRT was developed and the potential benefit of DTRT was investigated for different treatment sites. For this purpose, a dedicated optimization framework for DTRT was developed using the Eclipse Scripting Research Application Programming Interface (ESRAPI). The contours of the target and organs at risk (OARs) structures were exported by applying the ESRAPI and were used to determine the fractional volume-overlap of the OARs with the target from several potential beam directions. Thereby, an additional weighting was applied taking into account the relative position of the OAR with respect to the target and radiation beam, that is, penalizing directions where the OAR is proximal to the target. The resulting two-dimensional gantry-table map was used as input for an A* path finding algorithm returning an optimized gantry-table path. Thereby, the process is also taking into account CT scan length and collision restrictions. The A* algorithm was used again to determine the dynamic collimator angle path by optimizing the area between the MLC leaves and the target contour for each gantry-table path leading to gantry-collimator paths. The resulting gantry-table and gantry-collimator paths are combined and serve as input for the intensity modulation optimization using a research VMAT optimizer and the ESRAPI resulting in dynamic trajectories. This procedure was evaluated for five clinically motivated cases: two head and neck, one lung, one esophagus, and one prostate. Final dose calculations were performed using the Swiss Monte Carlo Plan (SMCP). Resulting dose distributions for the DTRT treatment plans and for the standard VMAT plans were compared based on dose distributions and dose volume histogram (DVH) parameters. For this comparison, the dose distribution for the VMAT plans were recalculated using the SMCP. In addition, the suitability of the delivery of a DTRT treatment plan was demonstrated by means of gafchromic film measurements on a TrueBeam linear accelerator. DVHs for the target volumes showed similar or improved coverage and dose homogeneity for DTRT compared with VMAT using equal or less number of dynamic trajectories for DTRT than arcs for VMAT for all cases studied. Depending on the case, improvements in mean and maximum dose for the DTRT plans were achieved for almost all OARs compared with the VMAT plans. Improvements in DTRT treatment plans for mean and maximum dose compared to VMAT plans were up to 16% and 38% relative to the prescribed dose, respectively. The measured and calculated dose values resulted in a passing rate of more than 99.5% for the two-dimensional gamma analysis using 2% and 2 mm criteria and a threshold of 10%. DTRT plans for different treatment sites were generated and compared with VMAT plans. The delivery is suitable and dose comparisons demonstrate a high potential of DTRT to reduce dose to OARs using less dynamic trajectories than arcs, while target coverage is preserved.

Fix MK ，Frei D ，Volken W ，Terribilini D ，Mueller S ，Elicin O ，Hemmatazad H ，Aebersold DM ，Manser P ... -  《-》

Impact of the gradient in gantry-table rotation on dynamic trajectory radiotherapy plan quality.

To improve organ at risk (OAR) sparing, dynamic trajectory radiotherapy (DTRT) extends VMAT by dynamic table and collimator rotation during beam-on. However, comprehensive investigations regarding the impact of the gantry-table (GT) rotation gradient on the DTRT plan quality have not been conducted. To investigate the impact of a user-defined GT rotation gradient on plan quality of DTRT plans in terms of dosimetric plan quality, dosimetric robustness, deliverability, and delivery time. The dynamic trajectories of DTRT are described by GT and gantry-collimator paths. The GT path is determined by minimizing the overlap of OARs with planning target volume (PTV). This approach is extended to consider a GT rotation gradient by means of a maximum gradient of the path ( G m a x ${G}_{max}$ ) between two adjacent control points ( G = | Δ table angle / Δ gantry angle | $G = | \Delta {{\mathrm{table\ angle}}/\Delta {\mathrm{gantry\ angle}}} |$ ) and maximum absolute change of G ( Δ G m a x ${{\Delta}}{G}_{max}$ ). Four DTRT plans are created with different maximum G&∆G: G m a x ${G}_{max}$ & Δ G m a x ${{\Delta}}{G}_{max}$  = 0.5&0.125 (DTRT-1), 1&0.125 (DTRT-2), 3&0.125 (DTRT-3) and 3&1‍(DTRT-4), including 3-4 dynamic trajectories, for three clinically motivated cases in the head and neck and brain region (A, B, and C). A reference VMAT plan for each case is created. For all plans, plan quality is assessed and compared. Dosimetric plan quality is evaluated by target coverage, conformity, and OAR sparing. Dosimetric robustness is evaluated against systematic and random patient-setup uncertainties between ± 3 mm $ \pm 3\ {\mathrm{mm}}$ in the lateral, longitudinal, and vertical directions, and machine uncertainties between ± 4 ∘ $ \pm 4^\circ \ $ in the dynamically rotating machine components (gantry, table, collimator rotation). Delivery time is recorded. Deliverability and delivery accuracy on a TrueBeam are assessed by logfile analysis for all plans and additionally verified by film measurements for one case. All dose calculations are Monte Carlo based. The extension of the DTRT planning process with user-defined G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ to investigate the impact of the GT rotation gradient on plan quality is successfully demonstrated. With increasing G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ , slight (case C, D m e a n , p a r o t i d l . ${D}_{mean,\ parotid\ l.}$ : up to‍-1‍Gy) and substantial (case A, D 0.03 c m 3 , o p t i c n e r v e r . ${D}_{0.03c{m}^3,\ optic\ nerve\ r.}$ : up to -9.3 Gy, case‍B, D m e a n , b r a i n $\ {D}_{mean,\ brain}$ : up to -4.7‍Gy) improvements in OAR sparing are observed compared to VMAT, while maintaining similar target coverage. All plans are delivered on the TrueBeam. Expected and actual machine position values recorded in the logfiles deviated by <0.2° for gantry, table and collimator rotation. The film measurements agreed by >96% (2%‍global/2 mm Gamma passing rate) with the dose calculation. With increasing G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ , delivery time is prolonged by <2 min/trajectory (DTRT-4) compared to VMAT and DTRT-1. The DTRT plans for case A and B and the VMAT plan for case C plan reveal the best dosimetric robustness for the considered uncertainties. The impact of the GT rotation gradient on DTRT plan quality is comprehensively investigated for three cases in the head and neck and brain region. Increasing freedom in this gradient improves dosimetric plan quality at the cost of increased delivery time for the investigated cases. No clear dependency of GT rotation gradient on dosimetric robustness is observed.

Loebner HA ，Mueller S ，Volken W ，Wallimann P ，Aebersold DM ，Stampanoni MFM ，Fix MK ，Manser P ... -  《-》

Dosimetrically motivated beam-angle optimization for non-coplanar arc radiotherapy with and without dynamic collimator rotation.

Bertholet J ，Zhu C ，Guyer G ，Mueller S ，Volken W ，Mackeprang PH ，Loebner HA ，Stampanoni MFM ，Aebersold DM ，Fix MK ，Manser P ... -  《-》

Development of a Monte Carlo based robustness calculation and evaluation tool.

Evaluating plan robustness is a key step in radiotherapy. To develop a flexible Monte Carlo (MC)-based robustness calculation and evaluation tool to assess and quantify dosimetric robustness of intensity-modulated radiotherapy (IMRT) treatment plans by exploring the impact of systematic and random uncertainties resulting from patient setup, patient anatomy changes, and mechanical limitations of machine components. The robustness tool consists of two parts: the first part includes automated MC dose calculation of multiple user-defined uncertainty scenarios to populate a robustness space. An uncertainty scenario is defined by a certain combination of uncertainties in patient setup, rigid intrafraction motion and in mechanical steering of the following machine components: angles of gantry, collimator, table-yaw, table-pitch, table-roll, translational positions of jaws, multileaf-collimator (MLC) banks, and single MLC leaves. The Swiss Monte Carlo Plan (SMCP) is integrated in this tool to serve as the backbone for the MC dose calculations incorporating the uncertainties. The calculated dose distributions serve as input for the second part of the tool, handling the quantitative evaluation of the dosimetric impact of the uncertainties. A graphical user interface (GUI) is developed to simultaneously evaluate the uncertainty scenarios according to user-specified conditions based on dose-volume histogram (DVH) parameters, fast and exact gamma analysis, and dose differences. Additionally, a robustness index (RI) is introduced with the aim to simultaneously evaluate and condense dosimetric robustness against multiple uncertainties into one number. The RI is defined as the ratio of scenarios passing the conditions on the dose distributions. Weighting of the scenarios in the robustness space is possible to consider their likelihood of occurrence. The robustness tool is applied on IMRT, a volumetric modulated arc therapy (VMAT), a dynamic trajectory radiotherapy (DTRT), and a dynamic mixed beam radiotherapy (DYMBER) plan for a brain case to evaluate the robustness to uncertainties of gantry-, table-, collimator angle, MLC, and intrafraction motion. Additionally, the robustness of the IMRT, VMAT, and DTRT plan against patient setup uncertainties are compared. The robustness tool is validated by Delta4 measurements for scenarios including all uncertainty types available. The robustness tool performs simultaneous calculation of uncertainty scenarios, and the GUI enables their fast evaluation. For all evaluated plans and uncertainties, the planning target volume (PTV) margin prevented major clinical target volume (CTV) coverage deterioration (maximum observed standard deviation of D 98 % CTV $D98{\% _{{\rm{CTV}}}}$ was 1.3 Gy). OARs close to the PTV experienced larger dosimetric deviations (maximum observed standard deviation of D 2 % chiasma $D2{\% _{{\rm{chiasma}}}}$ was 14.5 Gy). Robustness comparison by RI evaluation against patient setup uncertainties revealed better dosimetric robustness of the VMAT and DTRT plans as compared to the IMRT plan. Delta4 validation measurements agreed with calculations by >96% gamma-passing rate (3% global/2 mm). The robustness tool was successfully implemented. Calculation and evaluation of uncertainty scenarios with the robustness tool were demonstrated on a brain case. Effects of patient and machine-specific uncertainties and the combination thereof on the dose distribution are evaluated in a user-friendly GUI to quantitatively assess and compare treatment plans and their robustness.

Loebner HA ，Volken W ，Mueller S ，Bertholet J ，Mackeprang PH ，Guyer G ，Aebersold DM ，Stampanoni MFM ，Manser P ，Fix MK ... -  《-》